Supplements, Vitamin D, Omega-3 Fatty Acids, and Co-Enzyme Q10: What Really Works?

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1 Supplements, Vitamin D, Omega-3 Fatty Acids, and Co-Enzyme Q10: What Really Works? DAVID P. GOWMAN, D.O. S E C T I O N CHIEF, CARDIOLOGY P R O G R A M D I R E C T O R, CARDIOLOGY F E L L O W S H I P B O T S F O R D HOSPITAL F A R M I N G T ON H I L L S, M I

2 Objectives To address some of the most common supplements that patients are likely to ask about Describe the theory and mechanism of action Summarize most recent trials Provided current recommendations by the governing colleges (ACC/AHA)

3 Disclosures I have no disclosures pertinent to this presentation

4 Supplements - Niacin Niacin (Vitamin B3) Found naturally in plant and animal products Is a precursor in the formation of NAD & NADP Lowers LDL and Triglyceride Raises HDL Insufficient niacin in the diet can cause nausea, skin and mouth lesions, anemia, headaches, and tiredness (Pellagra)

5 Niacin Heart Protection Study 2- Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2- THRIVE). The latest and largest trial, NEJM July 7 th, ,673 adults aged yrs Baseline statin therapy was standardized Extended release niacin with laropiprant (to prevent flushing) was evaluated After 4 yrs, there was HDL, LDL and Trig; However No significant reduction in major vascular event (HR 0.96; CI )

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7 Niacin In light of negative outcome, more importantly were the adverse events GI, muskulo-skeletal, skin, infectious, bleeding, worsened glycemic control in diabetics 9% increase in the risk of death associated with niacin-laropiprant. Number needed to harm = 200, P=0.08 Niacin should not be used routinely, as recommended by the latest ACC/AHA lipid guideline

8 Antioxidant Vitamins Thought to be potentially useful in preventing atherosclerosis by retarding LDL oxidation and improving endothelial function, among other things Vitamin E studied in several primary and secondary prevention trials has not shown any significant CV benefit Not recommended Vitamin C, no specific RCT have been completed but review of cohort studies do not suggest CV benefit with routine use. Not recommended

9 Vitamin D Epidemiology study of 1,739 Framingham Offspring participants noted a significant CV risk was associated with decreased levels of 25-OH Vit D. Especially <15ng/mL. The risk was only noted in those with concomitant HTN. Vitamin D receptors have a broad tissue distribution that includes vascular smooth muscle, endothelium, and cardiac myocytes Vit D has a role in suppression of RAS. This was proved in knock-out mice without Vit D led to upregualtion of RAS with resultant HTN and LVH.

10

11 Associated CV Risk Hazard Ratio

12 Vitamin D In 2011 a meta-analysis was performed regarding therapy with Vit D and CV outcomes. Pooling across studies showed that the effects of vitamin D were non-significant on endpoints of death (RR, 0.96; CI ; P =.08), myocardial infarction (RR, 1.02; CI ; P =.64), and stroke (RR, 1.05; 95% CI, ; P =.59 Trial data available to date are unable to demonstrate a statistically significant reduction in mortality and cardiovascular risk associated with vitamin D The authors state, The quality of the available evidence is low to moderate at best

13 Vitamin D Currently no role for routine screening of 25-OH Vit D for CV risk Maybe be a role for general health or mineral bone health No recommendation for routine supplementation, but may be beneficial for those deficient in Vit D with HTN.

14 Can Vitamin D deficiency lead to T2DM? Low levels of vitamin D have been shown to be associated with increased risk of diabetes, but causality was not established Published last year, researchers conducted a mendelian randomization analysis of nucleotide polymorphisms found within genes related to 25-(OH)D, a marker associated with vitamin D status, synthesis and metabolism in nearly 100,000 participants. This was compared to a meta-analysis review of Vit D & T2DM They found no causal connection between vitamin D levels and the risk of developing type 2 diabetes

15 Omega 3 Fatty Acids (n-3 FA) Originally observed in 1960 s by Bang & Dyerberg noting very low incidence of MI in Inuit population, they hypothesized marine n-3 fatty acids might provide protection against atherosclerosis

16 Selected Omega 3 Trials GISSI Prevention Trial (2003) randomly assigned 11,324 survivors of recent MI to receive 1g of n-3 FA, Vitamin E or both ( no placebo) Vitamin E provided no additional benefit Study was limited by an open label design and >25% dropout rate

17

18 Selected Omega 3 Trials JELIS (2007 Japanese study) was study of 18,645 pts with hypercholesterolemia (>250 TC) to prevent major coronary disease All pts were on baseline statin and then randomly assigned 1:1 to receive 1800mg EPA After mean follow-up of 4.6 yrs a 19% relative risk reduction was noted Significant reduction in stroke noted LDL levels were not significantly different

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20 What about n-3 FA in HFrEF GISSI-HF was a randomized, double blind, placebo controlled trial to evaluate effect of fish oil on those with chronic HF and NHYA class II, III, or IV 1g of n-3 FA used Followed for 3.9 years

21 So, NNT = 44 pts for 3.9 yrs to avoid death or CV related hospitalization

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23 N-3 FA Recommendations AHA recommends all adults to consume fatty fish twice per week Herring, sardines, mackerel, salmon, halibut AHA also recommends those with CHD consume 1g EPA/DHA daily, either through diet or fish oil capsules Pts with trigs >500mg are recommended to take 2-4g EPA/DHA

24 Coenzyme Q 10 In mitochondrial function, coenzyme Q 10 has a unique function in oxidative phosphorylation and the generation of adenosine triphosphate The myocardial and skeletal muscle cells of patients with heart failure (HF) are in an energy-starved state; hence any increase in the ability to augment energy production or enhance efficient utilization is certain to have positive functional effects.

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26 This trial did suffer from recruitment issues, taking 9 years to complete, and should be taken into effect. Ideally prefer larger trial.

27 Coenzyme Q 10 There are NO recommendations for coenzyme Q10 Trial dosages cost between $50-100/month How about in statin induced-myopathy? Data on the effect of CoQ10 supplementation on myopathic symptoms are scarce and contradictory The routine use of CoQ10 is not recommended in statintreated patients No significant risk to supplementation as there is anecdotal evidence

28 References Heart Protection Study 2- Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE). NEJM 371;3 July 17,2014. ACCF Complementary Medicine Expert Consensus Document. JACC vol 46, No 1. July 5 th, 2005 Thomas Wang, et al. Vitamin D Deficiency and Risk of Cardiovascular Disease. Circulation January 29, Mohamed B. Elamin. Vitamin D and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. J Clin Endocrinol Metab. 2011;96: Raffaele Caterina. N-3 Fatty Acids in Cardiovascular Disease. NEJM 364; 25 June 23, Svend A. Mortensen, MD, DSc; et.al. The Effect of Coenzyme Q 10 on Morbidity and Mortality in Chronic Heart Failure (Q-SYMBIO). JCHF. 2014;2(6): ; and accompanying editorial. John Lee, MD; Et. Al. From: Vitamin D Deficiency: An Important, Common, and Easily Treatable Cardiovascular Risk Factor?. JACC. 2008;52(24): Condezo-Hoyos L, Mohanty IP, Noratto GD. Association between circulating 25- hydroxyvitamin D and incident type 2 diabetes: a mendelian randomization study. Lancet Diabetes Endocrinol October: /S (14)

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