Discovering Nutritional Deficiencies

April 2013, updated December 2014

In the early 1900’s, beriberi and pellagra were public health crises. Through a series of discoveries, researchers found that yeast could prevent both diseases. They subsequently found that yeast is rich in “B Vitamins”. They also discovered that there are multiple B Vitamins – not a single Vitamin B as was originally believed – and that these multiple B Vitamins are essential dietary substances. These discoveries significantly altered our understanding of diet and disease, so much so that the researchers were awarded Nobel Prizes.

Curing Beriberi, a Thiamine (B1) Deficiency

Beriberi is characterized by behavioral changes (confusion, irritability, and loss of appetite) that eventually lead to a loss of sensation, paralysis and, in extreme cases, heart failure. For centuries, beriberi was a public health problem in China, Japan and Southeast Asia. These populations relied on rice, and a standard practice was to remove the grain and bran from rice to produce white or “polished” rice. Notably, rural and poor families who could not afford to “polish” rice were not afflicted with beriberi.

It wasn’t until the late 1880’s when Dutch troops in the East Indies became afflicted with beriberi that the public health officials began to investigate the cause. Most thought that a bacterium – similar to cholera – might be the cause. The Hague tasked a 30-year old physician, Christiaan Eijkman, to identify the cause. He began controlled experiments with chickens and eventually found that unpolished rice cured and prevented beriberi among chickens. Gerrit Grijns expanded these tests with human subjects, and he and Sir Frederick Hopkins clarified that the condition was one of a dietary deficiency. In 1936, with help from Fleischman Yeast and Merck, Robert Williams – an American schoolteacher with a chemistry degree – was able to identify thiamine-deficiency as the cause of beriberi.

Eijkman and Hopkins won the Nobel Prize 40 years after Eijkman’s discovery. (This is a sore point for many Grijn supporters who suggest that Eijkman made the pioneering finding and Grijns reinterpreted it correctly.)

Curing Pellagra, a Niacin (B3) Deficiency

During that same period, pellagra mortality was a rapidly growing public health problem in the southern United States. Pellagra, in its most severe form, results in insanity and eventually death. In 1914, the US Public Health Service commissioned Officer Joseph Goldberger to study pellagra.

Unlike beriberi, pellagra affected the poor and those living in rural areas. Goldberger's theory that pellagra was associated with diet contradicted a commonly held medical opinion that pellagra was an infectious disease. After a series of human trials in orphanages, asylums and prisons, he observed that a well-balanced diet would return individuals back to health. By 1926, Goldberger had found that yeast could cure or prevent pellagra. Upon further laboratory work, Goldberger suggested that Vitamin B was comprised of at least two substances: an anti-neuritic factor and a heat stable “pellagra-preventive” (P-P) factor. Despite his careful experiments, Goldberger's discovery proved socially and politically unacceptable, and he made little progress in gaining support for the treatment of pellagra – many still believed pellagra was contagious. Unfortunately, Goldberger died of cancer in 1929.

It was not until 1937 when agricultural biochemists at the University of Wisconsin identified niacin-deficiency (i.e., Goldberger’s P-P factor) along with reduced levels of the amino acid tryptophan as the cause of pellagra. (Pellagra remains a public health problem in countries that rely on corn because when treated with lye, corn liberates niacin from its bound form.)

Although Goldberger was nominated five times, he was never awarded a Nobel Prize. The American Society of Biological Chemists recommended naming the P-P factor “Vitamin G” in his honor, however those efforts also failed as the factor was subsequently named “niacin” for nicotinic acid vitamin.

Preventing Neural Tube Defects, a Folic Acid Deficiency

Important vitamin deficiency discoveries did not cease in the early 1900s. In 1965, researchers hypothesized that folic acid deficiencies were causing birth defects. After several rigorous studies, the U.S. Public Health Service recommended in 1992 that all women of childbearing age consume folic acid daily through food fortification, supplementation, and diet, and as recent as 2009, the U.S. Preventive Services Task Force updated guidelines reinforcing these recommendations.

The Next New Nutritional Discovery

The 20th century was dedicated to preventing nutritional deficiency diseases. The 21st century will be dedicated to preventing obesity and its complications – hypertension, diabetes, coronary heart disease, osteoarthritis, and other chronic disorders. A growing problem in developing countries, obesity is not only associated with chronic disorders, but also with malnutrition, particularly deficiencies of iron, iodine, and vitamin A, affecting 2 billion people worldwide. Hopefully, the next new discovery will be how to change behavior – getting people to exercise more and to eat a nutritionally-balanced diet.


Sources:
Carpenter, K.J., “The Discovery of Thiamin”, Annals of Nutrition and Metabolism, pp. 219-223, November 2012
Lanska, D.J., “The Discovery of Niacin, Biotin and Pantothenic Acid,” Annals of Nutrition and Metabolism, pp. 246-253, November 2012
Crider K, Bailey L, and Berry R, “Folic Acid Food Fortification—Its History, Effect, Concerns, and Future Directions”, Nutrients, March 15, 2011