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Is the mainstream still cheating you out of the best health possible—with folic acid?!

by Dr. Jonathan V. Wright, MD

June 2010 Nutrition & Healing

Discover the stunning truth behind this essential “vitamin”—and the simple switch that’s much, much better for you

Do you remember a few years ago, when “mainstream” print and broadcast media were telling us that vitamin E was bad for our cardiovascular systems, and would increase our risk of heart attack? Turns out the whole thing was based on -you guessed it- researchers not copying Nature!

They weren’t using Nature’s own of vitamin E—a combination of alpha-, beta-, delta- and gamma-tocopherol, sometimes with alpha-, beta-, delta-, and gamma-tocotrienol—in the same percentages and combinations found in Nature. Instead, they had used alpha-tocopherol only in their research—and reported an increase in cardiovascular risk.

Fortunately, since then it has been pointed out that gamma-tocopherol is more important in protecting the heart than alpha-tocopherol. In fact, supplementing alpha-tocopherol alone depresses levels of gamma-tocopherol, so increased risk to the heart isn’t altogether surprising. What can we learn from this? It’s pretty obvious—using a natural substance in a way that goes against Nature’s perfect design can cause problems.

Given the news, responsible vitamin suppliers quickly replaced alpha-tocopherol-only forms of vitamin E with “mixed tocopherols,” combinations of alpha-, beta-, delta, and gamma-tocopherols.

In a similar turn of events, recently accumulating research has found that supplemental folic acid, incorrectly identified as a vitamin (it’s actually an oxidized vitamin) since its synthetic crystallization in the 1940s, may actually accelerate cognitive decline in some older individuals. It’s also being linked to increased risk of colon and rectal cancers, increased risk of childhood asthma born to folic-acid supplemented mothers, and accelerated growth of pre-existing cancers.

There’s enough research that Reader’s Digest magazine recently published an article warning readers about the dangers of too much folic acid. Unfortunately, the article showed that not only journalists, but even medical professionals still haven’t figured out that folic acid is not the same as the naturally occurring vitamin folate.

Six of one is NOT half a dozen of the other

According to the article, a university-affiliated medical doctor stated: “We’ve known for years that getting too little folate can promote cancer. Now it looks like getting too much folic acid could be harmful too.”

Like much of the medical mainstream, he used folic acid and folate as interchangeable terms.

But folic acid is not the same as folate!

Folic acid is a single type of molecule, crystallized in 1943 by a scientist working for the patent medicine company Lederle Laboratories, then a subsidiary of American Cyanamid Corporation. Folic acid is the fully oxidized form of naturally occurring folates, which are found in leafy and green vegetables such as spinach, asparagus, turnip greens, romaine, lettuce, broccoli, Brussels sprouts, and bok choy. Other sources include corn, beets, tomatoes, dried or fresh beans and peas, fortified sunflower seeds and some fruits, including oranges, grapefruit, pineapple, cantaloupe, honeydew melon, banana, raspberries, and strawberries. Liver (only organic, of course) and brewer’s and baker’s yeasts are good sources of folate, too.

But—and this is important to understanding the difference between folic acid and the various naturally occuring folates—none of these vegetables, fruits, liver or yeast naturally contain even one molecule of folic acid.

How the mainstream convinced us we need folic acid, and not folate

So why is folic acid so firmly entrenched in the public and mainstream professional mind as a vitamin? For the same reasons that mainstream professionals, science writers (who should know better), and the majority of the public think that horse estrogen and human estrogen are the same thing. It’s a combination of a sloppy understanding of biochemistry and some clever patent-medicine-company-supported and -promoted psychology.

First, the biochemistry. (Stay with me, it’s relatively easy.) Folate was originally isolated from brewer’s yeast and spinach in the 1930s. Once isolated and exposed to air it becomes unstable and breaks down, and is generally no longer useful in nutrition. But a small amount of natural folate can be transformed by oxidation (a natural process) into folic acid, a much more stable form with a very long shelf life.

While human and animal cells cannot use the folic acid molecule itself in their normal metabolic processes, human cells (principally the liver) can transform folic acid back into many of its metabolically useful folate forms. That’s why folic acid—despite not being found in food—can do so much nutritional good, the best-known example being the prevention of birth defects including spina bifida, cleft lip, and cleft palate.

As we grow older, though, our bodies are increasingly slow at transforming folic acid into usefully metabolized folates. That’s probably why scientists are finding that folic acid (not folate) is associated with cognitive decline in the elderly. Some of these studies have shown significantly elevated levels of un-metabolized (and therefore not useful) folic acid building up in the bloodstreams of supplemented older individuals.

In addition to worsening folic acid metabolism with age, there are also a significant number (as high as 5 percent or more in some populations) of survivable human genetic defects of folate metabolism which make it more difficult or, in some circumstances, impossible for sufferers to make metabolic use of folic acid.

Now, the psychology. Imagine you’re the sales and marketing arm of a patent medicine company. Which would you rather produce and sell: A then-process-patentable substance (folic acid) or an un-patentable substance (folate)? A substance with a longer shelf life (folic acid), or a substance that breaks down very rapidly on exposure to heat, cold, or light—even from “just sitting there” (folate)? A substance that’s less expensive to manufacture and process (folic acid), or a more expensive substance (folate)? The answer is pretty obvious—from a marketing point of view, folic acid wins every time.

And in this case, by great good luck, folic acid does do some good. It can be re-metabolized into various metabolically useful forms in most people—particularly younger people. So of course folic acid is promoted as a vitamin—even though it’s not found naturally in food—and manufacturers happily encourage everyone to speak of it interchangeably with folate, just as the Wyeth company so successfully confused Premarin with human estrogen in the public mind.

As usual, the mainstream way does more harm than the natural way

So since the 1940s, when physicians wanted to give their patients supplemental folate, they were taught to start with folic acid under one or another brand name. Even I was taught that at the University of Michigan in the 1960s. Supplement companies have sold folic acid, too, as it appeared to do the job, and there were for years no reports of harm. In fact there was very little, if any, research into potential harm.

But now that there is enough evidence of potential harm from folic acid, it’s time for all of us who want the benefits to switch back to the forms of folate found in food, which our bodies can use more efficiently and effectively than folic acid. Of course, we should always start by eating as much folate-containing food as possible, and as fresh as possible, too.

Remember, naturally occurring folates break down quite rapidly with heat, cold, light, even when they’re still in the food. Because of this naturally rapid breakdown, even the most avid vegetable and fruit eaters often need folate supplementation. (For a simple way to find out if you’re among them, see “Overlooked blood test could be the key to your good health” below.) Fortunately, about a year or two ago, responsible supplement suppliers began to make individual folate (not folic acid) supplements available. Some suppliers have just started to include various forms of folate in multiple vitamins and other combinations.

So it’s time to make folic acid supplements a part of history, and use only forms of naturally occurring folate when we use supplements. A little bit of folic acid (100 to 200 micrograms, the amount found in many multiple vitamins at present) is not likely to be a problem, but more taken daily for years just might raise your long-term risk of colorectal cancer or cognitive decline. If higher amounts are unavoidable (for example, until all prenatal vitamins switch from folic acid to folate), taking additional folate will very likely offset the folic acid still found in the multiple. If you’re apprehensive, consult a physician skilled and knowledgeable in nutritional and natural medicine.

It’s very likely that within a relatively short time enough responsible supplement suppliers will switch from folic acid to folate in all their supplements, individual and combination, so you won’t need to read all the labels so closely to make sure you’re getting folate and not folic acid.

One last point you may be wondering about: Is there such a thing as “too much of a good thing” when it comes to naturally occurring folate supplementation?

Unless you have vitamin B12 deficiency or cancer, it’s very unlikely to be a problem. In the case of vitamin B12 deficiency, supplemented folate—even naturally occurring folate—can “cover up” some of the deficiency signs in blood tests. But preventing that is simple: Take extra vitamin B12 whenever you take extra folate! Some suppliers even combine the two, or put them with the rest of the B-complex vitamins.

But if you have cancer, it’s of course best to discuss folate (not folic acid) supplementation with a physician skilled and knowledgeable in nutritional and natural medicine. To find one in your area, contact the American College for Advancement in Medicine. JVW

Where to get it: Naturally occurring folate in supplements

At present, two types of folates that occur naturally in foods are available as over-the-counter supplements. One is folinic acid, usually sold over-the-counter as “calcium folinate.” Calcium folinate is also available by prescription as Leucovorin®, which, unfortunately, is considerably more expensive and also contains FD&C yellow #10 and FD&C blue # 1, neither of which improves clinical results.

The other over-the-counter naturally occurring folate presently available is 5-methyltetrahydrofolate. It’s more expensive than over-the-counter calcium folinate, but more likely to be effective for individuals with “hidden” genetic defects in folate metabolism.

There’s also at least one B-complex and one multiple vitamin-mineral combination containing calcium folinate and methylcobalamin (the more metabolically active form of B12) available over-the-counter. By the time this newsletter is printed, it’s very likely more than one of each of these will be available, too.

The availability of supplemental folates that occur naturally in foods has solved another problem I’d been observing in a minority of individuals since the 1970s. Although the large majority of people who tested poorly for individually optimal levels of folate on a test called the neutrophilic hypersegmentation index (see “Overlooked blood test could be the key to your good health” below) significantly improved their levels by taking folic acid supplements, a small but significant number had little to no improvement at all. For this group, all I could tell them was to eat as much folate-containing food as possible, and forget the folic acid supplements.

But since supplemental calcium folinate and 5-methyltetrahydrofolate have become available, nearly every patient with a previously abnormal neutrophilic hypersegmentation index has improved with their use.

Overlooked blood test could be the key to your good health

If you’re serious about good health and longevity, or if you have any chance at all of becoming pregnant, there’s an inexpensive but critically important blood test that’s too often overlooked. Although it’s simple, quick, and easy to do, many clinical laboratories don’t do it because there’s “no demand.”

It’s called the “neutrophilic hypersegmentation index.” It is a mouthful to say, but for decades it has been—and still is—the best test of your personal folate status. Not how your folate level compares with other peoples’, but how optimal your own level is.

To do that, the neutrophilic hypersegmentation index (NHI) determines what percentage of your neutrophils—a type of white blood cell—were supplied with an optimal amount of folate while they were growing and maturing. Of course, optimal is 100 percent. But before we get into how to boost your own score, it’s important to know some of the scientific background that explains why this test is so important.

When neutrophils are “born” and “incubate” in bone marrow, their chromosomes—DNA—arrange themselves into five segments. A final step in neutrophil DNA maturation is re-arrangement of those five segments into three. Normal folate metabolism is a key to this final step. Very shortly after the five-to-three segment DNA re-arrangement, the fully mature neutrophil is released from the bone marrow into the bloodstream, where it lives out its months-long life doing its job—one very important part of which is defending our bodies against germs.

But if there isn’t enough folate, the neutrophil’s DNA stays in five (instead of three) segments. When the neutrophil is needed, it’s released into the bloodstream anyway, where it’s called a hypersegmented (too many segments) neutrophil. Fortunately, a hypersegmented neutrophil can still fight germs as well as a “regular,” three-segmented neutrophil.

Planning a family? Why you MUST have this test

After a blood sample is drawn, a technician with a microscope can easily see and count the number of DNA segments in each neutrophil. The “hypersegmentation index” is the percentage of five-segment neutrophils counted in a total of one hundred neutrophils.

Neutrophils, other circulating blood cells, and the cells that line our gastrointestinal tracts are the most rapidly dividing cells in our bodies. So if there’s a shortage of any of the three key nutrients for keeping cell division normal—folate, vitamin B12, and/or zinc—these rapidly dividing cells are likely to show the effects first. So the “neutrophilic segmentation index” actually tells us whether the most rapidly dividing cells in our bodies have enough folate. If these cells do, then it’s very likely that every cell in our bodies has enough folate.

One of the saddest test reports I’ve had to share with anyone was an NHI of 47 percent reported for a woman who was already pregnant. As you may have expected, her baby was born with a birth defect.

Every woman who has any chance at all of becoming pregnant should have this test done! If it’s abnormal, and she’s planning on a pregnancy soon, she should take a series of folinic acid injections (see above “Where to get it: Naturally-occurring folate in supplements”. ) right away, preferably with the methylcobalamin form of vitamin B12, so there’s enough folate (and B12) immediately available for any newly conceived infant.

Why the rush? Well, the most common birth defect—neural tube defect—occurs on days 27–29 after conception, before many women are even certain that they are pregnant.

For the rest of us (as well as newly-folinic-acid-injected potential moms) an abnormal NHI means you need to take a closer look at your diet and make some necessary adjustments—most notably adding in more sources of folate, particularly green vegetables, beans, peas, brewer’s yeast, and (organic only!) liver. A folinic acid or methylfolate supplement is important, too, at least until the test normalizes.

A basic nutrient for cancer and heart disease protection

But pregnancy—or the possibility of pregnancy—isn’t the only time folate levels are important. Folate (along with vitamin B12 and zinc) are all critical to normal cell division and DNA repair, which means they’re all essential tools for cancer prevention. Adequate folate lowers the risk of a variety of cancers, particularly in the gastrointestinal tract, but also breast, pancreatic, cervix, and lung.

It’s almost certain further research will add other cancers to this list. However, for those who already have cancer in any form, it’s not yet clear whether or not supplemental folate may accelerate cancer growth as fully oxidized folic acid has been found to do in some studies.

Along with vitamins B6 and B12, folate helps keep levels of the natural human metabolite homocysteine low in our bodies. Considerable research shows that increasingly higher homocysteine levels are associated with increasingly higher levels of cardiovascular disease and atherosclerosis.

It’s true that in 2008, researchers reported that supplemental folic acid (not folate), B12, and B6 were effective at lowering homocysteine but were ineffective in reducing “major cardiovascular events” and deaths, but (once again) it’s very likely that this study used folic acid—which isn’t as easily metabolized in older individuals (rather than methylfolate)— along with less-than-optimally active forms of vitamin B12 and B6.

So, despite this (likely flawed) study, if your homocysteine levels are high, I still recommend eating more folate-containing vegetables, and, if necessary, taking enough supplemental methylfolate, methylcobalamin, and pyridoxal phosphate to keep your level low. If you do, your risk of cardiovascular disease and atherosclerosis will likely be lower, too.

Research indicates that other benefits of supplemental folate may include reduction of stroke risk and macular degeneration, and improvement in depression, as well as improvement in memory and mental agility in older individuals.

When enough is enough

I’ve been using this test as part of routine “good health” testing for nearly everyone for over 30 years, and rarely see a result of under 5 percent (which shows insufficient folate). So the goal is always to bring that level as close to 0 percent as possible.

But if you want to be really “engineering precise,” a level of 1 to 2 percent hypersegmented neutrophils—meaning that 98 to 99 percent of those white cells received enough folate—may be the best outcome to aim for. Why isn’t 0 percent even better? An engineer friend once explained it like this: “Once I get to 0 percent, there’s no -10 or –20 percent reading to tell me that it’s 10 or 20 percent more than I really need, so I’m going to keep mine very slightly under rather than go over.”

It’s a good point—and leads to the next question: Is there any danger of “overdose” with folate? Except when cancer is already present, it’s not very likely. I’ve never seen it happen in over 35 years of practice. But no one knows for certain. So keeping your NHI at a level of 1 to 2 percent ensures that your folate levels are optimal without “overdoing” it.

And increasing folate-containing foods in the diet and (in the majority) adding supplemental folate almost always brings the test to that optimal level.

The NHI is simple enough to be done by any laboratory with a microscope and a skilled technician, but many labs still don’t do it. Why? Well, it requires a smear of blood on a microscope slide and isn’t done by machine. However, blood specimens can also be sent to Meridian Valley Laboratory  in Washington state, where state law makes it possible for individuals to order their own lab tests.


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