The research noted here is interesting given the present impression of folate as a generally beneficial supplement. Like most aspects of the interaction between diet and cellular biochemistry, matters turn out to be more complex and situational. Nothing is simple! As it turns out, reduced folate in older animals reduces anabolic activity, and thus may be touching on some of the same mechanisms that produce benefits to health in response to a lower calorie intake.
Folate, or vitamin B9, is an essential dietary component used in the body to form red blood cells, as well as DNA, RNA, and proteins. It is especially vital for children, young adults and pregnant women because of its role in growth processes. Researchers wanted to explore its impact in lesser studied age groups. To simulate the effects in older adults, the researchers cut folate from the diets of animal models at an age corresponding roughly to human middle-age. A comparison group was raised the same but continued a typical diet inclusive of folate.
The researchers found the female folate-limited models were able to transition quicker between carbohydrate metabolism and fat metabolism across night and day compared to females on a typical diet. “When you sleep, your metabolism burns fat. And when you’re awake and active, you’re typically burning carbohydrates for quicker energy. As you get older, it takes longer to switch between these fat-burning and carbohydrate-burning states, but this metabolic plasticity seems to be better maintained in animal models on a folate-limited diet.” The males on folate-limited diets had an overall increase in their metabolic rate during active periods, potentially helping them to maintain energy levels and physical activity. The folate-limited group maintained their weight and body fat into old age as opposed to the control group.
The research team began this work a few years ago by using methotrexate to reduce folate intake in yeast cells, then in the worm C. elegans. In both cases, cutting folate led the models to live longer. Looking forward, the team’s next step will be to repeat the experiment in more genetically diverse models, simulating the genetic diversity of humans. The researchers will also expand their study of novel compounds to limit folate intake, which could later transition to clinical trials.
In 1998, the U.S. mandated that staple foods, particularly grains, be “enriched” or “fortified” with folic acid and other B vitamins following the refinement process. While helpful for some age groups, it might do more harm than good for older adults. As a result, this research opens a new avenue for developing drugs to limit dietary folate uptake for individuals who don’t need as much, rather than cutting foods that contain folate or folic acid.
