BRAIN HEALTH AND DEMENTIA

• “I am my ‘connectome’.” Joseph Maroon, MD {mindful.org “The magnificent, wonderful, wild connected brain.”}
• “No man ever steps in the same river twice, for it is not the same river and he’s not the same man.” Heraclitus

          There are over 30 million symptomatic individuals with Alzheimer’s dementia worldwide and many more in the pre-symptomatic phase. {According to the 2009 World Alzheimer’s report.} In the US there are over 5 million individuals with Alzheimer’s dementia with an estimated annual cost of $200 billion. The number of individuals is projected to rise to 13 million by 2050.

“Almost 40 per cent of people over the age of 65 experience some form of memory loss. When there is no underlying medical condition causing this memory loss, it is known as “age-associated memory impairment,” which is considered a part of the “normal aging process”. Age-associated memory impairment and dementia can be told apart in a number of ways. Below are some examples.

     Tips for coping with normal age-related memory difficulties

• Keep a routine
• Organize information (keep details in a calendar or day planner)
• Put items in the same spot (always put your keys in the same place by the door)
• Repeat information (repeat names when you meet people)
• Run through the alphabet in your head to help you remember a word
• Make associations (relate new information to things you already know)
• Involve your senses (if you are a visual learner, visualize an item)
• Teach others or tell them stories
• Get a full night’s sleep {According to the Alzheimer’s Society of Canada.}”

About 60 to 70% of dementias are due to Alzheimer’s Disease. “The most common early symptom is difficulty in remembering recent events (short term memory loss). As the disease advances, symptoms can include problems with language,  disorientation (including easily getting lost), mood swings, loss of motivation, not managing self-care, and behavioral issues. As a person’s condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years.” {According to Wikipedia.} 2/3 of people with AD are women, and the risk of AD increases with menopause along with a decrease in brain activity.

There is a critical window of opportunity to detect cognitive impairment and to implement strategies for treatment: the earlier the better; preferably <5 years after menopause. A drop in estradiol levels causes a decrease in memory function, increased total body and neuro-inflammation, increased insulin resistance, with increased central adiposity and obesity. Cognitive impairment associated with type 2 diabetes is thought of as “Type 3 Diabetes”. Estradiol is neuroprotective and an antioxidant. The hormone symphony needs to be evaluated: start with evaluating insulin, then adrenal functions, then thyroid functions, then the sex hormones, then estrogen metabolism. Personalized Medicine is required to evaluate the whole picture. When evaluating studies, look at the data and not just the conclusions, because when pooling data in meta-analyses, BHRT results are diluted when included with horse urine estrogen and/or progestin studies.

 Appropriate memory management requires an accurate assessment and diagnosis. 1) Is the file clerk working? The frontal lobes accumulate information and put it into the memory file cabinet. As we get older: a) we don’t hear as well—information needs to be repeated to get it into the file cabinet; b) we don’t move as quickly—it takes longer to retrieve a memory; and, c) we don’t see as well—we need a hint or a cue to find the right memory, so it may take retrieval extra-time. 2) What is the diagnosis? The new memory file cabinet is the hippocampus and related structures. The old memory file cabinet is the cortex. The hippocampus attaches meaning and emotion to a memory. Alzheimer’s disease destroys the hippocampus. Information can’t be retrieved if no information is in the file cabinet. People with AD often get lost, lose things, and repeat stories and questions. Diagnosis occurs along a frequency and a spectrum of symptoms. Rapid forgetting is NEVER normal. 3) What is the cause for the memory loss? Is the dementia due to a vitamin deficiency? Depression? Vascular compromise? Frontal lobe trauma? etc. 50% of people with “mild cognitive impairment” develop AD: someone is concerned about memory, testing confirms impairment, but day-to-day functioning remains normal. With “subjective cognitive decline”: someone is concerned about memory, testing is normal, yet, over time impairment occurs, and by 7 years over 50% develop a diagnosable disorder. 4) Treat your memory loss. Due to an infection? Due to too much amyloid-beta? Tau proteins release sticky tangles which trigger inflammation which kills cells. Cells make acetylcholine. With decreased cells there is decreased acetylcholine available. Treatment with medications that stimulate acetylcholine helps delay symptoms for 6 to 12 months. Treatment is continued because stopping the medication will cause a rapid cognitive decline: losing 6 to 12 months in 2 weeks because the clock can’t be reversed. Mamentine is helpful for late-stage AD by keeping a person more alert and motivated. It is not a disease modifying medication. 5) Modify your lifestyle. Aerobic exercise increases the size of the hippocampus, especially at one year—improving the new memory file cabinet. {Cardiac fitness is best assessed by measuring VO2Max.} Exercise decreases depression and improves sleep. Sleep helps one to pay attention; helps transfer memories from the old storage cabinet to the new cabinet for “consolidation”; and, clears amyloid-beta during NREM sleep cycles. Sleep also triggers brain derived neurotropic factor which improves cell growth and memory. The Mediterranean Diet with extra-virgin olive oil is also supportive. 6) Strengthen Your Memory. Engage in novel, stimulating cognitive activities. Be involved in social activities. Keep a positive mental attitude. Pay attention to names: practice mindful attention; say the name out loud; make connections; create visual images; find something in their visual appearance to remind you of their name; then, repeat their name in minutes, hours, days. If you are trying to recall a name: relax and don’t block it. Think about things that you know about the person. Memory strategies take effort and work, but they are effective. Doing puzzles improves your ability to do puzzles, but does not improve overall brain health. However, they are much better than just watching TV.

                        OUR CONNECTOME

Our brains have over 100 billion neurons, with over 100 trillion synaptic connections. Our thoughts affect the architecture of our brain. Because, the brain is neuroplastic and keeps changing throughout life. “What fires together, wires together.” Certain mental health problems have ‘aberrant wiring diagrams’: such as, autism, early onset schizophrenia, and ADHD. There are functional and structural changes that correlate with the peculiar behavioral activities. There are neuroepigenetic factors responsible for neuroplasticity and modulation of the connectome. Our DNA is not our destiny: modifying epigenetic factors is the key to health. Epigenetic factors affect gene activation (transcription factors) that translate our DNA by RNA transcription for the manufacture of proteins. There are 4 key epigenetic factors: 1) Exercise; 2) Environment; 3) Nutritional factors; and, 4) Emotional Health. Intracellular oxidative stress creates inflammatory cytokines which amplify the oxidative stress and result in chronic inflammation, cardiovascular disease, and cancers.

For example, we can modify certain epigenetic factors involved in mood disorders, and move along the spectrum from vulnerability to resilience. Mental and physical exercises can help to heal traumas by re-wiring circuits with the strength of repetition. Repetition is critical. Neuroconnections are reinforced to enable us to improve and to strengthen our future capability. New learning stimulates neurogenesis. Literally, our thoughts can change the structure of our brains. Key supplements to support this enhancement include: Omega-3s, curcumin, resveratrol, NAD+, carnitine—molecules that support mitochondrial function.

CLUES TOWARDS AN UNDERSTANDING OF ALZHEIMER’S DEMENTIA    

 AD is multifactorial, although the causes are poorly understood. It is believed that about 70% of the risk for AD is genetic. Additional risk factors include: head injury, hypertension, obesity and depression.

Various inflammatory processes and cytokines may have a role in the pathology of Alzheimer’s disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in AD or a marker of an immunological response. Brain inflammation can be demonstrated approximately 20 years before the onset of cognitive problems. {Brain. 2016 Jan 26.} Neuronal function, measured by glucose metabolism, began to decline approximately 7 years before disease symptoms.

There have been 2 consistent findings in patients diagnosed with Alzheimer’s disease: 1) Neurofibrillary tangles caused by “tauopathy”; and, 2) amyloid-beta plaques.

“The Tau Protein hypothesis proposes that tau protein abnormalities initiate the disease cascade. In this model, hyper-phosphoralated tau proteins dissociate from microtubules within neurons, then mis-fold and begin to pair with other threads of tau forming insoluble aggregates. Eventually, they form neurofibrillary tangles inside nerve cell bodies. When this occurs, the microtubules are destabilized and disintegrate, destroying the structure of the cell’s cytoskeleton which collapses the neuron’s transport and intracellular communication systems. This may result first in malfunctions in biochemical communications between neurons and later in the death of the cells.”  {According to Wikipedia.}

Examining the orthodox “Amyloid-beta Hypothesis”:  “In 1991, the “amyloid-beta  hypothesis” postulated that extracellular amyloid-beta deposits are the fundamental cause of the disease. Accumulation of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell’s calcium ion homeostasis, induces programmed cell death (apoptosis). It is also known that amyloid-beta selectively builds up in the mitochondria in the cells of Alzheimer’s-affected brains, and it also inhibits certain enzyme functions and the utilization of glucose by neurons. Support for this postulate comes from the location of the gene for the amyloid precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21(Down’s Syndrome) who have an extra gene copy almost universally exhibit at least the earliest symptoms of AD by 40 years of age. Also, a specific isoform of apolipoprotein, APOE4, is a major genetic risk factor for AD. While apolipoproteins enhance the breakdown of amyloid-beta, some isoforms are not very effective at this task (such as APOE4), leading to excess amyloid buildup in the brain. Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer’s-like brain pathology with spatial learning deficits.

In 2009, this theory was updated, suggesting that a close relative of the amyloid-beta protein, and not necessarily the amyloid-beta itself, may be a major culprit in the disease. The theory holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by age-related processes in later life to cause the neuronal withering of Alzheimer’s disease. N-APP, a fragment of APP from the peptide’s N-terminus, is adjacent to amyloid-beta and is cleaved from APP by one of the same enzymes. N-APP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor 6 (DR6). DR6 is highly expressed in the human brain regions most affected by Alzheimer’s, so it is possible that the N-APP/DR6 pathway might be hijacked in the aging brain to cause damage. In this model, amyloid-beta  plays a complementary role, by depressing synaptic function.” {According to Wikipedia.}

Robert Moir is an assistant professor of Neurology at Harvard Medical School, who works with Rudolph Tanzi.  On December 18, 2017, Amy Proal published an Interview with Dr. Moir:  In that interview he discussed key concepts:  The “Grandmother Hypothesis” acknowledges that birth is a dangerous and potentially deadly time for women (and for  infants). Especially as a woman gets older, there is an increasingly high risk of death from childbirth. Menopause allows aging mothers to stop reproduction, and to survive to help with raising the younger generations. Because human infants take such a long time to mature to the point of independence, having a grandmother to help successfully raise the grandchildren ensures that their genetic material is passed on to future generations.  Any gene that would negatively impact grandmother survival and their valuable store of accumulated knowledge and experience would be selected against, changed, or eliminated. This is important to understand when considering the impact of amyloid-beta and its association (not cause and effect) with Alzheimer’s dementia. The genes for the production of amyloid-beta have been 100% preserved for over 400 million years. It is one of the most conserved proteins across species in Biology. Thus, amyloid-beta must serve an important purpose.

 THE INFECTION HYPOTHESIS:  Amyloid-beta self-assembles to build multiple differently shaped molecules called “oligomers”. Each particular oligomer structure has a unique antimicrobial activity. Thus, amyloid-beta is a crucial part of the “innate immune system” because it spontaneously generates a population of diverse oligomers able to target a broad spectrum of pathogens, and toxins released during infection. Oligomers are simpler, metabolically cheaper, and a far more ancient immune strategy than antibodies (part of the “adaptive immune system”). Amyloid-beta is found in jelly fish and all vertebrates and contributes to survival fitness. Thus, the initial idea that amyloid-beta was accumulated “junk” that is toxic to brain neurons must be false. In fact, with increasing knowledge about the brain’s microbiome, it is now understood that amyloid-beta is a crucial antimicrobial peptide (that can work against viruses, bacteria and fungi) that is one hundred times stronger than penicillin, and which is needed to prevent brain dysbiosis and disease. Thus, a re-thinking about the etiology of Alzheimer’s disease is required.

***THE ANTIMICROBIAL RESPONSE (PROTECTION) HYPOTHESIS OF ALZHEIMER’S DISEASE***

The “antimicrobial response hypothesis” merges the infection hypothesis with the amyloid-beta hypothesis. Amyloid entrapment provides immediate, effective protection from infections. However, chronic infections or dysbiosis results in brain inflammation which triggers a cascade of pathologic responses resulting in Alzheimer’s disease.

          The BRAIN HAS A MICROBIOME!!  Not including viruses, there are over 200 organisms in a healthy brain. Perhaps Alzheimer’s disease occurs when there is a disruption of this microbial community {just like with Chron’s colitis}. Certain key pathogens may “push” the community out of balance. Amyloid-beta arises to do battle in cases of brain microbiome dysbiosis (imbalance). Part of this response is inflammation. However, prolonged activation of this innate immune inflammation may lead to tissue damage and neuro-degeneration.

Amyloid-beta was discovered in 1984. Initially it was thought to occur only under disease conditions found in Alzheimer’s dementia. However, for 20 years it has also been found to be manufactured in normal brains. In experiments, if amyloid-beta is added to a broth of microbes, it will inhibit and kill a range of microbes. Further experiments in living organisms demonstrate that amyloid-beta plaques trap and neutralize microbes. There is mounting evidence associating Alzheimer’s disease with infectious organisms. Multiple studies show a positive correlation between Herpes Simplex Virus- 1 (HSV-1) and the incidence of Alzheimer’s disease. Several autopsy studies have found HSV-1 DNA in the tangles and plaques in the brains of humans and animals with Alzheimer’s disease. HSV-1 is more prominently found in the frontal and temporal lobes of damaged brains. And, when the classic sticky amyloid-beta plaque (associated with the disease) was placed in a test tube with nerve cells, the production of the classic signs of Alzheimer’s disease in those tissues was slowed. In addition to an infectious process, the immune pathways in Alzheimer’s disease may become dysregulated and pathological. {Ref:  Neuron, June 21, 2018, “Pathogen Hypothesis of Alzheimer’s disease”.} Human Herpes Virus 6A (HHV-6A) and Human Herpes Virus-7 (HHV-7) are associated with the cause and the progression of amyloid plaques, brain tangles, and the severity of Alzheimer’s disease. A Canadian study in 1982 suggested this association. And, a Swedish study in October 2014 also linked “cold sores” to Alzheimer’s dementia.}  In addition to the Herpes simplex virus {which has been detected 60% of the time}, Chlamydia pneumonia is also a candidate for brain infections. And, the slow progression of AD fits with the chronic nature of some systemic fungal infections, which can be asymptomatic and thus, unnoticed and untreated. Thus, there is no single pathogen driving the disease.        

THE GUT-BRAIN CONNECTION

The “Enteric Nervous System (ENS)” is separate from the Central Nervous System (CNS). It is composed of 2 thin layers of over 100 million nerve cells—more than in the spinal cord. The ENS lines the GI tract and controls blood flow, secretions and contractions. It also helps us to unconsciously “feel” (like a second brain) what is occurring in the GI tract. It has glial cells to support the gut neurons. It uses over 40 different neurotransmitters. It produces 50% of the body’s dopamine and 95% of the body’s serotonin. L. brevis can produce GABA. It has a barrier, similar to the blood-brain barrier, for protection. It may have its own memory (although it is not capable of thought). The gut and the brain are connected by the vagus nerve with about 90% of the signals going from the gut to the brain. {The vagus nerve also connects cardiac functions.} The bi-directional communication occurs by various physiological channels including autonomic pathways, neuro-endocrine pathways and neuro-immune pathways. {People with Parkinson’s disease have the same protein clumps in the ENS as in the CNS. And, people with Alzheimer’s disease have the same neurofibrillary tangles and amyloid plaques in the ENS as in the CNS. Thus, a gut biopsy may make earlier diagnosis possible.}

Both external and internal STRESS can create a challenge or a threat that disrupts an organism’s homeostatic balance. It can alter the composition and the function of the gut microbiota. For example, maternal stress can affect the fetal gut microbiome directly and through epigenetic factors. This can affect systemic dysregulation in early life and persist into adulthood. Potentiation of heightened anxiety may be transmitted because of this complex mixture of both biological factors as well as psychological factors that act in feedback loops. Chronic stress is associated with dysregulation of the Hippocampal-Pituitary-Adrenal (HPA) axis. (Irritable bowel syndrome results from a heightened gut sensitivity and limited ability to modulate an acute stress response.)

Changes in the microbiota may help to ameliorate psychological disorders. For example, if the gut microbiome is disrupted, there is a link with depression. A probiotic cocktail has been associated with improving depression on the Beck Depression Inventory. Also, L. helveticus can improve sustained attention in older adults. And, polyunsaturated omega-3 fatty acids can modify the gut microbiome resulting in improved cognition, dampened HPA activity with less anxiety and depression, and improved psychological well-being. Products of fermentation, short-chain fatty acids (SCFAs) travel via the vagus nerve where immune cells in the brain need them to mature. Also, certain gut bacteria live off chemicals generated in the brain which are transported to the gut. Vagus nerve traffic includes bacterial signaling molecules called “quorum sensing” molecules. It’s a two-way axis. Gut microbes and brain microbes may be “talking” and deciding what to do next!  Additionally, efferent nerves from the nasal bulb trace straight back to brain areas where amyloid-beta formation starts, and may be another primary source of entry for microbes. An important question is: can we modulate disease progression by manipulating the microbiome, or the gut-brain axis?

Amyloid has a general role in immunity. For example, diabetes is an amyloid disease. “Amylin” is produced in both type 1 and type 2 diabetes. At high levels, amylin is toxic to pancreas islet cells and highly pro-inflammatory. Yet, it is also protective against microbes, including E. faecalis which is a common cause of pancreatitis. Additionally, an amyloid is generated in the heart and has been linked to heart disease. Yet, it has antimicrobial protection. So, is amyloid-beta really the problem? It may be that prolonged microbial exposure with resultant inflammation and dysregulation of the immune system is the primary problem. Amyloid plaques, which trap and destroy microbes, are, therefore, found and associated with the diseases, but are not the cause of the disease.

A drug has been produced by Merck which lowers amyloid-beta without slowing the disease. Although, to date, the “amyloid is bad” idea continues to dominate, and most academic efforts are still focused on this model, because of costly drug trial failures, “Big Pharma” is now open to exploring alternative models. Current anti-inflammatory agents target the adaptive immune system, but don’t impact the innate immune system, and also don’t seem to have much impact on Alzheimer’s disease: perhaps because anti-microbial peptides, such as amyloid-beta, are a part of the primitive, innate immune system. For example, one target that is being examined is the gene “CD33”, which is an on/off switch for immune cells in the brain. Research is now being directed to manipulating this gene’s activity. Another line of research is combining anti-herpes virus drugs along with anti-amyloid drugs to influence early Alzheimer’s disease, and then targeting inflammatory molecules to possibly benefit later disease.

[***BE AWARE:  There are many supplements to slow viruses down. Consider using the amino acid Lysine, 1,000 mg to 3,000 mg daily, plus Zinc 20 mg/d, and Vitamin C at least 6,000 mg/day to boost your immune system. Other supplements to consider include: garlic, grapefruit seed extract, oil of oregano, and olive leaf extract.]

                         ***THE BREDESEN PROTOCOL***   

Cognitive decline is associated with a well orchestrated strategic downsizing of synaptic density. When there is a mismatch between the requirements from the many different inputs and what is required to maintain those synapses, something has to change in the neuro-remodeling. Essentially, early on anyway, giving up the ability to learn new information is sacrificed in order to retain all the important things which have already been learned during the rest of one’s life. For example, in younger women, estrogen receptor binding alters the cleavage of APP towards the desirable anti-Alzheimer’s side. However, with menopause and the withdrawal of sufficient estrogen to bind to these receptors, the cleavage of APP pushes towards the pro-Alzheimer’s side. Thus, looking for a “silver bullet” has been expensively unsuccessful. Perhaps what is required is a “silver buck-shot” approach. Dr. Bredesen has identified 36 factors which push APP cleavage towards supporting brain growth and maintenance. In order to prevent synaptic downsizing, all 36 factors need to be supported. His program is “programatic”, personalized and complex, and represents the future for treating chronic ills. Patients on the program noted symptom improvement in 3 to 6 months.

In a pilot study called “Reversal of cognitive decline: a novel therapeutic program” {Aging; 2014 Sept: 6(9):707-1 and, Integrative Medicine; 2015 Oct; 14(5):26-29}, Dr. Bredesen with the UCLA/Buck Institute offered personalized, multi-variate strategies for each patient and demonstrated REVERSAL OF MEMORY LOSS in 9/10 patients in their initial study!! {Now the study participants exceed 70 patients, and the findings remain consistently remarkable, and hopeful. However, when the program is not followed, cognitive decline is noted within 2 weeks!} For chronic diseases, a mono-therapeutic approach is simplistic, not optimal, and unsuccessful. [The paradigm shift began with the successful use of triple therapy for HIV.]  Although no patient followed all 36 recommendations, there seems to be a threshold number of modifications needed, which has yet to be determined, in order for symptom reversal to be noted {and seems to be >12 factors}. On follow-up evaluations, recommendations are “tweaked” to better fit with a person’s life-style, which simplifies yet optimizes its applications.

Dr. Bredesen addresses known associations with Alzheimer’s disease such as mitochondrial health, insulin resistance and the metabolic syndrome, metal homeostasis, chronic inflammation, hypertension, hypercortisolemia, hypothyroidism, high interleukin-6 levels, hypovitaminosis D; hyperhomocysteinemia, and hormonal deficiencies. Since there are at least 3 different categories of Alzheimer’s disease, with different responses to therapeutics, people need to be treated differently. A Functional Medicine approach is most appropriate: examining the cause(s) and treating the cause(s). Functional Medicine asks: Why did one develop this problem? How can it be reversed?

Metabolic profiling has distinguished at least three subtypes of Alzheimer’s disease. {Dale Bredesen, Aging, 2015 Aug; 7(8).} 1) Inflammatory: amnesic, occurring in the 70s with hippocampal atrophy, and increased inflammatory markers such as hs-CRP and globulin/albumin. It is associated with the APOE gene. 2) Non-Inflammatory: amnesic, occurring in the 80s, associated with metabolic abnormalities, but inflammatory markers are not increased. It is also associated with the APOE gene. {APOE4 exerts pro-inflammatory effects.} 3) Loss of long term memory maintenance: affecting relatively younger people in their 50s and 60s, with widespread cortical involvement, characterized by dyscalculia and aphasia, and a passive child-like demeanor, and often depression. Individuals are APOE gene negative. There is a striking association with zinc deficiency. Over 300 enzymes require zinc as a co-factor. Zinc deficiency causes increased inflammation, induces insulin resistance, decreases the immune responses, increases susceptibility to toxins and infections, increases harmful reactive oxygen species (ROS), decreases hormone functioning including decreased adrenal hormone support, increases gastrointestinal permeability, and increases susceptibility to copper toxicity. Thus, treatment with zinc can mitigate cognitive decline.

Zinc deficiency is common. Decreased gastric acidity (because of age and the common use of PPIs and antacids for reflux and gastritis) causes decreased zinc absorption. Alcohol use and a diet deficient in zinc, adrenal fatigue due to poor coping with stress, diabetes, toxin exposure, intestinal parasites, and aging all may result in a zinc deficiency. Measuring serum zinc is an insensitive test. If it is low, then zinc deficiency is severe. However, a normal serum zinc level may still indicate a significant zinc deficiency. A more accurate measurement would be evaluating the red blood cell zinc level.

  ***STRATEGIES used in the Bredesen therapeutic program included: a) eliminating all simple carbohydrates, gluten, and processed foods from the diet, and eating more vegetables, fruits and non-farmed fish. b) Meditating twice a day and beginning yoga to reduce stress. c) Sleeping 7 to 8 hours per night, up typically from 4 to 5 hours per night. d) Taking melatonin, methylcobalamin (vitamin B12), vitamin D3, fish oil, folate and CoQ10 daily. e) Optimizing oral hygiene by using an electric tooth flosser and an  electric toothbrush. f) Reinstating bio-identical hormone replacement therapy (if previously discontinued.) g) Fasting a minimum of 12 hours between dinner and breakfast. And, h) Exercising a minimum of 30 minutes, four to 6 days per week.

{Reference: Discover Magazine, December 2018, “Alzheimer’s Under Attack” by Linda Marsa, pp. 32-41.}

                   ARE LEAKY CAPILLARIES A CAUSE OF AD?

According to Nature Medicine {online, 2019 Jan 14 “Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction:” as reported in The People’s Pharmacy blog}  “Drug companies have invested heavily in medications that could lower levels of amyloid in the brain. To date the results have not been promising. The authors of the new research in Nature Medicine report that leaky blood vessels may play an independent and crucial role in cognitive decline and Alzheimer’s disease. ‘Our data show that individuals with early cognitive dysfunction develop brain capillary damage and BBB breakdown in the hippocampus irrespective of Alzheimer’s Aβ [amyloid beta] and/or tau biomarker changes, suggesting that BBB {blood-brain barrier} breakdown is an early biomarker of human cognitive dysfunction independent of Aβ and tau.’  The authors of the new research in Nature Medicine report that leaky capillaries can be detected long before Aβ and tau show up. ‘Our present findings support that neurovascular dysfunction may represent a previously under appreciated factor contributing to cognitive and functional decline, independent of the classic pathophysiological hallmarks of AD [Alzheimer’s disease].’

What causes leaky brain blood vessels or neurovascular permeability? The answer is complicated. Brain inflammation can do it. So can the resulting tissue trauma after head injury. Toxins and brain infections may also disrupt the blood brain barrier and lead to leaky blood vessels. Whether it is possible to reverse capillary permeability and delay or prevent the onset of dementia remains to be seen.”

IS THE CYANOBACTERIA TOXIN—BETA-METHYLAMINO-L-ALANINE (BMAA)– RESPONSIBLE FOR THE NEURODEGENERATION OF AD AND ALS?

          The ethnobotonist Paul cox has proposed that chronic exposure to the cyanobacteria (blue-green algae) toxin BMAA is linked to the neurodegeneration of AD and ALS. BMAA insinuates itself into protein chains in place of one of the 20 standard amino acids causing a protein mis-folding which triggers neuron death. Cyanobacteria are loaded with BMAA. The toxin gets into the food-chain via crabs, shrimp and other marine life that can be found in algae blooms. Preclinical studies suggest L-serine may benefit those exposed to the neurotoxin beta-methylamino-L-alanine (BMAA). Our cells can mistake BMAA for L-serine and misincorporate it into proteins, which can lead to cell death and may increase biological markers of Alzheimer’s. Laboratory studies indicate that L-serine may prevent misincorporation of BMAA and cell death. However, it is unclear whether L-serine affects biological markers of Alzheimer’s in the absence of such neurotoxins.

The amino acid L-Serine at a dose of 30 gm/day may slow the progression of AD by 85% (which is greater than with existing drugs). L-serine is essential for the synthesis of phosphatidylserine which is an essential component of all neuron cell membranes. It is also needed for the growth of neuronal processes.  Supplementation may inhibit brain inflammation. L-serine is safe for humans and relatively inexpensive. [NOTE: This is counter to the prevailing Amyloid-beta Hypothesis.]  L-serine is a naturally occurring dietary amino acid. It is abundant in soy products, sweet potatoes, eggs, meat, and some edible seaweed. (Also Note: there is a lot of L-serine in bacon.)  L-serine is also sold as a dietary supplement in capsule and powder forms. The dose used in an ongoing Alzheimer’s trial is 15 grams, twice daily, in the form of gummies. Most supplements come in the form of 500 mg capsules.   {Reported in Fortune, 1/18/2019 in an article by Rich Tetzeli}

                              SLEEP AND THE GLYMPHATIC SYSTEM

          SLEEP IS CRUCIAL:  The more waste products lying around the brain, the greater the chance for Alzheimer’s disease to take root. Since 25% of the body’s overall energy is regularly consumed by the brain, there are a lot of waste products to be cleaned up. The “glymphatic system” is the brain’s clean-up system. Specialized brain cells scavenge diseased and damaged bits of protein and metabolic waste. With age, these cells become impaired. Also, the neuron surrounding supportive glial cells shrink in size when sleeping, opening spaces between cells by as much as 60% which allows cerebral spinal fluid to be pumped through and clear out waste. Lymphatic vessels surrounding the brain then deliver the waste to the lymphatic system of the body which gets rid of the toxins. With aging, adults often struggle to get enough sleep, which impairs the clean up system. THUS, especially since NREM deep-wave sleeping is crucial for removing toxins, keeping a regular sleep schedule becomes increasingly important with aging. Irregular sleep hours and long day time naps can disturb an effective sleep cycle clean-up process. Also, sleeping on your side, in a fetal position, rather than on your back or stomach, does a better job of cleaning house. And, sleeping on your left side maximizes your body’s circulation, because most venous return travels up your right side and these veins can be compressed when you lie on them. However, getting good sleep is much more important than worrying about whether or not you sleep on your side, and what side you sleep on.

                       DEVELOP STRICT SLEEP HYGIENE HABITS

Here are some suggestions to try before considering a prescription medication. AVOID CAFFEINE (coffee, tea, caffeinated sodas), NICOTINE, and other  Stimulants such as chocolate, Sudafed or Afrin nasal spray, or, if that is too much of a challenge, then don’t use any for at least 6 hours before bedtime. AVOID HEAVY MEALS and  ALCOHOL before sleep. AVOID SUGARY OR SPICY FOODS 4 to 6 hours before bedtime. However, if awakening during the night is a problem, then try eating a light snack  of good fats (not carbs) before bedtime. A couple almonds, a few spoons of yogurt, a couple teaspoons of almond butter or peanut butter on a cracker can frequently do the trick. Drinking warm milk and/or eating a banana may help you get ready for bed. The amino acid tryptophan in these foods can help you to sleep.

Allow enough time for sleep. Most people need 7 to 9 hours of sleep each night. Fix a bedtime and an awakening time. Avoid napping during the day. And especially in the evening.  Arrange a sleep environment that is very dark, comfortable, quiet and cool {set the thermostat for 65 degrees in the bedroom} to facilitate falling asleep quickly and staying asleep. Use comfortable bedding and keep the room well ventilated. Block out all distracting noise. Consider a white noise generator. Reserve the bed for sleep and sex. Don’t use the bed as an office, work or recreation space. Let your body learn to associate the bed with sleeping. AVOID TV in the bedroom. Don’t take your worries to bed. Worrying is a prayer for that which you don’t wish to happen. Instead, practice relaxation techniques before going to bed. Yoga, deep breathing, visualizations, progressive muscle relaxation can all help relieve anxiety and muscle tension. Establish a pre-sleep ritual such as a warm bath (especially using Epsom salts—5 cups: the magnesium will relax your muscles), or a few minutes of reading or praying. Get into your favorite sleeping position. If you don’t fall asleep within 15-30 minutes, get up and go into another room and read until you get sleepy. Consider elevating the foot of your bed a few inches to increase circulation to your brain.  Regular AEROBIC EXERCISE is the best way to improve your sleep and modify pain. However, don’t do heavy exercise within 3 hours before bedtime because it raises your core body temperature and it takes several hours to return your core body temperature to normal. The best time for aerobic exercising is in the morning.

          COGNITIVE-BEHAVORAL THERAPY (CBT):  is the most effective psychological intervention to help with insomnia. It consists of a comprehensive program for educating and modifying behaviors.  The most effective use of CBT combines several of these methods. Rather than just relieving symptoms, it addresses the underlying cause(s) of insomnia. 1) Sleep Education: understanding the sleep cycles and learning how beliefs, behaviors and outside factors affect sleep. 2) Cognitive Control and Psychotherapy: helps control or eliminate negative thoughts and worries that keep one awake. It may help to eliminate worrisome beliefs about sleep such as a single restless night will make one sick. 3) Sleep Restriction: limiting the amount of time spent in bed rather than lying in bed awake which can become a habit leading to poor sleep. 4) Remaining Passively Awake: avoiding any effort to fall asleep. Worrying that one can’t sleep can keep one awake. 5) Stimulus Control Therapy: helps remove factors that condition the mind to resist sleep. Eg. One is coached to use the bed only for sleep and sex; and, to leave the bedroom if unable to sleep within 15 minutes. 6) Sleep Hygiene: changing basic lifestyle habits that can influence sleep: eg. Smoking or drinking caffeine late in the day; drinking a “nightcap” of alcohol; not regularly exercising; avoid napping; winding-down 2 hours before sleep time. 7) Relaxation Training: learning to calm the mind and body: eg. meditation, progressive muscle relaxation and hypnosis. 8) Biofeedback Training: learning to influence heart rate, skin temperature, muscle tension and skin electrical conduction. 9) Sleep Diary: keeping a detailed record of sleep patterns and influences for 2 weeks.

      ADDITIONAL KEYS TO MAINTAINING YOUR MEMORY:

• Physical Activity and Exercise: Regular exercise is a key to health, wellness and longevity. Regular exercise will help you to sleep better. Exercising increases blood flow to the brain helping to create new brain cells and blood vessels because of the increased Brain-Derived Neurotropic Factor (BDNF). This repairs and protects the brain cells from degeneration, both by repairing and restoring cellular mechanisms. Exercising releases endorphins and other chemicals that dull pain and improve your mood, especially decreasing your anxiety and lightening your depression. This helps with building and maintaining your resiliency.   Regular exercise enhances memory and quicker learning. Your work will be more productive. Also, you’re medical costs will be less. You’ll have decreased risks for developing chronic diseases: for example, you can help to prevent and treat dementias. The increased blood flow reduces toxins that cause aging and cell death, and reduces inflammation.

Some exercise is better than none, and even a little exercise can do you a lot of good. The goal is 150 min/week of aerobic activity. For time-conscious people: High Intensity Interval Training can produce the same results in half the time.  In addition to regular aerobic exercising, Total Fitness is achieved by enhancing your muscle strength, doing regular stretching, and, improving your balance and coordination. Your physical fitness is perhaps the best tool for minimizing cognitive impairment.

          RESISTANCE TRAINING increases your muscle mass, thus, generating more strength, and faster muscle force (power). Unless you over do it, you won’t become muscle bound. Resistance training also helps to make your bones more dense. Ten million Americans (80% are women) have osteoporosis (thin and breakable bones). {A decrease in sex hormones with aging helps to create this common problem.}  Resistance training also helps to improve your metabolism, increase your glucose tolerance (or, said another way, decrease your insulin resistance) and decrease your risks from type 2 diabetes. It also helps to decrease both coronary artery disease and cerebrovascular disease risks. Other than doing free weight lifting or using a dynamic weight resistance machine, such as a Nautilus device, there are various simple ways to do resistance training such as: Yoga, Tai Chi, Pilates, using flexible bands, sitting up and down using a chair and your own body weight, swimming, doing Zumba dancing, doing heavy gardening such as raking and digging, doing vigorous house cleaning, taking the stairs rather than using an elevator, jumping rope, etc. The stronger you are,  the more self-esteem, confidence, and positive thinking you will usually have.  However, because resistance training requires work and effort, only about 20% of people actually follow strength training recommendations. PLEASE DON’T BE LAZY.  Resistance exercises have an even greater impact on cognitive function than aerobic exercises. It increases blood flow to the brain, thus, increasing oxygenation and the provision of nutrients. It helps to promote angiogenesis from existing blood vessels and neurogenesis from stem cells in the hippocampus {an area responsible for organizing memories}. It increases the production of neurotransmitters: serotonin {which helps to regulate mood and sleep}, acetylcholine {which helps with cognition, learning and memory}, and GABA {the main inhibitory modulator}. It also increases neurotropins {proteins that regulate neuron survival}.  [Mavros, et. al. “Mediation of cognitive function improvements by strength gains after resistance training in older adults with mild cognitive impairment: outcomes of the study of mental and resistance training,” J. of the American Geriatric Society, October 2016.]

• The MEDITERRANEAN DIET: A diet high in fresh fruits and vegetables, whole grains, nuts and olive oil is optimal, along with eating fish and poultry in moderation, and red meat as a condiment. A 2017 study of 6,000 people eating a Mediterranean diet had a 35% decreased risk of cognitive impairment compared with people who didn’t. Remember: what’s good for the heart is good for the brain AND what’s good for the brain is good for the heart. Additionally, the “MIND” Diet optimizes neurological function: A) Focusing on increasing the ten brain healthy food groups: 1) Green leafy vegetables; 2) Other vegetables; 3) Nuts; 4) Berries; 5) Beans; 6) Whole grains; 7) Fish; 8) Poultry; 9) Olive Oil; and, 10) moderately drinking wine. And, B) Reducing or Avoiding brain damaging foods: 1) limiting pastries and sweets to under 5 servings per week; 2) limiting red meats to under four servings per week; 3) limiting cheese to one serving per week or less; 4) limiting butter or margarine to under 1 tablespoon per day; 5) limiting fried/fast foods to under one serving per week.
• Friends and Family: The social aspect of activities helps with persistence of activities as well as with providing encouraging feedback, which enhances learning new things. {According to Jo Ann Jenkins: AARP Bulletin, June 2018:}  Cognitive health is maintained with building strong social connections, reducing loneliness and social isolation, realizing a sense of purpose, and developing a more positive and optimistic outlook on aging. Social connections are important for health. People with close friends are more likely to get plenty of sleep, eat healthy foods, maintain peace of mind and have less stress, engage in brain healthy activities, and take on new challenges and hobbies. Loneliness is as bad as inhaling 15 cigarettes daily. It can decrease 8 years of life expectancy; decrease one’s quality of life; increase health care consequences and medical bills; and, mortality risk associated with loneliness is greater than for obesity. For many, having a sense of purpose is more important than making money. Having a meaningful life is associated with better health outcomes. And, optimism adds 7 1/2 years to life: people recover from disabilities better; there is a larger hippocampus (associated with organizing memory); there is less anatomic evidence of Alzheimer’s disease on brain MRI scans; and, there is an 80% decreased risk of CVD. The key is to approach each day with a smile of appreciation, and, then, having someone to share one’s purposeful life with.
• Managing Blood Pressure: High blood pressure damages small blood vessels in the brain, particularly in women, which is associated with dementia. Normalizing BP is very important.
• Managing Glucose Intolerance and Diabetes: Glycation is the process where sugar molecules react chemically with proteins in the body causing the proteins to cross-link and lose their functionality. Not only does this cross-linking prevent proteins from doing their intended jobs, it creates harmful molecules called Advanced Glycation End products (AGEs). Glycation causes inflammation that damages mitochondria, and mitochondrial dysfunction exacerbates glycation. This results in an age-accelerating cycle as glycated proteins accumulate in tissues throughout the body. Excess blood sugar causes “glycation” which damages enzymes and also damages small blood vessels in the brain. Insulin resistance sets the stage for neurofibrillary tangles and amyloid plaque accumulation. Thus, controlling glycation is very important.
• Smoking Cessation: Smokers have about a 60% increased risk of Alzheimer’s disease compared with non-smokers. Tobacco increases oxidative stress and produces cell-damaging free-radicals. Quitting smoking helps arteries become healthier within 6-months and helps to reduce strokes, which accelerate dementia.
• Avoiding Falls: Loss of consciousness for at least 30-minutes and repeated concussions can increase the risk of dementia by 4.5 times. Preventing falls can help the brain as well as help to avoid hip fractures and spinal compression fractures (associated with osteoporosis) which can seriously impair the quality of life and longevity.
• A Healthy Microbiome: Dysbiosis in the gut is associated with dementia. Healing the gut lining by eating bone broth, fresh fruits and vegetables, fermented foods, and supplementing with a mixture of soil-based spore-forming probiotics and a variety of lactobaccilli and bifidobacteria can keep the gut-microbiome healthy and balanced. I suggest reading the book “Eat Dirt” by Dr. Josh Axe.  
• Bioidential Hormone Replacement Therapy (BHRT): When BHRT is started with the sex hormones: estrogen, progesterone, and testosterone with menopause (and andropause), cognitive decline can be significantly delayed. Hormones are the strongest tools that we have to promote cognitive vitality: especially, melatonin, oxytocin, and thyroid hormone.

Melatonin helps promote restful and restorative sleep. It helps to decrease aluminum toxicity in the brain, calms nervous agitation associated with “sundowning”, and improves memory and cognitive function. Treatment involves at least 1 mg at bedtime. Sublingual dosing seems to work better than oral dosing. The higher the serum level of melatonin, the better the effects. It often takes 2-3 months for full improvement.

Oxytocin helps one to feel better and to feel cooperative, with decreased aggression, improved eye-contact, and increased facial smiling and flushing. It is the hormone of trust, affection and sociability. {Treatment: The dose is compounded—a  sublingual or nasal spray: 5- 10 IU 1-2x/day can reduce paranoid behaviors, meanness and aggression often accompanying dementias.}

Thyroid hormone helps one to be alert, motivated, and energized. Subclinical hypothyroidism is very common. Symptoms indicative of a low T3: memory is worse early in the morning, and, one is slow to find words (nouns). Treatment with Armour Thyroid to increase the free T3 level will improve blood flow in the brain, increase arousal and alertness, attention and wakefulness, increase brain excitability, increase glucose consumption and brain energy, and decrease brain inflammation. It takes 2 months to note some improvement and 10-12 months for a full improvement.

IGF-1 (associated with human growth hormone), estrogen and testosterone all help with long term memory. If there is a deficiency of IGF-1, there is severe and profound permanent memory loss. There is also a decrease in brain mass. Treatment helps to reverse atrophy, decrease anxiety, and improve both short-term and long-term memory. IGF-1 is inversely correlated with cognitive impairment. A high IGF-1 is linked to increased longevity, decreased cancers, and improved memory and cognition. High IGF-1 levels are linked with increased brain processing speed and increased perceptions. It crosses the blood-brain barrier and is neuroprotective. {Treatment is subcutaneous injections of 0.3-1 mg hs to decrease AD. It takes 2-4 months for initial improvement, then 24-36 months for full improvement. It is recommended that the SQ injections occur around the eyes to be located with vessels near the brain. Intranasal IGF-1 is another effective route through the olfactory bulb to the CNS. It can be used to help decrease infarct size, and repair functions after a stroke.

Vasopressin, pregnenolone, and triiodothyronine (unbound or Free T3) help with short-term memory.  Estrogen therapy decreases the risk of AD by 3 to 7 fold. It improves mood, releases depression, and protects the brain against ischemia. Testosterone helps to decrease hesitations and improve memory loss. Pregnenolone levels are higher in the brain than in the blood. It is a neurotransmitter that improves memory. The dose is 50 mg in the morning. Desmopression nasal spray can be used instead of vasopressin at a dose of 0.1 mg twice per day to help improve short-term memory.

• BE AWARE:  Microglia are immune cells which shoulder the responsibility for “brain cleanup”. They are rich in lysosomes which breakdown “junk proteins” with bursts of acid. Proton Pump Inhibitors (PPIs) commonly used to manage reflux esophagitis and gastritis pass through the blood-brain barrier and reduce the amount of acid contained in the lysosomes, which means they are less able to clear dangerous proteins which consequently results in cell death, inflammation, and neuronal dysfunction, typical of Alzheimer’s disease. (Eur J Neurosci. 2013;37(12):1949-61.) Even short term use of PPIs impairs cognitive function. In otherwise young, healthy adults, after just 7 days of exposure to a PPI, all had statistically and clinically significant impairment in cognitive functions. Omeprazole (Prilosec) was the worst offender. (Alzheimers Res Ther. 2015;7:79.)  

                           SUPPLEMENTS TO CONSIDER

I follow the principle: “First do no harm.” Alzheimer’s disease is a progressive and devastating problem for patients and their families. While there are no definitive studies for the following suggestions, these suggestions will not cause harm by following them.

A)  Supplements to slow viruses down (Anti-Viral)

1.  The amino acid Lysine, 1,000 mg to 3,000 mg daily
2.   Zinc 20 mg/d
3.   Vitamin C at least 6,000 mg/day to boost your immune system
4.   Garlic, Grapefruit Seed Extract, Oil of Oregano, and Olive Leaf Extract.

B)  Mitochondrial Support: nutrients to refuel the mitochondrion1. 

1.  D-Ribose 5 gm/tsp: 1-2 tsp up to 3 times/day
2.   ALA: 300-400 mg/day;
3.   CoQ10 200+ mg/day;
4.   NAD+: 100 mg/day; and,
5.   L-Carnitine: 2,000-3,000 mg/day. Also,
6.   Membrane phospholipids (NT factor)
7.   Glycation can also damage mitochondrial function. Pyrroloquinoline quinone (PQQ) and Taurine can also help to limit glycation and, thus, restore cellular energy. PQQ is a vitamin-like molecule that promotes the production of new mitochondria in cells. Taurine is an amino acid found in high concentrations inside mitochondria where it regulates the enzymes responsible for harvesting energy from food molecules.

C) Memory Support

1. ***The Ayurvedic herb known as “Brahmi” or “BACOPA” (bacopa monniera) can prevent and treat dementia without side-effects! It is a cognitive enhancer and neuroprotective agent. Studies demonstrate the improvement of new memory acquisition and information retention. Additionally, studies demonstrate improved accuracy for spatial working memory (which is critical for being able to find things and remember where they are). Bacopa also brings a calmness and clarity of mind. The typical dose is 500 mg/day. Studies demonstrate improvement of anxiety. (Also, in patients with schizophrenia, bacopa helps control symptoms.) Like the patent acetylcholinesterase inhibitor medications (such as Aricept and Exelon), bacopa suppresses acetylcholinesterase. It also increases the enzyme activity of the sodium-potassium pump which helps to repair oxidative damage. It has been found to improve memory, concentration, learning ability, reduce irritability, and improve energy and lessen fatigue. Triterpenide saponins and bacosides in the herb improve brain cell communication. Here’s a source for this: himalayausa.com. Another product combining bacopa plus additional complementary Ayurvedic herbs (from the same source) is called “MindCare”. In addition to improving cognitive function, it helps to ease stress and anxiety, combat mental fatigue, smooth digestive symptoms and bring calmness and clarity. The recommended dose is 2 caps twice daily with meals for about $34 per month.
2. *** I like a proprietary product from LifeExtension.com called “Cognitex” which combines 11 ingredients for brain protection and optimal function. 3 capsules daily contains: a) 600 mg of Alpha-Glyceryl Phosphoryl Choline which boosts levels of acetylcholine, which enables brain cells to communicate. b) 50 mg of Gastrodin which supports healthy levels of blood flow. c) 150 mg of Grape seed extract which boosts brain oxygen flow. d) 20 mg of Vinpocetine which increases circulation and brain cell conductivity. e) 100 mg of Phosphatidylserine which encourages improved concentration. f) 50 mg of Pregnenolone which promotes mental energy. g) Additionally, it includes 150 mg of wild blueberry extract, 125 mg of Ashwagandha extract, 50 mg of Uridine-5-monophosphate, and a blend of Perluxan hops extract and Rosemary extract which helps to facilitate neuron function and communications. Another proprietary product from the same company is called “Dopa-Mind” which is an extract from wild green oats that improves cognitive health and mental performance by inhibiting the MAO-B enzyme which then promotes healthy dopamine levels. Another proprietary product called “Dr. Cass’ Brain Cell Support Plus” from www.puretango.com contains similar compounds that can be helpful: Acetyl-L-carnitine, Cognizin citicoline, Dimethylaminoethanol, Phosphatidylserine, Ginko biloba, Gotu Kola, Huperzine A and Vinpocetine.
3. ***GINKGO BILOBA extract EGb 761, a dry extract of the leaves standardized to 22% to 27% ginkgo flavonoids has been extensively studied and a dose of 240 mg per day has similar efficacy to anticholinesterase medications currently approved for treatment of Alzheimer’s dementia (eg. Aricept, Razadyne, Exelon, and Namenda). Adverse effects were infrequent and included headache and dizziness. There were no increased bleeding events nor changes in coagulation parameters. Thus, it is an alternative first-line treatment for dementia. Find a supplement such as “Nature’s Way Ginkgold” that matches EGb 761.
4. ***MELATONIN: Melatonin is a hormone secreted by the Pineal gland in the brain. It influences stage IV sleep and REM dreaming sleep and improves the sleep pattern as well as the depth and quality of sleep. It is a body energizer and a mood enhancer. It affects the body’s circadian rhythms and modulates our immune function. It increases natural killer cells which helps against infections  and helps protect against cancer. Melatonin scavenges and neutralizes free radicals and it possesses potent anti-oxidative effects. After middle age, melatonin levels drop precipitously leaving our brains increasingly susceptible to the growing impact of oxidative damage. Such damage leads to the increased risk of neurodegenerative diseases and stroke and increased vulnerability to the effects of head trauma. A deficiency of melatonin causes poor sleep, irritability, hypersensitivity and anxiety and depression. Profound reductions in melatonin levels have been found in Alzheimer’s disease patients. “Sundowning” and sleep disorders such as insomnia, restlessness, and poor sleep quality occur in about 45% of Alzheimer’s dementia patients. Melatonin crosses the blood brain barrier and reduces inflammation.  When melatonin is supplemented early in the course of the disease, these changes can be ameliorated. Melatonin is an antioxidant and neuroprotective. It can reduce the damage caused by inflammatory amyloid beta proteins and tau proteins. It helps to reduce learning and memory deficits and slow the progression of cognitive impairment. It also prevents the production of alpha-synuclein, an oxidizing and inflammatory protein that accumulates in brain regions that control movement and balance with patients who have Parkinson’s disease. Additionally, it helps to neutralize existing adverse protein molecules for cellular cleanup, and, it helps to restore the normal activity of enzymes involved in dopamine production. It can be purchased over the counter. The “micronized” form is best. Some people find that an under the tongue product works better for them than an oral product. The dose range is 1 to 30 mg. The starting dose is usually 3 mg and the average dose for women is 3 to 10 mg and for men 5 to 15 mg. Vivid dreaming may be a side effect. If melatonin isn’t tolerated, you can support the production with methionine 500-1000 mg in the morning, 5-HTP 50-100 mg twice daily and a vitamin B complex with tryptophan 100-200 mg at bedtime. Improving sleep improves the immune system and improves the overall quality of life.
5. ***VIRGIN COCONUT OIL: While there are no scientific studies supporting the use of virgin coconut oil, it is a safe and tasty dietary supplement with no side effects. The proposed dose is 2 tablespoons (solid at room temperature) three times per day with meals. This provides an alternative (to glucose) energy source for the brain. This may also benefit other debilitating neurological diseases such as Parkinson’s disease and multiple sclerosis. Reportedly, it bypasses the need for insulin to be able to transport glucose molecules for nutritional energy into brain cells.
6. ***Magnesium-L-Threonate is a chelated form of magnesium that easily crosses the blood-brain barrier and assists in maintaining neurosynaptic connections, and inhibiting dysregulation of signaling pathways. There are proprietary products from LifeExtension.com called “Neuro-Mag Magnesium-L-Threonate capsules” and another product from www.reddremedies.com called “Brain Awakening” containing “Magtein” (magnesium threonate), Lion’s Mane (a mushroom used in Traditional Chinese Medicine), and “amla”—Indian gooseberry (used in Ayurvedic medicine) which purport stabilizing and improving cognitive function.  Magnesium is the “Great Relaxer”. Over 50% of the population is magnesium deficient due to soil depletion, food processing, and inadequate intake, coffee, tea and alcohol depletion, GI conditions that impair absorption, and medications that cause depletion: such as birth control pills, thiazide diuretics, PPIs, and asthma medications. Magnesium is a co-factor in over 300 enzymes, maintains normal muscle and nerve functions, and is crucial for bone, brain, and heart health. Treatment with magnesium can help relieve headaches, brain fog, muscle twitches and cramps, improve glucose management, alter/improve moods, improve fatigue and muscle weakness, and helps with anxiety and depression. Magnesium stabilizes ATP, signals methylation, and is important for de-toxification supporting glutathione production.
7. ***Supplementation with Omega-3 fatty acids (7 to 8 gms/day) plus alpha lipoic acid (600 mg/day) slows functional and cognitive decline in Alzheimer’s disease patients. Also, a study in the Journal of Alz. Disease by Nolan, et. al. In June 2018 demonstrated that supplementing with carotenoids plus fish oil improved memory, vision and mood.
8. ***Hericium erinaceus, commonly called “Lion’s Mane” mushrooms should be a staple in the prevention and treatment of neurological illnesses such as Alzheimer’s dementia and Parkinson’s disease. “Hericenones” are isolated compounds found to be able to cross the blood-brain barrier and stimulate the production of Nerve Growth Factor (NGF). NGF is necessary for brain cells to function and to heal. They also lower cell damage caused by beta amyloid peptide and lessen the apoptosis of neurons and other brain cells. “Dilinoleoyl-phosphatidylethanolamine” (DLPE) is another isolated compound that protects brain cells from oxidative damage in a variety of neurodegenerative diseases. A combined product of hericenones plus DLPE called “amyloban” proved superior to the prescription drug “Donepezil” in memory test of Alzheimer’s disease patients. Additionally, a study of women with mood disorders demonstrated improved standardized tests for depression and anxiety after 4 weeks of using Lion’s mane mushrooms. In a small study, patients with schizophrenia also showed improvement on standardized tests. Healthy subjects reported an improved sense of well-being, energy and mood after using Lion’s mane extract for 2 months. You can find safe, natural and effective Lion’s mane supplements in the form of a pill, liquid extract or powder to add to smoothies or cook with. One source to consider is mushroommatrix.com. Also, check-out writings and YouTube presentations by Paul Stammets.
9. ***Culinary doses of Sage, Rosemary and Curcumin may preserve memories and alleviate symptoms of dementia. A) SAGE: Salvia officinalis extract: 60 drops/day improved cognitive function and decreased agitation in one small study. In another study, 333 mg/day of sage extract improved thinking, recall and attention. B) ROSEMARY: 750 mg of dried rosemary leaf powder daily improved cognitive function in a small study. The aroma of rosemary’s essential oil improved concentration and cognitive testing performance. C) CURCUMIN prepared from the root of the turmeric plant: 2-8 GMS/day helps to reduce beta-amyloid plaques by pulling apart fibrils and stimulating macrophages to eat toxic accumulations. It is also a potent anti-inflammatory and anti-oxidative agent. There is a combination product called “Sage Memories” that includes 25 mg of lithium, 500 mg of niacinamide and 650 mg of extracts of sage, rosemary and curcumin in 4 capsules/day. This can be obtained on the internet at biotechpharmacal.com or www.tahomadispensary.com. This can be safely used for prevention and for treatment of early Alzheimer’s dementia.
10. Many people are functionally vitamin B12 deficient. Vitamin B12 is critical for hormone functioning, brain metabolism and in the energy cycle for every cell. With aging, vitamin B12 is poorly absorbed due to a lack of both hydrochloric acid and intrinsic factor in the stomach. Hydrochloric acid in the stomach is needed to release vitamin B12 from foods such as red meat, fish and dairy products, and “intrinsic factor” from the stomach is needed to absorb it. Acid suppressing medications and age impair the release and absorption of vitamin B12, which must be consumed on a daily basis, because it is water soluble, and eliminated if not utilized. Most people over age 40 are vitamin B12 deficient. {Use of Proton Pump Inhibitors and Histamine type 2 Blockers for acid reflux and for gastritis can also create a vitamin B12 deficiency.} An imbalance in the gut flora can also inhibit absorption. The medication Metformin, which is commonly used to manage type 2 diabetes, interferes with the absorption of vitamin B12. {A combination of these medications can make the situation even more likely and worse.} On a complete blood count (CBC) a mean corpuscular volume  (MCV)  >90 suggests a functional vitamin B12 and/or folate deficiency. NOTE: A serum vitamin B12 level can be in the normal range or high even while intracellular levels and especially central nervous system levels are low!!  Methylcobalamin is the most biologically active form of vitamin B12 that can cross the blood brain barrier without biotransformation to nourish the brain. Additionally, its methy group stimulates the neurotransmitter serotonin’s creation to enhance moods and it also protect against toxins damaging the brain. Methylcobalamin protects against glutamate-induced “excitotoxic” neurologic damage. Acute low vitamin B12 levels can manifest as mood changes: lack of motivation and feelings of apathy; mental fogginess, memory impairment, muscle weakness, and fatigue. Chronic low vitamin B12 levels can cause nerve damage, dementia and psychiatric problems that can mimic mental illness such as bipolar disorder, severe depression, paranoia or schizophrenia. Only about 12% of a dose of the cheaper, manufactured form of vitamin B12 called cyanocobalamin  is converted to the active form, and, the liver must detoxify the cyanide molecule binding it.  I restrict using cyanocobalamin to monthly injections to avoid accumulation of the cyanide moiety.  A case can be made for monthly up to weekly injections of Methylcobalamin. for anyone over 70 years old, and certainly sublingual vitamin B12 lozanges should be taken daily.  Additionally, you would need to take oral Folate 1 mg daily (NOT the oxidized synthetic form of folate known as “folic acid”). or the methylcobalamin injections can be compounded with 400 mcg Folate. The Folate may be part of a multivitamin/mineral complex.  Note: sunlight will destroy the natural forms of Folate: methylfolate, and folinic acid. Good food sources of Folate include: spinach and other deep green leafy vegetables, brewer’s yeast, beans (especially lima beans), cantaloupe, watermelon, wheat germ, and liver (from organically raised animals). Folate insufficiency and deficiency is a risk factor for skin cancer, colon, breast and other cancers.
11. The development of cognitive decline may be linked to oxidative damage. The antioxidant properties of mixed tocopherols and tocotrienols might be helpful in reducing oxidative damage in the brain. Foods that contain forms of vitamin E include: wheat bran, oat oil, coconut oil, grapeseed oil, meats, eggs, avocados, carrots, cauliflower, blueberries, almonds, and grapes. The best known source is palm oil, rice bran and oats. 100 to 200 mg daily as a supplement up to 1000 mg daily is safe. It is best absorbed when taken with food and separated in time by several hours from taking mixed tocopherol vitamin E.
12. Consider using Niacinamide (vitamin B3) 1 gm three times per day. Anticipate symptom improvement within 3 to 4 weeks. This treatment is very safe and only occasionally a person may experience nausea. The nausea usually resolves by reducing the dose to 500 mg three times per day. (Incidentally, niacinamide has been used along with vitamin C to help treat schizophrenia.)
13. Consider using lithium orotate or lithium aspartate 10 mg to 20 mg daily. Low dose lithium can remove aluminum from tissues for excretion from the body. It is speculated that aluminum toxicity is a factor in the development of Alzheimer’s dementia. Also, it can stimulate the growth of brain grey matter. (In an observational study, people with bi-polar disorder using lithium had half the risk of developing dementia as the group not using lithium.)  When using lithium, take flaxseed oil 1 tbs 1-3x/day plus mixed tocopherol Vitamin E 400 to 800 IU per day in order to avoid any possible toxicity. Naturally occurring mineral water containing lithium salts (lithium carbonate and lithium chloride) known as “Lithia water” has many testimonials to its health benefits. Some research demonstrates neuro-protective benefits of lithia water {Stroke 2003;34:1287-92.} Drinking lithia water improves mood and cognition {Biological Trace Element Research 1994;40:89-101.} Communities with naturally occurring lithia waters have lower suicide rates, mental hospital admissions, incidence of crime, and arrests related to drug addiction {British J of Psychiatry 2009;194:464-5.} Long term lithia water consumption is associated with increased life expectancy {Eur J Nutrition 2011 Feb;50(5):387-9.}
14. Berberine reduces the damage caused by beta-amyloid and reduces cognitive impairment. It also inhibits cholinesterase (similar to Aricept). Consider using 500 mg three times per day. (A high quality product can be obtained from tahomadispensary.com). Some people experience GI discomfort for the first 4 weeks of treatment including diarrhea, flatulence, constipation and crampy pains. Reducing the dose to 300 mg three times per day and then gradually increasing it back to 500 mg three times per day can help resolve these side effects. Also, because berberine isn’t well absorbed from the GI tract, because it isn’t very soluble in water due to P-glycoprotein, taking it along with milk thistle, which is a natural inhibitor of P-glycoprotein, approx. 100 mg (S. marianum containing 60% flavolignans) improves absorption. (Incidentally, milk thistle is good for protecting the liver. Milk thistle extract 600-800 mg/day can benefit any associated liver disease. A product called “European Milk Thistle” from www.LifeExtension.com combines milk thistle extract with phosphatidylcholine to improve absorption of the important component “silybin” which doesn’t dissolve well in water.)
15. SAFFRON (the spice):  a minimum of 15 mg twice per day: after a 16 week trial it proved to be safe and effective for mild to moderate dementia and was equally effective as Aricept for improving cognitive function scores.
16. A molecule found in Green Tea, epigallocatechin-3-gallate (EGCG), prevents the mis-folding of specific brain proteins:  the metal-associated-amyloid-aggregates associated with Alzheimer’s disease. It also broke down existing aggregate structures in the proteins that contained the metals: copper, iron and zinc.
17. Compounds in Cinnamon (cinnamaldehyde and epicatechin) reduce the aggregation of tau protein and beta-amyloid.  A derivative of cinnamon called MHCP (methylhydroxychalcone polymer) can also help prevent Type 2 diabetes as well as treat Type 1 and Type 2 diabetes. Any whole cinnamon product can be used if you are prepared to extract the desired water soluble fraction from the fat soluble fraction (which may be carcinogenic and genotoxic in large concentrations.) Anyone planning to use a 1 teaspoon of whole cinnamon daily should first boil it in water and then pour off the watery solution through a cheese cloth for use, discarding the solid remainder which contains the fat soluble fraction. OR, purchase MHCP from a health food store. A brand name product to consider is “Insulife” which contains the equivalent of 1 tsp of whole cinnamon along with chromium and other nutrients to be taken once per day in order to decrease insulin resistance. Choosing the right type of whole cinnamon IS important. Studies show that using Cinnamomum cassia or C. aromaticum  (Chinese cinnamon) is much preferred to the more common Cinnamomum zeylanicum (Ceylon or sweet cinnamon). The effective dose is 120 mg/d of the cassia extract.
18. Carnosine can help to reduce oxidative stress and prevent oxidative damage that can cause cellular dysfunction resulting in memory loss. Carnosine lowers blood sugar and insulin levels, blocks oxidative and glycation-induced tissue damage, enhances cardiac muscle function and the quality of life in patients with CHF, and improves cognitive function.   The dose is 500 mg twice daily.
19. ***Resveratrol can counteract the acetylation of tau proteins. Acetylation causes the tau proteins to collect and stick together leading to the development of neurofibrillary tangles commonly found in the brains of Alzheimer’s disease patients. Resveratrol can also activate the SIRT1 proteins and reduce inflammation and the activity of cell-damaging reactive oxygen species. Resveratrol can buffer damage by accumulated glutamate and quiet glial cell activation. It can benefit Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). Resveratrol has no specific dose guidelines—10 mg is effective and high doses are safe. Although a high content is found in red grapes, the best source for Resveratrol is eating boiled peanuts.
20. ***Pyrroloquinoline quinone (PQQ) can help to protect memory and cognition, promotes brain cell survival, and stimulates the formation of new mitochondria and improves the function of existing mitochondria. It also improves gait disturbance seen with Parkinson’s disease. It decreases brain inflammation and lowers the inflammatory markers C-reactive protein and interleukin-6. It stimulates the production of nerve growth factor that supports neurons by maintaining their plasticity and leads to formation of new nerve cells. It also protects nerve stem and progenitor cells from oxidative damage. Using PQQ reduced the size of brain damage associated with an ischemic stroke, even when administered after the stroke, and improved neurobehavioral scores. It reduces excessive glutamate stimulation of brain cells, excitotoxicity, which triggers apoptosis and is a factor in the development of neurodegenerative disorders, stroke and schizophrenia. People with diabetes are 60% more likely to develop dementia. PQQ helps protect the brain against damage caused by high blood sugar. PQQ also reversed the toxicity of beta amyloid proteins and alpha-synuclein, reducing oxidative damage caused by these malformed proteins. Recommended supplementation is 20 mg daily. It is best when combined with CoQ10 100 mg daily. Products are available from LifeExtension.com.
21. Vinpocetine (a periwinkle extract): It is beneficial for alertness, concentration, memory support and cognitive function. It improves circulation, increases levels of ATP/cellular energy in neurons, improves the brain’s utilization of glucose and oxygen, (in animal studies) accelerates the rate of learning by 40%, improves short-term memory, and increases the length of time that short term memory is retained. Additionally, it improves the circulation to the eyes, improving visual acuity; improves impaired hearing, vertigo and tinnitus; and, improves red blood cell flexibility that may help to prevent strokes. It activates the noradrenaline nerve cluster, the locus coeruleus, in the reticular activating system to improve alertness. It has a very low side-effect profile. The usual dose is 10 mg to 30 mg daily—typically 10 mg three times per day has been found to be most beneficial. While benefits can be noted  after only a few days of therapy, maximum benefit is seen when used for 3 months. High quality, pharmaceutical grade vinpocetine from Europe (rather than from China) can be obtained from TargetedNutrients.com.
22. Another proprietary product from TargetedNutrients.com is called “AMG” which combines the brain nutrients adenosine triphosphate, methylcobalamin and glucoronolactone.  Adenosine Triphosphate (ATP) is the primary source of cellular energy which the brain requires in prodigious amounts daily, more than any other organ. Additionally, ATP is required to accompany neurotransmitters for them to be functional. The glial cells (neuron regulators) use ATP to communicate. With inadequate ATP you will feel irritable, tired and depressed, have poor mental functioning, and it will seem like the burdens of stress are causing significant wear and tear. Methylcobalamin is the most biologically active form of vitamin B12 that can cross the blood brain barrier without biotransformation to nourish the brain. Additionally, its methy group stimulates the neurotransmitter serotonin’s creation to enhance moods and it also protect against toxins damaging the brain. Acute low vitamin B12 levels can manifest as mood changes: lack of motivation and feelings of apathy; mental fogginess, memory impairment, muscle weakness, and fatigue. Chronic low vitamin B12 levels can cause nerve damage, dementia and psychiatric problems that can mimic mental illness such as bipolar disorder, severe depression, paranoia or schizophrenia. Hydrochloric acid in the stomach is needed to release vitamin B12 from foods such as red meat, fish and dairy products, and “intrinsic factor” from the stomach is needed to absorb it. Acid suppressing medications and age impair the release and absorption of vitamin B12, which must be consumed on a daily basis, because it is water soluble, and eliminated if not utilized. Most people over age 40 are vitamin B12 deficient. Only about 12% of a dose of the cheaper, manufactured form of vitamin B12 called cyanocobalamin  is converted to the active form, and, the liver must detoxify the cyanide molecule binding it. Glucoronolactone promotes brain energy, enhances mental clarity and induces a mild euphoria. It reduces sleepiness, increases focus, lightens the mood, quickens reaction time, enhances stamina, and produces a sense of well-being. It is produced in the liver from glucose, and can be found in a variety of plant gums and other natural sources, including wine.
23. The amino acid Taurine  protects the brain from toxic chemicals, stimulates new brain cell formation, prevents brain cell death following a stroke helping to preserve neurological function, decreases the effects of toxic beta amyloid proteins, and improves blood sugar control. Additionally, studies suggest that Taurine can defend liver cells against free radicals and toxins, helping to reduce oxidative stress-induced liver injury that helps both alcohol induced liver disease and NAFLD.  Patients with chronic hepatitis taking 2 gm taurine three times daily for 3 months decreased serum markers of liver damage, markers of oxidative stress, and hyperlipidemia. A typical dose is 3 to 6 gm daily.
24. Quercetin is a plant flavonoid that can help protect the body and mind against pathological effects of pesticide exposure. Quercetin protects brain cells from excitotoxicity and reduces toxicity of beta amyloid proteins that accumulate. Glutathione is activated which protects against free-radicals. Quercetin increases brain expression of protective paraoxonase 2 which scavenges free radicals that damage mitochondrial membranes and cause them to lose their electrical potential. Quercetin limits brain cell death that produces neurodegenerative diseases. The typical dose is 150 mg to 400 mg/d. A combination of quercetin with resveratrol provides complimentary health benefits. Quercetin inhibits pesticide damage by preserving energy, fatty acid, and sex hormone metabolism, inhibiting oxidative stress, protecting against DNA damage, and preserving kidney and liver function.  NOTE: Pesticides are found in our food, air and water. Systemic pesticides mixed in with fertilizer and absorbed by plants through their vascular systems are impossible for consumers to wash off. Pesticides can result in conditions ranging from learning disabilities to Parkinson’s disease to cancers. Organophosphate pesticides lead to microtubule derangements and tau hyperphosphorylation—a hallmark of Alzheimer’s disease. Serum levels of DDE (a metabolite of DDT) were 3.8 fold higher in patients with Alzheimer’s disease. Similarly, 76% of patients with Parkinson’s disease (compared to 40% without disease) had detectable levels of the pesticide beta-hexachlorocyclohexane (beta-HCH).
25. CAT’S CLAW (Uncaria tomentosa): is from the Amazon rain forest with antioxidant and anti-inflammatory oxidole alkaloids in the bark which stimulate the immune system and polyphenols that impact neuroinflammation: Plaque-Tangles-Inflammation (PTI) for memory improvement {which seems to support the amyloid-beta hypothesis of AD: where plaques come first, then tangles, then inflammation, then microglia release cytokines which cause neuronal impairment and death.) Cat’s Claw is a natural inhibitor for the degeneration process. It decreases neuro-inflammation, decreases astrocytes and microglia, and improves memory. Focus and concentration are improved. {Alan Snow, PhD, “Memory Improvement with Cat’s Claw”, at the A4M conference 12/13/2018.}

                          ADDITIONAL CONSIDERATIONS

Studies in China have demonstrated efficacy for using intranasal near infrared red (NIR) LED light (810 nm pulsed at 10 Hz). The LED is inserted into the nostril and clipped to the nasal ala and used for 25 to 30 minutes per day, up to twice daily in patients with severe symptoms. There are no adverse side-effects. The Vielight 810 infrared LED (cost about $500) has deeper brain penetration than the 633 red (Qi-light—cost about $300). Both light systems have demonstrated improved cognitive function in patients with Alzheimer’s dementia, Parkinson’s disease, and after cerebral infarctions (strokes) and traumatic brain injury. Reportedly NIR can also help with insomnia, migraine headaches, mild cognitive decline, nasal allergies and acne. Depending on the severity of symptoms, results can be noticed from 10 days to several months. The light can destroy beta-amyloid plaques in Alzheimer’s disease and  lower serum 3-cholecystokinin-octapeptide levels in Parkinson’s disease.

          Near infra-red light acts like the red light spectrum for optimizing health. For Example:  MACULAR DEGENERATION:  Exposure to ultraviolet solar rays accelerates age-related visual loss. Wearing UV protective sunglasses outdoors can minimize this damage. Our round-the-clock use of smartphones and computers exposes our eyes to unnaturally high amounts of blue light which can damage the retina and other parts of the eye. Chronic exposure to blue light is associated with increased risk of developing age-related macular degeneration. Retinal damage is irreversible, so early and powerful protection is our only hope. Supplementing with multivitamins and xanthophyll carotenoids that include lutein, zeaxanthin, and meso-zeaxanthin can help to mitigate this loss. {Lancet. 2012;379(9827):1728-38.} They shield light sensing cells from photochemical damage and slow inflammatory reactions that aggravate light-induced damage, and can prevent development of blood vessel overgrowth that produces “wet” macular degeneration, (the leading cause of age-related blindness.) “MacuGuard” is available from www.LifeExtension.com.

Telomerase maintains telomere length; promotes lifespan; protects mitochondria from oxidative stress, and increases the survival of highly active cells, like neurons. The loss of telomerase can be slowed by using Omega-3 fatty acids, resveratrol, Vitamin D3, and curcumin, and by decreasing homocysteine levels.

According to literature and studies sponsored by the manufacturer, so please consider that there may be an economic influence, the only supplement found (so far) that increases telomerase is a proprietary product called “TA-65” from www.tasciences.com. It is derived from Astragalus membranaceus or “Huang Qi”. Astragalus is a nutritional supplement that has been shown to support immune health, and to help reverse some of the signs of cellular aging. It is a foundational herb in Traditional Chinese Medicine traditionally used to support energy levels and immune function. It contains Astragalosides (antioxidants), which support the integrity of the respiratory tract. The extract is predominantly the molecule cycloastragenol. In addition, the polysaccharides found in Astragalus are known for their immune supporting properties. Astragalus herb also supports deep immune functions by promoting normal levels of specific immune cells, and aids in their function. Astragalus appears especially effective when immune function is stressed by environmental or endogenous challenges.

Increasing telomerase prevents the constant erosion of our telomeres, and our lives, increasing our life span and our health span. Reportedly, TA-65 helps to protect the brain and the memory associated with short telomeres; protects the cardiovascular system by improving plaque stability; and, it is antiviral. It helps to improve glucose tolerance and decrease insulin, increases bone mineral density, reduces inflammation, decreases cytotoxic killer cells, improves BP, and reduces homocysteine levels. It reportedly improves the Metabolic Syndrome in 12 weeks. It also increases the function of the retinal pigment epithelium, thus, helping with macular degeneration. It decreases the number of senescent T-cells, and increases the number of naïve T-cells.

Additional things that can help to stabilize and/or increase telomere length include: the Mediterranean Diet, meditation and yoga, aerobic exercise, improved air pollution, decreasing ionizing radiation exposures, and, decreasing oxidative stress. (Older people are more vulnerable to radiation exposure because of telomere loss.)

Increasing telomerase will reportedly NOT increase cancers. (However, please note that cancers have an elevated amount of telomerase activity which helps to explain their immortality.) Short telomeres will increase the risk of cancers. Anecdotal reports say TA-65 has high bioavailability; improves presbyopic (age related decline in) near-vision, increases energy, increases attention and memory, improves peripheral neuropathy, increases aerobic capacity, decreases viral infections, decreases basal cell skin cancers, improves skin elasticity and coloration. Telomere length can be checked at UCLA Immunology Testing for about $350 with results in 10-14 days. There is no difference in the bioavailability of capsules vs. tablets. A standard dose is a 250 mg cap 1-2x/day. It should be taken on an empty stomach.

A 12 month study of 97 people showed the placebo group lost telomere length while the group taking 250 units of TA-65MD daily significantly increased the length of their telomeres. {Rejuvenation Research; 2016;19(6):478-484, and, Pinglira, et. al., Aging and Disease; 2017 Dec;8(6):868-886.} It helped prevent cognitive decline, decrease oxidative stress, stabilize and/or activate telomerase, improve macular degeneration, and, elongate telomeres which results in an increased lifespan. In a study with people infected with cytomegalo-inclusion virus (CMV) they had 2 times the increased degeneration of their telomeres vs. CMV negative people. Treatment with TA-65 increased their telomere length.

          BLUE (LED) LIGHT PROTECTION:  {According to a presentation by Dave Asprey called: “A Systems Approach to Metabolic Aging Through the Eyes,” at the A4M  International Congress in Las Vegas, 15 Dec 2018:}  Like food, light can be both a both a nutrient and a drug. Light exposure changes our biology and affects our cognitive function. The blue spectrum of light is like the high-fructose corn syrup of vision. Exposure to blue light increases insulin resistance, increases body fat weight, increase the incidence of CVD and strokes, and disturbs sleep. The dominant light spectrum in LED lights is blue. LEDs have economically replaced most incandescent light bulbs, and they dominate TV and computer screens and cell phone screens. Blue light hurts the eyes, slows mitochondrial function and decreases sleep quality. Blue light adversely affects the circadian rhythms, reduces melatonin release, decreases mitochondrial growth, increases depression and seasonal affective disorder (SAD), increases cancer risks, and increases anxiety.The red spectrum of light upgrade brain functions, energizes cells, and slows aging. Mr. Asprey advise everyone to wear orange colored glasses indoors to block out excessive blue light exposure. It will decrease eye stress, increase energy, improve blood sugar regulation, and improve sleep. The main effect of blue light is upon the mitochondria. It produces aging: increasing free radicals, damaging mitochondrial DNA, causes retinal ganglion cells melanopsin receptors to self-destruct—resulting in an increase in macular degeneration. Use red light bulbs after sunset, especially if you need to be up and functioning late at night, in order to protect your eyes, and help you to eventually sleep. Red lights also help to quickly resolve jet lag. Additionally, supplementing with bilberry extract, lutein, and astaxanthin in Krill Oil can also help to protect your eyes. Also, use red light strips or a red light bulb in your office to improve the ratio of blue to red light wavelengths. You will notice a decrease in your pain and inflammation, improved collagen density in your skin with decreased skin roughness, a reversal of photo-aging of your skin, increased nitric oxide production, and a rescue of neurons from apoptosis.

METFORMIN is a prescription medication with neuro-protectant properties. It activates AMPK: a cellular energy regulator. It reduces levels of an enzyme that generates beta-amyloid proteins; decreases the harmful effect of beta-amyloid on brain cell function; reduces levels of alpha-synuclein that causes damage in Parkinson’s disease; prevents the loss of dopamine-producing brain cells and improves motor coordination. In a 2016 study {J. Alzheimers Dis. 51(2):501-14}, older adults with mild cognitive impairment using Metformin 1,000 mg twice daily for 12 months had improved memory recall.

15 mg Nicotine patches, used with patients for 6 months who had early stages of Alzheimer’s disease, had neuroprotective effects with improvements in attention, memory and psychomotor speed, with excellent safety and tolerability, compared with using a placebo. While the many chemicals in tobacco (including anabasine, nornicotine, anatabine, cotinine, myosmine, and acetaldehyde) are highly addictive, pure nicotine is generally not addictive.

THIS IS VERY CONTROVERSIAL:  Based upon an hypothesis that autism, Alzheimer’s disease, Parkinson’s disease and other degenerative diseases of the brain are aggravated by mercury toxicity (found in thimerosol, formerly used in vaccinations as a preservative, and  older dental amalgams), a protocol has been developed by Dietrich Klinghardt, MD. He first recommends avoiding allergens and toxic foods in the diet such as gluten, dairy, and processed foods. Then, he adds sublingual vitamin B12 and folate to restore methylation which protects cells from toxins, including mercury. Most people’s immune systems can detoxify some mercury. However, 20% of the population has a genetic methylation defect which compromises their ability to detoxify mercury. He also recommends supplements to restore cellular metabolism {discussed in the book “The Puzzle of Autism” by Dr. Amy Yasko}. Finally, he adds transdermal-2,3-dimercapto-1-propanesulfonic acid (TD-DMPS) to chelate and eliminate mercury (and lead) from the central nervous system. {NOTE: if using TD-DMPS, take a balanced mineral supplement to replenish nutritional metals like zinc, copper, and molybdenum. It can be obtained from College Pharmacy at 866-828-8203.}

[Also, see my handout on “Toxin Management”]

A Potential New Test For AD:  The researchers analyzed the participants’ blood for a protein called neurofilament light chain that is released when brain cells disintegrate. The people with a gene for early Alzheimer disease had higher protein levels when first tested. Moreover, their levels of neurofilament rose steadily over time. The other participants had steady low levels of the protein.

Differences in the protein were detectable sixteen years before the expected onset of symptoms. Rapid increases in neurofilament light chain levels were also linked to brain shrinkage visible on scans. This preliminary test is not yet ready for clinical use, but the authors hope that it will someday allow doctor to diagnose Alzheimer disease when intervention might still make a difference.  {Preische et al, Nature Medicine, Jan. 21, 2019;  reported in The People’s Pharmacy, 1/25/2019.}

Optical Coherence Tomography Angiography (OCTA)– a tool for the early detection of AD:  {Reported by Yoon, et. al. Opthalmology Retina, on line March 11, 2019} Researchers at Duke Eye Center reported that by using OCTA imaging people with AD had fewer fine blood vessels and one layer of the retina thinner than people with mild cognitive impairment and with healthy cognitive functioning. This replicates a study done at the Goldschleger Eye Institute at Sheba Medical center in Israel. It is an early way to detect AD.

Dr. Chuck Wile is a supervising physician at Cheng Integrative Health Center/Doctor’s Weight Loss Center, Columbia, SC.  Dr. Wile served in the US Air Force Medical corp and is a retired Air Force Colonel.

          It is exhausting and frustrating when you have difficulty falling asleep or staying asleep. Sleep deprivation is not the same as insomnia. In sleep deprivation one has an adequate ability to fall asleep yet an inadequate opportunity to sleep. In insomnia, one has an adequate opportunity to sleep yet an inadequate ability to sleep with sufficient quantity and/or quality of sleep. Insomnia is defined as an inability to have adequate sleep 3 or more times per week for 3 months, without co-existing mental nor physical disorder that causes sleep impairment resulting in dissatisfaction with the quality and/or quantity of sleep AND daytime impairment or distress. 1/9 Americans meet these criteria with equates to over 40 million people. Women are twice as likely as men to suffer with insomnia. African Americans and Hispanic people experience insomnia more than Caucasians. About 2/3 people experience sleep impairment 1 night/week. There is an hereditary aspect to the problem 28 to 45 percent of the time (depending on the study). >$30 Billion per year is spent on medications for sleep in the USA.

          Our sleep-deprivation is caused by many socially engineered factors. Too much light, especially blue wavelength light from LEDs; use of alarm clocks because we have to punch time cards for work; room temperatures too high; the use of caffeine, tobacco and alcohol. Also, internal factors such as aging and worrying have a significant influence. Our over-active sympathetic nervous system  causes a release of the adrenal hormones Epinephrine and Norepinephrine that support a flight-flight-freeze response to threats to our survival {both real and imagined}, which increases our heart rate and blood pressure and keeps us alert). Also, with the release of Cortisol from the adrenals (which supports our ability to sustain stress) there is an additional stimulus to remain alert. These hormones also cause an increased metabolic rate with consequent increased core body temperature; stimulation of the thalamus gate-keeper to remain open for sensory input for processing by the cerebral cortex,; and, for the emotion generating area of the limbic system (the amygdala) plus the memory recollection center (the hippocampus) to remain active. The result is ALERTNESS thwarting sleep. PLUS, our sleep-procrastination is a problem. Due to our fears of missing out we amuse ourselves with late-evening TV and digital entertainments which can interfere with achieving a good sleep pattern.

          A Key Principal for managing insomnia is find the cause then treat the cause.

CAUSES OF INSOMNIA:   1) Acute Insomnia: Transient and short-term cause of insomnia include: jet lag; shift work; high altitude;  poor sleep environment: uncomfortable room temperature—too hot or too cold; excessive or unpleasant noise; situational stresses: illness or death of a loved one, unemployment, separation or divorce, exam prep; acute medical/surgical illness or hospitalization; use of stimulants such as caffeine, amphetamines, tobacco, cocaine, MDMA, methylphenidate, modafinil, and phentermine; withdrawal from alcohol, sedatives, stimulants; and, excessive mental or physical stimulation in the hours before bedtime. 2) Chronic Insomnia: is typically linked to psychiatric or medical conditions including: a) Common Psychiatric Conditions: anxiety with intruding ruminations, depression (which can also trigger hypersomnolence), mania (bipolar disorder), PTSD and schizophrenia. b) Chronic Medical Conditions:  pain, obstructive sleep apnea, restless leg syndrome and periodic leg movements, menopause or andropause, coronary artery disease with nocturnal dyspnea or angina, GERD, degenerative neurological disorders such as Parkinson’s disease and Alzheimer’s disease with dementia with nocturnal agitation, brain tumors, strokes, brain trauma, circadian rhythm disorder, medications such as stimulants for ADHD and narcolepsy, alcohol and drug users, nocturnal asthma and pregnancy.

          ***A thorough history and physical examination with diagnostic testing, especially considering a sleep lab study, is very important in order to make an appropriate diagnosis and precision treatment recommendations. Suggestions about supplements and medicinal essences are intended for educational purposes and are not prescriptions for managing your health concerns. Be sure to inform your physician of any supplements that you are taking in order to evaluate any possible conflicts with prescription medications.

DEVELOP STRICT SLEEP HYGIENE HABITS:   

           Here are some suggestions to try before considering a prescription medication. AVOID CAFFEINE (coffee, tea, caffeinated sodas), NICOTINE, and other  Stimulants such as chocolate, Sudafed or Afrin nasal spray, or, if that is too much of a challenge, then don’t use any for at least 6 hours before bedtime. AVOID HEAVY MEALS and  ALCOHOL before sleep. AVOID SUGARY OR SPICY FOODS 4 to 6 hours before bedtime. However, if awakening during the night is a problem, then try eating a light snack  of good fats (not carbs) before bedtime. A couple almonds, a few spoons of yogurt, a couple teaspoons of almond butter or peanut butter on a cracker can frequently do the trick. Drinking warm milk and/or eating a banana may help you get ready for bed. The amino acid tryptophan in these foods can help you to sleep.

           Allow enough time for sleep. Most people need 7 to 9 hours of sleep each night. Fix a bedtime and an awakening time. Avoid napping during the day. And especially in the evening.  Arrange a sleep environment that is very dark, comfortable, quiet and cool {set the thermostat for 65 degrees in the bedroom} to facilitate falling asleep quickly and staying asleep. Use comfortable bedding and keep the room well ventilated. Block out all distracting noise. Consider a white noise generator. Reserve the bed for sleep and sex. Don’t use the bed as an office, work or recreation space. Let your body learn to associate the bed with sleeping. AVOID TV in the bedroom. Don’t take your worries to bed. Worrying is a prayer for that which you don’t wish to happen. Instead, practice relaxation techniques before going to bed. Yoga, deep breathing, visualizations, progressive muscle relaxation can all help relieve anxiety and muscle tension. Establish a pre-sleep ritual such as a warm bath (especially using Epsom salts—5 cups: the magnesium will relax your muscles), or a few minutes of reading or praying. Get into your favorite sleeping position. If you don’t fall asleep within 15-30 minutes, get up and go into another room and read until you get sleepy. Consider elevating the foot of your bed a few inches to increase circulation to your brain.  Regular AEROBIC EXERCISE is the best way to improve your sleep and modify pain. However, don’t do heavy exercise within 3 hours before bedtime because it raises your core body temperature and it takes several hours to return your core body temperature to normal. The best time for aerobic exercising is in the morning.

          COGNITIVE-BEHAVORAL THERAPY (CBT):  is the most effective psychological intervention to help with insomnia. It consists of a comprehensive program for educating and modifying behaviors.  The most effective use of CBT combines several of these methods. Rather than just relieving symptoms, it addresses the underlying cause(s) of insomnia. 1) Sleep Education: understanding the sleep cycles and learning how beliefs, behaviors and outside factors affect sleep. 2) Cognitive Control and Psychotherapy: helps control or eliminate negative thoughts and worries that keep one awake. It may help to eliminate worrisome beliefs about sleep such as a single restless night will make one sick. 3) Sleep Restriction: limiting the amount of time spent in bed rather than lying in bed awake which can become a habit leading to poor sleep. 4) Remaining Passively Awake: avoiding any effort to fall asleep. Worrying that one can’t sleep can keep one awake. 5) Stimulus Control Therapy: helps remove factors that condition the mind to resist sleep. Eg. One is coached to use the bed only for sleep and sex; and, to leave the bedroom if unable to sleep within 15 minutes. 6) Sleep Hygiene: changing basic lifestyle habits that can influence sleep: eg. Smoking or drinking caffeine late in the day; drinking a “nightcap” of alcohol; not regularly exercising; avoid napping; winding-down 2 hours before sleep time. 7) Relaxation Training: learning to calm the mind and body: eg. meditation, progressive muscle relaxation and hypnosis. 8) Biofeedback Training: learning to influence heart rate, skin temperature, muscle tension and skin electrical conduction. 9) Sleep Diary: keeping a detailed record of sleep patterns and influences for 2 weeks.

***This handout is intended for sharing information. If you consider trying any non-prescription supplements, please discuss this with me so that we can be sure that there will be no drug-supplement adverse interactions, and to be sure that your choice may be good for your overall care and health.

NON-PRESCRIPTION ALTERNATIVES:

          These products will support and enhance normal sleep mechanisms. Consider using: 1) VALERIAN ROOT capsules– 150 to 300 mg of a standard extract (0.8% valeric acid). Use 1 capsule at bedtime. Note: it smells like dirty gym socks, however, it is an ingredient in many proprietary sleep aids because it is effective. Don’t take with alcohol. 2)  MELATONIN–this comes as capsules, drops and lozenges. Women should start at 1 mg to 3 mg at bedtime and increase the dose every 4-7 days to 3 to 10 mg (may use up to 30 mg); Men should start at 3 mg to 5 mg and increase the dose every 4-7 days to 10 to 15 mg (may use up to 30 mg). 3) LAVENDER ESSENTIAL OIL (to be used topically)–add to a warm bath before bedtime or use as aromatherapy by placing some drops in an air  infuser or sprinkled on bed clothes/bedding. 4) The following TEAS (which can also be used as tinctures)  have been found to be helpful: a) lemon balm, b) passion flower, c) chamomile, d) catnip, e) hops, and/or rooibos. 5) Consider 5-hydroxy-tryptophan (5-HTP) 50 to 200 mg at bedtime. (CAUTION: Don’t use this if taking an anti-depressant.) 6) Consider GLYCINE 3 gm at bedtime. People fall asleep quicker, drop into delta-wave sleep faster, and report increased alertness with less daytime drowsiness, improved memory performance and less fatigue. 7) Consider using an aqueous extract derived from peeled rhizomes and roots of a non-mouldy Noble KAVA cultivar, limiting use to 250 mg kavalactones daily for acute or intermittent use. This will minimize a very rare hepatotoxicity risk. It is wise to limit its use to 6 weeks at a time and discontinue its use if there is persistent nausea, jaundice or weight loss. Then, get liver enzyme testing if there are any adverse findings. Used wisely, kava is a safe and effective aid for good sleep and to relieve moderate anxiety. 8) ZIZYPHUS seed (Suan Zao Ren; red date; the spiny jujube) is a Chinese herb beneficial for sleep, menopausal symptoms and anxiety. The dose is about 4.5 gm of the dry seed extract. 9) Magnesium L-Threonate 1,000 to 2,000 mg taken at bedtime can be very helpful with sleep management. This form of magnesium most easily crosses the blood-brain barrier with comprehensive benefits for sleep, anxiety and cognitive function. {It can be obtained from www.LifeExtension.com.}  However, magnesium oxide 400-800 mg, magnesium glycinate 400-500 mg, and magnesium asporatate 400-500 mg can also be very effective. 10) SAMe (s-adenosylmethionine) 800 to 1600 mg daily can benefit insomnia. It promotes the function of the enzyme that converts N-acetylserotonin to melatonin. 11) A proprietary blend called “SleepCycle” from www.puretango.com  has Xylaria Nigripes or “Wulinshen” as a main ingredient. It is a fungus containing GABA which improves sleep, shortening the time to fall asleep while helping to stay asleep longer, awakening refreshed without bothersome side effects. In fact, it has the pleasant side effect of improving cognitive function and a sense of well-being. Wulinshen also seems to have a cumulative effect, improving sleep quality with continued use. Additionally, melatonin, 5-HTP, L-Theanine plus a blend of valerian, passion flower, lemon balm, Dong quai, Hops, polygala and Jujube are added to the mixture for additional sleep benefits. The recommended dose is 2 capsules 30 minutes before bedtime. 12)  Lactium is a protein hydrosolate that can be used to relieve stress and promote restful sleep without side effects. Drinking warm milk has often been suggested for promoting sleep. Unfortunately, adults no longer have the enzymes of a newborn child which allows the release of this relaxing milk peptide. Lactium 150 mg taken 1 hour before bedtime improves sleep quality and reduces the time for sleep onset after 2 weeks of use. There is no awakening-sedation nor addiction with continued use.  Additionally, bioactive milk peptides activate brain cell receptors for neurotransmitters that reduce anxiety, such as GABA, serotonin and dopamine. Unlike benzodiazepine drugs, which activate the same receptors but which can become habit forming, bioactive milk peptides induce relaxation and sleep without the disinhibition side effects that are associated with risk taking behavior with such drugs. Studies demonstrate supplementing with bioactive milk products compared with placebo additionally improved digestion, cardiovascular function, cognitive function and social difficulty and reduced the stress response, including elevated blood pressure, heart rate ad cortisol levels. {Eur J Nutr. 2005;44(2):128-32.} 13) If your main problem is an active mind ruminating about things that happened during the day or things that need to happen in the future, then consider using the amino acid L-Theanine 200 mg: take 1 or 2 tabs once or twice per day. 14) Passion Flower rebalances signals in the endocannabinoid system that acts like a dimmer switch to tone down the amount of neurotransmitters that get released. It is useful to help you fall asleep and to stay asleep and to restore your sense of a calm focus. It is safe to use with children. It has been found to be useful helping to calm kids with Autism and with ADHD. A good proprietary product is called “Neural Balance” and is available from www.neural-balance.com.  15) “PharmaGABA” is a proprietary product that modifies the natural neurotransmitter gamma-amino-butyric acid (GABA) in a fermentation process with the bacteria  Lactobacillus hilgardii. It can help to improve sleep quality and decrease awakenings. Additionally, it can help to relieve anxiety. The dose is 50 mg up to 200 mg daily.

OVER-THE-COUNTER MEDICATIONS:

          Antihistamines are used for the side-effect of drowsiness. {Histamine is a key neurotransmitter for alertness.} Typically they contain Diphenhydramine (Benadryl, Sominex, Sleep-Eez, Nytol) or Doxylamine (Unisom). Prescription Hydroxyzine (Atarax or Vistaril) may also be used. Side-effects include: daytime drowsiness, cognitive impairment, dizziness, drunken movements, urinary hesitancy, blurred vision, dry mouth and dry throat. Caution should be exercised in people with glaucoma, benign prostatic hypertrophy and cardiac dysrhythmias. BE AWARE: studies show in people >60 yo who use anti-histamines regularly have impaired memory and an increased risk for developing dementia!!

PRESCRIPTION ALTERNATIVES: 

          Caution: People who are recovering from alcoholism should AVOID using benzodiazepines, Zalepion (Sonata), Zolpidem (Ambien) and Eszopiclone (Lunesta) for insomnia because there is strong evidence of relapse associated with their use. Trazodone up to 100 mg at bedtime is the preferred medication for recovering alcoholics and people with an addiction history.

          “Sleeping Pills” are a misnomer. There is a significant difference between natural sleep and drug-induced SEDATION. Sedation does NOT equal sleep. Sedatives anesthetize the cerebral cortex but do NOT produce the electrical activity that is associated with sleep nor any of the restorative benefits! They produce an imbalance in the chemicals which  signal the brain to achieves normal sleep, and they  significantly limit restorative NREM slow-wave sleep. Also, the unconscious  “limbo state” produced can result in abnormal sleep behaviors which range from the harmless and humorous to the disturbing and dangerous.

          Currently there are no prescription medications used for sleep that enhance health and longevity. They all have serious potential side-effects. Thus, I believe that the risks do NOT outweigh the benefits of their use which, when compared to using a placebo, only minimally shortening the time for falling asleep. Compare this to the real risks of DEATH and CANCERS. The risk of death increases with the quantity used. For example in a 2 ½ year long study: ½ to 18 pills/year increased the risk by 3.6 times and >132 pills/year increased the risk 5.3 times. The risk of death occurs because of increased infections {since there is no immune benefit which is gained with natural sleep}; increased fatal car crashes; increased falls and consequent hip fractures {especially in the elderly}; and, increased heart disease and strokes. Especially worrisome is the fact that >50% of all sleeping pill prescriptions are for the elderly.

           In addition to the above non-pharmacological suggestions, I may be willing to prescribe A SHORT COURSE of medication for people who suffer from chronic insomnia. REMEMBER: the first-line therapy is CBT-I. Medications are intended only for short-term use (7 to 10 days) and really should never exceed 4 weeks. Unfortunately, they are being used off-label for extended periods of time.

          Weighing the risks versus benefits is fundamental. ALL of the sedative-hypnotics carry the risks of dependency, withdrawal and rebound insomnia. These include both the benzodiazepines and non-benzodiazepine hypnotics, although the older medications such as benzodiazepines carry a higher risk.  Anti-depressants can also be used for their side-effect of drowsiness.

1. Benzodiazepines:  non-selectively target receptor sites in the brain that modulate the effects of the neurotransmitter gamma-aminobutyric acid (GABA). There are 3 categories: a) Long-acting: common brands include: Clonazepam (Klonopin), Diazepam (Valium), Flurazepam (half-life 70-90 hours) and Quazepam (Doral). b) Medium-acting: common brands include: Triazolam (Halcion), Lorazepam (Ativan) and Temazepam (Restoril). c) Short-acting: common brands include: Alprazolam (Xanax) and Oxazepam. These may be useful for air-travelers who want to reduce the effects of jet lag. Side-effects for all the benzodiazepines include allergic reactions, including angioedema of the face; increased depression; respiratory depression; residual daytime drowsiness with risks of motor vehicle accidents and falls in the elderly; memory loss—sleep walking, sleep eating, odd mood states: significantly aggravated by drinking alcohol and using antihistamines; and, urinary incontinence, especially in the elderly. NOTE: I am concerned about some recent studies that show a strong association between using benzodiazepines and significantly increased risks for dementia. When used for 3 to 6 months, the risk of developing Alzheimer’s disease is increased by 32%. When used for more than 6 months, the risk increases to 84%. Also, these drugs cross the placenta and enter breast milk and should be avoided in pregnancy and with nursing. First trimester use is associated with cleft lip in newborns. Interactions: although relatively safe if taken alone in an overdose, benzodiazepines are potentially very dangerous for respiratory depression in combination with drinking alcohol. Prolonged use creates physical dependence making discontinuation very problematic. Withdrawal symptoms: can last for 1 to 3 weeks after stopping the drug and include gastrointestinal distress, sweating, cardiac dysrhythmias, and, in severe cases, hallucinations and seizures. Rebound insomnia: paradoxically, benzodiazepines can cause nocturnal sleep disturbance and anxiety. There is a higher incidence of these problems especially when using the short-acting drugs.
2. Non-Benzodiazepine hypnotics: although they have been advertised as causing less physical dependency than benzodiazepines, they are still subject to abuse. a) Ambien: typically induces sedation for 7 to 8 hours. AMBIEN IS A MEMORY ERASER RATHER THAN A MEMORY ENGRAVER. The FDA has recommended lowering the previous typical dose of 10 mg to 5 mg or lower, particularly for women who eliminate the drug more slowly than men. Although very popular, PLEASE NOTE: I choose NOT to prescribe Ambien because I believe that it is a dangerous drug which significantly impairs the memory and cognitive function. b) Lunesta: mayslightly improve both sleep maintenance and daytime alertness. It is the first medication approved to be taken on a long-term basis. c) Sonata: is short-acting lasting about 4 hours and useful for inducing sleep or for people with the inability to return to sleep once awakened in the middle of the night. d) Rozerem: is the only non-controlled medication. It targets melatonin receptors. However, I believe that it is an irrational choice: why not use OTC melatonin instead of the expensive prescription? e) Belsomra (suvorexant): is a new orexin-receptor antagonist being heavily advertised with a cute cuddly cat logo. “It might help you nod off a few minutes faster or stay asleep slightly longer, but that small benefit comes with some big safety concerns, such as being too drowsy to drive the next day or feeling like you can’t move or talk.” {ConsumerReports.com, July 12, 2015.} The FDA initially rejected doses of 30 to 40 mg because they posed too great a risk for causing motor vehicle crashes. The dose of 10 mg is no better than using a placebo. Compare: using Ambien 10 mg: sedated 20 min faster than a placebo and remained unconscious 34 min longer than placebo, with Belsomra 20 mg: sedated 6 min faster than placebo and remained unconscious 16 min longer than placebo. Neither are impressive nor, in my opinion, worth the risk. ***All these medications have serious side-effects: including daytime drowsiness and abnormal sleep behaviors: sleep-walking, sleep-eating, sleep-driving and social interactions with NO MEMORY for what has transpired. They impair short-term memory and can cause hallucinations and sleep paralysis. All these effects are augmented when consuming alcohol.
3. Anti-Depressants: are used predominantly off-label for the side-effect of drowsiness. They are NOT addictive. They can be useful for modifying the pain threshold if pain is a confounding problem aggravating insomnia. They can be useful for concomitant depressive symptoms. They are my drug of choice for chronic insomnia. The preferred agents block serotonin 5 HT2A or 5 HT2C receptors and lack strong cholinergic activity such as: {for initial dosing} Trazodone (Desyrel) 50 mg, Doxepin (Sinequan) 25 mg and Mirtazapine (Remeron) 15 mg.  Although the older tricyclic agents have a higher side-effect profile because of their strong cholinergic activity, they can also be useful, such as Amitriptyline (Elavil), Nortriptaline (Pamelor), Imipramine (Tofranil) and Desipramine (Norpramin). However, I am not cavalier about using the anti-depressants because they change the architecture and function of the brain. {READ: “Anatomy of an Epidemic” by Robert Whitaker, published in 2010.}

***Also, consider reading “The Sleep Revolution” by Arianna Huffington. AND, “Why We Sleep” by Matthew Walker, PhD.

          ***THE GLYMPHATIC SYSTEM:  The more waste products lying around the brain, the greater the chance for Alzheimer’s disease to take root. Since 25% of the body’s overall energy is consumed by the brain, there are a lot of waste products to be cleaned up. The glymphatic system is the brain’s clean up system. Specialized brain cells scavenge diseased and damaged bits of protein and metabolic waste. With age, these cells become impaired. Also, the neuron surrounding supportive glial cells shrink in size when sleeping, opening spaces between cells by as much as 60% which allows cerebral spinal fluid to be pumped through and clear out waste. Lymphatic vessels surrounding the brain then deliver the waste to the lymphatic system of the body which gets rid of the toxins. With aging, adults often struggle to get enough sleep, which impairs the clean up system. THUS, since sleeping is crucial to removing toxins, keeping a regular sleep schedule becomes increasingly important with aging. Irregular sleep hours and long day time naps can disturb an effective sleep cycle clean up process. Also, sleeping on your side, in a fetal position, rather than on your back or stomach, does a better job of cleaning house. And, sleeping on your left side maximizes your body’s circulation, because most venous return travels up your right side and these veins can be compressed when you lie on them. However, getting good sleep is much more important than worrying about whether or not you sleep on your side and what side you sleep on.

REF.  Dr. Elsie Taveras “Lack of Sleep linked to behavioral problems I kids”, March 2017, Reuters.com. “ Children who aren’t getting the recommended amount of sleep (>11 hours) have more difficulties with attention, with emotional control, wit reasoning, with problem solving, and also have behavioral problems.” …”The more chaotic and less predictable a sleep schedule, the more difficulty kids tend to have with sleep.” Consequences of sleep deprivation include: problems in school due to poor concentration, falling asleep in classes, problems with teachers; behavioral issues due to poor impulse control and bullying; mental disorders such as ADHD and depression; and, negativity and stubbornness resulting in a poor attitude and poor cooperation, isolation, poor performance, and poor social skills. While adults get lethargic with a lack of sleep, kids speed-up, become emotionally weak and violent, and have mood swings. They are unable to understand what is wrong with them.

SUGGESTIONS:

1. Maintain a regular bedtime and getting-up time, including weekends and holidays, if possible.
2. Create a winding-down time in the evening, and a relaxed bedtime ritual—eg. reading or telling stories together, and tucking-in for the night with a lullaby.
3. Avoid caffeine, colas, and chocolate at night.
4. Avoid heavy meals and sweets at night.
5. Keep the bedroom a comfortable temperature (around 65 degrees), with darkness and quiet.
6. Avoid all screens and music.
7. Exercise for at least 60-minutes daily, but not within 2 hours of bedtime.

EXERCISE AS MEDICINE AND ENHANCED PERFORMANCE

Dr. Chuck Wile is a supervising physician at Cheng Integrative Health Center/Doctor’s Weight Loss Center, Columbia, SC.  Dr. Wile served in the US Air Force Medical corp and is a retired Air Force Colonel.

“Eating alone will not keep a man well, he must also take exercise.” {Hippocrates, 400 B.C.)   

“Exercise is loathsome.” {Mark Twain}   

“The best exercise is the one you like because then you are likely to stick with it over time.” {Martin Bibals}        

“GET MOVING; KEEP MOVING; AND, DON’T STOP.” {Jordan D. Metzl, MD}

          Regular exercise is a key to health, wellness and longevity. In the early 1900s, Medicine shifted its focus from the prevention of disease to its treatment. Simultaneously and coincidentally, Americans fell in love with spectator sports. Physical activity was no longer the medicine for the masses, but it became the privilege of elite athletes. We forgot/ignored the benefits of exercising: Regular exercise will help you to sleep better. Exercising increases blood flow to the brain helping to create new brain cells and blood vessels because of the increased Brain-Derived Neurotropic Factor (BDNF). This repairs and protects the brain cells from degeneration, both by repairing and restoring cellular mechanisms. Exercising releases endorphins and other chemicals that dull pain and improve your mood, especially decreasing your anxiety and lightening your depression. This helps with building and maintaining your resiliency.

          Regular exercise enhances memory and quicker learning. Your work will be more productive. Also, you’re medical costs will be less. You’ll have decreased risks for developing chronic diseases: for example, type 2  Diabetes is both preventable and treatable, as well as CAD and CVD. Exercising helps to burn fat better for energy, causing fat cells to shrink. {Since muscle mass is heavier than fat, don’t be over-focused on your scales, because your weight may actually increase while your body fat decreases. The real question is do your clothes fit better?} You can help to prevent and treat dementias. The increased blood flow reduces toxins (beta-amyloid and alpha-synuclein) that cause aging and cell death, and reduces inflammation. You can protect your chromosomal telomeres and slow your cellular aging: exercise increases Nuclear Respiratory Factor 1 (NRF1) which protects telomeres from shortening. You can increase blood flow to your skin and help wounds to heal faster. By producing weight bearing muscle contractions, you can make your muscles grow, and, also, increase your bone density. You can decrease your risk for at least 13 different types of cancer, including breast, ovarian and colon cancers. Regular exercising can help with rehabilitation from strokes, and help to  improve other chronic physical diseases and emotional problems.

          You will experience few or no adverse side-effects. Your costs will be low or absent. Exercise is safer and more effective than any drug on the market for health. Although it is much easier to take a pill for what ails you, the risks and side-effects are much more problematic. Exercise benefits both young and old, women who are pregnant, and people who are well or ill. You don’t need a fancy health club, clothes or equipment. JUST MOVE. ***Some exercise is better than none, and even a little exercise can do you a lot of good.

          Humans are notoriously bad at assessing the long-term benefits and risks of their lifestyle choices. The promise that: “exercise is good for you” is not a strong enough motivator to make regular exercising a part of one’s daily lifestyle and choices. Here is a glimpse at the problem: only 20% of Americans get the recommended 150 min of strength and aerobic training per week. More than 50% of “Baby Boomers” take zero exercise per week. Over 80 million Americans (over 6 years old) are inactive. Many schools have eliminated Gym classes from their curriculums. Half of High Schools don’t have weekly PE classes. Only 15% of Elementary Schools require PE 3 days per week. The result is Exercise Deficit Disorder”. Long term consequences include: obesity;  increased osteoarthritis; increased low back pain; increased anxiety; increased depression; poor skin complexion; increased risks for heart disease, cancers, dementia, diabetes, and early death.

          Humans are motivated by immediate rewards. Although people are motivated for health and personal growth, knowledge alone is usually not sufficient to motivate change. And, the best motivation is not externally imposed, but, rather, elicited from within the person. The hardest part of any work-out regimen is getting started. Don’t be stopped by the most common excuses: “I’m too…busy, tired, lazy”. Know that exercise releases “feel good” endorphins, and there are ways to manage Delayed Onset Muscle Soreness (DOMs).

1. ***Rather than focus on how good exercise is for your health, {which it really, really is, but it is a nebulous standard}, focus instead upon how exercise will give you an energy boost, improve your mood, enhance your productivity, and improve your sleep.
2. PICK AN EXERCISE PROGRAM THAT YOU ENJOY. Forget the idea that exercise is supposed to hurt or feel like punishment, or else its not helping you– {“no pain, no gain”}, and, therefore, not worth doing. THIS ISN’T TRUE. If you enjoy something, then you will look forward to participating again, and, thus, you will most likely take the time to make the activity a part of your daily routine.
3. Make exercising a social opportunity. A friend will offer you encouragement and will help to keep you accountable to yourself (possibly because you want to avoid their judgmental disappointment and disapproval). Exercise can be a time for high quality personal connections with your friend(s).
4. Don’t back down from a little competition. A competitive atmosphere focuses on different qualities than a chummy  one does. With competition, the most active participants become the benchmarks to beat, and, thus, everyone’s activity level is increased. In a social group, people who drag their feet seem to draw the most attention, draw down the group energy, and give others an excuse for less participation.
5. Make exercising non-negotiable. Be sure to make yourself prominent reminders, and, become aware of your self-sabotaging triggers. Your goal is to make regular exercising an automatic choice.
6. Put money on the line. Studies show that people are motivated more by losses than by gains, and that they prefer getting rewards now rather than later. For example, if you are trying to lose weight, consider sending a donation, each day that you don’t meet your exercise goal, to an organization that you hate. AND, give yourself a non-food reward for accomplishing your goal.
7. Use a Fitness Tracker. {In order to avoid unrealistic expectations, be aware of  the caveat: a tracker can’t force you to change your behavior, it is merely a source of information.} First, establish your exercise baseline for a week. Then start your exercise program and evaluate your data over time, looking for any improvements. Then, understand what you changed so that you can do it again and continue improving. Once you have a realistic assessment of your abilities, it will be easier for you to commit yourself to an individualized program and a long term behavioral change. Remember, “it’s the learning, not the digits.” {Ref. Martin Gibala: “The One Minute Workout.”}        

                                                 AEROBIC EXERCISING:

1. Doing an aerobic exercise program for at least 30 minutes 3 times per week will maintain your body’s basal metabolic rate (BMR). Your weight will remain stable if there is a balance between caloric input and energy output. If you don’t have an aerobic program, and you restrict calories, your BMR will decrease to conserve energy during relative starvation. In order to lose weight and remain healthy, it is necessary to maintain a normal BMR, and then restrict caloric intake.  The WHO and US CDC recommend making your exercising goal be 150 minutes per week (divided however you choose) in order to effectively lose weight, achieve cardiovascular fitness, and enhance your overall health and sense of well-being. {This includes time for twice weekly muscle strengthening.} {NOTE:  For time-conscious people: ***High Intensity Interval Training can produce the same results in half the time.***} Think of your exercise as THE BEST MEDICINE you can give yourself. REMEMBER:  in order to prevent injuring yourself by over-doing it initially, because of your enthusiasm to see results quickly, when starting out: GO SLOWLY, and then steadily build up to your desired goal. And, more is NOT necessarily better. There is a “sweet zone”. Too much exercising can stress your joints and your heart-lung capacity.
2. Look OUTWARD (rather than the usual advice to look inward) to support your motivations for exercise. Motivation is often thought of as a quantity of inward reserve, and people often lament its absence as a personality flaw. Instead, manipulate your environment to support your motivation. For example, purchase an audiobook that you’ll really enjoy and look forward to listening to, and make it available ONLY when working out. Your desire to engage with the plot will support your motivation to exercise.
3. When choosing an aerobic exercise activity, have FUN! Pick something that you will enjoy doing so that you will incorporate it into your lifestyle changes. If you go power walking, walk with a partner that enjoys a good conversation. Or, vary your activities from working out at a gym, to swimming, to dancing in order to keep it fun. Or, create your own energetic music CDs so that you can crank up the volume for an exuberant work out. Try exercising mindfully: bring attention to your breath, your steps, your surroundings, and you will find that your pains will be alleviated.
4. If you choose RUNNING more is NOT better, especially as we get older. A 2 to 3 mile run is all that is needed. Runners with the greatest longevity ran at a slow to moderate speed for 1 to 2 hours/week. Time is required for recuperation after a work-out. After age 45, people generally have their joints feel better after a brisk walk compared to a run. Women runners have a greater risk to injuring their bodies than men. Women have higher arches, and, when running, point their toes outward, and land with a heel strike which increases their skeletal impact. Also, they generally have less hip and core body strength, have an anatomical shift in their hips and their knee alignments, and have increased body fat. {In contrast, women have more joint flexibility than men, and they are better at pacing themselves in a race.}  Remember that stretching and warming-up your muscles is important to preventing injuries. Also, remember to stretch again after running. If you suffer from arthritis, it is much better to participate in non-impact aerobic activities such as swimming, working out on a glider or an elliptical trainer, or rowing.
5.           However, a theory proposed by Dennis Bramble and Daniel Lieberman in a paper published in Nature in 2004 proposes that humans are born to run and to run far. The theory proposes that early humans evolved endurance adaptations for running to be able to chase prey animals “until the animals collapsed from exhaustion and heat stroke. Winning the footrace meant dinner. In addition to being furless, we have far more sweat glands than most other mammals, giving us an advantage over furrier animals that have to stop and pant to cool down. A larger gluteus maximus muscle—a big butt—is a distinctively human feature.We rely on it minimally for walking, but it’s crucial to stabilizing us when we run. Our legs have long tendons—that act like springs, helping generate force and reducing the energy cost of running. And they don’t seem to provide much benefit to walking, another piece of evidence that our bodies are made for running.” {Reported in Discover Magazine, July/August 2018, pp. 50-51.}
6.           “There are 2 types of muscle fibers: Type 1 (slower contracting or slow-twitch fibers) and Type 2 (faster contracting or fast-twitch fibers). Everyone has a mix of both fibers in their muscles. Fast-twitch fibers are for short, powerful bursts; they contract quickly but also fatigue quickly. Slow-twitch fibers have more mitochondria (the cell’s powerhouses that use oxygen to make energy) so they don’t fatigue as easily and are ideal for longer activities. Sprinters have more fast-twitch fibers, while endurance athletes have more slow-twitch. Although partly genetic, there’s some evidence we can train in order to change the proportion of fibers our muscle have.” {Reported in Discover Magazine, July/August 2018, p. 50.}
7. WALKING lowers your risks for diseases and probably will extend your life. Walking helps to keep you limber longer and helps to make you feel happier. In a study of 80,000 women, their risk of breast cancer was decreased by 42% by walking for a few hours per week. Other studies similarly demonstrate a decreased risk of kidney and prostate cancer mortality by walking. Walking has the lowest “quit rate” of any exercise. In a study of 400,000 Taiwanese who walked for 15 minutes daily, they lived 3 years longer than their sedentary peers. A 5-minute walk outdoors can elevate your mood and enhance your creativity, decrease your anxiety and depression, and increase your sense of well-being. SUGGESTIONS for success: pick-up your pace so that it becomes a power-walk rather than a stroll. {Maintain a pace that makes you a little breathless when walking and talking.} Count your steps: your goal is 7,000 to 10,000 steps/day, with 3,000 purposeful steps. Break-up your day into 50-step mini-walks every 45 minutes. Walk with a group for mutual support.
8. ***High-Intensity Interval Training (HIIT) alternates periods of intense exercise with periods of less-intense exercise or recovery time. “If you want the benefits of very time-efficient exercise, then you need to push hard. There is no way around that.” {Martin Gibals} For example, consider riding a stationary bike for 10-minutes 3 days per week for a total of 30 minutes per week: after a 3-minute warm-up, pedal very hard and fast for a 20-second spurt of intense energy, then pedal less hard for a minute, then repeating this sequence two additional times, followed by 3 more minutes of slower pedaling.
9.                                                       TOTAL FITNESS
10.           1)   In addition to regular aerobic exercising, Total Fitness is achieved by enhancing your muscle strength, doing regular stretching, and, improving your balance and coordination.
11.           2)  What counts as moderate-intensity exercise? Brisk walking, playing with your kids, dog walking, carrying heavy groceries, mowing the grass with a push mower, raking leaves, car washing, gardening, snow shoveling, etc. when done for at least 10-minutes at a time. ALL movement counts. Plus, to protect against injuries and to build muscle and bone, you need interval strength training. In addition to using free weights and resistance training, Tai Chi, Yoga and Pilates are excellent forms of strength training.
12.             3)  In studies, dynamic resistance training is superior to static (isometric) resistance training for building muscles through the full range of motion of your joints. Pilates and working out with Nautilus equipment are two example of effective dynamic resistance training.
13.             4)  RESISTANCE TRAINING increases your muscle mass, thus, generating more strength, and faster muscle force (power). Unless you over do it, you won’t become muscle bound. Resistance training also helps to make your bones more dense. Ten million Americans (80% are women) have osteoporosis (thin and breakable bones). {A decrease in sex hormones with aging helps to create this common problem.}  Resistance training also helps to improve your metabolism, increase your glucose tolerance (or, said another way, decrease your insulin resistance) and decrease your risks from type 2 diabetes. It also helps to decrease both coronary artery disease and cerebrovascular disease risks. Other than doing free weight lifting or using a dynamic weight resistance machine, such as a Nautilus device, there are various simple ways to do resistance training such as: Yoga, Tai Chi, Pilates, using flexible bands, sitting up and down using a chair and your own body weight, swimming, doing Zumba dancing, doing heavy gardening such as raking and digging, doing vigorous house cleaning, taking the stairs rather than using an elevator, jumping rope, etc. The stronger you are,  the more self-esteem, confidence, and positive thinking you will usually have.  However, because resistance training requires work and effort, only about 20% of people actually follow strength training recommendations. PLEASE DON’T BE LAZY.
14.               Resistance exercises have a greater impact on cognitive function than aerobic exercises. It increases blood flow to the brain, thus, increasing oxygenation and the provision of nutrients. It helps to promote angiogenesis from existing blood vessels and neurogenesis from stem cells in the hippocampus {an area responsible for organizing memories}. It increases the production of neurotransmitters: serotonin {which helps to regulate mood and sleep}, acetylcholine {which helps with cognition, learning and memory}, and GABA {the main inhibitory modulator}. It also increases neurotropins {proteins that regulate neuron survival}.  [Mavros, et. al. “Mediation of cognitive function improvements by strength gains after resistance training in older adults with mild cognitive impairment: outcomes of the study of mental and resistance training,” J. of the American Geriatric Society, October 2016.]

1.             5)  In my opinion, Hatha Yoga and Pilates are the best ways to completely stretch your muscles and joints, tone and strengthen your muscles, especially your “core” abdominal muscles, and achieve overall physical fitness, and mental, emotional and spiritual balance, inner harmony, and peacefulness.
2.             6)  I applaud the American Academy of Sports Medicine’s program: “Exercise Is Medicine”. They recommend that physicians should inquire about exercise with each health visit. They recommend following the 5 A’s approach: Ask, Advise, Agree, Assist, and Arrange. People should be asked about what barriers they face in order to exercise and what helps to facilitate their choice to exercise. After assessing a person’s physical activity level, the practitioner is advised to prescribe physical activities that the person will agree to pursue. Physical activity counseling can be offered along with referral resources to help facilitate the process. Within a person’s social and economic context, it is important to support and empower the person, just like a good coach, by emphasizing that they have both choices and competence. Motivational interviewing is useful to explore and resolve ambivalences and insecurities and to understand and encourage/support internal motivators for behavioral changes. By understanding a person’s values and goals, a health care provider can help people to envision a better future. Depending upon a person’s personality, they may choose to “leap-into the deep end of the pool” and make massive changes in their lifestyle, which can be disruptive and stressful.  Or,  they may choose to ease into the “shallow end of the pool” and take baby-steps, focusing upon small and measurable goals and achievements. Either way, the exercise prescription must be “patient-centered” and individualized in order to be effective for the long term. Setting goals work best when they are realistic, specific and present oriented. Challenges to maintaining changes is the rule and not the exception. Thus, it is very helpful to maintain a continued coaching partnership in order to  encourage and support a person’s health goals.

1.     SUPPLEMENTS TO CONSIDER FOR ENHANCED ATHLETIC PERFORMANCE

1. Consuming an over-abundance of calories for a long time will suppress the AMPK (adenosine monophosphate-activated protein kinase) system—the metabolic master switch. AMPK activation: reduces insulin resistance and supports glucose transport, inhibits the metabolic syndrome’s associated inflammation, increases utilization of stored fat for energy, improves mitochondrial fat burning, reduces weight gain by enhancing the effect of the anti-obesity hormone: adiponectin, and improves immune function and other bodily functions that support longevity. A suppressed AMPK system leaves the body in a state of continued energy storage and reduced energy utilization. Cutting calories forces the body to activate AMPK. Exercise is another powerful AMPK activating strategy. (Note: Only when you are adding exercising will calorie reduction be truly effective for weight loss.) ***For people who have problems exercising because of physical problems, there are supplements to promote AMPK activation.*** Two documented ingredients include:  a) Gynostemma pentaphyllum and b) Trans-tiliroside. A proprietary product is available, called “AMPK Activator” from www.LifeExtension.com. Also,  Hesperidin, found in citrus peel extracts and in orange juice, activates AMPK, as does the medication Metformin. AMPK activation helps to remove excess stored fat, particularly metabolic abdominal fat, and to decrease metabolic syndrome risk factors. Increased AMPK activity also normalizes hyper-activated mTOR activity. {Excessive mTOR accelerates cell aging and malignant transformation, and depletes stem cells.}
2. RE-FUEL YOUR MITOCHONDRIA:  “Mitochondrial Dysfunction” results in obesity, insulin resistance, diabetes, anxiety, depression, neuro-degenerative diseases, aging, chronic fatigue syndrome and fibromyalgia syndrome. {Consider: if the blood test Reverse T3 is high, then mitochondrial dysfunction is present.} The following NUTRIENTS can help to re-fuel the mitochondria energy generating centers in each cell:  a) D-Ribose 5 gm/tsp: 1-2 tsp three times per day. b) ALA (Alpha-Lipoic  or R-Lipoic Acid) 300 mg to 400 mg/day. c) CoQ 10 (or its activated form Ubiquinol) at least 200 mg/day. d) NADH (Nicotinamide Adenine Dinucleotide –reduced form) 10 mg twice per day. e) L-Carnitine 2,000 to 3,000 mg/day.
3. Short term supplementation with powdered cherries boosts athletic performance. Using 480 mg of powdered cherries caused half-marathon runners to average 13% faster finish times compared to taking placebos. Inflammatory markers were 47% lower, and there were attenuated markers of muscle catabolism, a better maintained redox balance, increased performance, and post-run muscle pain faded faster. {J Int Soc Sports Nutr. 2016 May 26.}
4.         Tart cherry juice is also helpful for osteoarthritis pain and other inflammatory conditions, particularly gout. It is easier to take when mixed in a fruit smoothie. For example, 100 patients with a history of gout received 1 Tbs of Brownswood Acres tart cherry juice concentrate [which can be obtained at Whole Foods] twice per day. 92% of the patients had >50% reduction in the number of gout attacks. Their uric acid levels did not change. Tart cherry constituents can switch critical genes off and on; modulate cell-signaling molecules like tumor necrosis factor; and, target multiple cardiovascular factors producing a 65% reduction in early mortality. Tart cherries surpass red wine and dark chocolate in antioxidant content. Tart cherries are rich in the flavonoid anthocyanin and contain novel anthocyanins absent from blueberries or bilberries. They also contain higher amounts of phenolics and anthocyanins than sweet cherries. It is useful for treating osteoarthritis, inflammation related to obesity and the metabolic syndrome, and lowering triglycerides associated with cardiovascular disease.
5.           Rich sources of polyphenolic compounds, such as tart cherries, play a neuro-protective role and exert a variety of anti-carcinogenic effects. 20 women were given 2, 10.5 ounce bottles of tart cherry juice or a placebo for 3 weeks. Those taking the cherry juice had reduced levels of the inflammatory marker C-reactive protein. Obese adults given 8 ounces daily of tart cherry juice for 4 weeks had markedly decreased inflammatory markers: sedimentation rates, tumor necrosis factor levels, and monocyte chemotactic protein. Runners were given tart cherry juice or a control drink for 5 days before, on the day of, and for 2 days after a marathon race. Runners drinking the tart cherry juice had significantly lower inflammation biomarkers (Interleukin-6 and C-reactive protein) than the placebo group. They also recovered isometric strength quicker and demonstrated an accelerated recovery following strenuous exercise. Runners in a double-blind trial participating in a 24-hour relay race drank two 355 ml beverages containing either tart cherry juice or a placebo daily for 1 week prior to the race and during the race. Both groups reported muscle pain after the race but the runners who drank tart cherry juice experienced a substantially smaller pain increase after the race.
6. Cordyceps sinensis extract is a parasitic fungus that grows on caterpillar larvae native to high altitude regions of China, Nepal and Tibet. It has pharmacologically active anti-oxidant, anti-inflammatory and lipid lowering properties. It enhances the immune system and increases stamina for endurance athletes through greater aerobic capacity and oxygen use. It stabilizes blood sugar metabolism and increases libido and sexual functionality.
7. Velvet Deer Antler (VDA) is a pillar of Traditional Chinese Medicine used to strengthen and replenish blood, reduce and reverse signs of aging, relieve pain and inflammation, overcome exhaustion, accelerate wound healing, reduce blood pressure, treat insomnia, relieve headaches, improve mood and memory, help infertility, restore vitality, heighten libido and increase muscle strength and endurance. One key component is a growth hormone called insulin-like growth factor “IGF-1”. This keeps muscles strong and helps to heal cartilage and tendon injuries. Also, glycosaminoglycans are plentiful which help to restore healthy cartilage. It contains Type II collagen along with a rich supply of minerals including potassium, sodium, calcium, copper, zinc, iron, selenium, magnesium and phosphorus. A proprietary product called “VDA Pure” can be obtained from www.VDAPure.com . The recommended dose is 2 caps daily before eating.
8. Asian ginseng (Panax ginseng) and Siberian ginseng (Eleutherococcus senticosus) “can be used as a tonic to combat feelings of lassitude and debility, lack of energy and ability to concentrate, and during convalescence,” according to the German Commission E advisory about herbs.  The suggested dose is 1 tsp steeped in a cup of boiling water to make a tea.  Ginseng can improve athletic performance when taken regularly for up to a month, and it can also beneficially stimulate the immune system.  It is an adaptogen for managing adrenal stress, and improves alertness, coordination and memory.
9. Dimethylglycine (DMG): is an amino acid adaptogen made in the liver which diminishes in quantity as we age. It was formerly promoted by athletes as “vitamin B-15”. DMG aids in critical processes associated with cellular respiration and energy production, immune response, and oxygen utilization in the body. It helps to prevent fatigue, improve physical endurance and performance, and supports mental clarity. DMG stimulates both antibody response and cellular immunity. It has also been used to support cardiac function in heart disease. Additionally, it makes all other nutrients taken with it work better. High quality DMG can be obtained from www.TargetedNutrients.com . Typically usage is 1 cap once or twice daily.
10. Beetroot juice can raise serum nitrate levels which can improve athletic performance, lower blood pressure and protect against glaucoma. Nitrate is metabolized to nitric oxide which helps to dilate smooth muscles, and improve blood vessel flexibility and tone. It enables athletes to use less oxygen while exercising at the same intensity, which makes exercising easier, and one can continue it for longer. Blood nitrate levels peak two to three hours after consuming beetroot, and remain elevated for six to nine hours. The key is to drink beetroot juice three hours before exercising, and take it daily to maintain higher blood levels of nitrate. One of the leading 2.4 ounce beetroot “sport shots”, called “Beet It”, provides 400 mg. Most blood pressure lowering studies have used 180 mg of beetroot juice daily. So, you could take half of “Beet It” one day and half the next. Serious athletes can use one or two shots daily. Two shots will saturate the blood stream and provide maximum benefits, so larger amounts will have no additional effects. Be aware, your urine may turn pink, but this is a harmless side effect.
11. Resistance training is supported by key nutrients. And, when used together, they  provide synergistic benefits: a) Whey Protein: helps to preserve lean body mass. Although the Institute of Medicine recommends 0.8 grams/kg body weight (which equals about 58 gm in an aging adult weighing 160 lbs), the optimal dose is 1.0 to 1.3 gm/kg body weight (which equals 73 to 94 gm in an aging adult weighing 160 lbs). b) Creatine:  improves the Type 2 (fast contracting) muscle fibers that commonly atrophy in older adults. It helps to increase muscle force, power and mass and to decrease fatigue. c) Branched Chain Amino Acids (BCAAs):  especially leucine, isoleucine and valine (which are also found in whey protein), helps to promote muscle tissue synthesis. Also, they help to decrease the perception of exertion and mental fatigue during exercising. d) Glutamine:  helps to replenish muscle stores of glycogen (a ready source of stored energy). Also, in healthy adults, taking 2 gm of the amino acid glutamine will increase the output of human growth hormone by four times. e) Vitamin D3:  helps to preserve Type 2 muscle fibers and to protect cognitive function. f) Carnitine:  is an amino acid which helps to transport fatty acids into the intracellular mitochondria for fuel for the production of ATP energy. It supports exercise recovery, enhances performance, and decreases general fatigue. Propionyl-L-carnitine helps to regulate levels of ATP. g) D-Ribose:  helps to facilitate ATP production and to facilitate the speed of muscle function recovery after high-intensity exercising.  h) Omega-3 Fatty Acids:  eicosapentaenoic acid (EPA) helps to preserve muscle mass. And, both decosahexaenoic acid (DHA) and EPA are anti-inflammatory, and help to manage sarcopenia. 6 gm of deep sea fish oil can help to eliminate muscle soreness after resistance training.

                   DELAYED ONSET MUSCLE SORENESS (DOMS)

          Immediate muscle soreness is due to the partial metabolism of glucose (for energy) into lactic acid, which accumulates waiting for increased oxygenation after an exertion has finished, in order to be fully metabolize into carbon dioxide and water: the “oxygen debt”. The results of the incomplete oxidation of glucose  into lactate resolves within a few hours after exercise. DOMS occurs a day or two later as a consequence of repairing the micro-tears in the muscles caused by the exercise. The soreness, stiffness, mild swelling, tenderness, decreased strength and decreased range-of-motion will resolve in a few days. And, with your next exercise, you will be stronger and DOMS will be milder. Since it takes time for healing, it is important to space-out your resistance training during the week.

          You CAN have gain without (a lot of) pain. Drinking 2 cups of tart cherry juice can reduce both exercise-induced  inflammation and DOMS. {Be aware of  consuming the extra calories.} NOTE: A pre-emptive use of NSAIDs the day before and the day of a long distance race did NOT reduce DOMS (compared to non-users), and the users had mild endotoxemia due to the consequent drug-induced leaky-gut. Using NSAIDs intermittently for pain management after exercising may be helpful, if needed. BOTH localized Cold Therapy and Heat Therapy can reduce joint and muscle soreness, but cold is superior. However, tub hopping from hot water to cold water and repeating, probably isn’t worth the effort. Therapeutic Massage can help with DOMS. {Most studies look at massage within 3 hours after exercising for at least 20 minutes.} A foam roller is a low-cost alternative for self-massaging.

                  PRECISION EXERCISE RECOMMENDATIONS

1. For Weight Management:  Initially, focus on adjusting your diet to decrease your total calorie intake.  Adjusting one significant lifestyle change at a time is a successful strategy to increase your own compliance and persistence. {For example, a decreased input of 500 cal/day equals 3,500 cal/week, which equals 1 pound of body fat reduced per week. Compare this to vigorous walking for 2 hours which equals using 500 cal.} In a 12-week comparison study, people who attended Weight Watchers lost about 9 lbs, versus people who simply worked-out at a Gym, who lost about 3 lbs. So, initially establish a structured eating-plan that you will adhere to, that includes reducing your portion size and the amount of food that you actually consume. And, for exercise, at first, simply determine to move more.
2.           Once you have experienced successful weight loss, then combine your dieting with exercise. {It becomes easier once you have lost some weight and feel better rather than when you feel heavy and lack energy.} Pair cardio training with resistance training. Cardio activities burns calories and resistance training keeps you toned so that you lose fat rather than muscle. People who regularly work-out are twice as likely to keep the weight off than those who don’t. Exercise stimulates hormones which signal burning more fat as fuel. Emphasize to yourself how much better you feel when you are active. This may help to cancel-out any feelings of deprivation which could result in self-sabotaging behaviors. Remember that exercising is NOT a free-license to binge eating.
3. To improve your Stress level, Self-Esteem and Mood:  In a 1999 study at Duke University, people who did aerobic exercise for 45-minutes 3x/week improved their moods equivalent to matched sedentary people using the SSRI Zoloft. Exercise increased their serotonin levels and their endorphin levels, and decreased their cortisol levels. The effect on mood only lasted for about 24 hours, so, regular exercise is the key to success. Mix-up your activities for fun and fitness: vary the kinds of exercise, frequency, timing and intensity. Remember that you need both cardio and strength training.
4. To increase your Energy and decrease your Fatigue:  try a low to moderate intensity exertion for 20 minutes, 3 to 4 times per week. You will feel better within 4 weeks for all conditions. The intracellular size and number of your mitochondria {energy centers} will increase. You will increase burning your fat for energy, decrease your insulin resistance with a consequent good decrease in your glycation process, and balance both your intracellular and extracellular salts and fluids. You will sleep better: fall asleep quicker, remain asleep longer, and awaken more refreshed. Exercise energizes you. Don’t give-in to feeling drained of energy. Fake yourself-out: instead of saying that you feel “too tired”, say that you will walk for just 10-minutes—you’ll likely go longer because you will start to feel better.
5. To ease chronic health problems and limit medical visits:  monitor yourself with a fitness tracking device such as FitBit or a Garmin watch. All movement counts. An encouraging 2013 study compared people doing short activity bursts, such as raking leaves or pacing when talking on the phone, with 150 min/week of aerobic bike riding. The groups had similar BP, lipid levels, waist circumference, and C-reactive protein inflammatory markers. When starting out: be sure to see a Pro and Go Slow. Increased endorphins will ease your pains. Try to minimize IMPACT aerobic activities: your joints will feel happier because they will be better lubricated and respond to inflammation more effectively, thus, easing your arthritis. Your heart rate and blood pressure will decrease, and your glucose intolerance will improve. Anticipate a slow and steady improvement.

                             EXERCISE AND CARDIOVASCULAR DISEASE

          An observational study published in Circulation, 5/15/2018, of 11,000 adults in the Atherosclerosis Risk in Communities (ARIC) study, demonstrated people doing 150 minutes of vigorous exercise weekly were 31% less likely to develop congestive heart failure (CHF). Couch potatoes who started exercising decreased their risk of CHF by 23%. This study supports the JAMA July 22/29, 2009 study of 20,000 male physicians who had a healthy lifestyle for more than 20 years who developed significantly less CHF. A similar study of 36,000 Swedish women published in the Archives of Internal Medicine, 5/11/2009 who were eating a DASH diet (to manage hypertension) along with doing regular exercise for 7 years had a 37% decrease in CHF.

                     THE PROBLEM OF SARCOPENIC OBESITY IN AGING

          After age 50 there is an exponential drop in muscle function. (This starts to occur after age 40 and accelerates after age 75.) Sarcopenia means a loss of muscle mass, strength and function. There is a faster decline in Type 2 (fast contracting) muscle fibers compared to Type 1 (slower contracting) muscle fibers. Therefore, there is a decreased speed of muscle contractions with aging. Evaluating muscle function and strength is more important than evaluating muscle mass. Muscle “power” is a function of force-strength and velocity. {Imagine the difference between just placing a fist against the side of a head (force) and then adding velocity to the fist placement (power)}. Power drops quicker than muscle mass. With decreased muscle power, especially in the core and lower extremities, there is decreased capacity to accomplish the functional tasks of daily living and an increased risk of falls and injuries, with an increased risk of consequent death. Because women start out with less power then men, older women have increased problems with a loss of balance and decreased muscle power which increases their risk of falls and hip and vertebral fractures (especially with their additional increased risk for osteoporosis.) This is primarily caused by suboptimal sex hormonal support, inadequate dietary protein intake and nutritional deficiencies, oxidative stress and inflammation. This is most often found in people who are physically sedentary and inactive.

          Obesity has become a significant increasing problem in America. In a study of nursing homes, in 1992 about 15% of patients (mostly women) had a BMI (Body Mass Index: weight divided by stature) of >30 (defining obesity). By 2002 the average BMI had increased to >25%. A fall risk for over-weight people was 15% compared to a fall risk for obese people of 25%. The combination of obesity plus sarcopenia (decreased muscle power) makes the loss of independence 2 to 3 times more likely because of diminished capacity for activities of daily living (ADL).

          Our aging population needs a combination of power training (eg. high velocity dynamic muscle resistance training using lower weights at higher speeds) twice per week along with aerobic interval training three times per week in order to improve their functional outcomes. While aerobic training helps the cardiovascular and cerebrovascular systems, resistance training provides superior protection against injuries. It stimulates human growth hormone which supports cell growth and regeneration. It also supports local mechano-growth factors. And, it enhances bio-identical hormone replacement therapy (BHRT) interventions.

           A report in the magazine The Week, 6/15/2018, (from reviewing an article on  MedicalNewsToday.com,) states that moving the large muscles of the legs (walking, climbing stairs, running) triggers brain stem cells to renew brain neurons. Researchers immobilized the hind legs of mice for 28 days then they examined the subventricular zone in their brains. They found a 70% decrease in neural stem cell activity. This helps to explain why people who are bedridden often deteriorate rapidly in their cognitive functions.

                                        JUST DO IT!   {Nike Shoes Slogan}

A good reference is “The Science Of Exercise” edited by Siobhan O’Connor and Mandy Oaklander, TIME Inc. Books, 2018.

One of the easy and probably the most effective exercise regimen is High Intensity High Interval Training (HIIT). HIIT can be done at almost all ages, almost anywhere, with or without any special equipment. Best of all, you can do it at home!

This is how to do it:

Warm up for 15 minutes, adding a few 20-second bursts at the end to prepare for the workout. Run, bike, or row for 30 seconds at a nearly all-out effort. Take three minutes active recovery and repeat the 30 on/3 off pattern five or six more times. Finish with a 10-minute cool down.  You can do this on a stationary bike, or in a swim pool, or outside on the grassland, or even up and down the stairs.  Of course, make sure you do this in a safe environment.  You don’t want to hurt yourself nor others who may be around.  Repeat this 3-5 times a week.

Healthy Eating Habits:

1. Eat your last meal at least 3 hours before your bed time (before 7 pm for most people).
2. Wait between 13 and 18 hours before you eat another meal.  In other words, if you eat your supper of the previous day at around 7 pm, then don’t eat breakfast until at least 8 am, or better, until 12 noon!  This is intermittent fasting (13-18 hours fasting without food, you can drink water though) allows your mitochondria (an important cellular organ in metabolism) to recover.
3. The first meal of the day should be the biggest,  should be heavily fat with 80-90% of the calories from healthy fat. One won’t feel much hungry throughout the day after such a fatty meal.
4. Try to fast for at least 24 hours a week (e.g., on a Saturday), drinking water only.

The above measures are proven to improve your health, improving your mitochondria and helps you to lose weight.

In our regular Monday Lecture Series, Dr. Cheng will present on Ketogenic Diet (KetoDiet for short) for Weight Loss and Health. Topics to be discussed include:

1. What is Ketogenic Diet?  Why (healthy) fats are good for you.  Why carbs are bad. KetoDiet, it‘s health benefits.
2. Why is KetoDiet a foundation for all chronic disease?
   1. Case studies of KetoDiet and nutritional therapy for autoimmune diseases like psoriasis, skin rash.
3. Nutritonal KetoDiet (for health or for chronic disease management) vs. Restricted KetoDiet (for cancer management).
4. How to eat on ketogenic diet, introduce some keto recipes.
5. Other factors in a healthy diet.
   1. Brief introduction to oxidative stress, mitochondrial health, and nutritional approach to health.
6. How to combine KetoDiet with our current weight management protocols to better manage your weight and other chronic diseases (autoimmune disorders, diabetes, heart disease and even cancer).

Date and Time: Apr. 2nd, 2018, Monday, at 1 pm.

Address: Cheng Integrative Health Center/Doctor‘s Weight Loss Center, 6149 St. Andrews Rd., Columbia, SC 29212 (across stree from Cici’s Pizza, in fornt of the K-Mart).

Dr. Richard Cheng, MD

Ketogenic means ketone producing.  ketone is produced when fats are digested.  So ketogenic diet means ketone producing diet, or in other words, ketogenic diet contains predominantly (healthy) fat, very little carbs and appropriate amounts of proteins. Ketogenic diet is different from Atkins diet, and is NOT a high fat diet.  The total calories one needs to consume is limited (to one’s needs).

Benefits of ketogenic diet:

1. weight loss
2. anti-inflammatory (anti-oxidant)
3. lower cancer risk
4. muscle strengthening
5. inhibiting appetite
6. reducing insulin levels (insulin inhibits fat release.  So this reduction in insulin release can help in more fat release and weight loss).

Ketogenic Diet:

1. Healthy fats calories, about 80-85% of the total calories.
2. Protein calories: about 10% of the total calories
3. Carb calories: 5-8%.

Healthy Eating Habits:

1. Intermittent Fasting: Every day there should a period of 13-18 hour without food intake, water is ok. One may choose either to skip breakfast or skip dinner.  Research shows this type of intermittent fasting boosts your mitochondrial (Mito) function.  Mito is the rechargeable battery in your cells.  Dysfunction of Mito is found to be a major contributor to most, if not all, chronic diseases esp. cancer, and aging, including obesity.
   1. Skipping breakfast. For example, if one finishes dinner at 7 pm, then do not eat anything until at least 8 am (13 hours fasting) or, even better, 11 am (16 hours).
   2. Skipping dinner: Don’t eat anything after 4pm.  Then eat breakfast at around 8-10 am (that’s 16-18 hours fasting).
2. Ketogenic Diet (see above). One other reason why I advocate ketoDiet is the drastic reduction of carbohydrates.  Carbs cause lots of problems, esp. today’s carbs are heavily contaminated by all sorts of pesticides, herbicides, more so than other foods.  Carbs like wheat are a major to cause to many GI problems such as leaky gut which contribute to our autoimmune diseases and symptoms.  Allergy is just one of them. (I have been on the KetoDiet for a while now.  I really feel the difference: improved stamina, reduced seasonal allergy symptoms (I used to take Zyrtec daily.  But now, even in this pollen season, I have gone a whole week without needing Zyrtec.  This is amazing since for the last 25 years, I have never, NEVER, skipped several days, let alone a whole week, without an allergy pill).

We will close at 12/25/2017, Monday, for Christmas holiday.

and close at 1/1/2018, Monday, for New Year holiday.

MICROBIOME AND  PROBIOTICS

          We have co-evolved with the microbiota. Probiotics are beneficial live microorganisms which when taken in adequate amounts confer a beneficial health effect on the host. Most are bacteria. Almost every society has consumed some type of fermented food. Using probiotics is SAFE. Approximately 5000 species of microbes reside in a healthy human body. 100 trillion microbes reside in a human body. This is 10 times the number of human cells and 100 times the number of human genes. Some people propose that we are not autonomous agents. Rather, we are biomolecular networks called “holobionts” with the host and microbial genomes referred to as “hologenomes”.

          The GI tract contains 90% of these microbes in a symbiotic relationship. The large intestine is one of the densest microbial ecosystems on the planet. The vagina is like a sparsely populated prairie compared to the lower gut which is like a rain forest teeming with life. People are very different from one another, but they are consistent with themselves. Two healthy Americans’ microbial communities can differ by as much as 90%, but an individual’s distinctive ensemble of bugs tends to stay stable over many years.

          Microbes predigest our food, chemically modify the pills we take, shape our immune system responses, and repel infectious invaders. Nearly ¾ of the body’s immune cells are in the Gut Associated Lymphoid Tissue (GALT). The microbial inhabitants of the GI tract stimulate the immune system for optimal functioning.  GALT immune responses differentiate between beneficial and harmful dietary proteins (antigens) and beneficial and harmful microorganisms (bacteria, viruses, parasites).  Probiotics activate B-lymphocytes , T-lymphocytes and macrophages, stimulate the complement system, and reduce responses to “like-antigens”.  They digest nutrients and compete for nutrients with pathogens; modify the local pH to create conditions unfavorable to pathogens; produce bacteriocins that inhibit pathogens; scavenge superoxide radicals; stimulate epithelial mucin production; enhance intestinal barrier functions; compete for adhesions with pathogens; and modify and metabolize pathogen derived toxins.

          Probiotics have several mechanisms for their clinical effects:  1) direct interaction with intestinal cells with effects on intestinal barrier functions.  Skin and mucosal surfaces have adherent normal bacterial flora which provides protective barriers where neutrophils attack and macrophages engulf and ingest foreign bodies. The complement system stimulates and mobilizes the phagocytes (clean-up cells).  2) Interaction with immune intestinal B-lymphocytes stimulates plasma cells to produce antibody immunoglobulins such as increasing IgA.  Also, T-lymphocytes (which include killer, helper, suppressor and memory cells)  produce stimulating chemicals (lymphokines) and destructive chemicals (lymphotoxins).  3) They modulate gut microbes and compete for gut nutrients and metabolic pathways.  4) They directly antagonize intestinal pathogens.  And, 5) they create metabolic effects.

***I strongly recommend using probiotics to help manage constipation;  diarrhea;  irritable bowel syndrome;  infant colic; and, especially while taking antibiotics and after using antibiotics***  Probiotics are found in fermented foods such as  yogurt, beet kvass, kefir, sauerkraut, and, kombucha. The easiest way to consume adequate amounts are in powder or capsule form. I recommend for children 5 to 15 billion count capsules (which can be opened  onto food or mixed in a drink) daily, and for adults 15 to 30 billion count capsules daily. There is no upper limit and no adverse side effects.  NOTE: As we age, we tend to selectively lose one of the main players in our colon, namely Bifidobacterium species. The best way to restore them is to consume them (look for Bifido-rich yogurt or probiotic capsules) and to provide them with the food they need to live on in our colons: lots of vegetables, a little fruit, and limiting (toxic) doses of sugar that might feed competing species.

          ALSO NOTE: ***soil-based spore-forming bacteria are essential for our health. They are “pseudo-commensuls” because they pass through the gut rather than establishing a home there. Our ancestors regularly consumed them when eating wild foods and drinking from ponds and streams. The spores not only survive traversing through the hydrochloric acid and bile salts of the stomach,  they are activated to viably reach the intestines. An excellent product {that is unfortunately only available through a health care provider}  is called “Mega-Sporebiotic” from Microbiome Labs which contains Bacillus indicus, HU36; B. subtilis, HU58; B. coagulans; B. licheniformis; and B. clausii.

          I also strongly recommend reading the book by Dr. Josh Axe, MD called “Eat Dirt”.

          Six host factors disrupt our natural gut bacteria balance:  1)  Antibiotics: disrupt the number and relative proportions of gut bacteria. 2)  Infant Formula: breast feeding transfers bacterial diversity from mother to baby. Caesarian section delivery also disrupts this normal transfer of flora.  3)  Excessive hygiene.  4)  Our Western Diet high in animal proteins, fats , sugars and refined carbohydrates. 5)  Modern medical treatments such as artificial ventilation, skin-penetrating devices, tubes and catheters and their attendant antibiotic use.  6)  Age. 

          Our immune system co-evolved with parasites. Their absence can profoundly affect immune regulation leading to physical and psychological consequences. IgE immunoglobulin evolved to help manage parasites. Because of our overly cleanly environment with minimal parasites, IgE now responds to allergens with manifestations of Allergic Rhinitis and Asthma. People who are infected with hookworms have a lower incidence of auto-immune diseases than parasite-free modern humans. People who have been immunized with Bacille-Calmette-Guerin (BCG) are not only protected against developing tuberculosis, but they are less likely to develop melanomas.

                                THE IMPORTANCE OF MULTIPLE SPECIES

          Although good bacteria can be found in small amounts in food, changing the entire ratio of gut bacteria requires substantial and consistent dosing with supplements providing potent levels of beneficial bacteria to enable their survival. {Therap Adv Gastroenterol. 2010 Sept;3(5):307-319.}  Two types of probiotic bacteria commonly used include Lactobacillus and Bifidobacterium. There are many specific types of the bacteria within each of these two broad groups, and health benefits associated with one type may be unique to that specific species and not hold true for others. This means that using multiple different species delivers better odds of reversing the negative effects of “dysbacteriosis”, a condition where there is an imbalance between good and bad bacteria. {Eur J Nutr. 2011 Feb;50(1):1-17 and Anaerobe. 2012 Aug;18(4):405-413.}

Probiotics and Allergy:  Lactobacillus and Bifidus reduce the risk of eczema for children when used by pregnant and breast-feeding women. Lactobacillus reduces symptoms of eczema/atopic dermatitis for children and adults. Probiotics prevent and treat food allergies. The neonatal gut starts out nearly sterile. Breast-feeding, the environment, use of antibiotics all influence the infant’s microflora. Probiotics play an important role in establishing and maintaining a child’s general health. There is also benefit in preventing upper respiratory tract infections.  Probiotics improve the endogenous intestinal barrier and enteral antigen balance; improve regulation of secretory inflammatory mediators; decrease the Th1/Th2 ratio and reduce serum IgE levels.

Probiotics for Infant Regurgitation:  In a randomized controlled trial, formula-fed infants (mean age: 6 weeks) received lactobacillus reuteri or placebo for 4 weeks. The median number of regurgitation episodes during the final 7 days was lower with active treatment than with a placebo: 1 vs. 4 episodes. {Eur J Clin Invest. 2011;41:417-422.}

Probiotics and Vaginosis:  The vagina and its microbiota form a finely balanced ecosystem dominated by  lactobacilli. Lactobacilli play an important role in maintaining a favorable vaginal acidic pH and hydrogen peroxide production. Probiotics can improve vaginal health, microbiota balance, and reduce and treat some vaginoses. For example, some women can prevent recurrent vaginal yeast infections by routinely douching with plain yogurt once per month. This replenishes normal vaginal flora with healthy probiotics that suppress yeast.

Probiotics for aspirin-induced GI damage: In a randomized trial, elderly patients taking 100 mg/day of aspirin who had unexplained iron deficiency anemia received L. casei (5.5 billion to 63 billion) for 3 months. Compared with a control group that did not receive probiotics, the L. casei group had significantly fewer small intestinal mucosal breaks and significant improvement in intestinal mucosal appearance. {J Gastroenterol. 2011;46:894-905.}

Probiotics before colonoscopy:  In a double blind study, constipated patients scheduled for colonoscopy received probiotics (Bacillus subtilis and Streptococcus faecium) or placebo 3 times daily for 2 weeks prior to the colonoscopy. Compared with placebo, the probiotics increased the proportion of patients who had a satisfactory bowel preparation (54.9% vs. 20.8%). {Dig Dis Sci. 1010;55:2344-2351.}

Probiotics may boost your mood. A gut full of beneficial bacteria seems to promote the production of brain neurochemicals that ease feelings of anxiety and depression, while an abundance of harmful  bacteria may actually trigger these symptoms.

                                                    TAKING “PREBIOTICS”

          Prebiotics are carbohydrates that feed the beneficial bacteria in your body. Prebiotics include: slightly green or under-ripe bananas; durum pasta or egg noodles; sourdough bread; boiled rice (especially arborio, S. Andrea, and originario); the pectin in green apples; onions, leeks, and garlic (raw or cooked); Jerusalem artichokes; asparagus; raw chicory root; cooked oats; blueberries; and cooked dried beans (pinto, black).

          Eating prebiotics feeds Akkermansia microphilia, a bacteria which helps to regulate the immune system; increases vitamin D receptors and helps to regulate their function; helps fat absorption; helps bile-salts to function as nutrient signaling molecules; and, causes decreased C. difficile in the gut. NOTE: CBD oil also helps to feed A. microphilia and helps improve gut health.

                                          SPECIFIC DISEASE BENEFITS

          Although research tying specific probiotic strains and species to particular diseases is still in its infancy, scientists have identified a few disease treatment benefits for six of the most studied probiotic species:

1. Lactobacillus acidophilus:  reduced diarrhea and improved bowel function in cases of radiation-induced enteritis. Increased HDL  (good) cholesterol.  Improved markers for metabolic syndrome, inflammation, and heart disease.  Improved allergy-driven immune response.  Improved markers  for ulcerative colitis and irritable bowel disease.   Increased control of blood sugar. Decreased   the DNA damage that can trigger malignant cell development.
2. Lactobacillus rhamnosus:   reduced diarrhea and improved bowel comfort in cases of radiation-induced enteritis. Improved markers for metabolic syndrome, inflammation, and heart disease. Reduced  allergic response to milk in milk sensitive patients. Improved markers for ulcerative colitis, Crohn’s  disease  and improved irritable bowel syndrome. Also, there is an important association with helping with weight loss.
3. Lactobacillus paracasei:  enhanced therapeutic management of minimal hepatic encephalopathy. Improved markers for metabolic syndrome, inflammation and heart disease in elderly patients. Improved markers  for ulcerative colitis.
4. Bifidobacterium lactis:  improved immune function in healthy elderly individuals. Greater weight  gain and less gut inflammation in preterm infants.  Improved  immune response and respiratory symptoms from birch pollen allergies in children. Increased control of blood sugar.
5. Bifidobacterium bifidum:  improved markers for liver inflammation and damage in alcohol-related liver disease. Improved inflammation profiles in ulcerative colitis.
6. Bifidobacterium longum:  reduced diarrhea and improved bowel function in cases of radiation-induced enteritis.  Increased  HDL cholesterol.  Improved  markers for ulcerative colitis and Crohn’s  disease. Decreased  the  DNA damage that can trigger malignant cell development.  They improve cognition and decrease stress physiology and behavior. {This was not noted when people were given Lactobacilli because different bacterial strains will cause different effects.
7. The probiotic Lactobacillus Reuteri lowers cardiovascular risk:  L. reuteri 30242 produces an enzyme called bile salt hydrolase which makes cholesterol less absorbable so that it becomes trapped in the gut and later excreted in fecal matter. Further cholesterol reduction comes from the organism’s ability to increase cholesterol metabolism, thereby promoting its breakdown and excretion. It additionally reduces inflammatory markers.  A proprietary product called “FlorAssist Heart Health Probiotic” is available from www.LifeExtension.com.  
8. Saccharomyces cerevisiae, is a yeast found in sourdough bread, which helps to normalize intestinal microbial flora and specifically relieve symptoms associated with irritable bowel syndrome. Also, Saccharomyces Cerevisiae-Derived Peptides (SCDP): 500 mg twice per day help to induce weight loss by limiting calorie intake by modulating appetite regulating hormones, reducing new fat production, reducing body weight and fat mass, and, most importantly, reducing the size and weight of dangerous abdominal fat. Having a waist circumference out of proportion to BMI is an important cardiovascular risk factor. A proprietary product is available from www.LifeExtension.com called “Eatless peptide complex”. {Additionally, Perilla frutescens is an herb in the mint family that has beneficial flavonoids, especially vicenin-2 and rosmarinic acid which inhibit excitatory nerve and muscle activity in the intestines, which relaxes gut motility and reduces pain perception. It reduces inflammatory signaling molecules. And, it also supports the intestinal barrier reducing permeability–leaky gut. A proprietary product containing 150 mg of Perilla leaf extract plus the probiotic Saccharomyces cerevisiae called “Tranquil Tract” is available from www.LifeExtension.com.
9. Another product combines a 15 billion colony forming unit blend of 6 different probiotics PLUS 4 types of BACTERIOPHAGES called “Florassist GI with Phage Technology”.  The addition of bacteriophages is designed to remove unwanted bacteria in the intestines to make room for the beneficial probiotics. Phage cocktails have been used successfully in numerous human clinical and therapeutic settings to treat common bacterial invaders, including staph, strep and E. coli. They have demonstrated an extremely strong safety profile. Phage therapy encourages the growth of healthy bacteria in the gut microbiome which can competitively reduce harmful bacteria. Developed more than 100 years ago, phage therapy is experiencing a revival with the rise of antibiotic-resistant bacteria.
10. S. salivarius strain BLIS M18 and Bacillus coagulans GBI-30, 6086 supplementation results in significant improvement in oral and gum health. S. salavarius produces enzymes that help break down dental plaque and neutralizes acid to maintain a healthy oral pH.  A low pH demineralizes teeth and creates an environment in which bad bacteria thrive. It produces “lantibiotics” that kill competing organisms associated with periodontitis and reduces levels of cytokines associated with gingivitis. Bacillus coagulans competitively inhibits the growth of Streptococcus mutans which contributes to tooth decay and also reduces the production of inflammatory cytokines that promote the inflammatory response. A proprietary product is available from www.LifeExtension.com called “Florassist Oral Hygiene”.
11. S. salvarius K12 promotes throat health by helping to regulate inflammation and reduce damage caused by organisms that reside in the throat. It produces locally acting lantibiotics that target and inhibit beta hemolytic streptococcal infections. Clinical studies demonstrate a significant reduction in strep throat infections in people supplementing with S. salivarius K12 lozenges. It also contributes to a reduction in viral sore throats attributed to a reduction in cytokine signaling molecules including interferon gamma. A proprietary product is available from www.LifeExtension.com called “Florassist Throat Health.”
12. The combination of Lactobacillus helveticus R0052 plus Bifidobacterium longum R0175 helps to restore normal neurochemical and hormonal balances that obviate the symptoms of anxiety and depression. This combination also helps to decrease anger and hostility scores and chronic stress levels, and improved mood scores, and reduced stress induced abdominal pain, nausea and vomiting. A proprietary product is available from www.LifeExtension.com called “Florassist Mood”.
13. Pu-erh Tea is a unique probiotic. It is made from Camellia senensis leaves in the Yunnan district of southwest China. Fully fermented black tea is aged under high humidity and molds and bacteria grow on the leaves. It has less caffeine than black tea and the bacteria produce a small amount of lovastatin which can help to lower lipids. It is an acquired taste because the tea may smell musty and taste stale.
14. Lactobacillus helveticus can improve sustained attention, especially in older adults.

          A probiotic that is 100 times more potent than the average probiotic is called “VSL#3” containing 3 species of Bifidobacterium, 4 species of Lactobacillus, and 1 species of Streptococcus. There are 450 billion bacteria in each flavored and unflavored packet that can be mixed into cold or room temperature beverage or soft foods, or a vegetarian capsule that contains 112.5 billion bacteria in each capsule. It can be obtained from www.vsl3.com. Prescription strength “VSL#3-DS” (double strength) contains 900 billion live cultures of bacteria. It is particularly helpful for gastrointestinal problems including IBS and Ulcerative colitis. There are no adverse effects nor risk of overdosing.

                                                   LEAKY GUT SYNDROME

          Leaky gut syndrome may be the underlying cause for developing and exacerbating auto-immune diseases.  Zonulin is a protein at the tight junction between the epithelial cells lining the small intestine which selectively opens up the space between enterocytes and allows certain substances to enter the body while keeping others in the gut.  It is thought that large protein molecules, foreign substances and even microorganisms can enter the blood stream when the space at the tight junction between cells in the small  intestine is wider than it should be. Antibodies then target these antigens that don’t belong in the body, and an immune response develops. Where an auto-immune disease develops is a function of the antibodies attacking similar proteins in the body. Thus, the same basic problem has many manifestations. The tight junctions between enterocytes are perpetually opening and closing in response to a plethora of stimuli such as food, hormones, inflammatory markers, and the dietary state. Certain microorganisms can hijack the cellular pathways at these tight junctions or increase the zonulin levels, leading to increased gut permeability. One of the most powerful triggers is gliadin, a protein found in wheat. Like gluten, it has been linked to celiac disease. The idea that a porous intestine directly leads to disease is controversial. However, physicians don’t know enough about the gut, which is our biggest immune system organ, so we need to acknowledge our ignorance and keep an open mind because this theory may indeed be an accurate explanation. Food sensitivities are real. I believe that probiotics are essential for management. Also, anecdotally, thousands of people have benefitted from a gluten/gliadin-free (wheat free) diet even if they test negative for celiac disease. Additionally, nutritional supplements such as glutamine can be beneficial. 

                                                                    DYSBIOSIS

          When the ratio 85% “good microorganisms” to 15% “problematic microorganisms” of a healthy gut is disturbed, a condition called “dysbiosis” occurs. Also, an overgrowth of certain organisms can cause this problem, such as an overgrowth of Candida albicans. For example, 2 phyla of anaerobic bacteria, Firmicutes and Bacteroidetes, are so-called “fat-bugs” because they are associated with obesity. Food emulsifiers and artificial sweeteners enhance the growth of these bacteria which also results in insulin resistance. These fat-bugs can cause food cravings and manipulate our behavior: they change the number of dopamine receptors AND also change the reward centers in the brain. We need the balanced 15% problematic bacteria to keep our GALT stimulated so that our immune system can help us to prevent and fight off an infection. The GI tract is really the external world inside us, so we need this protection.

                                                 THE GUT-BRAIN CONNECTION

          The “Enteric Nervous System (ENS)” is separate from the Central Nervous System (CNS). It is composed of 2 thin layers of over 100 million nerve cells—more than in the spinal cord. The ENS lines the GI tract and controls blood flow, secretions and contractions. It also helps us to unconsciously “feel” (like a second brain) what is occurring in the GI tract. It has glial cells to support the gut neurons. It uses over 40 different neurotransmitters. It produces 50% of the body’s dopamine and 95% of the body’s serotonin. L. brevis can produce GABA. It has a barrier, similar to the blood-brain barrier, for protection. It may have its own memory (although it is not capable of thought). The gut and the brain are connected by the vagus nerve with about 90% of the signals going from the gut to the brain. {The vagus nerve also connects cardiac functions.} The bi-directional communication occurs by various physiological channels including autonomic pathways, neuro-endocrine pathways and neuro-immune pathways. People with Parkinson’s disease have the same protein clumps in the ENS as in the CNS. And, people with Alzheimer’s disease have the same neurofibrillary tangles and amyloid plaques in the ENS as in the CNS. {Thus, a gut biopsy may make earlier diagnosis possible.} 

          Both external and internal STRESS can create a challenge or a threat that disrupts an organism’s homeostatic balance. It can alter the composition and the function of the gut microbiota. For example, maternal stress can affect the fetal gut microbiome directly and through epigenetic factors. This can affect systemic dysregulation in early life and persist into adulthood. Potentiation of heightened anxiety may be transmitted because of this complex mixture of both biological factors as well as psychological factors that act in feedback loops. Chronic stress is associated with dysregulation of the hippocampal-pituitary-adrenal (HPA) axis. Irritable bowel syndrome results from a heightened gut sensitivity and limited ability to modulate an acute stress response.

          Vaginally delivered infants have a different and increased variety of  microbiotia than babies born by C-section. (Variability in flora becomes similar by about 8-weeks.) Hospital use of antibiotics and different feeding patterns (bottle vs. breast-feeding) also affect neurobiological development. Aging adults in long-term facilities compared to living in their communities have less diversity in their gut microbiome. 

          Changes in the microbiota may help to ameliorate psychological disorders. A probiotic cocktail has been associated with improving depression on the Beck Depression Inventory. L. helveticus can improve sustained attention in older adults. Polyunsaturated omega-3 fatty acids modify the gut microbiota resulting in improved cognition, dampened HPA activity with less anxiety and depression, and improved psychological well-being.

                                                THE GUT-HEART CONNECTION

          Probiotics can reduce both systolic and diastolic blood pressures. The greatest effect is found when the baseline BP is elevated and when the daily consumption is >100 billion colony forming units for over 8 weeks duration. Lactobacilli help to reduce blood cholesterol levels. Some bacteria express the enzyme bile salt hydrolase which affects intestinal cholesterol reabsorption. Yogurts help to decrease total cholesterol andLDL-cholesterol and improve the LDL/HDL ratio. There is an inverse relationship between fiber consumption and CVD: the more fiber ingested, the less the risk for CVD. Prebiotics stimulate bacteria to produce butyrate which helps to lower cholesterol, triglycerides and atheroma plaques.

          Modifiable risk factors include: 1) Obesity: Germ-Free mice (GF-mice) are a useful model. They are leaner than wild mice. When there is a fecal transplant from obese mice to GF-mice, they become fatter than from lean mice donors. 2) Cholesterol levels: certain gut microbes, such as Eggerthella, Pasteurellaceae and Butyricimonas alter the bile acid pool which modulates hepatic and systemic lipid and glucose metabolism. 3) Toxic burden: microbes can directly alter chemical activity and structure; produce metabolites that compete for detoxification pathways; and, affect expression of detoxification enzymes. 4) Leptin and Insulin resistance: microbial fermentation of dietary fiber produces a short-chain fatty acid called butyrate which increases leptin expression in adipocytes and improves insulin sensitivity. 5) Inflammation: gut microbes mediate inflammatory signals. Age-associated dysbiosis causes increased inflammation and increased CVD. 6) Nutrient deficiency: gut microbes synthesize B-vitamins, vitamin K and vitamin C and some are absorbed by the host. However, “greedy microbes” may preclude absorption. 7) TMAO and Heart disease: Trimethylamine-N-Oxide (TMAO) is produced via microbial metabolism of choline to trimethylamine (TMA) with subsequent oxidation in the liver. An increased amount of TMAO is an independent risk factor of increased CVD. It is microbial dysbiosis, and not dietary choline, which is the problem.

          The liver is a key player between the gut and the heart during nutrient deprivation (that is, fasting). In fasted GF-mice, the heart relies upon glucose metabolism for energy. Evolutionarily,because the heart needs a constant supply of energy to function, it has the capacity to use different substrates, depending upon availability. In mammals, fasting conditions cause an increased production of ketone bodies in the liver which results in increased ketone utilization by the heart, brain and other tissues. Gut microbes can cause increased acetate production which increases the pool of hepatic Acetyl CoA which is the starting molecule for ketone production.

          Gut pathologies and CVD: 1) Dysbiosis: animals with hypertension have an increased Firmicutes to Bacteroides ratio, and they have decreased bacterial diversity and richness. Also, they have decreased butyrate and acetate microbial metabolites with resultant increased inflammation. People with chronic CHF also have decreased microbial diversity and diminished important bacterial genra. 2) Small Intestinal Bacterial Overgrowth (SIBO): is associated with increased arterial stiffness and decreased Matrix Gla Protein (MGP), which when activated prevents the calcification of blood vessels. Decreased MGP is related to decreased vitamin K absorption by the small intestines and/or to decreased vitamin K production by colonic bacteria. Also, SIBO causes systemic inflammation which is associated with increased CVD. 3) Infections: Chlamydia pneumoniae and Helicobacter pylori infections are associated with increased CVD. Patients with chronic CHF had increased quantities of pathogenic bacteria, including Campylobacter spp, Shigella spp, Salmonella spp, Yersinia enterocolitica, and Candida spp in their colons. Bacterial DNA can be identified in >50% of coronary plaques. 4) Intestinal Permeability: A “leaky gut” allows bacteria and their metabolites to enter the blood stream, triggering an immune response, and allowing them to become associated with the heart. TLR4, a receptor of the adaptive immune system, binds to lipopolysaccharides which are a component of gram-negative bacterial cell walls. This binding initiates inflammatory signaling. In mice, if the TLR4 receptor is ablated, there is decreased atherosclerotic plaque formation. Increased intestinal permeability both induces inflammation and weakens coronary plaque stability. {Plaque rupture is the trigger for an acute MI.} Patients with chronic CHF have increased intestinal permeability compared with healthy controls.

                                         SUGGESTIONS TO HEAL A LEAKY GUT

1. Eat probiotic rich foods—fermented foods like kefir, yogurt and sauerkraut.
2. Eat raw honey and bee pollen.
3. Get a dog or a cat for a pet.
4. Swim in the ocean.
5. Get grounded: “Earthing”.
6. Regularly take soil-based, spore-forming probiotics, such as “Megasporebiotics”.
7. Eat locally from Farmer’s Markets.
8. Substitute for cow’s milk: such as coconut milk, almond milk, hemp milk, rice milk, goat milk or sheep milk.
9. Substitute for wheat flour: coconut flour, almond flour, manioc (tapioca) flour, sprouted ancient grain flours such as buckwheat, sorghum, amaranth, quinoa and millet.
10. Choose healthy oils: coconut oil (or manna), olive oil, flaxseed oil.
11. Substitute for sucrose (table sugar): honey (especially manuka honey), green leaf stevia, maple syrup.
12. ***Use BONE BROTH: it contains gut sealing collagen, key amino acids (proline, glycine, and glutamine), and easily absorbed minerals.

NOTES:

• Coconut products are high in lauric acid which kills pathogenic bacteria and fungi.Fermented vegetables enhance nutrient absorption and provide both prebiotics and probiotics.
• Fermented daily products (kefir and yogurt) provide probiotics and decreased lactose.
• Cooked vegetables, especially boiled or steamed) are easier to digest than raw and are packed with vitamins, minerals and antioxidants.
• Grass-fed meats and wild-caught deep sea fish have increased omega-3 fatty acids.
• Soil-based organisms help heal the gut. a) Bacillus subtilis elicits an immune response that supports healing the gut lining and suppresses pathogenic bacteria. b) Bacillus coagulans improves nutrient absorption. Spores are activated by stomach acid and bile salts and produce lactic acid in the intestines which helps to reduce inflammation.
• Medicinal mushrooms, such as Cordyceps, Reishi, Shiitake, Lion’s Mane, and Turkey Tail, help to balance microbes in the microbiome. They supply prebiotics to keep them fed. They boost the immune system, detoxify chemicals and heavy metals, and help to reduce histamine release. They inhibit pathologic immune responses in auto-immune disorders, destroy tumors and cancer cells, and help to fight viruses and Candida. They act as adaptogens to balance cortisol and stress responses.
• Blue-green Algae, such as Spirulina and Chlorella, are nutrient rich.
• Beneficial yeast, such as Saccharomyces boulardii destroy pathogenic bacteria and improve diarrhea; relieve intestinal gas and bloating; repair intestinal wall mucus membranes; strengthen GALT; help inflammatory bowel disease; help acne; and, help destroy Candida albicans.
• Bentonite clay (1 teaspoon 3x/day) can help with constipation and cleansing the intestines. However, too much along with not enough water can be constipating.
• Bone Broth is nutrient dense, easy to digest, full of collagen and the beneficial amino acids proline, glycine and glutamine. It helps to decrease inflammation and heal a leaky gut by restoring the mucosal lining. It provides easily absorbed minerals such as calcium, phosphorus, magnesium, silicon and sulfur. It contains glucosamine which helps to stimulate and heal the immune system. Beef bone broth is high in types 1 and 3 collagen which helps the skin and nails. Chicken bone broth is hight in type 2 collagen which helps the gut and joint cartilage. Fish bone broth is high in type 1 collagen which helps to produce human type 1 collagen which is found in 90% of the body. Drink 1 to 2 cups of bone broth daily “to heal and seal”.

                                       CONSIDERATIONS FOR THE FUTURE

1. Treating colitis with fecal transplants to re-establish healthy gut flora in patients who have received antibiotics with consequent resistant C. Difficile infections.
2. Banking a patient’s own microbiome before chemotherapy in order to be re-inoculated them afterwards to speed their recovery.
3. Treating babies with microbes that shape the immune system to stave off autoimmune diseases like asthma and psoriasis. For example, c-section babies, who miss out on their mother’s vaginal flora through a passage through her vagina, can be washed with their mother’s vaginal fluid after birth to give them a similar protective advantage.

An Interesting story:  Soldiers stationed in Morocco during World War II were getting gravely ill with dysentery, and no one could figure out why or how to stop it. They noticed that locals weren’t getting as sick. When Moroccans began to get ill, they would follow their camels and eat the droppings. Although  this seems disgusting, we now know that the droppings were full of B. subtilis bacteria which cured the disease.

Dr. Chuck Wile, Seminar Series at the Cheng Integrative Health Center, on 12/4/17