Writing in the journal Nutrients, researchers from Midwestern University, Southern Illinois University, Carleton University and the University of Arizona analyzed adverse health effects in people consuming high amounts of folic acid as reviewed in studies collected through a search of the PubMed, Web of Science and Google Scholar databases.
“Our survey of the literature found that increased dietary intake of folic acid promotes inflammation, angiogenesis and neurotoxicity,” they reported.
“We also report negative actions of increased dietary intake of folic acid with vitamin B12 and genetic deficiencies in one-carbon metabolism. Increased dietary intake of folic acid also results in elevated levels of unmetabolized folic acid in the population, of which the impact on health risks has not yet been determined.”
They noted that the effects of overnutrition have largely been overlooked in research and acknowledged the scarcity of research in this area.
“We need to understand how unmetabolized folic acid impacts health function,” Nafisa Jadavji, PhD, an author on the paper, told NutraIngredients.
Concerns with overconsumption
One of few nutrients approved for health claims, folic acid offers numerous health benefits, particularly for women of childbearing age. Inadequate levels can increase the risk of giving birth to children with neural tube defects (NTDs). In 1998, the United States and Canada began fortifying foods with folic acid to reduce NTD rates, which spurred other countries worldwide to do the same.
As for other health indicators, the researchers pointed to a meta-analysis of 82,334 participants which showed that folic acid supplementation could reduce strokes by 10%.
Despite these benefits, overconsumption of folic acid can lead to negative interactions with vitamin B12 as older people are often deficient in the vitamin, and too much folic acid can make it worse, Dr. Jadavji said.
Additionally, 1C metabolic pathway dysfunctions may occur with increased folic acid intake, “including deficiencies in folic acid receptor functionality, altered enzyme expression and hidden malnutrition of other essential vitamins associated with 1C metabolism,” at least in mice models, the researchers explained.
“Over supplementation with folic acid can have a negative impact on health,” Dr. Jadavji said. “Folic acid supplementation should not exceed 1,000 mcg. If individuals have a polymorphism in MTHFR, folic acid supplementation is not adequate. They need to supplement with 5-MTHF.”
The review noted that in counties with mandatory fortification laws in place, individuals have continued to increase their dietary intake of folic acid beyond baseline levels.
Interaction with hypoxia
Findings highlighted how increased dietary intake of folic acid interacts with hypoxia—a reduction of oxygen in the body and a predominant feature of cardiovascular disease, including ischemic stroke.
“The mechanisms through which increased levels of dietary folic acid impacts health outcomes after hypoxia are poorly understood,” the researchers noted.
The review found that higher levels of folic acid intake promotes inflammation, angiogenesis and neurotoxicity.
“A baseline understanding of how stroke outcome and recovery are directly affected by folic acid levels can lead to studies of how the prototypical response to hypoxia by folic acid levels is additionally affected by modulations of frequency and intensity in stroke,” the researchers.
Precision gaining momentum
Precision nutrition is gaining more momentum, which allows researchers to explore the mechanisms behind individual responses.
“Adequate understandings of 1C metabolism condition in an individual can inform prophylactic management of stroke for demographics that are at higher risk,” the researchers wrote.
“Individualized measurements could include genetic testing for common polymorphisms in enzymes involved in 1C (e.g. MTHFR), plasma homocysteine levels, methylmalonic acid in blood or urine. This can be combined with other therapies to further improve the quality of life in at-risk individuals and improve overall health.”
Folate fortification laws should also be taken into account in terms of supplementation, Dr. Jadavji added.
The review of the literature emphasizes that “a more comprehensive understanding of the action between increased dietary intake of folic acid on disease outcomes could pave the way for improved public health guidelines.”
Source: Nutrients. doi: 10.3390/nu17071286. “How Increased Dietary Folic Acid Intake Impacts Health Outcomes Through Changes in Inflammation, Angiogenesis, and Neurotoxicity”. Authors: Siddarth Gunnala et al.
