The rise in widespread use of statins coincided with lifestyle changes in post–World War II America. As the population gradually migrated to car-friendly suburbs and became increasingly sedentary, the food industry began filling supermarket shelves with more processed “convenience” foods packed with high-fructose corn syrup, trans fats and other pro-inflammatory ingredients. Before long, coronary heart disease (CHD) became a major cause of death.
Despite an increasingly clear connection between diet and heart disease, pharmaceutical companies in the 1990s saw a burgeoning market for a class of drugs called statins, which block production of LDL in the liver, reducing its levels in the blood. And, by 1994, they had the research they needed to argue that these drugs could prevent heart disease.
The Scandinavian Simvastatin Survival Study, sponsored by pharmaceutical giant Merck, showed that the cholesterol-inhibiting drug, simvastatin (brand name: ZOCOR), could lower LDL levels by 25 to 35 percent and reduce myocardial infarction (heart attack) by 25 to 30 percent in those with normal cholesterol but who have other risk factors, like hypertension, smoking or diabetes.
With the advent of statins, our Big Mac nation was given license to stay the course: We kept consuming processed foods through the rollout of lovastatin, simvastatin and atorvastatin — otherwise known as Lipitor — which for many years has been the top-selling drug in the world. Just last year, rosuvastatin (brand name: Crestor) was approved as a preventive for healthy individuals with low cholesterol counts and no risk factor beyond an elevated level of C-reactive protein (CRP), a sign of inflammation in the body. Once prescribed statins, these people were advised to take them for life.
That’s when cardiologists and epidemiologists adept at reading statistics finally began breaking ranks. Their concerns about statins’ side effects were well placed. A study published in The Lancet in February 2010 showed statins could increase the risk of type 2 diabetes by 9 percent. Other recent studies have traced statins to headache, joint pain and abdominal pain, as well as linked the drugs to peripheral neuropathy, the sense of tingling and numbness or burning pain, often in arms and legs.
At UCSD, Golomb has been studying a series of lesser-known (but not less common) neuropsychiatric and cognitive side effects. Her interest began when, as a medical student in the late 1980s, she became aware of two studies linking cholesterol-lowering drugs to violent death. “In these studies, the decrease in death from heart disease was fully offset by increases in violent death from suicide, homicide and accident,” she says. Golomb’s neurobiology research told her the reports made sense. “Cholesterol is a very high fraction of the dry weight of the brain,” she says, and aids the function of neurotransmitters — the molecules of emotion and cognition that help the brain do its job. Force cholesterol levels down by artificial means, and brain infrastructure suffers. Her own paper on low cholesterol and violence was published in the Annals of Internal Medicine in 1998.
As word got out, Golomb’s lab received a steady stream of email from statin users with a wide range of problems neither reflected in the literature nor taken seriously by their doctors. The effects, documented in her multiyear study, include reduced energy and a lack of interest in activity, increased fatigue after exercise, erectile dysfunction, and a significant reduction in the ability to achieve orgasm. “Half the people who reported any symptom reported more than one,” Golomb adds.
This reflects what the evidence shows — a common mechanism based on statin disruption of the mitochondria, the energy-producing parts of cells. “We are conditioned to think of cholesterol as a nefarious substance that courses through the blood for the sole purpose of congealing in our arteries and causing cardiovascular disease, but there is a reason why evolution mandates that every cell in our body produces it, and that it circulate through our blood,” Golomb says.
So what’s a statin-taker to do? If you are experiencing troublesome side effects, but have heart disease or serious risk factors and can’t stop taking the drugs entirely, you may still want to consider taking a brief break from the med to see if it seems to be causing your symptoms. If so, you should ask your doctor to prescribe a different drug or lower your dose.
If you’ve been prescribed the drugs prophylactically, it may be time to talk with your doctor about getting off statins entirely. According to internist and clinical pharmacologist James M. Wright, MD, PhD, professor at the University of British Columbia, statins have no proven net health benefit as a preventive. As managing director and chair of the Therapeutics Initiative, a group that evaluates drug studies in Canada, Wright is an expert on meta-analyses — the large “studies of studies” — that take every last bit of data into account. His latest review of the data — and the most comprehensive to date — was published in the Therapeutics Letter in 2010: “Statins do not have a proven net health benefit in primary prevention populations,” he wrote, adding that the “claimed mortality benefit” for this group is “more likely a measure of bias than a real effect.”
The data is especially murky for people with elevated cholesterol but no other risk factors. “This is a gray area,” he notes. In short, there’s little credible evidence that attempting to lower a high cholesterol count with drugs is beneficial unless other risks are elevated as well.
Walter Willett, MD, chair of the department of nutrition at the Harvard School of Public Health, adds that even for those who need the drug, “statins only reduce risk of heart disease modestly, about 30 percent, and thus are not sufficient.” Lifestyle changes (see “Many Problems, One Cure,” page 65) are required to take patients the rest of the way. For many, making the right lifestyle changes is all that’s required.
Next: Halting Hypertension