Pellagra: History and Discovery

Pellagra, arising from insufficient niacin intake, derives its name from the Italian phrase "pelle agra," translating to rough skin. Originating in the Lombard dialect of Northern Italy, this term underscores the condition's most prominent clinical feature.

In 1735, Spanish physician Don Gaspar Casal identified pellagra among peasants in Spain's Asturia region, labeling it "mal de la rosa." This ailment exhibited classic symptoms like dermatitis, diarrhea, and dementia, often resulting in fatality. Casal's posthumous work in 1762 extensively elaborated on the condition, using a Spanish term that echoed the characteristic sunburn-like skin erythema associated with pellagra.

The initial documented cases of the disease in 1755 and 1762 provided an accurate description, linking it to spoiled maize. Pellagra emerged in Italy approximately 50-100 years later, persisting widely in the country during the nineteenth century, with Lombardy reporting 39,000 cases in 1862. Serbia and Southern Russia grappled with the disease in the early 20th century.

The term "pellagra" likely made its debut in 1771 in Milan, Italy, coining the name that denotes "rough skin." Frappoli in 1771 proposed the term, possibly tracing its origins to the "pellarella" documented in Milan in 1578.

In the first half of the 19th century, societal aspects of pellagra gained attention, particularly in Liberali's 1831 studies on the manic dementia linked to the condition. Pellagra vanished from Southern France around 1880, and by 1916, it had nearly disappeared in Italy for reasons that remain unclear.

In 1922, Goldberger and Tanner suggested that pellagra resulted from an amino-acid deficiency. Joseph Goldberger, an American physician and epidemiologist, is acclaimed in American clinical epidemiology for his pellagra studies in the early 20th century.

The 1937 discovery that pellagra is caused by a deficiency in niacin (nicotinic acid), a B vitamin, highlighted that the body's synthesis of this vitamin depends on the availability of the essential amino acid tryptophan, found in milk, cheese, fish, meat, and eggs.
Pellagra: History and Discovery

Discovery and history of niacin

Recognition that niacin is a vitamin in the early 20th century resulted from efforts to understand and treat a widespread human disease – pellagra.

Pellagra was probably first observed in 1735 in Asturias, autonomous community in Kingdom of Spain.

It was identified among the peasants by Don Gaspar Casal in 1735, soon after the maize was introduced into Europe. A loathsome skin disease, it was called “mal de la rosa” and often mistaken for leprosy.

Pellagra was already an epidemic in Europe in the 18th century, and in the first half of the 20th century it also started its spread in the United States of America, particularly among the poorest social classes.

In 1915, American epidemiologist and US Public Health Service officer Joseph Goldberger conducted a series of experiments on 11 healthy volunteer prisoners in a Mississippi jail and found that he could induce pellagra by altering their diets. He concluded that the disease was caused by the absence of some factor that was lacking in corn. He named it the P-P (for pellagra-preventative) factor.

In 1937, American biochemist Conrad Arnold Elvehjem and his colleagues successfully isolated the vitamin and demonstrated that pure nicotinic acid and nicotinic acid amide would reverse the pellagra and black tongue in dogs by feeding them the Goldberger diet.

He also isolated the P-P factor from active liver extracts, showing that this factor is actually nicotinic acid (subsequently named niacin for nicotinic acid vitamin).

The discovery of niacin as the antipellagra vitamin was announced by C. A. Elvehjem, R. J. Madden, F. M. Strong, and D. W. Woolley in 1937 (J. Am. Chem. Xoc. 59, 1767 (1937)),

During the following year a number of clinical trials were made which established beyond doubt the value of niacin in the treatment of pellagra, and that the acid or its amide should be regarded as the P-P (pellagrapreventive) factor.
Discovery and history of niacin

History and discovery of vitamin B3 (niacin)

Pellagra was first described in Spain by Don Gaspar Casal in 1735 after the introduction of maize into Europe from the America. Pellagra has sometimes been called the disease of the four Ds – dermatitis, diarrhoea, dementia and death.

In the 1920s, Goldberger in the United States reported that pellagra and black tongue in dogs responded to treatment with animal protein and also to boiled protein-free extracts of yeast.

Niacin was first described by chemist Hugo Weidel in 1873. It was extracted by Casimir Funk in 1912 while he was trying to find a cure for another disease known as beriberi, but he thought it to be thiamine.

Casimir Funk abandoned his work after finding that nicotinic acid had no effect on beriberi.

In 1915, American epidemiologist and US Public Health Service officer Joseph Goldberger conducted a classic series of observational and experimental studies in humans, combined with an extensive series of experiments with an animal model of the condition (black tongue in dogs).

Afterward, Conrad Elvehjem a biochemist from Wisconsin in 1937 extracted an active ingredient from livers that was referred as ‘pellagra-preventing factor’ and the ‘anti-black tongue factor’ called niacin.

In general, it has been termed as ‘vitamin PP,’ ‘vitamin P-P,’ and ‘PP factor.’ The name niacin comes from nicotinic acid + vitamin, to distance itself from the word nicotine, which the public knows as a toxic chemical found in tobacco.
History and discovery of vitamin B3 (niacin)

Functions of niacin in human body

Niacin (also known as vitamin B3) is the generic name for nicotinic acid (pyridine-3-carboxylic acid), nicotinamide (niacinamide or pyridine-3-carboxamide), and related derivatives, such as nicotinamide riboside.

Niacin is required for cell respiration and helps in the release of energy and metabolism of carbohydrates, fats and proteins, proper circulation, maintenance of healthy skin, functioning of the nervous system and normal secretion of bile and stomach fluids. Niacin is important for the development and function of the cells.

A sufficient intake of vitamin B3 (niacin) is important as it helps the body to
• convert food into glucose, used to produce energy
• produce macromolecules, including fatty acids and cholesterol
• DNA repair and stress responses.

Niacin is found in multivitamin/multimineral supplements. It is also available in B-complex dietary supplements and supplements containing only niacin. The two main forms of niacin in dietary supplements are nicotinic acid and nicotinamide.
Functions of niacin in human body

Niacin: An essential human nutrient

Niacin (also known as “vitamin B3” or “vitamin PP”) is the generic descriptor for two vitamers, nicotinic acid (pyridine-3-carboxylic acid) and nicotinamide (nicotinic acid amide).

Niacin is quickly and easily absorbed from the intestinal tract and distributed extensively to body tissue after being hepatically metabolized. It is converted by the body to its active coenzyme forms, nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate.

NAD and NADP where their oxidized forms, that is, NAD+ and NADP+ play an essential role in many biochemical reactions. The two coenzymes are required for oxidative reactions crucial for energy production, but they are also substrates for enzymes involved in non-redox signaling pathways, thus regulating biological functions, including gene expression, cell cycle progression, DNA repair and cell death.

Niacin is a B vitamin that's made and used by human body to turn food into energy. It is required for cell respiration and helps in the release of energy and metabolism of carbohydrates, fats and proteins, proper circulation, maintenance of healthy skin, functioning of the nervous system and normal secretion of bile and stomach fluids.

Niacin also helps the body make sex- and stress-related hormones and improves circulation and cholesterol levels.

Clinical evidence of niacin deficiency includes fatigue, poor appetite, diarrhea, irritability, headache, emotional instability and possible memory loss. These may lead to changes in the skin, mucosa of the mouth, stomach and intestinal tract and the nervous system.
Niacin: An essential human nutrient

Pellagra

Pellagra results from a niacin and/or tryptophan deficient diet. It is still endemic in areas of Africa and Asia because of poor nutrition and intake of certain cereals such as maize and jowar (Indian millet): the staple diet.

It is rare complication that typically manifests late in the course of the disease and should be treated with low doses of niacin supplements. Pellagra was first described in 1735 by Don Gaspar Casal by the name ‘mal de la rosa’ due to the reddish and glossy rash that he noted amongst the poor of Spain.

Casal recorded all the clinical characteristics and ascribed the disease to the unbalanced diets, based on maize, of poor peasants in the Asturia region of Spain. The next description of the disease came from Italy in 1771 when pellagra was given its name, meaning "rough skin".

Pellagra is a nutritional disorder that is characterized classically with three Ds, namely dermatitis, diarrhea and dementia. Pellagra is a clinical syndrome characterized by:
(1) symmetric photosensitive skin eruptions;
(2) gastrointestinal manifestations; and
(3) neurologic and psychiatric disturbances.
Pellagra

Food sources of vitamin B3

Niacin, also known as vitamin B3, the third water-soluble vitamin discovered. Niacin is the generic term for nicotinic acid (pyridine 3-carboxylic acid) and nicotinamide (nicotinic acid amide). Both are used to form the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) which play essential roles for the development and function of living cells in human body.

Niacin is found naturally in many foods, and is added to some foods.
• Poultry, beef, pork, anchovies and fish
• Some types of peanuts, nuts, legumes, and grains
• Enriched and fortified foods, such as many breads and cereals
• Whole grains and whole meal wheat flour

In general, food rich in protein, with the exception of tryptophan-poor grains (e.g., corn, wheat), can satisfy some of the requirement for niacin. Important food sources of tryptophan are meat, milk and eggs.

The amino acid tryptophan contributes as much as two thirds of the niacin activity required by adults in typical diets.

Peanut butter is an excellent source of niacin. Fruits and vegetables provide useful amounts, depending upon the dietary intake. Other useful sources are whole grain cereals, bread, tea, and coffee.

Human milk contains a higher concentration of niacin than cow’s milk. In plants, especially in mature cereal grains like corn and wheat, niacin may be bound to sugar molecules in the form of glycosides, thus significantly reducing niacin bioavailability.

B3 (niacin) is important as it helps the body to
• convert food into glucose, used to produce energy
• produce macromolecules, including fatty acids and cholesterol
• DNA repair and stress responses.

Most people in the United States get enough niacin from the foods they eat. Niacin deficiency is very rare in the United States.
Food sources of vitamin B3

Lack of niacin can cause pellagra

Pellagra results from a niacin and/or tryptophan deficient diet which produces psychosis and dementia, among other symptoms. Niacin, known as vitamin B3, is a water-soluble, vitamin of the B complex group of vitamins.

The earliest description of pellagra was that of the Spanish physician Don Gaspar Casal in 1763.Casal recorded all the clinical characteristics and ascribed the disease to the unbalanced diets, based on maize, of poor peasants in the Asturia region of Spain. The next description of the disease came from Italy in 1771 when pellagra was given its name, meaning "rough skin".

Pellagra mostly found in parts of India, China, and Africa where corn or maize as a staple food. The characteristic manifestations appear as dermatitis, diarrhea and dementia ("the three Ds") and can lead to death (the fourth D).

Causes of pellagra can be divided into primary and secondary. Primary pellagra is due to dietary deficiency. High leucine content in corn/maize prevents conversion of tryptophan to niacin, leading to deficiency of niacin. Secondary pellagra is due to defective absorption or metabolism of niacin/tryptophan.

Early neurological symptoms associated with pellagra include anxiety, depression, and fatigue; later symptoms include apathy, headache, dizziness, irritability and tremors. In early cases the manifestations are psychoneurotic; later, lesions affect the nerves. As the disease advances, patients become confused, disoriented, and delirious, then comatose and stuporous, and finally die.

Mental aberrations may pass to dementia: about 4-10 % of chronic pellagra patients developmental symptoms.

In the western world, it is almost eradicated due to fortification of flour with niacin.

Lack of niacin can cause pellagra 

Niacin deficiency

First documented in 1735 by a Spanish physician named Gaspar Casal the niacin deficiency disease pellagra was originally named ‘mal de la rosa,’ or ‘red sickness.’ Its due to the telltale redness that appears around the necks of people with the disease. 

Pellagra means ‘rough skin’ in Italian. The great pellagra epidemic in America’s South did not emerged until the early twentieth century. 

Because the niacin coenzymes NAD and NADP are involved in just about very metabolite pathway, niacin deficiency wreaks havoc throughout the body. It also that the depressive psychosis is assumed to be because of inadequate formation of the neurotransmitter serotonin as a result of tryptophan deficiency. 

The classical features of endemic pellagra are dermatitis, inflammation of the mucous membranes, diarrhea and psychiatric disturbances. The dermatitis often appears after exposure to sunlight and resembles sunburn. 

Pellagra condones to plaque people living in Southeast Asia and Africa however, whose diet lack sufficient niacin and protein. 

Niacin deficiency

Vitamin B - Niacin

Niacin is a water soluble B vitamin important for DNA repair and energy metabolism.

Niacin is the name for two similar nicotinic acid and nicotinamide. In 1867, nicotinic acid was produced from nicotine in tobacco. In the early 1940s, with its role as a vitamin established, it was renamed “niacin” so people wouldn’t confuse it with nicotine.

Niacin is part of coenzyme that participates in the production and breakdown of carbohydrates, fatty acids, and amino acids. It involved in at least 200 metabolic pathways.

It is also a compound that dilates blood vessel. Deficiency on niacin causes pellagra a (disease that causes diarrhea, dermatitis, nervous disorders, and sometimes death).

Pellagra is characteristically associated with maize based diets.

The disease pellagra has been known since the introduction of corn to Europe in the 1770s. The connection between pellagra and niacin was confirm in 1937 by an American scientist who reaching for the cause of pellagra.

In industrialized country, particularly among alcoholics, niacin deficiency may present with only encephalopathy.

Niacin comes form the diet, but the body can also manufacture it from the amino acid tryptophan, with riboflavin helping out in the process.

Adults require 13-20 mg niacin. In pregnancy, lactation and active muscular work, niacin requirement is further increased by 3-4 mg. Children require 5-16 mg niacin.

Most niacin in the American diet comes from meat, poultry, fish, nuts and peanuts an enriched and while grain products.

In grains, niacin is present ion covalently bound complexes with small peptides and carbohydrates, collectively referred to as niacin.
Vitamin B - Niacin

Food Source of Niacin, Vitamin B6, and Folic Acid

Food Source of Niacin, Vitamin B6, and Folic Acid
Niacin or Nicotinamide nicotinic acid
In Central Europe a niacin deficiency is likely only when the diet deviates greatly from the common practices.

Severe alcoholics are especially at risk. On average, more than twice the recommended intake is consumed with the diet, about half in the form of pre-synthesized niacin and half as tryptophan.

About 50% of the pre-synthesized niacin is derived from meat and fish, which also provide about 30% of the dietary tryptophan. About 25% of the tryptophan comes from milk and eggs.

Vitamin B6
The following foods contribute significantly or are rich vitamin B6;
Meat and liver
Certain types of fish (e.g. sardine, mackerel
Milk and its products
Certain types of cheese (e.g. camembert)
Whole grain products
Some types of vegetables (cabbage green beans)
Potatoes

Folic acid
Folate rich foods,, and those which contribute significantly to the dietary requirements are for example, certain types of vegetables (tomatoes, cabbage family, spinach, beets, cucumbers) bread and baked goods (especially those from whole grain flour). Potatoes, meat, liver, milk and milk products, some kinds of cheese, and eggs.

Wheat germs and soy beans are specially rich in folate.
Food Source of Niacin, Vitamin B6, and Folic Acid

B Vitamins – Niacin, Pyridoxine and Biotin

B Vitamins – Niacin, Pyridoxine and Biotin
Niacin (nicotinic acid) is one of vitamin B. This compound is part of an enzyme system regulating reduction reactions in the body. It is also a compound that dilates blood vessels. Deficiency of niacin causes pellagra (a disease that causes diarrhea, dermatitis, nervous disorders, and sometimes death). The requirement for niacin is about ten times that for thiamin. Beef, hog and lamb livers are excellent sources of niacin. Other organs and the musculature of these animals are good to fair sources.

Pyridoxine (Vitamin B6) is part of the enzyme system that remove CO2 from the acid group (COOH) of certain amino acids and transfers amine groups (NH2) from one compound to another in the body. It is also needed for the utilization of certain amino acids. Deficiency manifestations are dermatitis around the eyes, eyebrows, and angles of the mouth. They may so be a sensory neuritis and a decrease in certain white blood cells and increase in others. Bananas, barley, beef and beef organs, cabbage, raw carrots, yellow corn, lamb and the organs of lamb, malt ,molasses, peanuts, pork and the organs of hogs, potatoes, rice, salmon, sardine, tomatoes, tuna, wheat bran and germ, flour and yams are goods to excellent source of pyridoxine.

Biotin is reported to be a coenzyme in the synthesis of aspartic acid, which plays a part in a deaminase system and in other processes involving the fixation of carbon dioxide. Deficiency of this compound is unusual, but can be demonstrated by the feeding of raw egg white, which contains the substance, avidin, which ties up biotin. Deficiencies of biotin cause scaling skin, skin lesion and a deterioration of nerve fibers. Due to the production of biotin by microbiological flora of the intestine, the requirement for this compound is not known, Liver is an excellent source of biotin, and peanut, peas, beans, and whole cooked eggs are good sources.
B Vitamins – Niacin, Pyridoxine and Biotin