With more than 35 million people taking them, statins are among the most commonly prescribed drugs in the United States, as they are considered the most effective in lowering the “bad cholesterol” in our body. Since high cholesterol can lead to heart attacks, strokes, and other heart-related medical conditions, and given the fact that heart disease is the leading cause of death and stroke is the fifth leading cause of death in the United States, it’s not difficult to understand why so many people are taking statins.
According to one estimation, in 2020, the global sales of statins would have approached $1 trillion. Despite statins’ popularity, there is also skepticism and controversy over the use of these drugs.
In a review published in 2013 in the British Medical Journal (BMJ), the researchers argued that statins have no overall health benefit in the population with a 10-year cardiovascular disease risk of less than 10 percent, and that statins had been overprescribed to this population. The Lancet soon responded with articles arguing that the BMJ has caused harm to public health. The BMJ then responded by requesting England’s chief medical officer to conduct an independent review of the evidence for statins.
According to a review and meta-analysis published in March 2022 in JAMA Internal Medicine, 21 randomized clinical trials that examined statins’ effectiveness in reducing total mortality, heart attacks, and strokes were analyzed. The results showed that while statins’ relative risk reduction in comparison with people who didn’t take statins was 9 percent for deaths, 29 percent for heart attacks and 14 percent for strokes, the absolute risk reduction was only 0.8 percent, 1.3 percent, and 0.4 percent respectively. So the researchers concluded that the absolute overall effect of statins is moderate.
Although people have different opinions regarding the effectiveness of statins, it is generally agreed that there are risks associated with statin treatment. So statins may not be right for everyone. For instance, as aforementioned, if someone is at low risk for cardiovascular disease, then the benefits of taking statins may not outweigh the risks. And when deciding whether to start statin therapy, cholesterol level is not the only consideration.
Furthermore, according to a study published in 2016 in the Journal of the American College of Cardiology, 5 percent to 10 percent of people cannot tolerate statins well, due to side effects, some of which can be severe, including diabetes, rhabdomyolysis, and renal failure. Therefore, they must rely on other alternatives to control their cholesterol. Fortunately, besides other drugs, there are also some natural alternatives, from which they can select the ones most suitable to their needs.
Why Are Statins Considered the Most Effective in Lowering Cholesterol?
High cholesterol can lead to fatty deposits (atherosclerosis) in our blood vessels. As these deposits grow, they will cause the arteries to narrow, thus reducing the blood flow in them. Even worse, these fatty deposits can break abruptly to form a blood clot, which might lead to a heart attack or stroke.
Therefore, it’s critical for us to lower our blood cholesterol, and specifically the LDL (low-density lipoproteins) cholesterol, commonly known as the “bad cholesterol.” At early stages, plaque formation can be controlled by a healthy lifestyle, such as adopting a heart-healthy diet, exercising and quitting smoking. However, if these efforts fail to lower the cholesterol level, or the cholesterol level rises due to natural aging, doctors will then consider statin therapy.
Most of the cholesterol in our body is made by the liver. Statins (aka HMG-CoA reductase inhibitors) are a class of lipid-lowering medications. HMG-CoA (Hydroxymethylglutaryl-CoA) is a protein that plays a role in the biosynthesis of cholesterol. By blocking HMG-CoA, statins slow down the liver’s production of cholesterol and help the liver remove LDL cholesterol that’s already in the bloodstream, thus lowering LDL levels.
The statins available in the United States include atorvastatin (Lipitor), fluvastatin (Lescol XL), lovastatin (Altoprev), pitavastatin (Livalo, Zypitamag), pravastatin (Pravachol), rosuvastatin (Crestor, Ezallor), and simvastatin (Zocor). According to a study published in 2018 in the journal Medicina clínica (Barc), depending on the specific statin and dose, statins can lower LDL cholesterol by at least 25 percent, with the older statins being less effective than the newer ones.
As statins can slow down the liver’s production of cholesterol, they may help stabilize the existing plaques on blood vessel walls and prevent them from turning into blood clots. They may also reduce inflammation in the artery walls, thus possibly avoiding blood vessel blockages that can damage organs. Therefore, statins can also help lower the risk of heart attack and stroke.
Overall, statins can lower total cholesterol, LDL and triglyceride levels, while increasing high-density lipoprotein (HDL; the “good cholesterol”) concentrations. Studies have proven that the higher a person’s risk of heart attack or stroke, the greater the potential benefit of taking statins.
What Are Statins’ Potentially Severe Risks and Side Effects?
Despite the effectiveness of statins in lowering cholesterol, the adverse effects cannot be ignored. According to a paper published in 2016 in the official journal of the Taiwan Society of Cardiology, Acta Cardiologica Sinica, the overall incidence of adverse effects of using statins is 10.4 percent, but a large number of patients who experience myalgia (muscle aches) and other musculoskeletal side effects, which are the most common adverse effects, don’t report their cases.
Besides muscle pains, statins’ other commonly reported side effects include headaches, nausea, and joint pains. Some side effects disappear on their own as the body gets used to the medication. However, there can be severe and long-lasting symptoms, including:
1) Type 2 diabetes: Your blood glucose level may increase when you take a statin, which can lead to type 2 diabetes. According to a study published in 2019 in the journal Diabetes Metabolism Research and Reviews, taking statins can more than double a person’s likelihood of developing type 2 diabetes; and the longer one takes statins, the greater the risk of diabetes becomes, as blood sugar levels continue to escalate. Those taking statins for two or more years are at the greatest risk of developing new-onset-diabetes, with no differences observed by statin class or dosage.
2) Rhabdomyolysis: Although its incidence is less than 0.1 percent, rhabdomyolysis is a severe side effect that can cause muscle cells to break down and release the cell contents (including creatine kinase and myoglobin) into the bloodstream, resulting in severe muscle pain, kidney damage, and/or renal failure. The larger the statin dosage, the higher risk of rhabdomyolysis.
3) Liver damage: Statin use causes an increase in liver enzymes, which may lead to liver damage.
4) Strokes: For patients with a history of hemorrhagic strokes, taking statins may increase their risk of having another stroke.
3 Most Effective Natural Alternatives to Statins
For people that cannot tolerate statins, decline to use statins due to concerns about side effects, or are at a low risk for cardiovascular disease, there are other alternatives available. To be alternatives to statins, they must have similar effects on cholesterol.
Other drugs that are effective at lowering cholesterol and can be replacements for statins include PCSK9 inhibitors (can also lower the risk of heart attack and stroke), bile acid sequestrants (safest option but not as effective), and inclisiran (a recently approved medication that is very effective at lowering cholesterol).
Some people prefer natural remedies to medicines, which are chemical compounds. Fortunately for them, there are several options that can be effective at lowering cholesterol, without serious risks.
1) Red Yeast Rice Extract (RYRE)
Red yeast rice is a type of fermented rice, which was cultivated with the mold Monascus purpureus and has a bright reddish purple color as a result. Red yeast rice has long been used in traditional Chinese medicine to energize the body, help with digestion and revitalize the blood.
The extract from this type of rice has been found to be the most effective cholesterol-lowering nutraceutical on the market. It contains 14 active compounds called monacolins, which can inhibit the cholesterol synthesis in the liver. Among them, monacolin K appears to be the most efficacious, and it is chemically identical to the active ingredients in lovastatin and mevinolin, which are both statin drugs. Monacolin K is considered a safe supplement for managing high cholesterol in patients with no additional cardiovascular risk factors. According to a study published in 2019 in the Methodist DeBakey Cardiovascular Journal, consuming monacolin K within 10 mg of RYRE on a daily basis can reduce LDL cholesterol plasma levels between 15 percent and 25 percent in 6 to 8 weeks.
Other potential benefits of red yeast rice include improved heart health, as well as reduced inflammation and cancer risk. Furthermore, the existing RYRE products are usually less expensive than statins, especially the brand-name statin products.
The side effects caused by red yeast rice are generally very mild (especially when compared to statins’ rare but severe side effects), including abdominal discomfort, gas, headaches, heartburn and dizziness. In a study published in 2017 in the journal BMC Cardiovascular Disorders, 60 dyslipidemic patients with low to moderate cardiovascular risk received either red yeast rice or a statin drug, and it was discovered that red yeast rice caused less fatigue than the statin drug in these patients, while offering comparable cholesterol-lowering effects.
There is a lack of research into RYRE’s long-term safety. There have been concerns that red yeast rice is potentially toxic. However, in a meta-analysis published in 2019 in the journal Pharmacological Research, data from 53 randomized controlled clinical trials with a total of 8,535 subjects were analyzed. The researchers found a reduced risk of non-muscular adverse events and serious adverse events in the experimental group compared to the control group. And the study concluded that RYRE products are generally tolerable and safe.
One concern is that the existing RYRE products on the market are not standardized, as well as the monacolin levels within these products. The monacolin levels are generally not even shown on product labels. In a study published in 2010 in the journal Archives of Internal Medicine, researchers from Chestnut Hill Hospital, University of Pennsylvania Health System, analyzed and evaluated the monacolin and citrinin contents in 12 commercial RYRE products, and they discovered significantly different levels of monacolin in these products. Unfortunately, more than a decade later, there is still the need for red yeast rice products’ standardization, and there is still uncertainty about the best dose and monacolin content.
2) Barley
Certain functional foods might be considered an alternative or add-on therapy to statins.
Barley, a member of the grass family, is a common grain cultivated all over the world. However, barley is not extensively consumed in the diet of Americans. Barley taken in the form of beta-glucan (β-glucan) fiber is also considered one of the most effective cholesterol-lowering natural alternatives to statins.
Beta glucan is a specific form of soluble dietary fiber. In a controlled and randomized study published in 2017 in the British Journal of Nutrition, some participants with mild hypercholesterolemia were given breakfast containing 3 grams of low-molecular weight barley beta-glucan for 5 weeks. Increased bile acid synthesis was observed in all of these participants, indicating that increased bile acid synthesis may be the reason for the cholesterol-lowering effect of barley beta-glucan.
The liver uses cholesterol to produce bile acids. Our body removes these bile acids through defecation. After being consumed, beta-glucan enters the lumen of the small intestine, where it can bind to bile acids, by acting similar to a bile acid sequestering agent. As a result, bile acids get trapped, unable to be reabsorbed by the intestines. As bile acids are removed from the body, the liver then has to use more cholesterol to make new bile acids to replenish the bile acid pool. Therefore, the amount of cholesterol in the bloodstream gets lowered.
Beta glucan is found in certain types of plants, yeasts, bacteria, and fungi. Grains contain the highest concentration of beta glucan, including barley, oats, sorghum, rye, maize, wheat, and rice. Among them, barley typically has the highest beta-glucan content, followed by oats. Oats taken in the form of bran have a large amount of beta-glucan. However, its cholesterol-lowering ability is not as effective as barley.
In a small-scale study published in 2004 in the Journal of the American College of Nutrition, 18 moderately hypercholesterolemic men consumed controlled diet rich in whole wheat, brown rice, or barley for 5 weeks, and their fasting blood samples were collected. The researchers discovered that those given barley had their cholesterol levels reduced more than participants on wheat or brown rice. Also, barley was found to be able to reduce total cholesterol, LDL cholesterol, and triacylglycerol. The researchers concluded that adding barley into the diet can reduce cardiovascular risk factors.
According to the Food and Drug Administration (FDA), consuming at least 3 grams of barley beta-glucan per day can help reduce cholesterol levels and also risk of cardiovascular diseases.
The consumption or injection of beta-glucans through an IV may also cause side effects, including blood pressure changes, diarrhea, fever, chills, flushing, joint pains, dizziness, nausea and vomiting, rash, and excessive urination. Also, like other grains, barley contains gluten, so it’s not a suitable statin replacement for people allergic to gluten. However, beta-glucans are generally considered safe to consume and be used to lower cholesterol.
3) Tomatoes and Tomato Products
Tomatoes, whether dried or fresh, as well as tomato products (e.g. tomato juice, tomato paste) are among the best foods to lower cholesterol. Among these food items, the most healthy are carefully washed tomatoes with skin, since the tomato skin has the highest concentration of lycopene. Tomato juices have lost their fibers during processing, and ketchup and other tomato products may have a lot of additives, including salt, sugar, and preservatives, which can offset the health benefits of tomatoes.
According to a study published in 2012 in The Journal of Nutrition, women consuming at least 10 servings of tomato-based food products per week had clinically modest but significant improvements in total cholesterol level and the total cholesterol to HDL cholesterol ratio, compared with women consuming less than 1.5 servings of tomato products per week. Specifically, women consuming at least 10 servings were 31 percent less likely to have elevated total cholesterol and 40 percent less likely to have elevated LDL cholesterol, in comparison with the latter group.
Tomatoes are the major dietary source of lycopene, and in the United States, processed tomato-based products are the primary dietary lycopene source.
Lycopene is a non-provitamin A carotenoid and antioxidant, and it is the most abundant carotenoid in ripened tomatoes. It is lycopene that gives tomatoes, pink grapefruit, and other foods the red to pink colors. In tomatoes, the highest concentrations of lycopene are found in the skin. And in general, the darker the tomato skin, the more lycopene it contains. Also, cooking tomatoes for 30 minutes or more raises their lycopene levels. Lycopene has been extensively studied for its beneficial health effects in the recent decade, including reduced cholesterol and decreased risk of heart disease and cancer.
In a meta-analysis published in the journal Maturitas, researchers searched the PubMed and Cochrane databases for intervention studies between 1955 and September 2010 to analyze the effect of lycopene on blood lipids and blood pressure. They concluded that a daily lycopene intake of at least 25 mg is effective in reducing LDL cholesterol by about 10 percent, and this result is similar to the effect of low doses of statins. For this reason, lycopene can be an excellent alternative to statins in patients who are statin-intolerant.
According to a review published in 2012 in the journal Annals of Nutrition and Metabolism, tomato consumption has been associated with a decreased risk of atherosclerosis. In animal studies, lycopene and tomato products decreased plasma total cholesterol and LDL cholesterol and increased high-density lipoprotein cholesterol, thus improving the LDL/HDL ratio. In human macrophages, lycopene reduced intracellular total cholesterol. This reduction of intracellular cholesterol has been associated with a decrease in cholesterol synthesis through an inhibition of HMG-CoA reductase activity and expression, and a suppression of the synthesis of LDL receptors, thus preventing excessive amounts of cholesterol from accumulating in cells.
Also, lycopene can impair oxysterol-induced pro-inflammatory cytokines production in human macrophages, thus interfering with the formation of fatty deposits (plaques).
When consuming food products containing lycopene, make sure that the other foods in the same meal don’t negatively affect lycopene absorption. Furthermore, when consuming lycopene-containing food products, a lipid can increase its absorption by up to four times.
Furthermore, patients considering statins or other treatments should first adopt a healthy lifestyle to help improve their blood cholesterol levels, such as losing excess weight, doing exercises, and avoiding the consumption of saturated and trans fat.
