Findings raise red flag about aggressive cholesterol reduction; statins raise inflammatory omega-6s; omega-3s increase statins' protective power
by Craig Weatherby
Statin drugs such as Lipitor, Pravachol, and Lovastatin reduce the risk of heart attacks and other adverse coronary events by lowering LDL cholesterol, high blood levels of which are associated with greater risk of heart attack and sudden death.
However, many who die from heart troubles have normal LDL levels, while many people with elevated LDL levels never suffer a heart attack or other adverse cardiac event.
Since much uncertainty remains concerning the connections between elevated levels of LDL and risk of death or heart attacks, new findings—which link low cholesterol levels to increased cancer risk—should provoke discussion and research within the cardiology community.
This is especially true because the definition of "elevated LDL" being steadily ratcheted downward, more and more people are being prescribed increasingly potent statin drugs.
While statins drugs are generally anti-inflammatory—a desirable effect with regard to heart risks—they induce changes to the body's fatty acid profile that could explain an increased risk of cancer (Evans M et al 2004; Harris JI et al 2004; Jula A et al 2005):
- Statins may increase blood levels of a pro-inflammatory omega-6 fatty acid fat called arachidonic acid (AA).
- Statins may increase the ratio of omega-6 AA to omega-3 EPA and DHA. (They stimulate release of long-chain fatty acids from cell membranes, but provoke greater release of omega-6s than omega-3s.)
Omega-6 AA is an essential component of cell membranes and the immune system, and AA can induce cancer cells to commit “suicide” (apoptosis; Levine L 2003).
But as the new findings suggest, increasing your bodily ratio of pro-inflammatory AA to anti-inflammatory omega-3s over a period of years holds ominous implications. This is because, in cell and animal studies, omega-6s generally promote cancer cell growth while omega-3s generally inhibit cancer growth.
The omega-6-favoring effects of statins seem especially worrisome in light of the fact that most Americans already suffer from an overload of omega-6s in their cells, thanks to the gross excess of omega-6s in their diets.
Boston team finds low cholesterol raises cancer risk
Researchers at Tufts University School of Medicine near Boston analyzed data from 23 randomized, controlled clinical trials of statin drugs, involving 75,317 participants.
Two findings stand out as alarming in light of the growing treatment trend toward extreme cholesterol-lowering via high-dose statin therapy:
Liver toxicity rose with increased statin doses. The Tufts team proposed that treatment with moderate doses of several drugs may be safer than therapy with high doses of statins alone.
Patients with the lowest LDL levels were at significantly increased risk of all types of cancer, versus participants with higher LDL cholesterol levels.
As the Tufts team wrote, “…the risk of cancer is significantly associated with lower achieved LDL-C levels… Furthermore, the cardiovascular benefits of low achieved levels of LDL-C may in part be offset by an increased risk of cancer” (Alsheikh-Ali AA et al 2007).
Nutrition offers a serious alternative
The connection between total cholesterol levels or cholesterol profiles and adverse cardiovascular events or cardiac deaths is much weaker than we're led to believe (See “Does Fish Oil Lower Cholesterol? Does it Matter?”).
People are somewhat more likely to have a heart attack when they have one or more of three adverse cholesterol profiles:
- Very high total cholesterol levels
- High levels of small, dense LDL cholesterol (which can imbed in artery walls more easily)
- High levels of oxidized LDL cholesterol
However, other factors are equally powerful factors in heart attacks, sudden cardiac death, and strokes:
- Triglyceride levels
- Blood stickiness (platelet activation)
- Arrhythmias (irregular heartbeats)
Fish oil is known to improve all four of these risk factors substantially, and to reduce the risks of a second heart attack or sudden cardiac death: the mortality category that accounts for half of all heart-related fatalities.
This is not necessarily an either/or situation for folks being urged to take statins.
A large clinical study from Japan demonstrated that when heart patients took omega-3 EPA in addition to statins, they had 19 percent fewer adverse cardiovascular events compared to those taking statins alone (Yokoyama M et al 2007).
Insulin and leptin resistance also appear to rival cholesterol levels as predictors of cardiovascular risk, while impaired immune-cell response to arterial plaques, and homocysteine levels count as key risk factors.
If the very aggressive kind of cholesterol reduction recommended these days raises cancer risks, it seems wise to consider a more holistic approach to heart health—one that downplays drastic cuts in LDL cholesterol in favor of raising HDL cholesterol levels and reducing inflammation, blood pressure, stress, and the risk of arrhythmias.
There are many alternative anti-inflammatory agents available, including low-dose aspirin—which reduces colon cancer risk—and colorful, antioxidant-rich foods such as berries and red-orange-green vegetables, high consumption of which appears to reduce cancer risk as well as inflammation.
We recommend reading “Reverse Heart Disease Now,” the excellent book by holistic heart surgeon Stephen T. Sinatra, M.D. His book clarifies the cholesterol picture and identifies credible heart-health supplements such as omega-3s and Co-Q10.
- Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials. J Am Coll Cardiol. 2007 Jul 31;50(5):409-18. Epub 2007 Jul 16.
- Evans M, Roberts A, Davies S, Rees A. Medical lipid-regulating therapy: current evidence, ongoing trials and future developments. Drugs. 2004;64(11):1181-96. Review.
- Silva MA, Swanson AC, Gandhi PJ, Tataronis GR. Statin-related adverse events: a meta-analysis. Clin Ther. 2006 Jan;28(1):26-35.
- Castano G, Fernandez L, Mas R, Illnait J, Mesa M, Fernandez JC. Comparison of the effects of policosanol and atorvastatin on lipid profile and platelet aggregation in patients with dyslipidaemia and type 2 diabetes mellitus. Clin Drug Investig. 2003;23(10):639-50.
- Jula A, Marniemi J, Ronnemaa T, Virtanen A, Huupponen R. Effects of diet and simvastatin on fatty acid composition in hypercholesterolemic men: a randomized controlled trial. Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1952-9. Epub 2005 Jul 14.
- Harris JI, Hibbeln JR, Mackey RH, Muldoon MF. Statin treatment alters serum n-3 and n-6 fatty acids in hypercholesterolemic patients. Prostaglandins Leukot Essent Fatty Acids. 2004 Oct;71(4):263-9.
- Levine L. Does the release of arachidonic acid from cells play a role in cancer chemoprevention? FASEB J. 2003 May;17(8):800-2.
- Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007 Mar 31;369(9567):1090-8. Erratum in: Lancet. 2007 Jul 21;370(9583):220.