Your need for riboflavin (B2): MTHFR and other genetic variants

Riboflavin (Vitamin B2) is a water-soluble vitamin that is a cofactor for many enzymes in the body.  To put it in simpler terms: riboflavin is vitally important!

Riboflavin is a ribose sugar bound to a flavin molecule.  It is the precursor to FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide), which are coenzymes involved in numerous vital functions in our bodies. FAD is essential to the electron transport chain which is how your body produces energy in the mitochondria. FAD is also involved in detoxification as a cofactor for some CYP450 enzymes as well as for glutathione recycling.[ref]

Riboflavin also helps convert tryptophan to niacin, which in turn helps the body with vitamin B6.[ref]

Riboflavin is found in dairy products, eggs, liver, enriched flour, and in minor amounts in other foods. The US RDA is 1.6mg for adults, and most people are estimated to meet this with their daily food consumption.

If you don’t eat dairy, eggs, or liver, you may want to track your daily riboflavin consumption for a few days to see if you are getting the normal amount. Cronometer is a free online app that is great for keeping track of nutrients.

Riboflavin is absorbed from foods as they are broken down in the upper part of the small intestines. Excess riboflavin is excreted out through the kidneys and makes your pee yellow. [ref]

What are the signs of riboflavin deficiency?
Dietary insufficiency can cause angular cheilitis (cracks at the corners of the mouth), anemia, burning mouth, sore throat, and vision issues. A lack of riboflavin can also cause problems with iron absorption, leading to anemia.

People more likely to suffer from riboflavin deficiency include the elderly, women on birth control, vegans, and alcoholics. Riboflavin is also being investigated and used for cataracts.[ref][ref]

There is no known toxicity for taking too much riboflavin and there is not a safe upper limit set in the US.[ref]

Genetic variants that interact with riboflavin

There are several genetic variants that can cause an increased need for riboflavin.

MTHFR gene: codes for the enzyme needed to convert folate to methylfolate, a key component in the methylation cycle.

The C677T variant causes a change in the shape of the MTHFR enzyme and decreases its ability to bind to FAD.[ref] If you have high homocysteine (a marker for heart disease risk), several studies show that increasing riboflavin lowers homocysteine levels in those with the A/A genotype.  [ref][ref] Other research points to riboflavin lowering homocysteine levels only if vitamin B6 levels are adequate.[ref]

Additional research shows that low riboflavin status in women with MTHFR C677T

For those with the A/A genotype and high blood pressure, riboflavin (1.6 mg/day) lowered systolic blood pressure by 5 – 13 mmHg.  That is actually a pretty significant decrease from simply adding vitamin B2![ref]

Check your genetic data for rs1801133  (23andMe v4, v5; AncestryDNA):

  • G/G: typical
  • A/G: one copy of C677T allele (heterozygous), MTHFR efficiency reduced by 40%
  • A/A: two copies of C677T (homozygous), MTHFR efficiency reduced by 70 – 80%

Gene: FMO3
FMO3 (flavin-containing monooxygenase 3) variants can cause a decrease in the FMO3 enzyme, which breaks down certain nitrogen-containing amines and some sulfur-containing compounds. FMO3 is the primary way that the body breaks down trimethylamine. Decreased FMO3 activity can cause an increase in trimethylamine, which causes a fishy-smelling body odor.[ref]  Some people with mild FMO3 variants are helped with riboflavin.[ref]
These first four variants are more significant reductions in enzyme activity and are linked to TMAU (fish odor or strong body odor). Note that 23andMe doesn’t cover all the FMO3 variants that decrease the function.

Check your genetic data for rs28363581 (23andMe v5 only; ):

  • C/C: decreased FMO3 function
  • C/T: decreased FMO3 function
  • T/T: typical FMO3 function

Check your genetic data for rs3832024 (23andMe v5):

  • DD or -/-: decreased FMO3 function[ref]
  • DI or -/TG: decreased FMO3 function
  • II or TG/TG: typical FMO3 function

Check your genetic data for rs61753344 (23andMe v4, v5: AncestryDNA):

  • T/T: decreased FMO3 function[ref]
  • G/T: decreased FMO3 function
  • G/G: typical FMO3 function

Check your genetic data for rs1736557 (23andMe v4, v5; AncestryDNA):

  • A/A: decreased FMO3 function[ref]
  • A/G: decreased FMO3 function
  • G/G: typical FMO3 function

Check your genetic data for rs2266780 (23andMe v4, v5; AncestryDNA):

  • G/G: somewhat decreased FMO3 function [ref]
  • A/G: somewhat decreased FMO3 function
  • A/A: typical FMO3 function

Check your genetic data for rs2266782 (23andMe v4, v5; AncestryDNA):

  • A/A: decreased FMO3 function [ref][ref] increased risk of hypertension, especially in smokers [ref]
  • A/G: somewhat decreased FMO3 function
  • G/G: typical FMO3 function

Check your genetic data for rs909530 (23andMe v4 only ):

  • T/T: somewhat decreased FMO3 function [ref] (probably mild)
  • C/T: somewhat decreased FMO3 function
  • C/C: typical FMO3 function

Check your genetic data for rs909531 (23andMe v4 only):

  • C/C: somewhat decreased FMO3 function [ref]
  • C/T: somewhat decreased FMO3 function
  • T/T: typical FMO3 function


The electron transport chain is how your body produces most of its energy, in the form of A/TP, in the mitochondria of all of your cells.  This process is dependent on the FAD molecule, which is a flavin-containing molecule.  ETFDH codes for the electron-transferring-flavoprotein dehydrogenase, an enzyme that transfers electrons from FAD within the electron transport chain.  There are a few rare mutations that disrupt this enzyme, causing decreased energy production.[ref]

Check your genetic data for rs121964954 (23andMe i5007876 v4; AncestryDNA):

  • A/G: possibly pathogenic for multiple acyl-CoA dehydrogenase deficiency, riboflavin responsive [ref][ref]
  • G/G: typical

SLC52A3 Gene: (Riboflavin transporter, also known as C20Orf54)

The mutation listed below is possibly pathogenic for Brown-Vialetto-Van Laere, a rare neurological condition that is often normalized by high dose riboflavin.  [ref]

Check your genetic data for rs267606684 (23andMe i5008314 v4; AncestryDNA)

  • A/G: Brown-Vialetto – Van Laere syndrome possible[ref]
  • G/G: typical

SLC25A32 Gene: (encodes the mitochondrial FAD transporter)

Check your genetic data for rs147014855 (23andMe v4):

  • C/T: possibly pathogenic for exercise intolerance, responsive to riboflavin [ref] [ref]
  • C/C: typical


Diet and Supplements:

  • Dairy products and beef liver are naturally high in riboflavin. Three ounces of pan-fried liver give you 2.9 mg of riboflavin.
  • List of riboflavin content in various foods.
  • There are two forms of riboflavin in supplements:  riboflavin 5′-phosphatase, which is the active form and available online, and just plain riboflavin, which must be converted by the body.
  • Riboflavin is absorbed in the upper small intestines via a riboflavin transporter.  The guide for dietary reference intakes indicates that the body can’t absorb larger amounts of riboflavin at one time. When you take higher doses than your body can absorb, your urine will turn really yellow.

Additional Reading:


Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.