Depression and anxiety are neuropsychiatric diseases characterized by neurological dysfunction and poor mental health. Oxidative stress, which is caused by an imbalance in the concentration of reactive oxygen species and antioxidant compounds, may be one driver of neurological damage in the development of depression and anxiety. Findings of a new report demonstrate the ability of methyl donor supplementation to reduce oxidative stress in the brain and relieve depression and anxiety symptoms in rats eating a high-sugar diet.

Methyl donors (e.g., choline, betaine, folate, vitamin B12) are nutrients that provide a methyl group (one carbon and three hydrogen molecules) for a series of chemical reactions in the body. Methyl donors interact with the methyl carrier, S-adenosyl-L-methionine (SAM) and methylation enzymes to complete the transfer of a methyl group from the donor to a target protein, lipid, or nucleic acid. Methylation of nucleic acids in DNA and ribonucleic acids in RNA is necessary for epigenetic modifications and gene expression. Good dietary sources of methyl donors include egg yolks and soy foods (high in choline); whole grains (high in betaine); green vegetables (high in folate); and meat, dairy, and fortified products (high in vitamin B12).

Methyl groups may also have antioxidant properties that protect the body from oxidative damage due to environmental stress, such as a high sugar diet, and emotional stress. Previous research has demonstrated the ability of methyl donor supplementation to reduce the metabolic and neuropsychiatric impairments caused by a high sugar diet in rats.

The investigators fed 21 female rats a standard chow diet with either tap water (7 rats) or drinking water with 23 percent fructose added (equivalent to twice the sugar concentration of most sodas)(14 rats). After 10 weeks, the investigators gave half of the rats in the fructose group methyl donor supplements (i.e., choline, betaine, folate, and vitamin B12). The rats continued the study for an additional eight weeks. The researchers measured the effects of fructose and methyl donors on metabolism, behavior, and brain health.

A high-fructose diet caused increased weight gain, fasting glucose and triglycerides, and anxiety and depression behaviors compared to a standard diet. A high-fructose diet also increased oxidative damage and lipid peroxidation in the neurons of the hippocampus, a key brain region damaged by depression and anxiety. After eight weeks of methyl donor supplementation, this hippocampal damage was reversed, reducing depression and anxiety behavior. Methyl donor supplementation also normalized glucose, triglyceride, and cholesterol levels among rats consuming a high-fructose diet.

These results demonstrate the efficacy of methyl donor supplementation to reduce or reverse the promotion of obesity, metabolic disease, and depression and anxiety on a high-fructose diet in rats.

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• Learn more about methylation enzymes and epigenetics in this episode featuring expert Dr. Steve Horvath.