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

Vitamin A

Polar Bear (Sow), Arctic National Wildlife Ref...

Vitamin A is actually a group of compounds that include retinol and beta-carotene among others. The science behind it dates back to 1816 when scientists noticed nutrition deprived dogs developed corneal ulcers. It was later found to be a fat soluble vitamin (as opposed to water-soluble) meaning it is stored in the fat (along with vitamins D, E, and K).

Vitamin A is indeed important in maintaining good vision. It is also important for cell growth and differentiation, skin health, and the immune system. For women the recommended daily allowance (RDA) is 700 mcg and 900 for men. The widely considered upper safe limit is considered to be 3000 mcg.

Animal sources of vitamin A include cheddar cheese, eggs, butter, and liver. Plant source include carrots, broccoli, kale and spinach. Dandelion greens have a particularly high amount of vitamin A and are used in natural medicine.

Worldwide Vitamin A deficiency is a huge problem. Approximately one-third of children are estimated to be vitamin A deficient. Nearly a half a million children a year go blind each year due to vitamin A deficiency. It often presents first with night blindness. Also early on a condition called xerophthalmia occurs where the eye is unable to produce tears. This leads to eye dryness, then plaques and eventually ulcerations. Other symptoms include increased infections due to an impaired immune system and poor forming of tooth enamel.

Vitamin A overdose is a significant risk as it is fat soluble, which means the body stores it in fat cells so excess amounts cannot be cleared easily. Excess vitamin A in pregnant women has been shown to cause birth defects in their offspring (however vitamin A deficiency also causes issues for the fetus as well). Toxic levels can cause nausea, vomiting, hair loss, weakness, and headaches and can lead to osteoporosis. Liver damage has also been seen at high doses. However, it is interesting to note that these toxicities and teratogenicity (damage to unborn fetuses) are only seen with preformed vitamin A (retinoid) as found in animal sources of Vitamin A such as in liver or supplements with retinol or retinoic acid. It is not seen with carotenoid forms (such as beta-carotene) which are found in plant sources such as carrots and are molecules that have to be converted into vitamin A by the body. Carotenoids are water-soluble and not stored by the body hence they are rarely if ever toxic. Beta-carotene is the most common carotenoid in supplements but there are many more (approximately 500 known so far) but only about 10% of those are made into vitamin A. Therefore if one is going to supplement vitamin A levels they should avoid retinol or retinoid acid and instead try to get a supplement with a mixture of carotenoids.

Vitamin A research is severely limited due to its overblown risks for toxicity. Most people I know during medical school were told of a group of arctic explorers that died due to Vitamin A toxicity from eating polar bear livers. Of course liver is the richest possible source of vitamin A in the diet. It is also all in the preformed retinoid form which is the most toxic. I personally have never, not once, seen a case of vitamin A toxicity. And that is in spite of the fact that I live within a short drive of Herbalife headquarters and in southern California where people take supplements galore.

Vitamin A is most commonly used to treat Acne most commonly in the form of isotretinoin (Accutane). It is effective but does come with significant side effects and very high risk for birth defects if a woman becomes pregnant on it. Therefore women have to pledge to use contraception while using it.

Vitamin A is also used rarely for cancer in the retinoid form which is the active metabolite of vitamin A. Mostly it is used in rare pediatric tumors such as acute promyelocytic leukemia and neuroblastoma. The role of Vitamin A and cancer is still being evaluated as described in this study. Vitamin A may also play a role in cancer prevention.

Research has also shown that Vitamin A can dramatically decrease the complications and death rate from measles. It has also been shown since the 1990s that vitamin A helps to decrease morbidity and mortality from HIV, however this has not been adequately looked at and few if any doctors given Vitamin A to their HIV patients despite these results.

Vitamin A is still plagued with incomplete research due to a variety of reasons. Lack of profit of course is one, but also Vitamin A’s multiple forms and knowing which one to use for trials is not clear. Also complicating the matter is its risk for toxicity and teratogenicity. However, the risk is quite low for toxicity if given in reasonable doses and I feel naturopathic doctors could give us a lot of guidance as to what forms to use for supplementation as they have been using them for centuries.

There are many possible exciting avenues for research for vitamin A. The pharmaceutical industry is already trying to form more patentable versions for cancer treatment. It would be interesting to see if traditional vitamin A supplements (particularly mixed carotinoids) would help with cancer treatment.

However, I feel given the dramatic results from HIV and measles research that has already been done, the most promising avenues of research would be those for viral illnesses. Hepatitis C and HIV are two of the most devastating and costly viral illnesses we struggle with. Hepatitis C has a very high treatment failure rate and it would be fascinating to see if treatment with Vitamin A supplements in addition to normal treatment for Hepatitis C increased the treatment success rate. It would also be great to see if Vitamin A supplements decrease viral load levels in HIV patients on medication. Preliminary research already points to the fact that it likely does.

One main issue with the studies done so far is that they are often done with the active forms (retinoids) which carry the high risk for toxicity. It is possible carotenoids may not have the same effects as the body may regulate the conversion by the body to levels not high enough to see the effects achieved with direct supplementation with active retinol vitamin A. However, studies would be much easier, safer, and more generalizable to medical practice if carotenoids were used. Many studies have been done with beta-carotene but this is likely flawed. This is only one of over 50 carotenoids the body makes into Vitamin A and when you eat Vitamin A naturally you get many of these all at once. They do not come in isolation. Studies are showing that likely this mixture of carotenoids is what leads to the beneficial effects of Vitamin A, so supplementing one carotenoid in isolation may have little or no effect or may even been detrimental. If one is to supplement vitamin A the best way of course is with Vitamin A rich foods such as carrots or spinach. But for studies to allow for a placebo they would have to be given as pills to allow for a placebo. So mixed carotenoids would be best to allow for a good chance of beneficial effect while avoiding the toxicity seen with retinol or retinoic acid.

It is time we stop fearing this Vitamin and start using it to our advantage. It could end up being one of our most powerful weapons against viruses and maybe even cancer.

References

Vitamin A in cancer study – http://www.ncbi.nlm.nih.gov/pubmed/21073338

Vitamin A and breast cancer – http://www.ncbi.nlm.nih.gov/pubmed/12452454

Vitamin A and cancer prevention – http://www.ncbi.nlm.nih.gov/pubmed/15134535

Vitamin A and measles – http://www.ncbi.nlm.nih.gov/pubmed/12521271

Vitamin A and multivitamin in HIV – http://www.ncbi.nlm.nih.gov/pubmed/17368322

Beta Carotene and HIV – http://www.ncbi.nlm.nih.gov/pubmed/8450402

Vitamin A and Hepatitis C – http://www.ncbi.nlm.nih.gov/pubmed/23213086

Probiotics for Acne? Yep Bacteria may be the cure

Acne vulgaris

I recently had a great idea when thinking about probiotics.  They are used to recolonize the gut with good bacteria after a course of antibiotics killed them off. Well why can’t the same be done for the skin in acne patient? We all have bacteria all over our skin and antibiotics have been the mainstay of acne treatment for years but is only minimally effective. Maybe the problem with acne patients isn’t that they have bad bacteria, but instead maybe they lack good bacteria. So after a course of antibiotics maybe we need to be spreading good bacteria on their skin.

Well like most great ideas someone already beat me to it. Dr. Huiying Le at UCLA medical center examined the bacteria on acne patients’ skin and compared it to those with clear skin. They looked specifically at a bacteria called Propionibacterium Acnes which has been linked to acne for years. They found that acne patients had two strains that clear skin patients did not have that they dubbed RT4 and RT5. And, more importantly, they found a strain that clear skin patients had that acne patients did not have called RT6. And RT6 was found to have genes that ward off bacterial viruses and potentially may prevent colonization with bad strains.

So in yet another area we are finding that the answer may not be killing our microscopic friends but instead making sure we are carrying the right ones.

We have ignored these possible treatment options by using beneficial microbes for far too long but I am glad to see the increased interest in this field. If you want another very interesting example of our symbiotic relationship with microscopic organisms read about the possible link between hookworm and allergies.