Dr. Richard Cheng, Cheng Integrative Health Center

Question: Hi, multiple studies claim Vit C/E blunt hypertrophy and should thus be avoided.  I’d be interested in your opinion on this.

Answer: Whether antioxidants including Vit C blunt the effects of exercise on muscle strength has been one of my interests for a while, since I play badminton regularly (3-4 times a week and ~2 hours each time) for ~15 years.  In a nutshell, I am convinced that Vit C/E (and other antioxidants and mito nutrients) overall offer more health benefits and I have been taking high doses of these supplements (e.g., 10,000 mg or more of Vit C daily) for 15-20 years. And my health including my stamina and endurance is much better than before. I just mixed a bottle of water with 10,000 mg of Vit C, 1,200 mg of magnesium glycinate and 15,000 mg of glycine and ready to go to my badminton practice.

The relationship between vitamin C and E supplementation and muscle hypertrophy is more nuanced than simply claiming they should be avoided:

1. Mixed findings on hypertrophy: While some studies suggest vitamin C and E supplementation may blunt muscle hypertrophy, the evidence is not conclusive. One study found that “vitamin C and E supplement did not significantly blunt muscle hypertrophy during 10 weeks of training”[2]. Another study reported that supplementation “blunts increases in total lean body mass in elderly men after strength training”[3].

2. Potential negative effects on strength gains: Some research indicates that high-dose vitamin C and E supplementation may hinder strength development, though the effects appear to be relatively small. One study found a significant difference in strength gains between placebo and vitamin-treated groups[4].

3. Dose and timing matter: The negative effects were primarily observed with high doses of these vitamins. For example, one study used 1000mg/day of vitamin C and 235mg/day of vitamin E, which are much higher than the recommended daily allowances[5].

4. Importance of timing: Some experts suggest that timing of supplementation may be crucial. Taking antioxidants immediately before or after workouts may be more likely to interfere with muscle adaptations. It’s recommended to have them at least 2 hours prior to exercise and minimally afterwards[5].

5. Overall health benefits: Despite potential concerns for muscle growth, these vitamins still have important health benefits. The negative effects on muscle growth, if any, appear to be small and may not outweigh the overall health benefits for most people[5].

6. Individual variation: The effects may vary depending on factors like age, training status, and baseline nutrition[1].

In conclusion, while there is some evidence suggesting high-dose vitamin C and E supplementation may slightly impair muscle adaptations to strength training, the effects are likely small for most individuals. Rather than completely avoiding these vitamins, it may be more prudent to focus on proper timing and dosage, especially for those primarily concerned with maximizing muscle growth and strength gains.

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973181/
[2] https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/jphysiol.2014.279950
[3] https://www.researchgate.net/publication/279714994_Vitamin_C_and_E_supplementation_blunts_increases_in_total_lean_body_mass_in_elderly_men_after_strength_training
[4] https://examine.com/deep-dives/vitamin-c-and-e-supplementation-may-hinder-strength-training/
[5] https://www.reddit.com/r/Supplements/comments/faegv6/studies_have_found_that_antioxidants_like/

High-dose vitamin C (ascorbic acid) infusion has been explored as a potential cancer therapy, and recent studies suggest it may have varying effects based on individual patient characteristics, including ferritin levels. Ferritin is a blood protein that contains iron, and high levels (ferritinemia) can indicate excess iron storage in the body.

### Mechanism of Action

1. **Pro-oxidant Effect**:
– At high concentrations, vitamin C can act as a pro-oxidant, producing hydrogen peroxide (H2O2) in the extracellular space. This H2O2 can cause oxidative stress selectively in cancer cells, leading to their death, while normal cells typically remain unharmed.

2. **Role of Iron**:
– The pro-oxidant effect of vitamin C is enhanced in the presence of transition metals like iron. High ferritin levels suggest higher iron stores, which can catalyze the formation of reactive oxygen species (ROS) from H2O2.
– This increased production of ROS can induce more significant oxidative damage to cancer cells, potentially making high-dose vitamin C more effective in patients with high ferritinemia.

### Clinical Evidence

1. **Studies and Observations**:
– Some preclinical studies and clinical observations support the idea that the presence of elevated iron levels can enhance the cytotoxic effects of high-dose vitamin C on cancer cells. For example, a study published in *Redox Biology* (2015) showed that vitamin C’s cytotoxicity to cancer cells was potentiated by iron.

2. **Clinical Trials**:
– While clinical trials on high-dose vitamin C in cancer therapy have shown mixed results, they often highlight the importance of patient selection and the biochemical environment. Trials are ongoing to better understand the contexts in which vitamin C is most effective.

### Considerations

1. **Individual Patient Profiles**:
– The effectiveness of high-dose vitamin C may depend on individual iron metabolism and storage. Patients with high ferritin levels might experience more pronounced effects due to the enhanced pro-oxidant activity.

2. **Safety and Monitoring**:
– High-dose vitamin C infusions are generally well-tolerated, but monitoring is necessary to manage potential side effects and ensure safety, particularly in patients with iron overload conditions.

3. **Combination Therapies**:
– High-dose vitamin C is often explored as an adjunctive therapy alongside conventional cancer treatments. Understanding its interaction with iron levels can help optimize such combination therapies.

### Conclusion

High-dose vitamin C infusion may be more effective in cancer patients with high ferritinemia due to the enhanced pro-oxidant effect mediated by elevated iron levels. However, more research is needed to fully establish this relationship and determine the best clinical practices for incorporating vitamin C therapy based on ferritin levels. Personalized treatment plans considering individual metabolic profiles and comprehensive monitoring are essential.

### References
1. **Chen, Q., Espey, M. G., Sun, A. Y., Lee, J. H., Krishna, M. C., Shacter, E., … & Levine, M. (2007).** Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. *Proceedings of the National Academy of Sciences, 104*(21), 8749-8754. doi:10.1073/pnas.0702854104

2. **Doskey, C. M., Buranasudja, V., Wagner, B. A., Wilkes, J. G., Du, J., Cullen, J. J., & Buettner, G. R. (2016).** Cytotoxicity of pharmacological ascorbate in pancreatic cancer cells is enhanced by increasing extracellular iron. *Redox Biology, 10*, 274-284. doi:10.1016/j.redox.2016.10.011

3. **Harrison, F. E., & May, J. M. (2009).** Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. *Free Radical Biology and Medicine, 46*(6), 719-730. doi:10.1016/j.freeradbiomed.2008.12.018

4. **Monti, D. A., Mitchell, E., Bazzan, A. J., Littman, L., Zabrecky, G., Yeo, C. J., & Levine, M. (2012).** Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. *PLoS One, 7*(1), e29794. doi:10.1371/journal.pone.0029794

Lithium has shown promising potential as an anti-aging agent, based on several studies and research findings:

1. Telomere preservation: Long-term lithium treatment has been associated with longer telomere length in patients with bipolar disorder. Telomeres are protective structures at the ends of chromosomes that shorten with age, so preserving telomere length may slow cellular aging[9][10].

2. Oxidative stress reduction: Lithium has demonstrated the ability to reduce oxidative stress, which is a key factor in the aging process[10][12].

3. Epigenetic effects: Studies have found that lithium may influence epigenetic aging processes, potentially slowing down age-related changes in DNA methylation[10][12].

4. Neuroprotection: Lithium has shown neuroprotective effects, which could help maintain cognitive function with age[9][10].

5. Longevity increase: Analysis of a large observational cohort (UK Biobank) found that therapeutic lithium supplementation was linked to decreased mortality in individuals diagnosed with affective disorders[11].

6. Animal studies: Preclinical models have demonstrated potential anti-aging effects of lithium, although results in mice have been mixed[10][11].

7. Population studies: Higher lithium levels in drinking water have been associated with increased life expectancy and reduced risk of neurodegenerative diseases in some population studies[9].

However, it’s important to note that most research on lithium’s anti-aging effects has been conducted in the context of bipolar disorder treatment or animal studies. The effects of lithium supplementation for anti-aging purposes in the general population are not yet well-established. Additionally, lithium can have toxic effects at high doses, so any potential use as an anti-aging supplement would require careful dosing and medical supervision[9][11].

While these findings are promising, more research is needed to fully understand lithium’s potential as an anti-aging agent, determine optimal dosing for anti-aging effects, and evaluate its long-term safety and efficacy in healthy individuals.

Citations:
[1] https://www.amazon.com/Vegetarian-Capsules-Supplement-Supports-Behavior/dp/B017WNWT60?psc=1&smid=A3CBFC1H348Y1J
[2] https://www.truegether.com/listing.html?id=USER.06661928-137d-4d50-ab23-d1f66eef9999
[3] https://www.amazon.com/KAL-ActivMelt-Chelated-Bioavailability-Balanced/dp/B01HTML27Q?psc=1&smid=A35ALG3YA78R28
[4] https://www.lifeextension.com/vitamins-supplements/item02403/lithium
[5] https://novoslabs.com/product/novos-core/
[6] https://www.vitacost.com/best-naturals-lithium-orotate?CSRC=FGPF-817716018607
[7] https://www.walmart.com/ip/KAL-Lithium-Orotate-5mg-Low-Serving-Of-Chelated-Lithium-Orotate-For-Bioavailability-Mood-Support-In-Organic-Rice-Bran-Extract-Base-60-VegCaps/38425158?selectedSellerId=128447&wmlspartner=wlpa
[8] https://pureprescriptions.com/product/lithium-orotate-pure-encapsulations/?attribute_pa_size=180-capsules
[9] https://www.kcl.ac.uk/archive/news/ioppn/records/2018/december/lithium-might-work-as-an-anti-aging-drug-depending-on-your-genes
[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324565/
[11] https://www.aging-us.com/article/204476/text
[12] https://www.sciencedirect.com/science/article/am/pii/S0304394021004298
[13] https://pubmed.ncbi.nlm.nih.gov/34139318/

[14] Microdosing lithium Lithium | Neurologist Reviews Evidence and Top Brands (youtube.com)

[15] 锂，一种有前途的抗衰老剂 (zsxq.com)

Intermittent Fasting (IF) is an eating pattern that regulates the body’s metabolic function and promotes health by eating and fasting at set times. Here are several common intermittent fasting methods and how to practice them.

1. 16/8 Fasting
This is one of the most common and easy-to-follow fasting methods. The 16/8 fasting method means a 16-hour fasting period and an 8-hour eating period every day.

– Determine an 8-hour eating window that works for you, such as 12 noon to 8 pm.
– Eat two to three nutritious meals within the eating window.
– During the fasting period, only water, black coffee or unsweetened tea can be consumed.

2. 5:2 Fasting
This method involves eating normally five days a week and restricting calorie intake (usually 500-600 calories) on two days.

– Choose two days (non-consecutive) to go on a low-calorie diet, consuming 500-600 calories on each of these two days.
– You can eat normally for the remaining five days, but you should also pay attention to a balanced diet and not overeating.

3. Alternate-Day Fasting
Alternate-day fasting means fasting or a very low-calorie diet every other day.

– On the “fasting day”, only consume about 500 calories.
– On the “non-fasting day”, you can eat normally, but you also need to balance it.

4. Warrior Fasting
The Warrior Fasting method only has one four-hour eating window per day, usually in the evening.

– Maintain a light diet throughout the day, such as fruits or raw vegetables.
– Eat a rich dinner within the four-hour window in the evening.

5. Eat-Stop-Eat Method
This method is to fast for 24 hours once or twice a week.

– Choose a day (or two days) and fast for 24 hours from the end of the previous day’s dinner to the dinner time of the next day.
– During this time, only water, tea or black coffee can be consumed.

Practice suggestions
1. Gradually adapt: You can gradually extend the fasting time at the beginning to avoid sudden long-term fasting.
2. Stay hydrated: During the fasting period, drink plenty of water to keep your body hydrated.
3. Balanced nutrition: Make sure to consume enough protein, healthy fats, fiber and vitamins within the eating window.
4. Avoid overeating: Try to avoid consuming too much high-calorie, unhealthy food within the eating window.
5. Listen to your body’s signals: Pay attention to your body’s reactions. If you feel uncomfortable, you can adjust your fasting method or stop.

Notes
Consult a doctor: Before starting any fasting plan, it is best to consult a doctor or nutritionist to ensure that this diet is suitable for your health.

Through scientific and reasonable practice of intermittent fasting, it can not only help control weight, but also improve metabolic health, reduce the risk of chronic diseases, and improve overall health.

Raw spinach is high in oxalate which can contribute to the formation of kidney stones, particularly calcium oxalate stones.[1][3][4]

– Spinach contains higher concentrations of oxalate than most crops, and consuming a normal portion (50-100g) of raw spinach can result in a significant increase in urinary oxalate excretion.[1][3] This heightened oxalate load increases the risk of calcium oxalate kidney stone formation.

– Food frequency questionnaire studies have identified raw and cooked spinach as a major dietary source of oxalate in kidney stone-forming populations, despite its infrequent consumption.[3] This suggests that even sporadic intake of high-oxalate foods like spinach can contribute to stone risk.

– To reduce kidney stone risk, experts recommend limiting intake of high-oxalate foods like spinach, rhubarb, nuts, and certain berries for those prone to calcium oxalate stones.[4][5]

– Consuming calcium-rich foods like dairy products along with oxalate-rich meals can help bind oxalate in the gut and reduce its absorption.[3][4]

In summary, the high oxalate content of raw spinach is clearly associated with an increased risk of calcium oxalate kidney stone formation, especially with frequent or excessive consumption.[1][3][4][5] Moderation of raw spinach intake is advisable for individuals susceptible to this type of kidney stone.

Citations:
[1] https://enewsletters.k-state.edu/youaskedit/2017/08/15/spinach-and-kidney-stones/
[2] https://www.webmd.com/kidney-stones/kidney-stones-food-causes
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459305/
[4] https://www.health.harvard.edu/blog/5-steps-for-preventing-kidney-stones-201310046721
[5] https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-minute-what-you-can-eat-to-help-avoid-getting-kidney-stones/

For chronic cholecystitis (inflammation of the gallbladder), a low-carb/ketogenic diet combined with antioxidant therapy and liver detox can be beneficial in managing the condition.

A low-carb/ketogenic diet helps reduce inflammation in the body, including in the gallbladder[1]. It also promotes weight loss, which can alleviate pressure on the gallbladder and reduce symptoms[2].

Antioxidant therapy with vitamins like vitamin C, E, and selenium can help neutralize free radicals and reduce oxidative stress, which contributes to gallbladder inflammation[3].

A liver detox can help improve bile flow and flush out toxins that may be irritating the gallbladder[4]. This can involve:

– Increasing intake of bitter foods like arugula, dandelion greens, and artichokes to stimulate bile production.
– Consuming liver-supporting herbs like milk thistle, turmeric, and dandelion root.
– Avoiding alcohol, processed foods, and excessive fat intake to reduce liver burden.

It’s important to stay hydrated and consume adequate fiber to promote regular bowel movements and prevent bile stagnation[1][4].

Apple cider vinegar can also be beneficial as the malic acid helps thin bile and improve digestion[1].

While this combined approach can help manage chronic cholecystitis, it’s crucial to work closely with a healthcare professional, especially if considering gallbladder removal surgery. Proper medical supervision is necessary to monitor the condition and adjust the treatment plan as needed.

Citations:
[1] https://modernyum.com/keto-without-gallbladder/
[2] https://www.drberg.com/blog/6-keto-tips-for-a-sluggish-gallbladder
[3] https://keto-mojo.com/article/keto-without-gallbladder/
[4] https://doctoreden.org/gallbladder-pain/can-a-ketogenic-diet-cause-gallbladder-attacks/
[5] https://www.diabetes.co.uk/keto/keto-diet-safety.html

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/