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Study under review: Does high dose vitamin D supplementation enhance cognition?: A randomized trial in healthy adults
Introduction
Vitamin D has been suggested to play a role in numerous diseases outside of its established role in skeletal health. One of these areas is cognition. Observational evidence suggests that vitamin D deficiency has been linked to a 54% increased risk of developing dementia[1], 21% increased risk of developing Alzheimer’s disease[2], and 139% increased odds of developing general cognitive impairment[3]. These observations are also supported by experimental evidence in animals and cell cultures. Vitamin D receptors and the enzyme necessary to activate vitamin D (1α-hydroxylase) are located throughout the brain[4], and vitamin D and its metabolites have been shown to increase acetylcholine[5] levels and neuronal density[6], enhance neuroprotection[7], and promote the clearance of β-amyloid[8]. Vitamin D’s possible interactions with cognition are summarized in Figure 1. Granted, researchers don’t know whether these findings are relevant to humans.
Nonetheless, these observations raise an important question: can vitamin D supplementation improve cognition? One study in healthy young adults[9] answered “no” when comparing 5,000 IU of vitamin D3 to placebo over six weeks. However, only 10 of the 128 participants were vitamin D deficient at baseline and, as has been observed with changes in musculoskeletal health[10], changes in cognition may require more than six weeks to manifest. An analysis of the Women’s Health Initiative[11] reported that 400 IU of vitamin D3 had no effect on cognition over eight years, but subsequent vitamin D levels were not obtained and the dose may have been too low to have an effect.
The study under review is a randomized controlled trial evaluating two doses of vitamin D3, 4,000 and 400 IU per day, on a broad range of cognitive domains in healthy adults over 18 weeks. A predetermined subgroup analysis was also planned to assess only those individuals who were vitamin D insufficient at baseline.
Vitamin D has been associated with cognitive function in observational and mechanistic research, but supplementation interventions to date are scarce and have some limitations. The study under review was an 18-week randomized controlled trial evaluating the effect of vitamin D supplementation on a broad range of cognitive domains in healthy adults.
Who and what was studied?
What were the findings?
What does the study really tell us?
The big picture
Frequently Asked Questions
What should I know?
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