Biochemistry of Niasin

Niacin is vitamin B3. You use it to make NAD, the ultimate anti-aging molecule that repairs your DNA and lengthens your telomeres, and the most foundational molecule in our entire system of energy metabolism.

It is especially important to protecting your mind, your skin, and your gut.

• You use it to release all your neurotransmitters. This is why depression sets in as the earliest sign of deficiency and why, when it gets bad enough, it leads to suicidality or schizophrenia-like psychosis.
• You use constantly it to repair the microscopic damage done to your skin every time you step out into the sunlight. This is why red, inflamed skin appears on the backs of your hands or on your face when you’re deficient, but only if you get outdoors a lot.
• You use it to fuel the rapid turnover of cells in your intestines (the cells that absorb the nutrients in our food are replaced every 2-3 days!), and to repair those cells from the constant barrage of insults they face (think of everything those cells *don’t* let in our body 💩and the fact that *they* need to stare all that stuff down!) This is why deficiency will give you diarrhea and make you deficient in lots of other nutrients.
• You use it for lots of other things too, like participating with riboflavin to make the methyl group of methylfolate and recycle glutathione, the master antioxidant of the cell. You use it to recycle vitamin K, to support detoxification in the liver, and to synthesize cholesterol, fatty acids, neurotransmitters and nucleotides.

Who needs more? We all do!

Why? Because just aging alone depletes niacin and getting sick or developing diseases as we age depletes it all the more. Niacin repairs damage, so the more damage we face the more we consume.

In fact, this is why many people are taking supplements like nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), to slow the onset of aging, or to age more gracefully. Some people are even injected NAD!

But should we be?

And what about the dark side of niacin? We all know the flush -- the redness and itching that accompanies high-dose niacin that people take to lower cholesterol. At high doses, niacin can even damage the liver. How? By sapping methyl groups. Sapping methyl groups can give you liver failure when it’s *really* bad, but sapping them just a little can leave you feeling weak, emotionally stuck, or tied up in a mental funk.

In this two-part podcast series, Alex Leaf and I tackle all of these questions. Click the link to listen to part 1, where we teach you what niacin is and why you need it.

In part 2, two weeks from today, we’ll cover how to get niacin in foods, blood tests, and supplements.

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In this episode, you will find all of the following and more:

00:37 Cliff Notes

11:35 The stories of Julie, John, and Jane

17:36 Symptoms of pellagra: the three Ds of dermatitis, dementia, and diarrhea, and the fourth D, death

24:00 Speculative signs and symptoms of suboptimal niacin status

24:59 Symptoms of excess niacin

26:43 Excess niacin will reduce the supply of methyl groups, which can lower creatine synthesis and affect neurotransmitters, and is probably what underlies niacin-induced liver damage.

30:31 Explaining the stories of Julie, John, and Jane in the context of niacin deficiency or toxicity

34:25 Chemical properties of niacin

37:03 How niacin and nicotinic acid derived their names

38:58 Chemical structures of nicotinic acid, nicotinamide, nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and nicotinamide adenine dinucleotide (NAD)

42:51 The biochemistry of niacin

43:05 The differences between NAD(H) and NADP(H) in metabolism

47:03 NAD is often broken down to form ADP-ribose.

48:10 How PARPs (including PARP1 and tankyrase) and sirtuins use NAD to protect us from DNA damage, repair DNA damage, lengthen telomeres, and regulate gene expression

54:27 ADP-ribosyltransferases (ARTs)

56:43 The NAD metabolites cyclic ADP-ribose, linear ADP-ribose, O-acetyl-ADP-ribose, and NAADP are involved in regulating calcium transport, which is especially important for neurotransmitter release.

58:19 How the biochemistry of niacin explains the deficiency symptoms

01:03:23 The biochemistry of how we get niacin from foods and how we dispose of excess niacin

01:07:14 How the degradation pathways of niacin explain the liver toxicity and flushing reaction from different forms of niacin

01:22:08 Extended-release niacin

01:24:44 Rationale for nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) supplementation

01:33:38 Physiology of niacin absorption and circulation

01:40:47 Endogenous synthesis of niacin

01:41:20 Tracer studies of oral and intravenous nicotinamide riboside supplementation in mice

01:45:40 Estrogen is a strong regulator of the conversion of tryptophan to niacin.

01:47:41 Pharmacokinetic study of Niagen (nicotinamide riboside) supplementation in humans

Access the show notes, transcript, and comments here:

https://chrismasterjohnphd.substack.com/p/060-niacin-part-1-what-it-is-and