Vitamin B2 & Health
What is Vitamin B2 and What Does it Do?
This week, we will continue our exploration of the B vitamins with B2, also known as riboflavin. Riboflavin was first discovered as a yellow pigment in milk. (3) It is another water-soluble vitamin.
This important vitamin plays key roles in our ability to turn our food into energy, reduce oxidative stress/damage in the body, metabolize B6, folate, niacin, and iron, and metabolize medications and toxins. (1) This is not an insignificant list of accomplishments!
Functions:
Energy Production:
Riboflavin is directly involved in the production of energy from our food. Inside the mitochondria (the powerhouse of the cell) riboflavin in the form of FAD moves electrons around. This form of electrical energy is used to make ATP which is the chemical form of energy our bodies use. If you are interested in learning more about this process, it is taught in biochemistry courses as well as some biology and physiology courses. You can read an overview here or watch a video overview here if you like! (2)
Reducing Oxidative Stress:
As we remember from the previous article on vitamin E, oxidative stress results when there are more free radicals than antioxidants in a system. The result is inflammation, tissue damage, and disease. Anything we can do to reduce this oxidative stress is vital. Flavonoids, vitamin C, vitamin E, and a healthy lifestyle that avoids excess free radical production are options we have discussed so far this year. Now, let’s see where riboflavin plays its role.
Glutathione Recycling:
Glutathione is our main antioxidant inside cells. It protects fats inside our cells from being damaged by oxidation. Our bodies recycle glutathione regularly and riboflavin is needed in the form of FAD to do this. Without adequate levels of riboflavin intake, we cannot recycle our glutathione well enough, and damage can occur inside our cells - this is bad news! (3) When cells sustain enough injury, they die. When enough cells die, we reach the level of tissue injury which can then progress to organ injury, and system-wide complications.
Reperfusion Injury:
Reperfusion is the return of blood flow to tissues that have been denied blood. This can happen in several scenarios including physical injuries, stroke, and heart attacks. When blood returns to the area there is often an increase in free radicals and inflammatory chemicals which can create further tissue damage. Riboflavin has been shown in several animal studies to protect against this reperfusion damage. (3)
Uric Acid Production:
Yes, that uric acid - the same substance that can cause gout. Did you know that uric acid “is one of the most effective water soluble antioxidants in the blood”? (1) Uric acid, when in balance, is a very protective molecule. Situations that lead to excess uric acid production like consuming a lot of meat and alcohol tend to be inflammatory. We are often treating gout by reducing uric acid buildup with medications and avoiding purines which are nitrogen-containing molecules that are concentrated in organ meats, red meat, and alcohol. However, we get much better results when we also actively treat inflammation and oxidative stress.
Metabolism of Other Nutrients:
Different riboflavin metabolites (like FAD) are needed in the metabolism and activation of several nutrients including B6, niacin, and folate. This means that riboflavin deficiency can create the symptoms of a deficiency of B6, niacin, and folate!
This is of particular importance in those with a mutation in their 5,10-Methylenetetrahydrofolate reductase enzyme (MTHFR). Those with a mutation at the C677T loci (especially a homozygous mutation) are at increased risk of developing cardiovascular disease and certain cancers especially if their riboflavin and folate intakes are deficient.
Low levels of riboflavin can also interfere with iron levels. The correlation is clear, but the mechanism is not fully understood at this point.
Metabolism of Medications and Toxins:
Remember last year’s article about our Ever Loving Livers? In this article we outlined the many different roles our livers play, including metabolism of medications and toxins. Here we mentioned the cytochrome P450 enzyme family and their role in phase 1 detoxification. As a brief reminder, this phase makes molecules water soluble so that we can more easily transport them around and out of the body. Many oral medications benefit from this pathway becoming active after they are acted on by the liver. You probably guessed the punchline - we need riboflavin in the form of FAD to make cytochrome P450s work.
Disease Prevention:
As you can see, riboflavin plays a lot of roles in the healthy function of our bodies. Adequate levels are needed to prevent increased oxidative stress, turn our food into energy, activate some of our other nutrients, and detoxify our bodies.
When it comes to specific disease prevention, we see roles for riboflavin in preventing pre-eclampsia in those with C677T mutations of their MTHFR gene, cardiovascular disease, reperfusion injury following heart attack and stroke, and some cancers. (1)
Clinical riboflavin deficiency is called ariboflavinosis and can cause a rash inside and around the mouth including the tongue, seborrheic dermatitis (a moist scaly rash), growth of blood vessels on the cornea of the eye leading to issues with vision, and anemia. Ariboflavinosis is seen more often with alcoholism, anorexia, and dairy-free diets. This can all be prevented by meeting the daily recommendation for riboflavin.
Disease Treatment:
Diseases that benefit from treatment with riboflavin include: (1)
Cataracts
Migraines in adults
Trimethylaminuria (a condition that causes a fishy odor due to poor metabolism of choline)
Type II glutaric aciduria
ACAD9 deficiency
Brown-Vialetto-Van Laere syndrome
Hypertension in those with C677T mutations of their MTHFR gene
Corneal ectasia
Some cancers
Where to Find Riboflavin:
Like many other nutrients, humans cannot make our own riboflavin. We must consume it in our diets. Foods that are particularly rich in riboflavin include: eggs, lean meat, milk, and green leafy vegetables. (3) Refined grains are also often fortified with riboflavin. A multivitamin is another option for adding extra riboflavin.
Applications:
Wow, this is a lot of detail and a bit more information than the past few articles. Take a deep breath, and remember, you don’t need to memorize any of this!
First, if you do not include eggs, meat, or milk in your diet, consider a multivitamin/multimineral supplement. Next, aim for a minimum of 1.1 -1.3mg daily. The Linus Pauling Institute recommends 1.7mg daily, and since there is no known upper limit in how much you can consume safely, I also recommend aiming for 1.7mg.
Riboflavin is rapidly destroyed by light, so if you are choosing a multivitamin, look for one that has dark-tinted glass or an opaque bottle.
If you have a known MTHFR mutation (C677T), please be extra sure to get enough riboflavin! We will cover MTHFR mutations in the folate article in the coming weeks.
Additionally, consider extra riboflavin if you consume any of the following substances that can lower levels: (1)
Alcohol
Chlorpromazine
Tricyclic antidepressants
Quinacrine
Adriamycin
Phenobarbital
Next week, we will review Vitamin B3: Niacin
To our health!
References:
Higdon, J. “Riboflavin” Linus Pauling Institute (2000), https://lpi.oregonstate.edu/mic/vitamins/riboflavin accessed 9/29/2021
Bonora, M., Patergnani, S., Rimessi, A., De Marchi, E., Suski, J. M., Bononi, A., Giorgi, C., Marchi, S., Missiroli, S., Poletti, F., Wieckowski, M. R., & Pinton, P. (2012). ATP synthesis and storage. Purinergic signalling, 8(3), 343–357. https://doi.org/10.1007/s11302-012-9305-8
Ashoori, M., & Saedisomeolia, A. (2014). Riboflavin (vitamin B2) and oxidative stress: A review. British Journal of Nutrition, 111(11), 1985-1991. doi:10.1017/S0007114514000178
PubChem, “Flavin adenine dinucleotide” https://pubchem.ncbi.nlm.nih.gov/compound/643975#section=2D-Structure
Crash Course, “ATP & Respiration”, https://www.youtube.com/watch?v=00jbG_cfGuQ
CDC, “gout” https://www.cdc.gov/arthritis/basics/gout.html
CDC, “MTHFR Gene, Folic Acid, and Preventing Neural Tube Defects”, https://www.cdc.gov/ncbddd/folicacid/mthfr-gene-and-folic-acid.html