Nicotinamide

Nicotinamide, otherwise known as vitamin B3, is one of several related compounds, niacin being the most common. It is not a true vitamin, as we can make limited amounts when needed, which I will talk more about later. Due to its unique properties, nicotinamide and its metabolic derivatives, especially NAD, are used for biochemical functions too numerous to dive into in just one post, but a look into how many symptoms occur with deficiency is enough to prove its value throughout various systems of metabolism, cognition, mood, and fertility, to name a few. More than 400 enzymes require NAD to catalyze reactions in the body, which is more than for any other vitamin-derived coenzyme. (1) Furthermore, nicotinamide and n-methyl-nicotinamide are emerging as critical regulators of energy metabolism, epigenetics, aging, and longevity. (2)

RDA and Deficiency

The recommended daily allowance (RDA) for niacin is 16 milligrams per day for men and 14 milligrams per day for women. Deficiency is rare in the developed world, but it used to be a big problem in the United States south where poor diets based on corn were common. (3) Data from the 2015–2016 National Health and Nutrition Examination Survey (NHANES) found that the average daily niacin intake from foods and beverages was 21.4 mg for ages 2–19 [17]. In adults, the average daily niacin intake from foods and beverages was 31.4 mg in men and 21.3 mg in women. The analysis found only one percent to be deficient. The extreme form of niacin deficiency is called pellagra. The symptoms include skin rashes, red tongue, swollen tissues of the mouth, vomiting, headache, fatigue, apathy, depression, memory loss, poor cognition, dementia, disorientation, and even death. (4)

https://upload.wikimedia.org/wikipedia/commons/3/30/A_woman_suffering_from_chronic_pellagra_with_dermatitis_on_h_Wellcome_V0022634.jpg

Emergency Backup Sources Of B3

In deficiency states, the body has two mechanisms to obtain nicotinamide. One is to utilize the amino acid tryptophan to make nicotinamide at the expense of breaking down proteins in the body, which is not a good longterm solution as it leads to wasting. The other way is to increase the commensal bacteria in our guts that make nicotinamide. The downside to this is that it leads to dysbiosis and the potential for infectious diseases. (5)

Nicotinamide and Energy

One of the essential requirements for health and longevity lies in our ability to extract energy from our food. As I have discussed earlier in a previous post, the mitochondria are responsible for making ATP, which is the basic unit of energy. The reactions needed to make ATP are dependant on Nicotinamide Adenine Dinucleotide or NAD for short, and nicotinamide is required to make it. Hence, when vitamin B3 deficiency exists, fatigue and apathy are common.

Sources

Although plants do contain nicotinamide, the best sources of nicotinamide are meats, with liver topping the list. Just three ounces of liver supplies 91% of the RDA for men and 100% for women. Chicken breast is a close second. Tuna, turkey, salmon, anchovies, pork, and ground beef round out the list in decreasing order. The best plant source is peanuts, followed by avocado, brown rice, whole wheat, mushrooms, peas, and potatoes in decreasing order. To highlight the superiority of meat sources, one would have to consume half of a cup of peanut butter to get what three ounces of liver offers. (6) Furthermore, only about 30% of niacin from plants is bioavailable due to its binding to other chemicals, so in reality, the amount supplied by plants is misleading. (7) Supplemental vitamin B3 is available as niacin, and more recently, nicotinamide riboside. Since B3 is readily available from our food, supplementation is rarely necessary.

Use In Medicine

Niacin use, however, is common as an effective pharmaceutical agent for the treatment of high cholesterol and hypertension. The doses used are much higher than our typical physiological needs, resulting in a litany of side effects. The most common side effect is flushing of the face, head, neck, and chest. Other undesirable effects include itching, hives, nausea, vomiting, diarrhea, heartburn, headache, and aggravation of ulcers. Other more severe effects are liver toxicity, Cirrhosis, cardiac arrhythmias, diabetes, hair loss, and fainting. Nicotinamide does not cause flushing, nor does it lower blood pressure, but causes most of the same side effects as niacin. (8) One of the big dangers of excess niacin is that it has to be methylated prior to excretion. High doses of niacin can lead to poor methylation, which causes a host of symptoms. (9) Since diet and lifestyle changes can lower cardiac risk just as effectively as niacin, I see no reason why niacin use should be anything but one of the last resorts for treatment of dyslipidemia and hypertension.

Nicotinamide, Meat, and Their Role In Human History

Authors Williams and Hill claim that nicotinamide played a central role in human history. Their paper published in the International Journal of Tryptophan Research In March 2017 entitled “Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics” goes so far as to claim that “High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts.” You can follow the link in the article title for the details. They argue that humanity's quest for food to survive was less about calories and more about the nicotinamide found in the meat that enabled us to grow larger brains that helped us to dominate the planet. They posit that “adult human requirements to run such big brains are impressive enough, but during development, they are extraordinarily high with 80% to 90% of basal metabolic rate necessary in neonates – this is probably not possible after weaning without the use of animal-derived foods.”

The paper uses demographic and historical evidence to demonstrate the boom and bust nature of grain-based societies, which the graph below (taken from the article) illustrates beautifully.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417583/#!po=28.7037

On the left, modern humans and Neanderthals coexisted as high-level meat-eaters, until Neanderthals went extinct. Shortly after their extinction, agriculture flourished, and meat consumption decreased. On the extreme right of the graph, we see the boom and bust pattern typical of agriculturally based peoples. The affluent periods end with plagues and societal collapse. The recovering populations can eat more meat due to grazing land increases formerly used for raising crops.

They utilize more recent information that correlates meat consumption with longer life expectancies. You can see by the graph below that life expectancy increases with higher meat consumption.

The next chart shows the declining birth rates as meat consumption increases.

This next figure shows all three trends together. When populations consume more meat, they are more robust, but fewer individuals are born, The result is a population that slowly grows back to pre-collapse levels.

Finally, the authors claim that intelligence increases with higher nicotinamide consumption, as shown below.

From the data presented in the preceding charts, they layout specific historical events that seem to corroborate their theory.

Hunter-gatherers took eons to populate the earth, and the authors link it with low fertility supporting their hypothesis.
The Neolithic revolution (farming) resulted in a population explosion once the area under crops was large enough to have an effect around 5000 bc, doubling every 1000 years.
Ancient Rome was dependent on grains. Augustus was so concerned about the falling birth rate among the wealthy, who ate large amounts of meat that he penalized the childless. The population expanded and crashed with a 200-year long plague ending with invasion.
Europe, in 1348 livestock crashed due to a cattle plague resulting in the plague that decimated the human population. Arable land was turned back to pasture (as so much grain was no longer required). Meat became more available to the survivors as production stayed stable or increased with the invention of the plow. Meat and milk intake doubled between 1300 and 1450, fertility remained low, and the population rebounded, but it took two centuries.
The Mayans were a plant-based society whos remains show marked disease. They were known to capture humans for cannibalism, possibly to supplement their low meat diet. The Aztecs took prisoners for sacrifice to eat, not land as is usual, as they had no large domesticated grazing animals. The South American populations were devastated by the diseases the Europeans introduced, partially due to their B3-depleted, less robust constitutions. The introduction of cattle caused the populations to recover slowly.

Vitamin B3 and Your Mouth

Recurrent aphthous ulcers are very common and have been linked to low vitamin B3. The mechanism has not been elucidated. When I encounter a patient with a history of recurrent mouth ulcerations, I make sure that their diet is adequate for vitamin B3.

Conclusion

I am not so sure I totally agree with the claims that nicotinamide availability played THE central role that the authors claim above. I will say that vitamin B3 is one of the most critical nutrients for health, energy production in the body, wellness and longevity. Luckily, it is not difficult to obtain if you are eating a nutrient-rich diet.

Vitamin B3 and Its Central Role In Human History