Well, the GLP 1 agonists are new drugs, and carry a host of very negative potential side effects, even from what we’ve already seen, like stomach paralysis. I think crash dieting, extreme fasting, exhaustive exercise, low carb/keto diets, and extreme vegan diets are all safer, even though they all carry a lot of potential issues as well. Even risky medications like Orlistat, HCG, and phentermine are likely safer. Pretty much the only intervention that seems riskier to me is gastric bypass. So, while incredibly popular right now, I don’t think the GLP 1 agonists are very good benchmarks for safety.
Niacinamide, even in higher doses, is very safe. We have a long history of people using higher doses of Niacinamide and Niacin, thanks to Abram Hoffer and the orthomolecular doctors. I’m not sure exactly what line of thinking of Dr. Peat’s you are referring to. He did generally recommend a hundred milligrams a few times a day, but again, that was mostly general advice. He talked about experimentation with safe substances, like aspirin, and noted that a person could experiment with just aspirin in various doses, from a baby aspirin up to several grams a day. I don’t see why Niacinamide would be any different, and if anything, it would be safer than aspirin. Even taking a larger dose at once, it tends to be absorbed from the gut over time, so I don’t think the slow sipping of niacinamide in dissolved water would be necessary. It seems like it would be more of a complication, causing issues with compliance. Plus, niacinamide powder tastes very bitter, so that would be another issue.
Adding thiamine would be a very good thing, and there are studies also showing higher doses of thiamine helping to prevent weight gain on a high fat diet as well. In Haidut’s classic post on the NAD+/NADH ratio, he mentions that a combo of Niacinamide, Thiamine, Biotin and maybe Methylene Blue would be a very useful combo for practically all conditions, as they all help to stimulate metabolism.
https://lowtoxinforum.com/threads/nad-nadh-ratio-the-one-metabolic-cause-to-rule-them-all.20089/
MB can cause some potential issues of its own, likely to the MAO-A inhibition and interactions with red light. There are other things that can help oxidize NADH back to NAD+, like Alpha Lipoic Acid, Inosine, Pyruvate, CoQ10, and Pyrucet. Red Light itself may oxidize NADH back to NAD+, since it seems to lower lactate, and the pyruvate/lactate ratio is a good surrogate for the NAD+/NADH ratio.
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