As the global population continues to age, the importance of maintaining optimal health and well-being in older adults becomes increasingly crucial. One key factor that has gained significant attention in recent years is the role of vitamin D since aging is associated with a decline in the body’s ability to synthesize and utilize vitamin D efficiently (1). This, coupled with factors such as reduced sun exposure, limited outdoor activities, and decreased skin thickness, contributes to a higher prevalence of hypovitaminosis D in older adults. Studies have shown that up to 50% of older adults may have insufficient levels of vitamin D, which can have significant implications for their overall health and longevity (1).

Numerous studies have investigated the association between hypovitaminosis D and mortality risk, leading to the exploration of vitamin D supplementation as a potential intervention to improve health outcomes and reduce mortality rates. For instance, Chowdhury et al. (2) revealed, from a systematic review and meta-analysis of 73 observational studies and 22 RCTs, that low vitamin D levels were associated with an increased risk of all-cause mortality. Similarly, Gaksch et al. found in an Individual Participant Data meta-analysis including 26,916 participants and using standardized measurements of 25-hydroxyvitamin D (25(OH)D), that the hazard ratio for all-cause mortality comparing the lowest (0–12 ng/mL) to the highest (≥30ng/mL) category of 25(OH)D was 1.8 [95% CI: 1.4–1.9] (3). These results were strengthened by those of randomized controlled trials (RCTs) that tested the effect of vitamin D supplementation on mortality. One meta-analysis by Autier et al. (4), examining the association between vitamin D supplementation and mortality in 18 RCTs involving 57,311 participants, found that vitamin D supplementation was associated with a 7-percent reduction in all-cause mortality (summary relative risk for mortality 0.93 [95% CI: 0.87–0.99]). These findings were complemented by further meta-analyses, some being inconclusive (5) and others confirming the benefits of vitamin D supplementation on life expectancy (6). In all references, the subgroup analyses revealed potential benefits of vitamin D supplementation on survival in individuals with vitamin D deficiency at baseline, suggesting that it is not vitamin D supplementation per se that matters, but the correction of hypovitaminosis D. This consideration is fully consistent with the general literature on bone and non-bone effects of vitamin D (1, 7).

The whole question is then to understand how the correction of hypovitaminosis D can bring benefits, modest but significant, on life expectancy.

One central theory of aging relates to DNA exposure to free radical attacks as telomeres shorten during cellular mitosis, causing pathological aging. In this issue of the Journal of Nutrition, Health and Aging, Sabbir T Rahman and colleagues proposed an ancillary study within the D-Health randomized, double-blind, placebo-controlled trial to assess the effect of vitamin D supplementation on telomere length (8). A total of 1,519 Australian participants aged 60–84 years, 76.8% of them exhibiting sufficient 25(OH)D concentrations of more than 50 nmol/L at baseline, were randomized to 60,000 IU vitamin D3 per month (n=744) or a placebo (n=775). Results showed that the mean relative telomere length (T/S ratio) was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively) at 4 or 5 years after randomization, with no between-group differences even when accounting for age, sex, body mass index, and predicted baseline 25(OH)D concentration (8). This analysis suffered from some limitations described in the article which were primarily related to its conduction in post-processing, in particular the ignorance of the initial telomere length, which only made it possible to measure the final telomere length but prevented to evaluate a possible action of vitamin D on the telomere shortening, especially since the duration of follow-up and supplementation varied from one participant to another. Importantly, the results were above all limited by the fact that the vast majority of participants exhibited sufficient vitamin D concentrations before the start of the intervention. For the reasons mentioned above (7), it was therefore unlikely that this analysis would be able to show an effect (if any) of vitamin D supplementation on telomeres length and/or shortening. It should also be underlined that recent articles alerted on the fact that intermittent vitamin D supplementation with relatively high doses, as tested in the D-health study, are much less efficient than daily supplementation in improving different conditions independently of their capacity to increase serum 25(OH)D concentration (9).

Alternative explanations should also be considered to elucidate the benefits of vitamin D supplementation on life expectancy. In particular, vitamin D is a secosteroid hormone that exhibits multiple biological actions mediated by the vitamin D receptor present in almost all human tissues (1). Since vitamin D is needed for the regulation of cellular growth, function and protection, lower vitamin D status leads to multiple organ dysfunction, disability and unstable health status, which are all causes of deconditioning and mortality. Previous studies have reported potent associations between vitamin D deficiency and increased risks of various chronic diseases including cardiovascular disease, cancers, and respiratory infections (1).

One of the key mechanisms through which vitamin D exerts geroprotection is by regulating the immune system (10). Aging is associated with changes in immune function, referred to as immunosenescence, which can lead to increased susceptibility to infections and reduced ability to mount an effective immune response. Adequate levels of vitamin D have been shown to enhance immune function, reducing the risk of infections and improving overall immune response. This is particularly relevant in the context of respiratory infections, such as influenza and COVID-19, where vitamin D supplementation has been associated with decreased susceptibility and severity of the diseases (11).

Furthermore, vitamin D has been found to have anti-inflammatory properties, which can help mitigate inflammaging and the risk of chronic inflammation, a key driver of many chronic diseases (10). By reducing inflammation, vitamin D may help protect against the development and progression of conditions such as cardiovascular disease and certain types of cancer (1).

In conclusion, the impact of vitamin D and vitamin D supplementation on life expectancy is an area of growing interest and research. While the evidence suggests a potential benefit, further research is needed to establish a definitive link, including the impact on telomere shortening. Factors such as dosage, duration of supplementation, and individual variations in response need to be further explored. In the meantime, maintaining adequate vitamin D levels through a combination of sunlight exposure and (ideally daily) supplementation may be a prudent approach to optimize overall health and potentially improve life expectancy.