Vitamin D

Authored by Sumeet SharmaDr. Brianna Stubbs and Laya Rajan • 
July 10, 2016

Take Home Points

  • Vitamin D is synthesized endogenously, but can also be found in fatty fish, fish oils, meats and fortified milk.

  • Vitamin D crosses the blood brain barrier and has been associated with regulating neurotrophin growth and neurotransmitter signaling.

  • Deficiencies in Vitamin D may affect executive brain functions, such as the processing of information, working memory, and multitasking.

  • Many healthy individuals, particularly working professionals working indoors, may be asymptomatic and have vitamin D deficiency, due to decreased exposure to sunlight.

Name

Vitamin D, also known as cholecalciferol (Vitamin D3), ergocalciferol (Vitamin D2)

Structure

Vitamin D is endogenously synthesized from cholesterol. UV exposure from sunlight is a key component in this process.
VitaminD Synthesis Vitamin D biosynthesis

Source

Vitamin D is synthesized endogenously in the body and brain.

Vitamin D is also an essential nutrient found in fatty fish (such as salmon, tuna, flounder), fish oils, meats, eggs, and fortified milk. Many people also consume it in supplement form - Vitamin D3 is preferable to D2 as it is more efficiently absorbed.

Effects on the Brain

Vitamin D crosses the blood-brain-barrier, allowing it to be neurally active. Its receptors (proteins that bind vitamin D and carry out its cellular effects), are located widely throughout the brain.1

Vitamin D has been shown to regulate the synthesis of neurotrophins and neurotransmitters, molecules that regulate growth and signaling, respectively.2,3,4

Vitamin D levels in the blood are normally between 20-50 nanograms per milliliter of blood. Deficiencies in Vitamin D are associated with a host of negative neurological effects that affect executive brain functions, such as the processing of information, working memory, and multitasking in older individuals. A recent meta-analysis showed there is a 2.4X greater risk of cognitive impairment in older adults with low levels of Vitamin D.5,6,7,8,9

Data linking Vitamin D levels to improved cognitive performance in young, healthy adults is not conclusive. In a 2011 randomized placebo-controlled trial, vitamin D supplementation in healthy-young adults did not result in improvements in cognitive performance or mood states.10

However, low vitamin D levels were associated with depressed mood in a study of young adults in the US11. Daily supplementation of 4000 IU of Vitamin D ameliorated depressive symptoms in a study of adolescents with low Vitamin D [hogberg-2012-vitd-depression] but this result is not consistent across all populations. Current scientific consensus is that supplementation may be protective for healthy individuals, particularly in vitamin D deficient individuals.

As previously mentioned, many healthy individuals may be asymptomatic and still have vitamin D deficiency12. Working professionals are at particular risk for deficiency due to increased time spent inside. Vitamin D levels are at their lowest in the winter due to decreased exposure to sunlight.

Vitamin D deficiency is correlated with increased risk of Alzheimer's [annweiler-2013-vitd-alzheimers] and Parkinson's disease [knekt-2010-vitd-parkinsons], possibly due to its neuroprotective effects. However, at this time, further research is required to better characterize these relationships.

Effects on Longevity

Low 25-hydroxyvitamin D [25(OH)D] concentrations are associated with increased risk of mortality, and higher levels of vitamin D in blood predict lower overall mortality. In the largest meta-analysis including 850,000 study participants across 73 cohorts with ~66,500 deaths, comparing those with levels of 25(OH)D <25 nmol/l vs. those with levels ≥75 nmol/l, the relative risk of death was 1.50. The second largest meta-analysis, including 500,000 study participants, comparing those with levels of 25(OH)D ≤22.5 nmol/l vs. those with levels >75 nmol/l, the hazard ratio for death was 1.90. Studies suggest that the lowest mortality risk were found in individuals with 25(OH)D serum concentrations ranging from 75-88 nmol/l.

Vitamin D supplementation (2,000 IU a day of vitamin D3 for 4 months) was associated with increased telomerase by about 20%, as measured by telomeric repeat amplification, in overweight African Americans. This suggests improved telomere maintenance, counteracting obesity-induced acceleration of cellular aging.

How to take

Most vitamin D supplements come in "IU" or international units. The recommended daily allowance for Vitamin D is currently set at 400-800IU/day, for moderate supplementation, a 1,000-2,000IU dose of vitamin D3 is sufficient to meet the needs of most of the population.

Vitamin D should be taken with a good source of fat like fish oil for optimal absorption. It can be hard to get enough vitamin D from diet and sunlight alone, depending on where you live.

Side Effects

Vitamin D supplementation should not cause side effects. Combination with calcium supplementation may increase risk of kidney stone formation.

Safety

Vitamin D can be toxic at very high doses leading to hypercalcemia and calification. However, hypercalcemia only occurs at 25(OH)D levels above ~375 to 500 nmol/l with very extreme overdosing of vitamin D.

Vitamin D is approved as a dietary supplement component under provisions of the Dietary Supplement Health and Education Act of 1994. It is classified as generally recognized as safe (GRAS).

  1. Kalueff, A. V., & Tuohimaa, P. (2007). Neurosteroid hormone vitamin D and its utility in clinical nutrition. Curr Opin Clin Nutr Metab Care, 10(1), 12-19. doi:10.1097/MCO.0b013e328010ca18

  2. Brown, J., Bianco, J. I., McGrath, J. J., & Eyles, D. W. (2003). 1,25-dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett, 343(2), 139-143.

  3. Annweiler, C., Schott, A. M., Berrut, G., Chauvire, V., Le Gall, D., Inzitari, M., & Beauchet, O. (2010). Vitamin D and ageing: neurological issues. Neuropsychobiology, 62(3), 139-150. doi:10.1159/000318570

  4. Annweiler, C., Allali, G., Allain, P., Bridenbaugh, S., Schott, A. M., Kressig, R. W., & Beauchet, O. (2009). Vitamin D and cognitive performance in adults: a systematic review. European Journal of Neurology, 16(10), 1083-1089. doi:10.1111/j.1468-1331.2009.02755.x

  5. Etgen, T., Sander, D., Bickel, H., Sander, K., & Forstl, H. (2012). Vitamin D deficiency, cognitive impairment and dementia: a systematic review and meta-analysis. Dement Geriatr Cogn Disord, 33(5), 297-305. doi:10.1159/000339702

  6. Balion, C., Griffith, L. E., Strifler, L., Henderson, M., Patterson, C., Heckman, G., . . . Raina, P. (2012). Vitamin D, cognition, and dementia A systematic review and meta-analysis. Neurology, 79(13), 1397-1405.

  7. Balion, C., Griffith, L. E., Strifler, L., Henderson, M., Patterson, C., Heckman, G., . . . Raina, P. (2012). Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology, 79(13), 1397-1405. doi:10.1212/WNL.0b013e31826c197f

  8. Annweiler, C., Montero-Odasso, M., Llewellyn, D. J., Richard-Devantoy, S., Duque, G., & Beauchet, O. (2013). Meta-analysis of memory and executive dysfunctions in relation to vitamin D. J Alzheimers Dis, 37(1), 147-171. doi:10.3233/jad-130452

  9. Dean, A. J., Bellgrove, M. A., Hall, T., Phan, W. M., Eyles, D. W., Kvaskoff, D., & McGrath, J. J. (2011). Effects of vitamin D supplementation on cognitive and emotional functioning in young adults--a randomised controlled trial. PLoS One, 6(11), e25966. doi:10.1371/journal.pone.0025966

  10. Ganji, V., Milone, C., Cody, M. M., McCarty, F., & Wang, Y. T. (2010). Serum vitamin D concentrations are related to depression in young adult US population: the Third National Health and Nutrition Examination Survey. International Archives of Medicine, 3(1), 1-8. doi:10.1186/1755-7682-3-29

  11. Tangpricha, V., Pearce, E. N., Chen, T. C., & Holick, M. F. (2002). Vitamin D insufficiency among free-living healthy young adults. Am J Med, 112(8), 659-662.

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