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Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

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March 12 2018

Dear Mark: Folate Follow-up

By Mark Sisson
10 Comments

Dear_Mark_Inline_PhotoFor today’s edition of Dear Mark, I’m answering five questions taken from last week’s folate post comment board. Does folic acid increase cancer risk? It’s an open question, but I think we have a pretty good idea of where the research points. Next, what other nutrients can help people with MTHFR mutations? Is there anything else someone with a deleterious variant should focus on eating? Third, is folate good enough, or should you look specifically for 5-methyltetrahydrofolate? Fourth, how do I know if I have a MTHFR variant that increases the need for folate? And finally, what specific form of folate am I using in Master Formula?

Let’s go:

First, Terje asked:

Hi Mark. Would you care to also comment on potential increase cancer risks connected to folic acid? Particularly breast and prostate.

This is a common concern, mostly because folate has a strange relationship with cancer.

On the one hand, folate is critical for cell division, and, as you know, cancer is highly dependent on rapid cell division. Cancer cells consume a ton of folate. They demand it, so much that a class of anti-cancer drugs known as “anti-folates” block folate metabolism and arrest cancer cell proliferation.

On the other hand, folate is also critical for maintaining the integrity of our DNA. Folate deficiency can lead to DNA strand breaks (double helix is severed, must be repaired lest DNA rearrangement occur), increase the frequency of mutations, and cause cancer.

Overall, scientists haven’t found any strong links between folic acid supplementation and prostate or breast cancer. A 2013 meta-analysis of controlled human trials found no connections between supplementation and cancers of any kind, except for melanoma—for which folic acid was protective.

Those were results for synthetic folic acid. I’d have to imagine the links between folate and cancer are even more positive.

Meg made a great point:

Don’t forget the importance of choline to conserve folate stores. Some MTHFR mutants end up on megadoses of methylfolate and/or folinic acid, but the need for this would go down if they remembered to take phosphatydl choline, or to increase their consumption of foods like liver.

Great point. I’ll expand a bit.

If you don’t make/have adequate 5-methyltetrahydrofolate, either because you’re not eating enough of the precursors, you’re an MTHFR mutant (sounds pretty damned cool, actually), or you’re taking the wrong kind of folic acid/folate, choline can step up and perform many of the same tasks folate normally performs. This is a good way of getting around the folate deficiency, but you have to eat enough choline because your requirements will go way up. In one study, Mexican-American men with low folate status due to MTHFR mutations who took 2200 mg of choline per day (around 4x the normal daily dose) reduced DNA damage and improved cellular methylation.

MTHFR mutations might also increase glycine wastage. Since glycine is a crucial yet underappreciated amino acid that plays an important role in joint health, methionine metabolism, and sleep (to name a few functions), you’ll also want to eat more glycine in the form of gelatinous meats, bone broths, or collagen powder.

Creatine is another nutrient to consider. Normally, MTHFR mutations increase homocysteine, since there isn’t enough folate around to methylate it into methionine. Folks with MTHFR mutations who supplemented with creatine lowered their homocysteine levels, perhaps by regenerating tetrahydrofolate.

Susan asked:

I take a B complex, the label just lists folate. So I really should be looking for a B complex that lists 5-methyltetrahydrofolate instead?

Not necessarily. “Folate” is a good sign as well. Some “folates” are food-based folates; those will presumably have a spectrum of folate forms, just like you get in food.

Folic acid will always be listed as folic acid. You’ll know it when you get it.

Liz wrote:

I’ve been taking folic acid without any problems. How should I get checked if it’s the right one for me? If I don’t have MTHFR is it still relevant?

First, you’ll need to do a genetic test. You could ask your doctor to order one for you. They’ll probably deem it “elective,” badger you for taking an interest in your health, and refuse to order the test. You could order a dedicated MTHFR test online, but that wouldn’t be my first choice.

You get the most bang for your buck using a service like 23andMe, which gives you ancestry data and, if you pay a bit more, health data. Even if you order just the ancestry results, you’ll still get full access to the raw data that contains the health info, including MTHFR status. They just won’t do the analysis for you.

Once you have your 23andMe results, log in and download the raw data.

Submit the data to a service like Strategene for full analysis.

Read the Strategene report and look for A1298C and C677T. Those are the two main MTHFR gene variants.

The report will tell you if you have zero variants (two minuses; –) or if you’re homozygous (both father and mother passed it on; ++) or heterozygous (one of your parents passed it on; +-) for each mutation. Each “hit” (marked by a “+”) reduces your ability to make folate and increases your need for 5-methyltetrahydrofolate.

If you don’t have any MTHFR mutations, folic acid is probably safe… but you’re still better off getting your folate through food. And if supplementing, taking actual folate will work just as well and limit any potential side effects from excessive amounts of the synthetic version.

Again, if you have B12 deficiencies, folic acid will work better than “better” forms of folate.

Alex wondered:

Just because I have tried multiple types of methylfolate I was wandering if you are using the amorphous salt version (Thorne) or one of the crystalline versions (like Pamlabs medications or methyl-life)

The folate we use is calcium salt-based. The full name is L-5-Methyltetrahydrofolate calcium.

Thanks for reading, everyone. Take care!

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10 thoughts on “Dear Mark: Folate Follow-up”

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  1. I’m taking a prenatal vitamin (New Chapter) which cites the supplement as “Folate (as folic acid from culture media)”. A few people have had questions regarding whether this is folate or folic answer and the company’s response is as follows:

    “while New Chapter multivitamins such as Perfect Prenatal use folic acid as the base catalyst for B9-folate during our probiotic fermentation process, it is not the form found in the final product. New Chapter’s probiotic fermentation creates a whole-food complex form of B9- folate. You can learn more about the process on this website: http://www.newchapter.com/new-chapter-whole-food-fermented-multivitamins-made-differently#infographic

    Does anyone have any insight into this? I’m considering switching my vitamin if necessary but these were pretty expensive and check all the other boxes.

  2. I’m an mthfr mutant. Supplemental folate does not make me feel good. Supplemental Creatine and glycine however has been a great hack. I have fewer headaches, fewer food intolerances, and need less sleep.

  3. For fellow MTHFR mutants, don’t worry about it too much. First of all, it just means there’s reduced activity of the enzyme, not no activity. Second, like Mark mentioned, there are alternative pathways involving other methyl donors that will take some of the pressure off of the folate pathway, one of which involves choline.

    If you eat a relatively nutritious diet based on whole foods, someone with this mutation shouldn’t even really have to worry about supplementing — in the absence of a blood test confirming deficiency. Even in the broader population, most of whom are on the SAD, MTHFR mutations are only /weakly/ associated with a handful of health problems.

    It’s an extremely common genetic trait that may or may not have any serious bearing on health outcomes.

    And, as with the ubiquitous mutation that makes humans unable to synthesize vitamin C, there’s probably a compensatory mechanism elsewhere in the genome. Just eat good food.

    1. I’m dual MTHFR C677T, and I’ve been paying attention to Ben Lynch and his warnings about the dangers of this genotype. It would be interesting to see another educated perspective arguing that it’s not a big deal.

      1. I am double mthfr A1298C, and I just discovered that through 23andme a few months ago. I didn’t have a clue about these mutations until then. Blood tests showed I am deficient in folate, I was supplmenting with synthetic folate, pure encapsulations, but have since started consuming dessicated beef liver and marrow from ancestral supplements. I feel pretty good, more energy and a sense of all is well. Not gonna get too wrapped up in being a mutant 🙂

  4. Foods highest in folate (per 100g/3.6oz, excluding fortified/processed foods):
    Duck/goose liver, raw: 738 micrograms (mcg)
    Turkey liver, raw: 677mcg
    Yardlong beans, raw: 658mcg
    Mothbeans, raw: 649mcg
    Cowpeas, common, raw: 633mcg
    Mung beans, raw: 625mcg
    Adzuki beans, raw: 622mcg
    Chicken liver, raw: 588mcg
    Agar seaweed, dried: 580mcg
    Chickpeas, raw: 557mcg
    Pinto beans, raw: 525mcg
    Lentils, raw: 479mcg
    It does seem that cooking affects these folate sources differently. If you compare cooked (boiled, drained) legumes, lentils come out on top! (Although liver is still king.)

  5. The role of creatine is a bit different, a lot(like 40%) of the methylation donors generated in the cycle are used to make creatine. by supplementing it you conserve methyl donors(SAMe) because there is(as with all biological processes) a negative feedback loop

  6. Thank you Mark for posting. This is a really detailed article on folate or B vitamins. It’s true that supplements can further provide us with extra energy we need or even help our memory levels but it’s important to note that should be taken only if required and as an additive to a healthy nutrition plan, rather than a replacement.
    Thanks again