A recently published case series from the University of Chicago underscores the value of plant sterol supplements for managing elevated cholesterol in statin-intolerant patients at moderate to high risk for cardiovascular disease.

While statin therapy with accompanying lifestyle modification remains the preferred conventional intervention for treating dyslipidemias and reducing cardiovascular risk, many patients do not want to take statins, or are intolerant of them.

Plant sterols have long been recommended in the global medical guidelines to control cholesterol, primarily for patients who do not quality for pharmacotherapy, cannot tolerate statins, or who opt against prescription drug therapies.

“Over the last few decades, phytosterols have been established to provide a convenient, safe, and modestly efficacious adjunct to lipid-lowering therapies with reproducible effects.”

–Priya Pulipati, MD, University of Chicago Lipid Clinic

The need for effective statin alternatives to manage cholesterol is particularly acute at the primary care level. The American College of Cardiology recommends several non-statin therapies for cholesterol management, including plant sterols.

Sterols and stanols, which are basically the plant world’s analogue to cholesterol, competitively inhibit cholesterol absorption from intestinal micelles. Taken daily, they can lead to a 5-15% decrease in serum cholesterol within several weeks.

According to the FDA, foods containing at least 0.65 g per serving of plant sterol esters, eaten twice a day with meals for a total daily intake of at least 1.3 g, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease.

Dietary sources of plant sterols and stanols include green vegetables, whole grains, beans and legumes, nuts, and seeds. Olive oil, Sunflower oil, and other vegetable oils are also good dietary sources.

In the new case series, researchers at the University of Chicago’s Lipid Clinic looked at the potential impact of a novel chewable plant sterol supplement to lower elevated cholesterol in six moderate to high risk individuals. 

Developed by Piper Biosciences, this product was designed to provide practitioners with a clinical solution for their statin-intolerant patients, as well as for patients with elevated cholesterol who do not qualify for a prescription medication.

Priya Pulipati, MD, a preventive cardiology fellow at the University of Chicago,  and Michael Davidson, MD, Director of the university’s Preventive Cardiology program, documented changes in the lipid profiles of six patients taking daily packs of the sterol-containing gummies, providing 2.28 grams of plant sterol esters (1.4 grams of plant sterols) per day. The patients were instructed to take the supplements at meal time, twice daily.

These case studies showed impressive LDL-C lowering effects that exceed the more typical 5-15% reductions reported in larger studies and meta-analyses looking at the impact of plant sterols and stanols.

All of the patients in this case series showed clinically meaningful improvements in their lipid profiles.

• Patient 1 was a 72-year-old African-American female with a history of mitral valve prolapse and essential hypertension. Despite frequent counseling, the patient declined statins for over 10 years due to personal preference. Her estimated 10-year ASCVD risk score was 19%, representing intermediate to high risk. After 28 weeks of using the plant sterol supplement as monotherapy, her LDL-C decreased from 164 to 122 mg/dL, a 26% decrease.

• Patient 2 was a 30-year-old Caucasian female with parental history of early onset heart disease. Since the age of 23, she had tried multiple statins including the lowest dose of an alternate statin but experienced severe muscle side-effects prompting her to discontinue. By age 29, she was taking several OTC products (red yeast rice, L-methyl folate and krill oil), with no significant changes in her LDL levels, despite good compliance. The addition of the sterol gummies for 24 weeks, along with the other OTC products she was taking, yielded a 32% decrease in LDL-C (from 193 to 132 mg/dL).

• Patient 3 was a 64-year-old Asian male with no other medical co-morbidities. He was a non-smoker with no personal or family history of premature heart disease. After 6 weeks of chewable plant sterol therapy, while continuing to take a low-dose red yeast rice product, his LDL-C decreased from 203 (while taking red yeast rice alone) to 153 mg/dL–a 25% decrease.

• Patient 4 was a 66-year-old female with family history of heart disease. She had tried multiple statins over several years but experienced severe muscle side-effects that caused her to stop the drugs. She was started on ezetimibe 10mg daily with a reasonable LDL-C response (while on ezetimibe, LDL-C was 135 mg/dL). After the addition of the sterol supplement to her ezetimibe regimen, LDL-C decreased by an additional 12% after 30 weeks.

• Patient 5 was a 48-year-old Asian male without significant co-morbidities but with a family history of heart disease. He experienced non-specific muscular side-effects and cognitive impairment while taking statins, leading to discontinuation. The University of Chicago investigators started this patient on a combination of low dose rosuvastatin (5 mg daily), ezetimibe 10 mg daily, and chewable plant sterols, which reduced LDL-C from 182 to 53 after 16 weeks, a 71% decrease.

• Patient 6 was a64-year-old Caucasian female with a history of moderate aortic stenosis and essential hypertension, but no family history of premature heart disease. She tried and discontinued multiple statins due to severe muscular side effects. Her 10 year ASCVD risk score was 9.8%, representing intermediate risk. She began monotherapy with the sterol product, and after 72 weeks, her LDL-C improved from 156 to 122, a 22% decrease.

These case studies showed impressive LDL-C lowering effects that exceed the more typical 5-15% reductions reported in larger studies and meta-analyses looking at the impact of plant sterols and stanols.

This could be due to variability within a small sample size or to the adjunctive use of other treatments including OTC products (red yeast rice, folate, omega-3 supplements, etc), ezetimibe or low dose statins. Seen in that light, this case series does provide good examples of how healthcare providers can manage complex lipid cases through a combination of different modalities.

Palipati, Davidson and colleagues summarize the clinical indications for plant sterol therapy: “Patients with low to moderate ASCVD risk who do not qualify for pharmacotherapy, patients who decline pharmacotherapy, as an adjunct therapy in patients with high CVD risk with suboptimal LDL-C control on maximally tolerated lipid-lowering therapy especially in situations of statin and/or non-statin associated side-effects.”

They observed no side effects in these six cases, though they do note that potential side effects from plant sterols can include mild bloating, diarrhea, or constipation.

The authors conclude, “Over the last few decades, phytosterols have been established to provide a convenient, safe, and modestly efficacious adjunct to lipid-lowering therapies with reproducible effects. The evolving understanding of phytosterol function, metabolism, and interaction with patient-specific factors such as genetics has led to increased awareness and utility of this therapeutic option in clinical practice. Further research on the effects of phytosterols on cardiovascular outcomes is warranted.”

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