Using a Berlin cohort, a study published in GeroScience has uncovered a link between Vitamin D supplementation and a reduction of epigenetic age.
On the back of previous work
This study’s cohort consisted of 60- to 85-year-old participants in the Berlin Aging Study II (BASE-II). The researchers had previously used data from this cohort to determine a relationship between a lack of vitamin D and an accelerated epigenetic age. Their hypothesis was confirmed by the use of 7-CpG, a novel epigenetic clock that is strongly associated with chronological age . That study showed that people who are deficient in Vitamin D have an epigenetic age that is nearly a year more than average .
This new study set out to answer a different question: Does restoring Vitamin D through supplementation also reverse the effects on epigenetic age?
A long-term longitudinal study
To answer this question, this study’s authors utilized over a thousand participants who were approximately 68 years old at baseline and re-examined at an average age of 75. This group was roughly evenly split between men and women.
At baseline, nearly half of the participants were deficient in Vitamin D, and only 7% were taking supplements; in the follow-up portion, only a quarter were deficient, and a fifth were taking supplements. Both times, about three-fifths of the participants received their blood draws during the sunnier months of the year, when Vitamin D deficiency is less likely.
The researchers note only 55 people whose increases in Vitamin D can neither be explained by supplements nor by season. They also note that, while some people who were originally taking Vitamin D supplements had stopped, a full 82% of the supplement takers in this study had only begun after their baseline examination.
A quasi-interventional study
In order to analyze the effects of Vitamin D supplements, the researchers noted 63 people who had previously been deficient in Vitamin D but who became sufficient after supplementation. They then matched these participants (based on demographic data) to 63 people who were deficient and unsupplemented, marking them as the untreated group. Finally, after matching, another 63 unsupplemented but healthy people were utilized as controls.
The results were clear only for two of the five clocks: Participants who went from deficiency to sufficiency through vitamin D supplements were shown to be epigenetically younger by more than two and a half years according to the 7-CpG clock and a year and a quarter younger according to the Horvath epigenetic clock, which is also associated with chonological age. However, while some effects were visible on the Hannum, GrimAge, and Levine clocks, these differences were not statistically significant.
As expected, there were also no significant differences between the Vitamin D supplemented group and the people with naturally healthy levels of Vitamin D.
Despite the researchers’ efforts, this is still a longitudinal study and not a true, blinded effectiveness study. There was no placebo group, and the treatment, untreated, and healthy groups were established after the fact. The researchers also note multiple potential confounding factors, most notably that people taking Vitamin D supplements might have attempted to improve their health through other means as well.
With that in mind, it is likely that an ongoing lack of vitamin D is having an effect on epigenetics, but to prove the existence of such a causal relationship, a double-blinded study must be conducted. Fortunately for such future research, a double-blinded study has already been conducted on the safety of Vitamin D supplements.
 Vetter, V. M., Meyer, A., Karbasiyan, M., Steinhagen-Thiessen, E., Hopfenmüller, W., & Demuth, I. (2019). Epigenetic clock and relative telomere length represent largely different aspects of aging in the Berlin Aging Study II (BASE-II). The Journals of Gerontology: Series A, 74(1), 27-32.
 Vetter, V. M., Spira, D., Banszerus, V. L., & Demuth, I. (2020). Epigenetic clock and leukocyte telomere length are associated with vitamin D status but not with functional assessments and frailty in the Berlin aging study II. The Journals of Gerontology: Series A, 75(11), 2056-2063.