I try to spend as little time as possible zoning out on social media, but sometimes I spot posts that give me the heads up on health stories the mainstream press hasn’t yet caught up to.
The other day, I was surprised to see that “folic acid” was trending on X. On a day where “Gaza”, “Paris student protests”, “Ukraine”, “Houtis” and “Russian plague lab” should’ve been top of the feed, why was folic acid in the news?
First, some background . . .
After evidence emerged in the 70s that folic acid supplementation could reduce the incidence of neural tube defects, enrichment with folic acid in flour, rice, pasta and cereals was finally mandated in the U.S. in 1998.
Neural tube defects are among the most common disabling birth defects. They result from incomplete methylation in embryonic cells of the developing spinal cord in the early first trimester of pregnancy, to which women with insufficient folate levels are prone.
It’s estimated that around 20% of women of childbearing age are at risk of folic acid deficiency. Fruits, vegetables and whole grains—conspicuously absent in ultra-processed foods—are sources of folate, the natural source of vitamin B9. So is liver, something that most Americans don’t eat.
Neural tube defects can result in stillbirths; when babies with NTD survive, they can suffer from spina bifida, a condition which can cause difficulties with walking and bladder control.
Between food enrichment and encouragement of prenatal supplements delivering 400 mg of folic acid per day, the incidence of neural tube defects has declined by 28% in the U.S.—an estimated impact on 1000-1300 live births per year. And when it occurs, it’s less severe.
Nevertheless, the UK has been slow to adopt fortification. That is, until now. Enforcement is set to be mandated this December.
Resistance to fortification mounts
This has resulted in a firestorm of protests. One poster—a self-described retired GP and “TRUTHSEEKER”—wrote on “X”:
“No proper investigations were ever carried out into the longterm effects of adding synthetic folic acid to our food. It blocks the uptake of natural folate which protects us against cancers. We have seen an increase in cancers in younger people & cereals have been fortified with folic acid for decades. Is this a coincidence?
Folic acid does not need to be in our food. There are plenty of natural sources of folate. We do not even have good evidence that it protects against the neural tube defects that is the claimed reason for adding this. It has many other, potentially serious side effects . . . Please sign the petition to get this removed from our food.”
The UK campaign claims to have garnered 100K signatures.
So let’s look at the science behind the claims . . .
First what is folic acid and is it “synthetic”?
If the latter, we might suspect it to be an inferior form of vitamin B9, much as we think of manufactured beta carotene as a poor substitute for natural mixed carotenoids, or d-alpha tocopherol as an lesser stand-in for natural mixed tocopherol vitamin E.
It’s true that folic acid is a manmade synthetic. It doesn’t exist in nature. When consumed, folic acid requires multiple steps to be converted to its biologically active form, tetrahydrofolate, Some people, it is claimed, have weak pathways for processing folic acid. Food sources of folate, on the other hand, are more body-ready, bypassing roadblocks to conversion.
Is 5-methyl folate better?
Sometimes abbreviated 5-MTHF, also called l-methylfolate, 5-methyl folate is a premium ingredient that costs several times more than folic acid. It is often touted for treatment of high homocysteine, or for people who have MTHFR genetic variants that suggest a susceptibility to poor conversion of folic acid to its active forms.
Studies that claim its superiority are often tainted by association with companies that market the pricey ingredient.
In most head-to-head comparisons, folic acid delivers equivalent results, even in patients with high homocysteine, or those having MTHFR conversion glitches.
What about “unmetabolized” folic acid?
The argument has been made that in some individuals, poor conversion of supplemental folic acid—but not natural folate from food—to its active metabolites can result in a pile-up: Folic acid accumulates, with untoward results.
It is said that all that surplus folic acid can compete with natural folates, blocking their uptake.
Among the hypothesized risks are organ fibrosis, neurological damage, and immune suppression—maybe even cancer.
Anemia risk?
It has also been claimed that supplementing with folic acid (without accompanying B12) can disguise B12 deficiency anemia. But that argument disintegrates when we acknowledge that older adults, people with GI problems, consumers of certain meds, and devout vegans should be screened with readily-available B12 blood tests.
An autism cure?
There is one instance where that folate might deliver on that promise. Remember the flap about the Trump/RFK Jr. press conference that was supposed to be the big reveal about a “cure” for autism?
It was claimed that folate might be a panacea. But not just any kind. And only in rare instances, where autistic kids test positive for cerebral folate transport deficiency. In their brains, normal supplementation with folic acid won’t cut it, and may even block already weak receptors. The condition can be alleviated with high-dose folinic acid (Leukovorin), a prescription drug.
What about the cancer risk?
Folate is essential for methylation. Think of methylation as a way of turning on and turning off genes—a control switch, if you will. When it comes to cancer, there are oncogenes that predispose to cancer, and tumor suppressor genes that put the brakes on it. Therefore, it’s not surprising that folate has a paradoxical effect on cancer.
Moreover, folate acts within the nucleus to control the proper expression of DNA, the genetic blueprint of cells. Folate deficiency results in “genomic instability” which causes mistakes in transcription.
Why timing matters
On the one hand, folate has been shown to be preventive when it comes to cervical cancer and oropharyngeal cancer. I’ve leveraged high dose folate successfully in preventing progression to cancer in women with abnormal PAP smears, a form of pre-cancer.
On the other hand, folic acid supplementation has been shown to be associated with greater likelihood of progression to cancer in smokers.
And one of the earliest cancer drugs, methotrexate, works precisely because it blocks folate metabolism.
Therefore, timing may matter when it comes to folic acid administration in cancer. Every day in our bodies, mistakes in DNA replication create cellular mutations that have the potential to morph into full-blown cancer. Cancer suppressor genes, and transcription modifiers in the nucleus, activated by proper methylation, edit out these glitches before they threaten to replicate uncontrollably.
On the other hand, when active cancer might be present, in which a cell’s DNA is commandeered to crank out more copies of itself, vitamin B9 might fuel cancer proliferation. In patients recovering from cancer, I generally recommend they go easy on potent multis or B complex supplements because of the possibility of revving cancer growth.
But I don’t go so far as to tell them to avoid fortified foods.
Is folic acid fortification fueling a cancer epidemic?
A large 2013 meta-analysis attempted to address this question. Reassuringly, the researchers concluded:
“There are growing data and a continuing controversy over the effect of folic acid supplementation on cancer risk . . . Our findings indicate that folic acid supplementation has no significant effect on total cancer incidence, colorectal cancer, prostate cancer, lung cancer, breast cancer or hematological malignancy, but reduces the risk of melanoma.”
What’s the BOTTOM LINE on folic acid fortification?
These days, any government-imposed mandate in the name of “public health” has become a flash-point—think fluoridation, universal COVID vaccination, even bans on jumbo soda servings.
But every intervention—be it with drugs or supplements—entails a risk-benefit calculation. When it comes to folic acid administration, the evidence suggests true reduction in neural tube defects, a public health triumph.
Moreover, there may be unintended benefits of folic acid fortification for the populace at large. In addition to preventing folate deficiency anemia (inadequate B12 and iron are more common causes), folic acid may help reduce homocysteine, a pro-inflammatory metabolite considered a risk factor for cardiovascular disease.
So net/net, I consider folic acid supplementation a win. There are far more plausible explanations than its addition to foods for the uptick in cancer incidence in young people: ultra-processed foods replete with harmful synthetic additives; sugary drinks and confections; deficiencies of protective nutrients like vitamin D, omega-3s, and dietary polyphenols; pro-inflammatory, industrially-processed seed oils, binge-drinking; proliferation of environmental chemicals; intestinal microbiomes ravaged by antibiotics and glyphosate; microplastics; and soaring rates of obesity.
Given the abysmal diets consumed by many in the British Isles, it’s high time they get on board with folic acid supplementation.
What about 5-MTHF?
And yes, more research should be performed to ascertain whether or not 5-MTHF is a superior, cost-effective delivery system for B9 in general purpose nutritional supplements. Pricier may connote premium, but may just be costly overkill, the product of slick marketing. I remain skeptical, along with many thoughtful nutrition experts, like Dr. Alan Gaby, who points out:
“Another factor that argues against the routine use of 5-MTHF is that it is a relatively unstable molecule, whereas folic acid is more stable . . . One study found that up to 76% of the 5-MTHF in a prenatal multivitamin product was degraded after an unspecified period of time. In contrast, little or no degradation of folic acid occurred when it was included in the same prenatal multivitamin preparation.”
Special cases may prove the exception. There’s evidence that high-dose 5-MTHF can augment the benefits of SSRI/SNRI meds for depression. Because it readily crosses the blood-brain barrier, it holds promise for cognition. But this must be balanced against its potential to cause side effects like anxiety, irritability, racing thoughts, or insomnia, particularly in sensitive individuals or those with bipolar disorder.
More secrets remain to be unlocked about the optimal forms of, and use cases for, the vital nutrient family that is vitamin B9.
For a deeper dive on this subject, I recommend this excellent review by Deanna Minich, Ph.D., a frequent guest on Intelligent Medicine.
