6 replies to this topic

[Adam Karlovsky]

Whether niacin has the ability to reduce the risk of cardiovascular disease has been controversial up until now. Does this new meta-analysis sway anybody towards the use of niacin for longevity purposes?

 

How can you bump up low HDL levels and reduce your CVD risk?

A meta-analysis of 39 RCTs (N=117,411 patients) reviewed the cardiovascular outcomes (all-cause mortality, coronary heart disease mortality, nonfatal
MI, and stroke) of niacin (11 studies), fibrates (20 studies), and CETP inhibitors (8 studies), medications all known to increase HDL.

For the primary outcome of all-cause mortality compared with control groups, no significant effect was observed for either niacin, fibrates, or CETP inhibitors. Of the latter one, namely torcetrapib, even increased the morality risk.

A sign. reduction in nonfatal MIs was noted with niacin (7 trials, n=4,991; OR 0.69; 95% CI, 0.56–0.85) and fibrates (19 trials, n=46,043; OR 0.78; 95% CI, 0.71–0.86). Compared to patients on statins or fibrates, niacin reduced the risk still by 4% and 17%, respectively.

For the primary endpoint of cardiovascular death, neither niacin nor CETP inhibitors reduced cardiovascular mortality compared with the control
group. What it did do, however was to reduce the occurance of nonfatal MI
with niacin by 13% and that of coronary revascularization by 18%.

Unfortunately, new-onset diabetes was diagnosed more in the active arms (niacin or CEPT inhibitors) than in the control arms (6 trials, n=46,409; OR 1.2; 95% CI,
1.1–1.3) as well as niacin trials alone (5 trials, N not provided; OR 1.32; 95% CI, 1.2–1.5).

To my surprise, exercise and diet did not have consistent beneficial effects on HDL (exercise: 6 trials, n=387; effect size [ES] 1.0; 95% CI, –0.2 to 2.1; diet: 6 trials, n=402; ES –1.0; 95% CI, –2.1 to 0.2; diet and exercise: 6 trials, n=389, ES –0.8; 95% CI, –1.9 to 0.4).

 

https://www.facebook...24822924216523/

 

www.suppversity.com |

Haver, Amy, et al. "What interventions improve outcomes for patients with isolated low levels of high-density lipoprotein cholesterol (HDL-C)?." Evidence Based Practice 18 (): (2015). 

Edited by Adam Karlovsky, 20 February 2016 - 01:25 AM.

[docmaas]

Might the new onset diabetes be due mostly to the fact that the treatment groups were already less healthy than the control groups?  Fasting blood glucose or a1c numbers might elucidate.

[Junk Master]

I just love this part--

 

"To my surprise, exercise and diet did not have consistent beneficial effects on HDL (exercise: 6 trials, n=387; effect size [ES] 1.0; 95% CI, –0.2 to 2.1; diet: 6 trials, n=402; ES –1.0; 95% CI, –2.1 to 0.2; diet and exercise: 6 trials, n=389, ES –0.8; 95% CI, –1.9 to 0.4)."

 

[Darryl]

I would question the assumption in the Suppversity article that elevating HDL, per se, is protective. Someone at Suppversity should look at the trials of HDL raising drugs and more importantly, Mendelian randomization studies of HDL raising genes. HDL appears to be a coincident marker of good habits that benefit cardiovascular health by other means, but isn't causal.

 

On the other hand, niacin does elevate intracellular NAD+ with likely effects via sirtuins, and reduce endothelial inflammation. Of the measurable blood markers, niacin reduces LDL, Lp(a), and triglycerides, which appear to be causal in the genetic studies.

 

 

[Darryl]

Sources for the above:

 

Mendelian randomization questions a protective role for HDL in CVD:

 

Frikke-Schmidt R. et al. 2008. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. Jama,299(21), pp.2524-2532.

Haase CL et al. 2011. LCAT, HDL cholesterol and ischemic cardiovascular disease: a Mendelian randomization study of HDL cholesterol in 54,500 individuals. The Journal of Clinical Endocrinology & Metabolism, 97(2), pp.E248-E256.

Voight BF et al 2012. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. The Lancet, 380(9841), pp.572-580.

Holmes MV et al. 2014. Mendelian randomization of blood lipids for coronary heart disease. European heart journal, p.eht571.

 

Lipid independent effects of niacin relevant to CVD:

 

Knowles HJ et al. 2006. Niacin induces PPARγ expression and transcriptional activation in macrophages via HM74 and HM74a-mediated induction of prostaglandin synthesis pathways. Biochemical pharmacology, 71(5), pp.646-656.

Westphal S. and Luley C. 2008. Preferential increase in high-molecular weight adiponectin after niacin. Atherosclerosis, 198(1), pp.179-183.

Ganji SH et al. 2009. Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells. Atherosclerosis,202(1), pp.68-75.

Lee JM et al. 2009. Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: a randomized, placebo-controlled, magnetic resonance imaging study. Journal of the American College of Cardiology, 54(19), pp.1787-1794.

Plaisance EP et al. 2009. Niacin stimulates adiponectin secretion through the GPR109A receptor. American Journal of Physiology-Endocrinology and Metabolism, 296(3), pp.E549-E558.

Tavintharan S et al. 2009. Effects of niacin on cell adhesion and early atherogenesis: biochemical and functional findings in endothelial cells. Basic & clinical pharmacology & toxicology, 104(3), pp.206-210.

Digby JE. 2010. Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin. Atherosclerosis, 209(1), pp.89-95.

Hamilton SJ et al 2010. Niacin improves small artery vasodilatory function and compliance in statin-treated type 2 diabetic patients. Diabetes and Vascular Disease Research.

Wu BJ et al. 2010. Evidence that niacin inhibits acute vascular inflammation and improves endothelial dysfunction independent of changes in plasma lipids.Arteriosclerosis, thrombosis, and vascular biology, 30(5), pp.968-975.

Holzhäuser E et al. 2011. Nicotinic acid has anti-atherogenic and anti-inflammatory properties on advanced atherosclerotic lesions independent of its lipid-modifying capabilities. Journal of cardiovascular pharmacology, 57(4), pp.447-454.

Lukasova M et al. 2011. Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells. The Journal of clinical investigation, 121(3), pp.1163-1173.

Digby JE et al. 2012. Anti-inflammatory effects of nicotinic acid in human monocytes are mediated by GPR109A dependent mechanisms. Arteriosclerosis, thrombosis, and vascular biology, 32(3), pp.669-676.

Wu BJ et al. 2012. Niacin inhibits vascular inflammation via the induction of heme oxygenase-1. Circulation,125(1), pp.150-158.

Lipszyca PS et al. 2013. Niacin modulates pro-inflammatory cytokine secretion. a potential mechanism involved in its anti-atherosclerotic effect. Open Cardiovascular Medicine Journal, 7, pp.90-98.

Wanders D et al. 2013. Niacin increases adiponectin and decreases adipose tissue inflammation in high fat diet-fed mice. PLoS One, 8(8), p.e71285.

Hughes-Large JM et al. 2014. Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity.Atherosclerosis, 237(2), pp.696-704.

Kopp C et al. 2014. Nicotinic acid increases adiponectin secretion from differentiated bovine preadipocytes through G-protein coupled receptor signaling. International journal of molecular sciences, 15(11), pp.21401-21418.

Sahebkar A 2014. Effect of niacin on endothelial function: A systematic review and meta-analysis of randomized controlled trials. Vascular Medicine, 19(1), pp.54-66.

Si Y et al. 2014. Niacin inhibits vascular inflammation via downregulating nuclear transcription factor-κB signaling pathway. Mediators of inflammation, 2014.

Li Y et al. 2015. Nicotinic acid inhibits vascular inflammation via the SIRT1-dependent signaling pathway. The Journal of nutritional biochemistry, 26(11), pp.1338-1347.

 

I'll add here that many of these effects might be expected to inhibit a number of chronic diseases, so the lack of reporting on secondary effects in the niacin trials is disappointing, but perhaps to be expected given their their funding ("Just until we achieve significance in our primary endpoint").

 

The moderate increase in diabetes incidence was expected. Serious longevity practitioners (the ones practicing intermittent fasting or CR, maybe protein restriction, targeting 20-22 BMIs and < 70 LDL) should be at pretty low risk of either CVD or metabolic syndrome/diabetes.

 

 

Edited by Darryl, 10 February 2016 - 07:04 PM.

[niner]

I can't help but think that the disappointing outcomes on broad health metrics with niacin are related to its known effects on glycemic control.  Glycation is not your friend.  Maybe if it was combined with metformin it would be a winner.

[aribadabar]

I can't help but think that the disappointing outcomes on broad health metrics with niacin are related to its known effects on glycemic control.  Glycation is not your friend.  Maybe if it was combined with metformin it would be a winner.

 

Great point! How about taking niacin for its cholesterol-lowering properties and NAD+ boosting effect while mitigating the glycation downside with carnosine/beta-alanine?

Isn't this a "safer" approach than adding metformin?