Supplementation with vitamin D may be associated with slower epigenetic aging Original paper

This quasi-interventional study found that supplementation with vitamin D may be associated with slower epigenetic aging in older adults with vitamin D deficiency.

This Study Summary was published on June 28 2022.

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Aging is characterized by a progressive loss of physiological function and an increasing vulnerability to death.[1] In the most recent decade, researchers have developed several biomarkers to measure “cellular” age, which may differ from chronological age (the age of a person as measured from birth to a given date).

The marker most often used for cellular age is DNA methylation age (also called epigenetic age).[2] Different methods (also known as epigenetic clocks) are now available to measure DNA methylation age such as the 7-CpG clock,[3] Horvath’s clock,[4][5] Hannum’s clock,[6] PhenoAge,[7] and GrimAge.[8]

Interestingly, although chronological aging increases at the same rate for everyone, biological age does not.[9] This raises the question of what influences epigenetic aging and how can it be slowed down?

In recent years, researchers have identified many lifestyle factors such as diet,[10] smoking,[11] and exercise habits.[12] Another possible factor that may accelerate epigenetic aging is vitamin D deficiency, as shown by a recent cross-sectional study linking vitamin D deficiency to a higher DNA methylation age.[13] In this study, the same researchers analyzed the epigenetic age of the same cohort again after a follow-up period of 7.4 years to further explore the relationship between vitamin D and epigenetic aging.

The study

This cross-sectional, quasi-interventional study (i.e., an interventional study without random treatment assignment) examined the relationship between vitamin D supplementation and DNA methylation age in 128 healthy German adults (ages 65–94).

To conduct this quasi-interventional study, the researchers used the longitudinal data (i.e., observational data that is collected sequentially over time from the same population) of 1,036 German adults from a previous cohort study.[13] The treatment and control groups were selected so that both groups were vitamin D deficient at baseline but only the treatment group started vitamin D supplementation during the follow-up period. In other words, the researchers created the groups in such a way that vitamin D supplementation became the treatment. To allow for a valid comparison, the researchers matched the treatment and control groups based on age, sex, and morbidity. As a healthy control group, the researchers selected participants with sufficient vitamin D levels at baseline and throughout the entire follow-up period.

To determine the epigenetic age, the researchers measured five epigenetic clocks: the 7-CpG clock, Horvath’s clock, Hannum’s clock, PheoAge, and GrimAge. The researchers also calculated the difference between chronological age and epigenetic age.

The results

The vitamin-D-deficient treatment group who started vitamin D supplementation had a 2.4-year lower (7-CpG clock) and a 1.3-year lower (Horvath’s clock) epigenetic age compared to the vitamin-D-deficient control group. Also, the treatment group had a similar epigenetic age as the healthy control group after follow-up. However, no differences were found for the other three epigenetic clocks tested.


Even though this study used a quasi-interventional design (which is more powerful than an observational design), no causal conclusions can be drawn from this study. However, this study may spur future randomized controlled trials to further investigate a potentially causal effect of vitamin D supplementation on epigenetic aging.

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This Study Summary was published on June 28 2022.