vitamin D decreases cognitive impairment

A recent article found that 12 months of vitamin D supplementation improved cognitive function in patients with mild cognitive impairment (MCI). See (see cognitive benefit vit D jneuroetc2018 in dropbox, or doi:10.1136/ jnnp-2018-318594​ ).

Details:

-- 181 community dwelling patients from 6 areas in China met the inclusion criteria of being >65yo, no evident psych disorder (major depression, schizophrenia, bipolar), and MCI (as determined by the modified Petersen’s criteria: subjective memory complaint for at least 6 months, objective memory impairment for age and education (defined as being at least 1.5 SD below age- and education-matched controls on MMSE), essentially preserved ADLs, absence of dementia per DSM-IV

-- mean age 67, 46% male, 18% primary school education/56% middle school/26% high school or above, 96% married, BMI 25, 7% smoking, 12% alcohol, 14% diabetes, 40% hypertension, MMSE 23 (MMSE score 18-23 signifies MCI)

-- baseline 25(OH)D= 20 ng/mL; 1,25-D = 30 ng/mL

-- patients were randomly assigned to vitamin D3 400 international units per day for 12 months vs placebo

Results:

-- 25(OH)D increased from 19 to 23 ng/mL in those on supplements; 1,25-D increased from 30 to 34 ng/mL. no change in those on placebo

-- total cholesterol decreased from 4.92 ​mmol/L (190 mg/dL) to 4.4 (170 mg/dL), triglycerides from 1.8 (160 mg/dL) to 1.5 (133 mg/dL), HDL from 1.5 (58 mg/dL) to 1.0(39 mg/dL), LDL insignificant change. In the placebo group the HDL increased from 1.5 (58 mg/dL) to 1.6 (62 mg/dL) and the LDL from 2.4 (93 mg/dL ) to 2.5 (97 mg/dL)

-- cognitive function: the mean scores of information, digit span, vocabulary, block design, and picture arrangement were significantly better in the vitamin D supplement group than the placebo group, all with p<0.001

-- The full IQ (104, increasing to 109), verbal IQ (116 to 121), and performance IQ (9 to 11) were significantly increased as well with supplements, all with p<0.001. There were slight decreases in the placebo group in all of these measures

Commentary:

-- vitamin D seems to play a role in brain function and health.   

    -- Animal studies show a protective effect of vitamin D on cognition

    -- people who are severely deficient in vitamin D have a more than twofold increased risk of developing dementia [observational study: may be biases in that those with higher vitamin D levels may be doing other healthful things not accounted for]

    -- the human data on vitamin D supplementation and cognition is inconsistent

    -- an Australian study found that women with vitamin D insufficiency during pregnancy had a twofold higher likelihood that their children would later have clinically significant language difficulties [again, ?biases between the groups]

    -- also the studies are inconsistent on the effects of vitamin D on lipid levels, some finding that vitamin D supplementation decreased triglyceride, increased HDL, and decreased the highly atherogenic small dense LDL levels. Others, such as the study above, have not found this [higher total cholesterol is associated with Alzheimer’s as well as cognitive impairment overall]

-- a few issues with this study:

    -- minimal cognitive impairment can be the result of multiple causes and inconsistently leads to subsequent dementia (a recent autopsy study of 874 subjects found that 39% died with MCI, 47% died with dementia, and 14% died with intact cognition after 7.9 years. 74% were without Alzheimer’s disease neuropathologic changes, Lewy body disease, or hippocampal sclerosis. See Abner EL. Ann Neurol 2017; 81:549, or doi:10.1002/ana.24903 

    -- the study did not involve further diagnostic studies to determine the cause of MCI

    -- the dose of vitamin D was pretty low, and it might well be that a higher dose would have shown more benefit

    -- their lipid data was quite unexpected. In fact the atherogenic profile was significantly worse with vitamin D supplementation if one looks at the total cholesterol to HDL ratio. see http://gmodestmedblogs.blogspot.com/2014/03/vitamin-d-decreases-ldlincreases-hdl.html  for the Womens Health Initiative finding decreased in LDL and no change in HDL, TG with vitamin D. And, the relationship between statin effects on lowering LDL and cognitive decline is quite mixed in the large studies

So, an interesting article. Their results of low-dose vitamin D supplementation seem to be pretty consistent in improving several different markers of cognitive decline in patients with MCI. No doubt the causes of MCI and dementia itself are complex and intertwined. There are likely to be many factors not included in this or other studies, including exercise, diet, and other major lifestyle issues which seem to affect cognitive abilities (see http://gmodestmedblogs.blogspot.com/2016/06/interventions-to-delay-functional.html  for a recent review on interventions which delay functional decline in those with dementia). However, vitamin D receptors are found in many important areas of the brain, including the cerebellum, thalamus, hypothalamus, basal ganglia, and the hippocampus, suggesting that, evolutionarily, vitamin D is likely important to brain function (and, evolutionarily, humans developed in sun-drenched areas).

the bottom line to me: vitamin D is likely a factor in cognitive health, but clearly is not the only one. and, in general, it is not so surprising that studies looking at a single factor do not find that it, in and of itself, is determinant in such a complex outcome as cognitive function. But, especially for those of us who work in the northern sun-deprived climates, vitamin D deficiency is almost ubiquitous, is especially so in the elderly (decreased vitamin D conversion in the skin even with the same amount of sunlight), and, as far as I can tell, there is almost no contraindication to reasonably aggressive vitamin D repletion with this remarkably low cost vitamin that is only effectively available as a supplement for sun-deprived people

see http://gmodestmedblogs.blogspot.com/search?q=vitamin+d   for many blogs on vitamin D

geoff

If you would like to be on the regular email list for upcoming blogs, please contact me at gmodest@uphams.org

to get access to blogs since 8/15/17:

1. go to http://gmodestmedblogs.blogspot.com/ to see them in reverse chronological order

2. click on 3 parallel lines top left, if you want to see blogs by category, then click on "labels" and choose a category​

3. or you can just type in a name in the search box and get all the blogs with that name in them

to access older blogs from the BMJ website, from October 2013 until 8/15/17: go to http://blogs.bmj.com/bmjebmspotlight/category/archive/ 

please feel free to circulate this to others. also, if you send me their emails, i can add them to the list