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9 May 2016 - Vitamin D Council - Current research on vitamin D and dementia and Hill’s criteria for causation

John Cannell MD


Vitamin D is hardly ever out of the news these days - not least because insufficiency if not frank deficiencies of this key substance now affect the vast majority of the population in developed, and many developing, countries.

While best known for its role in building strong bones and teeth, Vitamin D is also critical for healthy brain development and functioning. While this is especially true in early life, this new research review summarises the increasing evidence that a lack of Vitamin D in older adults can contribute to age-related cognitive decline and dementia.

For details of the related research, see:

Professor Cedric Annweiler of the Angers University Hospital in France recently wrote a review paper on vitamin D and dementia to see if the current evidence meets Hill’s criteria for causation.

A remarkable JAMA-Neurology paper found those with the lowest vitamin D levels were three times more likely to develop dementia.

This paper along with others led Dr. Annweiller to investigate whether the evidence to date is strong enough to satisfy Hill’s criteria, which is a collection of findings seen when causation is likely. Here is what he found:

  • Temporality: Vitamin D deficiency precedes the onset of cognitive decline in cohort studies.
  • Strength of association: Low vitamin D is associated with cognitive disorders, with an odds ratio of greater than 2; meaning that the risk of cognitive disorders is more than twice as high in the case of low vitamin D.
  • Dose–response relationship: In most previous studies, higher 25OHD concentration was associated with better cognitive performance and decreased risk of dementia.
  • Consistency of findings: Significant observational evidence is available from cross-sectional and longitudinal studies, but interventional evidence is limited.
  • Plausibility: Vitamin D is involved in neurophysiology and neuroprotection of the brain.
  • Alternate explanations: Reverse causation (i.e., dementia precipitates hypovitaminosis D) is unlikely, because cohort studies show low vitamin D precedes dementia. Also, association between low vitamin D and dementia remains significant after adjustment for all potential confounders.
  • Experiments: Limited studies show cognitive improvements after vitamin D supplementation in the dementia and older patients.
  • Specificity: This criteria was not met. Although low vitamin D is very common among individuals with dementia, the prevalence of low D is too high in the general older population to be considered specific to dementia.
  • Coherence with known facts: Robust evidence exists that serum vitamin D status is a biological determinant associated with cognitive function in older adults.

He concluded: "The correction of hypovitaminosis D in older adults is justified from a cognitive perspective in preclinical studies and by a number of cross-sectional and longitudinal observational studies reporting direct associations between decreased 25OHD concentrations and cognitive disorders.”

It is important to remember that you can get dementia with a high 25(OH)D status as well. Maintaining a healthy D level simply reduces the risk of developing the disease.

About: John Cannell, MD

Dr. John Cannell is founder of the Vitamin D Council. He has written many peer-reviewed papers on vitamin D and speaks frequently across the United States on the subject. Dr. Cannell holds an M.D. and has served the medical field as a general practitioner, emergency physician, and psychiatrist.