Vitamin D Deficiency is Associated with a Substantially Increased Risk of All-Cause Dementia and Alzheimer Disease

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Vitamin D refers to a group of fat-soluble secosteroids (pro-hormones) responsible for increasing intestinal absorption of calcium, iron, magnesium, phosphate, and zinc, among other multiple functions.

For human therapeutic purposes, there are two important compounds in the vitamin D group:

  • Vitamin D2 (also known as ergocalciferol)
  • Vitamin D3 (also known as cholecalciferol)
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Vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease

A  number of research studies have indicated that low levels of 25-hydroxyvitamin D is associated with the development of dementia and ultimately Alzheimer’s disease.

In a study from October 2014, epidemiological evidence strongly suggests that circulatory levels of 25-hydroxyvitamin D below 50 nmol/l are associated with cognitive impairment and the development of dementia.  1    

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Figure 1. Circulatory levels of 25-hydroxyvitamin D below 50 nmol/l are associated with cognitive impairment and the development of dementia   (Source)

In another study from August 2014, researchers sought to determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. 

One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population–based Cardiovascular Health Study between 1992–1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992–1993.

During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease.

Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23–4.13) and 1.53 (95% CI: 1.06–2.21) compared to participants with sufficient concentrations (≥50 nmol/L).

The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02–4.83) and 1.69 (95% CI: 1.06–2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.

Researchers confirmed that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.  2

171 participants developed all-cause dementia

102 participants developed Alzheimer disease

The risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.

In a study from May 2014, researchers hypothesized that reduced plasma 25-hydroxyvitamin D (25[OH]D) is associated with increased risk of Alzheimer’s disease (AD) and vascular dementia in the general population.  They measured baseline plasma 25(OH)D in 10,186 white individuals from the Danish general population.

During 30 years of follow-up, 418 participants developed AD and 92 developed vascular dementia. Multivariable adjusted hazard ratios for AD were 1.25 (95% confidence interval [CI], 0.95-1.64) for 25(OH)D less than 25 nmol/L vs. greater than or equal to 50 nmol/L, and 1.29 (95% CI, 1.01-1.66) for less than the 25th seasonally adjusted 25(OH)D percentile vs. more than the 50th seasonally adjusted 25(OH)D percentile. Multivariable adjusted hazard ratios for vascular dementia were 1.22 (95% CI, 0.77-1.91) for 25(OH)D less than 50 nmol/L vs. greater than or equal to 50 nmol/L, and 1.22 (95% CI, 0.79-1.87) for less than or equal to the 50th vs. more than the 50th seasonally adjusted 25(OH)D percentile.

Researchers observed an association of reduced plasma 25(OH)D with increased risk of the combined end point of AD and vascular dementia in this prospective cohort study of the general population.  3

418 participants developed Alzheimer disease

92 participants developed vascular dementia

The risk of vascular dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.

Testing for Vitamin D levels in Blood Serum

Vitamin D levels in the blood serum can be tested with a blood draw test.  Both forms of vitamin D can be tested.  The names of the tests are:

  • 25-hydroxyvitamin D3 (cholecalciferol)
  • 25-hydroxyvitamin D2 (ergocalciferol)

The Vitamin D Council has written about the various levels of 25(OH)D and their recommendations of how much vitamin D3 to supplement to raise it to safe levels.

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The Vitamin D Council suggests that a level above 50 ng/ml and below 80 ng/ml is the ideal level to aim for. This is why the Council recommends that adults take 5,000 IU/day of vitamin D supplement in order to reach and stay at this level.

Foods that Contain Vitamin D2 and Vitamin D3

There are a limited number of foods that contain vitamin D2 and vitamin D3.  There are more of a variety of foods that contain vitamin D3 than vitamin D2.  Of all the foods that contain vitamin D2 and D3, none of them have high quantities, with maybe cod liver oil as the exception.

Because there are limited amounts of foods that contain vitamins D2 and D3, it is necessary to supplement with vitamin D3 to reach the acceptable levels of 25-OH-D.

Vitamin D2

Very few foods contain Vitamin D2:

All of the above listed foods contain less than 600 IU’s per 100 grams.

Vitamin D3

Most vitamin D3 found in food is from animal sources (fish, eggs, beef):

  • Lichen (Cladina arbuscula)
  • Cod liver oil (4.5 g (1 teaspoon) provides 450 IU (100 IU/g))
  • Salmon
  • Mackerel
  • Tuna
  • Sardines  (canned in oil)
  • Egg yolk  (cooked)
  • Beef liver  (cooked, braised)

Other than cod liver oil, all other foods that contain vitamin D3 contain less than 600 IU’s per 100 grams.

Very few foods contain vitamin D so the synthesis of vitamin D (specifically cholecalciferol) is through the skin. Dermal synthesis of vitamin D from cholesterol is dependent on sun exposure (specifically UVB radiation).  

Informational References:

Vitamin D Council

Vitamin D Day