Vitamin B3- Niacin or Nicotinamide

Ball-and-stick model of the niacin molecule, a...

niacin molecule, also known as Vitamin B 3 and nicotinic acid

Vitamin B3 is another one of the water-soluble B vitamins. It was first discovered in 1873 by Hugo Weidel during his studies of nicotine. Vitamin B3 is essential in multiple steps in metabolism and is needed for good adrenal gland and nervous system function. It is mostly obtained in the diet from animal sources such as chicken, beef, and fish. Liver and kidney and heart have the highest amounts. The best plant sources include shiitake mushrooms, nuts, whole grains, beans, avocados and dates. The body can also synthesize Vitamin B3 using the amino acid tryptophan.  Interestingly vitamin B3 deficiency became epidemic when corn started being adopted by Europeans as a food source after the discovery of the Americas (corn is native to central america and therefore was unknown in Europe until the 1500s). The Mayans and other native americans that ate corn did not have vitamin B3 deficiency. This was because they cooked the corn using a process called nixtamalization where they cook it in a limewater (calcium oxide lime, not the fruit) making it very alkaline. This made the corn more easy to grind and improved the flavor. However, it also released the Vitamin B3 which is otherwise bound and not bioavailable in corn and allowed it to be absorbed by the body, hence preventing vitamin B3 deficency in Mayans and other native americans. However, the Europeans who adopted corn did not understand the benefit of nixtamalization and therefore did not use this process, and an epidemic of vitamin B3 deficiency ensued.

The recommended daily allowance is approximately 14 to 16 mg/day. The upper tolerable limits is about 35 mg/day but the only side effect to this is skin flushing. Not until doses as high as 2000 mg or more are significant side effects seen, and even then are rare. Some liver toxicity, skin irritation or eczema, heart arrhythmias, increased blood glucose, eye problems, birth defects if given to pregnant women, and indigestion have all been reported. Supplements of Vitamin B3 come in two forms. Niacin is what is used most commonly by physicians to decrease cholesterol. It is used at very high doses (sometimes as much as 3000 mg) and can cause significant side effects at those doses and almost always causes flushing. Nicotinamide is what is used in most dietary supplements found in stores without a prescription. Niacin is converted into nicotinamide by the body so it has the same nutritional value. However that conversion plays a key role in lowering the cholesterol and causing flushing so nicotinamide does neither of these. Nicotinamide has much lower risk for toxicity as well.

Mild niacin deficiency can slow the metabolism causing fatigue and intolerance to cold. Severe deficiency causes what is referred to as pellagra. Pellagra causes a constellation of symptoms including diarrhea, skin irritation and darkening, inflammation of the mouth, dementia and other mental disturbances, and eventually death if not treated.

Niacin has been used since the 1950s as a cholesterol drug. Many studies have been done on the topic the best of which is likely the multicenter placebo controlled trial by Canner et al. With 3 grams of niacin a day subjects saw a 27% reduction in heart attack and 26% reduction in stroke and the cholesterol panel improved significantly as compared to placebo. 9 year follow-up of subjects showed an 11% reduction in mortality as compared to placebo. Overall the benefits seem clear but its role in combination with other cholesterol lowering drugs, more specifically with statins such as Lipitor,Zocor, and Crestor, is still being worked out. Also, the very high doses needed for cholesterol lowering does cause significant flushing which decreases compliance. However, it has not been looked at yet to see if lower doses that may not have as dramatic effect on cholesterol levels may still show stroke and heart attack prevention by other mechanisms. I feel this is an open question that should be addressed.

Test tube studies are showing evidence that vitamin B3 deficiency may increase the risk for cancer. Vitamin B3 deficiency seems to be associated with instability of genes which is a first step to forming cancer. A 1999 study by Jacobson et al from the University of Kentucky showed that one part of this may be vitamin B3’s role in supporting the tumor suppressor gene p53. They also showed a clear correlation of low vitamin B3 in tissues of people who had increased skin tumors such as squamous cell carcinoma. Kirkland from the University of Guelph in Canada also further explained how Vitamin B3 may decrease the risk for cancer (see link below).  A study done by Dr. Yong with OSHA (the national institute of occupational safety and health) in 2011 of 81 pilots who were exposed routinely to ionizing radiation due to their work found that those with the higher intake of Vitamin B3 had a significantly lower rate of DNA damage. However this was merely observation and not a randomized controlled trial so the effect cannot be definitively linked to Vitamin B3. Similar studies looking at Vitamin B3 intake in those with esophageal and throat cancer found a 40% reduction in risk in those eating 5 to 6 mg more per day.

Early data did show promise for Vitamin B3 to possibly treat and/or prevent type 1 diabetes. However this was followed up with good randomized trials including by Lampeter et al. and Greenbaum et al and unfortunately they found no benefit. The data when taken together show that it is possible that Vitamin B3 actually does help prevent destruction pancreatic insulin secreting cells that leads to diabetes type 1. However Greenbaum’s study showed that this effect may be offset by an increase in insulin resistance caused by high dose Vitamin B3. Basically you may be trading type 1 diabetes for type 2. This is still an open question.

The association of mental issues with pellagra has led some to look into niacin and mental conditions such as schizophrenia. Interestingly it was found that Schizophrenics do show less tendency to flushing when treated with niacin. Messamore from the Portland VA in a 2012 study showed that severity of schizophrenia correlated well with less tendency to flushing with niacin. Dr Puri in 2001 showed that this reaction has a 90% sensitivity and 75% specificity to schizophrenia and it has actually been proposed to use it as a diagnostic tool for schizophrenia. A randomized controlled trial of Vitamin B3 supplementation by Dr. Ramsay et al in 1970 was done with newly admitted schizophrenic patients and found no benefit, however I found no mention of the number of patients. Conversely, Hoffer et al in 1957 did a trial of 30 schizophrenics and found a 80% recovery in the vitamin B3 group vs 30% recovery with placebo. In a follow-up study by Dr. Hoffer he found 79.5% vs 41.9% recovery in the niacin group vs placebo group respectively. Morris et al in a 2004 study also showed that higher dietary intake of Vitamin B3 decreased the risk for Alzheimer’s disease dramatically. And studies as far back as 1953 and one in the 1970s showed some benefit of nicotinamide on depression but have never been followed up with any good randomized controlled trials.

A study by Dr. Melton all the way back in 1943 also showed a dramatic improvement in asthma is subjects treated with niacin. However, to the best of my knowledge this study was never followed up with a randomized controlled trial. In fact the only other trial I can find exploring the matter was a 1974 study by Dr. Bekier that showed a decreased allergic response in guinea pigs treated with nicotinamide.

Also a 2006 study out of the University of Pittsburg laid out the benefits of nicotinamide for inflammatory skin conditions such as acne and rosacea.

Overall vitamin B3 shows a lot of promise. I feel one main issue may be our overemphasis on niacin while neglecting the less toxic nicotinamide. I feel we need to investigate to see if we can get the same heart attack and stroke prevention (our real goal) from nicotinamide as we do with niacin. And nicotinamide’s role in the treatment of Alzheimer’s, schizophrenia, depression, bipolar disorder and other common psychiatric disorders needs to be determined. Lastly, vitamin B3’s role in treating acne and rosacea is definitely needs to be investigated further.

References

Vitamin B3 and tumor suppressor gene p53

Kirkland study on Vitamin B3 and cancer formation

OSHA pilot study

Vitamin B3  and throat cancer

Vitamin B3 and esophageal cancer

1998 Lampeter Diabetes type 1 and vitamin B3 study

Greenbaum study showing increased insulin resistance with Vitamin B3 high dose

Schizophrenia and skin flushing from Vitamin B3

Schizophrenia skin flushing Dr. Puri study

Vitamin B3 and Alzheimer’s

Dr. Melton 1943 study on Asthma and niacin

Guinea pig asthma and Vitamin B3 study

Article on Dr. Hoffer’s studies on Vitamin B3 and schizophrenia

Nicotinamide for acne and rosacea

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Vitamin B2- Riboflavin

English: One milliliter of (approximately) 0.1...

One milliliter of riboflavin

Next up in our vitamin march is Vitamin B2, also known as riboflavin. Riboflavin in our diet mostly comes from meat, dairy products, eggs, green leafy vegetables, almonds, or mushrooms. Yeast, liver, and kidney are particularly rich in riboflavin. Also, like thiamine riboflavin is found in cereal grains such as wheat and rice but again is mostly in the outer portion or the germ and therefore much of it is lost in processed grains (yet again, it is important to eat whole grains when possible). Riboflavin is easily destroyed by UV light so some recommend buying dairy products in containers that do not allow light to pass through.

This is the vitamin that gives your urine that neon yellow appearance if you take B vitamin supplements or a multivitamin with high doses of riboflavin. Riboflavin is important for energy metabolism and is required in the processing of other vitamins including Vitamin A, Vitamin B6, and Vitamin B3 and the absorption and processing of iron. It helps maintain normal adrenal gland and nervous system function.

The recommended daily allowance of riboflavin is 1.2 mg per day. However, the recommended daily allowance of Vitamin B2 (and for all the other vitamins) given the data we have should be seen more as a bare minimum for survival and not as a goal for intake per day. Like the other B vitamins, riboflavin is a water-soluble vitamin, so it is not stored by the body in significant amounts and if intake is not sufficient deficiency will occur quickly (within days or weeks). However, this water-soluble quality also makes riboflavin very safe to take in higher quantities as the excess is easily excreted by the body in the urine. However very high doses possibly may increase the risk for kidney stones and may cause some skin irritation. 

deficiency of riboflavin (a condition known as ariboflavinosis) usually presents with weakness, fatigue, dry cracked lips, inflammation of the mouth and tongue, sore throat and mouth ulcers. Dry scaly skin, irritation of the eyes, and anemia may also occur.

Some recognized uses of riboflavin are supplementation to infants receiving UV light for neonatal jaundice (the yellowing of the skin due to bilirubin from broken down red blood cells that is treated with the famous bili blanket) because the UV light breaks down the riboflavin in the baby’s blood. It is also used in conjunction with UV light that is used to sterilize pathogens in blood products that are donated and applied to the cornea before UV treatments for Keratoconus (a thinning and mis-shaping of the cornea into a cone shape).

There was some excitement when it was found that pregnant women who were riboflavin deficient had a nearly 5 times increased risk for preeclampsia. Preeclampsia is a condition in pregnant women of unknown cause where they develop protein in the urine and elevated blood pressure in the later stages of their pregnancy. The blood pressure can get dangerously high and it can progress to eclampsia which is when those with preeclampsia then have seizures. The hopes were that riboflavin supplemenation would prevent and treat this. However this was studied by Neurgebauer et. al in good placebo controlled trial in 450 pregnant woman, and they found no decrease in risk of preeclampsia with riboflavin supplementation.

Multiple studies have shown a decrease risk for cataracts in those that eat higher amounts of riboflavin. This would make sense as well as deficiency is known to cause eye irritation. However a good randomized placebo controlled trial of riboflavin supplementation to prevent cataracts has yet to be done despite this being one of the most common conditions of old age and cataract surgery is the most common surgery done on the elderly in America. Over 20 million Americans have catract and it affects 50% of those over the age of 80. The surgery for cataract is performed on approximately 3 million Americans per year and costs Medicare an estimated 3.4 Billion dollars per year.

Multiple smalls studies have also shown a benefit to migraine headache sufferers with riboflavin. When taken together the strength of these studies is quite strong and they were placebo controlled. There is also good science behind why this may work. Riboflavin helps with energy metabolism in the mitochondria (a part of cells that is devoted to energy production) and some studies have shown that oxygen metabolism by mitochondria may play a role in migraines. Interestingly the maximum benefit seemed to not be achieved until about 3 months of treatment. The reason for this is unclear.

I had also noted the symptoms of riboflavin deficiency are almost identical to a condition called mucositis that we see in many cancer patient’s receiving chemotherapy or radiation. Mucositis causes severe mouth, tongue and throat irritation and ulcers, sometimes to the point patients cannot eat. Sure enough, when I went to the literature there was evidence that riboflavin supplementation may prevent this. However it is still in the preclinical phase and trials on actualy patients have yet to be done. Vitamin E has also been shown to be effective. Topical Vitamin E seems to be more effective than Vitamin E pills.

Given the data I feel riboflavin needs to be tested in a large randomized study to see if it can alleviate mucositis. This is a debilitating condition that causes severe pain to cancer patient undergoing so much pain and suffering already.  We also need a large randomized trial to definitively assess the role riboflavin supplementation may play in cataract prevention.

However, I feel it would be appropriate to start migraine sufferers and elderly on B complex supplementation with the data we have given riboflavin’s almost complete lack of side effects and risk for toxicity. However in cancer patients undergoing chemotherapy and radiation with mucositis this would have to be looked at more closely as the supplementation’s effect on their chemotherapy and cancer is still not known. However topical Vitamin E seems very promising and giving it topically dramatically decreases any risk for interaction with chemotherapy or effect on the cancer.

References

Riboflavin and preeclampsiaNeugebauer J, Zanre Y, Wacker J. Riboflavin supplementation and preeclampsia. Int J Gynaecol Obstet

Riboflavin and cataracts

American Journal Epidemiology 1995 Diet and nuclear lens opacities

 
Riboflavin and Migraines