FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, May 18, 2025

When Good Nutrients Keep You Awake: Understanding and Managing Insomnia from Moderate to High-Dose Vitamin and Antioxidant Supplements

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

Introduction: When Supplements Disrupt Sleep

An 86-year-old physician with post-COVID spike protein syndrome, pulmonary fibrosis, and chronic oxidative stress sought my consultation after limited improvement under several prominent experts. He reported persistent insomnia triggered by moderate to high doses of supplements-particularly vitamin C, B-complex vitamins (especially niacin), vitamin D3, and other antioxidants. His condition includes pulmonary fibrosis, right heart failure, pulmonary hypertension, hormonal imbalances, and elevated oxidative stress.

While nutritional supplements are usually safe and beneficial, this case illustrates that even "good" nutrients can disturb sleep in vulnerable individuals, especially when taken at the wrong time or in overly rapid titration.

Why Do Nutrients Sometimes Cause Insomnia?

🔋 1. Mitochondrial Activation and Energy Surges

Many vitamins-especially C, B-complex, and mitochondrial cofactors like CoQ10 and PQQ-enhance ATP production and cellular respiration [1]. In sensitive individuals, this sudden boost in cellular energy can cause restlessness or insomnia, particularly if taken in the evening.

Vitamin B5 (pantothenic acid) deserves special mention. While essential for adrenal function, neurological repair, and sleep regulation, it may paradoxically disrupt sleep when consumed in high doses (around 400 mg/day). Dr. Stasha Gominak, a sleep specialist, has reported that excessive B5 can produce a "speed-like" effect, causing symptoms such as insomnia and restless legs, particularly in individuals with underlying microbiome-related B5 deficiency [2,3].

Her solution involves using a balanced B-complex with moderate B5 levels (~100 mg) combined with vitamin D3, which supports acetylcholine production and parasympathetic nervous system activity. This combination may restore microbial balance and improve sleep quality while reducing neuropathic pain and agitation. The likely mechanism involves B5's role in neurotransmitter synthesis, especially in acetylcholine-dependent pathways that regulate sleep and parasympathetic tone.

😰 2. Adrenal and Catecholamine Stimulation

Vitamin C and B5 are precursors for adrenal hormone synthesis (e.g., cortisol, epinephrine), and B6/B12/niacin increase dopamine and serotonin production. [3,4] In those with subclinical adrenal dysfunction or autonomic dysregulation, this can trigger a "wired but tired" state [4-6].

🔄 3. Disrupted Circadian and Hormonal Rhythms

Vitamin D3 modulates melatonin, cortisol, and clock gene expression [7]. L-carnitine, while supporting fat metabolism, may be stimulatory in some and is best taken early in the day. Many individuals intuitively take D3 with breakfast or lunch-when the sun naturally promotes its synthesis.

Age-related reductions in melatonin, thyroid hormone, and DHEA lower the buffer against stimulation, making older adults more susceptible to sleep disruption.

🧬 4. Methylation and Detox Overload

Niacin, B12, folate, and other methyl donors support detox and neurotransmitter metabolism. However, rapid detoxification or methylation shifts may trigger anxiety, vivid dreams, or restlessness. Some individuals are so overwhelmed that synthetic supplements may "jam" receptor signaling-a phenomenon Dr. Candace Pert alluded to when noting that 98% of all information transfer occurs at receptor sites [8].

Such patients may be "too toxic to detox," and improve better with food-based nutrients and minerals [9].

Hidden Sources of Stimulation

Modern supplement and beverage formulations are often contaminated with stimulants-caffeine or analogs-under names unfamiliar to consumers. Emergen-C now sells an "Energy+" version with added caffeine, and even non-coffee Starbucks drinks often contain stimulants [10]. Meanwhile, OTC sleep aids may combine melatonin with valerian or other sedatives, adding to the neurochemical chaos. Recreational exposure to THC, MDMA, or fentanyl derivatives further complicates biochemical balance.

Common Offenders: Nutrients Most Often Linked to Sleep Disturbance

Supplement	Common Problem Dose	Potential Mechanism
Vitamin C	> 2,000-3,000 mg/day	Adrenal + mitochondrial activation; diuretic
Niacin (IR/SR)	>500-1,000 mg/day	Methylation + dopaminergic stimulation
B-complex (esp. B5/B6/B12)	High potency	Neuroendocrine activation
Vitamin D3	>5,000-10,000 IU/day	Circadian/hormonal modulation
CoQ10, PQQ, ALA	Moderate-high doses	Mitochondrial stimulation
L-carnitine	AM use preferred	Fat metabolism + mild stimulation

What You Can Do: Practical Steps to Manage Sleep Disturbance from Supplements

1. ✅ Adjust Timing
   • Take stimulating nutrients (C, D, B vitamins, L-carnitine, CoQ10) only in the morning.
   • Avoid supplement cocktails after 2 PM.
2. ✅ Titrate Gradually
   • Niacin: start 100 mg/day → gradually increase to 500-1,000+ mg
   • Vitamin C: begin with 500-1,000 mg/day and divide doses
   • Introduce new supplements one at a time to observe effects.
3. ✅ Add Calming Nutrients
   • Magnesium glycinate or threonate: 500-1,500 mg/day, especially at night
   • Taurine, GABA, glycine, L-theanine: support relaxation and GABAergic tone
   • Melatonin (0.3-2 mg) or natural progesterone can improve sleep latency
4. ✅ Support Hormonal & Neuroendocrine Balance
   • Test and address:
     • TSH, free T3/T4, reverse T3
     • DHEA-S, morning cortisol, SHBG, testosterone
   • Consider thyroid or adrenal support under supervision.
5. ✅ Consider Red-Light Therapy (PBMT)
   • Red/NIR light (660-850 nm) in the evening supports mitochondrial recovery and circadian regulation. [11,12]
   • Promotes natural melatonin secretion and stress adaptation.

Conclusion

Nutritional therapy is not always benign-even with the best of intentions. Individuals with chronic illness, mitochondrial dysfunction, or hormone imbalances may react strongly to supplements that enhance energy or detox pathways.

But this paradox is manageable. With the right adjustments-dose, timing, combinations, and support for underlying dysfunction-most patients can continue using orthomolecular therapies while restoring restorative sleep.

About the Author

Richard Z. Cheng, M.D., Ph.D. is a practicing physician based in the USA and China, specializing in integrative and orthomolecular approaches to chronic disease and aging. He is Editor-in-Chief of the Orthomolecular Medicine News Service, a board-certified expert in Anti-Aging and Regenerative Medicine, and a Hall of Fame inductee of the International Society for Orthomolecular Medicine.

References:

1. Ames BN (2004) Delaying the mitochondrial decay of aging. Ann N Y Acad Sci 1019:406-411. https://pubmed.ncbi.nlm.nih.gov/15247055

2. Gominak S (2025) Heal your body every night while you sleep. Accessed online 2025-05-12: https://drgominak.com

3. Gominak SC (2016) Vitamin D deficiency changes the intestinal microbiome reducing B vitamin production in the gut. The resulting lack of pantothenic acid adversely affects the immune system, producing a 'pro-inflammatory' state associated with atherosclerosis and autoimmunity. Med Hypotheses, 94:103-107. https://pubmed.ncbi.nlm.nih.gov/27515213

4. Patak P, Willenberg HS, Bornstein SR (2004) Vitamin C is an important cofactor for both adrenal cortex and adrenal medulla. Endocr Res. 30:871-875. https://pubmed.ncbi.nlm.nih.gov/15666839

5. Kennedy DO (2016) B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review. Nutrients, 8:68. https://pubmed.ncbi.nlm.nih.gov/26828517

6. Folk J (2022) Feeling Tired But Wired: Anxiety Symptoms. AnxietyCentre.com. Accessed online 2025-05-12: https://www.anxietycentre.com/anxiety-disorders/symptoms/tired-but-wired

7. Gutierrez-Monreal MA, Duran RC-D, Moreno-Cuevas JE, Scott S-P (2014) A Role for 1α,25-Dihydroxyvitamin D3 in the Expression of Circadian Genes. J Biol Rhythms, 29:384-388. https://pubmed.ncbi.nlm.nih.gov/25231949

8. Pert CB (1999) Molecules Of Emotion: The Science Behind Mind-Body Medicine. Simon & Schuster, New York, 1999. ISBN-13: ‏ 978-0684846347

9. Dean C (2017) The Magnesium Miracle, (2nd Edition). Ballantine Books. ISBN-13: 978-0399594441.

10. Moyer L (2025) How much caffeine is in coffee, tea, soda, and other foods? Center for Science in the Public Interest. Accessed online 2025-05-12: https://www.cspinet.org/article/how-much-caffeine-coffee-tea-soda-and-other-foods

11. Hamblin MR (2017) Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys 4:337-361. https://pubmed.ncbi.nlm.nih.gov/28748217

12. Cheng RZ (2025) May is Sunshine Month: Rediscover the Healing Power of Light. Orthomolecular Medicine News Service. https://orthomolecular.org/resources/omns/v21n28.shtml

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