Episode 58: Chris Masterjohn, PhD talks about Why You Should Manage Your Riboflavin Status and How to Do It

Why You Should Manage Your Riboflavin Status and How to Do It

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Episode 58: Chris Masterjohn, PhD talks about Why You Should Manage Your Riboflavin Status and How to Do It

Riboflavin is the ultimate fat-burning nutrient. It makes even a bad MTHFR work right, and it keeps you looking young and beautiful forever.

Here’s everything you need to know about why you should manage your riboflavin status and how to do it.

In this podcast I join with Alex Leaf of Examine.Com. I focus on what riboflavin is and what it does, while Alex focuses on riboflavin supplements.

Going into this podcast I changed my mind about three important things:

  • While I had always discussed riboflavin as relevant to methylation and MTHFR, I had kept it in the back seat in my methylation protocol. Half way through recording this podcast I realized that it really deserves a front seat in my MTHFR protocol. In fact, it may be the case that there’s nothing wrong with the common MTHFR polymorphisms at all and that they only appear to hurt MTHFR activity because most of us aren’t getting enough riboflavin. And why aren’t we? Liver. Liver. We just have to eat liver.
  • In Testing Nutritional Status: The Ultimate Cheat Sheet, I had included HDRI’s erythrocyte glutathione reductase activity test as test for assessing riboflavin status. After doing the research for this podcast, I am now convinced that this test is only reliable as a marker of riboflavin status when the lab tests the enzyme activity with and without the addition of riboflavin, which HDRI doesn’t do. I will be revising the cheat sheet soon to rely solely on LabCorp’s whole blood riboflavin test for assessing riboflavin status.
  • I have, for years, believed that riboflavin 5’-phosphate (aka, flavin mononucleotide or FMN) supplements are better than plain old riboflavin, especially for people who are hypothyroid or have low adrenal status, since these conditions impair the activation of riboflavin to it’s 5’-phosphate form. After doing the research for this podcast I now believe that for healthy people it makes no difference and that for people with small intestinal pathologies, the cheaper, less fancy, plain old “riboflavin” is likely to be more effective.

In this podcast we being by considering the fictional stories of people who seem to have little in common. We then explain their stories by looking at the signs and symptoms of riboflavin deficiency. We consider the science of what riboflavin is, how it is used by the body, what it does for us, how to have great riboflavin status, and how to become deficient. We round this out with an extensive discussion of riboflavin supplementation.

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This episode is brought to you by Ancestral Supplements' “Living” Collagen. Our Native American ancestors believed that eating the organs from a healthy animal would support the health of the corresponding organ of the individual. Ancestral Supplements has a nose-to-tail product line of grass-fed liver, organs, “living” collagen, bone marrow and more… in the convenience of a capsule. For more information or to buy any of their products, go to https://chrismasterjohnphd.com/ancestral

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Riboflavin Show Notes

00:37 Introduction

01:46 Three things that I’ve changed my mind about while doing the research for this podcast

04:24 Cliff notes

14:13 Three stories of riboflavin deficiency

18:05 Signs and symptoms of riboflavin deficiency

21:31 Speculative symptoms of suboptimal riboflavin status

23:49 Chemical properties of riboflavin

27:22 Medical applications: infants with jaundice, eye surgery for keratoconus, and treatment of fungal keratitis

30:38 Chemical structure of riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD)

33:02 Riboflavin’s roles in the body: energy metabolism, the antioxidant system, methylation, detoxification, and other nutrient interactions

34:03 Riboflavin’s roles in energy metabolism

39:33 How the different macronutrients (carbohydrate, fat, and protein) affect the riboflavin requirement differently

46:05 Riboflavin’s role in the antioxidant system

50:12 Riboflavin’s roles in the methylation system

52:29 Riboflavin’s interactions with other nutrients: vitamin B6, niacin, and iron

55:47 Riboflavin’s roles in detoxification

57:44 Other riboflavin-dependent enzymes include NADPH oxidase, monoamine oxidase, and protein disulfide isomerase.

59:31 The physiology of riboflavin absorption

01:02:31 The physiology of riboflavin utilization and the importance of magnesium, ATP, thyroid hormone, adrenal hormones, and protein

01:06:43 The gold standard marker of riboflavin status is the erythrocyte glutathione reductase activity coefficient (EGRAC).

01:12:11 LabCorp’s whole blood riboflavin test, normalized to the concentration of blood hemoglobin, is the closest commercially available equivalent to the EGRAC.

01:14:02 Why urinary glutaric acid is not a specific marker of riboflavin status

01:14:54 Measuring riboflavin status should be done after an overnight fast, and biotin does not interfere with the test.

01:15:54 How the RDA for riboflavin was established

01:22:02 How much riboflavin is needed to optimize riboflavin status and maximally suppress the EGRAC?

01:27:25 Why high doses of riboflavin might be beneficial in cases of suboptimal magnesium, energy, thyroid, or adrenal status

01:31:04 Dietary sources of riboflavin

01:36:39 Free riboflavin is found in milk, fortified flours, and many riboflavin supplements.

01:38:55 Riboflavin is destroyed by light.

01:41:16 Riboflavin is produced in the colon, but it is unknown how much this contributes to systemic riboflavin status.

01:43:55 Factors that interfere with riboflavin status and utilization

01:51:02 Genetic defects in riboflavin metabolism and transport

01:53:50 How common is riboflavin deficiency and suboptimal riboflavin status?

01:58:36 Riboflavin supplementation for iron deficiency anemia

02:00:29 The relationship between riboflavin and the MTHFR C677T polymorphism and effects on homocysteine and blood pressure

02:09:32 Riboflavin supplementation and exercise performance

02:14:30 Whether or not riboflavin supplementation could impair adaptations to exercise

02:18:25 Riboflavin supplementation for migraines

02:25:06 Rapid fire questions

02:25:21 Does it matter whether we take free riboflavin or riboflavin 5’-phosphate?  

02:26:51 Should riboflavin be taken with food?

02:30:28 How often should you take riboflavin?

02:32:20 Does it matter if you take riboflavin in one dose or divided doses?

02:33:13 Are there any adverse effects of riboflavin supplements?

Riboflavin-Rich Foods

There are five tiers of riboflavin-rich foods:

 

  • Tier 1: Liver (2-5 mg/100g; lamb liver is best, New Zealand liver, perhaps due to pasture-feeding, is better than US liver)
  • Tier 2: Kidney, heart, and almonds (1-2 mg/100g)
  • Tier 3: Red meat, cheese, eggs, salmon, mushrooms, seaweed, sesame, wheat germ and bran (0.4-0.5 mg/100g)
  • Tier 4: Other meats and fish (0.2-0.4 mg/100g) and milk (0.2 mg/100g)
  • Tier 5: Whole grains, nuts, seeds, legumes, and vegetables (0.1-0.3 mg/100g)

 

Refined grains are fortified by law and usually would occupy tier 3.

Fat has no riboflavin. Refined sugar and unenriched refined flour have no riboflavin. Fat and sugar will displace riboflavin in the diet and make it all the more important to eat foods from the top tiers.

The RDA for riboflavin is 1.3 mg/d for adult men and 1.1 mg/d for adult women, adjusted upward for pregnancy and lactation, adjusted downward for youth.

I recommend adolescents and adults aim for 2-5 mg/d and that children adjust downward based on energy intake rather than body weight by getting 1-2.5 mg riboflavin for every 1000 Calories.

Blood Tests for Riboflavin

I recommend using LabCorp’s whole blood riboflavin. Quest’s plasma riboflavin should not be used.

For those willing to do a little experimentation, I believe it is possible that an improvement over LabCorp’s range can be obtained by estimating the erythrocyte riboflavin and correlating it with the values found in the scientific literature for the erythrocyte glutathione reductase activity coefficient, which is the gold standard marker of riboflavin status but which is not commercially available.

To run this calculation, get a CBC at the same time as the whole blood riboflavin.

Then, plug the values into this calculator:

This should give a result that is between 0.3 and 1.5. If it is way out of that range, there is a calculation error.

If this approach works, we should consider anything above 0.7 very good status, with 0.5 representing early deficiency and 0.4 representing moderate to severe deficiency, without ever seeing values below 0.3.

If you carry out the math, please let me know the results in the comments, and let me know how your results were similar or different from simply using LabCorp’s own range for riboflavin status.

Riboflavin References and Research

The Riboflavin chapter of Modern Nutrition in Health and Disease.

The Riboflavin section of the DRI report (Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline.)

The Linus Pauling Institute Micronutrient Information Center: Riboflavin

Berg, Biochemistry.

USDA Food Composition Database: Nutrient Search

Wacker. Riboflavin deficiency and preeclampsia. 2000.

Heelis. The photophysical and photochemical properties of flavins (isoalloxazines). 1982.

Lienhart. The human flavoproteome. 2013.

Masterjohn. The Antioxidant System.

Cashman. Some distinctions between flavin-containing and cytochrome P450 monooxygenases. 2005.

Tu. Oxidative protein folding in eukaryotes: mechanisms and consequences. 2004.

Said. Riboflavin uptake by the human-derived liver cells Hep G2: mechanism and regulation. 1998.

Said. Riboflavin uptake by human-derived colonic epithelial NCM460 cells. 2000.

Said. Uptake of riboflavin by intestinal basolateral membrane vesicles: a specialized carrier-mediated process. 1993.

Said. Recent advances in transport of water-soluble vitamins in organs of the digestive system: a focus on the colon and the pancreas. 2013.

Daniel. Hydrolysis of FMN and FAD by alkaline phosphatase of the intestinal brush-border membrane. 1983.

Iinuma. Synthesis of riboflavin by intestinal bacteria. 1955.

Arumugam. Enterotypes of the human gut microbiome. 2011.

Hoey. Studies of biomarker responses to intervention with riboflavin: a systematic review. 2009.

Bates. Human requirements for riboflavin. 1987.

Hustad. Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation. 2002.

Zempleni. Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans. 1996.

Choe. Chemical Reactions and Stability of Riboflavin in Foods. 2006.

McCormick. The fate of riboflavin in the mammal. 1972.

Anandam. Effect of the proinflammatory cytokine TNF-α on intestinal riboflavin uptake: inhibition mediated via transcriptional mechanism(s). 2018.

Balasubramaniam. Disorders of Riboflavin Metabolism. 2019.

Wallace. Multivitamin/mineral supplement contribution to micronutrient intakes in the United States, 2007-2010. 2014.

Madigan. Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people. 1998.

McKinley. Effect of riboflavin supplementation on plasma homocysteine in elderly people with low riboflavin status. 2002.

Fairweather-Tait. Riboflavin deficiency and iron absorption in adult Gambian men. 1992.

McNulty. Riboflavin Lowers Homocysteine in Individuals Homozygous for the MTHFR 677C→T Polymorphism. 2005.

Jusko. Absorption, metabolism, and excretion of riboflavin-5′-phosphate in man. 1967.

Dainty. Quantification of the bioavailability of riboflavin from foods by use of stable-isotope labels and kinetic modeling. 2007.

Hustad. Riboflavin as a determinant of plasma total homocysteine: effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. 2000.

Jacques. The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. 2002.

McNulty. Impaired functioning of thermolabile methylenetetrahydrofolate reductase is dependent on riboflavin status: implications for riboflavin requirements. 2002.

Moat. Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the MTHFR (C677T) genotype. 2003.

Guenther. The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. 1999.

García-Minguillán. Riboflavin status modifies the effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms on homocysteine. 2014.

Colombo. Riboflavin and migraine: the bridge over troubled mitochondria. 2014.

McNulty. Riboflavin, MTHFR genotype and blood pressure: A personalized approach to prevention and treatment of hypertension. 2017.

Wilson. Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial. 2013.

Horigan. Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C–>T polymorphism in MTHFR. 2010.

Wilson. Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up. 2012.

Manore. Effect of physical activity on thiamine, riboflavin, and vitamin B-6 requirements. 2000.

Winters. Riboflavin requirements and exercise adaptation in older women. 1992.

Powers. Bicycling performance in Gambian children: effects of supplements of riboflavin or ascorbic acid. 1987.

Tremblay. The effects of a riboflavin supplementation on the nutritional status and performance of elite swimmers. 1984.

Weight. Vitamin and mineral supplementation: effect on the running performance of trained athletes. 1988.

Hoffman. A Placebo-Controlled Trial of Riboflavin for Enhancement of Ultramarathon Recovery. 2017.

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15 Comments

  1. Hi Chris,
    Q about Riboflavin , calcium and parathyroid. If I have high blood calcium due to poor functioning parathyroid, would supplementing with Riboflavin help improve this condition or would it make it worse?

  2. Hi Chris, this is a little exciting for me. I have many of the symptoms linked to low riboflavin. My most concerning one is low iron, not responding to supplementing.
    How long would you expect to see iron increase in lab results after starting riboflavin supplementation?
    Thanks!

    1. There are many factors beyond B2 status. But if it helps, my ferritin level was 9 (male) and it took me over 2 years of B2 and iron supplementation to get it into normal. I also am missing my colon and am likely celiac . I ran out of B2 while supplementing it, so as I said a lot of individual factors.

  3. Hi Chris,

    I am heterozygous for MTHFR and have suffered from and mostly recovered from a 3 year mold injury over the last few years. I have taken methyl B12 years ago with no results. Last week, I began taking methyl B9 along with the methyl B12 and had some interesting results. Within 30 minutes, my vision changed quite a lot. Colors became brighter, and my vision more clear. My mental status became more clear. This went on for three days, and was a bit overwhelming. I would describe it as my brain being on fire, but in a good way. Just wondering what your thoughts are on this, if any.

  4. Not one word in this irresponsible page about the study showing that supplemented riboflavin, yes the ordinary vitamin B2, can destroy the lenses of the eye at doses only moderately above daily needs.

    Riboflavin is an awful vitamin, it’s the only B vitamin I refuse to take.
    Photoreceptor damage following exposure to excess riboflavin, by Eckhert CD1, Hsu MH, Pang N.
    Direct link on Pubmed:
    https://www.ncbi.nlm.nih.gov/pubmed/8270030

    1. This is an interesting point. There are a lot of studies showing the benefits of 3x RDA for prevention of cataracts. I have not read the study that you mention and am careful not to read too much into an abstract. I believe that it found that high doses of B2 was related to thinning of the photoreceptor layer in the retina. Of course, difference between species, whether the results were manipulated (purposely or not) by excluding other dietary antioxidants and other variables would be interesting to know. It will remain to be seen whether people with migraine who take 400mg daily are at increased risk for macular degeneration or other retinal disease. A very quick google search did not turn anything up but that does not mean that it is not ¨a thing¨.

  5. Fortunately, I tested my B2 status at the same time as a CBC a few weeks ago, so I gave your calculator a shot. Came up with 1.2. Value for B2 whole blood was 184 with the range being 137-370. Perhaps, having low hemoglobin made my status look not as good without taking into account my level of hemoglobin. I hadn’t flagged B2 as a problematic nutrient, but this gives me greater confidence that B2 status is pretty good. Thx!

  6. Hi Dr. Masterjohn,

    I am grateful for your website, you have a lot of helpful information here. Thank you so much. I am suffering a great deal from Hashimoto’s. I’m on the PHD diet which has helped me in so many ways, I can’t be more thankful to Paul Jaminet, I approached the PHD template when I was very weak. There has been a big improvement physically, but mentally, I’m suffering from terrible paranoia. My first experiences with this paranoia started when my endocrinologist overdosed me on T4 twice. It had went away. But now, it seems to coincide with PMS, and just seems to get worse and worse every period. I wonder if this was a result from the overdose, but I also suspect part of this issue is also a lack of progesterone. I have a history of fibroids and adenomyosis. Just the same, I can’t seem to shake this paranoia off anymore. It’s always there. I have one of the MTHFR C677T mutations. And I have one of the COMT H62H/VI58M mutations. Not sure if this could be exacerbating things, it’s all speculation. I had done 23andme a couple of years ago. Paul mentioned to me what you reported on Riboflavin, and I’d like to get tested for this. I don’t have scratches at the corners of my lips, but nonetheless, I’d like to find out. I’m in Canada so I can’t do it with Labcorp. How would I go about asking my laboratory for the proper riboflavin test? You mention whole blood and not plasma, should I specify in this manner? So basically I need to do a Riboflavin test, a CBC in order to get a result for my hemoglobin, and is that all?

    I appreciate your time.

  7. Hi Chris,
    Thanks so much for this. I have MTHFR and many other SNPs in the methylation pathway. The first time I supported the pathway, I got swollen and split tongue. The second, rashes, conjunctivitis, and a. cheilitis. B2 never came to mind as was supplementing the Bs. Finally, I decided to take B2 until urine changed colour. First day 1800 mg and the second 1600 mg (100mg/hr). I have since this time, been told that I may be celiac, have had my colon removed for polyposis and live with SIBO. No gram+ and have non-Candida yeast. My ferritin level was 9 and it took me 3 years to get it into the normal range. Supplementing hydrocortisone and thyroid meds. My aggressive support of the methylation pathway allowed me a 90% recovery from CFS. Perhaps a damaged gut contributing to a sub-optimal level of B2, setting the stage for other health problems. Only time to relay part of my health problems here. Could I just take enough B2 to change the colour of my urine and then back off a bit? It would exceed 300 mg a day and possibly 1+ gm. Sublingual tastes terrible. 64 year old male. All advice received considered non-medical.

  8. Hi Chris,

    What are your thoughts on Genova’s functional deficiency measurements of B2 on the ION panel?

    If fine there then we’re definitively good on B2?

    Thanks

    1. They are dubious and not definitive about anything. I strongly recommend avoiding the interpretive part of the panel.

  9. Chris,
    Since listening to this podcast I realised that I have had (in the past) many of these syptoms of deficiency including pre-eclampsia in both my pregnancies and unexplained anemia. I do take a b-complex from time to time so likely not too deficient now. I have sibo and other digestive problems so I assume this is why the deficiency. I went out and got the NOW brand 100 mg riboflavin to try. Taken it 4 days in a row and when I go to bed I feel like how I feel when I’m over-caffienated! So tired but wired and unable to fall asleep, waking up many times through the night. Why would this cause this? I have googled the heck out of it and coming up with nothing!
    Thanks!

    1. Probably correcting a deficiency too suddenly. See if you can get low-dose and titrate your way up slowly.

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