Various types of cabbage, and cauliflower, all sources of folate, in a basketShare on Pinterest
Scientists have found unexpected results about folate intake and aging in mice. bondarillia/Getty Images
  • Folates (vitamin B9) that are important early in life may pose difficulties for people from middle age onward, according to a new study.
  • The study found that reducing folate consumption in older mice allows them to more easily switch between night and day modes of metabolism, or from burning fats to burning carbohydrates.
  • Although folates are linked to healthy blood, older mice in the study showed no signs of developing anemia.
  • The study constitutes early research in this area but follows similar results in yeast cells and worms.

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.

When mice and people sleep, their metabolisms are focused on burning body fat. During waking hours, the task at hand is burning carbohydrates for the energy needed to perform the day’s activities.

The current study supports the researchers’ findings in a previous study in which they used methotrexate to limit folate consumption in yeast cells, and also reduced folate intake in the worm C. elegans. Both yeast and worms lived longer than the controls who consumed typical amounts of folates.

In the current study, a cohort of middle-aged mice — 52 weeks old — were placed on either a standard diet or a folate-deficient diet.

The researchers found no evidence of anemia in their folate-deprived group, meaning they somehow still had sufficient red blood cells. They also observed no reduced viability or reduced body weight. Males in this group, in fact, weighed more than their standard-diet counterparts.

The study did not explicitly explore the effects of late-life folate reduction on longevity since all mice were euthanized at 120 weeks. However, males on both diets and females appeared to have similar life expectancies.

The study is published in Life Science Alliance.

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.”

Routhenstein stressed that folates are “essential for various bodily functions, including DNA synthesis, cell repair, and red blood cell production.”

“They are particularly important during rapid growth phases,” she noted, “such as pregnancy and infancy, and support cell function and division in adults while helping to prevent anemia.”

“Folates are also very important for cardiovascular health, especially as we age. Folates reduce homocysteine levels — a risk factor for heart disease — support vascular cell repair, and may have anti-inflammatory effects,” said Routhenstein.

Some foods that contain folates are:

  • asparagus
  • avocados
  • Brussels sprouts
  • chickpeas
  • leafy greens
  • lettuce
  • liver (avoid if pregnant)
  • peas
  • spinach

An intriguing question raised by the study is how the folate-deprived mice still managed to have enough red blood cells to avoid developing anemia. “That’s an excellent question,” said Polymenis.

“It is important to remember that although these mice received no folate in their diet, they still had enough folate to maintain red blood cell functions. Their folate levels were 30-40% of those seen in the control mice that received folate in their diet,” he said.

The question remains: what is the source of those red blood cells?

“It is almost certainly from the bacteria in their gut,” said Polymenis. “So, diet is not our only source of folate.”

“Our study also suggests that maintaining a healthy gut microbiome is crucial, and may be sufficient for ensuring adequate levels of vitamins, such as folate, and preventing associated health issues.”
— Michael Polymenis, PharmD, PhD

It is well established that folates are important for nutritional health, at least for younger people. It is also worth noting that Polymenis’ team has worked so far with yeast, worms, and mice but has not demonstrated their hypothesis in people. This is why he suggests caution.

“We advocate for no changes in people. While we believe our study is promising and needs to be followed up, it is a relatively small one in mice. At this stage, it emphasizes the need for further research before advocating changes for older adults,” said Polymenis.

For now, Routhenstein said, “Folate remains important for overall health, including cardiovascular well-being, so it’s crucial to maintain a diet rich in folate-rich foods.”

“Consulting with a registered dietitian nutritionist is recommended to stay informed about new nutrition research and continue following established nutritional guidelines,” she added.

Polymenis proposed a possible means of implementing folate reduction for older people should his research’s findings be confirmed in humans.

Some foods currently contain nutritive additives — milk is fortified with vitamin D, and folic acid is added to cereals and breads, for example. He envisioned a time when a folate-reducing additive may become a means of easily reducing folate intake for those middle-aged and older people who don’t need it.