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Orthomolecular Medicine News Service, Feb 19, 2023

Save Lives and Improve Public Health:
Following the Data from Pellagra to Atherosclerosis

by Michael Passwater and Richard Passwater, Jr.

OMNS (Feb 19, 2023) History is an important teacher, as it can help us replicate good practices and avoid repeating harm.


First described in 1765 in Spain by Don Gasper Casal, pellagra is characterized by four Ds: dermatitis, diarrhea, dementia, and death. The first recorded case in the United States was in 1906 in Georgia. In 1912, South Carolina reported 30,000 cases with a case fatality rate of 40%. From 1906 - 1940, over 3 million Americans suffered from pellagra and over 100,000 deaths from the disease were recorded. Expert opinion suggested pellagra was caused by an unidentified germ. The Thompson-McFadden Pellagra Commission emboldened this popular misconception in 1914 by declaring the disease unrelated to diet.

However, Theophile Roussel, Kazimierz (Casimir) Funk, and Joseph Goldberger independently argued Pellagra was a dietary deficiency. [1] Funk suggested the disease in the US was related to a change in the milling practice of corn. Goldberger noted the disease was strongly associated with the 3 Ms of the poverty diet: meal (cornmeal), molasses, and meat. His observation of a lack of transmission of the disease from inmates or hospital patients to their guards or caretakers caused him to reject the popular belief of a germ in rancid cornmeal as the cause. By the 1920s, Goldberger, using research techniques unacceptable by today's ethical standards, had induced pellagra in multiple groups of people through dietary alterations, reproducibly cured the dreaded disease with daily doses of brewer's yeast, and demonstrated an inability to transmit the disease by exposing well-nourished humans to various tissue samples from Pellagra patients. [2] Nonetheless, the germ theory of pellagra persisted, and people continued to die from the preventable disease.

Finally, in 1937, Conrad Arnold Elvehjem at the University of Wisconsin proved that niacin (vitamin B3) cured pellagra, ending the germ vs. diet debate. [3] Biochemist and food science pioneer, Fred A. Kummerow, helped the food industry to add niacin to corn grits in 1943, and pellagra quickly became a rare and now largely forgotten disease. Niacin (C6H5NO2) is a small molecule with a big role in human health. Every cell in the human body uses niacin, and over 400 enzymes depend on niacin as a cofactor to complete reactions. People literally cannot live without niacin.

Atherosclerosis and essential fatty acids vs. trans-fats

Atherosclerosis is another deadly disease, like pellagra, that was exacerbated and prolonged by a change in food processing and misguided expert opinion. Restoring and maintaining the right amount of the right biomolecules in the right body tissues is the essence of Orthomolecular Medicine. Every cell is dependent on niacin for metabolism. Similarly, every cell in the human body is also dependent on lipids (fats), including cholesterol, for flexible protective membranes, mineral regulation, and cell signaling. Lipids comprise 50% of the human brain, and one lipid, docosahexaenoic acid (DHA), makes up one third of brain tissue. [4] Photoreceptors have the highest concentration of DHA fatty acids, [5] utilizing their curved side chains to provide membrane fluidity and enable molecules in the light activated enzyme cascade to rapidly diffuse within photoreceptor disks and produce the remarkable sense of vision.

In the early 1900s, partially hydrogenated vegetable oil was introduced into the US food supply. The partial hydrogenation process alters the chemistry of the essential fatty acids linoleic acid (omega-6) and linolenic acid (omega-3) resulting in 14 artificial (not found in nature) trans-fatty acids. A century later, the FDA estimated 37,000 food products contained artificial trans-fats, also referred to as industrially produced trans fatty acids (IP-TFA). These artificial lipids are incorporated into cell membranes throughout the body including the endothelial cells coating blood vessels. Once incorporated into cell membranes, artificial trans-fats cause inflammation and alter cell function. Disruption of the production of prostacyclin and thromboxane in the endothelium increases the risk of thrombosis and sudden death. [6,7]

Heart disease was rare in the US prior to 1900, but grew steadily from 1920 - 1960 along with increased cigarette smoking and trans-fat consumption, and today remains the leading cause of death. In 1957, Dr. Kummerow examined arteries from patients who had died of heart attacks and observed that the fatty deposits in the arteries contained artificial trans-fats. [8] Artificial trans-fats have also been associated with Type 2 Diabetes, several cancers, and GI tract inflammation. [9] In 1968, he helped negotiate an agreement with the edible oils industry to decrease trans-fats from 43% to 27% and to increase linoleic acid from 8% to 25% in margarines. In 1975, Dr. Kummerow testified before the Federal Trade Commission that eggs were healthy and dietary cholesterol was not the cause of heart disease. Dr. DeBakey was the only other invited expert witness who shared this view with the FTC. Dr. DeBakey was a pioneer in cardio-bypass surgery and observed that the need for bypass heart surgery was independent of cholesterol. Nonetheless, the final FTC ruling stated that egg producers could not say eggs were a good source of nutrition without also saying cardiologists believed eating eggs was one cause of heart disease.

Artificial trans-fats remained widespread in the US food supply while the public was advised to avoid eggs and other cholesterol containing natural foods due to a misattribution of cholesterol consumption with heart disease. Dr. Kummerow subsequently lost his NIH funding. Fortunately, private funding allowed his work to continue through 2014. In 1977, Dr. Richard Passwater put a challenge on the back cover of his book "SuperNutrition for Healthy Hearts" stating, "No one has ever shown that eating cholesterol causes heart disease. If anyone can step forward and prove that eating cholesterol causes heart disease, I will donate all my proceeds from this book to the American Heart Association." [10] No one took up the challenge. Cholesterol wasn't the problem (dietary cholesterol is a problem for obligate vegetarians such as chickens and rabbits lacking metabolic pathways to process meat. These animals are unsuitable for studies on human metabolism and cardiovascular disease.). Saturated fat wasn't the problem. Eggs weren't the problem. However, artificial trans-fats were a serious problem, along with oxidized lipoprotein(a).

In 2009, Dr. Kummerow petitioned the FDA to ban trans-fats. In 2013, he filed suit against the FDA to get them to follow the law and review his petition from 2009. In 2018, the FDA completed its review and banned the use of partially hydrogenated oil in most processed foods in the US, effective 2020. In 2018, WHO also called for the worldwide elimination of trans-fats by 2023, estimating 500,000 deaths per year result from the consumption of industrially produced trans-fatty acids. [11] Of note, increased magnesium intake is helpful in reducing the risks associated with consumption of artificial trans-fats. [12] However, avoiding any consumption of those "poisons" is best.

100 year old Dr. Kummerow discussed his public health concerns with trans-fats in this 4 minute YouTube video: Dr. Kummerow shared his personal diet in a 2014 interview celebrating his 100th birthday. He died in 2017 at the age of 102.

Passwater: What about your personal diet?

Kummerow: I eat an egg every day and drink three glasses of whole milk. I also eat meat or some kind of protein at every meal and lots of fruit and vegetables.

Passwater: What do you eat for breakfast?

Kummerow: I eat an egg scrambled in butter, one tablespoon of oatmeal and wheat berries (which is cooked ahead of time and kept in the refrigerator or freezer), a tablespoon of plain yogurt, a small banana, four stewed prunes and a tablespoon of chopped nuts. I also have one cup of whole milk and a glass of water.

Passwater: Do you eat mostly natural foods?

Kummerow: I don't eat processed or fried food. I eat fresh or frozen vegetables or fruit and meat that is baked or broiled.

Table 1: Dietary Fats

B vitamins and magnesium are Important cofactors for lipid metabolism. Vitamin E is a lipophilic (membrane bound) antioxidant especially important for preventing oxidation of membrane fatty acids thereby preserving their flexibility and function. This is important for all cells, and is especially critical for nerve cells to fill, release, and regenerate synaptic vesicles that eject neurotransmitters. The goal is to consume enough essential lipids, along with vitamin and mineral cofactors, and essential amino acids without consuming an excess of total calories. If calories need to be cut, carbohydrates are a good target as there are no essential dietary sugars. Non-steroidal anti-inflammatory drugs (NSAIDs such as ibuprofen, naproxen, celecoxib, or aspirin), statins, and IP-TFAs can inhibit healthy lipid metabolism. Although alpha-linolenic acid is the only essential omega-3 fatty acid, consuming longer-chain omega-3 lipids such as DHA and EPA, which enter cell metabolism downstream of the inhibition points in the omega-6 and omega-3 metabolic pathways, can help maintain important structural and cell signaling lipids. DHA and EPA can be metabolized into families of cell signaling lipids known as prostanoids, eicosanoids, elovanoids, and docosanoids. These lipids have many tissue-specific effects throughout the body, including regulation of inflammation, immunity, bleeding, clotting, vasodilation, vasoconstriction, eyesight, and memory. [13-16] Both the Mediterranean Diet and Ketogenic Diet have been associated with improved cognitive function. Both diet plans emphasize consuming healthy lipids, while minimizing intake of sugars and processed food.

Healthy lipids also promote a healthy intestinal microbiome which can increase production of peptides and lipids important for the immune system and nervous system. [17] The important relationship between the microbiome and the brain is referred to as the "enteric nervous system" or the "gut-brain axis". Here is a 4 min video to elaborate on this concept: Human Science (Part 1) - "The Gut Brain Axis, Microbiome & the power of Probiotics"


"If the experts say 'A' and the data say 'B'-go with the data" ~David Kritchevsky, 1993 [18]

Lipids do more than store energy. They are major essential components of every cell membrane, including brain cells and the cells lining blood vessels. Lipids also serve as cell signaling molecules regulating a wide variety of functions impacting all tissues in the body. A diet devoid of omega-3 and omega-6 fatty acids is as fatal as a diet devoid of niacin or any other vitamin. Two fatty acids are recognized as "essential" in the human diet because they cannot be made from other compounds - omega-6 linoleic acid and omega-3 linolenic acid. Additional lipids (for example, EPA, DHA) may be considered "semi-essential" as the body can make them, but cannot make them efficiently enough to reliably fulfill its needs.

The precautionary principle is prudent when considering adding substances not normally present in the human body to the food supply. Studying benefits and risks of an intervention prior to introduction, and monitoring impact after introduction is helpful to avoid widespread damage to large groups of people. Keen observation and an open mind to receive and analyze all available data is key to recognizing which components to purge and which to promote in the quest to optimize individual and population wellness.


1. Passwater RA (2014) From Pellagra to Trans Fats and Beyond - How a Legendary Nutritional Scientist Is Still Saving Countless Thousands From Premature Deaths. Vitamin Connection, Whole Foods Magazine. Sep 25, 2014.

2. Morabia A. (2008) Joseph Goldberger's research on the prevention of pellagra. J R Soc Med.101: 566-568.

3. The Discovery of Niacin at UW-Madison. July 12, 2017. PBS Wisconsin.

4. Bruce KD, Zsombok A, Eckel RH (2017) Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism. Front. Endocrinol. 8:60.

5. Organisciak DT, Vaughan DK (2010) Retinal light damage: mechanisms and protection. Prog Retin Eye Res.;29:113-134.

6. Passwater RA. (2014) From Pellagra to Trans Fats and Beyond - How a Legendary Nutritional Scientist Is Still Saving Countless Thousands From Premature Deaths (Part 2). Vitamin Connection, Whole Foods Magazine. Oct 21, 2014.

7. Kummerow FA (2013) Interaction between Sphingomyelin and Oxysterols Contributes to Atherosclerosis And Sudden Death. Am J Cardiovasc Dis. 3:17-26.

8. Johnston PV, Johnson OC, Kummerow FA (1957) Occurrence of trans Fatty Acids in Human Tissue. Science 11:698-699.

9. Ricciotti, E and Garret A. FitzGerald, GA. (2011) Prostaglandins and Inflammation. Arterioscler Thromb Vasc Biol. 31:986-1000.

10. Passwater, Richard A. (1977) SuperNutrition for Healthy Hearts. The Dial Press. ISBN-13:978-0803780354

11. WHO plan to eliminate industrially produced trans-fatty acids from global food supply. May 14, 2018.

12. Kummerow FA, Zhou Q, and Mahfouz MM (1999) Effect of Trans Fatty Acids on Calcium Influx into Human Arterial Endothelial Cells. Am J Clin. Nutr. 70:832-838.

13. Yang T, Du Y. (2012) Distinct Roles of Central and Peripheral Prostaglandin E2 and EP Subtypes in Blood Pressure Regulation. Am J Hypertens. 25:1042-1049.

14. Kaur N, Chugh V, Gupta AK. (2014) Essential fatty acids as functional components of foods- a review. J Food Sci Technol. 51:2289-2303.

15. Zhu L, Zhang Y, Guo Z, Wang M (2020) Cardiovascular Biology of Prostanoids and Drug Discovery. Arterioscler Thromb Vasc Biol. 40:1454-1463.

16. Bazan NG. (2018) Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection. Mol Aspects Med. 64:18-33.

17. Burke SN (2023) Ultra-Processed Foods Like Cookies Chips Frozen Meals and Fast Food May Contribute to Cognitive Decline. The Conversation. January 31, 2023.

18. Passwater RA (1993) Nutrient Interaction in Heart Disease Whole Foods Magazine. June 1993.

Further Reading

Penberthy WT (2022) NIACIN for COVID: How niacin, niacinamide, and NAD can help with Long Covid-19. OMNS Sep 20, 2022

McConnell S, Penberthy WT (2021) Reversing Chronic Kidney Disease with Niacin and Sodium Bicarbonate. OMNS Oct 14, 2021.

Levy TE, Hunninghake R (2022) Atherosclerosis is a Non-Healing Wound. OMNS Sep 8, 2022.

Saul AW (2011) Vitamin E Attached Again: Of Course. Because It Works OMNS Oct 14, 2011.

Spencer A, Saul AW (2010) Vitamin C and Cardiovascular Disease OMNS June 22, 2010.

Vitamin E Research Ignored by Major News Media. OMNS May 25, 2010.

Dyerberg, Jorn and Passwater, Richard (2012) The Missing Wellness Factors - EPA and DHA: The Most Important Nutrients Since Vitamins? Basic Health Publications, Inc.

Hoffer Abram, Harold DF, Saul Andrew W (2023) Niacin: The Real Story, 2nd edition.

Kummerow, Fred A. and Kummerow, Jean M. (2008) Cholesterol Won't Kill You But Trans Fat Could: Separating Scientific Fact from Nutritional Fiction in What You Eat. Trafford Publishing.

Kummerow, Fred A. and Kummerow, Jean M. (2014) Cholesterol is Not the Culprit: A Guide to Preventing Heart Disease. Spacedoc Media, LLC.

Enig, Mary G. (2000) Know Your Fats: The Complete Primer for Understanding the Nutrition of Fats, Oils, and Cholesterol. Bethesda Press.

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