Dr. Richard Cheng, Cheng Integrative Health Center

Niacin (vitamin B3) has been found to have synergistic effects with several other vitamins and micronutrients:

Omega-3 Fatty Acids
The combination of niacin and omega-3 fatty acids demonstrated a synergistic effect, significantly increasing LDL apoE/apoB ratios and LDL apoA1/apoB ratios, suggesting an enhanced cardiovascular benefit from the combination therapy[1].

Vitamin B12 and Folic Acid
Combining vitamin B12 with folic acid supplements optimizes the reduction in homocysteine levels, potentially amplifying the advantages in preventing cardiovascular disease[1].

Coenzyme Q10 and Vitamin E
The combination of coenzyme Q10 and vitamin E significantly reduced LDL cholesterol, increased HDL cholesterol, reduced atherogenic coefficient, and decreased visceral adiposity index in women with polycystic ovary syndrome, while the individual supplements did not have these effects[1].

Zinc and Vitamin A
Combined zinc and vitamin A supplementation synergistically reduced the prevalence of persistent diarrhea and dysentery in children[2]. Zinc and vitamin A also had a synergistic effect on improving biochemical indexes of vitamin A nutrition[2].

Chromium
Niacin and chromium have synergistic effects on blood sugar levels[4].

Other B Vitamins
Niacin acts synergistically with all B vitamins, especially vitamin B1 (thiamine)[4].

Vitamin C

Vitamin C (ascorbic acid) and nicotinamide (a form of vitamin B3) have been found to exhibit synergistic antimicrobial effects. [6-10]

In summary, key micronutrients that exhibit synergistic effects with niacin include omega-3 fatty acids, vitamin B12, folic acid, coenzyme Q10, vitamin E, zinc, vitamin A, chromium, and other B vitamins like thiamine[1][2][4]. These synergistic combinations can potentially enhance cardiovascular health, nutrient status, and metabolic parameters.

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600480/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585731/
[3] https://www.webmd.com/vitamins/ai/ingredientmono-924/niacin-and-niacinamide-vitamin-b3
[4] https://www.mikronaehrstoffcoach.com/en/micronutrients/micronutrient.322.html
[5] https://www.healthline.com/nutrition/niacinamide[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996180/
[7] https://link.springer.com/article/10.1007/BF00004512
[8] https://www.nature.com/articles/s41467-020-16243-3
[9] https://www.sciencedirect.com/science/article/pii/S1756464621002966
[10] https://www.sciencedirect.com/science/article/pii/S2352513416301284

Several vitamins, micronutrients, and supplements have been studied for potential synergistic effects when combined with near-infrared (NIR) or photobiomodulation therapy (PBMT):

Mitochondrial Support and Electron Donors
– Methylene blue: Acts as a photosensitizer and electron cycler, enhancing mitochondrial respiration.[1][2]
– Coenzyme Q10 (ubiquinol): A key component of the electron transport chain, may amplify mitochondrial effects of PBMT.[1][4]
– Quercetin: An antioxidant that can donate electrons and enhance mitochondrial biogenesis.[4]

Nitric Oxide Donors
– L-arginine and L-citrulline: Precursors for nitric oxide (NO) production, which is increased by PBMT and promotes vasodilation.[4]

Antioxidants
– N-acetyl cysteine (NAC): Boosts glutathione levels and may enhance PBMT’s effects on oxidative stress.[1][2]
– Molecular hydrogen: A selective antioxidant that may potentiate PBMT’s benefits.[4]
– Vitamin C: An antioxidant, but high doses may inhibit PBMT’s initial reactive oxygen species signaling.[1][2][4]

## Metals
– Iron and copper: Essential for mitochondrial function and energy production, deficiencies may limit PBMT efficacy.[4]

Photoprotection
– Niacinamide (vitamin B3): Protects against blue light and UV damage that could interfere with PBMT.[4]
– Carotenoids (beta-carotene, lutein, astaxanthin): Antioxidants that may enhance photoprotection.[4]

It’s important to note that while some supplements may enhance PBMT’s effects, high doses of certain antioxidants like vitamin C could potentially inhibit the initial reactive oxygen species signaling required for PBMT’s therapeutic mechanisms.[1][2][4] Proper dosing and timing of supplements in relation to PBMT may be crucial for optimal synergy.

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855677/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844808/
[3] https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-024-03593-4
[4] https://gembared.com/blogs/musings/enhance-red-light-therapy-supplements-topicals
[5] https://www.aslms.org/for-the-public/treatments-using-lasers-and-energy-based-devices/photobiomodulation

Niacin, a form of vitamin B3, has shown promise as a potential treatment for Alzheimer’s disease based on recent research:

Researchers at the Indiana University School of Medicine found that niacin, when used in animal models, can limit the progression of Alzheimer’s disease.[1][2][3] They discovered that niacin interacts with a receptor called HCAR2 present in immune cells associated with amyloid plaques in the brain. Activating this receptor through niacin stimulates beneficial actions from these immune cells, leading to fewer plaques and improved cognition in the animal models.[1][2][3]

Past epidemiological studies have also suggested that people with higher levels of niacin in their diet have a lower risk of developing Alzheimer’s disease.[1][5] Additionally, niacin is currently being tested in clinical trials for other neurodegenerative diseases like Parkinson’s and glioblastoma.[1][2]

Based on these findings, researchers believe niacin is a promising therapeutic target for Alzheimer’s disease that warrants further clinical investigation. A pilot clinical trial is currently being planned to study the effects of niacin on the human brain.[1][2]

In summary, the available evidence indicates that niacin, an FDA-approved drug, may help modulate the immune response in the brain and slow the progression of Alzheimer’s disease. More research is needed, but niacin appears to be a potentially valuable therapeutic approach worth exploring.[1][2][3]

Citations:
[1] https://www.the-scientist.com/could-vitamin-supplementation-help-alzheimer-s-patients-69897
[2] https://medicine.iu.edu/news/2022/03/niacin-alzheimers-research
[3] https://www.sciencedaily.com/releases/2022/03/220323151716.htm
[4] https://atm.amegroups.org/article/view/101529/html
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1739176/

Vitamin C plays an important role in the pathophysiology and potential treatment of Alzheimer’s disease (AD):

Several studies have found that vitamin C deficiency is associated with the progression of AD. Decreased plasma levels of vitamin C have been observed in AD patients[1]. Vitamin C is an essential antioxidant that is vital for proper neurological development and function[1]. Deficiency of vitamin C has been implicated in the disease progression of AD[1].

Treatment with high-dose vitamin C supplementation has been shown to have beneficial effects in AD. Studies in mouse models of AD found that high-dose vitamin C supplementation can reduce amyloid plaque burden in the brain, ameliorate blood-brain barrier disruption, and improve mitochondrial function[2][3]. This suggests that increasing vitamin C intake could be a protective strategy against AD-related pathologies[3].

Additionally, a critical review concluded that maintaining healthy vitamin C levels can have a protective function against age-related cognitive decline and AD[4]. However, the review also noted that simply taking vitamin C supplements may not be as beneficial as avoiding vitamin C deficiency through a healthy diet[4].

In summary, the evidence indicates that vitamin C deficiency is involved in the pathogenesis of AD, and increasing vitamin C intake, either through diet or supplementation, may have therapeutic potential for slowing or preventing the progression of AD[1][2][3][4][5].

Citations:
[1] https://www.frontiersin.org/articles/10.3389/fnagi.2022.970263/full
[2] https://www.sciencedaily.com/releases/2011/08/110818101645.htm
[3] https://www.nature.com/articles/cddis201426
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727637/
[5] https://news.vumc.org/2017/12/01/vitamin-c-deficiency-mitochondrial-dysfunction-alzheimers/

Alzheimer’s disease is a complex condition that affects memory and thinking abilities. While scientists are still uncovering its exact causes, inflammation and oxidative stress are believed to be key factors. Imagine inflammation as a kind of internal swelling in the brain, and oxidative stress as damage caused by harmful molecules. These processes can harm brain cells and lead to the formation of plaques and tangles, which are hallmarks of Alzheimer’s. Unhealthy lifestyle habits like poor diet, lack of exercise, and chronic stress can worsen these problems. Additionally, exposure to certain toxins in our environment, like heavy metals and chemicals, may also play a role. Plus, deficiencies in essential vitamins and hormones might contribute to the risk of developing Alzheimer’s. By understanding these factors, we can take steps to support brain health and reduce our risk of Alzheimer’s disease.

Alzheimer’s disease is a multifactorial neurodegenerative condition characterized by progressive cognitive decline and memory loss. While its exact cause remains elusive, research suggests that inflammation and oxidative stress play significant roles in its development and progression. Inflammation in the brain, often referred to as neuroinflammation, leads to the activation of immune cells and the release of pro-inflammatory molecules, contributing to neuronal damage and dysfunction. Oxidative stress occurs when there is an imbalance between the production of free radicals and the body’s antioxidant defenses, resulting in cellular damage. These processes can disrupt neuronal communication and contribute to the formation of characteristic Alzheimer’s plaques and tangles in the brain. Additionally, various lifestyle factors, including poor diet, lack of exercise, chronic stress, and inadequate sleep, can exacerbate inflammation and oxidative stress, further increasing the risk of Alzheimer’s disease. Moreover, environmental factors such as exposure to heavy metals and chemicals may also contribute to neurodegeneration. Furthermore, deficiencies in essential vitamins and micronutrients, hormonal imbalances, and genetic predispositions are believed to play roles in the development of Alzheimer’s disease. Understanding these multifaceted aspects of the disease is crucial for developing effective prevention and treatment strategies.

Oxidative stress is a key mechanism in the pathogenesis of Alzheimer’s disease (AD).

Oxidative stress, characterized by an imbalance between antioxidants and oxidants, is a major contributor to the neurodegeneration observed in AD. Increased production of reactive oxygen species (ROS) and free radicals can damage lipids, proteins, and DNA in the brain, leading to cellular dysfunction and death.[1][2][3]

Oxidative stress is an early and prominent feature of AD, occurring even before the accumulation of amyloid-β (Aβ) and neurofibrillary tangles, the hallmark pathological hallmarks of the disease.[4] Studies have found increased markers of oxidative damage in the brains, cerebrospinal fluid, plasma, and peripheral tissues of individuals with mild cognitive impairment and early-stage AD.[4][5]

Genetic and lifestyle risk factors for AD, such as mutations in presenilin genes and the apolipoprotein E genotype, are associated with increased oxidative stress.[2][4] Conversely, interventions that reduce oxidative stress, like caloric restriction, exercise, and antioxidant supplementation, have been shown to promote neuronal survival and potentially reduce the risk or progression of AD.[4][5]

In conclusion, overwhelming evidence from the search results indicates that oxidative stress is a key mechanism underlying the pathogenesis of Alzheimer’s disease, playing a central role in the neurodegeneration observed in this disorder.[1][2][3][4][5]

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840676/
[2] https://jamanetwork.com/journals/jamaneurology/fullarticle/775665
[3] https://www.mdpi.com/1420-3049/24/8/1583
[4] https://academic.oup.com/jnen/article/65/7/631/2646707
[5] https://www.mdpi.com/2076-3921/10/9/1479

Effective antioxidants for brain protection

Based on the search results, several effective antioxidants have been shown to provide neuroprotection and protect the brain:

Antioxidants like carotenoids, vitamin E, ascorbic acid (vitamin C), and flavonoids such as hesperidin can effectively inhibit oxidative stress and lipid peroxidation, thereby preventing brain aging and neurodegenerative diseases like Alzheimer’s disease.[1]

Enzymatic antioxidants in the brain like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) play a key role in protecting brain cells from oxidative damage.[2]

Non-enzymatic antioxidants such as reduced glutathione (GSH) and thioredoxin also help regulate oxidative stress and maintain brain homeostasis.[2]

Antioxidants that can readily cross the blood-brain barrier, like the pyrrolopyrimidine class of compounds, coenzyme Q10, and vitamin E derivatives, are particularly good therapeutic candidates for neurological disorders.[3]

Combining different types of antioxidants, such as vitamin E and vitamin C, or using antioxidants alongside other neuroprotective agents like iron chelators, may provide synergistic benefits in protecting the brain.[3]

Overall, the search results indicate that a variety of plant-derived and endogenous antioxidants can effectively protect the brain from oxidative stress-induced damage and neurodegeneration.[1][2][4]

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372124/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582347/
[3] https://jamanetwork.com/journals/jamaneurology/fullarticle/777432
[4] https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.729757/full
[5] https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01668-9

Vitamin C for brain protection

Vitamin C plays an important protective role in the brain and is highly concentrated in certain brain regions like the cerebral cortex, hippocampus, and amygdala.[1][2] Studies have shown several key mechanisms by which vitamin C benefits brain function:

– Vitamin C is a potent antioxidant that scavenges reactive oxygen species and protects the brain from oxidative damage.[1][2][3]
– It is a cofactor for enzymes involved in the synthesis of neurotransmitters like catecholamines and serotonin, supporting proper brain signaling.[1]
– Vitamin C promotes neurogenesis, neuronal differentiation, and synaptic plasticity, which are important for brain development and function.[2]
– It helps regulate calcium homeostasis and signaling in the brain, which is crucial for neuronal excitability and neuroprotection.[2]

Research indicates that vitamin C levels tend to decline with age and may be lower in certain neurological conditions like Alzheimer’s disease.[1][3][4][5] Supplementation with high-dose vitamin C has been shown to reduce amyloid plaque burden and improve pathological changes in animal models of Alzheimer’s.[5]

Overall, the evidence suggests vitamin C plays a vital role in maintaining healthy brain function, and ensuring adequate vitamin C status may help protect the brain, especially during aging and neurodegeneration.[1][2][3][4][5]

Citations:
[1] https://www.frontiersin.org/articles/10.3389/fnint.2020.00047/full
[2] https://www.mdpi.com/2076-3921/12/2/231
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622720/
[4] https://www.med.upenn.edu/ngg/assets/user-content/documents/journal-club-2023-2024/reduced-morris-blanco-2022-high-dose-vitamin-c-prevents-second-002.pdf
[5] https://www.nature.com/articles/cddis201426

Niacin for brain protection

Niacin, also known as vitamin B3, has several potential benefits for brain health and protection:

Niacin helps protect the brain from age-related cognitive decline. Studies have found that higher dietary intake of niacin is associated with a reduced risk of Alzheimer’s disease and improved cognitive function with aging.[1][2][3] Niacin is required to form nicotinamide adenine dinucleotide (NAD), a vital molecule for cellular functions, and NAD levels decline with aging. Supplementation with niacin may help slow down cellular aging in the brain.[1]

Niacin protects brain cells from stress and injury. It promotes the growth, development, and survival of brain cells (neurons), especially after injury or oxygen stress.[1][5] Niacin has shown benefits in animal models of traumatic brain injury, stroke, and other brain insults, often when combined with other compounds.[5]

Niacin may help treat certain psychiatric disorders. Some research suggests niacin deficiency may be linked to conditions like schizophrenia, and niacin supplementation may help manage symptoms in these disorders by restoring mitochondrial energy metabolism and neurotransmitter balance.[5][3]

However, more research is still needed to fully understand niacin’s mechanisms and optimal therapeutic applications for brain health and protection. Consulting a healthcare provider is recommended before taking niacin supplements, as high doses can cause side effects.[4]

[1] Niacin slows aging and promotes brain health according to the information provided in[1].
[2] Higher dietary intake of niacin is associated with reduced risk of Alzheimer’s disease, as stated in[1][2][3].
[3] Niacin may help treat certain psychiatric disorders like schizophrenia, as discussed in[5][3].
[4] High doses of niacin supplements can cause side effects, so consulting a healthcare provider is recommended, as mentioned in[4].
[5] Niacin protects brain cells from stress and injury, as described in[1][5].

Citations:
[1] https://www.medicinenet.com/what_does_niacin_do_7_benefits_and_5_side_effects/article.htm
[2] https://medicine.iu.edu/news/2022/03/niacin-alzheimers-research
[3] https://themindfulsteward.com/wellness/the-cognitive-benefits-of-niacin-vitamin-b3/
[4] https://www.healthline.com/nutrition/niacin-benefits
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412771/

Low omega-6 PUFA intake for brain protection

Low omega-6 PUFA intake may be beneficial for brain protection, according to the search results:

Polyunsaturated fatty acids (PUFAs) are essential for brain development and function. The ratio of omega-3 to omega-6 PUFAs is important, as it influences neurotransmission and other processes vital for normal brain function.[2]

Dietary deficiencies of long-chain PUFAs during brain development can impair neurodevelopment and cause permanent damage.[1] Increasing omega-3 PUFAs like EPA and DHA, while lowering omega-6 PUFAs like linoleic acid (LA), may provide optimal protection against conditions like depression.[1][3]

Some studies have found a negative relationship between omega-6 PUFA (specifically LA) intake and cognitive function.[4][5] This suggests that lowering omega-6 PUFA intake, particularly LA, may be beneficial for brain health and protection.[1][4]

In summary, the evidence indicates that a diet lower in omega-6 PUFAs, especially LA, and higher in omega-3 PUFAs like EPA and DHA, may be optimal for brain development and protection.[1][2][3]

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445635/
[2] https://journals.sagepub.com/doi/pdf/10.1177/070674370304800308
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065891/
[4] https://www.nature.com/articles/s41538-019-0061-9
[5] https://nutritionj.biomedcentral.com/articles/10.1186/s12937-020-00547-7

High omega-3 PUFA intake for brain protection

Omega-3 polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been shown to have beneficial effects on brain function and structure:

– Omega-3 PUFAs are essential components of neuronal cell membranes, comprising up to 40% of total brain fatty acids. They are crucial for normal brain development and function.[1][2]

– Higher omega-3 PUFA levels, as measured by the omega-3 index in red blood cells, are associated with larger hippocampal volumes and better abstract reasoning abilities in middle-aged adults.[3] The hippocampus is important for learning and memory.

– Omega-3 PUFA supplementation, especially EPA, has been linked to improvements in mood disorders, while DHA is more strongly associated with benefits in neurodegenerative conditions like Alzheimer’s disease.[2]

– In older adults with mild cognitive impairment, supplementation with omega-3s from fish oil has been shown to improve memory and learning performance.[4]

– The omega-3 fatty acids have anti-inflammatory properties and may help protect the brain from the detrimental effects of a high saturated fat diet.[5]

In summary, the evidence suggests that maintaining adequate omega-3 PUFA intake, particularly through dietary sources like fatty fish, may help preserve brain structure and function, especially as we age. Omega-3 supplementation may also provide benefits for those with mild cognitive impairments.[1][2][3][4][5]

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9641984/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404917/
[3] https://news.uthscsa.edu/study-links-omega-3s-to-improved-brain-structure-cognition-at-midlife/
[4] https://www.healthline.com/nutrition/omega-3-fish-oil-for-brain-health
[5] https://www.medicalnewstoday.com/articles/saturated-fat-may-interfere-with-creating-memories-in-the-aged-brain

Low carb/ketogenic diet and intermittent fasting for brain protection

The search results provide evidence that a low-carb ketogenic diet and intermittent fasting can have neuroprotective effects and benefits for brain health:

– The ketogenic diet, which is high in fat and low in carbohydrates, has shown promise in animal models and some clinical studies for protecting the brain against damage and improving cognitive function in conditions like Alzheimer’s disease, Parkinson’s disease, epilepsy, and traumatic brain injury.[1][3][4]

– The mechanisms by which the ketogenic diet may confer neuroprotection include increasing resistance to metabolic stress, enhancing alternative energy substrates like ketone bodies, and stimulating mitochondrial biogenesis.[3]

– Intermittent fasting, which involves periods of calorie restriction alternating with normal food intake, has also demonstrated potential benefits for brain health and cognitive function in animal studies. It may work through metabolic, cellular, and circadian mechanisms.[2]

– While the evidence is still limited, some studies have found intermittent fasting may help with conditions like epilepsy, Alzheimer’s, Parkinson’s, and mood/anxiety disorders.[2]

– The ketogenic diet and intermittent fasting appear to have complementary mechanisms of action in supporting brain function, such as elevating ketone bodies as an alternative brain fuel source.[1][2]

In summary, the available research indicates that a low-carb ketogenic diet and intermittent fasting regimens may offer neuroprotective benefits and help maintain or improve brain health, though more longitudinal studies and clinical trials are still needed to fully understand their effects.[1][2][4]

Citations:
[1] https://www.frontiersin.org/articles/10.3389/fnut.2021.782657/full
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470960/
[3] https://www.ncbi.nlm.nih.gov/books/NBK209323/
[4] https://news.stonybrook.edu/featuredpost/low-carb-diet-could-boost-brain-health-study-finds/
[5] https://biology.ucdavis.edu/news/keto-diets-muscle-and-brain-boost

BHRT (Bio-Identical Hormone Replacement Therapy) for brain protection

BHRT, or bioidentical hormone replacement therapy, may offer some protection against brain fog, cognitive decline, and even Alzheimer’s disease in women, but the timing and type of BHRT used is crucial.

The key points are:

– BHRT with estrogen and progesterone can help restore hormonal balance and alleviate brain fog and poor focus during perimenopause and menopause.[1] The pellet form of BHRT is convenient and allows for steady hormone release.

– Estrogen has been shown to have neuroprotective effects, promoting neuronal growth, reducing inflammation, and supporting brain function.[2][3] Estrogen-only BHRT in midlife (40s-50s) may reduce the risk of dementia by up to 32%.[5]

– However, starting BHRT too late, after age 65 or more than 10 years after menopause, may not provide the same benefits and could even increase the risk of dementia, especially if using a combination of estrogen and progesterone.[4][5]

– The timing of BHRT initiation appears crucial, with the “critical window” hypothesis suggesting BHRT is most beneficial when started around the time of menopause.[4]

– BHRT may be particularly helpful for women who are APOE4 carriers, a genetic risk factor for Alzheimer’s, as it has been associated with larger brain volumes in these individuals.[4]

In summary, BHRT can be a promising approach to protect brain health, but the optimal timing and formulation is important. Consulting with a provider experienced in BHRT is recommended to determine if it is the right choice.[1][3]

Citations:
[1] https://evexiasdenver.com/bhrt-pellets-for-brain-fog-and-poor-focus-during-perimenopause/
[2] https://www.lifeextension.com/magazine/2015/2/heal-traumatic-brain-injury-with-bioidentical-hormones
[3] https://www.hybridmedicalsolution.com/in-the-media/can-bhrt-reduce-the-risk-of-alzheimers-in-women/
[4] https://alzres.biomedcentral.com/articles/10.1186/s13195-022-01121-5
[5] https://www.cnn.com/2023/11/02/health/hormone-replacement-dementia-wellness/index.html

American Heart Association’s Irresponsible News Release of the Intermittent Fasting Study (orthomolecular.org)

This is for information exchange only.  Seek medical attention when necessary.

• Healthy lifestyle: sleep, exercise.
• Diet: Low-carb diet, avoid ultra-processed foods, avoid seed oils (high Ω-6 polyunsaturated fatty acids or Ω-6 PUFA).
• Nutritional supplements:
  • Vitamin C, 5,000-10,000 mg/day.
  • Or liposomal vitamin C, 1000-2000 mg/day.
  • B Vitamins,
  • Vitamin D3, 5,000 to 10,000 IU daily, make sure to maintain blood Vit d3 levels between 50 and  100 ng/ml.
  • Vitamin E, 200 IU/day.
  • Zinc: 25-30mg/day.
  • Liposomal glutathione, 1,000mg/day.
  • Or NAC (n-acetylcysteine): 1,000-1,500 mg/day.
  • Magnesium: 500-1,000 mg/day.
  • CoQ10: 200-400 mg/day.
  • Quercetin, 1,500 mg/day.
  • 3% hydrogen peroxide nebulization, when needed.
  • Other antioxidants such as melatonin.

Integrative Orthomolecular Medicine Recommendations for Sciatica

Richard Z. Cheng, M.D., Ph.D.

Caution: This is for information exchange only. Use it under the care of a trained and experienced healthcare provider.

Sciatica is a debilitating multi-factorial inflammatory disease. Elevated oxidative stress is a hallmark at the cellular biochemical level, is essentially the imbalance of too many toxins (oxidants) and insufficient antioxidants. Clinical management aiming for avoidance and reduction of oxidant toxins and supplementation of antioxidants offers a promising approach.

1. Lifestyle changes to start with a healthy diet:
   1. Low carb/ketogenic diet
   2. Intermittent fasting
   3. Avoid ultra-processed foods
   4. Avoid Omega-6 oil rich seed oils, replace instead with saturated or monosaturated animal-based fats such as butter, lard, avocado, olive oil or coconut oil.
2. Supplementation of antioxidant vitamins and micronutrients including especially high dose vitamins and other antioxidants. On top of a high dose multivitamin supplementation daily, consider adding:
   1. Vit B1, 500 -1,500 mg daily
   2. Vit B2, 500 -1,500 mg daily
   3. Vit C, 3,000 to 10,000 grams in divided doses daily
   4. Vit D3, 5,000 – 10,000 IU daily. Please note to monitor  blood  Vit D3 levels 2 times annually to keep Vit D3 blood levels between 50-100 ng/ml.
   5. Magnesium glycinate or citrate or threonate, 1,000 – 2,000 mg daily.
   6. Omega-3 oil: 4,000 – 8,000 mg daily
   7. Others: other antioxidants and mitochondrial nutrients, photobiomodulation therapy (near infrared, PBMT/NIR).

Oxidative stress plays a crucial role in sciatica

Oxidative stress has been implicated in various conditions, including spinal cord injury (SCI) and neuropathic pain. Studies have shown that oxidative stress is increased in patients with SCI, potentially contributing to the severity of pain (Fatima 2015). Similarly, in rats, hydroxychloroquine-induced oxidative stress has been linked to axonal atrophy in the sciatic nerve and muscle tissues (Uzar 2012). In the context of traumatic SCI, the combination of increased free radical production and low antioxidant levels leads to enhanced oxidative stress, suggesting a potential role for antioxidant therapy (Bedreag 2014). In the specific case of sciatic nerve injury, oxidative stress has been shown to play a role in the pathophysiology of peripheral neuropathy, with potential modulation by N-acetyl-l-cysteine (Naik 2006). Furthermore, prolonged constriction of the sciatic nerve has been found to affect oxidative stressors and antioxidant enzymes in rats, potentially contributing to locomotory deficits and hyperalgesia (Varija 2009). However, the relationship between neuropathic pain and oxidative stress is complex, with some studies showing changes in antioxidant activity in the spinal cord following nerve injury (Guedes 2006, Scheid 2013, Goecks 2012).

Low carb/ketogenic diet for sciatica

Research suggests that a low-carbohydrate/ketogenic diet may have potential benefits for individuals with sciatica. Yarar-Fisher (2019) found that a low-carbohydrate/high-protein diet improved metabolic health in individuals with spinal cord injury, a population that often experiences sciatica. Liśkiewicz (2016) and Field (2022) both reported positive effects of a ketogenic diet on nerve regeneration and neurological outcomes, respectively. Safari (2020) and Guarnotta (2022) demonstrated the efficacy of a low-calorie diet and a very low-calorie ketogenic diet in reducing pain and disability in chronic sciatica and improving metabolic parameters in hypercortisolism, respectively. However, it is important to note that individuals with spinal cord injury, who are more prone to sciatica, often have nutritional deficiencies and may require dietary intervention and education (Levine, 1992). Further research is needed to fully understand the potential benefits of a low-carbohydrate/ketogenic diet for sciatica.

High dose vitamins and antioxidants for sciatica

• B vitamins:

Research suggests that high doses of vitamin B12, a water-soluble vitamin, may be beneficial for treating pain conditions, including sciatica (Buesing 2019, Geller 2017, Wang 2018). Vitamin B12 has been shown to have a positive effect on pain intensity and disability in patients with low back pain (Mauro 2000). However, the specific role of high dose vitamin B1 in treating sciatica is not well-established. Further research is needed to determine the efficacy and optimal dosing of vitamin B1 for this condition. Vitamin B12 deficiency is common in spinal cord injury (SCI) and its replacement can improve neurological and psychiatric symptoms, including pain (Petchkrua, 2003).  Vitamins D, B3, and B12 have been shown to have consistent benefits in SCI patients (Pedroza-García, 2022). Systemic administration of vitamins C and E can attenuate neuropathic pain, including that induced by chronic constriction injury of the sciatic nerve (Riffel, 2016). Intramuscular vitamin B12 has been found to alleviate low back pain and related disability (Mauro, 2000). High-dose vitamin D therapy has been reported to completely resolve chronic pain in sickle cell disease (Osunkwo, 2011). Systemic administration of B vitamins can attenuate neuropathic hyperalgesia and reduce spinal neuron injury following temporary spinal cord ischaemia in rats (Yu, 2014). Tissue levels of vitamin B complex and vitamin B12 vary with progression of crush-induced peripheral nerve injury, suggesting potential benefits of supplementation in the acute period (Altun).

• Vitamin C

High dose antioxidants, particularly vitamins C and E, have been shown to have a positive impact on neuropathic pain and oxidative stress in the sciatic nerve (Riffel 2016, Riffel 2018). High-dose vitamin C has shown potential in treating spinal cord injury (Liao 2004) and reducing neuropathic pain (Riffel 2016). It has also been linked to a reduction in pain days in sickle cell disease (Osunkwo 2012) and a decrease in symptoms of chronic regional pain syndrome (Carr 2017). However, the effectiveness of high-dose vitamin C for sciatica specifically is not well-documented. Other treatments, such as thioctic acid and acetyl-L-carnitine, have shown promise in reducing sciatic pain (Memeo 2008). Further research is needed to determine the specific benefits of high-dose vitamin C for sciatica.

• Vitamin D

Research suggests that vitamin D deficiency is associated with chronic pain, including sciatica (Holick, 2004; Straube, 2009; Helde-Frankling, 2017; Kragstrup, 2011). Vitamins D, B3, and B12 have been shown to have consistent benefits in SCI patients (Pedroza-García, 2022). High-dose vitamin D3 supplementation has been shown to alleviate chronic pain in various conditions, including sickle cell disease (Osunkwo, 2011). However, the evidence for its effectiveness in treating sciatica specifically is limited. Further research is needed to determine the optimal dosage and potential benefits of high-dose vitamin D3 for sciatica.

• High dose antioxidants for sciatica

High dose antioxidants, particularly vitamins C and E, have been shown to have a positive impact on neuropathic pain and oxidative stress in the sciatic nerve (Riffel 2016, Riffel 2018). These antioxidants can also improve endoneurial blood flow, motor nerve conduction velocity, and vascular reactivity in the sciatic nerve (Coppey 2001). Alpha-lipoic acid, another antioxidant, has been found to prevent neural damage after a crush injury to the rat sciatic nerve (Senoglu 2009). However, further research is needed to explore the potential of these antioxidants in the treatment of acute spinal cord injury (Hall 2011).

References

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Recently, a reader reached out to me regarding a public figure who has been diagnosed with ALS, seeking insights and assistance. In response, I’ve prepared a comprehensive integrative analysis of ALS. This complex condition, similar to other chronic diseases, arises from multiple factors. Implementing a multifaceted and early intervention strategy is critical. Such an approach offers a significant possibility of enhancing quality of life and decelerating the progression of ALS, and it may even hold potential for reversing the course of the disease.

Abstract: This comprehensive review explores various factors and therapeutic strategies in the context of amyotrophic lateral sclerosis (ALS). It emphasizes the significant role of oxidative stress in both familial and sporadic ALS, exacerbated by environmental factors like heavy metals and pesticides. The study examines the potential links between heavy metal exposure, glyphosate in herbicides, and the risk of ALS, suggesting that these factors contribute to the disease’s progression through oxidative damage and immunomodulatory changes. It also discusses dietary considerations, such as the impact of ultra-processed foods and omega-6 fatty acids, highlighting the benefits of a ketogenic diet and the potential neuroprotective actions of a high-fat, low-carbohydrate regimen. The review delves into the role of antioxidants and high-dose vitamins B1, B12, C, and D3, noting their varied efficacy and the need for further research. Additionally, it explores emerging treatments like photobiomodulation therapy and methylene blue, underscoring the necessity for more extensive clinical trials to establish their effectiveness in ALS management.

Oxidative stress in ALS

Both familial ALS (fALS) and sporadic ALS (sALS) are associated with increased oxidative stress, which is believed to play a critical role in the dysfunction of motor neurons. Several studies have highlighted the involvement of oxidative stress in ALS, indicating that it is a major contributor to the disease’s pathogenesis. The interplay of genetic and environmental factors, such as exposure to various toxins and heavy metals, has been suggested to enhance oxidative damage in ALS. Additionally, research has focused on the potential therapeutic strategies targeting oxidative stress to improve the condition of ALS patients. Therefore, the evidence from various sources strongly supports the presence of elevated oxidative stress in ALS and its significance in the development and progression of the disease(1–4).

Environmental toxins in ALS

Multiple factors contribute to the elevation of oxidative stress, including environmental toxin overload such as heavy metals and pesticides.

The role of heavy metals in amyotrophic lateral sclerosis (ALS) is a topic of research interest. Heavy metals increase oxidative stress which in turn leads to cascades of immunomodulatory alteration of neurons in multiple sclerosis and amyotrophic lateral sclerosis(5). Several studies have suggested a potential association between heavy metal exposure and ALS. For example, a prospective cohort study found that lead and cadmium may be associated with an increased risk of ALS(6). Additionally, elevated levels of metals, including cadmium, lead, and zinc, have been linked to ALS etiology(7). Furthermore, the toxic metal hypothesis proposes that toxic metals may enter the nervous system, leading to damage and increased susceptibility to ALS(5,8). These findings suggest that there may be a relationship between heavy metal overload and ALS, although further research is needed to fully understand the mechanisms involved.

Glyphosate, the active ingredient in many herbicides, has been linked to an increased risk of amyotrophic lateral sclerosis (ALS). Research suggests that exposure to glyphosate-based herbicides may be intimately linked to the increased occupational risk of ALS in farmers, gardeners, and sportsmen and women(9). A study proposes that glyphosate contributes to ALS by mistakenly substituting for glycine, leading to mitochondrial stress, oxidative damage, and disruption of mineral balance, which can result in motor neuron damage seen in ALS(10). Additionally, glyphosate exposure has been associated with toxicity similar to paraquat, another herbicide linked to increased ALS risk(11). Furthermore, a cohort study found an excess of ALS cases among manufacturing workers exposed to 2,4-D, a herbicide, compared to other company employees(12). These findings suggest a potential connection between glyphosate exposure and the risk of developing ALS.

Ultra-processed foods and omega-6 rich seed oils and ALS

Recent evidence suggests that the consumption of ultra-processed foods is linked to a range of health risks, including a higher risk of dementia(13–15). Ultra-processed foods are defined as products that are high in added sugar, fat, and salt, and low in protein and fiber. They include items such as packaged baked goods, snacks, fizzy drinks, sugary cereals, and ready meals containing food additives. While there is no direct evidence linking ultra-processed foods to ALS, it is generally recommended to minimize the intake of these foods for overall health, including for individuals with ALS(16). Therefore, it is advisable for individuals, including those with ALS, to focus on consuming unprocessed or minimally processed foods and to limit the intake of ultra-processed items(13,16).

The relationship between seed oils high in omega-6 fatty acids and amyotrophic lateral sclerosis (ALS) is a topic of interest. While there is growing evidence linking omega-6 fatty acids to neurological diseases such as Alzheimer’s, the specific impact of these fatty acids on ALS is still being investigated.

One study found that a diet high in vegetable oils, particularly those high in omega-6 fatty acids, was associated with an increased risk of Alzheimer’s disease(17,18). Additionally, elevated levels of arachidonic acid, an omega-6 fatty acid, have been linked to brain changes commonly found in individuals with Alzheimer’s disease(18). This suggests a potential link between omega-6 fatty acids and neurological conditions. In the context of ALS, research has shown that higher blood levels of alpha-linolenic acid, an essential omega-3 fatty acid, were associated with a lower risk of ALS(19). Furthermore, elevated levels of arachidonic acid, an omega-6 fatty acid, have been shown to contribute to motor neuron dysfunction and death in ALS(20). While these findings suggest a potential association between omega-6 fatty acids and neurological diseases, including ALS, further research is needed to fully understand the impact of seed oils high in omega-6 fatty acids on the development and progression of ALS. Therefore, it is important to interpret these findings in the context of ongoing research in this field.

The ketogenic diet has been studied as a potential therapeutic approach for amyotrophic lateral sclerosis (ALS). Research suggests that a ketogenic diet, which is high in fat and low in carbohydrates and protein, may improve the survival and function of motor neurons in ALS and other neurodegenerative diseases(21). It is believed to have a neuroprotective action, improving mitochondrial function and increasing the production of the inhibitory neurotransmitter gamma-aminobutyric glutamate, which may help fix the imbalance between glutamate and GABA in the brains of ALS patients(22). Studies in ALS mouse models have shown that a high-fat diet, including a ketogenic diet, led to weight gain and prolonged survival(23). While there is evidence supporting the potential role of ketogenic diets in treating ALS, more research, including placebo-controlled clinical trials, is needed to determine their effectiveness(23). In conclusion, ketogenic diets have plausible mechanisms for treating ALS, but further research is required to establish their efficacy(24)

Selected antioxidants, vitamins and ALS

Antioxidants have been a subject of interest in the context of amyotrophic lateral sclerosis (ALS)(25). Several studies have highlighted the role of oxidative stress in the pathogenesis of ALS and the potential therapeutic strategies involving antioxidants. Antioxidants such as polyphenols, ascorbic acid, vitamins A and E, glutathione, melatonin, coenzyme Q, beta-carotene, and alpha-tocopherols have been studied for their potential benefits in ALS(1,26). Additionally, impaired antioxidant systems, such as the KEAP1-NRF2 system, have been implicated in ALS, and the activation of NRF2 as a potential therapeutic strategy has been discussed(27). However, it’s important to note that while some studies have suggested the potential benefits of antioxidants in the management of ALS, there is insufficient evidence of their efficacy based on well-designed randomized controlled trials. Therefore, while antioxidants remain an area of interest in the context of ALS, further research is needed to establish their effectiveness as a therapeutic approach(28).

High-dose vitamin B1, also known as thiamine, has been studied in the context of amyotrophic lateral sclerosis (ALS)(29). Research has shown that impaired thiamine metabolism is associated with ALS, leading to decreased adenosine triphosphate (ATP) production and potential neurodegenerative changes in motor neurons(30). Additionally, vitamin B1 has been considered a potential protector for the development of ALS, as it participates in oxidative metabolism, neuroprotection, and carbohydrate metabolism(31).

High-dose vitamin B12, specifically ultrahigh-dose methylcobalamin, has been studied for its efficacy in slowing the progression of early-stage amyotrophic lateral sclerosis (ALS). A randomized clinical trial conducted in Japan showed that ultrahigh-dose methylcobalamin was efficacious in slowing functional decline in early-stage ALS patients(32,33). The study used a 50-mg dose of methylcobalamin and found it to be safe and effective in slowing down functional decline in the early stages of ALS. However, it’s important to note that the effectiveness of high-dose vitamin B12 for ALS is restricted to early-stage patients, and further research is needed to determine its impact on patients in later stages of the disease. The evidence suggests that high-dose vitamin B12, particularly ultrahigh-dose methylcobalamin, may have potential benefits for patients with early-stage ALS. However, more research is needed to fully understand its impact on the disease and its potential use in later stages of ALS.

In the field of amyotrophic lateral sclerosis (ALS) treatment, there is growing interest in the potential role of high-dose intravenous (IV) vitamin C. People with ALS often take vitamin C supplements for its antioxidant properties, which are thought to possibly slow disease progression. Despite this common practice, studies to date have not conclusively demonstrated a significant impact of vitamin C intake, either dietary or supplemental, on ALS risk or progression. One study, in particular, found no substantial link between high intake of vitamin C and ALS risk (26), while another study from mainland China indicated that low serum vitamin C levels might be a risk factor for ALS (27). This suggests that vitamin C supplementation could be a consideration for ALS patients.

High-dose IV vitamin C is also being researched for other conditions, including cancer, with doses ranging from 1.5 g/kg to 2.2 g/kg(34). Given its high tolerance, safety profile, relatively low cost, and accessibility, vitamins C and E are commonly used by physicians and patients, even though clinical trials have yet to provide solid backing for their efficacy in ALS(28). Therefore, while high-dose IV vitamin C is promising in other medical areas, its specific effectiveness and safety in treating ALS remain to be fully explored through further research.

High-dose vitamin D3 has been studied as a potential therapy for amyotrophic lateral sclerosis (ALS). While some studies have reported positive effects of vitamin D in ALS patients, the evidence is not conclusive. A systematic review and meta-analysis found that only one randomized trial reported a slight improvement in ALSFRS (ALS Functional Rating Scale) with a higher dose of vitamin D, but no significant effect was observed in observational studies(35). Another study suggested that vitamin D may impact disease progression and muscle function in ALS, but the establishment of an optimal dose and safety of high-dose vitamin D in ALS patients requires further investigation(36). Additionally, low vitamin D levels have been linked to worse movement loss in ALS, but taking vitamin D supplements was associated with a faster decline, indicating a complex relati(37)onship between vitamin D levels and disease progression(38). While there is some evidence supporting the potential benefits of vitamin D in ALS, further research is needed to confirm its efficacy and safety in high doses for ALS patients.

The search results provide a mixed picture of the potential benefits of high-dose vitamin D3 in ALS. Some studies suggest a possible role for vitamin D in ALS, while others emphasize the need for further investigation to establish the optimal dose and safety of vitamin D supplementation in ALS patients.

Therefore, it is important to consult with a healthcare professional before considering high-dose vitamin D3 as a therapy for ALS.

Other mitochondrial agents (PBMT, methylene blue) and ALS

Photobiomodulation therapy (PBMT), also known as low-level laser therapy (LLLT), has been studied for its potential beneficial effects in the treatment of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Research suggests that PBMT may have beneficial effects on neural activity and may become a veritable therapy for neurodegenerative diseases, including ALS(37,39,40). One study specifically investigated the use of PBMT in a SOD1 transgenic mouse model of ALS, reporting potential benefits(40). While the research shows promise, it’s important to note that more extensive clinical trials are needed to determine the effectiveness of PBMT in treating ALS.

Methylene blue is being studied for its potential in treating amyotrophic lateral sclerosis (ALS). However, the results of these studies are mixed. Several studies have shown that methylene blue fails to produce neuroprotective effects in mouse models of ALS, as it has no effect on motor neuron loss, toxic protein aggregation, or motor function in the tested models(41,42). On the other hand, there are also studies demonstrating the potential benefits of methylene blue in ALS treatment, suggesting that it can rescue toxic effects associated with ALS-related proteins(43). Further research is needed to determine the effectiveness of methylene blue in treating ALS.

Hormones and ALS

Research suggests a complex interplay between sex hormones and neurodegenerative diseases such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). In AD, lower levels of free testosterone and higher levels of luteinizing hormone have been observed in men, potentially influencing the disease’s risk(44). Both estrogens and androgens have been shown to have neuroprotective effects, with their age-related loss increasing vulnerability to AD(45). Inflammation, a key factor in AD, is also influenced by sex steroid hormones(46). In ALS, reduced levels of free testosterone have been found, suggesting a potential role in the disease’s pathophysiology(47). However, the use of hormone therapy in postmenopausal women with ALS has not been found to be protective(48). These findings highlight the need for further research to fully understand the role of sex hormones in these neurodegenerative diseases.

In conclusion, the management of amyotrophic lateral sclerosis (ALS) offers promising avenues through a holistic approach that targets the diverse aspects of the disease. Acknowledging the pivotal role of oxidative stress, influenced by both genetic predispositions and environmental factors such as heavy metals and glyphosate, it is crucial to actively mitigate these elements. Nutritional strategies, especially the reduction of ultra-processed foods and omega-6 rich seed oils, along with the potential neuroprotective benefits of a ketogenic diet, should be embraced. The use of antioxidants and high-dose vitamins B1, B12, C, and D3 is particularly encouraging. These supplements, with their emerging evidence of efficacy, hold great promise in the fight against ALS and warrant deeper exploration in clinical research. Additionally, innovative treatments like photobiomodulation therapy and methylene blue, which focus on enhancing mitochondrial health, are exciting prospects. The interplay of hormones in ALS also presents a potential therapeutic pathway, deserving of careful consideration and research. Ultimately, a personalized treatment plan, underpinned by ongoing advancements in research and a positive outlook on the potential of vitamins and antioxidants, is key to empowering patients and healthcare professionals in managing ALS.

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Marathon running and similar intense exercise activities do seem to increase oxidative stress levels. A study from the Linus Pauling Institute at Oregon State University found that intense exercise such as marathon running can raise oxidative stress. This increase occurs as the body struggles to detoxify the free radicals produced when muscles use oxygen at a rate 100-200 times higher than their normal rate. The study also noted that this intense exercise depletes vitamin levels, specifically vitamin E, which is known for its antioxidant properties. This suggests that the body’s natural capacity to manage oxidative stress is overwhelmed during such intense physical exertion.

Furthermore, a systematic review on the effect of running exercise on oxidative stress biomarkers investigated various biomarkers that predict oxidative stress status among runners. The outcomes included assessments of oxidative damage markers such as malondialdehyde (MDA), protein carbonyl (PC), and total antioxidant capacity (TAC), among others. The study concluded that running exercise does not elicit a response to specific biomarkers of oxidative stress. Instead, oxidative damage markers of lipids, proteins, and various enzymatic and non-enzymatic antioxidants are expressed according to the individual’s training status.

These findings indicate that while intense endurance activities like marathon running do increase oxidative stress, the extent and specific impact may vary based on individual factors like training status and overall health.

1. Thirupathi A, Pinho RA, Ugbolue UC, He Y, Meng Y, Gu Y. Effect of Running Exercise on Oxidative Stress Biomarkers: A Systematic Review. Front Physiol. 2021 Jan 20;11:610112. doi: 10.3389/fphys.2020.610112. PMID: 33551836; PMCID: PMC7854914.
2. Marathon runners deplete vitamins, raise oxidative stress | Oregon State University