Vitamin D

Authored by Sumeet Sharma and Laya Rajan

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.
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. Older guidelines suggest a dose of 600IU, or 800 if you're above 70 years old. However, it is believed that the optimal daily dosage is closer to 4000 IU.

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).