Researchers found that low folate intakes may improve metabolic health and promote healthier aging in animal models, casting doubt on the common belief that high folate intakes are universally beneficial. The study suggests that optimal folate levels may vary by age, and advocates for personalized dietary guidelines.
New research suggests that reducing folate in the diet may increase metabolic flexibility.
In a study published in the journal Life Science Alliance, scientists from Texas A&M AgriLife Research found that reducing folic acid intake led to healthier metabolism in aging animal models, a finding that calls into question the conventional belief that high intakes of folic acid are universally beneficial to health.
The research was led by Dr. Michael Polymenis, professor and associate director of graduate programs in the Department of Biochemistry and Biophysics in the College of Agriculture and Life Sciences at Texas A&M University.
Lead researcher Michael Polymenis, PhD, and Heidi Blank, PhD, first author of the study published in the journal Life Science Alliance. This is the latest study in the researchers’ continuing investigation of the effects of folic acid in biological models. (Eun-Gyu No, PhD/Texas A&M AgriLife)
Folic acid, a B vitamin essential for cell growth and development, is widely known to help prevent birth defects. Folic acid is found naturally in foods such as green leafy vegetables and is commonly added to refined grains. Although folic acid is widely consumed, the long-term health effects of consuming large amounts of folic acid over a lifetime are unknown.
The researchers found that restricting folate in animal models reduced processes related to growth and the formation of new cells, while increasing metabolic flexibility, which Polymenis said could lead to healthier aging.
“Optimal folate intake may vary with an individual’s age,” he said. “Higher folate intakes in early childhood are important for growth and development, while lower folate intakes in later life may be beneficial for metabolic health and longevity.”
The study supports the concept of precision nutrition and advocates for personalized dietary recommendations, a pillar of research at the Texas A&M AgriLife Institute for Health Advancement through Agriculture (IHA), of which Polymenis is an affiliate member.
Polymenis said further research is needed to explore the mechanisms behind this phenomenon and develop safe and effective therapeutic interventions to promote healthy aging.
Other Texas A&M AgriLife researchers involved in the project include:
The study’s authors include: Heidi Blank, PhD, research scientist in the Polymenis lab and first author on the study; David Threadgill, PhD, chair of the Department of Nutrition; Patrick Stover, PhD, professor in the Department of Nutrition; Charlie Johnson, PhD, director of Texas A&M AgriLife Genomics and Bioinformatics Services; and Marcel Brun, PhD, assistant director of Texas A&M AgriLife Genomics and Bioinformatics Services.
Changing needs throughout the lifespan
Folate, or vitamin B9, is an essential dietary component used by the body to form red blood cells. DNA, RNAand protein. Polymenis said vitamins are especially important for children, adolescents and pregnant women because they play a key role in the growth process.
He and other researchers at Texas A&M AgriLife wanted to explore the effects of folic acid in an age group that hasn’t been studied much. To simulate the effects on older people, the researchers cut folic acid from the diets of animal models at an age roughly equivalent to middle age in humans. A comparison group was raised identically but continued to eat a typical diet that included folic acid.
The researchers found that folate-restricted female models were able to switch between carbohydrate and fat metabolism more quickly throughout the day and night compared to women on a typical diet.
“When you sleep, your metabolism burns fat,” Polymenis says, “and when you’re awake and active, you typically burn carbohydrates for faster energy. As we age, it takes us longer to switch between fat-burning and carbohydrate-burning states, but this metabolic plasticity seems to be better maintained in animal models on a folate-restricted diet.”
Men who consumed a folate-restricted diet had an overall increased metabolic rate during active periods, which may help maintain energy levels and physical activity.
Blank said the folate-restricted group maintained their weight and body fat into old age, in contrast to the control group, and there was no sign of anemia or other negative health effects in the folate-restricted model, even though folate is important for the production of red blood cells.
Folic acid is found naturally in foods such as leafy green vegetables and avocados. Folic acid, a synthetic version of folate acidis often added to grains after they have been refined. The word comes from folio, which has the same root as foliage, because of its abundance in leafy green vegetables. (Sam Kraft and Laura McKenzie/Texas A&M AgriLife)
Series of studies
Polymenis said he and his team were not surprised to see that the folic acid-restricted group aged healthier.
The team first used methotrexate to reduce folate uptake in yeast cells a few years ago, and then began doing this with the roundworm C. elegans: in both cases, cutting out folate extended the lifespan of the models.
The team’s next step is to repeat the experiment in more genetically diverse models to simulate human genetic variation.
The researchers will also expand their investigation of new compounds to limit folate intake, which could later move into clinical trials.
Folate-restricting therapy
Packing nutrients into commonly consumed foods, such as vitamin D in milk and calcium in fruit juice, has proven useful in solving public health problems. For example, the thyroid problems that plagued the United States in the early 20th century were the result of widespread iodine deficiency, but this was solved by adding iodine to the salt consumers ate.
In 1998, the United States mandated that staple foods, especially grains, be “fortified” or “fortified” with folic acid and other B vitamins through refinement processes. This is beneficial for some age groups, but may do more harm than good for older adults.
As a result, Polymenis said the study opens up new avenues for developing drugs to limit dietary folate intake for people who don’t need as much folate, rather than reducing the synthetic folate or foods that contain folic acid that’s often added to foods and supplements.
However, Polymenis said he doesn’t recommend avoiding folic acid altogether.
“Our findings suggest that older adults may need less folate than they currently get,” he said. “There is still a lot of research to be done in this area, but we would not recommend that anyone completely eliminate folate from their diet.”
Reference: “Dietary folate restriction in old age reduces biosynthesis without compromising healthspan in mice” Heidi M Blank, Staci E Hammer, Laurel Boatright, Courtney Roberts, Katarina E Heyden, Aravindh Nagarajan, Mitsuhiro Tsuchiya, Marcel Brun, Charles D Johnson, Patrick J Stover, Raquel Sitcheran, Brian K Kennedy, L Garry Adams, Matt Kaeberlein, Martha S Field, David W Threadgill, Helene L Andrews-Polymenis, Michael Polymenis, 23 July 2024, Life Science Alliance.
Translation: 10.26508/lsa.202402868
