Vitamin D and cognitive function

'Correlation is not the same as causation' is an important theme in science, demonstrating how one always needs to be a little guarded about making too much of research linking one variable with another from a purely observational point of view.

I similarly apply such a principle to the findings reported by Rolf Jorde and colleagues [1] and the suggestion of "an association between serum 25(OH)D and cognition". Serum 25(OH)D levels by the way, refers to the measurement of calcifediol in serum, the biological precursor to the active form of vitamin D - the so-called sunshine vitamin/hormone.

Jorde et al report findings based on the the Tromsø Study [2], a population-wide initiative initiated in the early 1970s in Tromsø attempting to "help combat the high mortality of cardiovascular diseases in Norway." With a participant group in the thousands, the Tromsø Study has already provided a wealth of scientific information (see here) well beyond its original intentions (see here) and with vitamin D very much in mind (see here).

On this occasion, researchers looked at vitamin D levels and cognitive functions as measured by various psychometric schedules including the Mini–Mental State Examination (MMSE). Some 4500 participants were initially screened and tested for vitamin D levels and cognitive functions in a cross-sectional manner. Further: "in a prospective study serum 25(OH)D was measured in samples from 1994 and compared to cognitive function tested in 3436 subjects in 2001 and 2044 subjects in 2007." Just for good measure, researchers also looked for the presence of genetic polymorphisms in the vitamin D receptor (VDR) gene.

The results pointed towards to some rather interesting trends perhaps requiring greater scientific scrutiny. "In the cross-sectional study all tests were positively associated with serum 25(OH)D levels with ~5% better performance in subjects in the highest versus lowest serum 25(OH)D quartile." In other words bearing in mind that correlation ≠ causation, vitamin D levels 'might' play some role in cognitive ability specifically "in subjects older than 65 years." In the prospective portion of the study: "serum 25(OH)D from 1994 similarly predicted cognitive function 7-13 years later." Such observations have led to calls for "randomized controlled trials... to establish causality."

Once again reiterating that two correlating values do not a causative relationship make, this is not the first time that vitamin D and cognition have shown up on the peer-reviewed research radar. The literature on vitamin D and cognition with ageing [3] and dementia in mind [4] is testament to the interest in a possible link. That being said, I wouldn't want anyone to believe that such a relationship between vitamin D and cognition is straight-forward given that ageing for example, includes an array of biological processes that might link into both vitamin D levels and cognitive ability [5]. That also such a relationship does not appear to be present in children and young adults [6] provides a word of caution for those who might see vitamin D as the new nootropic of choice.

Still, these results are interesting and alongside other research from Jorde et al [7] suggest that the extra-skeletal input/effects of vitamin D are deserving of quite a bit more study and appreciation...

Music: R.E.M. - Everybody Hurts

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[1] Jorde R. et al. Vitamin D and cognitive function: The Tromsø Study. J Neurol Sci. 2015 Jun 7. pii: S0022-510X(15)00350-0.

[2] Jacobsen BK. et al. Cohort profile: the Tromso Study. Int J Epidemiol. 2012 Aug;41(4):961-7.

[3] Toffanello ED. et al. Vitamin D deficiency predicts cognitive decline in older men and women: The Pro.V.A. Study. Neurology. 2014 Dec 9;83(24):2292-8.

[4] Nagel G. et al. Serum Vitamin D Concentrations and Cognitive Function in a Population-Based Study among Older Adults in South Germany. J Alzheimers Dis. 2015 Feb 3.

[5] Visser M. et al. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003 Dec;88(12):5766-72.

[6] Tolppanen AM. et al. The association of circulating 25-hydroxyvitamin D and calcium with cognitive performance in adolescents: cross-sectional study using data from the third National Health and Nutrition Examination Survey. Paediatr Perinat Epidemiol. 2011 Jan;25(1):67-74.

[7] Jorde R. et al. Neuropsychological function in relation to serum parathyroid hormone and serum 25-hydroxyvitamin D levels. The Tromsø study. J Neurol. 2006 Apr;253(4):464-70.

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Jorde R, Mathiesen EB, Rogne S, Wilsgaard T, Kjærgaard M, Grimnes G, & Schirmer H (2015). Vitamin D and cognitive function: The Tromsø Study. Journal of the neurological sciences PMID: 26092373