Posted May 20, 2018: by Bill Sardi
Main points
For more than two decades it was known that women could reduce their risk of having a baby with a birth defect (spina bifida) with vitamin therapy before action was taken to remedy the situation. Given that only an estimated 29% of women of reproductive age were taking a folic acid supplement, health authorities reticently motioned to start folic acid food fortification, concerned that this B vitamin might mask vitamin B12 deficiency and result in untold morbidity.
In 1996, the United States Food and Drug Administration required enriched grain products with folic acid (vitamin B9) fortification to reduce the risk of birth defects (neural tube defects — spina bifida, anencephaly) in newborns. At the time researchers also hypothesized that B9 fortification might offer a secondary benefit of reducing blood serum homocysteine concentrations in the population as a whole, which might lead to a decline in death rates due to cardiovascular disease and stroke.
Food fortification of flour and cereals with folic acid was shortly followed by a doubling of the average blood serum folate concentration, from 6.6 nanograms/milliliter to 15 nanograms/milliliter blood sample, and an average 14 percent reduction of the serum homocysteine concentration. As hypothesized, the reduction in homocysteine levels was associated with declining mortality rates due to stroke and cardiovascular disease. Only recently has it been reported that folic acid adequacy dramatically reduces the risk for stroke, especially among high-risk individuals.
So this preventive health measure has produced positive health benefits but also some unanticipated negative results that were obviously not evident two decades ago.
We live in the post food fortification era. Folic acid intake is at unprecedented high levels due to food fortification. Universal food fortification with folic acid to prevent birth defects has retrospectively led to the realization that over-supply of folic acid has resulted in a decline in immunity (via decreased natural killer cell activity), a masking of vitamin B12 deficiency with its accompanying symptoms (short-term memory loss, burning feet, backaches, chronic cough, fatigue), and many other maladies.
Folic acid supplementation may now be harmful for some people. Un-metabolized folic acid levels nearly double in folic acid-fortified human populations.
Un-metabolized folic acid is indicative of intake beyond the metabolic capacity of the body. In developed countries with food fortification programs tiny amounts of un-metabolized folic acid have become common in blood samples yet no overtly apparent health problems were readily noted with food fortification. But two decades following the mandated fortification of food with folic acid, there is real cause for concern.
The primary problem is that metabolism of folic acid is slow. It takes at least 5 hours to eliminate excess folic acid. At least half of fortified populations consume more than 363 micrograms of folic acid per day in addition to natural folate from their diet. That is an unprecedented intake level.
While studies with rats were used to determine metabolism rates of folic acid dietary supplements, lab rats metabolize folic acid much faster than humans. One study shows folic acid conversion to its active folate form varies by 5-fold from individual to individual.
It has been determined that among healthy postmenopausal women with a diet low in folate (less than 233 micrograms per day), those who consumed folic acid supplements exhibited enhanced immunity as evidenced by greater ability of white blood cells (natural killer cells) to kill pathogens.
However, 78% of individuals who consumed a folate-rich diet and used 400 micrograms or more of folic acid supplements had un-metabolized folic acid in their blood samples and alarmingly experienced a 23% reduction in natural killer cell activity!
Said another way, people who eat healthy foods rich in folate and who take a folic acid supplement may be overdoing it.
Synthetic folic acid, the oxidized form of vitamin B9, is not the form of this vitamin in fresh foods (green leafy vegetables, spinach, broccoli). Folate is the natural form. To convert to folate, folic acid in dietary supplements must be converted to folate (tetrahydrofolate) by a key enzyme (dihydrofolate reductase or DHFR).
The extremely slow rate of conversion from folic acid to folate, limited by the variable activity of the DHFR enzyme, results in undesirable amounts of un-metabolized folic acid in the blood circulation.
Health authorities say folic acid supplementation is beneficial for most people but the occurrence of oversupply, above the Tolerable Upper Intake Level of 1 milligram (1000 micrograms) may result in disease substitution rather than disease prevention, replacing a decline in birth defects for a host of other maladies. To make matters worse, with no concern over metabolic and genetic problems involved in vitamin B9 nutriture, some narrow-minded researchers suggest there is no toxicity associated with mega-dose folic acid supplementation whatsoever, only a masking of B12 deficiency that produces neurological damage. After decades of debate, scientific controversy prevails.
But actually supplementation over ~200 micrograms of supplemental folic acid combined with folate-rich foods will often produce potentially problematic levels of un-metabolized folic acid.
Methyl folate (methylated folate) is the predominant form of active vitamin B9 in the body. It is produced enzymatically via another enzyme (methylenetetrahydrofolate reductase or MTHFR). Added problem: about 30%-50% of humans are unable to properly metabolize folic acid due to an inherited gene mutation.
Physicians don’t commonly order blood testing for the MTHFR gene mutation. Since there are so many people affected by this gene mutation and mass genetic testing is impractical, folic acid supplement users should just presume they have the mutation and only consume multivitamins that provide methyl folate rather than folic acid.
There is the real possibility that individuals with the MTHFR gene mutation who take folic acid may suffer some unintended health consequences when supplementing their diet with multivitamins that include folic acid, the most common source of supplemental folic acid.
This MTHFR gene mutation can result in unordinary high levels of an undesirable protein (amino acid) called homocysteine in the blood circulation. High homocysteine levels are associated with many health problems, stroke being a primary life-threatening one. Mothers are also more likely to experience miscarriages if they have this gene mutation.
A troubling report shows that among individuals with the MTHFR gene mutation, migraine headaches and stiffness of carotid (neck) arteries were more prevalent and upon further examination a significant percent actually had lesions in their brain.
The masses with the MTHFR gene mutation are also prone to migraine headaches, muscle tenderness, insomnia, fatigue, memory loss, brain fog, and mental depression.
One wonders how many people with acute psychiatric disorders and/or major depression either can’t adequately metabolize folic acid to methyl folate or have the MTHFR gene mutation given that the provision of methyl folate (not folic acid) to depressed and schizophrenic individuals resulted in a striking improvement in their mental illness.
Psychiatric nurses have called for the use of methyl folate rather than folic acid among patients with mental disorders to rule out MTHFR gene mutation as the origin of their disease.
Fortunately undetectable levels of un-metabolized folic acid are found in newborns and their mothers. Folic acid does not seem to accumulate in newborns.
Certainly, a decline in natural killer cell activity directly correlates with an increase in cancer risk because this class of white blood cells directly destroys malignant cells. But there is even more concern over folic acid metabolism and cancer.
Folic acid is required for DNA repair and therefore protects against the initiation of cancer but once malignancy has begun may enhance its growth. Indeed, anti-folate drugs (methotrexate) are used to quell cancer growth. Figuring out the proper approach to folic acid in public health paradigms has been perplexing for health authorities.
The handwriting is on the wall. Makers of vitamin supplements are asleep at the switch. Over a decade ago I wrote a now out-of-print book calling for multivitamins to be updated. My text called for iron-free/copper-free multi’s. Soon thereafter brands of multivitamins were sold, sans iron and copper.
Most multivitamins were formulated years ago before many of the revelations of molecular medicine became apparent. A crying need now is to simply substitute methyl folate for folic acid in multivitamins, the most common source of supplemental B vitamins. Any concern over vitamin B9 masking a B12 deficiency is eliminated as all multivitamins provide B12.
This author was fearful to bring up this problem knowing vitamin supplement antagonists would have a field day blaming all of the aforementioned health problems on innocent vitamin pills. At this point, finger pointing doesn’t get the risk eliminated. Before there really is scaremongering over folic acid, it would be appropriate to remove folic acid and replace it with methyl folate in multivitamins. Foot dragging being common, this author was pressed to formulate a multivitamin that encompasses the advancements in molecular medicine made over the past two decades. Well-formulated multivitamins are the best health insurance one can buy.
Addendum: as an aside, folic acid supplementation has dramatically reduced but has not eradicated birth defects. Vitamin D deficiency has only recently been identified as an additional nutritional factor in the occurrence of birth defects (spina bifida)
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