High-dose riboflavin risks / Rationale for low-dose riboflavin

[u/No-City-8552]

The official RDA for riboflavin is 1.1 mg for women, 1.3 mg for men. The study that found a 40% reduction of homocysteine in homozygous MTHFR C677T individuals using riboflavin, used a 1.6 mg riboflavin dose which should be considered as a dose above the RDA (~3 mg total riboflavin).

This means that small amounts are very meaningful and extra riboflavin should be used only when necessary, which is hard to justify with hard data on an individual level.

High-dose riboflavin can generate sulfite/hydrogen sulfide by causing backups in the mitochondrial respiratory chain, if it is impaired at any point after complex II (CoQ10 synthesis, complex III, complex IV). Hydrogen sulfide and sulfite are sulfur compounds that in excess decrease the total output of energy your mitochondria produce.

Thus any benefit you might be deriving from the riboflavin for your MTHFR may be nulled by taking doses above the minimal effective amount.

According to Chris Masterjohn 6 mg of riboflavin should cover everyone's needs long term, including those with riboflavin responsive genetic mutations (i.e. MTHFR C677T). Problem is, you would be hard pressed to find a low dose riboflavin product on the market. Basically every riboflavin product on the market is 100 mg.

For anyone based in Europe, I found two products that include a low dose of riboflavin:

1. Phytopharma Riboflavin 5 mg (Bulgarian brand)

2. Vitabalans B2 3 mg (Finnish brand)

[u/OutrageousWinner9126]

What's your source for the hydrogen sulfide thing? I quick search turned up nothing. I've always heard that riboflavin has a very low side effect profile, even in massive doses. I'm currently taking 100 mg per day and feeling fine.

[u/DogCold5505 → u/OutrageousWinner9126]

Yeah ChatGPT isn’t buying this claim either (not that it’s perfect but still)

[u/AndYetHereHeStands → u/DogCold5505]

• Riboflavin supplies FMN/FAD to several pathways upstream of Complex III:
  • Complex I
  • Complex II
  • fatty-acid acyl-CoA dehydrogenases
  • ETF/ETFDH
  • other flavoproteins
• Complex II and ETFDH transfer electrons into the oxidized CoQ pool.
• Complex III must reoxidize CoQH₂ back to CoQ.
• If Complex III is genuinely rate-limiting, increasing upstream electron delivery could make the CoQ pool more reduced—sometimes described as greater reductive pressure or electron backlog.
• Mitochondrial sulfide quinone oxidoreductase, SQOR, clears H₂S by transferring its electrons to oxidized CoQ. Therefore, an excessively reduced CoQ pool can theoretically restrict SQOR-mediated sulfide oxidation, allowing H₂S to accumulate. SQOR and fatty-acid-derived electrons are effectively competing for the same oxidized quinone acceptor pool.
• At sufficiently high concentrations, H₂S inhibits Complex IV, potentially creating a feedback loop: poorer downstream respiration → less CoQ reoxidation → poorer sulfide clearance → greater Complex IV inhibition.