Vitamin B7- Biotin

Yet one more B vitamin (and more to come) Vitamin B7 also known as Vitamin H or Biotin is also important in metabolism and the production of fatty acids and cell growth. It assists in the transfer of carbon dioxide in the body and aids in maintaining normal blood sugar. It also assists in normal adrenal function and for maintaining a healthy nervous system and metabolism

Most of our biotin actually does not come directly from food but from the bacteria in our intestines. It is found in many foods but only in small amounts. Foods that are rich in biotin include green leafy vegetables such as swiss chard and organ meats such as liver. The recommended daily allowance is 30 mcg/day.

Low biotin levels have been found in some populations most notably alcoholics, people who have had part of their stomach removed, the elderly and those with low stomach acid. Consumption of raw egg whites can induce deficiency due to a protein in them call avidin that binds very strongly to biotin making it unavailable for absorption by the body. Cooking egg whites breaks down this protein so cooked egg whites do not deplete biotin.

Deficiency is rare and causes hair loss, eye irritation, scaly red rash around the mouth, nose and genitals and neurologic symptoms such as fatigue, depression, or hallucinations.

No animal or human studies have shown any signs of toxicity even at high doses.

Biotin, like folic acid, seems to become depleted easily during pregnancy and deficiency also increases the risk for birth defects. Therefore woman who are or plan to become pregnant are recommended to take a prenatal vitamin with biotin in addition to folic acid.

A 2006 study by Singer et al showed that chromium and biotin supplementation together significantly improved glucose levels and triglycerides in diabetics. This was confirmed in a 2008 study by Albarracin et al, and a 2013 study by Sahin et all done with rats showed the likely enzymes affected by this supplementation that explain this beneficial effect.

Veterinarians had been using biotin for defects in hooves and claws for decades so some scientists started to look into if it would work for brittle nails in humans. And indeed some small uncontrolled studies have shown that biotin is effective in treating brittle nails.

Some studies back in the 1960s showed that biotin injections given to a nursing mother could improve seborrheic dermaitis in the infant. These were small studies and were not placebo controlled. No large follow-up studies have been done. Two very small (less than 20 patients) studies were done giving biotin directly to the infants and found no effect of biotin on seborrheic dermatitis.

Overall biotin deficiency seems rare and supplementation, much like the other B vitamins, has been rarely studied and its effect on disease has hardly been explored at all. However, I feel the research concerning diabetes is compelling and this combined with the research on Vitamin B1, thiamine improving neuropathy in diabetics makes a strong case that all diabetics should be on vitamin B complex supplementation. It would be an easy study to do by randomizing diabetic patients to placebo and vitamin B complex and monitor them over a couple of years for complications from diabetes and glucose levels to see if there is any statistical difference. Overall the research into biotin is sparse and few conclusions or recommendations can be made from what we have.

References

Chromium and Biotin for Diabetics – 1) http://www.ncbi.nlm.nih.gov/pubmed/17109595

2) http://www.ncbi.nlm.nih.gov/pubmed/17506119

3) http://www.ncbi.nlm.nih.gov/pubmed/23211098

Brittle nails 1) http://www.ncbi.nlm.nih.gov/pubmed/17763607

2) http://www.ncbi.nlm.nih.gov/pubmed/8477615

3) http://www.ncbi.nlm.nih.gov/pubmed/2648686

Biotin for nursing mothers of infants with Seborrheic dermatitishttp://www.ncbi.nlm.nih.gov/pubmed/4243742

Biotin given to infant for seborrheic dermatitis- http://www.ncbi.nlm.nih.gov/pubmed/132601

Vitamin B6- Pyridoxine

Yet another one of our laundry list of B vitamins, Vitamin B6, also known as pyridoxine, is water-soluble and very important in metabolism. Discovered in 1934 by a Hungarian doctor named Paul Gyorgy its active form is called pyridoxyl phosphate. It is essential for multiple parts of metabolism of amino acids and for gluconeogenesis which is the body’s ability to make glucose for energy using glycogen and fat stores in the body. It is also essential for neurotransmitter synthesis which are the brain’s communication molecules. It also aids in the synthesis of histamine and hemoglobin. Lastly it directly affects gene expression and when present can decrease the expression of glucocorticoids and increase the synthesis of albumin. All making this vitamin very important in many essential functions of the body.

Vitamin B6 is found in a wide variety of food including meat, vegetables (most notably carrots, and spinach), bananas and nuts. In plant sources it is in the form pyridoxine which is quite stable but in meats and animal products it is in the form of pyridoxal or pyridoxamine which are far less stable and prone to break down during cooking and food processing. Yet again, in grains it is mostly in the outer shell and germ so it is lost in highly processed grains (so I will say it again, if you eat grains eat the WHOLE grain). 

Deficiency causes mostly skin manifestations including seborrheic dermatitis (dry, itchy, scaly, flaky, red patches of skin on the face and head), tongue inflammation, angular chelitis (inflammation of the corners of the mouth), and intertrigo (inflammation of the skin folds). It can also cause neurologic manifestations such as sleepiness and neuropathy. Deficiency is rare in the healthy population but diseases such as diabetes, HIV, kidney disease, and rheumatoid arthritis seem to put people at risk for deficiency even if they take in enough Vitamin B6. Medications such as steroids and seizure medications can also deplete vitamin B6.

Toxicity has never been seen from food sources but at doses of 1000 mg a day (770 times the recommended daily allowance) in supplement form has been reported to cause a neuropathy that can lead to pain and numbness in the legs. The recommended daily allowance is 1.3 mg. Likely closer to 50 mg per day is conducive to good health and it should be taken in conjunction with the other B vitamins in a B complex if it is going to be taken in supplement form.

Studies of Vitamin B6 to treat diseases are lacking. A 1992 study by Deijen et al. was a well designed placebo controlled trial and showed that vitamin B6 improved memory, most prominently long-term memory. A 2002 study by Bryan et al had the same finding. A 1999 study by Wyatt etl al. reviewed 9 studies with over 900 patients and found that a dose of 100 mg per day of Vitamin B6 may be beneficial for treating the symptoms of PMS. However they do mention that many of the studies were of poor quality so larger studies should be done. Some have thought that Vitamin B6 would be useful in treating depression given that it is needed to help make neurotransmitters including serotonin. A review in 2005 by William et al of the available placebo controlled trials for vitamin B6 in depression found no statistically significant benefit. Two studies have shown that Vitamin B6 may help alleviate morning sickness during pregnancy. The first was a 1991 study by Sahakian et al. and the second was in 1995 by Vutyavanich et al. Both showed statistically significant benefit.

Overall like many of the B vitamins Pyridoxine has gone mostly unstudied in its role to treat disease. It does seem to possibly have some small effect on memory and nausea during pregnancy and is likely safer than pharmaceutical drugs during pregnancy if taken in low doses. PMS also seems to be a promising use. Both of these need larger better studies to establish a clear role. But mostly I feel it is a mistake to take each of the B vitamins in isolation. Their metabolism is intricately woven together and taking too much of one can deplete or compete with the others. I feel it is best to take them as nature usually gives them to us in B complex form. Of course the safest and best way is by eating plenty of vegetables and nuts.

References

Vitamin B6 and memory 

Vitamin B6 and memory #2

Vitamin B6 and PMS

Vitamin B6 and morning sickness 1991

Vitamin B6 and morning sickness 1995

Fibrinogen and Fibrates- A New Approach to Preventing Heart Attacks

Coronary angiogram of a man

Coronary arteries

This is revisiting a topic I covered earlier in my post Hypertension Maybe Your Blood’s Too Thick. Basically I reviewed the literature on the topic of viscosity of blood possibly leading to high blood pressure. One key protein that is implicated in thickening the blood is fibrinogen. It is involved in the inflammatory pathways and blood clotting. It seems by research that in normal levels it keeps a good balance of helping the immune system and preventing major bleeding while not causing too many clots or inflammation. But when the level is too high is seems to increase the risk for coronary artery disease leading to heart attacks. A 1999 study Eriksson et al. showed that those in the highest 25% of fibrinogen levels had 3 times the risk for coronary artery disease than those in the lowest 25% even after controlling for other coronary artery disease risk factors. Many other studies have shown the same relationship including Onohara 2000, Bolibar 1993, De Luca 2011, Montalescot 1998, Lima et al 2012, and many more. In fact looking closely at the data fibrinogen is likely a more accurate predictor of risk for heart disease than cholesterol.

So one may ask why isn’t my doctor following my fibrinogen level, and if its high why aren’t they treating it? Well before I would have said because we have no known treatment to lower fibrinogen but then I found data showing this is not true. Multiple studies have shown that the pharmaceutical class of drugs referred to as fibrates do decrease fibriongen. This includes drugs such as fenofibrate and gemfibrozil which are usually used to treat a certain type of cholesterol when it is high called triglycerides. They do this pretty well but studies for outcomes did not show a huge benefit therefore they are not commonly used. However, they have never been tested in patients with high fibrinogen, they have only been studied in patients with high cholesterol or triglycerides. As far back as 1999 de la Serna et al. showed that fenofibrate decreased fibrinogen by 15%. In fact there was a study as far back as 1989 by Leschke et al showing that fenofibrate dropped fibrinogen levels from a mean of 300 to 250. They also showed a significant improvement in blood viscosity and using myocardial scintigraphy (a study to look at blood flow to the heart) they showed an improvement in blood flow to areas of the heart that previously were not getting adequate blood flow in all subjects they evaluated. It was however a small study. This drop in fibrinogen is not seen with statin drugs which are the most commonly used cholesterol drugs today.

And then of course there are the always forgotten and neglected natural medications. A 2009 study by Hsia et al. showed that nattokinase (a supplement derived from fermented soy and commonly used in Japan) can decrease fibrinogen levels by 9%. And a recent rat study May 2013 by El-Sayed et al showed curcumin (the ingredient believed to be the main active ingredient of turmeric) can decrease fibrinogen along with multiple other cardiovascular risk factors as well.

There are many more studies, too many to cite them all. Given the vast amount of data we have and considering that it goes back as far as the 1980s it is way overdue to do a study where we take a group of patients with high fibriongen levels and radomize them to fenofibrate (or another fibrate, or curcumin or nattokinase) and see if they get a significant drop in fibriongen. Then more importantly follow them to see if that translates into a significant decrease in the risk for heart attack and/or stroke. Given that fibrinogen is intricately involved in inflammation and blood clot formation it only seems logical that reducing it would translate into huge health benefits. It’s about time to find out if we should be more concerned about our fibrinogen level than our cholesterol.

References

Studies showing relationship of fibrinogen to coronary artery disease

http://www.ncbi.nlm.nih.gov/pubmed/9888868- Eriksson et all.

http://www.ncbi.nlm.nih.gov/pubmed/11129810 – Onohara et al.

http://www.ncbi.nlm.nih.gov/pubmed/8498300 – Bolibar et al.

http://www.ncbi.nlm.nih.gov/pubmed/21080031- De Luca et al.

http://www.ncbi.nlm.nih.gov/pubmed/9717059, Montalescot et al.

http://www.ncbi.nlm.nih.gov/pubmed/23049444, Lima et al.

Fibrates and fibriongen

http://www.ncbi.nlm.nih.gov/pubmed/10460070 – de la Serna et al

http://www.ncbi.nlm.nih.gov/m/pubmed/2731478/- Leschke et al

Natural supplements and fibrinogen

http://www.ncbi.nlm.nih.gov/pubmed/19358933- Hsia et al

http://www.omicsonline.org/efficacy-of-curcumin-in-reducing-risk-of-cardiovascular-disease-in-high-fat-diet-fed-rats-1948-593X.1000082.php?aid=16486- El Sayed et al.

My Humble Opinion on Nutrition

Food for Life distributes food on an internati...

I have taken part recently in some interesting conversations on nutrition and I thought I would put down my current views on the topic. I will preface this with the fact that as an internal medicine physician my formal training in nutrition is minimal at best. The level of education on nutrition offered in even the most prestigious medical schools these days is embarrassing. We did not have even one course on nutrition and the whole topic was summed up in a few lectures over the course of my four years of medical school. In residency it was hardly ever mentioned. For something as important as what we put in our bodies multiple times a day and given that it in my opinion has the largest effect on health than any other behavior, this is appalling. So what I have learned about nutrition has been learned through my wife who is a naturopathic doctor and had extensive education on nutrition during her training, from self research and reading. There are two books that I have recently read that I highly recommend. Whole by T Colin Campbell (the researcher behind the famous China Study) which discusses not only nutrition and its role in our health but much of what is wrong with our current medical research and medical care delivery system. The second is In Defense of Food by Michael Pollan who also wrote The Omniovore’s Dilemma.

 

In my research I have found a few key facts. First, there has been very little research on food and nutrition. Again, I blame this mostly on the lack of profit incentive for the research to be done. No patented drug or medical device can come from the research hence no money. Therefore the investment simply is rarely made. Second, is that nutrition is far more complex than most of us think it to be, therefore studies that are done in test tubes or rats are often mistakenly and with disappointing results generalized to humans. Studies showed that foods high in vitamin C were good for you so supplementing vitamin C must be good for you. But experience has not shown this to be the case. Food high in beta carotene seemed to prevent cancer but supplementing it increased cancer. Same for vitamin E. So what is the problem? How come our research never seems to allow us to get to those isolated chemicals in food that make us so healthy? How come we are no closer to that pill that can make us healthy no matter what we eat now than we were 20 years ago?

 

The problem is complexity. With the micro-nutrients (minerals and vitamins) that we have isolated so far we have only scratched the surface of the over 10,000 phytochemicals in foods. Phytochemicals are plant made chemicals that have biologic functions in our body. So why can’t we simply isolate these and take them in pill form to achieve immortality and perpetual youth? Because we don’t even know what all of them are, or what they do to the body.

 

When you eat one piece of fruit you are likely taking in hundreds of phytochemicals. The quantity depends on the health of the soil that plant was grown in, how the growing season was that year, rainfall, sunshine, pests, symbiotic fungi and other organisms in the soil, how ripe the fruit was when it was picked, and even what time of day it was picked. Then when you eat that piece of fruit those chemicals will act on each other. Some blocking the absorption of others and others facilitating the absorption. Then as they act on your body some will deplete other nutrients in your body or increase them. And your body will change what it takes from the food based on its needs and current health. If the body needs more of a nutrient it will take in more and if it does not need it will not. Or absorption may be impaired by an infection or damaged gastrointestinal tract.

 

So when we see that a specific nutrient has antioxidant capabilities in a test tube, that does not mean that it will when combined in food form or in our bodies, or even that more antioxidant intake is what our body needs at that time. The only way to tell if an isolated nutrient of food is good or bad for us is to randomize a group of people to either receive the nutrient or food or not and compare the two groups. However, these studies are rarely done due to many issues I have discussed before. But these are really the only studies conclusions can be absolutely drawn from and that is why those studies are the final and necessary step before approving any pharmaceutical drug. But even pharmaceutical drugs prove the point as even though they are designed to have one desirable effect such as lower cholesterol or blood pressure they all have a long list of side effects because our knowledge of the complexity of the human body is still in its infancy.

 

So in the face of all this complexity what is one to do when deciding what to eat? Well in everything I have learned and come to believe I think it comes down to the basics of eating what evolved to eat as much as possible. Our diet has changed dramatically in the last 10,000 years since the spread of agriculture. And with industrialization our diet has changed even more in the last 100 years than in any other time in history. The problem is evolution does not act that fast and so our bodies are unable to adjust to such rapid change. And our changes in diet are based on taste preference and convenience, not on what is healthy for us. And the few health related food choices we make are based on very superficial and limited information.

 

Human history has shown us that humans can survive on a wide variety of foods. From Eskimos to Bedouins the climates we can survive in and the diets associated with the climates are amazingly diverse. But surviving on a diet and thriving on it are two very different things. Animals can adapt to survive on new food sources quickly as those that cannot survive on it die off and only those that can survive to reproduce. But the selective pressure between those that thrive on the diet and look healthier and have more energy get more mating opportunities separating them from those that merely survive but do not thrive on the diet can take hundreds of thousands if not millions of years. To put the time scale of evolution in perspective if you took all the time since the beginning of dinosaurs to now and compressed it into one day the dinosaurs would have existed for the equivalent of 18 hours. Humans would have been on earth now for the equivalent of 10 minutes. So the selective pressures on humans from evolution have been minimal at best. Most of our evolution happened before humans walked the earth.

 

With this in mind I find the best reference for what we should eat to be Chimpanzees and Bonobos. We share a common ancestor with these primates in the not too distant past and genetically they are the most similar to us than any other living thing on the planet. We share over 98% of our DNA with Chimpanzees. However, while our diet has changed dramatically in the last 10,000 years and even more so in the last 100, chimpanzees and Bonobos eat very similar diets to what our common ancestor would have eaten.

 

So what is this diet? It is the exact same diet that most of the research done on diet is showing us is healthy. A mostly plant-based diet with as wide a variety of plants as possible and very little lean meat. Chimpanzees eat about 60% fruit, 38% vegetables, nuts, seeds, leaves, and 2% meat (usually in the form of monkeys). There are usually well over 100 different types of plants in a Chimpanzee’s diet. And there are no refined grains in this diet such as wheat, corn or rice.

 

Given this I do not find it surprising that study after study shows that plant-based food decrease the risk for cancer and heart disease. That vegetarians and vegans have lower risk for diabetes and hypertension. That eating meat increases the risk for heart disease and cancer. In fact one study I have highlighted before showed that a vegan diet was better for diabetics by every health measure they looked at than the American Diabetes Association Diet.

 

Chimpanzees and their ancestors have had time to adapt so that they not only survive but thrive on this diet. Over millions of years mammals have been eating adaptations to this diet and with each generation those that are healthier, more robust appearing, stronger, and had more energy had more chance to mate and increase their numbers. This subtle pressure takes a long time, much longer than the 10,000 years that agriculture has been prevalent.

 

Only after the widespread use of agriculture did refined grains such as rice, wheat, and corn enter our diet in large amounts. And only after farming came about did we start to eat meat that was from domesticated animals such as cows and pigs that is much fattier and has much more omega 6 fatty acids which are inflammatory than omega 3 fatty acids which are anti inflammatory. The animals we ate prior to this we monkeys, deer, rabbit, squirrel and a myriad of other lean, wild and much healthier animals. Our ancestors used to eat about 50% omega 6 fatty acids and 50% omega 3. Today that ratio is about 15 to1 in the average Western diet. And only after farming did meat become such a large proportion of our calories.

 

There is no doubt we have evolved to the point where we can survive on this diet but given the increasing spread of heart disease, diabetes, cancer, and obesity it is clear we have not evolved to thrive on it.

 

I feel much more research on a microscopic scale will need to be done before we even have what we could consider a beginning to understanding the effect food has on our body. And I would love to see far more studies that randomize people to certain diets so we can actually draw some conclusions from them. Lets do a study randomizing people to a diet with naturally occurring foods with no refined grains or processed food and very little meat (preferably lean meat high in omega 3) and compare that to the American Heart Association diets, or ADA, or TLC, or Atkins diets. Diet is the most important health recommendation we make to a patient so it should be evidence based.

 

Until that happens I think we are best suited to staying on the diet we have evolved to thrive on. Clearly eating what we can survive on is not working.

 

USPSTF- No Evidence for Vitamins

I have to take a break from our stroll down vitamin lane to comment on a statement put out by the US Preventative Services Task Force. The statement reads that there is not enough evidence to recommend for or against vitamin and mineral supplements to prevent cancer or cardiovascular disease. They also condition this statement with the fact that it does not apply to women who are or may become pregnant, children, hospitalized patients, the chronically ill, or those with a nutritional deficiency.

I am not sure where to begin with this so I will just start with the fact that I agree with this statement, but it deeply frustrates me and it is not followed by a call to arms to mobilize all resources we have to remedy this ignorance. The fact that almost all of the vitamins and minerals have been known for over 100 years and yet still to this day we cannot recommend for or against them for the top two killers of people in America attests to the scarcity of good studies done on vitamins and minerals. These substances should have been exhausted as possible treatments LONG before we started inventing new foreign substances to put into our body to do this job. This goes to the very heart of the reason I started this blog. These studies need to be done. We should have known the answer to this long ago.

Secondly this brings up a main issue I have with much of the vitamin research that is done. Very little of it is devoted to treating illness. Often they look at large groups of healthy individuals and try to see a difference between the vitamin group and the placebo group. No pharmaceutical company would allow any of their drugs to be submitted to such research because it is really hard to make healthy people more healthy. The size and cost of a study that would have to be done to pick up the small benefit that may be conferred would not be tolerable. But this is the type of research vitamins are put through most often and not surprisingly no conclusions can be drawn from the studies.

One may notice that I comment mostly on studies looking at using vitamins, herbs or minerals to treat disease, not to maintain health. The reason for this is I feel supplementing vitamins in isolation to maintain health is likely a lost cause. Yes, a multivitamin is likely good to avoid deficiency but by itself it is unlikely to make the difference between health and disease. The reason being is that a multivitamin is amazingly incomplete. We are just in the beginning of understanding micronutrients. A multivitamin only provides a handful of the over 10,000 phytochemicals founds in plants that help us to maintain health. When you eat one single piece of fruit you are ingesting hundreds of chemicals. Each one of these interacts with the absorption and action of the others. And your body, depending on its needs at that time will increase or decrease its absorption of those chemicals at that time. Not to mention the variation in the amount of chemicals in that fruit based on the health of the soil, the ripeness of the fruit, and even the time of day it was picked. Despite this vast variation our bodies have evolved to get exactly what it needs from these plants to be healthy and active.

When a person is healthy and eating the kinds of foods they should be eating (organic fruits, vegetables, nuts, seeds and a small amount of lean omega 3 rich meat) it all works like an orchastra in perfect harmony. And when we come in with our mega-doses of vitamins and minerals in a untargeted way we are like a child banging on their drums trying to add something meaningful to the music. We add nothing and only cause imbalance. Drug companies know this and so they design their drugs to fix a specific problem, and do not try to design drugs that make healthy people healthier.

But that brings us to all those exceptions they mentioned (pregnant women, children, the chronically ill, hospitalized, and nutritionally deficient). This is where we need the research to know when these vitamins and minerals may play a role. The orchestra is not in harmony and needs help. We have nothing to add to an orchestra that is already playing a beautiful symphony in perfect harmony. We are no where close to the level of knowledge it will take to add anything to this. However, if the cello player is a bit off, we may be able to correct this with targeted therapy with a vitamin, mineral, herb, and if all those fail maybe then a synthetically made pharmaceutical.

Chimpanzees, our closest genetic relative on earth, demonstrate that supplements are likely not the answer to preventing cardiovascular disease and cancer. The rates of these diseases in chimps is drastically lower than in humans. They live in harmony with nature eating the diet that millions of years of evolution have evolved them to eat. They get their dizzying array of phytochemicals not in the form of supplements but in the form of over 100 different types of plants that they consume.

Our bodies are from the earth and we are made up of the same elements as the earth. We need constant replenishment of these minerals to stay alive and healthy. The only way we can keep this healthy connection to the earth is to eat healthy plants that have taken in those minerals and vitamins and incorporated them into themselves.

To date no supplement can replace this. Therefore I urge everyone not to wait for that magic supplement that will replace everything in a healthy diet. You will be waiting for a very long time. To date those 10,000 phytochemicals come in only one safe and reliable form, unprocessed, organic fruits and vegetables and other plant based foods.

However, many studies such as the ones I have highlighted in this blog have pointed toward a role for vitamins, minerals and herbs in treating disease. I just hope statements such as these put out by the USPSTF will not detract from the goal of getting the needed research done to find safer, more effective treatments that bring us back to health rather than artificially alter our bodies with chemicals our bodies are not genetically designed to handle.

Vitamin B5- Pantothenic acid

Vitamin B5 is not a very well-known vitamin but still very important. Another one of the water-soluble B vitamins, and like the others it is very important in metabolism. It was discovered in 1933 by Roger Williams. It is found in small amounts in almost all foods but higher amounts are found in grains, beans, eggs, and broccoli. Avocados have a particularly high amount of Vitamin B5

Given the abundance of vitamin B5 in foods deficiency is extremely rare. When it is deficient it can cause severe fatigue, numbness, tingling, muscle cramps, and in severe cases adrenal insufficiency.

There are no known cases of toxicity from Vitamin B5. Extremely high doses may cause diarrhea but no severe reactions have ever been noted. The body seems extremely capable of handling high doses of B5.

Given its ubiquitous nature and rare incidence of deficiency few studies have been done looking at pantothenic acid in treating disease. A derivative of pantothenic acid called patethine was studies by Gaddi et al in 1984 and found to have a significant cholesterol and triglyceride lowering effect with little or no side effects. To the best of my knowledge this is not being used by physicians in any significant number but is sold widely over the counter.

There was some interest in using pantothenic acid for wound healing but all major double-blind studies done in humans showed no major benefit.

One recent interesting study done by Giraldi et al. studied pantothenic acid to help alleviate postoperative ileus. Postoperative ileus is when the intestines no longer contract normally for a period of time after surgery causing severe constipation, abdominal bloating and discomfort. It is most commonly seen after abdominal surgeries but can been seen after almost any major surgery and often lasts days significantly prolonging hospitalizations and delaying time to when the patient can eat. In Giraldi’s study they found a signficant faster resolution of the ileus in those that received pantothenic acid as compared to placebo.

Given the studies that have been done so far pantothenic acid and pantethine should be studied further as a cholesterol lowering drugs. In fact, given that niacin has already proved to be so useful a study should be done looking at B complex supplementation with all the B vitamins and see how that affects cholesterol and triglycerides. This preliminary study on ileus should be followed up as well given currently we have no treatment to speed recovery from postoperative ileus leading to increased morbidity and wasted resources using more hospital days. But overall there is a general lack of literature on pantothenic acid and our understanding of its role in the treatment of disease is in its infancy.

References

Patethine for cholesterol study – http://www.ncbi.nlm.nih.gov/pubmed/6365107?dopt=Abstract

Pantothenic acid and wound healing

Pantothenic acid and postoperative ileus

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