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Integrative Medicine and Hyperlipidemia

Dr. Ather Ali, ND, MPH, MHS (c)Associate Research Scientist, Department of PediatricsIntegrative Medicine Specialist, Yale Stress CenterDirector, Integrative Medicine at Yale

Atatürk ÜniversitesiMay 2014

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Why do we care about hyperlipidemia?

Lancet. 2005 Jan 29-Feb 4;365(9457):434-41.

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Relative risks…

• A 23 mg/dL (0·6 mmol/L ) difference in TC corresponds to about a 27% relative difference in CHD risk

• Positive relationship between TC and ischemic stroke – Hemorrhagic stroke – not as clear

• Stronger relationship in younger persons

Lancet. 2005 Jan 29-Feb 4;365(9457):434-41.

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Not just LDL

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Relative vs. Absolute risk

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Be realistic

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Why do patients choose integrative care?

• Broader focus on disease prevention and overall health• Considerations of self-empowerment, being ‘natural’

Katz DL, Ali A. Prevention, health of the public and integrative medicine. Commissioned for the Summit on Integrative Medicine and the Health of the Public.  Institute of Medicine of the National Academies. February 2009.

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Conventional Treatment

• Lifestyle modification– Weight loss, aerobic exercise, increase PUFA/MUFA, reduce

saturated and trans fats• Pharmacotherapy – statins being the most prevalent

choice– 26 % reduction in overall mortality– Not fully explained by reduction of LDL only– Beneficial in primary prevention as well

• May be attributed to plaque stabilization; reversal of endothelial dysfunction; inhibition of monocyte recruitment; decreased thrombogenicity; and a reduction in inflammation after MI

• Niacin / fibrates / bile acid sequestrants / absorption inhibitors

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An integrative medicine approach

• Holistic approach– “Treat the person, not labs…”– Therapeutic approach focused on reducing CVD risk

• Emphasis on healthy lifestyle• “Less invasive” therapies are desired

– Subjective definitions– Where does EDTA chelation fit here?

• Other risk factors– Inflammation (CRP)– Stress / Emotional health– Sleep

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Integrative Medicine: Fundamentals

• Prevention / Risk Reduction– Lifestyle interventions

• Mind-body aspects• “Less-invasive” pharmacologic interventions

– Natural products– Dietary supplements

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‘Healthy Living is the best revenge’

• 23,153 German participants aged 35 to 65 followed for ~ 8yr

• 4 factors– never smoking– BMI < 30 – 3.5 hr/wk + of physical activity, – Healthy diet (high fruits, vegetables, and whole-grains;

low meat).

• All 4 factors - 78% lower risk of of all chronic disease– type 2 diabetes, 93%– myocardial infarction, 81%– stroke, 50%– cancer, 36%

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Emotional Health

• Chronic stress and depression are associated with type 2 diabetes, CVD, and stroke

• The “disease prone personality” includes anger, hostility, anxiety, and depression – Associated with CVD, asthma, peptic ulcer, arthritis

• Higher levels of anger are associated with worse cardiac outcomes– 2- to 3-fold increase in angina, acute MI, or sudden cardiac

risk– Dose-response relationship

• Survival / optimism

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Healthy personalities…

• Intimate relationships, close friendships, and sense of community all predict more favorable health outcomes– Those with a sense of belonging and intimacy have more

pronounced recovery from MI, surgery, and cancer (Ornish 1998).

• Difficult to “fix”– Perhaps increased motivation to do so.

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Dietary Aspects

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Anti-inflammatory diet: rationale

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Anti-Inflammatory Diet: Emphasize

• Omega-3 fatty acids– salmon, sardines, walnuts, freshly ground flax

seeds or oil and soy foods. • Whole grains

– low glycemic load/high whole grains may have a protective effect against systemic inflammation in diabetic patients

– glycemic load significantly associated with hs-CRP in healthy middle-aged women,

independent of conventional CVD risk factors• Brightly colored fruits and vegetables

– Berries, onions, apples– Contain antioxidant phytochemicals with anti-

inflammatory properties. • Monounsaturated fatty acids (omega-9 or oleic acid)

– Improve cholesterol levels when replacing saturated fats

– Olive oil, avocado, almonds, cashews

Curr Opin Lipidol. 2007 Feb;18(1):3-8Am J Clin Nutr. 2002 Mar;75(3):492-8.

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Utility in Rheumatoid Arthritis

• 68 patients with RA were randomized to western diet vs. anti-inflammatory diet x 3 mo +/- fish oil (crossover)

• With diet - – # of tender and swollen joints

decreased by 14% (+ placebo)And with the addition of fish oil:– significant reduction in the

numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P<0.01).

– higher enrichment of EPA in erythrocyte lipids

– lower formation of LTB4, TXB2 and prostaglandin metabolites

Rheumatol Int. 2003 Jan;23(1):27-36.

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Portfolio diet

• 46 adults randomly assigned to 1 month of: – CONTROL DIET: Low saturated fat diet, based on whole

grains and lowfat dairy (n=16; control)– CONTROL plus lovastatin, 20 mg/d (n=14) – PORTFOLIO: a diet high in plant sterols (1.0 g/1000 kcal),

soy protein (21.4 g/1000 kcal), soluble fiber (9.8 g/1000 kcal), and almonds (14 g/1000 kcal) (n = 16)

JAMA 2003;290:502-510.

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Plant Sterols/Stanols

• Plant sterols and stanols reduce LDL– Consuming 1.7 g/d can reduce CVD risk more than reducing

saturated fat

N Engl J Med 1995;333:1308BMJ 2000;320:861–4.

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Other ‘functional foods’

• Soy foods – tofu, tempeh, and miso can reduce LDL– 20 g daily

• EtOH (1-2 glasses/d) increases HDL• Flaxseed – source of soluble fiber

– Reports of reduced LDL and TC– High doses – 30-50g/d

• Flax oil may not work as well

N Engl J Med 1995;3333:276–82.J Am Coll Nutr 1993;12:501–4.Br J Nutr 1993;69:443–53.

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Cocoa and Dark Chocolate

Am J Clin Nutr. 2008 Jul;88(1):58-63.

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Antioxidants - Rationale

Role of oxidized LDL in atherosclerosis• Endothelial damage• Alteration in vascular tone• Monocyte/macrophage

recruitment• Increased uptake of LDL by

macrophages, with foam cell formation

• Induction of growth factors• Increased platelet aggregation• Formation of autoantibodies to

oxidized LDL

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Vitamin E and other antioxidants

• Vitamin E– Popular in 1990s antioxidant craze– Most recent studies are negative, possibly harmful

• Vitamin C– Some evidence to reduce LDL and TC– 100mg usually sufficient, though many usually supplement

1g or greater

• Green Tea– Promising on LDL/HDL, though results mixed

• In general, we recommend antioxidant containing foods over antioxidant supplements

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Popular Natural Products

• Chromium– Mixed results in total cholesterol, HDL, LDL. – Component of ‘glucose tolerance factor’– Marketed as ergogenic aid– Our trial showed no benefit; recent trail showed no benefit

• Garlic – Early trials compelling; recent results are weak

• Guggul– Mixed results – American vs. Indian populations?

• Policosanol (sugar cane derived)– Dose for dose equivalence to statins on TC, LDL, HDL in

multiple Cuban studies– U.S., Canadian, and German studies failed to replicate

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Red Yeast Rice

• Used in TCM for at least 1200 years to “invigorate the body, aid in digestion, and revitalize the blood” – Used as a red food coloring

• Active ingredient is 0.2% monocolin K = lovastatin• Can reduce cardiac events (used 0.8% monocolin K)• 4870 patients followed 4.5 years after MI

Am J Cardiol 2008;101:1689

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Coenzyme Q10

• Found in inner mitochondrial membrane– Involved in ATP production– “ubiquinone” – electron transport chain

• 100 mg/day has been shown to reduce pain levels of patients on statins

• Antihypertensive effects

Am J Cardiol 2007;99:1409

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“TLC”+ supplements

• 74 hypercholesterolemic adults randomized• Baseline LDL = 154-157 mg/dL• 40 mg simvastatin vs [High dose fish oil (~800 mg w3; 2

caps tid) + 2.4-3.6 g g red yeast rice + 3.5 hr/week education on diet, exercise, stress reduction]

Mayo Clin Proc. July 2008;83(7):758-764

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Integrative Medicine Recommendations

• Focus on CVD risk reduction rather than lipid panel optimization

• Lifestyle first – Mediterranean/anti-inflammatory diet, exercise, sleep, emotional health

• Functional foods• CoQ10 if taking statin• Fish oil / Omega-3 fatty acids• Consider Red Yeast Rice as equivalent to statin

– Useful for those insistent on ‘natural’ therapies– Need to monitor LFTs and myalgias

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Resources

• Yeh GY, Davis RB, Phillips RS. Use of complementary therapies in patients with cardiovascular disease.Am J Cardiol. 2006 Sep 1;98(5):673-80.

• Becker DJ, Gordon RY, Morris PB, Yorko J, Gordon YJ, Li M, Iqbal N. Simvastatin vs therapeutic lifestyle changes and supplements: randomized primary prevention trial.Mayo Clin Proc. 2008 Jul;83(7):758-64.

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This work was supported by a grant from

National Center for Complementary and Alternative MedicineNational Institutes of HealthU.S. Department of Health and Human Serviceswww.nccam.nih.gov