We take a look at the common dietary supplement niacin.
Niacin is a common dietary supplement with a long research history and more than a few tricks up its sleeve. Recent human trials have shed new light on its possible role in addressing mitochondrial dysfunction and aging.
What is niacin?
Niacin is a form of water-soluble vitamin B3. It was discovered in 1937 by biochemist Conrad Elvehjem. It was originally used to treat pellagra, a disease caused by vitamin B3 deficiency which causes skin lesions, diarrhea, dementia, and even death.
This compound is now commonly marketed as niacin and is the third of eight presently known B vitamins.
Niacin was originally called nicotinic acid because it can be created by the oxidation of nicotine with nitric acid. However, people knew nicotine as the addictive chemical in tobacco, so the name niacin was used instead. Niacin comes from the words NIcotinic ACid vitamIN.
Niacin in food
Foods rich in niacin include chicken, tuna, turkey, peanuts, coffee, kidney beans, pork, and bacon. Meats are generally the highest in niacin content by a large margin.
But, this may not be practical for dietary reasons where people cannot or choose not to eat meat. Fortunately, niacin supplements are available for those struggling to get enough in their diet or are biohacking.
There are two versions of nicotinic acid available: a regular variety and a slow-release variety. The slow release version is sometimes called ‘delayed action’ or ‘persistent release’. Slow-release nicotinic acid is not recommended for regular supplementation, as it carries the risk of liver damage . Only take slow-release nicotinic acid when directed to do so by a qualified physician, and only for the stated duration.
The recommended daily amount of niacin for adult males is 16 milligrams (mg) a day and for adult women who aren’t pregnant, 14 mg a day.
What’s the difference between regular niacin and “no-flush” niacin?
There are also some brands selling “no flush” niacin, this is inositol hexaniacinate (a different form of vitamin B3) and is not the same thing. Inositol hexanicotinate does support energy metabolism and is used by the nervous system. But, no studies have shown it has any effect on cholesterol levels and does not work in the same way as niacin.
What does niacin do?
Niacin is essential for the normal function of the nervous system and the maintenance of healthy skin and mucous membranes. Niacin helps the body convert food (carbohydrates) into fuel (glucose), which the body uses to produce energy. This means that a common sign of niacin deficiency is fatigue. Niacin can also help reduce blood pressure.
As a precursor of nicotinamide adenine dinucleotide (NAD+), niacin can increase levels of NAD+ in cells. NAD+ is involved in the repair of DNA [2-3], and, recently, the mechanism of how NAD+ repairs DNA was discovered .
In metabolism, NAD+ is a coenzyme involved in redox reactions, helping to move electrons from one reaction to another. NAD is found in two forms in cells. NAD+ is an oxidizing agent; it accepts electrons from other molecules and becomes reduced. This reaction forms NADH, which is then used as a reducing agent to donate electrons. These electron transfer reactions are the primary function of NAD+ , but NAD+ is also involved in other cellular processes. It is associated with the sirtuins, which are closely linked to longevity in mammals.
Potential niacin benefits
There are a number of potential health benefits associated with niacin.
Niacin and cholesterol
Niacin increases high-density lipoprotein (HDL) cholesterol and reduces low-density lipoprotein (LDL) cholesterol [5-7]. It is often used to control blood pressure and cholesterol levels. Especially in patients at risk of heart disease, dyslipidaemia, hypercholesterolemia, or hyperlipidemia.
It blocks production of very-low-density lipoprotein (VLDL) in the liver and, consequently, its byproduct, LDL . VLDL transports both triglycerides and cholesterol. Once in the circulation, VLDL is broken down, releasing triglycerides for energy use by cells or for storage in the adipose fat tissue. Once triglycerides their composition changes into intermediate-density lipoprotein (IDL). Later, when the amount of cholesterol increases, IDL becomes LDL.
Niacin can raise HDL by as much as 30-35 percent. This effect is caused by a reduction of cholesterol transfer from HDL to VLDL and delayed clearance of HDL . The drug also lowers total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, and lipoprotein. While some studies dispute that niacin reduces the risk of stroke and heart attack, clinical trials suggest that it does.
Niacin and heart disease
The CLAS study, a two-part, randomized, placebo-controlled, angiographic trial, combined colestipol-niacin therapy in 162 subjects . Two-year results (CLAS-I) showed a decreased progression of atherosclerosis and an increased regression. A subgroup of 103 subjects was treated for four years (CLAS-II). Blood lipids, lipoprotein-cholesterol, and apolipoprotein were monitored during the trial. After four years, a significant number of subjects showed non-progression (52% vs. 15% placebo-treated) of coronary artery lesions. Also some saw regression (18% vs. 6% placebo-treated) of coronary artery lesions.
Significantly fewer drug-treated subjects developed new lesions in native coronary arteries (14% vs. 40% placebo-treated) and bypass grafts (16% vs. 38% placebo-treated). These results confirm the CLAS-I findings and indicate that regression can continue for at least four years.
Targeting patients with coronary disease and low HDL cholesterol, the HATS study looked at niacin plus simvastatin, antioxidant-vitamin therapy, a combination of these therapies, and a placebo . The antioxidant therapy was composed of vitamin E, 1000 mg of vitamin C, 25 mg of natural beta-carotene, and 100 μg of selenium. Simvastatin plus niacin provided marked clinical and angiographically measurable benefits against coronary artery blockages compared to antioxidant-vitamin therapy and the placebo.
Potential concern for taking niacin
One concern about niacin that is sometimes raised is a 2016 study that suggested that niacin increases blood glucose levels. Thus, it has been suggested that it may contribute to new-onset diabetes. A meta-analysis was made of 11 randomized trials to confirm whether or not a link exists between niacin therapy and new-onset diabetes .
The trials were found by a search of the Cochrane database and EMBASE between the years 1975-2014. Inclusion criteria consisted of randomized controlled trials on niacin and its cardiovascular effects on 50 or more non-diabetic participants. This was conducted as a 2-armed study with a total of 26,340 participants; of these, 13,121 were assigned to the niacin therapy group, and 13,219 were assigned to the control group.
Of the 26,340 total participants analyzed, 725 in the niacin group and 646 in the control group developed new-onset diabetes. The use of niacin was shown to be associated with a moderately increased risk of developing diabetes compared to a placebo. However, the cardiovascular benefits of niacin therapy may outweigh the risk of developing diabetes.
Niacin increased NAD+ in human trials
In 2020, a human trial showed that niacin increases NAD+ significantly . Participants were given an escalating dose of niacin, starting at 250 mg a day and rising to 750-1000 mg a day over a 4-month period. Finally a 10-month follow-up treatment period. The participants formed two groups: a group of individuals with mitochondrial myopathy and a group of healthy age-matched people consisting of two healthy people. There were two healthy people for each patient with mitochondrial myopathy. All participants in the trial were given the same escalating niacin regimen.
The researchers reported that niacin increased muscle NAD+ levels by 1.3-fold by the 4-month mark. This increased to 2.3-fold after 10 months in the mitochondrial myopathy group. The healthy control group saw no such increase, which suggests that NAD+ levels are regulated in skeletal muscle tissue and only increase when levels are below normal, as happens in mitochondrial myopathy. This may also be the case during aging, which also reduces efficient mitochondrial function.
Whole-blood NAD+ was also reported to have increased by 7.1-fold in the study group and 5.7 in the control group after 4 months compared to the participants’ baseline. There was a further increase to 8.2-fold compared to the baseline by the 10-month mark. This confirms that niacin does reach the bloodstream in significant amounts and is not removed by the liver.
Niacin appears to improve body composition
The researchers also reported that niacin improved body composition, and participants saw a decrease in whole-body fat percentage in controls and increased muscle mass in both the control and study groups. After 10 months, participants saw increased muscle strength. They noted that hepatic fat was reduced by half and visceral fat by a quarter; both of these fat deposits are associated with an increased risk of metabolic syndrome.
The researchers also considered the previously mentioned risk of niacin increasing blood glucose levels. The study results showed that niacin did indeed increase fasting glucose levels in both study groups following 4 months of supplementation. However, glycosylated hemoglobin, which reflects long-term glucose levels, was not affected.
Niacin side effects
A typical side effect of high-dose niacin is the “niacin flush” reaction, which can potentially cause a burning, tingling, and itching sensation on the skin. This flushing is harmless and typically subsides within 30 minutes to an hour. The flush reaction is normally the most intense after the first dose and normally diminishes with continued use of niacin as the body grows used to it. Its severity may also be reduced by starting at a low dose (50-100 mg), taking an aspirin or white willow extract beforehand, and drinking water.
As mentioned previously, slow-release/sustained release niacin carries the risk of liver damage so be careful when purchasing . If you experience any adverse effects, cease taking niacin immediately and consult your doctor.
There is also some concern that niacin can deplete methyl groups  and raise homocysteine, an amino acid. Vitamins B12, B6 and folate break down homocysteine to create other molecules but when high homocysteine levels are a risk factor for heart attacks . It may be possible to reduce homocysteine levels by restoring methyl groups using supplements such as trimethylglycine (TMG).
This article is only a very brief summary, is not intended as an exhaustive guide, and is based on the interpretation of research data, which is speculative by nature. This article is not a substitute for consulting your physician about which supplements may or may not be right for you. We do not endorse supplement use or any product or supplement vendor, and all discussion here is for scientific interest.
Source: Lifespan.io is a nonprofit advocacy organization and news outlet covering aging and rejuvenation research.
Author: Steve Hill