Folic Acid: Killer or Cure-All? (Mark Hyman, MD)

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Folic Acid: Killer or Cure-All? (Mark Hyman, MD)


Mark Hyman, MD

Practicing physician and pioneer in functional medicine

Posted: June 5, 2010 08:00 AM


Nutrition Tips: Folic Acid: Killer or Cure-All?


Anyone trying to prevent heart disease and cancer is probably thoroughly confused by competing research and news reports about folic acid. In some studies it reduces the risk of cancer (i) and in others it seems to increase the risk. (ii) The media grab attention with scary headlines like the recent Prevention article "Is Your Breakfast Giving You Cancer," and the confused consumer of healthy food and vitamin supplements goes back to burgers and fries and throws their supplements in the trash.


Unfortunately, science is never black and white and confusion is easy to come by -- even for trained scientists. (iii) The fortification of our food supply with folic acid in 1998 reduced spina bifida birth defects by 19 percent. A good thing. But by some estimates it may have caused an additional 15,000 cancers deaths a year. Oops. Now what?


The answer is elemental. As in chemistry, biochemistry to be exact. It all comes down to this: Man-made molecules do funny, unpredictable things because they don't work with our normal biochemical pathways. Nature made molecules we have consumed for millennia work with our bodies.


And therein lies the big problem with the nutrient known as B9. Folic acid, the molecule that is used to fortify our food supply, is used in most studies and in most vitamins. It is a man-made, funny looking molecule -- a fully oxidized, synthetic chemical compound that seems to cause all the mischief. It costs less and is more stable than the nature-made form of this nutrient.


On the other hand, the nature-made form or forms, called "folates," do not seem to cause problems. This molecule is often found in foliage -- dark green leafy vegetables, hence the name folate. This can enter your normal biochemical pathways and gets properly metabolized. The folic acid may not be converted or metabolized by the body, increasing cancer and disease risk. The excess folic acid becomes oxidized and promotes free radical production and genetic instability leading to cancer and other disease.


Now it gets a bit more complicated. We are all biochemically individual and genetically unique, and about 35 percent of us have a genetic variation in a gene called MTHFR that helps neutralize the folic acid. If this doesn't work well, then more of the folic acid accumulates from the fortified food and supplements we consume. Those who have this gene are at increased risk of colon cancer because they produce more pre-cancerous colon polyps. In fact, high dose folate supplementation in these people reduced their risk of polyps. (iv)


The good news is that you can take the nature-made form of this nutrient -- called methyl folate (and there are a few forms of that too). This is what should be in food and vitamin supplements. Many conscientious companies are now using only this form of the nutrient, but it is more expensive.


Here's what you should do:


Don't eat fortified foods! If it needs to be fortified with folic acid, that is because it has been impoverished and refined in the first place (think white flour, white rice, cereals and processed foods). Just eat real, whole fresh food!


Look at your supplement label! If it says "folic acid" then find another vitamin that has the words "L 5 methyl-tetrahydrofolate" or "5 formyl tetrahydrofolate" on the label.


Now for those who want know a little bit more about the reason why folate and its companions B6 and B12 are the most critical and health promoting hit parades in the nutrient world.


The Secret of Folate: The Magic of Methylation


Taking just a few vitamins CAN optimize the function of ALL your body's systems. It's true. But you have to know what to take, what form of the nutrients and you have to know why these supplements work ...


In this blog, I am going to discuss one of the most important biochemical processes for long-term health and how to keep it functioning optimally with supplements and other strategies. This process is called methylation because it involves moving around a chemical group called methyl, which consists of one carbon and three hydrogen molecules.


Unfortunately, many people suffer from one or more of the eight factors that negatively impact this biochemical process, so problems in this area are widespread, though many don't realize they are suffering.


However, there are MANY things that you can do to optimize this critical biochemical process that may have a dramatic impact on your health. In today's blog I will review the eight factors that can lead to problems in this area, and outline 12 tips that will help you optimize this essential part of your biology.


But first, I'd like to tell you about two of my patients with seemingly unrelated health problems that were actually caused by a breakdown in this biochemical process. And I want to share a study done on Chinese babies who had a birth defect known as spina bifida.


All three -- my two patients and these Chinese babies -- were affected by the exact same thing ...


What an Elderly Golfer, a College Professor, and Chinese Babies have in Common


One of my patients, Mr. Roberts, was an 88-year-old businessman who didn't let his age slow him down. He still golfed three times a week, worked two days a week, flew around the world in his private jet, and was "romantic" once a week with a wife 30 years his junior. He also loved his six ounces of Grey Goose vodka every night.


Of course, he did have some health problems. Mr. Roberts had been treated well for mild heart disease. His doctor even recommended 800 mcg of folic acid and 250 mcg of vitamin B12 -- megadoses by any standard.


Mr. Roberts also had a check-up at the Mayo Clinic and was told that he was healthy, despite having mild anemia and large red blood cells. Yet he still complained of mild fatigue and trouble with his short-term memory. Plus, I noticed a slightly wide gait common in someone with poor balance.


Then there was Mr. McNally, a Boston college professor who was 50 years old, fit and lean but wore a worried look as he walked into my office.


He recounted the sad tale of his seven brothers. Four had died of a heart attack and three others had had bypass operations at a young age. Concerned about his own fate, he ate a low-fat diet, exercised regularly, didn't smoke, had normal blood pressure and cholesterol levels, and took antioxidants and a multivitamin. Perhaps his only vice was the multiple Starbuck's grande lattes he downed each day. Living under a constant state of impending doom, Mr. McNally came to me asking for a stress test to see how his heart was doing.


Strange as it may seem, these two men reminded me of my time in China. When I lived in Beijing, a study was done on a group of women in Harbin, the northern most industrial city in the Gobi desert, just north of Beijing. It seemed that there was an unusually high rate of birth defects in the area, specifically spina bifida or neural tube defects.


The Chinese have a tradition of holding weddings during the Chinese New Year in February. In Harbin, many of the babies born nine months later had birth defects. This study sought to determine what the link was and found that the major factor was the lack of fresh greens or vegetables in the Gobi desert in the middle of winter.


Interestingly, these Chinese babies, Mr. Roberts and Mr. McNally all had something very important in common. They all had inadequate levels of specific vitamins, either acquired or genetic, and their methylation systems were not working properly as a result. I'll explain more about what "methylation" is in a second. First let's analyze the similarities in these cases.


Take Mr. Roberts. Our romantically active 88-year-old took high doses of B vitamins. But he still had very high levels of homocysteine and methylmalonic acid -- indicators of folic acid and B12 deficiency.


Mr. McNally had similar problems. Our college professor had a genetically sluggish metabolism of homocysteine which caused extremely high levels of this toxic amino acid to build up in his blood. This was the likely cause of all the heart disease in his family.


Again we see a similar set of problems in those Chinese babies. Their mothers were conceiving in the middle of winter, when their folate intake was low from the absence of fruits and vegetables. This is what triggered such a high rate of birth defects. This was the reason that food was fortified with the synthetic form of folate called folic acid, which as it turns out is biochemically quite different in its effects.


The common link in all three of these cases is a problem with methylation. Let me tell you more about that that actually means.


Methylation is a key biochemical process that is essential for the proper function of almost all of your body's systems. It occurs billions of times every second; it helps repair your DNA on a daily basis; it controls which genes are turned on or turned off; it controls homocysteine (an unhealthy compound that can damage blood vessels); it helps recycle molecules needed for detoxification; and it helps maintain mood and keep inflammation in check.


To keep methylation running smoothly you need optimal levels of B vitamins. Without enough B vitamins methylation breaks down, and the results can be catastrophic. In these cases we see more birth defects like spina bifida (as with the Chinese babies), more cases of Down's syndrome, and more miscarriage.


A breakdown in methylation also puts you at higher risk for conditions like osteoporosis, diabetes, cervical dysplasia and cancer, colon cancer, lung cancer, depression, pediatric cognitive dysfunction (mood and other behavioral disorders), dementia, and stroke. And like Mr. Roberts and Mr. McNally, you may be at higher risk for cardiovascular disease.


To avoid all of these problems, the key is to optimize methylation. That means avoiding the things that cause your methylation to break down, testing to find out how well your methylation is working and including the things that support proper methylation. Let's look at how to do that.


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. 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.


4. Malabsorption. Conditions like digestive diseases, food allergies, and even aging can reduce absorption of nutrients.


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.


7. Other conditions. These include hypothyroidism, kidney failure or having only one kidney, cancer and pregnancy.


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. Like our friend Mr. Roberts, 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).


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. Take probiotic supplements 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.


• 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.


Now I'd like to hear from you ...


Do you have symptoms of poor methylation?


What are you doing to optimize this process?


Do you take B-vitamin supplements? Have you noticed any results?


Please share your thoughts by adding a comment below.


To your good health,


Mark Hyman, M.D.




(i) Jaszewski R, Misra S, Tobi M, Ullah N, Naumoff JA, Kucuk O, Levi E, Axelrod BN, Patel BB, Majumdar AP. Folic acid supplementation inhibits recurrence of colorectal adenomas: a randomized chemoprevention trial. World J Gastroenterol. 2008 Jul 28;14(28):4492-8.


(ii) Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, McKeown-Eyssen G, Summers RW, Rothstein RI, Burke CA, Snover DC, Church TR, Allen JI, Robertson DJ, Beck GJ, Bond JH, Byers T, Mandel JS, Mott LA, Pearson LH, Barry EL, Rees JR, Marcon N, Saibil F, Ueland PM, Greenberg ER; Polyp Prevention Study Group. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6;297(21):2351-9.


(iii) Bland J. Systems biology, functional medicine, and folates. Altern Ther Health Med. 2008 May-Jun;14(3):18-20. Review.


(iv) Lightfoot TJ, Barrett JH, Bishop T, Northwood EL, Smith G, Wilkie MJ, Steele RJ, Carey FA, Key TJ, Wolf R, Forman D. Methylene tetrahydrofolate reductase genotype modifies the chemopreventive effect of folate in colorectal adenoma, but not colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2008 Sep;17(9):2421-30.


Mark Hyman, M.D. practicing physician and founder of The UltraWellness Center is a pioneer in functional medicine. Dr. Hyman is now sharing the 7 ways to tap into your body's natural ability to heal itself. You can follow him on Twitter, connect with him on LinkedIn, watch his videos on Youtube and become a fan on Facebook.


    * Copyright © 2010, Inc.


Thank you

Thank you for giving clear and useable information about a complex subject. Last summer I was treated with low dose (Insulin Potentiation) chemotherapy, or IPT, for a triple negative breast cancer. One of my doctors tested me and found me positive for MTHFR. However, he didn't seem to know much about it. When I asked him what I shoud do he gave me a liver shot and said that should help! Yikes! I have a genetic defect and one or two liver shots should help??? I'm no doctor or biochemist, but I knew that was not a sufficient answer. Another doctor knew a bit more, and put me on methylated B12 and Deplin, a high dose methylated folate, but again, he didn't know a lot more than that. Recently I met a woman who works for Dr Rawlins and she put me onto his website, where I got more information and started the protocol he outlines. I'm hoping that will help. Your information adds greatly to my store of knowledge. In some reading I've done I have come to understand a few of the things about myself that seem odd and different from others: 1. Drinking much alcohol (I only tried this once or twice when very young) makes me throw up, I suppose because I don't detoxify alcohol very well. 2.  Facial recognition has always been difficult for me, and I learned on Dr Rawlins' site this is a symptom of MTHFR. 3.  I've never felt very well balanced on my feet, and have taken many falls. I even had a psychic tell me once: "This is very strange, but I'm getting 'Be careful where you put your feet.'" You mention the 88-year-old man having a wide gait. In my case, I don't seem to lift my feet sufficiently and trip easily. 4.  I've been very interested in nutrition since the mid 1960s. I've always eaten better than most people, yet I got cancer. Indeed, there is a lot of various cancers in one side of my mother's family, but I've never heard of it in my dad's.   5.  There is a history of depression coming from my dad's side, including my grandmother, sister and myself before I discovered 5HTP and tyrptophan. My granddaughter seems affected by this, too. Finally, I'd like to know if I can quote your writings on my blog, or another, future blog, with attribution. I began this blog while doing cancer treatment in Arizona last summer, as a way of keeping in touch with friends and family, but it is open to others.

sister just got tested

My sister just tested positive for two of the genes my mom had one dad had the other defect.  I am the oldest sister and been diagnosed with Fibro also suffer from a fall 15 years ago.

I hurt so bad everyday I sometimes wonder if life is worth it, but don't worry anyone my religion would never allow that.  That being said I was at my witts end with the pain and suffering will start juicing next week to improve my health, and planning on getting test myself because our Folate levels are non existent besides the fact our vitamin D is way below normal.  She will start prescription meds right away and just taking the supplements for a month she said it's a miracle how good she feels so she is mailing me her over the counter supplements so I can start ASAP. It's actually cheaper for her because health insurance will help pay so it's only around $20.00 a month.  Can you believe it $20.00 and I might have some kind of a life now, by the way my daughter has it also I guess it's passed down.  Maybe now my granddaughter and my daughter who is hurting all the time, gets strange rashes, is allergic to everything we've known all along something is just not right with her we thought she was in for a lifetime of Fibro like me I will post an update when I get tested and start on the supplements. I wish there were current blogs, so I could bounce this off someone.

June 16, 2012

Been taking supplements of Vitamin D and L-Methylofolate for maybe three weeks now and yes, I'm up more from bed everyday and I feel like something is happening to my body. I have had what I call a real roller-coaster ride with the up's and down's of the headaches that are pretty awlful so far so good. I will continue to update you. Life seems much better now.

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