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I just got done doing a TON of research into riboflavin. I recorded a podcast on it with Alex Leaf of Examine.Com, where I focused on the basic science and Alex focused on the outcomes of supplementation studies. You can find that here.

One of the fascinating things we stumbled on is the possibility that the famous MTHFR polymorphisms — variations in the gene that uses riboflavin to make the methyl group of methylfolate — only decrease MTHFR activity because most people in whom the activity has been measured have mediocre riboflavin status.

Alex found some key studies supporting this and blogged about them here.

Here are the key findings:

  • Using experiments in bacteria, where the part of the MTHFR enzyme that binds riboflavin is similar to humans and other animals, the reason that the polymorphisms decrease enzyme activity is because they make the enzyme bind to riboflavin more weakly. At low riboflavin concentrations, the enzyme has poorer activity. However, at high enough riboflavin concentrations, enzymatic activity is restored to normal.
  • In humans who have the MTHFR C667T polymorphism, all of the elevated homocysteine is concentrated among people who have poor riboflavin status.
  • 1.6 milligrams of riboflavin per day decreases homocysteine, and this decrease is highly concentrated among people with the C677T MTHFR polymorphisms who also have poor riboflavin status. In them, 1.6 milligrams of riboflavin decreases homocysteine a whopping 40%!

And how many people have poor riboflavin status? It's generally assumed that riboflavin deficiency is rare in the developed world. Only 10% of Americans consume less than the RDA and clinical deficiency is rarely reported. But rarely does anyone study whether people have biochemical evidence of poor riboflavin status. A recent study in the UK found that a whopping 75% of boys, 87% of girls, and 41% of adults had blood markers of poor riboflavin status.

Why?

Because the best source of riboflavin is liver, and we don't eat liver any more. Because the next best sources of riboflavin are heart, kidney, and almonds. We don't eat heart or kidney and few people make large amounts of almonds a daily staple. The next best sources are red meat, cheese, eggs, salmon, mushrooms, seaweed, sesame, wheat germ, and wheat bran. But you have to eat lots of these foods to get enough riboflavin and most people don't. They are either demonized (red meat, cheese, and in some circles eggs) or they are used once or twice a week at most (salmon) or as minor portions of dishes (everything else in the list, if they are used at all). And while some people do load up on red meat and cheese, often the rest of their diet is rather terrible because they are not health-conscious.

Another reason might be that poor magnesium status and any kind of problem with energy metabolism — like hypothyroidism, adrenal stress, or insulin resistance — hurts riboflavin retention. So we have worse food selection riding on top of poor metabolic health and poor magnesium status. Less riboflavin is coming in, and more is going out. We're left with a double-whammy on our riboflavin status.

If suboptimal riboflavin status is truly widespread, and if that is the reason why the C667T and the A1298C polymorphisms lower MTHFR activity, it suggests that riboflavin should really be central to our thinking of how to deal with methylation issues.

But it also helps explain something else: why almost everyone has at least one of these genetic variations. Only about 10-15% of the population doesn't have either one! In fact, they are combined in such a way that there is almost an even spread across the population. There are six possible combinations of the different MTHFR alleles, producing a continuous gradation of MTHFR activity from 100% of full activity in the best case to 25% of full activity in the worst. Roughly 15% or so of people fall into each one of the six combinations, leading to an even spread of MTHFR activity across the population.

This distribution is compatible with a tradeoff, as if both low methylfolate and high methylfolate levels had equal advantages and disadvantages. That's conceivable.

But if these variations in enzyme activity are just a result of having crappy riboflavin status, then another explanation emerges: from an evolutionary perspective, these variations proliferated because they just didn't matter. Our ancestors had better riboflavin status than we did. They ate more riboflavin. They ate more magnesium and peed out less of it. They held on to their riboflavin better because they had better magnesium status and better metabolic health. They could get away with MTHFRs that didn't bind riboflavin as tightly because they had so much riboflavin around.

So, what do we do about this?

First, I have revised my MTHFR protocol. My MTHFR protocol is laid out on my Start Here for Methylation page. While that page has always mentioned riboflavin, until now it had given riboflavin a back-seat consideration. I have now moved riboflavin to the driver's seat. The first point in the MTHFR protocol is to aim for 3 milligrams of riboflavin per day.

Here's how I suggest doing that:

On one or two days a week, eat four ounces of liver, ideally from beef, bison, or lamb. On the other days, consume one “liver equivalent,” mixed and matched from the following foods. These foods supply 1/2 of a liver equivalent: kidney, heart, and almonds. These foods provide 1/6 of a liver equivalent: red meat, cheese, eggs, salmon, mushrooms, seaweed, sesame, wheat germ, and wheat bran. On days that you cannot meet the food requirement for a liver equivalent, take a low-dose riboflavin supplement or B complex providing 3-5 milligrams of riboflavin. For example, you could use a half a dropper of this liquid riboflavin supplement.

It's important to note that endurance exercise, weight loss, high-fat diets, and sunlight exposure all increase your riboflavin requirement substantially. If two or more of these apply to you and you have low MTHFR activity, your riboflavin requirement could be closer to 5 milligrams per day.

It's also important to note that we don't know yet just how close to maximal the extra riboflavin can get your MTHFR working. It might be the case that enough riboflavin completely normalizes the MTHFR enzyme.

Since we don't know for sure, my recommendation isn't to get extra riboflavin and then forget everything else. Rather, I recommend getting enough riboflavin first and foremost, and then still engaging the rest of the protocol by increasing choline, getting enough folate and protein, and considering supplementation with creatine and either collagen or glycine on an as-needed basis.

Think how different this is than trying to make up for low MTHFR activity by taking extra methylfolate. One methylfolate molecule goes into your body, stays inside your cells for 200 days, and every day has 18,000 methyl groups added to it using MTHFR. If you have a 75% decrease in that, you're losing 13,500 of those recycling events. You can't take 13,500 times the normal dose of methylfolate. I have no idea what it would do but I know it's not safe. Methylfolate is one of the primary normal food forms of folate, and I think it's great. You need to get enough folate, so getting normal, reasonable doses of methylfolate into your diet makes complete sense. But adding more to make up for low MTHFR activity is ludicrous.

Doubling your riboflavin intake from 1.5 mg to 3 mg may normalize MTHFR activity, or get close. You help the enzyme work right, and then those 13,500 lost recycling events are suddenly recovered.

Taking riboflavin to support the enzyme is high-impact. Loading up on methylfolate is not.

This is why it's really important to understand the biochemistry and to delve into the biochemical literature.

In addition to revising my MTHFR protocol on the Start Here for Methylation page, I have updated it in Testing Nutritional Status: The Ultimate Cheat Sheet as well.

By the way, I just released version 1.2 of the Cheat Sheet yesterday. The niacin and riboflavin sections have been completely overhauled, and it is now available in four formats instead of three: in addition to the traditional PDF, Kindle book, and iBook, I now have it as a Printer-Friendly PDF, where the hyperlinks are replaced by page number references, so you can flip through it as easily as you can click through the digital versions.

If you've already purchased the cheat sheet, you should have an email in your inbox giving you version 1.2 as a free update. If you don't have it yet, you can get it here and you can use the code NEWSLETTER at checkout to get $5 off.

The third thing I've done is I've added the riboflavin podcast to the podcast series on managing nutritional status.

In the next few months, Alex and I are going to produce a podcast on each nutrient. I'm going to intensively research all the basic science, the food, the markers of nutritional status, and the dietary requirements, and Alex is going to research supplementation outcomes. These are often clocking in at over 3 hours, so they will often be released in two parts. For example, this Friday part 1 of our niacin podcast will come out and part 2 will come out two weeks from Friday. If you want to get notifications when each new episode comes out, you can sign up for notifications here.

As we research each nutrient, I expect we will stumble on more discoveries like this. So after each podcast, I'll be revising that nutrient's section in the cheat sheet and releasing the next version as a free update.

If I stumble upon any more amazing discoveries like this one, I'll be sure to let you know with an email! So, if you're not on my email list, you can sign up here.

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87 Comments

  1. It’s also possible that riboflavin deficiency is caused/exacerbated by chronic hypervitaminosis A. It is actively discussed on this (huge) forum thread: https://raypeatforum.com/community/threads/grant-genereuxs-theory-of-vitamin-a-toxicity.24722/
    As many people have found relief following a “low vitamin A diet” (NOT zero!) , and riboflavin is actively involved in the metabolism of vitamin A, I certainly think it could explain a lot.
    After following this approach for 9 months myself, I can attest to its effectiveness. It seems to be a smoother way than taking extra B2. It is of course slower but I have found that, more often than not, slow is the way to go when it comes to healing the body.

    1. If you are deficient, you will have awful symtoms… try and see if you become a “wired/tired/insomniac”, speaking from experience…. if so, you need to go very slow working from even one drop of liquid riboflavin up to a full dropper for some. It may take a while to replete and other co factors may be necessary. Based on my experience and readings as I’m still tryi ng to replete B2 in order to absorb B12.

  2. Thank you so much for putting out this important information! When I first got my gene test results, I thought I would have to take lots of supplements, but then I found this article and came to realise that I don’t have “bad” or “dirty” genes, I just don’t do well with this nutrient-poor modern food. But when I eat organ meats my methylation cycle kicks in fully and I feel great and fully myself! And my homocysteine goes down to just 6. No need to take methylfolate or all the other supplements they try to sell you! I think you’ve nailed it, and that the same principle applies to most other enzymes affected by polymorphisms too. For example, I also have a homozygous polymorphism in HNMT, and used to get the typical symptoms of high histamine like itchy swollen mosquito bites and carsickness. But now I noticed that whenever I eat organ meat, my histamine quickly goes down to normal, so it seems the enzyme works well enough if it gets enough SAM-e. So now I eat almost nothing but organ meat all day and my body is perfectly happy that way!

  3. I am C677T homozygous. I supplemented for years with some results, never supplemented a full B complex, always MethFolate, b12. Recently I got tired of dividing pills, fussing every day…so I found a low dose B-Complex that has ALL B vitamins, including riboflavin. After only a couple of weeks, I feel better than I have for years and years and years. Though only empirical, I believe that riboflavin is a huge part of finding normalcy. And I take only 1 pill a day which is an extremely low dose, but I make it an consistent low dose. I recommend a good B-Complex that has the right folate and B12 types. Don’t disregard this article, my experience points to support.

  4. I don’t think I’ve seen a weaker argument in a while.

    ***

    Using experiments in bacteria, where the part of the MTHFR enzyme that binds riboflavin is similar to humans and other animals, the reason that the polymorphisms decrease enzyme activity is because they make the enzyme bind to riboflavin more weakly. At low riboflavin concentrations, the enzyme has poorer activity. However, at high enough riboflavin concentrations, enzymatic activity is restored to normal.
    In humans who have the MTHFR C667T polymorphism, all of the elevated homocysteine is concentrated among people who have poor riboflavin status.
    1.6 milligrams of riboflavin per day decreases homocysteine, and this decrease is highly concentrated among people with the C677T MTHFR polymorphisms who also have poor riboflavin status. In them, 1.6 milligrams of riboflavin decreases homocysteine a whopping 40%!
    ***

    bacteria? Homocysteine?

    I guess the genetic test I took for conversion of folic acid to methyfolate was a lie. If only they knew that a b-vitamin was the cause.

    I guess I should listen to this nonsense instead and stop my Deplin tomorrow.

    Or perhaps not.

    Lyle

  5. Im compound heterozygous mthfr.
    I have had devastating reactions to supplemental methylfolate, glutathione in any most forms. (afraid to try transdermal) and some forms of b12.
    I have reduced brain function – mild neurological defecits and depression as a result.
    even too many leafy greens has been problematic.
    I would like to try riboflavin but am afraid of yet another crash.
    any thoughts?

  6. Crazy, I read about this a month or two ago and was wondering if MTHFR was actually not that serious of a problem genetically, if you’re just missing the key nutrients. I read these two things:
    1. http://www.fuckportioncontrol.com/blog/2016/8/9/the-cure-for-gluten-allergy
    2. http://clinchem.aaccjnls.org/content/49/2/295
    I started taking R5P after reading that, and to be honest, didn’t feel too much difference but maybe haven’t given it long enough. (I’m homozygous 677t)
    I wanted to see if adding betaine to boost the whole process was worthwhile? I also have the PEMT and BHMT problems in my choline pathways.
    Love your work and thank you!

  7. I don’t understand the reasoning behind the “13,500 times the normal dose of methylfolate.”

    If MTHFR efficiency is 25%, wouldn’t it only require 1.0/0.25 = 4 times the amount of methylfolate to produce those 18,000 methyl groups, rather than 13,500 times?

  8. I just stumbled upon a review article about folate, thiamine and riboflavin transporters and there is an interesting piece about parts of the body maintaining very specific concentration of riboflavin in plasma. I’ll quote it here and leave the link in the end.
    In that light, I wonder if it’s even possible to get high enough level of FAD to restore normal efficiency of MTHFR. What do you think?

    Quote from the article:

    R[iboflavin] enters brain from blood at the BBB by a saturable system (KT ~ 0.1 μM) dependent on 52A2 [7,48-53]. From the extracellular space of brain, brain cells accumulate R by facilitated diffusion (presumably by 52A2) and rapidly convert the R to FMN and FAD [7,41]. Total riboflavin (mainly FMN and FAD) in rabbit brain (~10 μM) turns over by ~ 50% in several days [7]. One great surprise was the finding that the CP via OAT3 rapidly clears R out of CSF [7,39]. In fact 2 hours after the intraventricular injection of tracer concentrations of R and mannitol into CSF of unanesthetized rabbits, there is only 2% as much R in CSF as the passively distributed mannitol [7,39]. There is as yet no physiological explanation for the rapid active efflux of R from CSF into blood via OAT3 in CP
    [end of quote]

    Link: https://www.omicsonline.org/open-access/vitamin-transport-diseases-of-brain-focus-on-folates-thiamine-and-riboflavin-2168-975X.1000120.php?aid=25603
    (see the section about riboflavin)

  9. This is very interesting information. Thank you. For years now, part of what I’ve been taking is between 34.75 and 69.9 mg of riboflavin/day (and 28% of that is riboflavin 5′ phosphate – the activated form). And it has been part of an improvement. But as I am not asymptomatic, however, my experience suggest that riboflavin intake alone does not necessarily normalize the MTHFR cycle.
    So the article is good, but I’d take the “just” out of the title.

  10. Instead of eating liver, why not just start adding nutritional yeast to your diet daily? Then you get a bunch of riboflavin but also many other B vitamins. It’s delicious, vegan and is a complete protein.

    1. Because if you do the numbers, you’ll find that you’d have to use quite a lot of those flakes to get anywhere near your daily requirement, and you get a ton of histamine and glutamate along with such a large amount. Even if you don’t have histamine intolerance, the temporary spike in blood levels of both will do you some harm.
      Why not just eat liver? It’s highly nutritious, cheap, ethical as long as general demand is low, and fully paleo.

      1. Paleo is a fad. Also, liver has HIGH copper levels, which can drive some people mad…

        And newsflash: A ‘temporary’ spike in blood sugar is NORMAL.

  11. Chris, your notes on riboflavin requirement could well be correct and seem plausible, but liver is NOT a way to fix this.

    Remember it’s the ratios and balance of B vitamins that not only promote methylation but also mineral uptake and a number of regulatory functions.

    Beef or lamb liver are both extremely high in B12, iron and vitamin A. All of which would put a much bigger strain on a person that might have a higher B2 intake requirement.

    The b2 in liver isn’t enough to offset the above in my experience, and it can even be detrimental.

    1. J: Beef liver is one of the top food sources of B2. So it makes no sense to say this is not a viable way to address B2 deficiency. The high B12 and A and Iron content in liver… how on earth is this going to detrimentally effect B2 status?

    2. I don’t quite get that either. After all, our body is very good at regulating the amount of iron it absorbs. And since the B Vitamins are water soluble, it can easily throw out any excess it doesn’t need. Vitamin A is fat soluble, so it’s not as easy to get rid of it… however after six months of eating mostly organ meat, I still am not showing any signs of retinol overdose. And in my experience, the B2 in organ meats does get my MTHFR enzyme to work well.
      There are all kinds of nutrient ratios we are supposed to watch out for, but more and more I am starting to think that they don’t really matter so much as long as we are getting enough of all of them, which most people don’t.

  12. So I’ve been trying riboflavin for a week and a half now. Seems to be helping, thanks.

    Not sure I buy the organ meats explanation. Have tried liver pills for years and always gotten headaches. I believe many of us are “copper heads” (too much copper) and I think the headaches are from too much copper in the liver (pills are ~35%) Maybe we’re being exposed to too much lead and mercury at the same time – i.e. multiple things going on?

    I eat extremely healthy and eat meat, cheese, eggs, spinach, beets, squash, mushrooms, rice, seaweed, and almonds almost every day; salmon once a month. That’s not enough to give me 3 -5 mg/day? Thanks

    Wish I had seen this 2005 study sooner: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.105.580332?fbclid=IwAR0WXOPu92edjNu0UWTyaquHY-JVGvumMSeX-10uecT4PGkdqbG4MlY9CxI&

  13. I disagree with your conclusion. I’m not a Dr. but it seems to my logic that you’re arguing “which came first, the chicken or the egg?”

    Yes, riboflavin deficiency (as well as quite a few other deficiencies) are almost always present in those with MTHFR, but most of what I’ve read says that it’s the MTHFR that causes the inability to properly make use of the minerals and nutrients that causes the deficiency, not the other way around.

    When my son was born will all of the genetic markers for MTHFR except spinabifuda, he was born that way despite my efforts to eat a very riboflavin and magnesium rich diet (yes, plenty of liver, leafy greens, eggs, cheese… etc.). I took very expensive specially formulated food based vitamins specifically made for good absorption, but MTHFR doesn’t care now many minerals and nutrients are given, it won’t process them unless they be a specific type.

    MTHFR is a very real genetic disorder written right into the DNA, and while eating well and taking the correct vitamins ought to be able to decrease negative symptoms associated with MTHFR, it is most certainly not just a nutrient deficiency.

    1. Thank you for saying this. As a geneticist, I am in agreement with you. It’s not ok to extrapolate from bacteria and be so cavalier with people’s lives and the viability of their eggs and babies. Riboflavin is included at nearly 7,000% of the rda in Thorne Methyl Guard Plus. Yes, it’s important. No, the MTHFR mutations are NOT just a riboflavin deficiency, and this author ought to be ashamed of themselves for so grossly misleading people.

    2. I agree….I have always done ALL of those things during and after childbearing, and still have all of the symptoms of MTHFR as well as my children. Of course after I learned the details I have changed my multi supplement, but have always eaten organ meats, eggs, AND taken b vitamins.
      Disagree with this theory….

      1. In my opinion, the reason none of those measures work is three-fold:
        – beef liver is a bad way of increasing B2 because it is very high in both copper and biogenic amines which will cause lots of stress on an already diseased metabolism. Frequently these patients will suffer from copper dysregulation (low ceruloplasmin, high free copper) and/or histamine intolerance.
        – taking a B-complex or multi (like Thorne methyl guard) is an even worse idea since almost all of these supplements are always extremely high in vitamins B3, B6, B9, B12. This is important because B2 is needed for the body to be able to use these vitamins (yes, even in when taken in their so called activated form). So, instead of increasing your B2 pool, you’re actually decreasing it even further. High vitamin D intake is another reason.
        – increasing magnesium status is also crusial (as highlighted in this article) and actually a lot more difficult than people think. Getting enough through food is seemingly impossible (due to soil depletion). A good magnesium supplement is a must (think malate, glycinate, threonate). Secondly getting magnesium inside of your cells is an issue. I for myself have noticed that giving patients good magnesium supplments frequently does not elevate their eythrocyte Mg level. What is needed are the cofactors required for cellular uptake, especially B6 and B2 to activate B6 once it is inside the body (taking P5P as a supplement does not alleviate this!)

        So, a good regimen would be plain riboflavin, starting at low dosage (3-5mg), about 300-600mg magnesium and of course a healthy diet (I would recommend the Ray Peat approach minus the liver). Absolutely no other supplements!! Also I would test for histamine (and possibly salicylate) intolerance by cutting all food sources from the diet for at least 4 weeks. If present, avoiding amines will quickly subdue lots of symptoms and decrease strain on the metabolism.

        1. ‘So, instead of increasing your B2 pool, you’re actually decreasing it even further. High vitamin D intake is another reason.“

          Are you saying that vitamin D can deplete B2? I can’t find this information anywhere

          1. In PubMed there are papers on the relationship of D3 and B2, but everyone should avoid too much D3. It’s definitely a level that should be checked if people supplement. It’s very damaging to have too much.

          2. From the Handbook of Behaviour, Food and Nutrition; Volume 1, p2437: “In addition, vitamin B2 deficiency may significantly affect the activity of vitamin D hydroxylases.
            The enzymes 25-hydroxylase and 1a-hydroxylase are members of cytochrome P-450 superfamily.
            The consecutive syntheses of 25(OH)D3 (calcidiol) from cholecalciferol and 1a,25(OH)2D3 (calcitriol,
            the active form of Vitamin D) from calcidiol are expected to be reduced vitamin B2 deficiency.
            This may occur because of both decreased prosthetic heme incorporation (secondary to reduced
            heme synthesis due to low PLP production) to hydroxylases and limited prosthetic FMN/FAD incorporation
            to NADPH-dependent cytochrome P-450 reductase”

            here is a thread on another forum that discusses the issue: https://forums.phoenixrising.me/threads/riboflavin-and-vitamin-d.15446/

        2. What supplement do you use please ? I also have Homozygous C667 T my homocysteine levels are normal I suffer bad depression and anxiety it is quite cyclic. Any advice would be very Appreciated. I live in Australia.

          1. Unfortunately a low dose B2 supplement doesn’t exist at this point. So either you can try to open up a capsule and dilute the powder yourself, or you can try to get more B2 from foods: maple syrup is quite good for this purpose; also lean beef/veal, dark turkey meat are good sources because animal derived B2 has a greater bioavailability than B2 from plant sources.
            But go slow with it, because some frail patients even react to the slightest increase of B2. You should aim for 150% RDI to start with, around 2mg/day (foods + supplement). Going to fast, will cause a metabolic crash that can last a couple of weeks.

        3. That is so interesting! Thanks for sharing your opinion! How would one increase ceruloplasmin? And for riboflavin, is the activated form better?

        4. Oh gawd. I was starting to believe what you’re saying, until you mentioned Ray Peat. He has NO credibility in the scientific community.

          Next you’re going to be telling us we need more Coca Cola and potato juice…

    3. Wow, well said and I completely agree with you! It’s a struggle and it’s real, I have 677 & 1298 X2! Not very many doctors are very knowledgeable about it and much like this article, their grabbing straws trying to be the “hero”, though I don’t like or appreciate the constant downplay.

      1. What’s the big deal, check your b2 first and go from there.
        I have the same genetics issues but the low B2 was my culprit after 10 years!

    4. Huh? Why would you expect your diet to influence your child’s “genetic markers”? Do you mean epigenetic markers or physical manifestations? And isn’t the fact that he didn’t get spina bifida evidence that your diet and supplement regimen worked well?

    5. These aren’t genetic ‘mutations’, they’re genetic polymorphisms — and VERY common.

      It’s all about how they’re expressed, which can be due to a LOT of things, like the environment, stress levels, past traumas that are effecting current stress levels, etc.

  14. Is riboflavin beneficial for those with MTHFR a1298c homozygous? Or is it only beneficial for those with C677T? Thank you.

    1. It’s beneficial for both. I use Thorne Methyl Guard Plus, because it has everything. This author is being awfully cavalier with our lives, my miscarriages, and he’s dead wrong. It’s not ok to mislead people like that, I’m disgusted.

  15. So I test low on B2 and I have mildly elevated homocysteine. Also have had my thyroid removed. But every time I try to supplement with either Riboflavin 5′-Phosphatethetic B2 I get massive heart thumps. I do have both single C677T and A1298C. I do eat a clean diet with lots of almonds and red meat. Any thoughts on why I cannot tolerate supplementing?

      1. Soak nuts like they used to In the old days and you don’t have the “antinutrient” problem.

    1. I’m not an expert but two possibilities come to my mind:
      – B2 has antimicrobial properties, maybe you have some chronic infection and are getting a Herxheimer reaction.
      – B2 is needed to utilize B1 and to convert B6 to its active form. A lack of B1 or B6 will cause increased endogenous production of oxalate by your body, and since you eat almonds which are extremely high in oxalate you will definitely have lots of it stored in your body, disrupting your metabolism in many ways. Now if the production of oxalate suddenly gets shut off this causes a drop in blood levels, and so the body jumps at the opportunity to throw some of this poison out and will often get a bit too much out of storage and into the blood at once, which can cause very unpleasant symptoms.
      The problem with almonds is not the lectin content, but the extremely high oxalate content. Our bodies can deal with a certain amount of oxalate per day, but not with such huge amounts. When too much oxalate has accumulated in your body you will end up deficient in sulphate and this will result in gut dysbiosis and leaky gut, and only then do lectins become a problem. I’m no longer sensitive to lectins now and my thyroid works normally too now that it no longer has oxalate crystals in it. Was that why yours was removed?

  16. Most supplements I see for riboflavin are 100mg or more, way more than your recommended 6 mg. Is that too much?

  17. Mind blown!! I first read this article a few days ago and filed it away in my mind under “stuff to remember in relation to MTHFR”. This morning my pregnant daughter who’s been struggling with recurrent UTI/Kidney infections (she’s also been seeing a urologist with a “take this antibiotic for the duration of your pregnacy to keep things in check and we’ll sort it out when you aren’t pregnant”) for months mentioned that the multi vitamin she had recently run out of had always helped and whenever she missed a day (or ran out) her issues would flare up. She also said she had quit taking D-mannose as it did not seem to help. I thought it was odd that a prenatal vitamin would have any effect so I stopped by to get her some more of that particular brand and to more carefully inspect the label. It turns out that Nature’s Plus Prenatal has 15 mg of B2 (riboflavin)! This woman has a slew of markers for MTHFR, has been in counseling for her hot mess of emotions, and although was not tested for MTHFR, her Dr. and I agreed, it was a safe assumption.
    Not only did her physical symptoms abate while on this particular multi vitamin, she was back to acting (and feeling) like her old self…noted by both myself and her therapist. Is it posdible MTHFR could effect an ability to fight infection? This is extremely encouraging to this mom of 9 (4 teens and a preteen with oppositional defiance, depression, anxiety…) also a newly certified Functional Medicine Health Coach! I’ll be following this closely. Thank you!

    1. She may find that 1000-2000mg of vitamin C per day will do as well as taking antibiotics constantly. Lowering or eliminating refined sugar would likely help a lot too.

    2. A d-mannose binding lectin deficiency, a genetic immunodeficiency, can also increase susceptibility to UTI’s and upper respiratory infections.

    3. Recurrent UTIs are usually due to oxalate, please look into this topic in some depth as there is a lot to learn. I would recommend that your daughter lowers the oxalate content of her diet very slowly while still pregnant and lactating, as a sudden drop would trigger oxalate dumping which would harm the baby. Having too much oxalate in your body isn’t exactly good for a developing baby either though.
      Don’t listen to the ignorant person recommending high dose Vitamin C, because if you take more than 250mg per day some of it will convert to oxalate. There may be some short term benefit but it isn’t worth the long term consequences.
      Quite probably the riboflavin affected the MTHFR enzyme and this will have had positive effects, but maybe also the B1 and B6 prevented some endogenous oxalate production by her body.

      1. Oh and of course it’s a bad idea to keep on taking antibiotics for recurrent UTIs, because you risk permanently killing off some of the strains of bacteria in your gut that degrade some oxalate for you. Many of these are lactobacilli and bifidobacteriae of which some can be re-seeded through probiotics, but the most important one is oxalobacter formigenes. Many common antibiotics kill this one and once you’ve lost it, there is currently no way to get it back, because it is a strict anaerobe and thus hard to put into a probiotic capsule. Then you will have to follow a very low oxalate diet rather than just a low one.

  18. When you say hearts are a good source of riboflavin, does that include chicken hearts and/or duck hearts too, or is this benefit exclusive to mammalian hearts?

  19. Would 6 capsules of Ancestral Supplements – Liver (per day) equal 1 daily dose of riboflavin? Thank you, this article is a wealth of information.

  20. Hi Chris, thank you for sharing this information! I am a little confused about the form of riboflavin that should be taken for the homozygous C677T mutation. Some recommend the activated form – riboflavin 5 phosphate and others recommend regular riboflavin. Is one better than another for this mutation? Thank you again for your information, Kimberly

  21. Hi. I’m still learning about all of this since I found out I have 2 mutations. Heterozygous., I’m taking mythlcobalin Bs and B12 through multivitamins one being smarty-pants organic for women . Not sure if I’m doing things right .just saw this post about riboflavin. I guess I need to see a pathway doctor. 🤷‍♀️🤦‍♀️😳🥺

  22. That sounds like a lot of liver. Would heavy metals levels in that liver not be an issue?

    1. Livers don’t store toxins, they just process them. That’s a myth borne of total ignorance about how the body works.

  23. Brewer’s yeast isn’t on your list but it seems to be very high in riboflavin. A lot higher than any of the vegetarian sources listed above.

  24. Do you have a perspective of unfortified nutritional yeast? Sure, kind of a processed food, but an easy win on the B2/B6 front. Thanks for all your work! Pretty crazy moment to be a human, derived from an environment now distant enough that we can’t see it, that assumed environment constants in shaping our genetic structure, and now experiencing a wholly different environment, to which we may or may not be arbitrarily adapted in a vast array of known and unknown ways.

  25. Hi Chris
    Did you come across any information about how much riboflavin is used up to convert 6mg of pyridoxine hydrochloride typically found in supplements into active form?
    Thanks
    Sapna

    1. I am interested in more information about this as well. There are only 2 options available to me from the company I order from here in British Columbia. One is 100mg of ‘riboflavin’ 90 caps/$7.50. The other is 50 mg of “BioCoenzymated Riboflavin 5′-Phosphate” or listed as “riboflavin 5′-phosphate sodium” for $8.48/bottle of 30 caps.
      To get even one gram per day would cost $6.33 per day for one person (X 2 for my husband) and require 20 caps per 1 gram!
      The non converted riboflavin option has 6 times the mg per bottle but if little is converted then not much point. This looks expensive to accomplish not matter how one looks at it. I think I will be finding a way to dehydrate and encapsulate liver powder, as well as swallow frozen raw pieces again as I once did. Pretty hard to choke down 4 ounces that way though! Liver is a difficult taste to get used to when one was a vegetarian most of ones life as well as 5 yrs of it vegan. I’ve managed to eat some now and then, but after a number of bites it’s hard not to gag. Will have to keep the nose pinched and try wash it down!

      1. “1 gram”?? you mean milligrams, right? You don’t want to take B vitamins in Grams, you’re gonna hurt yourself. In fact, some B vitamins are only good in MICROgrams (mcg)

  26. Thank you for this. Do you think the 6 liver capsules a week and eating liver alternatives every day, would be enough? How much meat and salmon would I need on top of the 6 liver caps would I need? Looks like a supplement might be in order.

    1. 6 liver capsules per *week* gives you practically nothing. You need 6 per *day* to equal one serving a week.

      1. Sorry, a typo on my behalf – it was meant to read 6 capsules a day!

        If I eat 6 capsules a day, how much of the additional sources would I require before needing to substitute?

    1. Very cool, but this product’s formulation is a little silly.

      For example, the “activated” B2 (a complete BS term) is worthless in its “activation” because the phosphate will be completely hydrolyzed before absorption.

      Meanwhile they use pyridoxine HCl, when they should have P5P. The phosphate of P5P will also be hydrolyzed, but what will be left over is pyridoxal, which, unlike pyridoxine does not have to be converted in the liver using riboflavin and a polymorphic enzyme to pyridoxal.

      Very, very backwards.

  27. Do you think that a daily dose of 6mg riboflavin is too much over a long term basis on top of a clean diet? I don’t eat liver often but plenty of the other foods mentioned.

    I just started taking Mitochondrial Nutrition PQQ from Restorative Formulations (https://www.restorativeformulations.com/products/rf-all-products/mitochondria-nutrition-pqq-60-caps/) and have been feeling much more energy, endurance, focus, and cognition. I haven’t noticed any side effects other then neon yellow urine which you disclosed in a recent podcast.

    Most of the B-Vitmains are included in this formula at significant levels about RDA. I am hetero MTFHR and also do your other recommendations (choline, glycine, creatine, etc.).

    Do you think a supplement with these levels could present issues over the long term? I don’t want to over do it.

    Thanks for all the great content!

    1. I don’t think 6 mg riboflavin is too much long-term.

      However, I do think 200 mcg selenium is too much long-term if you aren’t testing plasma selenium.

      The P5P in that product is a little high for someone to take without having a reason to, but doesn’t strike me as dangerous.

      1. Would you feel safer about taking only one capsule per day for a total of 100mcg selenium?

        I don’t want to build up toxicity but I would like to take this supplement long term as a convenient baseline support.

      2. Is a feeling of nausea a sign that a recent dose of selenium was too much? I can’t stand the smell let alone the taste. Same with the stronger B vits. Is this a forewarning to me to pay attention to? Or just a wimpy excuse on my part? I’d love it to be the former (so I don’t have to take the foul stuff… haha!!) xx

    1. It’s in the list of references. I just list them in the podcasts. If I get to it in the future with write-ups I’ll do in-text citations.

  28. Can kids take this riboflavin supplement and how much? My son is 11 years old, is compound heterous MTHFR, does not feel good most of the time and has no energy.

    1. I recommend scaling doses for kids according to Calories. So consider this recommendation 3 milligrams per 2000 Cal and adjust it according to Cal intake for children.

  29. Why sunlight disturbs B2 metabolism? I ask because we see people with adverse sun reactions with both Mast Cell disorders as well as both secondary and primary porphyria. Is there something related to vitamin D here? Many thanks. A

      1. Weird, I read that ultraviolet radiation can hurt the C677t enzyme also….hmmm maybe our ancestors lived in less sunny places and ate lots of meat??

  30. Great article, but it’s not a cause and effect kind of situation. Dr Ben Lynch can explain it way better than I can so I suggest you watch him on you tube. MTHFR may not be the only polymorphism you have, although getting your raw gene data and the interpretation is helpful it’s just another tool in your tool box. One very important missing link is that methylfolate and B12 work together to methylate and manage a number of things like choline, homocysteine synthetic supplements ingested along with sodium, magnesium, calcium and phosphorus all play an integral role.
    Oh, not sure either if serum riboflavin is the best method to identify levels…..
    Louise

    1. Louise,

      What do you mean “it’s not a cause and effect kind of situation”?

      Yes, it is cause and effect. That’s why taking 1.6 mg B2 *causes* a 40% decrease in homocysteine among MTHFR C677T homozygotes.

      I’m well aware of the interactions in the pathway. I’ve discussed them extensively in the resources listed at chrismasterjohnphd.com/methylation

      I *am* sure what the best test of riboflavin available is, and I discussed the rationale extensively on the riboflavin podcast: https://chrismasterjohnphd.com/2019/02/16/manage-riboflavin-status/

      Chris

      1. Thanks. I’m homozygous C677T and I’ve come to realize that all B vitamins are essential. I am now taking a B-complex that includes the right B12 and all the rest. I added Selenium, too.

  31. I have recently started taking Mitochondria Nutrition PQQ from Restorative Formulations (https://www.restorativeformulations.com/products/rf-all-products/mitochondria-nutrition-pqq-60-caps/) every day and feel a noticeable difference in my energy, cognition, focus, and endurance.

    I have taken many of the nutrients in this formula separately before, just not riboflavin that I’m aware of outside of a desiccated liver supplement. I’ve noticed my urine being more neon yellow earlier in the day after supplementing but no other side effects.

    I have MTHFR but only heterozygous. I follow most of your recommendations for methylation that you have listed and detailed. This formula has 6mg of riboflavin, do you think this might be too much to consume every day on top of diet over the long term? Same goes for the other B-Vitamins in this formula, do you feel they are overdone? Most are significantly over the RDA.

    I am active but not training like an athlete or anything. Just looking for a good overall safety net to my already clean diet and this formula really appears to check a lot of boxes. Riboflavin seems like a really interesting nutrient!

    Thanks for all you do!

  32. I get more than your recommended amount of riboflavin in my multivitamin as riboflavin 5-phosphate sodium. Is that sufficient? Also, just curious about a product that you recommend that I have purchased, Ancestral Supplement’s Grassfed Beef Organs. If I take the six recommended capsules, would that equate to a full serving of organ meat (I beleive you recomend 4oz)?

    1. That would equate to one serving a week, if you take them every day.

      The multivitamin should be sufficient, though if you have any impairments in energy metabolism (thyroid, adrenal, insulin) or poor magnesium status you might have poor retention and it would be best to spread it evenly across meals.

      1. Would you please post the references used to compose educational and medical treatment oriented post? It would be nice to have them to reference as citations in our own publications and research moving forward.

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