Remember what you see with vitamin D

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.