Vitamin B3 (Niacin)

Powers energy production

All forms of B3 (nicotinic acid, nicotinamide and nicotinamide riboside) end up as NAD⁺, the cell's main electron shuttle. Burning fuel means removing electrons from it, and NAD⁺ is what picks most of them up. It becomes NADH at several stages:¹

• Glycolysis (one step, glyceraldehyde-3-phosphate dehydrogenase);
• The gate into the mitochondria, where pyruvate becomes acetyl-CoA (pyruvate dehydrogenase, which also needs B1, B2 and B5);
• Three steps of the TCA cycle, and every round of fat breakdown.

NADH then carries those electrons to Complex I of the electron transport chain. Their energy pumps protons and drives about 2.5 ATP per NADH. NAD⁺ is recycled over and over: the body's small NAD pool turns over many times a day. A related form, NADPH, does the opposite job. It supplies electrons to build fats and cholesterol and to recharge glutathione.

You can see energy failure from niacin shortage in pellagra, the classic "three Ds": dermatitis on sun-exposed skin, diarrhoea and dementia, then death. It was epidemic in the early-1900s American South among people who lived on corn. Corn's niacin is chemically bound and unavailable unless the corn is soaked in lime (nixtamalised), as in traditional Mesoamerican cooking. The tissues that fail first are the ones that turn over fastest or use the most energy: skin, gut lining and brain.²

Repairs DNA

NAD⁺ is not only an electron carrier. Some enzymes use it up. Two families matter here:¹

• PARPs (PARP1 especially) detect DNA strand breaks within seconds. They split NAD⁺ and build long chains of ADP-ribose at the damage site, which call in the repair machinery. Heavy DNA damage can drain a cell's NAD⁺ in minutes.
• Sirtuins (SIRT1–7) remove acetyl tags from histones and metabolic enzymes. They also use up one NAD⁺ each time. They link the cell's energy state to gene silencing, mitochondrial biogenesis and stress resistance.

Tissue NAD⁺ falls with age in animals and in some human tissues. Part of the reason is that the enzyme CD38 breaks down more of it, and part is chronic DNA-damage signalling. That is the basis for the interest in NAD "boosters".¹

Human evidence. The clearest human result is in skin. In the ONTRAC trial, 386 people with a history of skin cancer took 500 mg of nicotinamide twice a day or placebo for a year. The nicotinamide group had 23% fewer new non-melanoma skin cancers and fewer precancerous lesions. Sunlight drains NAD⁺ in skin cells, and nicotinamide helps them keep repairing UV damage. The benefit disappeared once people stopped taking it.³ Claims that boosters slow ageing in general aren't yet backed by human outcome trials.

Supports the brain

Neurons use a lot of energy and depend heavily on NAD⁺, both to make energy in their mitochondria and for SIRT1/SIRT3 activity. They're also unusually sensitive to NAD⁺ loss after injury. When an axon is cut, an enzyme called SARM1 destroys the local NAD⁺, and that is what makes the axon degenerate. Adding NAD⁺ precursors delays the process in animal models. The "dementia" of pellagra, which reverses with niacin, is the human proof that the brain needs a steady supply.^1,2

Human trials are early. In the NADPARK trial, 30 people newly diagnosed with Parkinson's took 1,000 mg/day of nicotinamide riboside or placebo for 30 days. NR was safe and raised NAD⁺ in the brain, measured by brain scanning (MR spectroscopy). People whose brain NAD⁺ rose showed changes in brain metabolism and slight clinical improvement.⁴ That's a phase I safety-and-signal study, and larger trials are under way. For now, what's established is that the brain needs adequate B3. Whether extra B3 protects the brain is still being tested.

Intake & safety

The RDA is 14 mg/day for women and 16 mg/day for men, in niacin equivalents. The body can also make about 1 mg of niacin from every 60 mg of tryptophan, using enzymes that need B6 and B2, so a high-protein diet covers much of the need. Meat and fish are the richest sources.

Top foods

• Chicken breast: about 10–11 mg in 3 oz
• Tuna (light, canned): about 8 mg in 3 oz
• Salmon: about 7–8 mg in 3 oz
• Turkey: about 6–10 mg in 3 oz
• Beef: about 5–6 mg in 3 oz

Deficiency

Pellagra is now rare in wealthy countries. It still occurs with heavy drinking, malabsorption, carcinoid tumours (which use up tryptophan), the drug isoniazid, and diets built around unprocessed corn.² Early signs are tiredness, a sore red tongue, and a sunburn-like rash on sun-exposed skin (the "Casal necklace" around the neck). Later come diarrhoea, depression, confusion and dementia.