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

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.

 

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

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

Vitamin B1- Thiamine

Next up is one of the B vitamins, Vitamin B1, otherwise known as thiamine. All living things need thiamine. However, plants, bacteria and fungi can produce their own. Animals such as ourselves have to obtain it in our diet. Thiamine was the first water-soluble vitamin discovered. It was first recognized in 1884 when a surgeon general in the Japanese Navy Kanehiro Takaki noticed health benefits when a more varied diet was used on Navy ships instead of just the standard white rice predominant diet. This change in diet helped to alleviate many of the nerve and heart problems seen in the sailors. Unfortunately the Japanese navy did not feel it was worth the expense of the more varied diet.

Thiamine and other B vitamins are important for breaking down starch, sugars and carbohydrates to use as energy and also play a key role in nerve signal transmission. These functions make thiamine important for energy levels, the nervous system, muscle health and the digestive system.

Thiamine is found in a wide variety of foods but the highest concentration is in yeast, pork, and beans. The main source of thiamine in the diet is from grains. However, yet another reason to eat whole grains rather than highly processed ones is that thiamine is mostly found in the outer layers and germ of the grains that are removed during processing. In the US thiamine is added back in to processed flour. Thiamine is not stored by the body so symptoms of thiamine deficiency can form after even short periods of not eating enough (in as little as 2 weeks).

The recommended daily allowance for Thiamine is 1.4 mg. However some studies have shown benefits to higher doses up to 50 mg. It is likely the lower limit for ideal health lies somewhere around 5 mg or greater as it has been observed that the bodies absorption of thiamine decreases above this level. There are no adverse effects to excess thiamine as it is a water-soluble vitamin and excess amounts are easily excreted by the body in the urine.

Thiamine deficiency causes two main well know syndromes. The first one is Beriberi. Dry beriberi is a disease mostly of the peripheral nerves (those nerves further down than the spinal cord). This causes what is called a peripheral neuropathy where these nerves are damaged causing numbness, tingling, weakness, difficulties walking, and abnormalities in the reflexes. Wet beriberi has all of these symptoms from peripheral neuropathy but also leads to heart failure as well. It is called wet because the heart failure leads to a back up of fluid into the lungs and lower extremities causing swelling/edema. When treated the heart failure can improve rapidly but peripheral nerves can regenerate themselves (unlike central nerves like those in the spinal cord and brain) but this process takes months to correct.

Thiamine deficiency causes central nerve problems in the brain as well. In developed countries this usually happens in alcoholics as alcohol interferes with thiamine uptake by the body and displaces food in the diet that is normally the source of thiamine. It causes two conditions referred to as Wernicke encephalopathy and Korsakoff syndrome. But they so commonly happen together that they are often referred to as a blanket term Wernicke-Korsakoff syndrome. The Wernicke encephalopathy is a constellation of problems with eye movements, altered mental status, and difficulties walking. Kosackoff is a thiamine deficiency induced severe impairment in memory. Thiamine deficiency can also lead to visual disturbances.

Thiamine is mostly only used in medical practice whenever a person struggling with alcoholism is admitted to the hospital. They are routinely given thiamine to help prevent Wernicke-Korsakoff syndrome. Other than that thiamine is rarely used in medical practice.

Some studies have looked at the role of thiamine in Alzheimer’s disease. This article described some of the results showing that thiamine supplementation does show benefit in the cognition of those with Alzheimer’s disease. As this study showed there is an issue with many of the studies done with thiamine as they will often use doses as low as 3 mg per day which is likely lower than what the average person should be eating a day. The elderly absorb thiamine even less effectively than younger people so treatment doses should likely be well in excess of 10 mg but studies rarely do this. Giving IV is another option but this limits using the results for the general public as outpatients. However, what studies have been done show little or no benefit and studies looking at thiamine levels in the cerebrospinal fluid (CSF) showed no correlation with the level and risk for Alzheimer’s. Therefore it seems unlikely that thiamine will play a major role in the treatment of Alzheimer’s. However supplementation or increased intake in the diet may help a little. (however studies do show that Vitamin A may play a role in the treatment of Alzheimer’s Dementia. Please see my previous post and this study.)

In heart failure some studies have shown that thiamine deficiency may play a role, which is logical given the known syndrome of wet beriberi. However, even in patients with heart failure due to other reasons such as coronary artery disease these patients often receive a diuretic called lasix to help keep fluid levels low in the body. It has been shown that lasix causes increased excretion of thiamine which leads to low levels further worsening heart failure. Finally this was studied in a well designed but disgracefully small study (9 patients). The study showed a 4% improvement in cardiac function (which in heart failure patients is a lot) with thiamine supplementation. There is also a well-known heart failure in alcoholics called alcoholic cardiomyopathy which could easily at least partially be explained by thiamine deficiency yet few of these patients receive thiamine supplementation at home. And then there is a large group of what we call idiopathic cardiomyopathies where patients have heart failure of unknown cause. Despite not being able to find a cause thiamine deficiency is rarely if ever entertained and thiamine is equally rarely given. Given the data I see no reason why every single hear failure patient shouldn’t be given thiamine supplementation. Many of them are on lasix anyway which deplete thiamine and may further worsen their heart failure. And in a small group we may find that thiamine deficiency was the sole cause of their heart failure and they will be cured. The study to look into the effect of thiamine on heart failure would be easy to do with a randomized controlled trial. However, given thiamine’s almost complete lack of risk for toxicity and being very cheap I see no reason not to give all heart failure patients thiamine now with the data we already have.

Early studies are showing too that thiamine may be especially helpful for diabetics especially in preventing damage to peripheral nerves which can cause a condition called diabetic neuropathy, which causes tingling, pain, or numbness in the toes, feet and legs. This article even lays out how thiamine deficiency may play a key role in the damage to blood vessels that lead to heart disease, eye problems and strokes in diabetics.

This placebo controlled trial showed an improvement in energy levels, mental clarity and response times with thiamine supplementation of 50 mg/day. This was in individuals who at baseline had what was considered adequate thiamine intake and levels.

Thiamine and cancer is being actively investigated. It has been shown that thiamine levels are very low in cancer patients. However, this does NOT mean that thiamine deficiency causes or even increases the risk for cancer. It is entirely possible that the thiamine deficiency is caused by the cancer or is actually part of the body’s defense mechanisms against the cancer. One supporting piece of information for this is the observation in one study that cancer growth actually increased at doses a few times higher than the recommended daily allowance. However it has also been shown that thiamine doses thousands of times higher than the RDA dose actually inhibit cancer growth. This is an ongoing area of investigation and will be very interesting to watch going forward. But given the current data giving thiamine to cancer patients without thiamine deficient symptoms would not be advisable as data to date shows no benefit and possible harm.

Overall with the data we have so far the role of thiamine in heart failure and diabetes should be investigated with larger placebo controlled trials. But given its almost complete lack of toxicity and the data we already have so far likely all patients with heart failure and all diabetics should be on a relatively high does of thiamine (about 50 mg) daily.

Thiamine is a prime example of how vitamins can serve as medicine while being far cheaper and safer than modern pharmaceuticals.

References

Thiamine and Alzheimer’s http://www.ncbi.nlm.nih.gov/pubmed/22218733

CSF thiamine levels and Alzheimer’s http://www.ncbi.nlm.nih.gov/pubmed/12111441

Vitamin A and Alzheimer’s – http://www.ncbi.nlm.nih.gov/pubmed/22221326

Lasix, heart failure and thiamine – http://www.ncbi.nlm.nih.gov/pubmed/1867241

Small but well designed thiamine study – http://www.ncbi.nlm.nih.gov/pubmed/22057652

Thiamine and Diabetic neuropathy – http://www.ncbi.nlm.nih.gov/pubmed/21342411, http://www.ncbi.nlm.nih.gov/pubmed/19057893

Article on thiamine and its role in vascular damage in diabetics – http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376872/