PIPER LDL (PLANT STEROL ESTERS 1.14 G): Information for Healthcare Providers

Summary: Plant Sterols

From the 2016 American College of Cardiology Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering (1)

Mechanism of action: Not fully elucidated, but in part related to displacement of cholesterol from the micellar phase. Phytosterols decrease cholesterol content of micelles and hence reduce its transport towards the intestinal brush border membrane. May also interfere with transporter-mediated processes of cholesterol uptake via NPC1L1 protein and ABCG5 and ABCG8 transporters (1)

FDA-approved claims: Foods containing at least 0.65 g per serving of plant sterol esters, eaten twice a day with meals for a daily total 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 by lowering blood cholesterol (1,2)

Dose and route of administration: 1-3 g PO per day consumed with meals either once daily or in divided doses

Mean % LDL-C reduction: Consumption of 2 g/day of phytosterols reduces LDL-C by 5%–15%. LDL-C reduction plateaus at doses above ∼3 g/day (1)

Adverse effects: Phytosterol esters have "generally recognized as safe" (GRAS) status in the US. Potential safety concern regarding phytosterol consumption in patients with phytosterolemia. Side effects may include mild bloating, diarrhea, or constipation (1)

Drug–drug interactions: Bile acid sequestrant administration should be separated from phytosterol use by 2-4 hours to avoid binding of the latter in the gut (1)

CV outcomes trials: The effect of phytosterols on cardiovascular morbidity and mortality has not been determined (1)

Summary: PIPER LDL Healthy Cholesterol* Gummies (plant sterol esters 1.14 g)

Recommended patient selection: 1) patients with elevated cholesterol in whom statins are not indicated, 2) patients taking statins, as an adjunct to achieve LDL-C targets or 3) patients who are statin intolerant

Medical guidelines: Plants sterols have been recommended by the American College of Cardiology (1), National Lipid Association (3), American Diabetes Association (4), European Society of Cardiology (5), European Atherosclerosis Society (5,6), and the National Institutes of Health (National Cholesterol Education Program ATP III) (7). Plant sterols are also in the treatment guidelines for familial hypercholesterolemia

Dosing: 2 chewable gummies twice a day around meal time. Each daily pack provides 4 gummies for a daily dose of 2.28 grams of plant sterol esters (or 1.4 grams of plant sterols)

Manufacturer: Piper Biosciences was founded by a Stanford School of Medicine professor and is advised by leading preventive cardiologists. Each lot is third party tested. PIPER LDL is used clinically at top academic lipid centers, and over 2000 healthcare provider offices across the country

Patient samples: Please fill out our samples request form to request patient samples for your office

Read how our product is being used clinically (case report from Univ. of Chicago Lipid Center)

What are plant sterols?

Plant sterol supplementation is commonly recommended by physicians to lower cholesterol* and is part of the treatment guidelines of American College of Cardiology (1), National Lipid Association (3), American Diabetes Association (4), European Society of Cardiology (5), European Atherosclerosis Society (5,6), and the National Institutes of Health (National Cholesterol Education Program ATP III) (7). Plant sterols are present in small amounts in vegetable oils, nuts, fruits and vegetables. According to the US National Institutes of Health, consuming ~2 g/day of plant sterols, as part of a healthy diet, can lower LDL- C levels by 5-15%, within several weeks (8).

Plant sterols are ubiquitous in plant-based foods. In a normal Western diet, the average daily intake of plant sterols is about 300 mg, but can be as high as 600 mg in vegetarians (6). Since it is unlikely that patients can ingest the recommended 2 grams of plant sterols solely through food, medical societies recommend plant sterol supplements. According to the U.S. Food and Drug Administration (FDA): Products containing at least 400 mg of plant sterols per serving, eaten twice a day with meals for a daily intake of at least 800 mg as part of a diet low in saturated fat and cholesterol may reduce the risk of heart disease by lowering blood cholesterol (2).

How do plant sterols reduce cholesterol?

Similar to soluble fiber, plant sterols help block the re-absorption of cholesterol in the small intestine. This can reduce LDL (bad) cholesterol by 5-15% while not affecting HDL (good) cholesterol or triglyceride levels (8).

According to the National Lipid Association (3):

"One mechanism by which [plant sterols] lowers LDL-C is reducing intestinal cholesterol absorption by competing with cholesterol for limited space in mixed micelles. This makes less cholesterol available to the enterocytes for transport via Niemann-Pick C1-Like 1 transporters. A second mechanism is that an increase in the intracellular level of [plant sterols] in the enterocytes triggers an up-regulation of adenosine triphosphate-binding cassette transporter (ABC) G5 and ABCG8 that move sterols (including cholesterol) out of the enterocytes and into the intestinal lumen. The net result of these actions is to reduce hepatic cholesterol content, which then results in an up-regulation of hepatic LDL receptors that remove apo B-containing lipoproteins from the blood, thus lowering the blood cholesterol concentration, particularly LDL-C."

Are plant sterols a drug? Are they regulated by FDA?

Plant sterols are not a drug. They are classified as a dietary supplement by the FDA when they are marketed with an FDA-authorized claim about the link between plant sterols and the risk of heart disease. Plant sterols have been used clinically for over 60 years. From the 1950’s to 1980’s, drug maker Lilly marketed Cytellin, a plant sterol formulation to treat hypercholesterolemia. More recently, plant sterols have been made available as a dietary supplement in the United States and FDA mandates manufacturers produce these supplements in accordance with current Good Manufacturing Practices. Plant sterols and stanols are one of the rare categories of supplements in which FDA allows disease-related efficacy claims. According to FDA: "Products containing at least 400 mg of plant sterols per serving, eaten twice a day with meals for a daily intake of at least 800 mg as part of a diet low in saturated fat and cholesterol may reduce the risk of heart disease by lowering blood cholesterol (2)."

Which medical societies recommend plant sterols?

American College of Cardiology, 2016
2016 ACC Expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk. Journal of the American College of Cardiology 2016; 68.

American Diabetes Association, 2016
Standards of Medical Care in Diabetes. Cardiovascular Disease and Risk Management. Diabetes Care 2016; 39.

National Lipid Association (USA), 2015
National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2. Journal of Clinical Lipidology 2015;9.

European Atherosclerosis Society, 2014
Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Consensus statement of the European Atherosclerosis Society. Atherosclerosis 2014; 232.

National Cholesterol Education Program ATP III, (National Institutes of Health), 2001
Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)

How well do plant sterols work? How many studies have been published?

According to the United States NIH (8):

“As with soluble fiber, plant stanols and sterols help block the absorption of cholesterol from the digestive tract, which helps to lower LDL—without affecting HDL or triglycerides. Studies show that a daily intake of about 2 grams of either stanols or sterols reduces LDL cholesterol by about 5–15 percent—often within weeks.”

According to the National Lipid Association (3):

“There is a large evidence base supporting the LDL-C-lowering effect of [plant sterols], which has been summarized in multiple meta-analyses. The meta-analyses conducted by Law et al. and Katan et al. were the first to examine the effects of [plant sterols] on cholesterol levels…More recently Musa-Veloso et al. conducted the largest meta-analysis on [plant sterol] consumption, which included 114 trials representing 182 trial arms and evaluating LDL-C lowering dose-response effects separately for plant sterols and plant stanols.”

Which patients are candidates for plant sterols?

According to the National Lipid Association (3), plant sterols can be integrated into the lifestyle therapies recommended to patients with low or moderate cardiovascular risk. Other lifestyle therapies include reducing saturated fat intake, increasing intake of soluble fiber, etc.

According to the European Atherosclerosis Society (6): “Plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high-risk patients who fail to achieve LDL-C targets on statins or are statin-intolerant.”

How much plant sterols does this product contain?

One pouch of this product provides 4 gummies which supplies a total of 1.4 grams/day of plant sterols (from 2.28 grams/day of plant sterol esters). The patient should be encouraged to eat a heart-healthy, plant-based diet which will provide additional plant sterols to achieve the 2.0 grams per day target.

What are the ingredients?

Active Ingredient: Plant Sterol Esters (1.14 grams per serving)

Other Ingredients: Organic Tapioca Syrup, Organic Raw Cane Sugar, Water, Pectin, Citric Acid, Natural Flavors, Sodium Citrate, Fruit and Vegetable Colors (Grape, Carrot, Apple, Elderberry Concentrates), Organic Sunflower Oil, Organic Carnauba Wax.

Who is Piper Biosciences?

Piper Biosciences is a California-based company that has strong academic ties through its founder and through its advisory group of world-renowned preventive cardiologists. Piper Biosciences was founded by a professor at Stanford University School of Medicine who sought to create nutritional products focused on metabolic health, based on the medical guidelines.

How do I prescribe?

If you are a healthcare provider, please fill out our samples request form. We may be able to provide samples for your patients.

Other questions?

References