4 D's of Pellegra and physiology of how they happen?

"modern maladaptations" (1) related to Pellagra. I would like to a summary of an article which is an interesting theory to consider at the very least. NAD+ is an important part of energy metabolism and its reduction to NADH for dehydrogenase reactions in the mitochondria seems to require a constant supply of NAD+ by diet or by gut microbes (1). One major dietary source of NAD+ (via nicotinic acid) is meat (1). As you point out when meat availability is low, Pellegra may result (1).

I'll see if I can summarize this paper, but it has some interesting epidemiological graphs that I'd like to present to you. First, the argument goes that there does appear to be a symbiotic relationship that is theorized to have developed during "feast or famine" days of hunter gatherer period of human evolution (1). As such, when meat is scarce and fiber type foods are eaten in its place, the gut microbes will use the starch eaten to produce NAD+ (1). In days of feast and famine, the symbiosis worked well. But as meat ingestion has steadily become a staple in the diet of the affluent, and high fiber starchy food a staple in the non-affluent we get a divergence of effects. In the nonmeat eaters, you can see Pellegra. In the meat eaters, you are seeing modern illness in the form of immune reactions and dysbiosis as a stronger immune response is mounted against gut bacteria (all from 1). 

Here are some of the interesting graphs from the article (I hope I adequately explained the steps in the thinking to get to these graphs):

First it is of interest that TB rates went down as meat ingestion goes up... (pre-medical rx):

So, stronger immune reactions against the gut microbes help with infection, but in its place with more consistent meat ingestion we have modern disease (I'm just showing the correlation, not causation of course) of cancer and diabetes, as well as allergies:

Interesting here the difference between areas of possible Niacin excess versus deficiency and the resulting conditions (as per source 2):

So, the article argues that niacin toxicity is associated with a group of conditions that are modern:

And recommends that you tread the middle ground with niacin supplements:

Sorry if not clear, I left many gaps and its clear this is a working hypothesis, but I found it an interesting way to work through some topics with Niacine. The article can be found online here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419340/ (Links to an external site.)Links to an external site.

Source: Lisa J Hill and Adrian C Williams. Meat Intake and the Dose of Vitamin B3 – Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures? Int J Tryptophan Res. 2017; 10: 1178646917704662.