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
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?
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
USDA Food Composition Database: Nutrient Search
Wacker. Riboflavin deficiency and preeclampsia. 2000.
Lienhart. The human flavoproteome. 2013.
Masterjohn. The Antioxidant System.
Iinuma. Synthesis of riboflavin by intestinal bacteria. 1955.
Arumugam. Enterotypes of the human gut microbiome. 2011.
Bates. Human requirements for riboflavin. 1987.
McCormick. The fate of riboflavin in the mammal. 1972.
Balasubramaniam. Disorders of Riboflavin Metabolism. 2019.
Fairweather-Tait. Riboflavin deficiency and iron absorption in adult Gambian men. 1992.
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.
Colombo. Riboflavin and migraine: the bridge over troubled mitochondria. 2014.
Winters. Riboflavin requirements and exercise adaptation in older women. 1992.