Can Vitamin B3 (Niacin) Stave Off Dementia?

Dementia is an umbrella term that includes multiple neurodegenerative conditions that lead to cognitive and functional impairments. Alzheimer’s disease (AD) is the most common form, expected to affect approximately 13.8 million people in the US by 2060.^[1]

The exact origins of AD remain unclear, but factors such as genetics, lifestyle, and environmental influences are all thought to contribute to its development. Various studies have evaluated the potential of vitamin B3 subtypes—nicotinamide in particular—to affect cognitive disabilities such as AD. Let’s take a closer look.

Vitamin B3 and cognitive function

Niacin (nicotinic acid), nicotinamide (niacinamide), nicotinamide mononucleotide (NMN), and nicotinamide riboside (NR) are related compounds within the family of B3 vitamins.

Researchers writing in Aging Cell explain that nicotinamide is a precursor for NAD+, which plays a crucial role in longevity-related cellular processes by acting as a critical coenzyme during metabolic reactions that are directed to the mitochondria. These metabolic responses produce ATP via oxidative phosphorylation.^[2]

Declines in NAD+ stores across multiple tissues have been identified as a common pathological element in aging-related diseases. The brain, highly dependent on energy, shows marked reductions in NAD+ during aging.

What the research says

Studies show that nicotinamide supplementation defends against brain-specific insulin resistance in these neurodegenerative processes and supports myelin regeneration in demyelinating disease. Some of these studies are outlined below.

• In a 2022 clinical trial conducted by the Aging Cell authors, oral administration of nicotinamide riboside (500 mg twice daily) to healthy elderly subjects augmented NAD+ levels in neuronal extracellular vesicles and reduced Aβ42, pJNK, and pERK1/2—kinases linked to insulin resistance and neuroinflammation.

• Another recent study found that nicotinamide promotes myelination in both in-vivo and ex-vivo models, including a lysolecithin (LPC)-induced demyelination model and cortical slice cultures.^[3]

• In a placebo-controlled study presented at the 2023 Alzheimer’s Association International Conference, 1,500 mg nicotinamide—given twice daily to participants with mild cognitive impairment due to AD—significantly improved Clinical Dementia Rating-Sum of Boxes scores. Secondary AD biomarkers in cerebrospinal fluid showed no significant changes, though phospho-tau181 and total tau trends were favorable.^[4]

• A study analyzing NHANES 2011-2014 data on 2,523 older American adults linked higher dietary niacin intake to improved cognitive function. The results depicted an L-shaped dose-response relationship, indicating a threshold beyond which additional niacin intake does not yield further cognitive benefits.^[5]

Mechanisms

Permeation through blood-brain barrier

Vitamin B3’s ability to cross the blood-brain barrier facilitates its direct pharmacological impacts on the central nervous system. This is evidenced by PET imaging that demonstrates cerebral uptake following intravenous administration in patients with neurodegenerative diseases.

Nicotinamide promotes the phagocytosis of amyloid-beta plaques by upregulating a healthy microglia/macrophage response. This phagocytosis reduces plaque burden and alleviates cognitive decline in AD mouse models.

Lipid metabolism

Nicotinamide also regulates lipid metabolism disruptions often linked with the ApoE gene. It enhances liver X receptor expression, promotes lipid turnover, and maintains central nervous system lipid balance.

Gut-brain axis

Nicotinamide’s effects also extend to the gut-brain axis, influencing neurodegeneration through intestinal health.^[7]

Supplementation guidelines

The FDA has prohibited the marketing and sale of NMN as a dietary supplement, categorizing it under potential new drug investigations.^[8] This decision might pave the way for more rigorous development and evaluation of nicotinamide derivatives as therapeutic drugs.

While other nicotinamide supplements are still available OTC, you should explicitly discourage their unsupervised consumption due to the risk of toxicity. These reactions can include skin flushing, itching, hypotension, liver damage, and gastrointestinal symptoms.^[9]

For neurologists advising patients on dietary intake of vitamin B3, recommend dietary sources like poultry, beef, fish, fortified cereals, and breads; plant-based sources include nuts, legumes, and grains.