Quote from David on May 14, 2024, 11:18 pm

@ggenereux2014

Below is a slightly edited older post from the end of 2021 about how many patients with pellagra (niacin deficiency) seemed to be helped by just eating more protein. I heard Kelsey Kenney talking about nicotinic acid being more of an amino acid than a vitamin and I think it fit quite well with this older post of mine. I think Kelsey Kenney have said sometime that she first heard that Dr. Carl Peiffer said nicotinc acid being more of an amino acid than a vitamin.

Note how the "discovery" of vitamin A is connected to the University of Wisconsin and many similar people working at the same institution: Department of Agricultural Chemistry, University of Wisconsin

This department then became connected to the foundation that Harry Steenbock later created:
Wisconsin Alumni Research Foundation (WARF)

 

Hi!

In this post I will look at the early discovery of vitamin B3 (Niacin/Nicotinic acid). The post picture is of Conrad Arnold Elvehjem (1901-1962) who is credited with discoverying vitamin B3 as essential. The attached portait picture is made by Aaron Bohrod, the University of Wisconsin’s artist-in residence from 1948-1973:
https://madisonstories.com/2007/11/13/more-than-pictures-at-an-exhibition-reflections-on-aaron-bohrod-a-life-and-still-life-at-the-james-watrous-gallery/

Vitamin B3 deficiency is said to be the cause of the awfully looking sickness, pellagra, so there is where I started to look. The first ones said to have shown pellagra was a dietary deficiency was Dr. Joseph Goldberg, C. H. Waring and David G. Willets in a 1915 paper called:

"The Prevention of Pellagra: A Test of Diet among Institutional Inmates".
https://www.jstor.org/stable/4572932?seq=1#metadata_info_tab_contents

After reading about how they stopped pellagra from relapsing in all subjects, except one, just by introducing more protein-rich foods; I can't stop to think about this study Dr. Smith have posted about how low protein diets can in and of itself create cholestasis:
https://pubmed.ncbi.nlm.nih.gov/7100632/

Quote from the 1915 study on pellagra:
"It is beside the present purpose to enter into a discussion of the etiology of pellagra. In order that the position of the writers may be clear, however, it is pointed out that they are not to be understood as meaning that pellagra is necessarily due to a lack or deficiency of fresh animal or leguminous protein food. All that they wish to say at present is that the dietary "fault" upon which in their judgment the development of pellagra essentially depends is capable of being corrected or prevented by including in the diet a suitable proportion of these foods."

More protein and the awful looking disease of pellagra seems to go away but as they say in the 1915 study they don't really know exactly why but do believe fresh food like meat and milk is important. The 1915 study make this quote about an earlier Thompson-MacFadden Pellagra Commission which from big amounts of data could not finding any food connected to preventing or causing pellagra:

"In fact, it is believed by the writers [of the 1915 Goldberg et. al. study] that an analysis of the commission's data from this point of view will show, for instance, that there does exist, or may exist, in a group of cotton-mill villages an inverse proportional relation between degree of pellagra morbidity and the percentage of families using fresh meat and milk "daily" and "habitually."

This was before the common use of pasteurization of milk, which aning other things denatures lactoferrin. The first pasteurized milk ordinance was published in 1924, in the November issue of Public Health Reports.
https://web.archive.org/web/20150404034511/https://www.oie.int/doc/ged/d9152.pdf

See below a quote of a pellagra case report about a 46 years old male who gave himself pellagra from abstaining from meat, probably due from protein deficiency. Severe alcholism, famine and other reasons for serious malnutrition also causes protein deficiency and a weakened body. Protein deficiency seems to me like the main culprit for causing pellagra.
"THE USE OF NICOTINIC ACID IN THE TREATMENT OF PELLAGRA" by T. Spies et. al. https://jamanetwork.com/journals/jama/article-abstract/280223

"Case 6.—P.L., a white man, aged 46, treated through the courtesy of Dr. Ogden H. Baumes and Dr. Harry Fry, had a normal dietary history until March 1937, when, because of albuminuria and high blood pressure, here restricted his diet to sweets, fats and vegetables and refrained from eating meat, eggs or milk. In October he noticed an abnormal red color and excruciating pain of his tongue. These symptoms progressed, and two weeks later he noticed reddening of the mucous membranes of his entire mouth and throat.

He returned to his physician November 8 and was told to eat meat. He ate about 1 ounce (30Gm.) of beef that day. We saw him on the following day and observed that his lips and the mucous membranes of his mouth were swollen and fiery red. On November 9 he was again seen, and since his mouth had not improved he was given 100 mg. of nicotinic acid every hour for five hours. On the morning of November 11 the tongue and oral mucous membranes appeared much improved and were no longer painful. The same dosage of nicotinic acid was repeated that day. November 12 the mouth and tongue were normal, and the patient was told to continue taking the nicotinic acid for an additional two days. He was also told to eat meat at least three times a week. He followed this regimen, but because of his fear of eating large amounts of meat he ate only an ounce three times a week, with the result that ten days later his tongue again became somewhat painful. By the end of another week the pain had increased, and the mouth and tongue became abnormally red. We saw him at this time and observed that the pellagrous glossitis and stomatitis were not as severe as during the previous attack. They disappeared after the administration of 1,000 mg. of nicotinic acid.

Observations on this patient showed that the ingestion of nicotinic acid promptly produced healing of the pellagrous glossitis and stomatitis and that the patient relapsed when administration of the nicotinic acid was discontinued while he continued to take essentially the same diet."

Next I will take a look at Conrad Arnold Elvehjem (1901-1962) who is credited with finding two forms of niacin (vitamin B3). But first a link to the place where Conrad Arnold Elvehjem studied and worked his whole life, the University of Wisconsin.

The University of Wisconsin, Wisconsin Alumni Research Foundation (WARF), Elmer Verner McCollum, Harry Steenbock and Edwin Bret Hart are all connected throught the discovery of vitamin A (1913) and the production of vitamin D by UV-radiation (1923) were both discovered by a small group of people working in the Department of Agricultural Chemistry at the University of Wisconsin. The blood thinner Warfarin is named after the foundation WARF: WARF-arin. All these different people working in the same department at the same university overlapping in their time there. Edwin Bret Hart was the graduate advisor for Harry Steenbock (1886-1967), just like he later was for Conrad Arnold Elvehjem (1901-1962). I believe that both Stephen Moulton Babcock (1843-1931) and Edwin Bret Hart (1874-1953), were superiors/supervisors for Elmer Verner McCollum, at the Department of Agricultural Chemistry, University of Wisconsin-Madison.

Edwin Bret Hart (1874-1953) was also mentor for an upcoming biochemistry PhD student, Conrad Arnold Elvehjem (1901-1962), from 1925-1927 and Conrad's PhD thesis which was on the importance of copper in iron-deficiency anemia.

Conrad Arnold Elvehjem later became a full professor in 1936 and in 1937 he discovered two chemical compositions of vitamin B3, nicotinic acid and nicotinamide, which is his biggest known fame.
https://en.m.wikipedia.org/wiki/Conrad_Elvehjem

This is a 1937 paper called: "FURTHER STUDIES ON THE CONCENTRATION OF THE ANTIPELLAGRA FACTOR" by C. J. Koehn Jr. and C. A. Elvehjem.
https://www.jbc.org/article/S0021-9258(18)74475-X/fulltext

"Dann (5), working with human pellagrins, has shown that lactoflavin [riboflavin] is inactive in the treatment of pellagra and that, when these patients were subsequently administered liver extract, remission of symptoms resulted."

Fried beef liver contains about 17.3 mg /100 g according to myfooddata.com, so they tried to concentrate just the niacin from liver extracts.
https://tools.myfooddata.com/nutrition-comparison/782310/100g/1

Take a look at how awful the diet (in weight percentages) was fed to the puppies (dogs) in the study to give them pellagra symptoms:

Yellow corn: 72%
Purified casein: 18%
Cottonseed oil: 5%
Cod liver oil: 2%
Calcium carbonate: 1%
Calcium phosphate: 1%
NaCl: 1%

The subsequent paper by Elvehjem published in 1938 is the paper that showed that the importance of nicotinic acid, and is called:
"THE ISOLATION AND IDENTIFICATION OF THE ANTI-BLACK TONGUE FACTOR" by Carl Arnold Elvehjem, et. al.
https://www.jbc.org/article/S0021-9258(18)74164-1/fulltext

Their estimation of niacin concentration in liver by that study seems quite correct since they find 17.3 mg niacin per 100 g of liver, so they don't seem to have screwed everything up but I didn't look to closely at that paper.

"If there has been no appreciable loss during the preparation of liver extract from liver, we may conclude that 100 gm. of fresh liver contain about 25 mg. of potential nicotinic acid amide."

Still from looking at some of these earliest vitamin B3 papers I see the connection to the chemical industry, since nicotinic acid (oxidized nicotine) was already produced by the Eastman Kodak Company. The same company that supplied nicotinic acid to the early studies when they didn't use several steps to purifiy what they believe to be nicotinic acid from a liver extract. I have seen nicotinic acid mention for its use within photograpy. I guess this photograpic chemical (nicotinic acid) later was sold as a supplement by the Eastman Kodak Company (Eastman Chemical Company was at the time a subsidiary to the Eastman Kodak Company).

On the way out just want to add a few more things on Conrad Arnold Elvehjem (1901-1962) from this news article which was written after his death.
https://www.newspapers.com/image/?clipping_id=54877749&fcfToken=eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJmcmVlLXZpZXctaWQiOjQwMDY5OTkyMSwiaWF0IjoxNjQwMjQ1MjY3LCJleHAiOjE2NDAzMzE2Njd9.D9OlDeOyKK9XtAtHTELrZuqfMU9iBv4PqZVgBbCvoSw

Accomplishments of Conrad Arnold Elvehjem (1901-1962):

Past president of The American Institution of Nutrition.
Member of the Academy of Arts and Sciences (1953-)

Awards:
Mead Johnson award for research in vitamin B Complex (1939)
[A bad sign to me since the company "Mead Johnson" was created by one of three Johnson brothers, the other two brothers gave the name to the pharmaceutical giant Johnson & Johnson]

Grocery Manufacturers of America Award (1942)
Willard Gibbs medal of the American Chemical Society (1943)
Nicholas Apert medal (1948)
Osborne-Mendel award from the American Institute of Nutrition (1950)
Laster award in medical research from the American Public Health Association (1952)
Charles F. Spencer award for contribution to food and agricultural chemistry (1956)
American Institute of Baking Award (1957)
Nutrition Foundation Award (1961)