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046: Niacin, Part 1: What It Is and Why You Need It

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Mastering Nutrition

046: Niacin, Part 1: What It Is and Why You Need It

Mastering Nutrition Episode 46

Chris Masterjohn, PhD
Mar 1, 2019
3
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046: Niacin, Part 1: What It Is and Why You Need It

chrismasterjohnphd.substack.com

Introduction

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. This is part 1, where we teach you what niacin is and why you need it. 

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

Show Notes

00:37 Cliff Notes

5:31 The stories of Julie, John, and Jane

11:32 Symptoms of pellagra: the three Ds of dermatitis, dementia, and diarrhea, and the fourth D, death

18:02 Speculative signs and symptoms of suboptimal niacin status

19:10 Symptoms of excess niacin

20:45 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.

24:30 Explaining the stories of Julie, John, and Jane in the context of niacin deficiency or toxicity

28:18 Chemical properties of niacin

31:08 How niacin and nicotinic acid derived their names

33:00 Chemical structures of nicotinic acid, nicotinamide, nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and nicotinamide adenine dinucleotide (NAD)

37:05 The biochemistry of niacin 

37:57 The differences between NAD(H) and NADP(H) in metabolism

41:07 NAD is often broken down to form ADP-ribose.

42:10 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

48:31 ADP-ribosyltransferases (ARTs)

50:47 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.

52:28 How the biochemistry of niacin explains the deficiency symptoms

57:37 The biochemistry of how we get niacin from foods and how we dispose of excess niacin

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

01:16:12 Extended-release niacin

01:18:57 Rationale for nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) supplementation

01:27:39 Physiology of niacin absorption and circulation

01:35:04 Endogenous synthesis of niacin

01:35:37 Tracer studies of oral and intravenous nicotinamide riboside supplementation in mice

01:40:00 Estrogen is a strong regulator of the conversion of tryptophan to niacin.

01:42:07 Pharmacokinetic study of Niagen (nicotinamide riboside) supplementation in humans

Niacin Links and Research

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Khera AV, Patel PJ, Reilly MP, Rader DJ. The addition of niacin to statin therapy improves high-density lipoprotein cholesterol levels but not metrics of functionality. J Am Coll Cardiol [Internet]. 2013 Nov 12;62(20):1909–1910. Available from: http://dx.doi.org/10.1016/j.jacc.2013.07.025  PMID: 23933538

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Garg A, Sharma A, Krishnamoorthy P, Garg J, Virmani D, Sharma T, Stefanini G, Kostis JB, Mukherjee D, Sikorskaya E. Role of Niacin in Current Clinical Practice: A Systematic Review. Am J Med [Internet]. 2017 Feb;130(2):173–187. Available from: http://dx.doi.org/10.1016/j.amjmed.2016.07.038  PMID: 27793642

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Fricker RA, Green EL, Jenkins SI, Griffin SM. The Influence of Nicotinamide on Health and Disease in the Central Nervous System. Int J Tryptophan Res [Internet]. 2018 May 21;11:1178646918776658. Available from: http://dx.doi.org/10.1177/1178646918776658  PMCID: PMC5966847

Chi Y, Sauve AA. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. Curr Opin Clin Nutr Metab Care [Internet]. 2013 Nov;16(6):657–661. Available from: http://dx.doi.org/10.1097/MCO.0b013e32836510c0  PMID: 24071780

Dollerup OL, Christensen B, Svart M, Schmidt MS, Sulek K, Ringgaard S, Stødkilde-Jørgensen H, Møller N, Brenner C, Treebak JT, Jessen N. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr [Internet]. 2018 Aug 1;108(2):343–353. Available from: http://dx.doi.org/10.1093/ajcn/nqy132  PMID: 29992272

Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun [Internet]. 2018 Mar 29;9(1):1286. Available from: http://dx.doi.org/10.1038/s41467-018-03421-7  PMCID: PMC5876407

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Soudijn W, van Wijngaarden I, Ijzerman AP. Nicotinic acid receptor subtypes and their ligands. Med Res Rev [Internet]. 2007 May;27(3):417–433. Available from: http://dx.doi.org/10.1002/med.20102  PMID: 17238156

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