Niacin is shorthand for the two main forms (or vitamers) of vitamin B3: nicotinic acid and nicotinamide. These vitamers work in different ways and have different therapeutic uses. For instance, nicotinic acid, but not nicotinamide, can change the concentration of lipids in the blood in a positive way. This led to the development of Niaspan, a prescription medication that is used to lower LDL (“bad”) and increase HDL (“good”) blood cholesterol levels.
Both nicotinic acid and nicotinamide are readily available in animal-based foods such as meat, poultry, and fish, and plant-based foods such as nuts, legumes, and grains.
Niacin’s classic role is as a building block for nicotinamide adenine dinucleotide (NAD). More than 400 chemical reactions in the body need NAD, from metabolizing all the nutrients in the foods we eat to many functions that happen within the cells, including gene expression and DNA repair. Niacin likely plays significant roles we’ve yet to uncover.
Studies have shown that people with higher levels of niacin in their diet have a diminished risk for Alzheimer’s disease. A prospective study followed 3,718 men and women ages 65 and older for six years, kept questionnaires on their diets, and had periodic cognitive assessments. Researchers reported in the Journal of Neurology, Neurosurgery, and Psychiatry that people with the highest niacin intake had lower rates of Alzheimer’s disease and cognitive decline, compared with people with the lowest intake. They concluded that niacin may protect against both Alzheimer’s and cognitive decline in aging.
The Coronary Artery Risk Development in Young Adults, or “CARDIA” study, with results published in 2017 in The American Journal of Clinical Nutrition, followed its participants—3,136 men and women ages 18 to 30 from Chicago, Minneapolis, Oakland, and Birmingham, Ala.—for up to 25 years. The study measured dietary and supplemental B vitamin intake of niacin, folate, vitamin B6, and vitamin B12, and found that a higher intake of B vitamins, niacin in particular, throughout young adulthood was associated with better cognitive function scores in middle-age years.
In contrast to others in the field of Alzheimer’s research who are focused directly on amyloid plaques and finding therapeutics that target them, our research centers on the activity of immune cells in the brain and how their response to amyloid plaques act as a central contributor to Alzheimer’s disease.
This particular research project began five years ago to build on those earlier findings regarding niacin and Alzheimer’s. While niacin was used in other models of Alzheimer’s, nicotinic acid has not. No one before had discerned between the types of niacin. For this research, we used Niaspan and mice specifically engineered to get Alzheimer’s disease by modifying certain genes.
Data from previous studies show that the brain doesn’t convert nicotinic acid into NAD as other organs do. Different things happen. Most importantly in terms of Alzheimer’s disease, it activates a receptor called HCAR2 in the brain’s microglia. Microglia are immune cells that play roles in brain infections and inflammation and have been linked to amyloid plaques.
When niacin activates the receptor, it stimulates beneficial actions from these immune cells. We found protective and therapeutic effects in the mice given Niaspan. The mice who did not receive it had worsening cognitive impairments and greater amyloid deposits. The results suggest that modulating microglia activity through HCAR2—specifically targeting the neuroimmune response to amyloid in the brain—might be effective for preventing or treating Alzheimer’s disease.
As exciting as this finding is, it’s too early to extrapolate what it means to human beings. All we know for sure right now is that we can reverse the disease effects in a mouse genetically transformed to develop Alzheimer’s disease.
Our primary goal for this year is to move to a clinical study on people to be sure nicotinic acid has a beneficial effect and to find the right dose. We gave mice a dose equivalent to the one that people are started on to manage blood lipids and lower than the maintenance dose. If you currently take Niaspan for high cholesterol, you may indeed be getting an anti-Alzheimer’s benefit.
We know that niacin helps with memory, so make sure you’re getting it in your diet. According to the Office of Dietary Supplements in the National Institutes of Health, plant-based foods provide about 2 to 5 mg of niacin per serving, mainly as nicotinic acid. It’s too soon to say whether you should be supplementing with nicotinic acid to prevent Alzheimer’s.
People who take the very high doses of Niaspan must be regularly monitored by a physician. It comes in an extended-release form that allows slower, more gradual absorption and helps avoid side effects of high-dose niacin like flushing.
Our work also includes investigating nicotinic acid’s effect on amyloid- and tau-driven disease. At other institutions, it’s currently being tested in clinical trials as a possible therapeutic for Parkinson’s disease and glioblastoma (an aggressive form of brain cancer), following the thesis that nicotinic acid modulates the brain’s immune response.