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The Little Known (But Crucial) Difference Between Folate and Folic Acid


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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.

Many health professionals would even argue that folate and folic acid are essentially the same nutrient. While folic acid is often considered to be a supplemental form of folate, there is an important distinction between these two different compounds. For women past childbearing age, and for men in general, excessive doses of the synthetic form of this nutrient are not necessary, and may even be harmful.

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.

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. (78) 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.

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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 romaine lettuce, spinach, asparagus, turnip greens, mustard greens, parsley, collard greens, broccoli, cauliflower, beets, and lentils. (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.

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The Adapt Naturals Core Plus bundle features two products that contain folate. Bio-Avail Multi, a multivitamin/multimineral and phytonutrient blend, contains 680 mcg of the most active form of folate, methyltetrahydrofolate. Bio-Avail Organ contains a blend of five organ meats (live, kidney, heart, pancreas, and spleen), which are among the highest sources of folate in the diet.

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. Solgar is a good brand, but there are several others that typically use 5-MTHF including Designs for Health, Thorne, Metabolic Maintenance and Pure Encapsulations.

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.



Join the conversation

  1. Does this mean the standard 400mcg of folic acid in most/all multivitamens even if from a whole food source is going to increase our risk for cancer???? I’m soo confused!!!! …

    What about consuming superfood sources HIGH in folate? Is this the same risk??

    thank you.

    • Hi! Great question. I believe he’s saying that folic acid (synthetic) is dangerous while folate (natural and found in greens) is safe and healthy. Hope this helps! 🙂

    • Elle, there is actually no such thing as folic acid from whole food sources. Some vitamins say they are whole food sourced but if it says it contains folic acid it is the synthetic version being added to it.

  2. what I would like to know: is [6S]-5-methyltetrahydrofolic acid another name for [6S]-5-methyltetrahydrofolate or is it folic acid misnamed? The front of my supplement bottle states “”methylfolate” but the back does not quite agree. I am a retired environmental analytical chemist but my schooling did not prepare me for this.

    • My understanding it that they are the same thing (and not folic acid) but you might directly ask the company to see what they have to say. Which one is it?

    • Wondering the same thing. The supplement I was advised to take for MTHFR is called Methyl Factors from Nutra Biogenesis. It contains: 10mg Vitamin B-6 (from pyridoxal-5-phosphate monohydrate), 400mcg Folate (from folic acid, 6S)-5-methyltetrahydrofolate, glucosamine salt), & 25000 mug Vitamin B-12 (from methylcobalamin). Is this good for MTHFR?

  3. Just wondering if you had any thoughts on quatrefolic? It seems to be the glucosamine salt of 6S-MTHF. The company claim that it is more bioavailable than 5-MTHF, but I’m not altogether sure how much research has been done into it. Might there be any issues with people with digestive problems taking the glucosamine off, or if you have a leaky gut do you tend to absorb the whole quatrefolic, glucosamine still attached? Or is the glucosamine bond really weak and will just unattach itself, no matter whether you are on PPIs, have no stomach acid and poor digestive enzymes? Just wondering. Anyone know?

  4. Jessica is WRONG. Adding a proton to folinic acid does not make folic acid! I am also a chemist who is compound heterozygous MTHFR, and a member of several Facebook groups concerning these mutations. I think she is looking at the situation with a classical chemistry thought process, which does not fit here. JMO.

    Folic acid should be avoided, as much as possible. The end product for the enzyme pathway is L-5MTHF, however, those with homozygous COMT snps may have to supplement with folinic acid due to methyl group sensitivity.

    HERE is the difference between folic acid/5-MTHF/folinic acid:

    Thank you,
    Carol w

    • Carol, thanks for the link, it is very helpful. However, I think you misquoted Jessica. She didn’t refer to folinic acid in her post. She referred to the difference between folic acid and folate. Like her, I think the only difference between FOLIC acid and folate is the protonation state depending on pH. I welcome correction if I am misunderstanding something.

    • Hi Carol,

      I was wondering if you could help answer a question I posted up there. I saw a naturopath who recomended I take l-5-MTHF but I’m not sure if she had any genetic tests done on me. The stuff I take cost $27 a bottle which is a bit outside my price range. Would it be possible to get the same benefits from whole foods like leafy greens and whatnot and save the money I spend on the medicine?

    • Hi there Carol,
      Thanks for the link. I read through it but not being a chemist I couldnt glean the difference between Folic Acid/ Folinic Acid / Methyl folate. Would you be able to give me some info?

      I am MTHR c167 heterogenous. I also have several COMT homogenous polymorphisms. I recently started taking Methyfolate but it doesnt seem to agree with me – I have had palpitations and mild insomnia – though its very difficult to be sure its the methylfolate or its a reverse placebo effect, as I was aware of the potential side effects.

      It seems strange though as I have previously tolerated other methyl groups quite well. For example I was taking methylcolabim for a time before I could source hydroxycolabim, without any incident.

      Why could it be that only mehylfolate gives me problems?

      Would you then recommend Folinic Acid instead?
      What is the difference between the two?
      With regards to Folic Acid, I appreciate that I can’t metabolise it so well, but why is it actively bad for me?

      Thanks so much for your help.

      • You can get detox symptoms from adding in methylfolate. Start very, very slow, like a fraction of a pill or sprinkle of a capsule and work up very slowly. Otherwise you can easily over tax your systems. Detox is good but it’s not good for you if it’s making you ill.

  5. Chris,
    I want to thank you for this blog. I am a chemist. I have been pondering this issue for quite some time as the difference between folic acid and folate is only one proton. Folic acid is NOT the oxidized version of folate as you state; it is the protonated version. So it made no sense to me AT ALL that people were pushing folate over folic acid…. because when it hits your stomach at pH 1 or 2, all of it will be folic acid, and when it hits the small intestine at much higher pH, it will be mostly folate.

    After reading what you wrote, I realize finally that the important part is not whether you buy folate or folic acid…. but it is whether or not you get TETRAHYDRO-folate or TETRAHYDRO-folic acid. Both forms exist. The tetrahydro is the adding of four hydrogens to the structure – it is the reduced form. It is the reduced form whether or not the carboxylic acid is protonated (folic acid) or not (folate).

    I really wish all of the bloggers and people that write about this would emphasize the tetrahydro more. That’s what matters. Folate/folic acid ARE the same (it just depends on the pH of the solution they are immersed in). Folate and tetrahydrofolate are not and are not easily converted.

    • Jessica,

      You really confused me towards the end of your post. I thought I was tracking with you, but at the end it seemed like when you said that “Folate and tetrahydrofolate are not and are not easily converted,” well I took that to mean that those forms are not easily converted in the body – ie. they are not bio-available, they are not useful. Is that what you meant? Is 5-MTHF in fact that best to supplement with? Where the supplements suggested in the article are best bet as far as supplements are concerned?

    • Hi Jessica

      I would like to converse with you as you are a chemist. I am a student with the International Foundation of Nutrition and Health. It is the position of many of the researchers from the early days (late 1800s to mid 1900s) that synthetic vitamins ARE NOT COMPARABLE to vitamins found in whole foods, because the whole food is comprised of a complex of factors that support the “vitamin effect”. When this became evident from many researchers at the time, it became evident that in processing food in order to make it commercially viable, the consequence would be malnutrition of the population, leading to degenerative diseases occurring at younger and younger ages and the onset of genetic predispositions. In response, the industrialist said that they would fortify food. When the scientist said NO, nature doesn’t work that way, they scientist were silenced. Find out about Dr. Wiley, the first head of the FDA and what happened to him for starters. What we are seeing now, in my understanding, is finally, at long last, the truth is having a hard time being covered up because it keeps rising to the surface, like cream. If you want to read more about that, I highly recommend a book by Judith DeCava called The Truth about Vitamins and Antioxidants.

    • I agree with Jessica in that folate/folic acid is comparable and that the body will not note a difference with them. The key in this material is two-fold. First, it is a Methyl-Folate. The number 5 postion on the pteridine ring is methylated. That is a major factor that increases solubility/availability and eliminates one step the body MUST take in the liver to create the vitamin required for the methyl-transferase cycle. Second is more minor in the tetrahydro aspect. Full protenation of the molecule will is important, but not necessarily for ease of incorporation into the enzymatic pathways.

      Biochemist – 35 years in enzymology.

      • I did not do good on a huge dose from compounded MTHYL. However, MD Essentials 5 in 1, two a day was perfect. Also There is a Two a Day vitamin online through walmart with perfect D3 and MTHF. $19.99. My Dr. carries this line as well in office. Both of these in fact. So maybe to have small amount is ok. Large amount and I could not add. So you have to start small. Not everyone is def in the same amount. Maybe it’s just the blood test picking up whats circulating and not DNA, I DK. Maybe the University stands to lose money if people actually get well but they said the studies showed no improvement. Idk im not a scientist. Just a mom. True as I have Alpha One and my liver does not convert a whole hell of a lot of things. You give me a bowl of cereal and milk and I’m out like a light from the sugar and milk in grade school. No paying attention whatsoever. Still to this day. I now science wants to fortify the world, they will have to, look at the land and animals and all of the injections to mass produce animals that make the animal fat and sick and so it trickles down to us. IT is wrong. Cant everyone just fast and stay home on sundays. hmmmm….seems to me God knew what he was talking about.

    • Hi, Jessica. You obviously know much more about this than I do, but I’ve been researching and trying to understand all the different forms of folate and came across this article written by Emily Deans: http://evolutionarypsychiatry.blogspot.com/2011/08/folate-beginning.html

      Towards the beginning she says: “Let’s just start with a diagram, and an explanation for those of us who were taught some basic organic chemistry. Folate does not equal folic acid. I know. It’s weird. For all the other acids, -ate equals -ic acid (such as phytate and phytic acid), but for whatever reason, folate = dihydrofolate, and folic acid equals synthetic folate that is used to fortify foods in the US and in multivitamins.” I don’t know basic organic chemistry, but it seems she is speaking to your logical assumption that folate and folic acid are the same and saying this isn’t true. Now as far as why this isn’t true or in what ways they are different, I don’t know. I apologize if I’m just misunderstanding this and making it even more confusing. It is all quite over my head at this point.

  6. I’ve been reading about Folic Acid and Folate all day and still nto sure I know the right answer.

    My fiance’ had a child previously that has spina bifida but I do not know if he has any of the genes or the mother. We then had a perfectly healthy child (was much younger then and did not research anything, just listened to the doctors) we are wanting to try for another one now and am not sure what I should be taking. Any help?

  7. Hi– I’m so glad I found this site. I am a 56 year old woman in menopause, and recently had a blood panel run as part of a functional medicine exam. (Lots of issues that no one seems to be able to figure out…but I digress…) The doctor said I my folic acid was low and that I should take a supplement. (She recommended a brand, but I can’t remember what it was off hand.) This direction seems contrary to what I’m reading here. Should I pursue further information before taking a supplement? Thank for any help!

  8. Hi all – I’m looking for a trustworthy, reliable resource where I can find the max levels of vitamins and minerals recommended during pregnancy. As one example, the prenatal I am taking contains 800mcg of folate, but I also need to take a calcium supplement as the prenatal doesn’t afford enough (125mg) per the recommendations I’ve found (1,300mg). The calcium supplement I’m looking at will add another 400mg. Thanks, I appreciate any assistance.

  9. Quite a lot of info to absorb regarding gene mutations. My DNA results show several issues including the MTHFR/A1298C, C677T and a few others. I had a supplement program (called “your natural prescription”) customized for me by xRMD Corp. Has anyone had positive or negative experience with this company or program? Do you have any comments on this?

  10. I have MTHFR and my doctor has me taking a multi vitamin as well as 1mcg of folic acid. Should I not be taking this? I had a blood clot in 2013 and this is how the found my blood disorder. After reading this I’m unsure as to whether I should even be taking the folic acid.

    • Correct. You need folate or folinic acid, not folid acid. Your body cannot deal with the folic acid if you have that gene situation. I have it too and just found out about it. I am taking folinic acid 800 mg and in just a very short time like a week or two the joint pain in my hand went away. Really amazing. I just assumed I would have it the rest of my life since I am getting older!

      You can buy multiple vitamins that are healthy (such as having folate or folinic acid rather than folic acid, etc,. They cost a little more, but hey, what is worth more than health? Very little.

      • Hello, I was searching about this defect and found your comment. I dont know if I have the defect or not, but I’ve been having serious difficulty getting pregnant, and when I do, I suffer miscarriages. I have stiff fingers and joint pain in my hands when I wake up in the mornings. Your comment about having your pain disappear, caught my eye. Could you share more about the pain and how you got rid of it, and other symptoms you had, and how it affected you? This connection could be huge for me.

        Thank you profusely.

        • Hi – Please know that I am not a health professional and I understand very little about the chemical process involved in all this. Although it took me ten years to get pregnant ( then had four children rapidly), I did not have any confirmed miscarriages. I started taking natural folate because I have had chronic major depression since childhood (as well as allergy-induced asthma). Once I saw I had this gene defect, I thought maybe I should try the natural folate to see if it helped. I don’t believe it affected my depression or allergies, but it took away the joint pain in my right hand knuckles almost immediately (like within a week or two)! And the joint pain has not returned. This was unexpected. I am taking “Source Naturals” MegaFolinic, 800 Mcg 120 Tablets. This cost about $9 on Amazon. The whole gene thing is really complex, though, and you may need the help of a specialist if you have serious conditions.

        • I should add that I had all my genetic profile done for $99 on the 23&me website several years ago. I highly recommend it as something really fun to do in addition to the possibility of finding out useful information like this! 🙂

          • I would LOVE to do the 23&me test that showed all that for $99 but did you know our government outlawed it here in the US supposedly because it would cause paranoia and a DR should be present to better interpret your results. Now we have to pay hundreds to find out the same info plus the Dr visit. My insurance doesn’t cover it. You are lucky you got this info before the law changed.

              • Had testing done with 23andme earlier this year and they are only providing ethnographic information now.

                • 23andME offers your raw data. It may be on a tab on the home screen. Find it and download it with Promethease Report online. I think it cost me five or ten dollars. Promethease with then send you a zip file that you download and unzip. Amazing stuff will be discovered.

                • Or, if you just want to know specific genetic results (such as MTHFR status), you can get that by looking directly at the raw data on 23andme.

            • CJ

              23andme is not outlawed. They are not allowed to interpret the raw data. you get all your genetic raw data and you have 3rd party interpret it for a small fee or donation. Genetic Genie, Livewello, are a few that can do this right online. Takes minutes.

              • Chuck is so right that the 23andMe test has not been outlawed. The FDA didn’t like the health reports that 23andMe issued, so people from the U.S ordering tests on or after 11/22/13 can’t see their health results. 23andMe is still issuing the reports for people outside the U.S. and for those that ordered before that cutoff date.

                In addition to the sites Chuck mentioned, there are a couple other worthwhile interpretation sites: 1) MTHFR Support Variant Report and 2) Promethease . Furthermore, for information on any SNP, you can find out what your alleles are by looking them up on the Browse Raw Data feature of your 23andMe test, which can be accessed at https://www.23andme.com/you/explorer/

                • Correct. Even for those of us who joined a long time ago and who got the health reports, we still had to go through the work of uploading the raw data into a third party site to really know whether we had the folate problem. It takes a little searching and work (and I might have paid $30 or something to a third party site to upload my genome. Hard to remember for sure).

            • They still run all of your info here in the U.S. Just had mine done. Then I went on genetic genie and got all my MTFHR info for a donation and promethease for 5.00 broke down all my genetic health info for me.

          • I will check the 23andme site. Here in Canada, the healthcare system in my Province of Alberta is not functioning well. Earlier this year, the media reported that the gov’t Alberta Health Services executives misspent $800,000 of taxpayers’ money on roaming charges! Also, many physicians seem ‘out to lunch’. I am middle-aged and have spent the last 10 years seeking treatment for chronic pain (my entire body hurts). Now I am waiting for a referral to a Neurologist. I want to get comprehensive testing, but it is not available here even if someone wants to pay for it! I am interested in whether I have a genetic problem. It seems that there is more opportunity in the US for people wanting comprehensive health testing.

            • I hope you have read kressers work and given up grains…try reading “healing back pain, the mind body connection ” by John E. Sarno.

            • I am a biologist from Poland that worked in Cnada for over 10 years. I contracted “fibromyalgia” noone could cure which is excruciating pain. I ame back to Poland out of fear of dying. Tan wen to UK for work and cure . So far no one can help me and I a feel sorry for anyone who suffers pain. I am a “supplement ” junkie and made mistake for taking foilic acid without consultation. It i understand is necessary to get genetic profile before applying any therapy. I am interested with anything that combats p a i n (from hell ) that I can bearly stand. Could folate defficiency be the cause ???. Please, help if you know something. I would appreciate any feedback. Respectfully, Sylvia

              • Hi Sylvia,

                First, have you had your diagnosis checked and double checked? Second, have they checked for poisons, such as arsenic?

                Last, my first go to supplement is B12. I had many things starting to go wrong with me from the top of my head to the tips of my toes until I started taking B12. My feet and legs hurt so much that I could barely walk. Two weeks after I started with B12, I could walk with no problem! So, I would start with 20,000 micrograms of sublingual methylcobalamin. After that, I would EAT folate, meaning any food I could that is known to naturally have folate in it. This whole thread is confusing to me, but the one thing that I think I got from it is that people do not seem to have a problem with folate in (organic) foods.

                I take a number of vitamins and herbs. I am not 100% yet, but I am getting close. My biggest problem now is VERY HIGH blood pressure.

                The vitamins and herbs, besides B12, that have helped me feel better the most are Magnesium, D3, Iron, B2, and Turmeric.

                Some people like bee product therapy. Some people like supervised, medical fasting. Personally, I would check it out thoroughly if I were told to go on a low fat diet, because I think fats are very important, especially where nerves are concerned.

                Unfortunately, fibromyalgia is another disease that the medical community knows very little about, so you will have to educate yourself. Good luck.

              • Hey Sylvia:
                Just read your post on fibromyalgia. True fibromyalgia according to Dr William Wong who started World Nutrition long ago is essentially excess fibrin in the body essentially choking off the nerve endings. Much more common in Female then male since it is estrogen dependent if I recall correctly. I have seen men and women with true fibro eliminate their condition with a round of systmeic enzymes called Vitalzyme XE (the professional grade). They are nothing more then systemic enzymes which levels we produce fall as we age. Yours in health,

                • David S.,

                  You know, I saw some female (I think doctor) on a religious show well over 10 years ago now. At the time, I only half paid attention to her because she seemed a little flaky, but now I wish I had gotten her name and the title of the book she wrote because she was right about quite a few things, one of them being that, for various reasons, we all have too much estrogen in our systems, and it is starting to cause problems. Considering what you just said, and a few other observances over the years, she might be onto something. If so, have you heard of any way to lower, or at least not increase our estrogen?

                • Chris K: To be honest, other than staying far from any and all soy products which is added to so many packaged foods to increase the protein content. We do not even feed any soy to our farm animals, nor do we feed any gmo seed/foods. We grow most of what we consume. It is difficult at best to avoid the hormone disrupters everywhere around us. From plastics to grocery receipts and beyond, they are everywhere. So I guess the long answer, is not that I am aware of…. Sorry, but it seems like Chinese herbal remedies might be a place to begin looking, perhaps something that binds with estrogen ?
                  Sorry, I could not be of more help.
                  Yours in health,
                  PS I should be getting my labs back soon for hypercoagulation disorder and will be requesting your opinon very soon. I will do some looking in the mean time and see if I can come up with some better possible suggestions.

        • Meme
          Check out a facebook group called “Lovenox Ladies++Clotting Disorders++TTC” you will find a wealth of information and awesome support here. I have also had miscarriages and belong to that facebook group.

    • 1 mcg is a tiny amount so maybe you mean 1 mg (which is a very large amount). Either way, yes I’d avoid it if it is really folic acid. I’d also look at what is in the multi as you are probably getting a double-dose of folic acid. If you really need a multi (most people don’t) find one that has an active form of folate rather than folic acid.

  11. My wife is getting over a blood clot caused by folic acid poisoning, when she never bothered with folic acid supplements. Is there a union of people being organized with a web site that can stop all foods from being fortified with folic acid. In my opinion folic acid is a dangerous replacement for folate and should be highly regulated.

  12. Dear Chris (Kresser),
    In this article regarding Folate vs. Folic Acid you give reference footnotes to the facts stated in your article: where can one access these references as I do not see them listed at the end of the article where one usually finds them??? Thx.

    • Throughout the article, you’ll see number links formatted like this: (3). Click on the blue number to view the reference.

  13. INTERESTING, I just read some of the comments.
    Whether one needs Folate or Multi-vitamin,.. or not – some of the main issues are:
    1- Consuming wrong combination of foods, like meat with bread
    2- Taking supplements that have unallowable impurities
    3- Taking one type of vegetable for a certain need, like spinach for folate, discarding the fact that Spinach has too much oxalate that affects kidneys and even arteries.
    4- Low consumption of raw materials and too much cooked food
    5- Certain GMO’s – like arsenic, folate, dyes in grains, azo dyes in certain vegetables
    6- OVER-EATING, as well as eating in certain hours without being hungry, some consume too much sugary stuff others eat NO fat and NO cholesterol, both contributes to many health problems.
    7- Too much animal proteins that provide, arsenic, anti-biotic, hormones,…
    8- Un-balanced microbiome owing to undigested food or wrong combination.

    • I’m afraid you are misunderstanding. If a person has the MTHFR 1298C &/or 677T genes…you can not absorb what you need from a balanced diet…..no matter how balanced your diet is. This is my case. So a blanket statement like yours can be dangerous to the lives of many persons. I agree a balanced proper diet is what everyone needs but that alone will not help people like me.

  14. Hi all. I have a question. I am pregnant and my diet is very healthy. I eat every day spinach, fruits, vegeies. I do not take prenatal vitamins or folate. I search before one cup of spinach it’s appr 250 mcg or folate. For pregnant woman need to take 400 mcg each day or more. But as I told I eat a lot of fresh vegies. I ve got terrible skin problems from all vitamins in a pills especially vitamine group B (wich is folate/folid acid). So huge problem so once I even had to go on roaccutane after taking vitamins. My doctor still incourage me to take folate as a pill. But I explained her and also as I know our mothers 50 years ago did not take any vitamins while they were prignant by us. Of course I am still worry bc the sociaty and internet almost push you to take vitamins (pills) as it something without what human could not be. Are there many people like me who prefer to eat natural food than pills?

    • Hi Bonnie. Yes, there are people like you who prefer to get vitamins from diet and yes you can get what you need without supplements. The history of the link between folate intake and birth defects is that some groups of women around the world had been found to have higher rates of birth defects associated with low dietary folate intake, particularly when pregnancies were in winter months and there was inadequate access to green vegetables. Various governments decided to combat the issue by fortifying foods with artificial folate (folic acid) and recommending that people take supplements. With a healthy diet, none of that is necessary and, as the original article suggests, eating a lot of folic acid is probably not healthy.

  15. I tested positive for a DHFR mutation but not an MTHFR mutation. Any suggestions on prenatal vitamins that I should look into? Thanks!


  16. I’m utterly confused as to why you would say it was hard to reach the RDA of folate through diet. There are a large number of common foods that have 25% or more of the RDA per serving. I don’t see how anyone on a “real food” diet could possibly be folate deficient. Some leafy greens and nuts every day, a little liver once a week, maybe some legumes from time to time, and you’re good to go. I did notice that this is one nutrient that spinach is much higher in than kale, so I’ll go back to letting myself eat some spinach.
    Also, all you people in the comments section who are fretful that you’ve been on prenatals for years while trying to conceive, note that the only substantive difference between a woman’s multi and a prenatal is the whacking high dose of iron in the prenatal. Since the need for iron increases only in the second trimester, taking the prenatal before you are pregnant is just extra years of constipation and nausea. A women’s multi will have the folate/folic acid needed to prevent neural tube defects (although note that neither has the choline necessary for that purpose, so keep up with the egg yolks).

    • I believe he was referring to pregnancy and the extra needed and not those who aren’t pregnant.

    • Might be an issue if you have a MTHFR gene mutation, in which case a serious combination could leave you folate deficient regardless of how ‘healthy’ you diet is. With this mutation methyl folate would be a better choice.

      • How would an MTHFR polymorphism leave you folate deficient if you are eating a healthy diet and getting adequate folate from natural sources? The known MTHFR polymorphisms affect the body’s ability to convert folic acid to folate, but folic acid is a synthetic food additive, not naturally occurring in food. MTHFR polymorphisms do not affect one’s ability to utilize naturally occurring folate.

        • That is not entirely true. Mthfr affects the body’s ability to process B9. Those of us with the gene mutation cannot process folic acid at all. It just builds up as a toxin in our system. Different combinations of the mutation affect the enzymatic activity differently. For example, if you are compound heterozygous (one mutation on each of the two markers), your enzymatic activity , i.e. the ability to methylate folate, is at approximately 40% of someone who has no mutation. So while I could get a lot of my folate from my food, I would have to eat more than a “normal” person. If you are homozygous on the 677 marker (a mutation on both dna strands), your enzymatic activity is closer to 15%. For those individuals, supplementation with folinic acid or methylfolate really is a must.

          • Sorry but what you said is not correct in a few ways. First, your statement that “Those of us with the gene mutation cannot process folic acid at all” is incorrect. The percentages that you cited actually refer to to the ability to convert folic acid into useable form so, although they are reduced, they are definitely not zero. For someone heterozygous for C677T, the rate is around 65% meaning that the majority of folic acid is still converted into useable form (if homozygous it’s lower, like 10-30%). This is why many physicians tell people with MTHFR polymorphisms to just take more folic acid. If you take enough, you will eventually get enough converted to usable form. However, that logic ignores the fact that too much folic acid is not healthy, which brings us back to natural folate in food. The MTHFR polymorphisms do not in any way affect the body’s ability to convert that into useable form; (the percentage that you cited had to do with folic acid), so you in fact do not have to have more of it than someone without the polymorphism. Finally, although you see the term all over the internet, “mutation” is not the scientifically correct term for what we are talking about. They are polymorphisms, which are very common. Mutations, by definition, are very rare, and affect 1% or less of the population. Kind regards.

            • David with due respect you are wrong and Anne is right. Folic acid is synthetically produced and is not tolerated by someone with a C677T Polymorphism. The reduction that you write about is in regard to natural folate in our diet. I have personal experience with this. My wife had me taking supplements for male fertility it was a high amount of Folic Acid in about a weeks time I had a neurological attack. Ankles swelling, hand and feet numbness, muscle twitches etc. Scary time! Had every type of test done and no answers. Symptoms went away because I was not taking any supplements. Started taking the supplements again and guess what happen. Did some research on MTHFR, took a test from 23&ME and found out that I am Homozygous for C677T.

              Here is Dr. Ben Lynch’s take on it:

              “supplemental and enriched folic acid foods should be avoided by those afflicted with MTHFR C677T mutations because the MTHFR mutation has partially destroyed the MTHFR enzyme which is required to process folic acid completely.

              Natural foods with folate should be consumed by all with MTHFR mutations as food folate helps make other forms of folic acid which are needed for various functions.

              Those with C677T MHTFR mutations do not process folic acid into 5-MTHF.

              If folic acid does not turn into 5-MTHF, folic acid levels build up. Elevated folic acid has potential to stimulate pre-existing cancer cells.

              That said, it is unwise to provide supplemental folic acid to anyone with MTHFR C677T mutations.

              However, what one should understand is there is an already methylated, active form of folic acid available. This is L-5-MTHF and is available via supplement form over the counter and is also available by prescription only.”

              • Chuck I have C677T and A1298C mutations. Do you know if it’s ok for me to be taking the 266 mcg folate (“as folic acid” the label says) per day? Based on what I think I’m reading here it is NOT ok. Thanks in advance.

                • Ruthie

                  I would say do not take it if it comes in the form of Folic Acid. Go on Mthfr.net
                  Lots of good info here.
                  Check out this link http://mthfr.net/mthfr-c677t-mutation-basic-protocol/2012/02/24/
                  Everyone is different but you need to start slow. I started taking 400mcg of L-5 methylfolate and 1000mcg of B12 methylcobalamin and felt great for a week. Wow is all i can say. I have never had any supplement make such a positive dramatic change in me. But then the honeymoon was over. I got irritable, strung out, depressed. I over did it. My body was not use to handling this new supply of methylated b9& b12. Stopped taking for a few days then started again with a quarter of what i originally started out with. And gradually worked my way up. It has worked for me but it is a balancing act and a work in progress. Start with Mthfr.net website there are others like mthfrsupport.weebly.com

              • Hi Chuck. Thanks for the comments, but the facts remain that everything I have said is correct, most of what Anne said is incorrect, and your experiences do not in any way disconfirm what I have said.

                My original point was that MTHFR polymorphisms do NOT affect the body’s ability to deal with natural folate in food. I’m not talking about folate added to food in the form of folic acid, but natural folates (as mentioned in the original article). That point is a scientific fact, and the fact that you had a bad experience taking too much folic acid from supplements in no way questions my point.

                My second point (made in my reply to Anne) was that people with MTHFR polymorphisms have a REDUCED ability to metabolize folic acid, NOT A COMPLETE INABILITY. How much that ability is reduced depends on the polymorphism, but even people homozygous for C677T have about 30% activity.If you were taking very large doses of folic acid, I don’t doubt that it could cause you problems (I said that earlier) but that doesn’t mean that people like you (or me) have a complete inability to metabolize folic acid. Although I would recommend consulting the primary scientific and medical literature rather than relying on information coming from people who sell supplements, even the source that you cited confirms my point. You quoted him as saying ” MTHFR mutation has PARTIALLY destroyed the MTHFR enzyme which is required to process folic acid COMPLETELY.” You cannot just ignore the words “partially” and “completely” and conclude, as Anne wrote above that “Those of us with the gene mutation cannot process folic acid AT ALL”. That is simply false and, as I noted, is even inconsistent with the information on the site that you mentioned.

                However, this doesn’t mean that folic acid is a good thing, and I do try to avoid it. You will not find anything on the site you mentioned that says people with MTHRF polymorphisms have a reduced ability to metabolize natural folate, because they do not. You can also easily get the RDA or even the upper tolerable limit for folate from foods (such as those mentioned above). The only reason why you should take a methylfolate supplement would be to take in an excessive amount of it. For example, prescriptions folate is 7.5 X the upper tolerable limit for folate intake. Is that actually helpful for people with MTHFR polymorphisms? That is an empirical question that has yet to be answered scientifically.

                So, to summarize, two facts remain:
                1) MTHRF polymorphisms do not affect the body’s ability to utilize natural folates in the diet.
                2) People with such polymorphisms have a REDUCED ABILITY, but not INABILITY to utilize folic acid.
                Kind regards.

                • For some reason, I am unable to reply to the comments of Kelly, so I’ll reply here. Neither of the references provided by Kelly even mention MTHFR, so they are not relevant to the question of how MTHFR polymorphisms affect conversion of folic acid. A good, recent review of the overall subject, in a peer-reviewed journal, is at Nazki, F. H., Sameer, A. S., &, Ganaie, B. A. (2014). Folate: Metabolism, genes, polymorphisms and the associated diseases. Gene, 533, 11-20. http://dx.doi.org/10.1016/j.gene.2013.09.063

                  As I stated earlier, the rate of enzyme activity (for converting folic acid into useable form) is about 65% for C677T heterozygous and about 30% for homozygous.

                  Whether or not that is “greatly reduced” depends on your definition of “greatly”, but it is definitely not “completely” as repeatedly stated earlier by other people commenting on the article.
                  Kind regards to all.

                • David,
                  I so enjoyed reading the Chuck/David exchanged…For many reasons, but namely that (presumed) strangers were able to have a conversation that was not overly abbreviated and, despite disagreement and misunderstanding, did not result in personal attacks.

                  May I inquire as to your thoughts on genetic testing becoming a standard part of preventive care? Specific to MTHFR and the ethical and legal implications for the standardization of more comprehensive genetic testing as well.

                  I recently came to the realization that I am Heterozygous for MTHFR 677. My mother continually sends me links to nutritional research and questions how it may be effecting our family, much of which I disregard out of necessity, but I happened to follow up on MTHFR and look into my old 23 and Me raw data (thank you FDA for not completely shutting them down). It took a bit of searching to decode the data, but Sure enough (despite my mothers suspicion that I have a 1298 mutation, which I don’t) I do have 677 AG. Good to know, this definitely has immediate health implications for me…And now I can nag my father (whom my mother is no longer able to nag, as they were divorced years ago) to STOP taking the large amounts of Folic Acid he is currently on, switch to 5-MethylTetraHydraFolate or better yet, re-evaluate the need for supplemental Folate with genetic and possibly Spectracell testing.

                  ANYWHO…You see that I have little ability to abbreviate myself, hence my appreciation of your complete information.

                  RE MTHFR. As stated, I am pleased to have this personal info, but given the large number of us who have some degree of issue with methylation, I am extremely curious about whether it is becoming standard practice to advise Pregnant patients against taking Folic Acid supplements unless they are known to NOT have this issue.

                  Certainly, the concern over Neural tube defects is warranted, but I have a loved one who had stage 3 breast cancer diagnosed at 18 weeks pregnancy. Who knows how long the cells were present, but the growth was very sudden and profound. Previously I would have thought that it may be pregnancy related growth hormones that increased the incidence of, or at least growth of the cancer. However, I now question the possibility of whether un-metabolized Folic Acid (and the supposed decreased ability of those of us with 677 to rid ourselves of environmental toxins) that may increase the incidence of certain cancers. (FYI she has responded well to chemo, was able to carry to close to term, has a healthy baby boy and we are hopeful about the future)

                  Of course, looking into my genetic code also got me thinking about whether there are other genetic links with nutritional triggers to things like PROM or amino acid chains…….. The darned noggin NEVER stops, there is a domino effect.

                  I woke up at 4 am thinking about MTHFR and the implications for pregnant patients.

                  Another thought has to do with the process by which these tests become more widely available to the general public. Must we only come to discover individual traits and nutritional needs after suffering the consequences?

                  Your point regarding sound nutrition being the best option is well taken. However, for many of us, it is knowing the WHY of the magic pills not being a good option that gives us incentive to make better choices.

                  I just wonder if there is any way to expedite what has been the painfully slow process of moving from sound research, to making the information from said research available to patients and practitioners.

                  Thank you for your patience with my sleepy eyed brainstorming.


                • This is a reply to Stephanie’s comments, which are below as I am seeing the board. I don’t see an option to reply directly to her comment, so I’m replying here. Regarding your question, yes, I see genetic testing as eventually being a standard part of preventative medicine. That is the general logic of personalized medicine. However, as I see it, there are currently at least two obvious problems with the practice. One is that we know too little about how various SNPs interact. When you do genetic testing you typically get results based on individual SNPS, and many times you will see opposite facts (e.g., you have a higher and lower risk for the same problem). Thus, we often don’t really know what to do based on those individual and sometimes conflicting results. Second, the effect sizes for various SNPS are often very small, and much smaller than for environmental factors. People then make a big deal out of the findings associated with the SNPs but don’t pay enough attention to environmental factors. Those are my thoughts, at least.
                  Kind regards

                • Hi David,

                  I know this is a year old post, but I was hoping you could help me understand something about MTHFR. Why is being homozygous for 677t a problem at all then? If we remove synthetic folic acid from our diet and eat adequate amounts of natural folate, shouldn’t we be able to methylate as well as everyone else? I believe your description of the issue is spot on btw. I just would like to know if this is a manufactured issue on many levels. However, I would be the first to admit that I have been helped methylated B’s. Please include any links to articles and studies that illuminate the issue further. Here is a good one I found. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708334/

  17. I have been taking Hallelujah Acres brand B12 B6 & Folate sublingual tablets because they have the word Folate on the label. However, I have a question about what they say on the back of the bottle. It says: “Folate (as [6S]-5-Methyltetrahydrofolic acid, glucosamine salt) Quatrefolic.” When I first saw that it said that, I wondered if it really is folate like it says. I still take them but today when I reread your article, I decided to ask my question. I hope someone can reassure me that I really am taking folate and not folic acid when I take these tablets.

    • Susan, Quatrefolic is the glucosamine version of folate – you’re good.

      • Thank you, Molly, for answering my question. It’s reassuring that the Hallelujah Acres brand is the right kind of B12.

    • Many B100 brands list in order- Folate (folic acid).

      Is this listing both next to each other incorrect in that folate is NOT the prefered form folic acid?

      • James,
        Folate is an umbrella for many different forms of Vitamin B-9. Folic acid is a folate. L-5-MTHF (methyltetrahydrofolate) is a folate. 6S]-5-Methyltetrahydrofolic acid is a folate. There are also many intermediary forms of folate that get formed in the folate cycle.

        When a manufacturer lists Folate (folic acid), folic acid is the specific form of folate found in that supplement. If a manufacturer just says folate, you can expect that it contains folic acid. Other folate forms are much more expensive and I would expect the manufacturer to specifically state if it is a form of methyltetrahydrofolate.

        Also, you don’t want to buy just methyltetrahydrofolate, because that probably means it is in a racemic form (L & R) where only half is the right configuration to be active. You want either L-5-methyltetrahydrofolate or 6S]-5-Methyltetrahydrofolic acid, because those are the biologically active forms of MTHF.

  18. I had a wild, scary bad cognitive reaction to a low dose of T.R. 5-mthf. It took me months to recover-although the worse was on the first week 🙁 after I took the first dose
    I think that folate is not for everyone. Interestingly I don’t have bad reactions to Folic Acid but I still don’t know if is helping, too early to tell.

      • I agree, I found with a few extra supplements my tolerance to methyl folate increased. Try niacin, MSM and inositol. Avoid folic acid if you have methylation issues.

  19. Hi, I have severe anxiety and am wanting to try a combination of folinic acid and methyl b12 as it has worked well for some. I have tried almost everything, so am hoping this is the one. I was wondering if anyone could give me advice on dosages on both the above. TIA

    • Hi Jo,

      I started with folinic alone, and did so by taking 800 micrograms a couple times a day, and very soon realized that it really helps with sleep (and thus anxiety), and so ended up making sure that I take one (I empty the capsule) under my tongue about 45 minutes before bed — works really well, for me anyway.

      Then you can add methylb12 or hydroxob12 in a few days to a couple weeks or so, but take it (under your tongue) in the mornings, as it’s known to help reset circadian rhythm, so it could keep you awake if you take it too late.

  20. I just wanted to add that I had a negative reaction to methylfolate at just 200 mcg that I don’t see listed by others very often: venous insufficiency. I am 31 years old, at a healthy weight, and possessive of no risk factors for that condition. It was the methylfolate. Blood pooled in my feet, turning them purple, and caused painful sores on my toes. It happened in my hands also, but with less severity. My doctor prescribed horse chestnut, which had no effect. Cutting way down on the methylfolate is what finally caused the venous insufficiency to resolve fully. But it took me a full YEAR to discover the cause, because no one else lists it. So I hope this helps someone, somewhere, who suddenly developed venous insufficiency upon supplementing with methylfolate!

    • Wow, Shauna! So sorry to hear about that horrendous time you went through, but really happy to hear you discovered what was causing the problem. All of us are so different from one another, and this is a great example of that, and encourages us to remember there are no “cookie-cutter” answers. Thank you so much for sharing this. Blessings!

    • Hey Shauna,

      I’ve just been reading about the MTHR gene and the two ways it can affect people. I know thrombosis is involved in one mutation of this gene called C677T and you may have been overdosing on folate when your body already produces too much but I’m not an expert so maybe read these and ask your doctor – http://www.emed.com.au/anxiety-and-the-mthfr-gene/ also http://www.emed.com.au/folic-acid-or-folinic-acid-which-is-best/. Hope this helps you. This is all related so found this article really helpful for me.

    • I’m sorry to hear that. I felt like a zombie after the first-and last- dose of folate. I’ll never take that supplement again 🙁