Low Vitamin D Associated with Higher Risk of Dementia and Stroke
Vitamin D is similar to a hormone with widespread influence on human health and disease. Low levels have been associated with a variety of serious conditions.
This post reviews a prospective study of 427,000 people. (See reference below) The researchers evaluated the risk of dementia and stroke in relation to vitamin D blood levels among other parameters.
Vitamin D levels can be confusing because there are two ways to report the measurement. In the United States, levels are typically reported out using ng / mL. Other countries use nmol / l. To avoid some confusion, I think of 20 in the US is equal to 50 outside of the US. This study reported levels in nmol / l.
There is some consensus about vitamin D deficiency. (See chart below)
Optimal levels are hotly debated. This is an area of my active research. We will discuss this more in a future post.
Here is the bottom line from this study:
Low vitamin D was associated with lower a significantly higher risk of both dementia and stroke. This means vitamin D levels are a modifiable risk factor for these devastating brain conditions.
Now, let’s dive into the data. A quick reminder: a hazard ratio is the ratio of chance of an event occurring in the treatment arm divided by chance of an event occurring in the control arm.
Vitamin D levels below 50 nmol/l had a higher risk of dementia. Significantly low vitamin D levels (< 25 nmol/l) had a hazard ratio of 1.79 for dementia. Levels between 25-49.9 had a hazard ratio of 1.24.
Interestingly, levels above 125 nmol/l had a hazard ratio of 0.81. That is about 50 ng / ml. People in this zone had a LOWER risk of dementia. There were only a few people in this category in the study but I believe we need to investigate if vitamin D levels in this zone could be protective against dementia. (See graphic below)
The researchers also found a threshold vitamin D level for dementia. The reference point was set at 50. Levels below this had an increased risk of dementia. Levels above had a lower risk of dementia. (See graphic below)
Significantly low vitamin D levels also had a higher risk of stroke. The hazard ratio was 1.40 for levels below 25 and 1.15 for levels between 25 and 49.9. There was no lower hazard ratio for levels about 125. (See graphic below)
The paper helps us understand why vitamin D is critical for our brains.
“A protective effect of higher 25(OH)D on brain health is biologically plausible and
could be explained by at least 3 potential mechanisms. First, the presence of vitamin
D receptors in the hypothalamus has suggested a neurosteroid function for active
vitamin D, promoting the growth and maturation of neurons. Second, there may be
vascular mechanisms as active vitamin D has been associated with reduced
thrombosis and regulation of the renin–angiotensin system. Third, replete
concentrations of active vitamin D may act as a neuroprotectant through the
suppression of excess inflammatory neurovascular damage caused by
proinflammatory cytokines and attenuation of amyloid proteins, commonly observed
in Alzheimer disease.”
This is a powerful paper that should change how we think about dementia and stroke. Too often we think they are not preventable. This data strongly suggests we should correct any vitamin D deficiencies to reduce the risks of both dementia and stroke.
Research should also explore if higher levels are protective.
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Navale et al 2022
Background: Higher vitamin D status has been suggested to have beneficial effects on the brain.
Objectives: To investigate the association between 25- hydroxyvitamin D [25(OH)D], neuroimaging features, and the risk of dementia and stroke.
Methods: We used prospective data from the UK Biobank (37– 73 y at baseline) to examine the association between 25(OH)D concentrations with neuroimaging outcomes (N = 33,523) and the risk of dementia and stroke (N = 427,690; 3414 and 5339 incident cases, respectively). Observational analyses were adjusted for age, sex, ethnicity, month, center, and socioeconomic, lifestyle, sun behavior, and illness-related factors. Nonlinear Mendelian randomization (MR) analyses were used to test for underlying causality for neuroimaging outcomes (N = 23,901) and dementia and stroke (N = 294,514; 2399 and 3760 cases, respectively).
Results: Associations between 25(OH)D and total, gray matter, white matter, and hippocampal volumes were nonlinear, with lower volumes both for low and high concentrations (adjusted P-nonlinear ≤ 0.04). 25(OH)D had an inverse association with white matter hyperintensity volume [per 10 nmol/L 25(OH)D; adjusted β: –6.1; 95% CI: –11.5, –7.0]. Vitamin D deficiency was associated with an increased risk of dementia and stroke, with the strongest associations for those with 25(OH)D <25 nmol/L (compared with 50–75.9 nmol/L; adjusted HR: 1.79; 95% CI: 1.57, 2.04 and HR: 1.40; 95% CI: 1.26, 1.56, respectively). Nonlinear MR analyses confirmed the threshold effect of 25(OH)D on dementia, with the risk predicted to be 54% (95% CI: 1.21, 1.96) higher for participants at 25 nmol/L compared with 50 nmol/L. 25(OH)D was not associated with neuroimaging outcomes or the risk of stroke in MR analyses. Potential impact fraction suggests 17% (95% CI: 7.22, 30.58) of dementia could be prevented by increasing 25(OH)D to 50 nmol/L.
Conclusions: Low vitamin D status was associated with neuroimaging outcomes and the risks of dementia and stroke even after extensive covariate adjustment. MR analyses support a causal effect of vitamin D deficiency on dementia but not on stroke risk. Am J Clin Nutr 2022;00:1–10.