Pellagra: Interesting Alert-NIH

WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite the treatable dementia and psychosis, pellagra is often under-diagnosed, especially in developed countries and alcoholic patients. Pellagra should be routinely suspected in alcoholic patients because the response to appropriate treatment is typically dramatic.


Alcoholic Pellagra as a Cause of Altered Mental Status in the Emergency Department ~ Source-NIH

BACKGROUND:

Pellagra, which is caused by a deficiency of niacin and tryptophan, the precursor of niacin, is a rare disease in developed countries where alcoholism is a major risk factor due to malnutrition and lack of B vitamins. Although pellagra involves treatable dementia and psychosis, it is often underdiagnosed, especially in developed countries.

CASE REPORT:

In Japan, a 37-year-old man presented to the emergency department with altered mental status and seizures. Wernicke encephalopathy and alcohol withdrawal were suspected. The patient was treated with multivitamins, which did not include nicotinic acid amide, and oral diazepam. Despite medical treatment, his cognitive impairment progressively worsened, and eventually, pellagra was suspected. His response to treatment with nicotinic acid amide was substantial, and he was discharged without any long-term sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite the treatable dementia and psychosis, pellagra is often underdiagnosed, especially in developed countries and alcoholic patients. Pellagra should be routinely suspected in alcoholic patients because the response to appropriate treatment is typically dramatic.

Pellagra and Alcoholism

In many cases, diagnosing pellagra involves seeing if your symptoms respond to niacin supplements. ~Healthline

How is it treated?

Primary pellagra is treated with dietary changes and a niacin or nicotinamide supplement. It may also need to be given intravenously. Nicotinamide is another form of vitamin B-3. With early treatment, many people make a full recovery and start feeling better within a few days of starting treatment. Skin improvement may take several months. However, if left untreated, primary pellagra usually causes death after four or five years.

A Biochemical Perspective ~ Source NIH

Historical and clinical aspects of pellagra and its relationship to alcoholism are reviewed from a biochemical perspective. Pellagra is caused by deficiency of niacin (nicotinic acid) and/or its tryptophan (Trp) precursor and is compounded by B vitamin deficiencies. Existence on maize or sorghum diets and loss of or failure to isolate niacin from them led to pellagra incidence in India, South Africa, Southern Europe in the 18th century and the USA following the civil war.

Pellagra is also induced by drugs inhibiting the conversion of Trp to niacin and by conditions of gastrointestinal dysfunction. Skin photosensitivity in pellagra may be due to decreased synthesis of the Trp metabolite picolinic acid → zinc deficiency → decreased skin levels of the histidine metabolite urocanic acid and possibly also increased levels of the haem precursor 5-aminolaevulinic acid (5-ALA) and photo-reactive porphyrins.

Depression in pellagra may be due to a serotonin deficiency caused by decreased Trp availability to the brain. Anxiety and other neurological disturbances may be caused by 5-ALA and the Trp metabolite kynurenic acid.

Pellagra symptoms are resolved by niacin, but aggravated mainly by vitamin B6. Alcohol dependence can induce or aggravate pellagra by inducing malnutrition, gastrointestinal disturbances and B vitamin deficiencies, inhibiting the conversion of Trp to niacin and promoting the accumulation of 5-ALA and porphyrins. Alcoholic pellagra encephalopathy should be managed with niacin, other B vitamins and adequate protein nutrition. Future studies should explore the potential role of 5-ALA and also KA in the skin and neurological disturbances in pellagra.


Pellagra encephalopathy following B-complex vitamin treatment without niacin. ~ Source NIH

Pellagra is caused by nicotinic acid deficiency; it is rarely encountered in developed countries, and it is mainly related to poverty and malnutrition, as well as with chronic alcoholism. We report the case of an alcoholic patient who was diagnosed with pellagra and administered B-complex vitamin tablets that did not contain niacin. A few weeks later, the patient developed nervousness, irritability, insomnia and, consequently, delusional ideas and hallucinations, for which he had to be hospitalized. After his admission, the patient manifested loss of consciousness and myoclonus. All of his symptoms (cutaneous, neurological, and psychiatric) resolved fully with treatment with niacin in combination with other B-complex vitamins. All undiagnosed encephalopathies in alcoholic patients should be treated with multiple vitamin therapy, including nicotinic acid.


Pellagra: rekindling of an old flame. ~ Source

Pellagra is a disease largely associated with alcohol abuse, poverty, and malnutrition and is very common in developing countries. However, in the wake of “slimmer is better” fads and the ever-growing population of patients infected with human immunodeficiency virus, it may be on the surge in the United States. This vitamin deficiency disorder, though easy to diagnose and treat, can be easily missed and requires a high index of suspicion. We describe a case involving a patient who presented with the classic triad of “diarrhea, dermatitis, and dementia” and was promptly diagnosed and appropriately treated.


Treating secondary pellagra usually focuses on treating the underlying cause. However, some cases of secondary pellagra also respond well to taking niacin or nicotinamide either orally or intravenously.

While recovering from either primary or secondary pellagra, it’s important to keep any rashes moisturized and protected with sunscreen.

Pellagra is a serious condition that’s caused by low levels of niacin, due to either malnutrition or an absorption problem. If left untreated, it can cause death.

While primary pellagra responds well to niacin supplementation, secondary pellagra can be harder to treat, depending on the underlying cause.

Niacin: No flush, No good.

More on niacin: No flush, no good

Several readers wrote in wanting to know more about why we don’t recommend no-flush niacin products. A little bit of background will help us explain.

The term niacin comes from nicotinic acid vitamin, but it’s used to refer to both nicotinic acid and a closely related molecule, nicotinamide. Both nicotinic acid and nicotinamide are necessary to prevent pellagra, a disease that causes skin inflammation, diarrhea, and dementia. After they were first discovered in the 1930s, nicotinic acid and nicotinamide were known for a time as the pellagra-preventing vitamins.

In the mid-1950s, researchers discovered that nicotinic acid — but not nicotinamide — was remarkably effective at lowering cholesterol and triglyceride levels. We talk about niacin having these good effects, partly because niacin appears on ingredient and nutrition labels, but strictly speaking, it’s just nicotinic acid that does.

Nicotinic acid — but again, not nicotinamide — also triggers the release of prostaglandins that cause flushing, a more severe and sometimes uncomfortable form of the blushing that occurs when we’re embarrassed. So researchers have looked for ways to chemically package nicotinic acid so it retains its cholesterol- and triglyceride-lowering effects but doesn’t turn people red-faced.

Inositol hexaniacinate looked like it might be the answer. It’s a combination of six molecules of nicotinic acid (thus hexaniacinate) and one molecule of inositol. The hope was that it would break down slowly so the nicotinic acid would hit the bloodstream gradually and not cause flushing.

Results in rabbits were promising. But in a number of trials conducted in people in the late 1970s, the compound had little, if any, effect on cholesterol. Other research has shown peak levels of nicotinic acid in the blood from inositol hexaniacinate were a tiny fraction of those seen after a person took crystalline or sustained-release forms of niacin.

The niacin in every no-flush product we’ve seen comes as inositol hexaniacinate. The no-flush claim is true enough, but the credible evidence we know of suggests that you aren’t likely to see the cholesterol or triglyceride benefits, either. For a niacin product to have an effect on cholesterol and triglyceride levels, the niacin must be in the form of nicotinic acid — not inositol hexaniacinate or nicotinamide.

Effects of Niacin on Brain Function and Cognition

Brief Summary: The purpose of this study is to determine the effects of Niagen (nicotinamide riboside, vitamin B3), on NAD levels, brain function including cognition and blood flow in people diagnosed with mild cognitive impairment (MCI).
Detailed Description: Niagen is a patented formula which is the first and only commercially available form of Nicotinamide Riboside (NR). It has been proven in basic science studies as a highly effective NAD booster, but it also works as a vitamin B3 supplement.[BECAUSE IT IS VITAMIN B-3] NAD helps pass energy from glucose to other pathways in the cell. Niagen (Nicotinamide Riboside, vitamin B3) is one of the most effective NAD+ precursors to support cellular health.
The purpose of this study is to determine the effects of Niagen (nicotinamide riboside, vitamin B3), on NAD levels, brain function including cognition and blood flow in people diagnosed with mild cognitive impairment (MCI).

Ages Eligible for Study: 65 Years and older   (Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: Yes

Inclusion Criteria:

  • Previously diagnosed with MCI based on inclusion criteria of Texas Alzheimer’s Research Care and Consortium (TARCC) study (IRB: HSC20090535H). We are enrolling both genders, all races and ethnic groups.
  • Two week washout period for participants who were taking opioids or a dose of niacin over 200mg.

Exclusion Criteria:

  • Previously considered as healthy individuals without a MCI or Alzheimer’s disease diagnosis based on exclusion criteria of the TARCC study (IRB: HSC20090535H).
  • Neurological, psychiatric or active systemic medical disease
  • Diabetes
  • Moderate or severe depression and/or anxiety as determined the Geriatric Depression Scale (GDS) and the Geriatric Anxiety Scale (GAS), respectively
  • Diagnosis of dementia
  • Hearing, vision, motor or language deficits
  • Alcohol or drug abuse
  • Implantation of metal devices
  • Administration of Alzheimer’s drugs, anticholinergics, neuroleptics, anticonvulsants, opiates, systemic steroids, and mood-stabilizers.
  • No opioid use while participating in study

NAD or Niacin Therapy?

They are the same thing. One has a clinical name the other a vitamin store name. The same horse with a different name.

Pellagra be damned…8)

Type of vitamin B3 safely boosts levels of important cell metabolite

First clinical trial for nicotinamide riboside(VITAMIN B-3 Metabolite) shows promise<—NO/LOW FLUSH NIACIN

Self-study precedes clinical trial

~Source – University of Iowa

Prior to the formal clinical trial, Charles Brenner conducted a pilot human study—on himself. In 2004, he had discovered that NR is a natural product found in milk and that there is a pathway to convert NR to NAD+ in people. More than a decade of research on NR metabolic pathways and health effects in mice and rats had convinced him that NR supplementation had real promise to improve human health and wellness. After consulting with the UI’s institutional review board, he conducted an experiment in which he took 1 g of NR once a day for seven days, and his team analyzed blood and urine samples from him using mass spectrometry. The experiment showed that Brenner’s blood NAD+ increased by about 2.7 times. In addition, though he reported immediate sensitivity to flushing with the related compound niacin, he did not experience any side effects taking NR.


History of NAD(niacin therapy)-nicotinamide riboside.

  • Has been used since the late 1960s in intravenous form to significantly lessen withdrawal from a variety of drugs and alcohol.
  • Mechanism not clear. <–Anti-microbial. Specifically, Antihelmintic. That is anti-worm. Reversing the effects of pellagra and retraining the gut to correct any SIBO.
  • Limitation is that recovery tends not to be complete with IV NAD alone.
  • With addition of [specified amino acids complex], recovery is found to be significantly more profound, complete and lasting.

What Is NAD Therapy?

NAD, or nicotinamide adenine dinucleotide, is a naturally occurring co-enzyme of [NIACIN], vitamin B-3, that helps cells in our bodies produce energy. It does so by converting the energy we get from food into cellular energy. Administering lab-produced NAD will boost the levels of the chemical in someone’s body, but they will need to be administered more to sustain that level. NAD therapy can assist with brain function, DNA repair, and repair signals between molecules for cellular communication. Lastly, it aids in DNA repair. Only with a combination of NAD and regular therapy and support can someone stay on the path of recovery.

As a person abuses drugs and alcohol, their natural amount of NAD is depleted. This makes it more difficult for them to convert the energy that is broken down from food. It is even speculated that people who naturally produce less NAD are more likely to develop an addiction and potentially a co-occurring disorder. Other reasons the body’s natural reserve of NAD would be depleted are:

  • Post-traumatic stress
  • Anxiety
  • Depression
  • Chronic traumatic encephalopathy (CTE)
  • Alzheimer’s
  • Parkinson’s
  • Neurodegenerative diseases
  • Aging

All of these co-occurring disorders can drain one’s energy, and there are many ways to boost NAD in the body by exercising; eating vitamin-rich foods; fasting; eating protein; eating raw foods. Many of these practices are introduced to people in treatment for substance abuse disorders. For instance, yoga and fitness centers are available to encourage healthy lifestyle practices, boost endorphins and will produce lost NAD. Dietary plans can include vitamin-rich foods to boost dopamine and can produce NAD in the brain. Most patients need roughly 6 to 10 days of infusion to feel effects. Often times, individuals enjoy the pleasant feelings, they are less inclined to abuse substances.


Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.

~Source – Nature.com

The first controlled clinical trial of a newly discovered form of vitamin B3, nicotinamide riboside (NR), has shown that the compound is safe for humans. The study also shows NR increases levels of a cell metabolite that is critical for cellular energy production and protection against stress and DNA damage. Studies in mice have shown that boosting the levels of this cell metabolite—nicotinamide adenine dinucleotide, known as NAD+—can produce multiple health benefits, including resistance to weight gain, improved control of blood sugar and cholesterol, reduced nerve damage, and longer lifespan. Levels of NAD+ diminish with age, and other studies have suggested that loss of this metabolite may play a role in age-related health decline.

Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.

~Source – Nature.com

We report that human blood NAD+ can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD+ with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide.

Thoughts-2019/12/10

A.A. as described in The Big Book, The 12 Traditions and 12 Steps is simply a framework. There is nothing living about these things. They are the first principles laid down as foundational stones. We A.A.’s or members of A.A. are as living stones formed over this framework. It is a framework that is inhabited by personalities. Sometimes these personalities that inhabit the framework grow strong in their own self interests. Not all of those individuals are healthy and sometimes hurt other people along the way to achieve their self interests.

Nicotine, Niacin and Double Vision

A cursory study into tobacco use by teenagers appears to have discovered a new door into the causes of teenage smoking.  Nicotine has long been accepted as the addictive portion of tobacco products, but what is apparently little known is that nicotine and niacin (vitamin B3) are analogues.  An examination into this previously untrod avenue may yield significant new data into the treatment of teenage tobacco use.

Much research has been done establishing that teenagers do use tobacco, but very little has looked into the actual causes and none could be found on E.R.I.C. that has been done from the aspect that tobacco may fulfill a nutritional need.

As a parent of six children and a non-traditional graduate student, adolescent smoking is something I have had to deal with at least six times. As a graduate student with a grounding in communication, it is of primary concern to me, with all the information targeting teen smoking, that there has not been a more significant effect on the target audience — adolescents.

The Federal Interagency Forum on Child and Family Statistics (1998) shows a steady increase in smoking in that while 9% of the children in the 8th grade surveyed admitted to smoking every day, 24.6% of the 12th graders smoke daily.

The Federal Interagency Forum offered no answers but did recommend more study.

The statistics would seem to show that Festinger’s Theory of  Cognitive Dissonance (Festinger, L. 1957) does not apply to smoking.  Applying  Festinger’s theory, a greater amount of resources dedicated to preventing teen smoking should have led to a greater decrease in teen smoking, but that does not seem to be the case.  In fact, the opposite seems to have occurred. The teenagers exposed to the larger amount of anti-smoking information (the 12th Graders) were almost 3 times as likely to be smokers. This led me to ask whether the addictiveness of nicotine might have some influence on why a theory like Festinger’s, so well grounded in other areas, did not seem to work here.

Teenagers use tobacco.  That is an established fact.  What is up for contention is why do teenagers use tobacco, in spite of all the propaganda cultural pressure aimed at telling them not to. Many court cases have been fought on this issue but there is still little current information due to the mutability of the subject matter, children.

If teenager’s diets are niacin deficient and their bodies know what their minds don’t ( and their teachers won’t tell them), that niacin and nicotine are the same thing, their bodies would make them crave tobacco as the source of a necessary nutrient, but being a matter of taste, they would not be able to describe it scientifically.  An anecdotal reply might be — “I don’t know why I like it; I just do,”  with no understanding that it’s fulfilling necessary needs of the nervous system, like orange juice provides antioxidants for the body..  B Complex vitamins are just as important as vitamin C.  A lack of vitamin C compromises the immune system; a lack of B vitamins compromises the nervous system.

Another example is Iodine. Iodine is a poison but it is also a necessary nutrient. The body only needs a thimble full of Iodine for a lifetime but without that thimble full a lifetime is only a few years. The endocrine system self destructs without it. A smoker may only get a thimble full of Niacin from a lifetime of smoking (10-20mcg per cigarette), but at least they have that lifetime to discover and correct the problem (poor diet, alcoholism or malabsorptive bowel), which is how to get the Niacin without the other 43 carcinogenic substances the American Cancer Society has identified in Tobacco smoke.

The intention of this study is to discover if teenage tobacco use, smoking and other, may be the result of a niacin deficient diet, not tobacco advertising.  There may appear to have been an intentional deception in hiding the fact that niacin and nicotine are basically the same thing, but simply put, it’s because until now there has been no funding to look at tobacco from the point of view of a nutritional function. Tobacco has been used for a wide range of other maladies from Asthma ( Niacin prevents Histamine release Robert Thompson Cybervitamins.com) to Bowel obstruction (A Modern Herbal guide 1931).

My argument is that the real cause has been overlooked in the “rush to judgment” and nutritional deficiencies have been misdiagnosed as mere addictions, subject to whim and will. The body needs niacin and it knows nicotine will work if niacin isn’t available. This is not a conscious function.

The objective is to decrease adolescent smoking by removing the dietary deficiency, hence the body’s need for the nicotine. The U.S. RDA for niacin ranges from about 15mg to about 20mg per day, but to get that much a person needs to eat a serving of chicken , a serving of turkey, a serving of Spinach and a bowl of fortified cereal each day or smoke 2 packs of cigarettes.

This shed an entirely new light on the problem of teen smoking. It meant that teens might not be smoking because it was “cool” or because the nicotine was addictive; it might be because tobacco was fulfilling a nutritional deficiency in their diets.  Niacin deficiency is common outside the United States and, in its severest form, Pellagra, it can kill.  It is rare in this country because since Dr Goldberger discovered niacin as a nutrient in 1895, corn meal and wheat flour have been fortified much the same way as salt is fortified with iodine.

Iodine, as a substance, is a poison, but in very small amounts, it is required by the body for thyroid function and preventing unwanted growths like goiters. A body requires less than a thimbleful of iodine for a lifetime, but without that thimbleful, it doesn’t have a life. Niacin is similar in that it doesn’t take a lot (20 mg RDA) and too much is toxic. A single gram of niacin is toxic to most humans.

Niacin, like iodine, is hard to find in the diet without supplementing it somewhere.  For example, to receive the Recommended Daily Allowance (RDA) of niacin (20 mg), a person would need to eat 3 servings of poultry, 3 servings of pork and a baked potato with skin to get 20 mg of natural niacin. Other alternatives would include 5 bowls of fortified cereal or 15 servings of french fries. Another problem is that some people with gastrointestinal problems have trouble absorbing niacin, even if it is in the diet.

I realized that there was nothing wrong with Festinger’s Theory; what was wrong was the current view of nicotine as a cultural or behavioral symptom. A person has only 2 choices when it comes to oxygen, do it or die. The same choice applies to niacin and iodine. Without it we die.  Lack of niacin or iodine may not be as quick a death as a lack of oxygen, but the results are just as certain.

The result of this information was the formulation of a theory that teenagers may be smoking to fulfill the nutritional need for niacin. In order to test this, a comparison will be done comparing teen smoking and diet. The best way to do this is with a controlled survey of the high schools. If the information from the survey supports that teen smoking has a dietary link, then efforts will be made to improve the nutritional levels of that segment of our society that seems to have the least concern for nutrition, teenagers.

Vitamin B-3, Popcorn and Recovery

William Griffith Wilson, or Bill W., is regarded as the father of addiction treatment due to his leadership in establishing Alcoholics Anonymous. While Bill W. pioneered a movement that has helped millions achieve sobriety, in the final years of his life, he explored how alternative treatment methods, such as Niacin (a precursor to NAD Therapy), could improve the recovery process.

Vitamin B-3 Therapy Reports

The Vitamin B-3 Therapy-2nd Communication

The Vitamin B-3 Therapy-3rd Communication

Why does it work? What is it working on?

Skin flushing is one major side effect of the therapeutic use of nicotinic acid and the primary reason for non-adherence to treatment. Flushing is caused by the activation of phospholipase A2, an enzyme that stimulates the production of a specific lipid from the prostanoid family called prostaglandin D2. Prostaglandin D2, synthesized by antigen-presenting cells of the skin and mucosa (i.e., the Langerhans cells), can induce the dilation of blood vessels and trigger a flushing response. ~LINK

ANTIGEN: a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies.

Nicotine, Niacin and Double Vision

Linus Pauling Institute – NIACIN Deficiency – Got [pop]Corn?

The late stage of severe niacin deficiency is known as pellagra. Early records of pellagra followed the widespread cultivation of corn in Europe in the 1700s. The disease is generally associated with poorer social classes whose chief dietary staple consisted of cereal like corn or sorghum. Pellagra was also common in the southern United States during the early 1900s where income was low and corn products were a major dietary staple. Interestingly, pellagra was not known in Mexico, where corn was also an important dietary staple and much of the population was also poor. In fact, if corn contains appreciable amounts of niacin, it is present in a bound form that is not nutritionally available to humans. The traditional preparation of corn tortillas in Mexico involves soaking the corn in a lime (calcium oxide) solution, prior to cooking. Heating the corn in an alkaline solution results in the release of bound niacin, increasing its bioavailability. Pellagra epidemics were also unknown to Native Americans who consumed immature corn that contains predominantly unbound (bioavailable) niacin.


Niacin deficiency or pellagra may result from inadequate dietary intake of NAD precursors, including tryptophan. Niacin deficiency — often associated with malnutrition — is observed in the homeless population, in individuals suffering from anorexia nervosa or obesity, and in consumers of diets high in maize and poor in animal protein. Deficiencies of other B vitamins and some trace minerals may aggravate niacin deficiency. Malabsorptive disorders that can lead to pellagra include Crohn’s disease and megaduodenum. Patients with Hartnup’s disease, a hereditary disorder resulting in defective tryptophan absorption, have developed pellagra. Carcinoid syndrome, a condition of increased secretion of serotonin and other catecholamines by carcinoid tumors, may also result in pellagra due to increased utilization of dietary tryptophan for serotonin rather than niacin synthesis. Further, prolonged treatment with the anti-tuberculosis drug isoniazid has resulted in niacin deficiency. Other pharmaceutical agents, including the immunosuppressive drugs azathioprine(Imuran) and 6-mercaptopurine, the anti-cancer drug 5-fluorouracil (5-FU, Adrucil), and levodopa/carbidopa (Sinemet; two drugs given to people with Parkinson’s disease), are known to increase the reliance on dietary niacin by interfering with the tryptophan-kynurenine-niacin pathway. Finally, other populations at risk for niacin deficiency include dialysis patients, cancer patients, individuals suffering from chronic alcoholism, and people with HIV (see HIV/AIDS below). Further, chronic alcohol intake can lead to severe niacin deficiency through reducing dietary niacin intake and interfering with the tryptophan-to-NAD conversion.

Praying Atheists

As a member of A.A. we often speak of our best efforts ending up with us in the proverbial gutter. Oh the overactive irony in that an atheist find himself spending every day in a church and praying nonetheless.

That’s me. Go figure. A praying atheist.

“The focus of prayer is not the self…it is the momentary disregard of our personal concerns.” ~Abraham Joshua Heschel

Further reading…