Ever since we launched our B-complex product Energin almost 10 years ago, we have been getting emails about why the product does not contain folic acid and vitamin B12. I keep answering by saying that both of those vitamins have been linked to higher risk of cancer, and as such have stubbornly resisted demands to add those 2 vitamins to the product. Now, the study below adds another good reason to not take folate supplement in adulthood – reduced folate intake may increase lifespan. Interestingly, the mechanism of action for lifespan extension by folate restriction is that dietary folate deficiency seems to restore metabolic flexibility – a hallmark of youth. While we easily switch between burning carbs and fat in our childhood and early adulthood, that flexibility declines as we age. Very old (or sick) people burn predominantly fat, even in the presence of sufficient glucose intake. This lack of metabolic flexibility is likely driven by a steady decline in thyroid function as we age, which results in compensatory increase in adrenal activity, with the end result being that older people are in a state of chronic stress even when undisturbed, which results in excessive lipolysis and thus dominance of fat oxidation as per the Randle Cycle. Whether restricting dietary folate results in increased thyroid function, reduced adrenal hyperactivity, or both remains to be discovered. Be that as it may, the main (indirect) finding of the study seems to be that lifespan is metabolically controlled, and restoring youthful metabolic profile can extend lifespan.
https://pubmed.ncbi.nlm.nih.gov/38260683/
“…Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual’s age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.”
“…A new study suggests that while consuming folates is considered healthy for everyone — and it clearly benefits the young — it may result in metabolic issues for older individuals. The study of mice from Texas A&M University’s AgriLife Research found that lower levels of folates, the naturally occurring form of vitamin B9, facilitated the transition from sleep metabolism to waking metabolism…The study’s senior author, Michael Polymenis, PharmD, PhD, who teaches biochemistry and biophysics at Texas A&M, told Medical News Today, “As we age, we cannot switch quickly from one mode of metabolism (e.g., burning fat while we sleep) to another (e.g., burning carbs when we wake up). Quick transitions are necessary to meet our body’s on-demand needs.” Michelle Routhenstein, MS, RD, CDCES, preventive cardiology dietitian at EntirelyNourished.com, who was not involved in the study, explained, “During the day when active, the body primarily uses carbohydrates for energy, with higher insulin levels facilitating glucose uptake. At night, insulin sensitivity decreases, shifting metabolism toward using stored fat, as the body’s energy needs are lower, and growth hormone levels increase.” “As we age,” said Polymenis, “our bodies become less adept at adjusting their fuel source in response to changing needs, which can affect overall health and energy levels.”
