Aging and Vitamins B2 ( Riboflavin ) and B3 ( Niacin )

Both vitamin B3 (niacin) and vitamin B2 (riboflavin) share with coenzyme Q10 the critical role of hydrogen movers in the mitochondrial energy equation. As fuel in the form of glucose is broken down via oxidation, hydrogen atoms are metabolized or "broken off" and "picked up" by vitamins B3 and B2, which are reduced, respectively, to form NADH and FADH2.
         
Essentially, every cell in the human body requires energy in the form of adenosine triphosphate, or ATP. Our cells can make ATP via two methods: anaerobically (in the cytoplasm) and aerobically (in the mitochondria).  Aerobic metabolism by far yields the greater amount of energy to the body.

We know that during times of extreme exercise such as running a marathon, cells can become depleted of oxygen, and anaerobic metabolism continues within the muscle cells. The by-product of this oxygen-depleted state is lactic acid, which builds up in the muscles and is reabsorbed in a couple days once the exercise stops and aerobic metabolism resumes.
          
Vitamin B3 and B2 deficiencies, however, can also compromise aerobic metabolism within the mitochondria.  That is because reduced vitamin B2, in the form of FADH2 and reduced vitamin B3, in the form of NADH, carry the hydrogen molecules produced during oxidation to the electron transport chain (for conversion to ATP.)
          
In medical school, we all memorized NADH and FADH2 as components of the Krebs cycle (aerobic metabolism) without realizing these are reduced forms of vitamin B3 and B2. Here's a recap of how NADH and FADH2 work. Reduced B3 and B2 (NADH and FADH2) carry hydrogen molecules (generated by the oxidation of acetyl CoA) to the inner mitochondrial membrane, where Coenzyme Q10 (located on the inner membrane) "kicks" these hydrogen protons into the space in between the two membranes (the electrons separated from the hydrogen molecules continue to move along the inner membrane, through the cytochromes, and eventually join with oxygen as the final acceptor to make water.) 

As the protons build up in between the two membranes, a gradient is formed, and the protons then flow from the intermembraneous space back into the inner mitochondrial space; this flow of protons is what energizes ATP synthase, also located on the inner mitochondrial membrane, to make ATP. This is also the process that is blocked by statin drugs via blockade of HMG-CoA reductase, which is a necessary enzyme to make Coenzyme Q10.

NADH (reduced vitamin B3) delivers 88 percent of the hydrogen atoms that ultimately make ATP via the electron transport chain. This is because for every mole of glucose oxidized by aerobic metabolism, 10 NADH are generated; each NADH makes 3 ATP for a total of an additional 30 ATP.

FADH2 (reduced vitamin B2) delivers 12 percent of the hydrogen atoms that ultimately make ATP via the electron transport chain. This is because for every mole of glucose oxidized by aerobic metabolism, 2 FADH2 are generated; each FADH2 makes 2 ATP for a total of an additional 4 ATP.

Vitamin B2 and B3 deficiencies are easy to detect clinically.  B3 deficiency presents most frequently with a bilaterally-symmetrical butterfly-shaped rash across the nose and cheeks.  B2 deficiency presents as angular cheilosis (cracking in the corner of the mouth) and redness around the eyes and eyelids.  B2 / B3 deficiencies also lead to hair loss and mouth sores; and a coated tongue is also frequently found in these individuals.
 
To recap, niacin or vitamin B3 is essentially responsible for 30 of the 38 potential ATP moles that can be made from one mole of glucose, via anaerobic metabolism and aerobic metabolism.  This nutrient, therefore, needs to be well understood by any medical practitioner, as it is a potential "bottleneck" of energy-production within the mitochondria.  Every cell needs ATP to do whatever it is that that particular cell does.  A lack of B3 therefore severely hampers any cell's ability to generate energy to perform its unique function, and a deficiency in B3 results in the conversion of acetyl-coenzymeA into cholesterol.
          
The RDA of vitamin B3 (about 20 mg/day) was determined in the 1950's and 1960's, by inducing pellagra in thousands of human subjects, and then measuring urinary metabolites of niacin to determine what daily requirement would prevent pellagra.  There are meager amounts of niacin in fruits and vegetables.  Niacin is found mostly in whole grains and nuts; processing (milling) of grains destroys most of the niacin in grains...and not too many people munch on raw sunflower seeds (a good source of niacin.)
          
The USDA library also documents the amount of niacin found in meats, which seems to be the greatest source of niacin.  This however, is pure presumption.  There is little to no niacin in meat.  There is tryptophan (5HTP) in meat, which is converted to niacin provided there is sufficient vitamin B6 or pyridoxine (every 60 mg of tryptophan can potentially make 1 mg of niacin, and it is this potential that is listed in the USDA nutrient charts in regards to recording the niacin available in meat. If you eliminate this presumption from the formula, you will readily find that most diets do not meet the RDA for niacin.)
         
The problem here is that much of the U.S. meat supply is laden with hormones, and hormones deplete vitamin B6 (that is because B6 delivers hormones to the active sites of the target cells.) Routine use of birth control pills and hormone replacement therapy further compounds the problem of B6 and hence niacin deficiency.
         
From the preceding it is obvious that we have very little information on desirable intakes of Vitamins B3 and B2 for seniors. The RDA is 20 mg for healthy males up to 50 years of age. This is likely an appropriate dose for any adult, male or female, having symptoms suggestive of mitochondrial deficiency along with a reasonable diet. Seniors often have illnesses and are on medications many of which may interfere with vitamin intake, particularly with water-soluble vitamins, which are not stored. Doses of niacin many times the RDA have been used for cholesterol reduction in tens of thousands of people.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

Updated December 2015
 

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