Vitamin B3
1. Introduction – What is the product, chemical/botanical basics, mechanism of action
Vitamin B3, also known as Niacin, is a water-soluble B complex vitamin essential for human health [1]. The term Vitamin B3 encompasses two primary forms: nicotinic acid (Niacin) and nicotinamide (Niacinamide or Nicotinamide) [2]. While both forms provide Vitamin B3 activity, they have different pharmacological profiles, particularly concerning the common side effect of flushing [2].
Chemical/Botanical Basics
Niacin and Niacinamide are precursors to the vital coenzymes Nicotinamide Adenine Dinucleotide (NAD+) and Nicotinamide Adenine Dinucleotide Phosphate (NADP+) [1]. These coenzymes are crucial for over 400 enzymatic reactions in the body, making them fundamental to cellular metabolism [1].
Mechanism of Action (Metabolic)
The primary mechanism of action is through the synthesis of NAD+ and NADP+. These coenzymes act as hydrogen ion acceptors and donors in essential oxidation-reduction reactions [1]. These reactions are integral to:
- Glycolysis and pyruvate metabolism
- Protein and amino acid metabolism
- Pentose biosynthesis
- Fatty acid metabolism
- Synthesis of high-energy phosphate bonds [1]
Mechanism of Action (Dyslipidemia)
At pharmacological doses, niacin (nicotinic acid) has a distinct mechanism for affecting blood lipids. It works by:
- Inhibiting lipolysis (fat breakdown) in adipose tissue.
- Reducing the liver’s formation of triacylglycerol.
- Inhibiting the synthesis of apolipoprotein B-100 and hepatic very-low-density lipoprotein (VLDL).
- Increasing the fractional catabolic rate of HDL-apolipoprotein A-1 (Apo A-1), which is key to reverse cholesterol transport [1].
2. Chemical Composition/Key Bioactive Roles
The key bioactive compounds of Vitamin B3 are its two primary forms and the coenzymes they form.
| Compound Name | Chemical Classification | Key Bioactive Role |
|---|---|---|
| Niacin (Nicotinic Acid) | Pyridine-3-carboxylic acid | Precursor to NAD+ and NADP+; used pharmacologically to modify blood lipids [1]. |
| Niacinamide (Nicotinamide) | Pyridine-3-carboxamide | Precursor to NAD+ and NADP+; commonly used in supplements and skincare as it typically does not cause flushing [2]. |
| NAD+ (Nicotinamide Adenine Dinucleotide) | Coenzyme | Essential coenzyme for cellular energy production and metabolic redox reactions [1]. |
| NADP+ (Nicotinamide Adenine Dinucleotide Phosphate) | Coenzyme | Essential coenzyme for anabolic reactions like fatty acid and cholesterol synthesis [1]. |
3. Health Benefits – Detailed health benefits with scientific evidence
Lipid Management and Cardiovascular Health
Niacin, particularly in its nicotinic acid form at high doses, is an FDA-approved treatment for dyslipidemia [1].
- Cholesterol and Triglyceride Reduction: Therapeutic doses can reduce total cholesterol by up to 25%, LDL-C by up to 15%, and triglycerides by up to 50% [1].
- HDL Elevation: Niacin has the highest efficacy among lipid-modifying agents for raising High-Density Lipoprotein (HDL) cholesterol, with increases of 15% to 35% [1].
- Atherosclerosis: When used as an adjunct to diet and bile acid-binding resins, niacin can help slow the progression of atherosclerotic disease [1].
Treatment of Pellagra
Niacin is used to treat Pellagra, a disease caused by severe Vitamin B3 deficiency, which manifests with dermatitis, diarrhea, and dementia (the “3 Ds”) [1].
Skin Health and Anti-Inflammatory Effects
Niacinamide is widely used in dermatology for its anti-inflammatory properties and its role in improving the skin barrier function [2].
- Topical Use: Topical nicotinamide has shown positive cosmetic outcomes in conditions like discoid lupus erythematosus [1]. It is also commonly used to treat acne and improve skin texture [2].
- Blood Pressure: A 2021 study in Chinese adults suggested a relationship between increased dietary niacin intake and a decrease in blood pressure levels among individuals with new-onset hypertension [2].
4. Dosage and Usage – Recommended dosages, food sources if applicable
Recommended Dietary Intake (DRI)
The Dietary Reference Intakes (DRIs) for niacin are given in milligrams of Niacin Equivalents (NE), where 1 NE equals 1 mg of niacin or 60 mg of the amino acid tryptophan.
| Group | Recommended Daily Intake (RDI) [2] | Maximum Daily Intake (UL) [2] |
|---|---|---|
| Men (19+ years) | 16 mg NE | 35 mg NE |
| Women (19+ years) | 14 mg NE | 35 mg NE |
| Pregnant Women | 18 mg NE | 35 mg NE |
| Breastfeeding Women | 17 mg NE | 35 mg NE |
Therapeutic Dosage
For the treatment of dyslipidemia (under medical supervision), doses are significantly higher:
- Typical Therapeutic Range: 1000 to 3000 mg/day (1-3 grams) for refractory cases [1].
- Administration: Niacin is available in immediate-release, extended-release, and sustained-release formulations, which are not interchangeable [1].
Food Sources
Niacin is naturally found in a variety of foods, including:
- Red meat (beef, pork)
- Poultry and fish
- Brown rice
- Nuts, seeds, and legumes
- Whole-grain cereals [2]
5. Safety and Precautions – Side effects, contraindications, drug interactions, warnings
Side Effects
| Category | Side Effect | Details |
|---|---|---|
| Common | Niacin Flush | Redness, warmth, and itching of the skin, especially on the face and neck. This is common with immediate-release niacin (nicotinic acid) and is less frequent with niacinamide [2]. |
| Gastrointestinal | Upset stomach, diarrhea, abdominal pain [2]. | |
| Serious | Hepatotoxicity | Liver problems (elevated transaminases, active hepatic disease) [1, 2]. |
| Serious | Metabolic | Changes to glucose levels (glucose intolerance), gout (increased uric acid) [2]. |
| Overdose | Rapid heartbeat, severe skin flushing with dizziness, nausea, vomiting, rash [2]. Doses between 2,000 and 6,000 mg/day can cause serious side effects [2]. |
Serious Warnings and Contraindications
- Cardiovascular Risk (NEW WARNING): A 2024 study published in Nature Medicine identified a new pathway where a terminal metabolite of excess niacin, 4-methyl-nicotinamide (4-PY), promotes vascular inflammation and contributes to increased cardiovascular disease risk [3]. This suggests that excessive, non-therapeutic supplementation may be harmful.
- Contraindications: Niacin is contraindicated in individuals with:
- Active hepatic disease or unexplained transaminase elevation [1].
- Active peptic ulcer disease [1].
- Arterial bleeding [1].
- Hypersensitivity to niacin [1].
- Precautions: Patients with a history of liver or kidney disease, diabetes, or high blood pressure should consult a doctor before use [2]. Niacin should not be used to self-treat high cholesterol [2].
Drug Interactions
Niacin can interact with several medications and supplements [2]:
- Statins: The combination of niacin and statins (e.g., atorvastatin, simvastatin) may increase the risk of muscle damage (myopathy) [2].
- Antihypertensives: Niacin can lower blood pressure, potentially leading to excessive hypotension when combined with blood pressure medications [2].
- Diabetes Drugs: Niacin can affect glucose levels, requiring adjustment of diabetes medication [2].
- Blood Thinners: May increase the risk of bleeding [2].
- Alcohol: Increases the risk of liver problems [2].
- Supplements: Caution with ginkgo biloba and certain antioxidants [2].
6. References
- Peechakara, B. V., & Gupta, M. Vitamin B3. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK526107/
- WebMD. Niacin (Vitamin B3): Benefits and Side Effects. Retrieved from https://www.webmd.com/diet/supplement-guide-niacin
- Ferrell, M., et al. A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. Nature Medicine, 30, 424–434 (2024). https://www.nature.com/articles/s41591-023-02793-8
Category: Vitamin
