Dyslipidaemia

| Practice points|

• Omega-3 fatty acids dose-dependently reduce plasma triglyceride (TG) levels in those with elevated TGs, may increase high density lipoprotein-cholesterol (HDL-c) when TG level is high, reduce risk of cardiac death, coronary events and overall mortality in those at high risk for cardiovascular disease and are generally safe and well tolerated. Any side effects are mild (gastrointestinal discomfort, fi shy refl ux)• Plant sterols reduce total and low density lipoprotein-cholesterol (LDL-c) and can be used as an adjunct to cholesterol-lowering medication• Oat betaglucan reduces total and LDL-c, improves blood lipid profi le and may assist with regulation of postprandial insulin response• Coenzyme Q10 (CoQ10) is important for endothelial function, heart health and energy production. It may replenish plasma CoQ10 levels reduced by statin therapies

| Description |

• A major modifi able risk factor for the development of atherosclerosis and consequent cardiovascular diseases1; defi ned as elevation of total plasma cholesterol (TC), TGs, or both, or low HDL-c that contributes to the development of atherosclerosis.2• A rise in LDL-c directly infl uences the development of atherosclerosis, and LDL-c oxidation is an independent risk factor for cardiovascular disease1

• Low plasma HDL-c is a strong and independent risk factor for cardiovascular disease.3 Every 1mg/dL increase in HDL-c may lead to a reduction in the incidence of coronary heart disease by 2-3% independent of other factors1

• Potentially modifi able risk factors for cardiovascular disease include infl ammation, oxidation, high glucose and insulin resistance. The endothelial dysfunction that is promoted by dyslipidaemia and these other factors is a major contributor to atherosclerosis and the development of cardiovascular disease4,5,6,7,8

| Management principles |

Medical management includes the following goals:9• LDL-c <1.8 mmol/L• HDL-c > 1.0 mmol/L• TG <2.0 mmol/L• Education on the modifi able behavioural risk factors of diet and lifestyle

Complementary medicines

| Primary recommendations |

OMEGA-3 FATTY ACIDS: EPA AND DHA

Mechanism of action• Decrease hypertriglyceridaemia, alone or as adjunctive therapy16,17,18,19

• Attributed to activation of hepatic transcription factors resulting in increased β-oxidation of fatty acids and decreased activity of TG-synthesising enzymes resulting in a smaller fatty acid pool in the liver for very low density lipoprotein (VLDL) synthesis and

lower VLDL-TG secretion17

ResearchReviews of randomised controlled trials have found:• A dose-response relationship exists. The higher the baseline TG level, the greater the response. There appears to be no effect at doses below 2 g/d, with increasing effect at higher doses19,20

• Reductions of TG at optimal doses may be from 25–35% up to 45% in the presence of severely elevated TG levels19

OMEGA-3 FATTY ACIDS: EPA AND DHA

CARDIOVASCULAR

| CARDIOVASCULAR | 2

Dosage and formulationDosing should be based on EPA+DHA, not total fi sh oil.Optimal TG-lowering doses of EPA+DHA are3-4/g day.19 Adverse effectsUp to 3 g/d EPA+DHA is generally recognised as safe (GRAS).23

InteractionsClinical studies with surgical patients fi nd no clinically signifi cant bleeding risk when omega-3 supplements are taken with aspirin or warfarin33

Unlikely: Doses >3 g/d EPA+DHA may increase the risk of bleeding with warfarin, aspirin, antiplatelet drugs23

Benefi cial effect with statin medication22

Possible additive effect with antihypertensive drugs. Can be used together with monitoring23

PLANT STEROLS (phytosterols)

Mechanism of action• Reduce intestinal absorption of cholesterol by partly inhibiting cholesterol absorption in the gut24

Research• A meta-analysis of randomised controlled trials found decreases in TC and LDL-c concentrations24

• The Australian Heart Foundation concludes a daily intake of around 2 g/d may reduce LDL-c levels by approximately 10%25

Dosage and formulation2 g/d from dietary or supplemental formsNo benefi t from taking >3 g/d24,25,26

Adverse effectsNot recommended in pregnancy or breastfeeding.InteractionsPossible benefi cial effect with statin medication: may increase drug effect26

PLANT STEROLS (phytosterols)

| Secondary recommendations |

OAT BETA-GLUCAN (OBG)

Mechanism of action• Forms a viscous layer at the absorptive surface of the small intestine which decreases uptake of dietary cholesterol and reabsorption of bile acids31

• Slows gastric emptying and lowers the rate of glucose absorption27

• Behaves as a prebiotic, supporting growth of benefi cial intestinal microbial fl ora which may support cholesterol metabolism27,28,30

ResearchMeta-analysis of randomised controlled trials found29

• OBG may decrease LDL-c 0.25 mmol/L and TC 0.30 mmol/L• LDL-c lowering greater with higher baseline levels• Greater effect in subjects with diabetes• No signifi cant effect on HDL-c or TGs• No evidence that higher doses or duration of treatment (range: 2–12 wk) infl uenced results Dosage and formulation≥3 g/d29

Adverse effectsNo adverse effects expected at recommended dose.InteractionsMay increase the glucose-lowering effect of anti-diabetic medications.May have an additive effect with lipid-lowering medications which may be benefi cial.Oats contain gluten. The majority of adults and

children with coeliac disease can tolerate oats however some cannot. It is recommended that there is regular follow-up if a patient with coeliac disease chooses to consume oats.

COENZYME Q10 (CoQ10)

Mechanism of action• May improve endothelial function at high doses (300 mg) by increasing activity of antioxidant enzymes (glutathione peroxidase, catalase and superoxide dismutase)8,34

• Inhibits the oxidation of LDL-c34

ResearchSeveral reviews have found CoQ10 supplementation may help replenish plasma/serum Co Q10 levels reduced by statin therapies with a daily dose of ≥100 mg/day33,35,36

Dosage and formulation100-300 mg/day8,33

Adverse effectsWell tolerated – adverse effects reported in <1% of patients (dizziness, GI upset)InteractionsMay increase or decrease the anti-coagulant effect of warfarin. A clinical trial found no interaction but case reports exist of changes to INR. Monitor patients or avoid combination.23 HMG-CoA-reductase inhibitors decrease plasma CoQ10. Supplementation may be benefi cial.23

May have additive effects with antihypertensive drugs. Supplementation may be benefi cial.23

REFERENCES 1. De Oliveira Barbara Rosa, C et al. Impact of nutrients and food components on dyslipidemias: What is the evidence? Adv Nutr 2015; 6:703-11 2. Merck Manual professional version available at http://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/lipid-disorders/dyslipidemia. Viewed 8.3.16 3. Kontush A. HDL-mediated mechanisms of protection in cardiovascular disease. Cardiovas Res 2014;103:341-49 4. Australian Heart Foundation. Absolute cardiovascular disease risk management. Available at https://heartfoundation.org.au/images/uploads/publications/Absolute-CVD-Risk-Quick-Reference-Guide.pdf. Accessed 7.3.16 5. Boudi, FB. Risk factors for Coronary Artery Disease. Medscape. Available at http://emedicine.medscape.com/article/164163-overview. Accessed 22.2.16 6. Lenna S, Han R, Trojanowska M. ER stress and endothelial dysfunction. IUBMB life. 2014;66(8):530-537. Doi:10.1002/iub.1292 7. Dessi, M et al. Atherosclerosis, dyslipidemia, and infl ammation: the signifi cant role of polyunsaturated fatty acids. HIndawi Publishing Corporation 2013. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767348/pdf/ISRN.INFLAMMATION2013-191823.pdf. Accessed 22.2.16 8. Bor-Jen Lee, Yu-Fen Tseng, Chi-Hua yen and Ping-Ting Lin. Effects of coenzyme Q10 supplementation (300mg/day) on antioxidation and anti-infl ammation in coronary artery disease patients during statins therapy: a randomised, placebo-controlled trial. Nutrition Journal 2013;12:142-150 9. National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand. Reducing risk in heart disease: an expert guide to clinical practice for secondary prevention of coronary heart disease. Updated 2012. Available from http://heartfoundation.org.au/images/uploads/publications/Reducing-risk-in-heart-disease.pdf 10. Cramer, H et al. Effects of yoga on cardiovascular disease risk factors: a systematic review and meta-analysis. Int J Cardio 2014; 173(2): 170-83 11. Sarvottam K, Yadav RK. Obesity-related infl ammation and cardiovascular disease: Effi cacy of a yoga-based lifestyle intervention. The Indian Journal of Medical Research. 2014; 139(6):822-834 12. Australian Heart Foundation website. Blood cholesterol. Available at http://heartfoundation.org.au/your-heart/know-your-risks/blood-cholesterol. Accessed 22.2.16 13. Mente, A et al. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med 2009; 169(7):659-669 14. Catapano, AL et al. ESC/EAS guidelines for the management of dyslipidaemias. The task force for the management of dyslipidaemias of the European society of cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 2011; 217S: S1-S44 15. Chiva-Blanch, G et al. Latest evidence of the effects of the Mediterranean Diet in prevention of cardiovascular disease. Curr Atheroscler Rep 2014; 16:446 16. Skulas-Ray AC, Kris-Etherton PM, Harris WS, Vanden Heuval J, Wagner P, West SG. Dose-response effects of omega-3fatty acids on triglycerides, infl ammation, and endothelial function in healthy persons with moderate hypertriglyceridaemia. Am J Clin Nutr 2011;93(2):243-52 17. Egert S, Kannenberg F, Somoza V, Erbersdobler H, Wahrburg U. Dietary �-Linolenic Acid, EPA, and DHA have Differential Effects on LDL Fatty Acid Composition but Similar Effects on Serum Lipid Profi les in Normolipidaemic Humans. J Nutr 2009;139:861-8 18. Hill AM, Buckley JD, Murphy KJ, Howe PRC. Combining fi sh-oil supplements with regular aerobic exercise improves body composition and cardiovascular disease risk factors. Am J Clin Nutr 2007;85:1267-74 19. Pirillo A, Catapano A. Omega-3 polyunsaturated fatty acids in the treatment of hypertriglyceridaemia. Int J Cardiol 2013;170:S16-S20 20. Nestel, P et al. Indications for Omega-3 Long Chain Polyunsaturated Fatty Acid in the Prevention and Treatment of Cardiovascular Disease. Heart, Lung and Circulation 2015; 24:769–77921. Balk, EM et al. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: A systematic review. Atherosclerosis 2006; 189:19-30Atherosclerosis 189 (2006) 19–30 22. Minihane A. Fish oil omega-3 fatty acids and cardio-metabolic health, alone or with statins. European Journal of Clinical Nutrition 2013; 67:537-40 23. Blackmores Institute 2015. Complementary Medicines Interactions Guide 7th ed. 24. Ras, RT et al. Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations – A meta-analysis of randomised controlled studies. Atherosclerosis 2013; 230:336-346 25. Australian Heart Foundation. Summary of Evidence on phytosterols/stanol enriched foods. www.heartfoundation.org.au January 2007 26. Simons LA. Additive effect of plant sterol-ester margarine and cerivastatin in lowering low-density lipoprotein cholesterol in primary hypercholesterolaemia. Am J Cardio. 2002; 90:737-40 27. Daou, C and Zhang, H. Oat Beta-Glucan: Its Role in Health Promotion and Prevention of Diseases. Comprehensive Reviews in Food Science and Food Safety 2012; 11:355-365 28. El Khoury, D et al. Beta Glucan: Health Benefi ts in Obesity and Metabolic Syndrome. J Nur Metab. 2012;doi: 10.1155/2012/851362 29. Whitehead A, Beck E, Tosh S, and Wolever T, Cholesterol-lowering effects of oat �-glucan: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2014;100:1413–21 30. European Food Safety Authority (EFSA), Scientifi c Opinion on the substantiation of a health claim related to oat beta-glucan and lowering blood cholesterol and reduced risk of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/20061, EFSA Journal 2010;8(12):1885 31. Othman RA, Moghadasian MH. Cholesterol-lowering effects of oat �-glucan. Nutr Rev 2011;69(6):299–309 32. Desbats, MA et al. Genetic bases and clinical manifestations of coenzyme Q10 (CoQ10) defi ciency. J inherit Metab Dis 2015; 38:145-156 33. Braun L, Cohen M. Herbs & Natural Supplements. 4th edition. Chatswood: Elsevier, 2015 34. Belardinelli R, Tiano L, Littaru GP. Oxidative stress, endothelial function and coenzyme Q10. BioFactors 2008;32:129-33 35. Littlefi eld, N and Luthy, KE. Statins’ effect on plasma levels of Coenzyme Q10 and improvement in myopathy with supplementation. Journal of the American Association of Nurse Practitioners 2014; 26:85-90 36.Langsjoen PH and Langsjoen AM. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzym Q10. A review of animal and human publications. BioFactors 2003; 18:101-111

| Diet and lifestyle recommendations |

Exercise: At least 30 minutes of moderate-intensity physical activity on most, if not all, days of the week.9 Regular yoga practice may also be benefi cial10,11

Establish and maintain healthy weight:9 Chronic adiposity is associated with metabolic imbalance leading to dyslipidaemia, diabetes, hypertension and cardiovascular diseases11

Quit smoking: High TGs may result from tobacco smoking12

Dietary management:9• Limit trans unsaturated fatty acid (tFa) intake to <1% of total energy intake9 (trans fats are produced in the partial hydrogenation of vegetable oils, and can also be found in limited amounts in dairy products and some meats)13

• Limit salt intake to ≤ 4g day9

• Limit alcohol intake to no more than 2 standard drinks per day9

• Daily consumption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)9• 2-3 g of plant sterols per day9

• Dietary fi bre, as in legumes, fruit, vegetables and wholemeal cereals14

The Mediterranean Diet may reduce cardiovascular events via reducing blood pressure; improving glucose metabolism, lipid profi le, and lipoprotein particle characteristics; and decreasing infl ammation and oxidative stress.15 Include high intake of extra virgin olive oil, nut, fruits, vegetables, legumes, and whole grain cereals; a moderate intake of fi sh, poultry, dairy and wine (always with meals); and a low intake of red meat, sweets and industrial bakery products13,15

Contact education@blackmoresinstitute.org Healthcare Professional Advisory Service 1800 151 493 Website blackmoresinstitute.org