New report says risks are downplayed and benefits overstated
One in four adult Americans suffers from heart disease.
And statin-type drugs can reduce the risk of deaths from cardiovascular disease (CVD) as well as the risk for developing CVD — a benefit called “primary prevention”.
Statins are synthetic modifications of cholesterol-lowering compounds found in red yeast rice, which also curb harmful inflammation and blood clotting.
Back in 2001, an expert panel at the National Heart, Lung, and Blood Institute (NHLBI) released new guidelines that would result in 36 million Americans — nearly 20 percent of the adult population — taking statins.
Partially in response, the proportion of adults 40 years and older who were prescribed statins grew from 17.9% in 2003 to 27.8% in 2013 — with statins being prescribed to significantly fewer women, racial/ethnic minorities, and uninsured people.
But the NHLBI’s 2001 advice —and similar guidance in 2016 from the US Preventive Services Task Force — seem to underplay the side effects of statins in relation to their preventive benefits in specific risk groups.
Those groups' advice to expand use of statins also seems to underplay the heart-risk reductions achievable with lifestyle measures like diet, stress reduction, weight control, supplements, and exercise.
Now, a new evidence analysis from Swiss scientists suggests that the benefits of statins — especially amongst older people — have been exaggerated in relation to the frequency and severity of side effects.
In contrast, the American Heart Association (AHA) just issued reassuring conclusions about the safety of statins — ones that largely contradict the Swiss scientists’ conclusions.
Let’s examine these conflicting conclusions, and then look at conflicting advice about who should take statins.
Finally, we’ll review some of the natural ways to reduce cardiovascular risk or ameliorate the adverse side effects of statins.
Swiss study decries dismissal of statin side effects
Most medical studies use “expected risk for cardiovascular disease (CVD) during the next 10 years” to guide recommendations on use of statins.
However, as the Swiss scientists wrote, “how harms were considered and weighed against benefits is often unclear.”
So, the Swiss researchers examined all the available evidence concerning the benefits and side effects of a preventive dose of statins (Yebyo HG et al. 2018).
In addition, they questioned healthy people about the importance to them of certain statin side effects versus their potential benefits.
Finally, the Swiss scientists compared the benefits and side effects of four commonly used statin drugs.
Based on all that data, the researchers calculated reasonable statin-prescription thresholds for men and women in different age groups between 40 and 75 years.
And they concluded that too many people — especially seniors — are being prescribed statins. As lead author Dr. Milo Puhan said, “… statins are clearly recommended too often today.”
In fact, the Swiss teams’ new thresholds would halve the number of people prescribed statins, due to these calculations:
- Among people aged 70-75, the Swiss team calculated that the benefits of statins only outweigh the damage from possible side effects when the risk of suffering a heart is attack or stroke over the next 10 years equals or exceeds 21%.
- Among men and women aged 40-45, the statin-prescription threshold was set slightly lower, at 10-year risks of 14% and 17% or higher, respectively.
The Swiss researchers also found that two of the four statin drugs studied, atorvastatin and rosuvastatin, had a significantly better balance of benefit and harm than the other two (simvastatin and pravastatin).
Before deciding whether to take a statin drug, Dr. Puhan recommends considering — in consultation with a doctor — your personal risk of cardiovascular disease versus the risk of adverse side effects.
American Heart Association downplays statin side effects
The American Heart Association (AHA) just published a study which concluded that the benefits of statins far outweigh any risk of side effects, which they called very low.
The authors of the new report reviewed dozens of studies — mostly clinical trials — dating back at least 20 years (Newman CB et al. 2018).
Muscle pain, muscle weakness and Type 2 diabetes rank as the most commonly reported side effects of statins.
But the paper’s authors found that muscle pain and weakness were rare among participants in the clinical trials, and that these symptoms couldn’t be tied to actual muscle damage.
Further, they found no convincing evidence that statins promote other conditions sometimes blamed on the drugs, including cancer, cataracts, cognitive dysfunction (“brain fog”), peripheral neuropathy, erectile dysfunction, or tendonitis.
But not all studies agree that statins are so harmless: see "Speaking of harm: Do none", below
The standoff over statins
High levels of certain forms of cholesterol raise heart risks.
So statins are seen as key allies in "primary prevention", which is the effort to reduce major risk factors for cardiovascular disease.
But should statins be the first resort for treating high cholesterol?
The evidence on that score is mixed, compared with clearer evidence that statins benefit people with heart disease and those who’ve suffered a heart attack or stroke.
Two major health organizations provide differing prescription guidelines for statins: The American College of Cardiology/American Heart Association (ACC/AHA) and the United States Preventive Services Task Force (USPSTF).
Both groups’ guidelines cover people between the ages of 40 and 75 with no history of cardiovascular disease and triglyceride levels of 400 mg/dL or higher.
And both groups agree that anyone in this age group with an LDL cholesterol level of 190 mg/dL or higher should be taking a statin drug.
But that’s where the guidelines of the two organizations diverge.
The American College of Cardiology/American Heart Association (ACC/AHA) offers these statin-prescribing criteria in 2013:
- LDL-cholesterol of 190 mg/dL or higher; or
- Diabetes and LDL-C of 70 mg/dL or higher; or
- Ten-year atherosclerotic cardiovascular disease (ASCVD) risk of 7.5% or greater and LDL-cholesterol of 70 mg/dL or higher.
The 2016 United States Preventive Services Task Force (USPSTF) provided these statin-prescribing criteria in 2016:
- LDL-C of 190 mg/dL or higher; or
- At least one cardiovascular risk factor (hypertension, diabetes, dyslipidemia, or smoking) and 10-year ASCVD risk of 10% or greater.
At first blush, these guidelines seem very similar, but each would result in markedly different numbers of Americans being prescribed statins.
Last year, researchers from Duke University and Canada’s McGill University calculated the difference in the number of statin prescriptions that would result from universal adoption of each organization’s guidelines (Pagidipati NJ, et al. 2017).
Under the 2016 USPSTF guidelines, an additional 15.8% of diagnosed heart patients would be prescribed statins, over and above the 21.5% of heart patients currently taking statins.
By comparison, adherence to the ACC/AHA guidelines would result in an additional 24.3% of heart patients being prescribed statins.
As the Duke-McGill team wrote, “… adherence to the 2016 USPSTF recommendations for statin therapy, compared with the 2013 ACC/AHA guidelines, could lead to a lower number of individuals recommended for primary prevention statin therapy, including many younger adults with high mean [average] long-term CVD risk.”
Of course, this leaves unanswered the question of whether statins are the only effective (and practical) approach to lowering cholesterol levels and the related risk for heart attacks, strokes, and sudden cardiac death.
Before we discuss natural approaches to reducing risk, let’s look at the issue of age, and the risks of harm from statins.
What about people aged 75 or older?
Most studies of primary cardiovascular prevention only include people younger than 75 years.
Yet, according to the Centers for Disease Control and Prevention (CDC), nearly half of all adults aged 75 or older are taking statins.
However, as one expert recently told The New York Times, “For people over age 75… there was not sufficient evidence to reach a conclusion. As with many clinical trials, the major statin studies mostly haven’t included patients at advanced ages.”
This means that some elders taking statins don’t need them and may suffer side effects for no purpose, while others who aren’t taking statins might benefit from the drugs.
One obvious concern about giving seniors statins is that many already take multiple medications, some of which interact unfavorably with statins.
And — despite the AHA’s recent statement concerning the frequency and cause of such muscle aches and fatigue — up to 30% of people taking statins report muscle symptoms.
Because many statin questions remain unanswered when it comes to seniors, the prevailing sentiment should be “first do no harm.”
Speaking of harm: Do none
Statins are linked to a variety of negative side effects — mostly muscle- or liver-related — which range from minor to (rarely) dangerous.
However, because statins are relatively new drugs, it’s not clear whether their systemic effects produce damage that hasn’t yet become apparent.
Statins work in part by blocking the enzyme needed to produce cholesterol in the liver, but they also interrupt 20 other essential biochemical processes — some of which, ironically, are crucial for maintaining cardiovascular health.
For example, statins reduce levels of coenzyme Q10 (CoQ10), which is essential to cellular energy production, with the highest levels found in your heart, brain, and liver.
This is a particularly concerning side effect, since coQ10 helps stop risky oxidation of LDL-type cholesterol and may itself help lower cholesterol levels. Aim for 100-200 mg of CoQ10 per day.
Low levels of CoQ10 are associated with fatigue, accelerated aging, and many different chronic diseases.
And 50 to 75 percent of people diagnosed with cardiovascular disease suffer from low levels of CoQ10 — as do many people at high risk of heart attack or who have diabetes or high blood pressure.
Cardiologists typically prescribe CoQ10 to people taking statins, but that’s not universal, and it’s not clear that supplements can fully eliminate the CoQ10 deficiency created by statin therapy.
What about cancer?
Like two evidence reviews published last year, the recent AHA evidence review found no evidence that statins raise the risk for cancer of any kind.
And there’s evidence that statins may help control aggressive breast cancers with poor outcomes (e.g., inflammatory and triple-negative breast cancers).
But on the minus side — contradicting the AHA’s recent study — one recent study linked statin use to higher risks for colorectal and pancreatic cancers (Fujimoto M, et al. 2015).
Natural aids and allies
If you have high cholesterol and are leery of statins, it makes sense to consider alternatives — in careful consultation with a doctor you trust.
Natural strategies include eating a healthy diet, getting regular exercise, and at least three supplements backed by evidence of efficacy: plant sterols, omega-3 fatty acids, and red yeast rice (a natural source of statins).
These waxy, naturally occurring substances occur throughout the plant world, but abound in legumes and some seeds, including sunflower and sesame seeds.
Sterols reduce inflammation in the arterial wall, which is a key driver of plaque buildup and the risk of arterial plaque bursting and causing dangerous blood clots.
Plant sterols are so effective that the American Heart Association and the National Cholesterol Education Program recommend them for lowering elevated cholesterol levels. Aim for 2,000 mg daily.
Omega-3 fatty acids
Omega-3 essential fatty acids from fish or supplements improve cholesterol profiles, lower triglyceride levels, reduce inflammation, and prevent blood platelets from becoming sticky.
Those effects probably explain why omega-3s help prevent strokes and cardiovascular disease and reduce the risk of sudden cardiac death, second heart attacks, or congestive heart failure (see Heart Failure Findings Favor Omega-3s over Statin Drug).
And the recently published results of two large clinical trials support their heart-healthy reputation: see Omega-3s Score 2nd Big Heart Win and Omega-3s’ Heart Value Vindicated in Long, Large Clinical Trial.
Supplemental omega-3s (e.g., fish oil) appear to enhance and even rival the cardiovascular benefits of statins, and rival statins when it comes to reducing the risk of death from any cause: see Omega-3s Add to Statin Drugs' Cardio Benefits, Omega-3s Seen Rivaling Statins at Reducing Risk of Death, and their links to related reports.
(Conversely, there’s good evidence that we’re consuming far too much omega-6-rich cooking oil — an excess that fosters a pro-inflammatory environment in blood vessels: see Vegetable Oils Debunked for Heart Disease and its links to related articles.)
Whether you’re taking a statin or not, aim for 1,000-2,000 mg of omega-3s a day, either from supplements or a combination of fatty fish and supplements: for example, a 6-ounce serving of wild sockeye salmon provides almost 2,000 milligrams of omega-3s.
Red Yeast Rice
Statin drugs were created after the discovery that red yeast rice lowers cholesterol levels.
Red yeast rice extract contains naturally occurring lovastatin, which is the same active chemical in the synthetic statin drug called Mevacor.
Synthetic statin drugs were created primarily because — unlike natural products such as red yeast rice — they can be patented.
The amount of lovastatin in typical red yeast rice extracts is much lower than the amount in Mevacor.
Nonetheless, red yeast rice extract can cause the same side effects as synthetic statins, including abnormal liver test results and muscle weakness (myopathy). However, because red yeast rice typically contains less lovastatin than its pharmaceutical counterpart, side effects are less common.
It’s important to note that different brands of red yeast rice contain different amounts of lovastatin, and the amounts can vary among batches.
To learn more about this ancient Chinese folk remedy, see Yeasty Rice Rivals Statin Drugs.
Talk to your doctor before taking red yeast rice extract — he or she will probably want to monitor your liver function — and don’t take it along with prescription statins.
- Cleveland Clinic Health Library. Cholesterol Reduction: Red Yeast Rice and Plant Stanols. Accessed at https://my.clevelandclinic.org/health/articles/17417-cholesterol-reduction-red-yeast-rice-and-plant-stanols
- Fujimoto M, et al. Association between Statin Use and Cancer: Data Mining of a Spontaneous Reporting Database and a Claims Database. Int J Med Sci. 2015;12(3):223-33.
- Gu Q, et al. Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003-2012. NCHS Data Brief/CDC. Dec 2014;177.
- Islam MM, Yang HC, Nguyen PA, Poly TN, Huang CW, Kekade S, Khalfan AM, Debnath T, Li YJ, Abdul SS. Exploring association between statin use and breast cancer risk: an updated meta-analysis. Arch Gynecol Obstet. 2017 Dec;296(6):1043-1053. doi: 10.1007/s00404-017-4533-3. Epub 2017 Sep 22. Review.
- Kazi DS, Penko JM, Bibbins-Domingo K. Statins for Primary Prevention of Cardiovascular Disease: Review of Evidence and Recommendations for Clinical Practice. Med Clin North Am. 2017 Jul;101(4):689-699. doi: 10.1016/j.mcna.2017.03.001. Review.
- Kim SH, et al. Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability. Eur J Clin Nutr. 2011 Jan;65(1):110-6.
- Kris-Etherton PM, et al. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002 Nov 19;106(21):2747-57.
- Leaf A. Historical overview of n-3 fatty acids and coronary heart disease. Am J Clin Nutr. 2008 Jun;87(6):1978S-80S.
- Lee BJ, et al. A significant correlation between the plasma levels of coenzyme Q10 and vitamin B-6 and a reduced risk of coronary artery disease. Nutr Res. 2012 Oct;32(10):751-6.
- Lewis SJ, et al. Effect of pravastatin on cardiovascular events in women after myocardial infarction: The Cholesterol and Recurrent Events (CARE) trial. J Am Coll Cardiol. 1998 Jul;32(1):140-6.
- Murakami R, Chen C, Lyu SY, Lin CE, Tzeng PC, Wang TF, Chang JC, Shieh YH, Chen IF, Huang SK, Lin HW. Lovastatin lowers the risk of breast cancer: a population-based study using logistic regression with a random effects model. Springerplus. 2016 Nov 8;5(1):1932. doi: 10.1186/s40064-016-3606-2. eCollection 2016.
- Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL 2nd, Goldstein LB, Chin C, Tannock LR, Miller M, Raghuveer G, Duell PB, Brinton EA, Pollak A, Braun LT, Welty FK. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2018 Dec 10:ATV0000000000000073. doi: 10.1161/ATV.0000000000000073. [Epub ahead of print]
- Pagidipati NJ, et al. Comparison of Recommended Eligibility for Primary Prevention Statin Therapy Based on the US Preventive Services Task Force Recommendations vs the ACC/AHA Guidelines. JAMA. 2017;317(15):1563-7.
- Petretta M, Costanzo P, Perrone-Filardi P, Chiariello M. Impact of gender in primary prevention of coronary heart disease with statin therapy: a meta-analysis. Int J Cardiol. 2010 Jan 7;138(1):25-31. doi: 10.1016/j.ijcard.2008.08.001. Epub 2008 Sep 14.
- Ras RT, et al. LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies. Br J Nutr. 2014 Jul 28;112(2):214-9.
- Singh RB, et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens. 1999;13:203-8.
- Span P. You’re Over 75, and You’re Healthy. Why Are You Taking a Statin? NYT. Jan 5 2018.
- Stone NJ, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1-45.
- Studer M, et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med. 2005 Apr 11;165(7):725-30. Review.
- Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, Ward K, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD004816. doi: 10.1002/14651858.CD004816.pub5. Review.
- U.S. Preventive Services Task Force. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Recommendation Statement. Am Fam Physician. 2017 Jan 15;95(2). Accessed at https://www.aafp.org/afp/2017/0115/od1.html
- US Preventive Services Task Force, Bibbins-Domingo K, et al. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force Recommendations Statement. JAMA. 2016;316(19):1997-2007.
- Van Wyhe RD, Rahal OM, Woodward WA. Effect of statins on breast cancer recurrence and mortality: a review. Breast Cancer (Dove Med Press). 2017 Dec 1;9:559-565. doi: 10.2147/BCTT.S148080. eCollection 2017. Review.
- Yebyo HG, Aschmann HE, Puhan MA. Finding the Balance Between Benefits and Harms When Using Statins for Primary Prevention of Cardiovascular Disease: A Modeling Study. Ann Intern Med. 2018 Dec 4. doi: 10.7326/M18-1279. [Epub ahead of print]