Examining nutrition strategies to influence DNA methylation and epigenetic clocks: a systematic review of clinical trials

Nutrition has powerful impacts on our health and longevity. One of the mechanisms by which nutrition might influence our health is by inducing epigenetic modifications, modulating the molecular mechanisms that regulate aging. Observational studies have provided evidence of a relationship between nutrition and differences in DNA methylation. However, these studies are limited in that they might not provide an accurate control of the interactions between different nutrients, or between nutrition and other lifestyle behaviors. Here we systematically reviewed clinical studies examining the impact of nutrition strategies on DNA methylation. We examined clinical studies in community-dwelling adults testing the effects of nutrition interventions on i) global DNA methylation and its proxies, and ii) epigenetic clocks. We included 21 intervention studies that focused on the effects of healthy nutrition patterns, specific foods or nutrients, as well as the effect of multivitamin or multimineral supplements. In four studies on the methylation effects of healthy dietary patterns, as defined by being rich in vegetables, fruits, whole-grains, and nuts and reduced in the intake of added sugars, saturated fat, and alcohol, two of them suggested that a healthy diet, is associated with lower epigenetic age acceleration, one of them reported increases in global DNA methylation, while another one found no diet effects. Studies examining epigenetic effects of specific foods, nutrients, or mixtures of nutrients were scarce. For both folic acid and polyunsaturated fatty acids, the available independent studies produced conflicting findings. Although more evidence is still needed to draw firm conclusions, results begin to suggest that healthy dietary patterns have positive effects on DNA methylation. Additional evidence from large randomized-controlled clinical trials is needed to support the effects of healthy nutrition on the DNA methylome.