Niacin (vitamin B3) plays critical roles in cellular metabolism, cardiovascular health, and inflammation. It is one of the most studied vitamins in clinical research.

What Is Niacin?

Niacin (also known as vitamin B3) is one of the water-soluble B vitamins. Niacin is the generic name for nicotinic acid (pyridine-3-carboxylic acid), nicotinamide (niacinamide or pyridine-3-carboxamide), and related derivatives, such as nicotinamide riboside.

All tissues in the body convert absorbed niacin into its main metabolically active form, the coenzyme nicotinamide adenine dinucleotide (NAD). NAD is a cofactor for more than 400 enzymes, which is more than for any other vitamin-derived coenzyme. NAD is also converted into another active form, the coenzyme nicotinamide adenine dinucleotide phosphate (NADP), in all tissues except skeletal muscle.

NAD and NADP are required in most metabolic redox processes in cells where substrates are oxidized or reduced. NAD is primarily involved in catabolic reactions that transfer the potential energy in carbohydrates, fats, and proteins to adenosine triphosphate (ATP), the cell’s primary energy currency. NAD is also required for enzymes involved in critical cellular functions, such as the maintenance of genome integrity, control of gene expression, and cellular communication. NADP, in contrast, enables anabolic reactions, such as the synthesis of cholesterol and fatty acids, and plays a critical role in maintaining cellular antioxidant function. (Source: NIH)

Is Niacin Safe?

It is common among health practitioners to believe that too much niacin can cause liver damage. This is only true of sustained release niacin [1]. In fact, if you give sustained released niacin, YOU MUST regularly test transaminases to monitor for liver damage. Regular niacin is safe.

No symptoms for early liver damage: Transaminases will increase for many patients a long time before hepatic damage occurs. However, like iron overload the symptoms are either not there or are mild at best.  Hence, if the sustained release niacin has increased the transaminases and the patient is not told to have them checked then the hepatic problem could increase from inflammation to certain damage.

Although the use of regular niacin will cause a transient flushing effect, it will not cause the hepatic toxicity associated with sustained release forms.  It is wise to check liver enzymes, especially when using sustained release niacin.

Niacin Studies:

Niacin and Cholesterol

Combination niacin/statin on cholesterol and lipid profiles: The effect niacin has on lipid profiles has been extensively studied. Several studies have demonstrated that niacin in combination with a cholesterol lowering drug is more effective than the statin alone when it comes to improving lipid profiles.

In studies, niacin potentiated the effectiveness of cholesterol lowering medication. It helped to not only lower cholesterol, but also improve the lipid profile in the studies that combined it with a statin. LDL was lowered, triglycerides were lowered, and HDL was increased [2-5]. Some of the studies improvements in the vascular endothelium and arterial health [6,7].

Niacin (alone), cholesterol and lipid profiles: There are many studies that combine niacin with cholesterol medication to improve lipid profiles. Niacin, however, produces results on its own.

One study looked at 60 patients who were randomly chosen to receive niacin or a placebo.  Niacin favorably changed the lipid profiles of the test group. At a dosage of 2,000 mg/day, total cholesterol decreased by 12.1%, LDL cholesterol by 16.7%, triglycerides by 34.5%, and lipoprotein(a) by 23.6%; HDL cholesterol increased by 25.8%. Flushing was the most commonly reported side effect; flushing episodes tended to decrease with time despite an increasing dose of niacin [7]. Another study, with 200 subjects obtained similar results [8], as did a host of other studies [10-16].

Niacin, Blood Sugar, and Diabetes

Niacin, insulin insensitivity, metabolic syndrome, and type 2 diabetes:  The cardiovascular benefits of niacin have been specifically studied in patients with insulin insensitivity. The authors of one meta-analysis had this to say, “This study found that niacin supplementation could improve lipid profiles without affecting the glycemic levels for patients with type 2 diabetes. Additional large-scale RCTs should be conducted to evaluate the long-term effectiveness of niacin supplementation.” [17]

Another study showed that the mechanism for niacin’s improvement of lipid profiles in patients with metabolic syndrome could be linked to reduction in inflammation [18]. The researchers found that high dose niacin may have a negative effect on insulin insensitivity, so there had to be another mechanism for the improvement of the lipid profiles. They found that niacin was anti-inflammatory, as it helped reduce c-reactive protein and TNF.

Niacin and Cardiovascular Health

Vascular health: Niacin improves the health of the vascular endothelium [19-21]. According to one study, improvement in the vascular endothelium is experienced by patients with low HDL. The authors of one study stated, “Recent studies suggest that HDL-C directly improves endothelial function. Nicotinic acid (niacin) effectively raises serum HDL-C. We therefore hypothesized that treatment with niacin improves endothelial dysfunction in patients with coronary artery disease. [20]”

Niacin can lower fibrinogen levels. The authors of one study stated, “This study demonstrates that niacin supplementation decreases plasma fibrinogen and low-density lipoprotein cholesterol in subjects with peripheral vascular disease randomized to receive niacin, warfarin, antioxidants, or placebo. Changes in fibrinogen levels are highly correlated with changes in low-density lipoprotein cholesterol (r = 0.61; p < 0.009) in subjects taking niacin. [21]”

Cardiac health: Niacin is cardioprotective. It reduces the chance of having a cardiovascular event. Authors of one study state, “The consensus perspective derived from available clinical data supports that niacin reduces CVD events and, further, that this may occur through a mechanism not reflected by changes in high-density lipoprotein cholesterol concentration. [22]”

Another study shows that niacin can help healing after an MI and can help prevent a repeat heart attack. The authors stated, “Niacin decreased the occurrence of 6-year MI and 15-year total mortality similarly among patients with or without metabolic syndrome. [24]”

Most of the niacin studies concern cholesterol, arterial health, and cardiovascular issues. A large portion of the studies concern niacin’s use as an adjunct to cholesterol lowering medication. Another body of studies, however, show its use without drug therapy. Niacin’s value goes beyond lower cholesterol.  Studies show that it lowers LDL and triglycerides, while increasing HDL. There are a few niacin studies that show it may have other clinical uses.

Niacin and Kidney Disease

Kidney: Elevated serum phosphate levels have been independently associated with increased mortality risk among this population of patients with chronic kidney disease. Phosphate excess has been implicated in the substantial cardiovascular morbidity and mortality observed among people who receive dialysis.

One study examined the effect of randomized treatment with niacin (1500 or 2000 mg) or placebo on temporal changes in markers of mineral metabolism in 352 participants with eGFR<60 ml/min per 1.73 m2 over 3 years [25]. The use of niacin lowered serum phosphorus.  In another study, the researchers concluded that niacin may be a novel treatment for this issue [26].

Niacin and Other Health Issues

Parkinson’s disease: One study looked at neuroinflammation in Parkinson’s disease (PD) [27]. The researchers concluded, “Low dose niacin supplementation may be beneficial in PD, boosting anti-inflammatory processes and suppressing inflammation. Varied niacin dosages for longer durations may further reveal the potential role of anti-inflammatory interventions in PD progression.”

Macular degeneration: The study found on macular degeneration and niacin is just another demonstration of niacin and arterial health [28]. Niacin causes vasodilation of the arterioles in the eye. The authors called for further studies to examine it as a treatment.

Erectile dysfunction: Once again, this is another instance of niacin improving vascular health. One study found that niacin had the potential to resolve erectile dysfunction, with no other therapy. The authors concluded, “Niacin alone can improve the erectile function in patients suffering from moderate to severe ED and dyslipidemia.” [29]

Niacin remains a clinically relevant nutrient for cardiovascular and metabolic support. While its use as monotherapy has declined with widespread statin use, evidence continues to support its anti-inflammatory and vascular benefits, particularly in metabolic syndrome and endothelial dysfunction.

References:

  1. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK548176/
  2. Am J Cardiol. 2003 Mar 15;91(6):667-72 Comparison of once-daily, niacin extended-release/lovastatin with standard doses of atorvastatin and simvastatin (the ADvicor Versus Other Cholesterol-Modulating Agents Trial Evaluation [ADVOCATE])
  3. Am J Cardiol. 2003 Mar 15;91(6):667-72 Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol <100 mg/dl in patients with hyperlipidemia and coronary artery disease
  4. Am J Cardiol. 2008 May 15;101(10):1428-36. Comparison of the safety and efficacy of a combination tablet of niacin extended release and simvastatin vs simvastatin monotherapy in patients with increased non-HDL cholesterol (from the SEACOAST I study)
  5. N Engl J Med. 2011 Dec 15;365(24):2255-67. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy
  6. Diab Vasc Dis Res. 2010 Oct;7(4):296-9. Niacin improves small artery vasodilatory function and compliance in statin-treated type 2 diabetic patients (tested in combination with statin)
  7. Am J Cardiol. 1998 Dec 17;82(12A):35U-38U; discussion 39U-41U. Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study
  8. Arch Intern Med. 1991 Jul;151(7):1424-32. Niacin revisited. A randomized, controlled trial of wax-matrix sustained-release niacin in hypercholesterolemia
  9. Am J Med. 2012 Oct;125(10):1026-35 Extended-release niacin acutely suppresses postprandial triglyceridemia
  10. Am J Cardiol. 2003 Jun 15;91(12):1432-6. Effects of extended-release niacin on lipoprotein subclass distribution
  11. Am J Clin Nutr. 2008 Jul;88(1):30-7 Postprandial triglyceride responses to aerobic exercise and extended-release niacin
  12. 2016 Nov;65(11):1664-1678 Effect of extended-release niacin on plasma lipoprotein(a) levels: A systematic review and meta-analysis of randomized placebo-controlled trials
  13. Am J Cardiol. 1998 Dec 17;82(12A):35U-38U; discussion 39U-41U. Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study
  14. Arch Intern Med. 1991 Jul;151(7):1424-32. Niacin revisited. A randomized, controlled trial of wax-matrix sustained-release niacin in hypercholesterolemia
  15. Am J Cardiol. 2000 May 1;85(9):1100-5. Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia
  16. Arch Fam Med. 1996 Nov-Dec;5(10):567-75. Clinical trial of wax-matrix sustained-release niacin in a Russian population with hypercholesterolemia
  17. Medicine (Baltimore). 2020 Jul 17;99(29):e21235 Effectiveness of niacin supplementation for patients with type 2 diabetes: A meta-analysis of randomized controlled trials
  18. J Clin Lipidol. 2018 May-Jun;12(3):810-821.e1. Niacin action in the atherogenic mixed dyslipidemia of metabolic syndrome: Insights from metabolic biomarker profiling and network analysis
  19. Vasc Med. 2014 Feb;19(1):54-66. Effect of niacin on endothelial function: a systematic review and meta-analysis of randomized controlled trials
  20. 2009 May;204(1):216-21 Effects of oral niacin on endothelial dysfunction in patients with coronary artery disease: results of the randomized, double-blind, placebo-controlled INEF study
  21. Int J Clin Pract. 2007 Nov;61(11):1942-8 The effects of extended-release niacin on carotid intimal media thickness, endothelial function and inflammatory markers in patients with the metabolic syndrome
  22. Am J Cardiol. 1998 Sep 1;82(5):697-9, A9 Effect of niacin supplementation on fibrinogen levels in patients with peripheral vascular disease
  23. J Am Coll Cardiol. 2013 Jan 29;61(4):440-446 The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression
  24. Am J Cardiol. 2006 Feb 15;97(4):477-9 Benefits of niacin in patients with versus without the metabolic syndrome and healed myocardial infarction (from the Coronary Drug Project)
  25. Clin J Am Soc Nephrol. 2018 Jan 6;13(1):36-44. The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD
  26. Am J Nephrol. 2014;39(6):484-90 Effect of niacin on FGF23 concentration in chronic kidney disease
  27. J Neuroimmunol. 2018 Jul 15;320:76-79 Niacin modulates macrophage polarization in Parkinson’s disease
  28. Curr Eye Res. Jul-Aug 2006;31(7-8):629-34. Effect of niacin on retinal vascular diameter in patients with age-related macular degeneration
  29. J Sex Med. 2011 Oct;8(10):2883-93 Effect of niacin on erectile function in men suffering erectile dysfunction and dyslipidemia