Updated September 13, 2020

Link to Niacin
Link to Tryptophan

Tryptophan and niacin deficiency causes pellagra. The main symptoms of pellagra are dermatitis, dementia, and diarrhea. This is because niacin deficiency is most noticeable in body parts with high rates of cell turnover, such as your skin or gastrointestinal tract.

In the late 1800’s eastern civilization (North America, Canada and Europe) was eating more corn (maize) as a staple food. Corn contains niacytin, a form of niacin that humans can’t digest and absorb unless prepared properly. South American culture had figured out that corn needed to prepared by “nixtamalization,” in which the whole kernel is treated with a solution of alkali such as limewater (calcium hydroxide, NOT the lime fruit). (This process also removes up to 97–100% of aflatoxins from mycotoxin-contaminated corn). In 1901, the Beall degerminator was patented and used to separate the grit from the germ in corn processing. However this process of degermination without nixtamalization reduces the niacin content of the cornmeal by 90%. Today, this process is employed in the production of tortillas and tortilla chips (but not corn chips), tamales, hominy, and many other items. There is no precise date when the technology was developed, but the earliest evidence of nixtamalization is found in Guatemala’s southern coast, with equipment dating from 1200–1500 BCE.

In 1915, Joseph Goldberger, a well-regarded researcher, was assigned to study pellagra by the Surgeon General of the United States. He showed pellagra was linked to diet by observing the outbreaks of pellagra in orphanages and mental hospitals. Goldberger noted that children between the ages of 6 and 12 (but not older or younger children at the orphanages) and patients at the mental hospitals (but not doctors or nurses) were the ones who seemed most susceptible to pellagra. Goldberger theorized that a lack of meat, milk, eggs, and legumes made those particular populations susceptible to pellagra. By modifying the diet served in these institutions with “a marked increase in the fresh animal and the leguminous protein foods,” Goldberger was able to show that pellagra could be prevented. By 1926, Goldberger established that a diet that included these foods, or a small amount of brewer’s yeast prevented pellagra.

Most of the niacin in mature cereal grains is present as niacytin, which is niacin bound up in a complex with hemicellulose which is nutritionally unavailable. In mature corn this may be up to 90% of the total niacin content. The preparation method of nixtamalization using the whole dried corn kernel made this niacin nutritionally available and reduced the chance of developing pellagra. Niacytin is concentrated in the aleurone and germ layers which are removed by milling. The milling and degerming of corn in the preparation of cornmeal became feasible with the development of the Beall degerminator which was originally patented in 1901 and was used to separate the grit from the germ in corn processing.[49] However this process of degermination reduces the niacin content of the cornmeal.

The US did not implement Goldberger’s recommendations until ____ by requiring all flour/corn (? clarify) to be fortified with niacinamide, which continues to this day. Canada waited another year or so, but would fortify the corn sent to Europe due to European demand.

https://en.wikipedia.org/wiki/Pellagra

https://en.wikipedia.org/wiki/Nixtamalization

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Dermatitis related to pellagra usually causes a rash on the face, lips, feet, or hands. In some people, dermatitis forms around the neck, a symptom known as Casal necklace.
Primary pellagra is caused by diets low in niacin or tryptophan. Tryptophan can be converted to niacin in the body, so not getting enough can cause niacin deficiency.

Primary pellagra is most common in developing countries that depend on corn as a staple food. Corn contains niacytin, a form of niacin that humans can’t digest and absorb unless prepared properly.

Secondary pellagra occurs when your body can’t absorb niacin. Things that can prevent your body from absorbing niacin include:alcoholism
eating disorders
certain medications, including anti-convulsants and immunosuppressive drugs
gastrointestinal diseases, such as Crohn’s disease and ulcerative colitis
cirrhosis of the liver
carcinoid tumors
Hartnup disease
niacin synthesis, since B6 (pyridoxine) is a required cofactor in the tryptophan-to-niacin reaction.

Several therapeutic drugs can provoke pellagra. These include the antibiotics isoniazid, which decreases available B6 by binding to it and making it inactive, so it cannot be used in niacin synthesis,[11] and chloramphenicol; the anti-cancer agent fluorouracil; and the immunosuppressant mercaptopurine.[10]

If maize is not nixtamalized, it is a poor source of tryptophan, as well as niacin. Nixtamalization corrects the niacin deficiency, and is a common practice in Native American cultures that grow corn. Following the corn cycle, the symptoms usually appear during spring, increase in the summer due to greater sun exposure, and return the following spring. Indeed, pellagra was once endemic in the poorer states of the U.S. South, such as Mississippi and Alabama, where its cyclical appearance in the spring after meat-heavy winter diets led to it being known as “spring sickness” (particularly when it appeared among more vulnerable children), as well as among the residents of jails and orphanages as studied by Dr. Joseph Goldberger.[12]

Third, it may be caused by excess leucine, as it inhibits quinolinate phosphoribosyl transferase (QPRT) and inhibits the formation of niacin or nicotinic acid to nicotinamide mononucleotide (NMN) causing pellegra like symptoms to occur.

The native New World cultivators who first domesticated corn (maize) prepared it by nixtamalization, in which the grain is treated with a solution of alkali such as lime. Nixtamalization makes the niacin nutritionally available and prevents pellagra. When maize was cultivated worldwide, and eaten as a staple without nixtamalization, pellagra became common.

In 1937, Conrad Elvehjem, a biochemistry professor at the University of Wisconsin-Madison, showed that the vitamin niacin cured pellagra (manifested as black tongue) in dogs. Later studies by Dr. Tom Spies, Marion Blankenhorn, and Clark Cooper established that niacin also cured pellagra in humans, for which Time Magazine dubbed them its 1938 Men of the Year in comprehensive science.

Research conducted between 1900 and 1950 found the number of cases of women with pellagra was consistently double the number of cases of afflicted men.[41] This is thought to be due to the inhibitory effect of estrogen on the conversion of the amino acid tryptophan to niacin.[42] Some researchers of the time gave a few explanations regarding the difference.

unknown toxin in corn.[31] The Spartanburg Pellagra Hospital in Spartanburg, South Carolina, was the nation’s first facility dedicated to discovering the cause of pellagra. It was established in 1914 with a special congressional appropriation to the U.S. Public Health Service (PHS) and set up primarily for research. In 1915, Joseph Goldberger, assigned to study pellagra by the Surgeon General of the United States, showed it was linked to diet by observing the outbreaks of pellagra in orphanages and mental hospitals. Goldberger noted that children between the ages of 6 and 12 (but not older or younger children at the orphanages) and patients at the mental hospitals (but not doctors or nurses) were the ones who seemed most susceptible to pellagra.[32] Goldberger theorized that a lack of meat, milk, eggs, and legumes made those particular populations susceptible to pellagra. By modifying the diet served in these institutions with “a marked increase in the fresh animal and the leguminous protein foods,” Goldberger was able to show that pellagra could be prevented. By 1926, Goldberger established that a diet that included these foods, or a small amount of brewer’s yeast, prevented pellagra.

Casimir Funk, who helped elucidate the role of thiamin in the etiology of beriberi, was an early investigator of the problem of pellagra. Funk suggested that a change in the method of milling corn was responsible for the outbreak of pellagra,[50] but no attention was paid to his article on this subject.

Pellagra developed especially among the vulnerable populations in institutions such as orphanages and prisons, because of the monotonous and restricted diet. Soon pellagra began to occur in epidemic proportions in states south of the Potomac and Ohio rivers. The pellagra epidemic lasted for nearly four decades beginning in 1906. It was estimated that there were 3 million cases and 100,000 deaths due to pellagra during the epidemic.

Casimir Funk, who helped elucidate the role of thiamin in the etiology of beriberi, was an early investigator of the problem of pellagra. Funk suggested that a change in the method of milling corn was responsible for the outbreak of pellagra, but no attention was paid to his article on this subject.

Pellagra developed especially among the vulnerable populations in institutions such as orphanages and prisons, because of the monotonous and restricted diet. Soon pellagra began to occur in epidemic proportions in states south of the Potomac and Ohio rivers. The pellagra epidemic lasted for nearly four decades beginning in 1906.[51] It was estimated that there were 3 million cases and 100,000 deaths due to pellagra during the epidemic.