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Riboflavin (Vitamin B2), MTHFR, and Genetics

Key takeaways:
~Riboflavin (vitamin B2) is a water-soluble vitamin that is a cofactor for many enzymes in the body.
~It is vital for energy production in the mitochondria and is also a key component of your body’s detoxification system.
~ Genetic variants can increase your need for riboflavin. Interestingly, research shows that riboflavin is incredibly important for people with MTHFR variants.

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What is riboflavin and why is it important?

Riboflavin, also known as vitamin B2, is synthesized from a ribose sugar bound to a flavin molecule. Thus the name ribo-flavin.

This is an essential vitamin for many important cellular functions. Riboflavin 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 an essential component of the electron transport chain, which is how your body produces energy in the mitochondria.

  • FAD is important for producing energy both from carbohydrates and through fatty-acid oxidation.[ref]
  • FAD is also involved in detoxification as a cofactor for some CYP450 enzymes as well as for glutathione recycling. FAD can participate in many different reactions in the body because it can easily donate and accept electrons. It can exist in different redox states (FADH2, FADH).[ref]

Within the mitochondria, FAD and FMN are also integral to activating the various enzymes that protect cells from oxidative stress, thus making adequate riboflavin essential for healthy mitochondria. Conditions that are related to mitochondrial dysfunction and reliant on FAD and FMN include Parkinson’s disease, Alzheimer’s, migraines, Complex I deficiency, Alper’s syndrome, multiple sclerosis, and Kearns Sayre syndrome.[ref]

Riboflavin deficiency can also play a role in mitochondrial dysfunction in the development of cardiovascular problems.[ref]

Riboflavin also helps convert tryptophan to niacin (vitamin B3), which in turn activates vitamin B6.[ref]

What are the symptoms of riboflavin deficiency?

A lack of riboflavin can show up as:

  • angular cheilitis (cracks at the corners of the mouth)
  • anemia
  • burning mouth
  • sore throat
  • cataracts

Riboflavin deficiency can also cause problems with iron absorption, leading to iron-deficiency anemia.

Who is at risk of riboflavin deficiency?
People more likely to suffer from riboflavin deficiency include the elderly, women on birth control, vegans, and alcoholics.[article]

Mothers who are breastfeeding may also need more riboflavin because breast milk contains a lot of riboflavin and FAD.[ref]

For most people eating a balanced diet, full-on riboflavin deficiency is considered rare. Most people meet the recommended daily allowance of 0.9-1.3 mg/day.[ref]

However, there is a difference between not having a severe deficiency and getting an amount that is optimal for your specific needs, taking into account genetics and lifestyle.

Riboflavin absorption from foods and transport:

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.

Riboflavin is absorbed from foods as they are broken down in the upper part of the small intestines, so people with intestinal disorders that inhibit absorption could have problems with riboflavin deficiency.

Additionally, riboflavin must be transported within cells and into the mitochondria. Riboflavin-specific transporters are found on the outer membrane of the mitochondria. Rare mutations in this transporter (SLC52A2 gene) cause Brown-Vialetto-Van Laere syndrome, which is a rare neurological order that may be helped by riboflavin supplementation in some cases.[ref]

Benefits of supplemental riboflavin:

Clinical trials are an excellent way to know if a supplement is effective for most people. Genetic variants (below) can also clue you in as to whether you may need more riboflavin than normal.

Here’s what randomized clinical trials show:

Concussion recovery:
A randomized placebo-controlled trial investigated the efficacy of supplemental riboflavin for concussions. The trial involved 52 participants with sports-related concussions. Half took 400 mg/day of riboflavin and half received a placebo. The riboflavin group recovered twice as fast (10 days vs. 22 days).[ref]

Numerous studies and clinical trials have investigated high-dose riboflavin supplementation for migraines. While riboflavin may not be a panacea for everyone with migraines, it is inexpensive, non-toxic, safe, and effective for some migraine sufferers. For example, one study found that 400 mg/day of riboflavin cut migraine frequency in half after three months of treatment. (This is better than trial outcomes for many expensive migraine prescription medications and injections that have serious side effects!).[ref][ref][ref]

Eye health:
Riboflavin is also being investigated and used for preventing cataracts.[ref][ref]

Throat health:
Riboflavin is also important in the esophageal mucosa. A study in China examined the effects of using riboflavin-fortified salt in certain townships. The groups that received the riboflavin-fortified salt had lower rates of esophageal cancer.[ref]

Inflammatory Bowel Disease:
In patients with Crohn’s disease, riboflavin (100mg/day) decreased inflammatory markers significantly in three weeks.[ref]

Riboflavin supplementation and safety:

Vitamin B2, riboflavin, is a water-soluble vitamin. There is no known toxicity for taking too much riboflavin and no upper limit set in the US.[ref]

Excess riboflavin is excreted out through the kidneys and makes your pee yellow — really yellow.[ref]

Riboflavin Genotype Report:

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Lifehacks for boosting riboflavin:

Riboflavin Supplements:

There are two forms of riboflavin in supplements: riboflavin 5′-phosphatate, which is the active form, and just plain riboflavin, which must be converted by the body.

Riboflavin is available in two forms:

  • riboflavin 5′-phosphatate (R5P), the active form
  • riboflavin (B2), which must be converted by flavokinase

Both are inexpensive supplements, so it doesn’t cost a lot more to get the R5P active form. There is no known upper limit for riboflavin supplementation.[ref]

Member Content:

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Why join Genetic Lifehacks?

~ Membership supports Genetic Lifehack's goal of explaining the latest health and genetics research.
~ It gives you access to the full article, including the Genotype and Lifehacks sections.
~ You'll see your genetic data in the articles and reports.

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.