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.