Niacin, otherwise known as vitamin B3 or nicotinic acid, is an essential vitamin required for various processes in the body. A water-soluble member of the vitamin B group, it plays a key role in energy metabolism, supporting the conversion of nutrients obtained from food into usable energy. It’s also important for the health of the skin, nervous system, and digestive tract. Niacin is found in the diet from a variety of whole and processed food sources, including some packaged items as a fortifying micronutrient.
Aside from its role as a vitamin, niacin has therapeutic uses too, particularly for the improvement of the blood lipid (fat) profile and thus reducing cardiovascular disease risk. It was first described as a lipid-lowering agent in 1955 [1] and remains the oldest lipid-lowering drug to date [2].
In this article, we will define what “flush niacin” and “no-flush niacin” are, explain the differences between them, and explore their impact on health. If you're looking for a deeper dive into niacin, you can read more about it in our previous blogs on comparison with nicotinamide and whether or not it can cross the blood-brain barrier.
What Is “Flush Niacin”?
When used by itself or in combination with a statin, niacin safely and effectively addresses dysregulated lipid abnormalities and has been used therapeutically for decades [3]. It increases high-density lipoprotein (HDL) cholesterol (the “good” cholesterol) by between 20 and 40% in most patients. What’s more, pro-atherogenic lipid markers, such as low-density lipoprotein (LDL) cholesterol (the “bad” cholesterol) and triglycerides, are decreased [2,4]. Niacin has beneficial effects on the size of lipid particles in the blood, favoring cardio-protective HDL and bringing about clinically meaningful outcomes such as reduced cardiovascular events and morbidity [5-7]. It has been shown to slow the progression of atherosclerotic cardiovascular disease in people with known coronary artery disease [8].
Although niacin has numerous beneficial effects on blood lipids, patient adherence to long-term therapy is often compromised by flushing, a common side effect of niacin administration.
Flushing is characterized by the reddening and warmth of the skin, due to cutaneous vasodilation that is sometimes accompanied by itching or tingling. Niacin causes this by activating the niacin G protein-coupled receptor 109A (GPR109A) [9] in dermal Langerhans cells, leading to prostaglandin release, which subsequently acts on the capillaries in the skin [3]. Flushing can be rapid in onset and last around 1 hour, causing the patient transient discomfort. Tolerance to flushing does develop rapidly, often as quickly as within one week [10]. Other side effects of niacin include gastrointestinal discomfort and, in the case of extended-release formulations, a greater risk of liver toxicity [4].
For the purposes of this article, “flush niacin” refers to traditional niacin supplements such as immediate-release and extended-release formulations [8].
What is “No-Flush” Niacin?
No-flush niacin is a commercially available formulation of niacin that ostensibly seeks to avoid the flushing effect of traditional niacin supplements [11]. The most common form is inositol hexanicotinate, which pairs niacin with inositol and nicotinamide. This formulation slowly releases niacin as the body breaks it down, leading to a controlled release that prevents the rapid surge in prostaglandins that causes the flushing effect. Of course, this slower release also leads to a more limited availability of active nicotinic acid, reducing its therapeutic effectiveness.
No-flush niacin does not have the same beneficial lipid-modifying effects as traditional niacin preparations (i.e., HDL, LDL, and triglycerides are largely unaffected) [12]. These findings therefore challenge the idea of supplementing with no-flush niacin products from a therapeutic standpoint.
Metabolic and Safety Considerations for Niacin Products
From the perspective of metabolism, immediate-release niacin formulations quickly saturate the nicotinamide pathway (a high-affinity, low-capacity pathway) and are then predominantly metabolized through the conjugation pathway, producing more flushing but not liver toxicity [13]. In contrast, long-acting niacin is very slowly absorbed and metabolized through the nicotinamide pathway, and because of this, long-acting niacin rarely causes flushing. It does, however, increase the risk of serious, dose-related hepatotoxic effects. Extended-release niacin has an intermediate absorption rate, with a more balanced metabolism between the two pathways. As a result, there is less flushing and less risk of hepatotoxicity, at least with daily doses of 2 g or below.
A Comparison of Flush and No-Flush Niacin
As discussed above, flush niacin (both immediate and extended release) has been shown to improve lipid profiles and reduce cardiovascular disease risk, whereas no-flush niacin does not appear to have any benefits in this respect. However, the flushing effect, which is a variable yet manageable feature of niacin supplementation, is rare to non-existent with no-flush products. The bottom line is that the flushing effect can be mitigated with gradual dosing and food intake.
Strategies to Manage Niacin Flushing
Around 5 to 20% of people discontinue niacin treatment due to flushing, and there are several strategies to minimize the impact of this. Flushing can be reduced by taking niacin with meals (or at bedtime with a low-fat snack), avoiding exacerbating factors (such as alcohol or hot beverage consumption), and taking 325 mg of aspirin 30 minutes before niacin dosing [14]. Research advises that an initially slow niacin dose escalation from 0.5 to 1 g per day for 8 weeks can be a great starting point, followed by a jump from 1 to 2 g per day in a single step, and then gauge the response. With effective support, treatment with aspirin, and careful dose escalation, compliance with niacin treatment can be greatly improved, with benefits for blood lipids and the prevention of cardiovascular events.
Dietary Sources of Niacin
For those who do not require high-dose supplementation, dietary sources of niacin may suffice. Animal-based foods rich in niacin include chicken, turkey, fish (e.g., tuna, salmon), and liver. Plant-based sources include peanuts, sunflower seeds, brown rice, and fortified cereals. The Recommended Dietary Allowance (RDA) for niacin is 16 mg/day for men and 14 mg/day for women. The RDA for pregnant women is 18 mg per day, and for breastfeeding women it is 17 mg per day.
Conclusion
In this article, we have clarified the differences between flush and no-flush niacin. For decades, flush niacin has been the gold standard for improving lipid profiles and reducing the risk of cardiovascular events. Despite the inconvenience of flushing, it offers substantial benefits for managing dyslipidemia, and the negative impact of flushing can be minimized with several strategies. Conversely, no-flush niacin provides better tolerability but lacks evidence supporting its efficacy, making it less suitable for therapeutic purposes. Should high-dose niacin administration be required (i.e., obtaining the required amount from the diet is not possible), no-flush niacin should be avoided. Of course, the choice should ultimately be based on individual health needs in consultation with a healthcare professional.
References
[1] R. Altschul, A. Hoffer, J.D. Stephen, Influence of nicotinic acid on serum cholesterol in man, Archives of Biochemistry and Biophysics 54 (1955) 558–559. https://doi.org/10.1016/0003-9861(55)90070-9.
[2] T.C. Villines, A.S. Kim, R.S. Gore, A.J. Taylor, Niacin: The Evidence, Clinical Use, and Future Directions, Curr Atheroscler Rep 14 (2012) 49–59. https://doi.org/10.1007/s11883-011-0212-1.
[3] V.S. Kamanna, S.H. Ganji, M.L. Kashyap, The mechanism and mitigation of niacin-induced flushing, International Journal of Clinical Practice 63 (2009) 1369–1377. https://doi.org/10.1111/j.1742-1241.2009.02099.x.
[4] J.M. McKenney, J.D. Proctor, S. Harris, V.M. Chinchili, A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients, JAMA 271 (1994) 672–677.
[5] Clofibrate and niacin in coronary heart disease, JAMA 231 (1975) 360–381.
[6] P.L. Canner, K.G. Berge, N.K. Wenger, J. Stamler, L. Friedman, R.J. Prineas, W. Friedewald, Fifteen year mortality in Coronary Drug Project patients: Long-term benefit with niacin, Journal of the American College of Cardiology 8 (1986) 1245–1255. https://doi.org/10.1016/S0735-1097(86)80293-5.
[7] J.M. Drood, P.J. Zimetbaum, W.H. Frishman, Nicotinic Acid for the Treatment of Hyperlipoproteinemia, The Journal of Clinical Pharma 31 (1991) 641–650. https://doi.org/10.1002/j.1552-4604.1991.tb03750.x.
[8] A.J. Taylor, L.E. Sullenberger, H.J. Lee, J.K. Lee, K.A. Grace, Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: A Double-Blind, Placebo-Controlled Study of Extended-Release Niacin on Atherosclerosis Progression in Secondary Prevention Patients Treated With Statins, Circulation 110 (2004) 3512–3517. https://doi.org/10.1161/01.CIR.0000148955.19792.8D.
[9] Z. Benyó, A. Gille, J. Kero, M. Csiky, M.C. Suchánková, R.M. Nüsing, A. Moers, K. Pfeffer, S. Offermanns, GPR109A (PUMA-G/HM74A) mediates nicotinic acid–induced flushing, J. Clin. Invest. 115 (2005) 3634–3640. https://doi.org/10.1172/JCI23626.
[10] R.H. Stern, J.D. Spence, D.J. Freeman, A. Parbtani, Tolerance to nicotinic acid flushing, Clin Pharmacol Ther 50 (1991) 66–70. https://doi.org/10.1038/clpt.1991.104.
[11] J.M. Backes, R.J. Padley, P.M. Moriarty, Important Considerations for Treatment with Dietary Supplement versus Prescription Niacin Products, Postgraduate Medicine 123 (2011) 70–83. https://doi.org/10.3810/pgm.2011.03.2265.
[12] R.B. Norris, “Flush‐Free Niacin”: Dietary Supplement May Be “Benefit‐Free,” Preventive Cardiology 9 (2006) 64–65. https://doi.org/10.1111/j.1520-037X.2006.04736.x.
[13] J. McKenney, New Perspectives on the Use of Niacin in the Treatment of Lipid Disorders, Arch Intern Med 164 (2004) 697. https://doi.org/10.1001/archinte.164.7.697.
[14] T.A. Jacobson, A “Hot” Topic in Dyslipidemia Management—“How to Beat a Flush”: Optimizing Niacin Tolerability to Promote Long-term Treatment Adherence and Coronary Disease Prevention, Mayo Clinic Proceedings 85 (2010) 365–379. https://doi.org/10.4065/mcp.2009.0535.
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