Plant Sterols - A Metabolically Active Medicine

Part I: Cholesterol

Plant sterols and stanols, also known as phytosterols, are a class of steroid-like molecules naturally found in plants such as vegetables, nuts, and vegetable oils.^[1] Over 200 plant sterols have been identified; some of the most commonly occurring plant sterols include beta-sitosterol, campesterol, and stigmasterol.^[2] Plant sterols are structurally similar to human cholesterol, and as such they are able to modulate its absorption and metabolism in the body.^{[1, 3]} They are also postulated to possess a variety of anti-inflammatory and possible hormone-modulating effects. The majority of this article will focus on applications relating to cholesterol, including current cholesterol guidelines, while the remaining section will summarize use in the area of prostate health.

The language used in guidelines of major medical associations has been slowly inching towards the suggestion that virtually every person on the planet will benefit from taking a statin (a class of prescription medications whose primary purpose is to lower LDL-cholesterol or “bad” cholesterol).^[4] Such a view is not shared by all, and eloquent discussion questioning the use of such medications has been widely published.^[5] Current guidelines of the American Heart Association have identified “four statin-benefit groups”, and recommendations are as follows.^[4]

1. All individuals with established cardiovascular disease should be prescribed a statin medication.
2. Otherwise healthy individuals with a LDL C level greater than 5.0 mmol/L should be prescribed a statin.
3. Individuals with diabetes ages 40–75 with an LDL C level greater than 2.0 mmol/L should be prescribed a statin.
4. All individuals with an estimated 10-year risk of heart disease of 7.5% or greater (Framingham Risk Score) and an LDL C level greater than 2.0 mmol/L should be prescribed a statin.

While the use of statin medications among individuals who have survived a heart attack is generally accepted as appropriate (point “1” above), the general application of statins across the other three groups described deserves scrutiny. A number of diet-and lifestyle-based approaches exist that are highly effective at lowering cholesterol levels, and deliver the added benefit of lowering disease risk even further through their simultaneous effects on blood pressure, body weight, blood glucose control, etc. Plant sterols offer a nonpharmaceutical strategy to help achieve blood cholesterol levels in line with current recommendations, and their impact on cholesterol management is the focus of this article.

Plant Sterols - A Metabolically Active Medicine
Part II: Functional Foods

In part I we reviewed recommendations for cholesterol management. Plant sterol–enriched foods have been shown to effectively lower blood cholesterol levels. With this in mind, Health Canada has approved health claims for a number of foods enriched with plant sterols.^[1] Such items are called “functional foods.” Specific foods included in this group are various spreads, mayonnaise, margarine, calorie-reduced margarine, salad dressing, yogurt and yogurt drinks, and vegetable and fruit juices.^[1] While approximately 2–3 g plant sterols are considered a “therapeutic dose” based on existing research, some functional foods may contain up to 1 g per serving. Use of plant sterols has been shown to reduce LDL cholesterol by approximately 10%.^[1] With respect to safety when consumed by the population at large, Health Canada states that there are no concerns with consumption of up to 3 g in adults, and up to 1 g in children.^[1] Patients on cholesterol-lowering medications who wish to use plant sterol–containing functional foods are advised to inform their physician; however, it seems unlikely that any adverse interactions would be anticipated. A number of studies have demonstrated additive beneficial effects from use of plant sterols in combination with statins, the most common class of cholesterol medication. A systematic review and meta-analysis combined data from eight randomized controlled trials assessing the combined effects of plant sterols and statin medication.^[2] Collectively, these studies showed that the combination lowered total cholesterol an average of 14.01 mg/dL and LDL cholesterol by 13.26 mg/dL.^[2] In patients with diabetes, already on statin therapy, the addition of a vegetable oil spread containing 3 g per day plant sterols resulted in better reductions in total cholesterol as well as LDL-cholesterol compared to statin therapy alone.^[3] After four weeks, total cholesterol was reduced by 9.6% in the plant sterols plus statins group, compared to 7.8% in the statin-only group; LDL cholesterol decreased by 16.4% in the plant sterols plus statins group, compared to 14.8% in the statin only group.^[3] Finally, in another study of 54 patients already on stable statin therapy, the addition of a margarine containing either 2.5 g plant sterols or 2.5 g plant stanols was shown to reduce LDL-cholesterol by 8.7% and 13.1% after 85 weeks.^[4] It appears that supplementation with plant sterols or stanols in the form of functional foods can have an important role and sizeable effect in the achievement of healthy cholesterol levels. In subsequent parts of this series, we will examine the use of plant sterols as a natural health product, as well as lesser-known effects on the prostate.

Plant Sterols - A Metabolically Active Medicine
Part III: Plant Sterol Supplementation

In part II we reviewed the role of plant sterol–enriched functional foods. Unfortunately, many of these foods are highly processed, such as fortified margarines and salad dressings. For individuals who wish to benefit from the cholesterol-lowering effects of plant sterols without the trans fats and other byproducts of processed foods, supplementation in the form of a pill or capsule is the alternative. A cholesterol blood test consists of five markers, including total cholesterol, low-density cholesterol (LDL, bad cholesterol), high-density cholesterol (HDL, good cholesterol), triglycerides, and the ratio of total cholesterol to HDL. A wealth of scientific data has shown that supplementation with approximately 2 g plant sterols can lower LDL-cholesterol (“bad cholesterol”) by between 10 and 15%.^{[1, 2, 3]} There is also evidence suggesting that plant-sterol supplementation can also lower triglycerides by a small amount of about 6%.^[4] A 2013 review and meta-analysis evaluating plant-sterol supplementation in the form of a capsule found that use of between 1 and 3 g plant sterols per day with meals (2–3× per day) led to a decrease in LDL cholesterol of 12 mg/dL (0.31 mmol/L), and that this was similar to effects achieved through use of functional foods.^[5] The mechanism of action for plant sterols’ effects on cholesterol appears to be their ability to interfere with cholesterol absorption in the gut.^[1] Plant sterols appear to compete with cholesterol for incorporation into the emulsified micelles that are then absorbed into the cells lining the intestine.^[1] More recently, the process of transintestinal cholesterol excretion (TICE) has been discovered.^[1] In this process, there is direct secretion of cholesterol from the bloodstream back into the intestine for excretion, and this has been demonstrated in animals.^[1] Plant sterols appear to activate this pathway, providing another mechanism for the cholesterol-lowering activity of plant sterols. Since plant sterols interfere with uptake of dietary cholesterol, they need to be consumed simultaneously with meals in order to be effective. Consumption of 500 mg three times daily with each meal is often recommended for cholesterol lowering.

Plant Sterols - A Metabolically Active Medicine
Part IV: Benefit for the Prostate?

In addition to cholesterol lowering, a lesser-known but similarly science-based application of plant sterols is in the area of prostate health. Benign prostatic hypertrophy (BPH), or “enlarged prostate,” is a condition affecting over 50% of men over the age of 50, with symptoms including difficulty urinating, weak stream, urinary frequency, and waking at night to urinate. These symptoms are a result of the enlarged prostate placing increased pressure on the bladder and the urethra. BPH is caused in part by the effects of dihydrotestosterone (DHT), a highly active metabolite of testosterone produced by the enzyme 5 alpha reductase. In fact, finasteride, the front-line pharmaceutical treatment for BPH, is an inhibitor of this enzyme. Animal studies show that beta-sitosterol also possesses the ability to inhibit 5 alpha reductase.^[1] Of course, the elegance of natural medicines is that these agents are not limited to a single mechanism; in a model of chronic prostatitis, administration of plant sterols was able to reduce levels of proinflammatory cytokines including IL 1beta, TNF alpha, as well as prostate expression of proinflammatory COX 2 and 5 LOX enzymes.^[2] Interestingly, the activity of the well-known and extensively researched herb, saw palmetto, on improving BPH has been attributed in part to its phytosterol content.^[3] Human studies confirm these effects. A literature review published by the Cochrane Library assessed data from 519 men taking part in four randomized, placebo-controlled, double-blind trials of beta-sitosterol for BPH.^[4] Overall, the review found that beta-sitosterol improved urinary symptom scores and flow measures. There were also improvements in peak urine flow, residual volume, but not prostate size. One of the largest studies was conducted in Germany, including 200 patients treated with 60 mg per day beta-sitosterol or placebo for six months.^[5] Patients receiving beta-sitosterol experienced approximately threefold greater improvement in prostate symptoms compared to the placebo group, measured as the modified Boyarsky score and the International Prostate Symptom Score. There was also an improvement in urine-flow parameters, though not in prostate size. Other studies have used higher doses, up to 130 mg per day, and shown similar improvements.^[6]