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Supplement

Vitamin D

Hormone-vitamin key for bone, immunity and muscle; deficiency is very common.
Category
Scientific evidence
High
Number of findings
10
Sources
Our own summaries · Cited studies
Recommended dose and how to use
1,000–2,000 IU/day of vitamin D3 (more if deficient or overweight), with a meal containing fat. Ideally adjust according to lab tests (target ~30–50 ng/mL).

How to take it

1,000–2,000 IU/day of vitamin D3 (more if deficient or overweight), with a meal containing fat. Ideally adjust according to lab tests (target ~30–50 ng/mL).

Safety

Safe in this range; occasional megadoses are no better. Take with K2 if sustained high doses are used.

Interactions

Corticosteroids and some anticonvulsants reduce its effect; orlistat lowers its absorption.

Effect by goal · level of evidence

Fibromyalgia

improves Very high summary of trials (A)
Moderate improvement (G:A)

3 trials · 175 participants: moderate improvement in fibromyalgia symptoms (especially with baseline deficiency).

See the study (Grade A) →

Fractures and bone

improves (with calcium) High Cochrane (AAA)
Small reduction

Together with calcium it slightly reduces fractures, especially in older people or those with deficiency; on its own, barely.

See the study (Cochrane) →

Respiratory infections

reduces Moderate meta-analysis (AAA)
≈ −10% risk

Reduces the risk of respiratory infections, more so if deficient.

View the study (meta-analysis) →

Mortality

association Moderate meta-analysis (AAA)
Association

Low vitamin D is associated with higher mortality; correcting the deficiency is the priority.

View the study (meta-analysis) →

Depression

no clear effect Low review (A)
No clear effect

Inconsistent evidence; useful mainly if deficient.

View the study (review) →

Hashimoto's

no clear effect Low summary of trials (A)
No effect in Hashimoto's (G:D)

5 trials · 310 participants: supplementation raises plasma vitamin D levels but does NOT improve Hashimoto's signs or TSH. Correcting deficiencies remains reasonable for other reasons.

See the study (Grade D) →

In depth

⏱ 3 min read

Vitamin D is, technically speaking, a steroid hormone and not a vitamin in the conventional sense of the term: it is produced in the body when the skin is exposed to ultraviolet B radiation from the sun, and its active form regulates the expression of more than 900 genes, approximately 5 percent of the protein-coding human genome, which makes it one of the broadest genetic regulators that exist and explains why its deficiency has been associated with such a heterogeneous and seemingly unconnected spectrum of diseases.

Approximately 70 percent of the United States population has vitamin D insufficiency or deficiency according to Endocrine Society criteria, and the problem extends similarly to much of the Western world; the highest-risk groups are people with dark skin, older adults, people with obesity, those living at high latitudes, those who work indoors, exclusively breastfed infants, and those taking certain common medications such as some antihypertensives, antibiotics, and antituberculosis drugs.

Synthesis is more complex than it seems

Vitamin D synthesis is a multistep process that requires not only sun exposure but also heat, and continues in the liver and kidneys through a series of hydroxylase enzymes that depend on magnesium for their activity; this means that magnesium deficiency can directly impair vitamin D metabolism even when sun exposure is adequate, establishing an interdependence between these two nutrients that has important practical implications for anyone who wants to optimize their vitamin D levels.

Vitamin D3 is significantly more effective than vitamin D2 at raising serum concentrations of 25-hydroxyvitamin D, the main circulating marker: a crossover trial in healthy young people found that D2 was about half as effective as D3 at maintaining serum levels, and another study found that D2 supplementation was associated with a decrease in 25(OH)D3 levels, suggesting that the two forms are not interchangeable and that D3 should be the default choice in any supplementation protocol.

Vitamin D and the brain

People with higher brain concentrations of vitamin D were 25 to 33 percent less likely to have dementia or mild cognitive impairment at their last evaluation before death, according to a study that measured vitamin D directly in four brain regions of 290 participants who had donated their brains for research; those with higher brain vitamin D concentrations also showed better working memory, episodic memory, word recall, and perceptual processing speed.

In a study of more than 12,000 adults free of dementia at baseline, those who took vitamin D supplements over a ten-year follow-up period were 40 percent less likely to develop Alzheimer's disease, with a 33 percent reduction even among carriers of the APOE4 gene, which is the most important genetic risk factor for this disease; most interesting was that vitamin D appeared to counteract the excess Alzheimer's risk usually seen in women, suggesting sex-specific neuroprotective effects that deserve further research.

Exercise amplifies vitamin D metabolism

A finding that connects two of the most powerful tools in preventive medicine: regular physical exercise not only mobilizes vitamin D stored in adipose tissue but actively optimizes its metabolism throughout the body in ways that oral supplementation does not replicate; in a ten-week trial conducted during the winter, participants who exercised four sessions per week fully maintained their levels of active vitamin D, whereas sedentary participants experienced a 15 percent drop in that same form, with the risk of reaching deficiency by late winter.

Vitamin D and synergy with vitamin K

There is an important biological interdependence between vitamin D and vitamin K that most supplementation protocols ignore: vitamin D promotes the production of several proteins that require carboxylation, a vitamin K-dependent process, in order to function properly; among these proteins, osteocalcin stands out, which promotes calcium accumulation in bones and teeth, along with matrix Gla protein, which inhibits vascular calcification, the process associated with the development of cardiovascular disease and kidney dysfunction, which makes vitamin K a logical complement to any high-dose vitamin D supplementation protocol.

References

  1. Holick, M.F. (2007). Vitamin D deficiency. N Engl J Med 357, 3.
  2. Wacker, M.; Holick, M.F. (2013). Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol 5, 1.
  3. Bouillon, R. et al. (2019). Skeletal and extraskeletal actions of vitamin D: Current evidence and outstanding questions. Endocr Rev 40, 4.
  4. Forrest, K.Y.; Stuhldreher, W.L. (2011). Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res 31, 1.
  5. Manson, J.E. et al. (2019). Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 380, 1.
  6. Autier, P. et al. (2014). Vitamin D status and ill health: A systematic review. Lancet Diabetes Endocrinol 2, 1.
  7. Zittermann, A. (2003). Vitamin D in preventive medicine: Are we ignoring the evidence? Br J Nutr 89, 5.
  8. Bikle, D.D. (2014). Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21, 3.
  9. Bikle, D.D. (2012). Vitamin D and the skin: Physiology and pathophysiology. Rev Endocr Metab Disord 13, 1.
  10. Cantorna, M.T. et al. (2004). Vitamin D status, 1,25-dihydroxyvitamin D3 and the immune system. Am J Clin Nutr 80, 6 Suppl.

Information, not medical advice. Scientific evidence reflects the quality of the studies.

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