All information we provide online or on social media is for education and information exchange only and should not used as medical advise. You should consult your physician for medical care.
Due to high volume of questions that we receive, we apologize that we may not be able to answer all of them.
We take an integrative/holistic view of health and disease management. To provide responsible medical advises, we need detailed medical history including lab reports and an interview (in office or online) in a consultation format. Should you need a consultation, please feel free to call (803)233-3420 or email: info@drwlc.com. Thank you.
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Low carbohydrate diet and ketogenic diet are rapidly becoming the “new” most recommended diets for diabetes, weight loss and metabolic syndrome patients. These diets work very well for most people and lower their blood sugar levels, and body weight. In fact, I recommend low carb/ketogenic diet (with varying degree of strictness for different diseases. For patients with diabetes, cancer and autoimmune diseases, I usually recommend more strict ketogenic diet along with limits on foods with high plant toxins such as lectins, phytoalexins and oxalates etc.
However a small percentage of people may see a rise in their fasting blood sugar after a prolonged period of very low carb or ketogenic diet. Why is this and is this something to be concerned of?
There are several possible reasons why your fasting glucose may rise even if you are on a low carb or ketogenic diet.
Dawn Phenomenon. This refers to the rise of glucose in early mornings due to diurnal changes of our hormones, esp. cortisol. Normally cortisol levels rise in the morning, preparing us for a day’s work ahead. Cortisol increases our alertness, mobilizes energy for our body’s use by raising blood sugar levels. This is normal and happens to everyone. People who are on low carb or ketogenic diet, tend to have more marked Dawn Phenomenon. Usually there is no need for concern of dawn phenomenon. However, we do need to be aware of overreacting adrenal glands which may secret higher than normal amounts of cortisol when under high stressed (early phase of adrenal fatigue or adrenal insufficiency). When this happens, you need to seek out a trained doctor (usually a functional medicine doctor) for help.
Adaptive Glucose Sparing, this is also called physiological insulin resistance. This may happen to those who have been on very low carb or ketogenic diet for quite a while and their body is used to burning fat as fuel (so called keto adapted or fat adapted), with much reduced need for glucose. Under these circumstances, glucose is reserved for tissues that need glucose for energy mostly or even absolutely. Fats can only be metabolized as fuel through a biochemical process called TCA cycle in the mitochondria the little powerhouse in our cells. But a few types of cells don’t have mitochondria such as red blood cells and the cells in some part of our eyes. Some of our immune cells also adapted to use mostly glucose as fuel in a process called aerobic glycolysis (in layman’s term: fermentation without oxygen, since these cells are charged with a duty to enter infected sites where oxygen is scarce). Most other types of cells including our brain cells can burn fat as fuel. After being on low carb/ketogenic diet for a prolonged period, our body has adapted to burning fat as fuel and reserving glucose for those cell types that require glucose for energy. So most of our body cells (especially our muscles) learned to “reject” glucose as fuel, sparing glucose for those tissues that have a higher need for glucose. This is called physiological insulin resistance, different from pathological insulin resistance. This is also part of the reason why fasting glucose may rise for those who have been on prolonged low carb/ketogenic diet. No need to worry.
Measurements of our glucose metabolism: Fasting Blood Glucose, HbA1c, HOMA-IR. Fasting blood glucose in only one measurement at a particular time. HbA1c measures the average glucose level over the past 3 months or so, hence, it’s a better measurement of your recent past glucose levels. But fasting glucose and HbA1c only tells part of the story. A better assessment is to take into account both blood glucose and insulin levels. HOMA-IR stands for homeostatic model assessment of insulin resistance.
HOMA-IR = (Blood glucose (mMol/L) * Insulin) / 22.5 or
HOMA-IR = (Blood glucose (mg/dL) * Insulin) / 405
HOMA-IR results:
Excellent Insulin Sensitivity: < 1
Early Insulin Sensitivity: > 1.9
Severe Insulin Resistant: > 2.9
Take 2 different scenarios:
Patient A, fasting glucose of 96, fasting insulin 4 uIU/mL, HOMA-IR: (96 x 4) / 405 = 0.94
Patient A’s fasting glucose is higher than Patient B’s. However, when both fasting glucose and insulin are counted, Patient B is at greater risk for diabetes and metabolic complications in the future.
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Vegetable oils and seed oils like soy, canola, sunflower, grapeseed, corn, safflower, peanut and rice bran oil are loaded with omega-6 linoleic acid (LA), which acts as a metabolic poison when consumed in excess. Anything over 10 grams a day will cause problems in the long run
Seed oils are incredibly proinflammatory and drive oxidation in your body. This oxidation, in turn, triggers mitochondrial dysfunction that then drives the disease process
Soybean oil has been shown to cause irreversible genetic changes in the brains of mice. This was true both for unmodified soybean oil and soybean oil modified to be low in LA. Both produced pronounced effects on the hypothalamus, which regulates metabolism and stress responses
A number of genes in the mice that were fed soybean oil were not functioning correctly, including a gene that produces oxytocin, the “love hormone.” About 100 other genes also affected. These changes could have ramifications for energy metabolism, proper brain function and diseases such as autism and Parkinson’s disease
Olive oil and avocado oil are commonly adulterated with cheaper seed oils, and even pure olive oil is loaded with LA. If you’re in the habit of eating olive oil, you may want to limit your intake to 1 tablespoon per day or less
Your choice of cooking oil can make a profound difference in your health. I’ve often warned against the use of soybean oil. Not only is partially hydrogenated soybean oil loaded with trans fat, which has been linked to heart disease,1 it’s also a source of an omega-6 fat called linoleic acid (LA), which is highly susceptible to oxidation and is typically from GMO seeds.
The problem results once you start to digest this fat, as you break it down into harmful sub-components called advanced lipid oxidation end products (ALEs) and oxidized LA metabolites (OXLAMs) that can cause significant damage at the cellular level. For example, an ALE called 4HNE is a mutagen known to cause DNA damage. Studies have shown there’s a definite correlation between elevated levels of 4HNE and heart failure.
Additionally, LA breaks down into 4HNE faster when the oil it is contained in is heated.2 This is largely why cardiologists recommend avoiding fried foods. ALEs and OXLAMs also play a very significant role in cancer and heart disease.
LA-Rich Soybean Oil Linked to Obesity and Diabetes
In 2015, a UC Riverside research team found soybean oil induced obesity, insulin resistance, diabetes and fatty liver in mice.3 Two years later, they confirmed this by showing soybean oil modified to be low in LA caused less obesity and insulin resistance than the unmodified soybean oil.4
Then, in 2020, that same team published research5,6 showing soybean oil, both the modified and unmodified versions, actually produced genetic changes in the brains of mice, and they were not for the better. However, this time LA was not the primary culprit.
Soybean Oil Linked to Genetic Changes in the Brain
In this surprising study,7 the researchers compared diets high in three different types of fat.
Soybean oil, which has a high LA content
Soybean oil modified to be low in LA
Coconut oil
It is surprising, because I would have thought that the LA produced the damaging effects, but LA was ruled out. So, they have identified yet another reason to avoid consuming soy products. As reported by the UC Riverside, the researchers:8
“… did not find any difference between the modified and unmodified soybean oil’s effects on the brain. Specifically, the scientists found pronounced effects of the oil on the hypothalamus, where a number of critical processes take place.
‘The hypothalamus regulates body weight via your metabolism, maintains body temperature, is critical for reproduction and physical growth as well as your response to stress,’ said Margarita Curras-Collazo, a UC Riverside associate professor of neuroscience and lead author on the study.
The team determined a number of genes in mice fed soybean oil were not functioning correctly. One such gene produces the ‘love’ hormone, oxytocin. In soybean oil-fed mice, levels of oxytocin in the hypothalamus went down.
The research team discovered roughly 100 other genes also affected by the soybean oil diet. They believe this discovery could have ramifications not just for energy metabolism, but also for proper brain function and diseases such as autism or Parkinson’s disease …
[T]he research team has not yet isolated which chemicals in the oil are responsible for the changes they found in the hypothalamus. But they have ruled out two candidates.
It is not linoleic acid, since the modified oil also produced genetic disruptions; nor is it stigmasterol, a cholesterol-like chemical found naturally in soybean oil. Identifying the compounds responsible for the negative effects is an important area for the team’s future research …
‘The dogma is that saturated fat is bad and unsaturated fat is good. Soybean oil is a polyunsaturated fat, but the idea that it’s good for you is just not proven,’ [UC Riverside toxicologist Frances] Sladek said.
Indeed, coconut oil, which contains saturated fats, produced very few changes in the hypothalamic genes. ‘If there’s one message I want people to take away, it’s this: reduce consumption of soybean oil,’ [assistant project scientist Poonamjot] Deol said …”
Seed Oils — A Most Harmful Ingredient in the Modern Diet
While that UC Riverside study claimed the genetic changes in the brain applied only to soybean oil and no other vegetable oils, there are loads of other research showing vegetable oils, also known as seed oils, are some of the most harmful foods you could eat.
In the video above,9 Dr. Chris Knobbe, an ophthalmologist and founder and president of the Cure AMD Foundation, a nonprofit dedicated to the prevention of age-related macular degeneration (AMD), gives an excellent synopsis of why seed oils are the unifying mechanism behind westernized chronic diseases like heart disease, obesity, cancer and diabetes. Some of the points he makes are:
Heart disease, now the leading cause of death in the U.S.,10 was virtually unknown in the 19th century. The same goes for cancer, which caused 0.5% of deaths in 1811 and 5.8% of deaths in 1900 — spiking to more than 31% of deaths in 2010.11
A similar pattern emerged for diabetes, which was rare in the 19th century and had a prevalence of 0.37% in 1935. By 2020, there was a 28-fold increase in 85 years, to a prevalence of 10.5%.
Obesity? Same story. With a prevalence of just 1.2% in the 19th century, obesity increased 33-fold in 115 years, to a prevalence of 39.8% in 2015.12 By 1990, meanwhile, 24% of U.S. adults were diagnosed with metabolic syndrome, which is a combination of high blood pressure, dyslipidemia, insulin resistance, hyperglycemia and visceral obesity.
By 2015, 88% of U.S. adults failed to meet five criteria for metabolic health, measured by blood glucose, triglycerides, HDL cholesterol, blood pressure and waist circumference.13
Macular degeneration and osteoarthritis followed similar striking increases, causing Knobbe to ask, “What was so ubiquitous during this time that could have prompted these changes?” Dietary history provides the answer, with the introduction of four primary processed foods — sugar, industrially processed seed oils, refined flour and trans fats — acting as the culprits.
Seed Oils Are Incredibly Proinflammatory
Download Interview TranscriptThe problem with seed oils is that they’re incredibly proinflammatory14 and they increase excessive oxidative damage in your body. This oxidative stress, in turn, triggers mitochondrial damage and dysfunction that then drives the disease process. Several studies15,16,17,18,19,20,21 have demonstrated the truth of this.
The OXLAMs (LA metabolites) are also cytotoxic, genotoxic, mutagenic, carcinogenic, thrombogenic, atherogenic and obesogenic.22 Then, there’s the issue of direct toxicity from pesticides and herbicides.
Most of the vegetable oils produced today — especially canola, corn and soy — are made from genetically engineered crops and are therefore a significant source of toxic glyphosate exposure. According to Knobbe, the reason these oils have been able to remain in the food supply, despite their high toxicity, is because they’re not acute biological poisons, but chronic ones.23
Seed oils were introduced into the U.S. diet in 1866. By 2010, they made up 32% of Americans’ diet, which amounts to 80 grams per person per day.24 In contrast, in 1865, most people would have only about 2% to 3% of their caloric intake from omega-6 LA from butter, lard and beef tallow.
Ancestrally raised animals had very low omega-6, but this changed significantly once animals started being raised in concentrated animal feeding operations (CAFOs). CAFO pork, for example, can contain up to 20% omega-6 fats, thanks to them being fed a diet high in omega-6 grains.25 The results of this dietary change have been significant.
Today, omega-6 fats make up anywhere from 20% to 30% of the average person’s daily calories, with 80% of it being LA. Instead of 80 grams per day, your goal is to get it under 7 grams per day. That would but you into the healthy percentage range of LA that our ancestors from a mere 150 years ago consumed.
According to a report by Jeff Nobbs,26 6 in 10 Americans have a chronic disease, and heart disease, asthma, cancer and diabetes have increased 700% since 1935. During this time, Americans have been smoking and drinking less, exercising more and eating “healthier” according to conventional guidelines to lower saturated fat and sodium. Nobbs, too, believes seed oil is the missing link that explains why Americans keep getting sicker.
Processed Seed Oils Harm Your Health in Many Ways
Aside from oxidation, inflammation and mitochondrial dysfunction, processed seed oils and vegetable oils like soybean oil also harm your health in other ways. For example, they’ve been found to:27
Damage the endothelium (the cells lining your blood vessels) and cause an increase in penetration of LDL and very low-density lipoprotein (VLDL) particles into the subendothelium.28
In other words, these oils get integrated in your cell and mitochondrial membranes, and once these membranes are damaged, it sets the stage for all sorts of health problems. With a half-life of 600 to 680 days,29 it can take years to clear them out of your body. They also get incorporated into tissues such as your heart and brain. One result of this could be memory impairment and increased risk of Alzheimer’s disease. Canola oil, in particular, has been linked to Alzheimer’s.30
Make your cell membranes more permeable, allowing things to enter that shouldn’t.
Make your cell membranes less fluid, which impacts hormone transporters in the cell membrane and slows your metabolic rate.
Inhibit cardiolipin,31 an important fat in the inner membrane of your mitochondria that needs to have non-damaged fat to perform optimally and facilitate optimal function of the electron transport chain and production of ATP.
Cardiolipin also works like a cellular alarm system that triggers apoptosis (cell death) by signaling caspase-3 when something goes wrong with the cell. If the cardiolipin is not saturated with DHA, it cannot signal caspase-3, and hence apoptosis does not occur. As a result, dysfunctional cells are allowed to continue to grow, which can turn into a cancerous cell.
Inhibit the removal of senescent cells, i.e., aged, damaged or crippled cells that have lost the ability to reproduce and produce inflammatory cytokines that rapidly accelerate disease and aging.
Strip your liver of glutathione (which produces antioxidant enzymes), thereby lowering your antioxidant defenses.32
Inhibit delta-6 desaturase (delta-6), an enzyme involved in the conversion of short-chained omega-3s to longer chained omega-3s in your liver.33
Impair your immune function and increase mortality from COVID-19. Saturated fat, on the other hand, may lower your risk of death.34 The authors of that study noted that unsaturated fats “cause injury [and] organ failure resembling COVID-19.”
More specifically, unsaturated fats are known to trigger lipotoxic acute pancreatitis, and the sepsis and multisystem organ failure seen in severe cases of COVID-19 greatly resembles this condition. In short, linoleic acid contributes to the inflammatory domino effect that eventually kills some people with COVID-19.
Make your fat cells more insulin sensitive, thereby causing insulin resistance.35
How to Avoid These Dangerous Fats
Considering the profoundly serious damage they cause, eliminating seed and vegetable oils from your diet can go a long way toward improving your health. This includes soy, canola, sunflower, grapeseed, corn, safflower, peanut and rice bran oil.
Also, be mindful of olive oil and avocado oil, as both are commonly adulterated with cheaper seed oils. That said, even pure olive and avocado oil are loaded with LA. If, like me, you’re in the habit of eating olive oil, I would strongly encourage you to limit your intake to 1 tablespoon per day or less. In my view, olive oil is not a magic bullet and if you are already consuming 80 grams of LA per day, it will only worsen, not help, your health.
To avoid these oils, don’t cook with them, of course, but also avoid processed foods, condiments, fast foods and restaurant foods. If you eat out, you’re undoubtedly eating unhealthy amounts of seed oils, as most restaurant foods are loaded with it.
Fried foods, dressing and sauces tend to be key culprits. Your best bet is to prepare most of your food at home, so you know what you are eating and, in the case of seed oils, what you’re not.
Conventionally raised chicken and pork are also very high in LA, and therefore best avoided. As mentioned earlier, CAFO animals are routinely fed grains such as corn, and as a result, their meat becomes high in LA, as the corn is loaded with it. You can learn more about this in Joe Rogan’s interview with Dr. Paul Saladino, author of “The Carnivore Code.”
How Much Linoleic Acid Is Too Much?
Many now understand that your omega-6 to omega-3 ratio is very important, and should be about 1-to-1 or possibly up to 4-to-1, but simply increasing your omega-3 intake won’t counteract the damage done by excessive LA. You really need to minimize the omega-6 to prevent damage from taking place.
Ideally, consider cutting LA down to below 7 grams per day, which is close to what our ancestors used to get before all of these chronic health conditions, including obesity, diabetes, heart disease and cancer, became widespread. If olive oil puts you over the limit, consider cooking with tallow or lard instead.
If you’re not sure how much you’re eating, enter your food intake into Cronometer — a free online nutrition tracker — and it will provide you with your total LA intake. The key to accurate entry is to carefully weigh your food with a digital kitchen scale so you can enter the weight of your food to the nearest gram.
Cronometer will tell you how much omega-6 you’re getting from your food down to the 10th of a gram, and you can assume 90% of that is LA. Anything over 10 grams is likely to cause problems.
Number of cancer chemotherapy drugs are ever increasing!
Cancer treatment costs are ever increasing！
But are cancer patients, families and the society as a whole really benefiting from the ever increasing cancer care costs?
The following data will show that the cancer patients, families and the society do not receive significant benefits. Then,
Who are really benefiting from these ever increasing cancer care costs?
Cancer is a top chronic disease, with 1.9 million new cancer diagnoses and killing more than 600,000 Americans in 2021 (1). Globally, there were 23.6 million new cancer cases and 10 million cancer deaths in 2019, “global burden of cancer is substantial and growing” (2).
Chemotherapy has been the standard treatment for cancer over the past decades. The chemo drug market is $USD 141 billion in 2021 and is expected to double in the next few years to reach ~$USD 290 billion in 2028 (3).
With that much money spent on chemo drugs, are these chemo drugs helping cancer patients? Let’s look at some large scale epidemiology studies.
Nearly 20 years ago, a group of Australian scholars studied the impact of cytotoxic chemo drugs on cancer patients 5-year survival rate, a standard measure of chemo drugs in the USA and Australia. They concluded disappointingly in their paper (4):
“As the 5-year relative survival rate for cancer in Australia is now over 60%, it is clear that cytotoxic chemotherapy only makes a minor contribution to cancer survival. “
Another group of scientists studied the impact of chemo drugs on cancer patients in the United Kingdom (5).
“The NHS Cancer Drugs Fund (CDF) was established in 2010 to reduce delays and improve access to cancer drugs, including those that had been previously appraised but not approved by NICE (National Institute for Health and Care Excellence). After 1.3 billion GBP expenditure, a UK parliamentary review in 2016 rationalized the CDF back into NICE.”
The authors concluded: We conclude the CDF has not delivered meaningful value to patients or society.
A 2017 study published on Nature looked at the global impact of chemo drugs worldwide. They concluded (6):
Of the 277 cancer chemo drugs in clinical trials from 2011 to 2015, 85% had no clinical effect;
The more expensive the cancer chemo drug, the less the clinical effect;
In the low- and middle-income countries, high-tech cancer treatments do more harm than good to patients.
A 2020 JAMA paper studied the 90 FDA approved new cancer drugs between 2000 and 2016. They authors concluded (7):
“In this study, data available at the time of FDA drug approval indicated that novel cancer therapies were associated with substantial tumor responses but with prolonging median overall survival by only 2.40 months. Approval data from 17 years of clinical trials suggested that patients and clinicians typically had limited information available regarding the benefits of novel cancer treatments at market entry.”
The above large scale data from the USA, The United Kingdom, Australia and the whole world spanning the past ~20 years, clearly show lack of evidence of beneficial impact of these very toxic cancer drugs to cancer patients, their families and the society as a whole.
How did they ever become the standard cancer therapy?
Don’t these substantial data indicate the significant flaws in the oncology industry from drug approval process, marketing and all the way down to individual cancer patient management?
Global Burden of Disease 2019 Cancer Collaboration, Kocarnik et al. Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019. JAMA Oncol. 2021 Dec 30. PMID: 34967848.
Morgan G, Ward R, Barton M. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clin Oncol (R Coll Radiol). 2004 Dec;16(8). PMID: 15630849.
Aggarwal et al. Do patient access schemes for high-cost cancer drugs deliver value to society?-lessons from the NHS Cancer Drugs Fund. Ann Oncol. 2017 Aug 1. PMID: 28453615;
Sullivan R, Pramesh CS, Booth CM. Cancer patients need better care, not just more technology. Nature. 2017 Sep 19. PMID: 28933447.
Ladanie et al. Clinical Trial Evidence Supporting US Food and Drug Administration Approval of Novel Cancer Therapies Between 2000 and 2016. JAMA 2020 Nov 2. PMID: 33170262;
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Dr. Andrew Saul, editor-in-chief, Orthomolecular Medicine News Service (orthomolecular.org) today shared with us of his the Epoch Times interview sometime ago, on Vit C and Covid-19.
During the interview, Dr. Saul discussed the abundant research and clinical data of VC’s (indisputable, my word) anti-viral effects, VC on Covid-19 and the censorship on VC. He also discussed my involvement of VC on Covid-19. We were the first to report using VC for Covd-19 and also promoting VC for Covid-19 worldwide.
“Not only did they do a good interview; they also released part 2 a week later. Very unlike most newspapers, they did not edit out comments I made: practically everything I said was in the published articles.” Said Dr. Saul.
The Epoch Times, a NYC based newspaper with 1.5 million readership, interview can be found at:
95% of melatonin in your is made inside your mitochondria (via Cytochrome C) in response to near-infrared radiation (NIR) from the sun.
Only 5% of melatonin is produced in your pineal gland at night.
Mitochondria are the powerhouse of our cells for energy production (in the form of ATP). Lots of free radicals are also produced as byproducts. Excessive free radicals, if not neutralized promptly, will cause damage to mitochondria and other cellular structures.
Mitochondrial dysfunction is observed in most, if not all, chronic diseases, esp. cancers, neurodegenerative diseases (Alzheimer’s, Parkinson’s), cardiovascular diseases, autoimmune diseases and diabetes.
Melatonin is a powerful antioxidant. Melatonin and other antioxidants, such as Vit C, Vit E and glutathione, protect the health of mitochondria and other cellular structures by neutralizing these excessive and harmful free radicals (reactive oxygen species, ROS).
Unfortunately, we usually don’t take melatonin during the day as it will make you sleep. So we need to get exposure to sunshine. Good news is that the NIR portion of sunshine is highly penetrable. You don’t need to necessarily be directly under the sun. Even in the shade, under the tree or around lots of green plants, you’ll get lots of NIR radiation. [1]
Regular sunshine exposure not only increases your Vit D3 levels, but also your melatonin.
We all know by now that Vit D3 is critical for your health, not just for your bone health, but also for the overall health, including your immunity. During this Covid-19 pandemic, there’s been much scientific research that shows low Vit D3 levels are highly correlated with the high infection and mortality rates of Coivd-19. We have been asking you to get more sunshine in order to boost your immunity. Melatonin is one of the powerful antioxidants that we have been promoting for the fight against Covid-19.
We all thought melatonin is produced at night in the pineal gland and when the sun is up and your eyes are exposed to the light, melatonin production stops. New research begins to show that actually the melatonin produced in the pineal gland is only a very small portion of the total melatonin in your body, only 5% to be exact. 95% of melatonin is actually produced in your cells (in mitochondria, the powerhouse of your cells), under the near infrared (NIR) light in the sunshine. [2]
Melatonin (from the Pineal Gland):
Melatonin protects against cancer via multiple pathways
WHO classifies circadian disruptive shift work as a probable carcinogen (Group 2A).
Reduced cancer incidence in “totally” blind people (due to lack of melatonin production inhibition by light in these people). [3]
Melatonin has potent antioxidant activity
Melatonin is produced within mitochondria in response to sunlight and provides targeted protection of mitochondria from free radicals.
Mitochondria is protective against a range of diseases characterized by mitochondrial dysfunction, including cancers, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases and diabetes. Practically mitochondrial abnormality is found in most if not all chronic diseases where such research has been done.
Melatonin may play a role in the prevention and treatment of Alzheimer’s and Parkinson’s diseases (oxidative stress appears to be a key mechanism) and even in Covid-19. [4]
References:
Twohig-Bennett C, Jones A. The health benefits of the great outdoors: A systematic review and meta-analysis of greenspace exposure and health outcomes. Environ Res. 2018 Oct;166:628-637. doi: 10.1016/j.envres.2018.06.030. Epub 2018 Jul 5. PMID: 29982151; PMCID: PMC6562165.
Zimmerman S. and Reiter, R. 2019. http://www.melatonin-research.net/index.php/MR/article/view/19
Feychting M, Osterlund B, Ahlbom A. Reduced cancer incidence among the blind. Epidemiology. 1998 Sep;9(5):490-4. PMID: 9730026.
Reiter RJ, Ma Q, Sharma R. Melatonin in Mitochondria: Mitigating Clear and Present Dangers. Physiology (Bethesda). 2020 Mar 1;35(2):86-95. doi: 10.1152/physiol.00034.2019. PMID: 32024428.
Debate on diet is abundant, whether it’s low carb, low fat or high protein. But there is little doubt in the medical literature that caloric restriction offers abundant health benefits.
I am just finishing a 48 hours fasting, as I am writing this article.
A group of scientists from Yale University and the Pennington Biomedical Research Center recently reported on Science in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) clinical trial showed that a 14% calorie intake reduction improves health with improved metabolic and immune responses, over a period of 2 years.
We have been advising our patients/clients to go on healthy diet including caloric restriction (via intermittent fasting) and low carb/ketogenic diet, nutritional supplementation for weight loss, metabolic disease management for decades with excellent results. We have helped tens of thousands of patients to successfully lose weight. We have improved or cured diabetes, high cholesterol, coronary heart disease, autoimmune diseases, chronic fatigue syndrome and even cancer.
You can achieve caloric restriction via intermittent fasting. I often start a patient acute acute inflammatory state esp. those with autoimmune diseases.
The following is from a woman in her 70s with acute inflammatory skin rash. In addition to high dose Vit C and TotoCell Nutrition, I also placed on caloric restriction, low carb/ketogenic diet. She fasted for a week and saw significant reduction in inflammation. The following composite picture is her skin rash change in a month. She’s been having these red, itching rask for a long time. The one on the right is taken 1 month after treatment, showing significant improvement.
I also reported a local lady here in Columbia SC with skin rash, abdominal pain and fatigue. After being on dietary changes and nutritional supplements, she rapidly recovered.
I have been on intermittent fasting and low carbohydrate diet for ~10 years. I also follow a cyclic ketogenic diet. My stamina and health are in great shape. I compete on the badminton court 3-4 times a week, 2 hours each time against people 10-30 years younger than me. And yet many younger players seem to get tired more easily than I do. Of course, in addition to low carb/ketogenic diet, I also take nutritional supplements including high dose Vit C, TotoCell Nutrition (my own formula containing optimal doses of vitamins, antioxidants and nutrition boosting energy metabolism). I am on BioIdentical Hormone Replacement (BHRT) as well to promote my overall health and slow down the aging process.
Ref:
Spadaro O, Youm Y, Shchukina I, Ryu S, Sidorov S, Ravussin A, Nguyen K, Aladyeva E, Predeus AN, Smith SR, Ravussin E, Galban C, Artyomov MN, Dixit VD. Caloric restriction in humans reveals immunometabolic regulators of health span. Science. 2022 Feb 11;375(6581):671-677. doi: 10.1126/science.abg7292. Epub 2022 Feb 10. PMID: 35143297.
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What can we, the consumers learn from the tragic failure of resveratrol hype?
The heat of Resveratrol for antiaging started earlier this century after some research shows increasing an enzyme called SIRT2 doubles lifespan in yeast1,2, making people to anticipate lifespan extension of humans. SIRT2 gene is also suggested as the reason why people benefitted from calorie restrictions (fasting)3,4. David Sinclair’s lab published a paper in 2003 that resveratrol extends lifespan of S. cerevisiae5. But S. cerevisiae is a single cell organism, quite different from animals such as mice or humans. In 2006, Sinclair’s lab again showed resveratrol improves health and survival of obese mice to make them live almost as long as normal mice3. David Sinclair co-founded a company called Sirtris Pharmaceuticals based on these findings. GSK later bought Sirtris for $720 million. But then other researchers began to wonder why they couldn’t repeat Sinclair’s resveratrol results and the suspicion that the original data was flawed began to surface6. Activating sirtuins can extend lifespan of worms and flies, however their effects on aging are vulnerable to confounding genetical factors7. When these confounding factors are properly controlled, resveratrol’s effects on aging disappeared7. Besides, the benefits of calorie restriction have nothing to do with Sirt2 gene7. This is quite a blow to the scientific foundation of the claim that resveratrol could extend lifespan. There is even some research to show that blocking Sir2 genes may extend lifespan8. It turns out that it’s not resveratrol that activated SIRT1 gene, it’s an artificial dye that was responsible for the Sirt1 gene activation, and resveratrol itself does not activate SIRT1 gene, reported by separate laboratories9,10. So by now, it’s clear that the observation of resveratrol activation of Sirt1 is a lab error. GSK’s $720M dollars investment was based on flawed lab data. A more recent study further shows that resveratrol’s effects are not by activation of SIRT gene but by “induction of low-level replicative stress”11. So resveratrol only “activates” SIRT gene under certain specific conditions in laboratory but not in vivo (inside human body). But GSK is not giving up without a fight. GSK is dumping more money on clinical trials of resveratrol12. But GSK is fighting an uphill battle: 1. Resveratrol is poorly absorbed; 2. The small amount that is absorbed is quickly destroyed at the liver (don’t forget resveratrol is a plant based chemical and there is “foreign” to our body. Our body naturally tends to defend against these “foreign” chemicals by destroying them in the liver. Plant chemicals that are not naturally existing in human are mostly toxins. At low doses, these plant toxins may induce some health benefits by causing “stress” related biological responses from our body. This process is called hormesis.); 3. Resveratrol activates Sirt gene only under very specific conditions that are not found usually in human bodies. GSK (Sirtris) developed a resveratrol derivative called SRT 501 which has a better absorption. There is an ongoing clinical trial of SRT50112. SRT501 was used as a treatment for patients with refractory or relapsed multiple myeloma. The clinical trial was terminated early due to severe side effects including nephrotoxicity13. Over 150 trials using resveratrol has been done with no clear clinical benefits14. Take this randomized, double blind and placebo controlled trial15. Resveratrol of up to 1000 mg for 16 weeks, but no effect on inflammation control was observed. Even worse, those received resveratrol showed an elevation of cholesterol levels. Resveratrol also blunts the positive effects of exercise training16,17.
The National Institute on Aging Interventions Testing Program (ITP) is a government agency responsible for testing of hopeful drugs. Resveratrol didn’t pass the criteria of the National Institute on Aging Interventions Testing Program (ITP). However, ITP was directly told to test resveratrol. ITP ran the resveratrol test 6 times, but all tests still showed negative results of resveratrol18. Over $2B was spent on resveratrol studies over the past 20 years without clear evidence that resveratrol is helpful to health. Facing the mounting evidence against his original hype that resveratrol is a “fountain of youth” from which he benefitted tremendously, he continues to defend his positions to the extend he began to tell lies19.
Important lessons that we, the consumers, should learn from this resveratrol saga/scandal are:
Lab research results don’t equal to clinical results on humans. Scientific experiments are done under specific conditions, often different from those of humans.
Health/medicine is such a vast field that most consumers don’t have the necessary training in the field to really understand these, often falling prey to these hypes.
What can you do, as a consumer, to protect yourself from falling into prey? My advice is to find a medical doctor (not a basic scientist) who has education, training and experience in both basic science and clinical medicine, who puts patients’ health ahead of financial interests.
References:
Kaeberlein, M., McVey, M. & Guarente, L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev13, 2570–2580 (1999).
Swaminathan, N. The Fountain of Youth at the Bottom of a Wine Bottle? Scientific American https://www.scientificamerican.com/article/the-fountain-of-youth-at/.
Baur, J. A. et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature444, 337–342 (2006).
Lee, S.-H., Lee, J.-H., Lee, H.-Y. & Min, K.-J. Sirtuin signaling in cellular senescence and aging. BMB Rep52, 24–34 (2019).
Howitz, K. T. et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature425, 191–196 (2003).
Pezzuto, J. M. Resveratrol: Twenty Years of Growth, Development and Controversy. Biomol Ther (Seoul)27, 1–14 (2019).
Burnett, C. et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature477, 482–485 (2011).
Fabrizio, P. et al. Sir2 blocks extreme life-span extension. Cell123, 655–667 (2005).
Beher, D. et al. Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity. Chemical Biology & Drug Design74, 619–624 (2009).
Pacholec, M. et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem285, 8340–8351 (2010).
Benslimane, Y. et al. Genome-Wide Screens Reveal that Resveratrol Induces Replicative Stress in Human Cells. Mol Cell79, 846-856.e8 (2020).
Sirtris, a GSK Company. A Phase II, Open-Label, Clinical Study to Assess the Safety and Activity of SRT501 Alone or in Combination With Bortezomib in Patients With Multiple Myeloma. https://clinicaltrials.gov/ct2/show/NCT00920556 (2018).
Popat, R. et al. A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. Br J Haematol160, 714–717 (2013).
Curry, A. M., White, D. S., Donu, D. & Cen, Y. Human Sirtuin Regulators: The ‘Success’ Stories. Front Physiol12, 752117 (2021).
Kjær, T. N. et al. No Beneficial Effects of Resveratrol on the Metabolic Syndrome: A Randomized Placebo-Controlled Clinical Trial. J Clin Endocrinol Metab102, 1642–1651 (2017).
Gliemann, L. et al. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol591, 5047–5059 (2013).
Olesen, J. et al. Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men. J Physiol592, 1873–1886 (2014).
Strong, R. et al. Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci68, 6–16 (2013).
Brad Stanfield, MD. Resveratrol – The Unfortunate (& Scandalous) Story.
Amjad, S. et al. Role of NAD+ in regulating cellular and metabolic signaling pathways. Molecular Metabolism49, (2021).
Posted inAnti-Aging/Functional Medicine|Comments Off on What can we, the consumers, learn from the tragic failure of resveratrol hype?
Good news to older adults: It’s not too late to start exercise with a good nutrition program, you may be as young as young people in their 20s (with respect to muscle NAD+, energy metabolism).
Top science journal “Nature” recently (February 17, 2022) reported:
“Furthermore, we found that in the older adults, NAD+ muscle abundance positively correlated with muscle and mitochondrial health parameters. Taken together, these results show that NAD+ is lower in aging human muscle and that NAD+ abundance is directly associated with the healthy aging state of the individual.”
These researchers found that NAD+ is one of the most depleted metabolites with age, as it declines significantly with age. Among older adults who maintained exercise and good nutrition, their (60-85 years of age) NAD+ levels remained normal, even comparable to those of younger adults (in their 20s). This is very encouraging and interesting in the field of anti-aging medicine. This is yet another piece of evidence supporting the importance of mitochondrial energy metabolism in aging. Staying active with good nutrition, especially nutrients that support mitochondria and energy metabolism, is essential for anti-aging.
They also found that these metabolic changes that occur with aging can be reversed by exercise a nd nutrition. This is great for seniors: it’s not too late to start exercising and improve nutrition! Another important takeaway from this study is that glutathione is in high demand within cells as we age. Therefore, supplementing with glutathione or the nutrients used to produce glutathione is crucial. Unfortunately, ordinary glutathione is poorly absorbed orally, with the exception of liposomal glutathione, which is highly absorbed by the gastrointestinal tract. Glutathione precursors such as NAC are commonly used to increase intracellular glutathione levels.
Ref:
Janssens, GE, Grevendonk, L., Perez, RZ et al. Healthy aging and muscle function are positively associated with NAD+ abundance in humans. Nat Aging (2022). https://doi.org/10.1038/s43587-022-00174 -3
Posted inAnti-Aging/Functional Medicine|Comments Off on Good news to older adults: regular exercise with good nutrition slows down aging
About nutritional supplements, the following issues are what I have learned from orthomolecular medicine and anti-aging/functional medicine.
1. RDA vs. ODA. RDA: RDA (Recommended Daily Allowance) is set by FDA and tends to be on the low end for most people. ODA (Optimal Daily Allowance) is based on nutritional studies and is what should be recommended. Most nutritional supplements on the market follow RDA, not ODA.
2. Variety: A good nutrition program should be broad based to include most of the essential nutrients. Research shows that deficiency in vitamins (A, Bs, C, D, K2 etc) and minerals (such as magnesium, selenium) have reached a pandemic level.
3. Antioxidants: Increased oxidative stress (due to excess of toxins and insufficient anti-oxidants intake) is the common biochemical mechanism of most chronic diseases and aging. Supplementation of a wide variety of anti-oxidants, therefore, is essential for optimal health.
4. Mitochondrial nutrition: Mitochondrial dysfunction is another significantly under recognized issue. Most, if not all, chronic diseases and aging have mitochondrial dysfunction. Maintain and/or repairing mitochondrial function is of paramount importance in health maintenance and disease management. Mitochondrial nutrition is part of this program. We included most major mitochondrial nutrients in our TotoCell Nutrition.
5. Most adults have excess calcium and iron. Calcium and iron supplementation without testing is harmful to our health. Yet, I have not seen a multi-vitamin product that doesn’t‘ contain calcium (or iron).
Many years ago, when I started anti-aging/functional medicine, I was buying various supplements on the market for myself. Eventually, I found myself taking 20-30 capsules/tablets daily. Yes, they do make me feel better and more energetic. I also gave them to my parents and they told me they felt better too. The only problem is that there are too many capsules and tablets. That the same problem I had. As a result, I had no choice but to formulate our own TotoCell Nutrition which contains all the vitamins, antioxidants, and nutrients for mitochondria and for bone and heart health and that doesn’t contain any unnecessary preservatives or additives, conveniently packaged for home or travel use). Many of our patients have been taking it with great results. Our products are not for retail sale. It‘s only for our patients and clients under our supervision.
