Doctors call for caution; Omega-3s may offer comparable cardiac help
by Craig Weatherby
If you ever watch television, or read any news periodical other than Modern Goat Farming, you’ve seen the ubiquitous ads for the cholesterol-lowering drugs known generically as statins (e.g., Lipitor, Zocor, Mevacor, and Pravachol).
Statins rank among the top-selling drugs in the world, with sales of about $14 billion in 2003, and combined 2004 advertising expenditures of $417 million. Nor is the enthusiasm for statins limited to advertising outlets and pharmaceutical stock holders. Reportedly, many cardiologists joke that statins should be added to the water supply.
It’s clear that statins offer real benefits, at least to certain people. But a more balanced view is in order, especially in light of efforts to sell them without a prescription.
Statins: benefits versus hype and potential
Statin-type drugs can lower "bad" (LDL and VLDL) cholesterol and reduce the risk of heart attack and death among people diagnosed with heart disease.
Statins work by blocking an enzyme that the liver uses to produce cholesterol, thereby lowering both total cholesterol and LDL or “bad” cholesterol. Statins also appear to reduce blood clots and inflammation of blood vessel walls. Among people with a history of heart disease, they help prevent heart attacks and reduce the risk of death from heart disease.
Large studies such as the CARE [Cholesterol And Recurrent Events] trial, show that statins deliver relatively modest benefits. After five years of the study, 5.7 percent of participants had died from heart disease in the untreated control group, compared to 4.6 percent in the statin-treated group.
Moreover, the modest reductions in cardiac deaths and adverse events shown in most trials were neither dose-related nor fully accounted for by improvements in cholesterol levels. Instead, these benefits may stem more from statins’ substantial anti-inflammatory effects.
Although most cardiologists remain bullish on statins, some are skeptical about how widely their benefits apply. While statins have been shown to extend life among middle-aged men with a history of heart disease, the evidence of benefit for women and seniors is weaker.
More to the point, while statins are great at reducing cholesterol levels, in most cases their impacts on cardiac health can be matched—even exceeded—by adopting a cholesterol-lowering, anti-inflammatory diet.
Drug companies have petitioned the FDA for approval to sell statins without a prescription, as so-called OTC (over the counter) drugs. (These are the same folks who objected strenuously to OTC sale of red rice yeast dietary supplements rich in natural statins!)
However, some doctors fear that people will take OTC statins whether or not they would be indicated in their particular circumstances. And although the most frequent statin side effects—nausea, diarrhea, constipation, muscle aches—are relatively uncommon and fairly benign, others, including elevated liver enzymes, nerve damage, and myopathy (muscle breakdown) can even be fatal (About 50 people taking Bayer’s Baycol brand statin died before it was pulled from distribution).
Dosage is also a key issue in the OTC-statins debate. According to Jay Cohen, M.D., Associate Professor at the University of California, San Diego, “The lowest available dose of Lipitor, the best-selling statin in America, is far stronger than millions of patients require to achieve their target LDL-C [“bad” cholesterol level].”
When drug companies asked the FDA to approve OTC statins, their filings revealed the effectiveness of very low doses in lowering LDL cholesterol levels for many patients. Yet, as a 2001 review article noted, “Overuse of statin therapy was found among 69% of patients undergoing primary prevention, and among 47% of patients undergoing secondary prevention.”
Statins and Co-Q10
Statins reduce blood levels of C0-Q10, which is an important internally produced antioxidant, high levels of which are closely associated with better cardiac health. As one representative study found, “Even brief exposure to atorvastatin causes a marked decrease in blood CoQ(10) concentration. Widespread inhibition of CoQ(10) synthesis could explain the most commonly reported adverse effects of statins, especially exercise intolerance, myalgia, and myoglobinuria.”
Omega-3s and cardiac prevention
As we’ve seen, the preventive powers of statins against adverse cardiac events and deaths stem as much or more from their anti-inflammatory effects as from their cholesterol-lowering effects.
Given that key fact, and the known adverse effects of statins, it seems reasonable that physicians should recommend lifestyle changes before prescribing drugs. The preponderance of evidence indicates that cardiovascular disease is, in essence, an inflammatory disorder affecting the arteries.
Thus, the first preventive steps cardiac patients take should include adoption of an anti-inflammatory diet: that is, a diet low in sugars, refined starches, and saturated or hydrogenated fats, and high in fish and colorful (hence, antioxidant-rich) vegetables and fruits.
To quote Barry Sears, Ph.D., author of the bestselling “Zone” diet books, “If you want to reduce heart disease, then your best bet is reducing silent inflammation, and the most cost-effective way to do that is to take a lot of fish oil. The only side effect of fish oil is that it makes you smarter.”
While we lack the number and size of studies on omega-3s that exist for statins, the research we do have shows that marine-source omega-3s exert beneficial effects on several key cardiac risk factors—including arterial flexibility and the stickiness of blood platelets. Research also shows that omega-3s reduce the risk of arrhythmia and strokes, and may help preventing other serious cardiac events.
These are the conclusion drawn by the authors of three recent scientific articles that reviewed the evidence on marine-source omega-3s and cardiovascular disease risks:
- “…long-term administration of omega-3 PUFA (1 g daily) significantly decreased the risk of overall (-20%), cardiovascular (-30%), and sudden death (-45%). At variance from the orientation of a scientific scenario largely dominated by the "cholesterol-heart hypothesis", GISSI-Prevenzione results indicate omega-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction.”
- “This meta-analysis suggests that dietary and non-dietary intake of n-3 polyunsaturated fatty acids reduces overall mortality, mortality due to myocardial infarction, and sudden death in patients with coronary heart disease.”
- “Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.”
- “Daily intake of omega-3 fatty acids for a mean duration of 37 months decreased all causes of mortality by 16% (relative risk 0.84, 95% confidence interval [0.76; 0.94]) and the incidence of death due to MI by 24% (0.76, [0.66; 0.88]). No significant effect was found for the other outcomes."
It goes without saying that anyone at risk of heart disease should consult a physician. And it makes sense to focus prevention efforts on safe nutritional strategies with broad health benefits.
- Marchioli R. [Omega-3 polyunsaturated fatty acids and cardiovascular diseases] Minerva Cardioangiol. 2003 Oct;51(5):561-76. Review. Italian.
- Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2002 Mar;112(4):298-304.
- Yzebe D, Lievre M. Fish oils in the care of coronary heart disease patients: a meta-analysis of randomized controlled trials. Fundam Clin Pharmacol. 2004 Oct;18(5):581-92.
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- Nawrocki JW, Weiss SR, Davidson MH, Sprecher DL, Schwartz SL, Lupien PJ, et al. Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMGCoA reductase inhibitor. Arteriosclerosis, Thrombosis, and Vascular Biology, 1995; 15(5):67882.
- Bertolini S, et al. Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia. Atherosclerosis, 1997; 130(12):1917.
- Cilla DD Jr, Whitfield LR, Gibson DM, Sedman AJ, Posvar EL. Multipledose pharmacokinetics, pharmacodynamics, and safety of atorvastatin, an inhibitor of HMGCoA reductase, in healthy subjects. Clinical Pharmacology and Therapeutics, 1996; 60(6):68795.
- Rundek T, Naini A, Sacco R, Coates K, DiMauro S. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch Neurol. 2004 Jun;61(6):889-92.
- Vrecer M, Turk S, Drinovec J, Mrhar A. Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke. Meta-analysis of randomized trials. Int J Clin Pharmacol Ther. 2003 Dec;41(12):567-77.
- Abookire SA, Karson AS, Fiskio J, Bates DW. Use and monitoring of "statin" lipid-lowering drugs compared with guidelines. Arch Intern Med. 2001 Jan 8;161(1):53-8.
- Collins R, Armitage J. High-risk elderly patients PROSPER from cholesterol-lowering therapy. Lancet. 2002 Nov 23;360(9346):1618-9.
- Matsuo T, Iwade K, Hirata N, Yamashita M, Ikegami H, Tanaka N, Aosaki M, Kasanuki H. Improvement of arterial stiffness by the antioxidant and anti-inflammatory effects of short-term statin therapy in patients with hypercholesterolemia. Heart Vessels. 2005 Feb;20(1):8-12.
- Stoll LL, McCormick ML, Denning GM, Weintraub NL. Antioxidant effects of statins. Drugs Today (Barc). 2004 Dec;40(12):975-90.
- Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG; PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002 Nov 23;360(9346):1623-30.
- Merck and Company. Nonprescription Mevacor. FDA Advisory Committee Background Information, FDA Website, June 2000: www.fda.gov/ohrms/dockets/ac/00/backgrd/3622b1b.pdf.
- Bristol-Myers Squibb. Advisory Committee Meeting Briefing Book for the Rx to OTC Switch of Pravachol (Pravastatin Sodium). Joint Meeting of Nonprescription Drugs Advisory Committee and Endocrinologic and Metabolic Drugs Advisory Committee, 2000: www.fda.gov/ohrms/dockets/ac/00/backgrd/3622b2a_part1.pdf.