The Folic Acid Deception
The little known but crucial difference between folate and folic acid
Article by Chris Kresser
I if I asked you which of these vitamins was found naturally in food, folate or folic acid, would you know the answer? If not, you’re in good company. Medical professionals, nutrition experts, and health practitioners frequently mix up the two, simply because the terms are often used interchangeably.
What’s the difference between folate and folic acid?
Folate is a general term for a group of water soluble b-vitamins, and is also known as B9. Folic acid refers to the oxidized synthetic compound used in dietary supplements and food fortification, whereas folate refers to the various tetrahydrofolate derivatives naturally found in food. (1)
The form of folate that can enter the main folate metabolic cycle is tetrahydrofolate (THF). (2) Unlike natural folates, which are metabolized to THF in the mucosa of the small intestine, folic acid undergoes initial reduction and methylation in the liver, where conversion to the THF form requires dihydrofolate reductase. The low activity of this enzyme in the human liver, combined with a high intake of folic acid, may result in unnatural levels of unmetabolized folic acid entering the systemic circulation.
Several studies have reported the presence of unmetabolized folic acid in the blood following the consumption of folic acid supplements or fortified foods. (3) Human exposure to folic acid was non-existent until its chemical synthesis in 1943, and was introduced as a mandatory food fortification in 1998. (4) Food fortification was deemed mandatory due to overwhelming evidence for the protective effect of folic acid supplementation before conception and during early pregnancy on the development of neural tube defects (NTD) in newborns.
Risks associated with excessive folic acid intake
While the incidence of NTDs in the United States been significantly reduced since folic acid fortification began, there has been concern about the safety of chronic intake of high levels of folic acid from fortified foods, beverages and dietary supplements.
(5) One of the major risks associated with excessive intake of folic acid is the development of cancer. (6) In patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods, treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality. In the United States, Canada, and Chile, the institution of a folic acid supplementation program was associated with an increased prevalence of colon cancer. (7, 8)
A randomized control trial found that that daily supplementation with 1 mg of folic acid was associated with an increased risk of prostate cancer. (9)
Researchers have hypothesized that the excessive consumption of folic acid in fortified foods may be directly related to the increase in cancer rates. Excess folic acid may stimulate the growth of established neoplasms, which can eventually lead to cancer. The presence of unmetabolized folic acid in the blood is associated with decreased natural killer cytotoxicity. (10) Since natural killer cells play a role in tumor cell destruction, this would suggest another way in which excess folic acid might promote existing premalignant and malignant lesions.
A high intake of folic acid might mask detection of vitamin B12 deficiency and lead to a deterioration of central nervous system function in the elderly. In one study, consumption of folic acid in excess of 400 micrograms per day among older adults resulted in significantly faster rate of cognitive decline than supplement nonusers. (11) Another study found a higher prevalence of both anemia and cognitive impairment in association with high folic acid intake in older adults with a low vitamin B12 status. (12) As vitamin B12 deficiency is a common problem for many older adults, these studies suggest that high folic acid intake could cause serious cognitive consequences in the elderly.
Folate from natural food sources is best
Despite the risks associated with high levels of folic acid intake, it is well established that adequate folate intake from the consumption of folate-rich foods is essential for health. Folate aids the complete development of red blood cells, reduces levels of homocysteine in the blood, and supports nervous system function. It is well known for its role in preventing neural tube defects in newborns, so women of childbearing age must be sure to have an adequate intake prior to and during pregnancy.
Excellent sources of dietary folate include vegetables such as green lentils, romaine lettuce, spinach, avocado, asparagus, turnip greens, mustard greens, parsley, collard greens, broccoli, cauliflower and beets. (13) Not surprisingly, some of the best food sources of folate are calf’s liver and chicken liver.
You can supplement with folate if your dietary intake is inadequate. Look for products that contain the Metfolin brand, or list “5-methyltetrahydrofolate” or “5-MTHF” on the label. Avoid products that say “folic acid” on the label. Make sure to check your multivitamin, because most multis contain folic acid and not folate.
Women planning on becoming pregnant should consume between 800 and 1200 mcg of folate per day for several months before the start of pregnancy. Unless you’re consuming chicken or calf’s liver and substantial amounts of leafy greens on a regular basis, it’s difficult to obtain this amount from diet alone. If you’re pregnant or trying to get pregnant, I recommend supplementing with 600-800 mcg of folate per day, depending on your dietary intake. Health Leads is a good brand, but there are several others that typically use 5-MTHF.
All other people, such as men and older women, should be able to get plenty of folate in a diet with adequate vegetable consumption, and do not need to supplement.
8 Factors that Affect Your Methylation Process
Eight major factors negatively impact methylation. They are:
1. Genetics. Like an estimated 20-30 percent of us, you could be genetically predisposed to high homocysteine.
2. Poor diet. The word “folate” comes from “foliage.” You need to eat plenty of leafy greens, beans, fruit, and whole grains to get adequate levels of vitamins B6 and B12, betaine and folate (all in the right nature-made forms). Egg yolks, meat, liver and oily fish are the main dietary sources of vitamin B12 — so long-term vegan diets can be a problem, so supplements for B12 such as methylcobalamine can be taken instead.. Plus, certain compounds can raise levels of homocysteine and deplete the B vitamins. These include excess animal protein, sugar, saturated fat, coffee and alcohol. Irradiation of food depletes nutrients, so foods treated this way may be lower in B vitamins, too.
3. Smoking. The carbon monoxide from cigarette smoke inactivates vitamin B6.
5. Decreased stomach acid. Aging and other conditions can reduce stomach acid — and therefore absorption of vitamin B12.
6. Medications. Drugs like acid blockers, methotrexate (for cancer and arthritis and other autoimmune diseases), oral contraceptives, HCTZ or hydrochlorthiazide (for high blood pressure) and Dilantin (for seizures) can all affect levels of B vitamins.
8. Toxic exposures. Some toxins such as mercury can interfere with vitamin production.
Watch out for these factors and you will go a long way toward protecting your methylation.
Measuring Your Own Methylation Process
To find out if your methylation process is optimal, ask your doctor for the following tests:
1. Complete blood count. Large red blood cells or anemia can be a sign of poor methylation. Red blood cells with a mean corpuscular volume (MCV) greater than 95 can signal a methylation problem.
2. Homocysteine. This is one of the most important tests you can ask for. The normal level is less than 13, but the ideal level is likely between six and eight.
3. Serum or urinary methylmalonic acid. This is a more specific test for vitamin B12 insufficiency. Your levels may be elevated even if you have a normal serum vitamin B12 or homocysteine level.
4. Specific urinary amino and organic acids. These can be used to look for unusual metabolism disorders involving vitamins B6 or B12 or folate, which may not show up just by checking methylmalonic acid or homocysteine.
12 Tips to Optimize Your Methylation Process
Just as there are many causes of poor methylation, there are lots of things that support its proper functioning. Here’s how to optimize methylation and prevent conditions like heart disease, cancer, dementia, depression and more.
1. Eat more dark, leafy greens. You want to eat l cup a day of vegetables like bok choy, escarole, Swiss chard, kale, watercress, spinach, dandelion, mustard, collard or beet greens. These are among the most abundant sources of the nutrients needed for optimal methylation. You can’t get too much folate from food.
2. Get more Bs in your diet. Good food sources include sunflower seeds and wheat germ (vitamin B6), fish and eggs (vitamin B6 and B12), cheese (B12), beans and walnuts (vitamin B6 and folate), leafy dark green vegetables, asparagus, almonds, whole grains (folate) and liver (all three).
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3. Minimize animal protein, sugar and saturated fat. Animal protein directly increases homocysteine. Sugar and saturated fat deplete your body’s vitamin stores.
4. Avoid processed or refined foods and canned foods. These are depleted in vitamins.
5. Avoid caffeine. Excess amounts can deplete your B vitamin levels.
6. Limit alcohol to three drinks a week. More than this can deplete your B vitamin levels.
7. Don’t smoke. As noted above, smoking inactivates vitamin B6.
8. Avoid medications that interfere with methylation. See notes on this above.
9. Keep the bacteria in your gut healthy. Make probiotic yogurts and use other measures to make sure the bacteria in your gut are healthy so you can properly absorb the vitamins you do get.
10. Improve stomach acid. Use herbal digestives (bitters) or taking supplemental HCl.
11. Take supplements that prevent damage from homocysteine. Antioxidants protect you from homocysteine damage. Also make sure you support methylation with supplements like magnesium and zinc.
12. Supplement to help support proper homocysteine metabolism. Talk to your doctor to determine the best doses and forms for you. Here are a few suggestions:
• Folates Amounts can vary based on individual needs from 200 mcg to one mg. Some people may also need to take preformed folate (folinic acid or five formylTHF, or five methyl folates) to bypass some of the steps in activating folic acid.
• Vitamin B6: Take two to five mg a day. Some people may need up to 250 mg or even special “active” B6 (pyridoxyl-5-phosphate) to achieve the greatest effect. Doses higher than 500 mg may cause nerve injury.
• Vitamin B12: Doses of 500 mcg may be needed to protect against heart disease. Oral vitamin B12 isn’t well absorbed; you may need up to 1 or 2 mg daily. Ask your doctor about B12 shots or doses you can take under the tongue. Here is our B12 (Methylcobalamin version, which is the best)
• Betaine: This amino acid derivative is needed in doses from 500 to 3,000 mg a day, depending on the person.
By working to optimize your methylation you can protect yourself from virtually all the so called “diseases of aging.” When you do, you will be well on the road to lifelong vibrant health.
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