The Role of One-Carbon Metabolism in Healthy Brain Aging

Abstract

Aging results in more health challenges, including neurodegeneration. Healthy aging is possible through nutrition as well as other lifestyle changes. One-carbon (1C) metabolism is a key metabolic network that integrates nutritional signals with several processes in the human body. Dietary supplementation of 1C components, such as folic acid, vitamin B12, and choline are reported to have beneficial effects on normal and diseased brain function. The aim of this review is to summarize the current clinical studies investigating dietary supplementation of 1C, specifically folic acid, choline, and vitamin B12, and its effects on healthy aging. Preclinical studies using model systems have been included to discuss supplementation mechanisms of action. This article will also discuss future steps to consider for supplementation. Dietary supplementation of folic acid, vitamin B12, or choline has positive effects on normal and diseased brain function. Considerations for dietary supplementation to promote healthy aging include using precision medicine for individualized plans, avoiding over-supplementation, and combining therapies.

Keywords: choline; folic acid; healthy aging; neurodegeneration; one-carbon metabolism; vitamin B12.

Figure 1

Simplified cellular one-carbon (1C) metabolism. B-vitamins are pleiotropic molecules, as they are involved in nucleotide synthesis, DNA repair, methylation, and transsulfuration. In this review, we focus on the impact of increasing dietary levels of folic acid, vitamin B12, and choline (red text). A control diet with adequate levels will also be used. Abbreviations: folate receptor, FR.