Phytosterols are known as one of the most effective nonpharma solutions to control elevated cholesterol levels. But which phytosterol form is the most effective at lowering cholesterol? And what other health benefits can these botanicals afford the consumer? Mark J Tallon, PhD, investigates
Some of the buzz products (at least in European markets) over the past few years have been phytosterol-fortified margarines, milks, yoghurts and cereals that lower cholesterol. According to Frost and Sullivan, the sterol market has an estimated worth of $184.6 million, which will double to $395.2 million by 2012.1 This growth is set to expand globally with food fortification outside of margarines now accepted by many countries including Australia and New Zealand.
Global acceptance of sterols by food and beverage markets is in no small part due to the diligent work carried out by research scientists investigating cardiovascular disease. However, even though its success has in many ways pigeonholed sterols, novel research into new areas is beginning to break these barriers and will be discussed further in this article. Although the education job behind sterols has been good, some confusion exists with the relative health benefits among sterols, stanols and ester-bound phytosterols. Before moving onto the latest studies, it may be helpful to clear up these misconceptions.
Phytosterols are generally delivered in two forms (sterols and stanols), and from two primary sources (tall oil and soybean oil).2 Stanols are produced by hydrogenating sterols, but the products related to phytosterols don't just stop there. Because fats are needed, solublilised-sterol food sources such as margarines were an excellent delivery system. However, the advent of low-fat sterol/stanol-fortified cereals has led to the esterification application to overcome the issue of solubility (addition of long-chain fats to enhance solubility). But is there a difference in bioavailability and effectiveness between esterified phytosterols and those delivered in free form?
In 2002, research from Brandeis University (Switzerland) helped answer these questions regarding the effectiveness of free vs ester-based phytosterols.3 The study compared the effects of free phytosterols, sterol esters and stanol-ester supplementation on cholesterol. The results showed that all three sources of phytosterols equally reduced plasma cholesterol levels (circa 50 per cent), and discovered no difference in their abilities to lower cholesterol. Some interesting issues this raises include the influence phytosterol particle size and dispersal rate play within the gut, and whether the additional time for hydrolysis of ester forms of phytosterols influences activity within the gut. These issues are still unanswered within the literature and may offer future approaches for novel IP and product development.
Cardio and beyond
Phytosterols are thought to act by displacing dietary cholesterol in gut micelles, thereby inhibiting free cholesterol absorption through the gut.4 Although this has been known for some time, more recent work has begun to show additive and synergistic effects when added to other nutrients and pharmaceuticals, and in conjunction with exercise. The following is an overview of these issues and new links to phytosterol health benefits exceeding that of cholesterol metabolism.
Exercise has previously been shown to favourably influence blood-lipid and cholesterol levels.5 However, little evidence exists regarding the combination of exercise and phytosterols. Recent research has attempted to address these issues by studying the effect of nine weeks of plant stanol-fortified and non-fortified margarine.6 During the last four weeks of margarine supplementation, participants expended 400kcal on a treadmill five days a week (2,000kcal/week).
The sterol group experienced a decrease in total cholesterol (-10 per cent), LDL cholesterol (-13 per cent), and triglyceride (-18 per cent) concentrations after four weeks; the placebo group had no change.6 Additionally, four weeks of aerobic exercise increased HDL cholesterol (HDL-C) by 21 per cent in the placebo group and by four per cent in the stanol group. The total cholesterol:HDL-C ratio decreased significantly in the stanol group, but not in the placebo group. These findings confirm that stanols and exercise are effective in reducing blood cholesterol and that supplementation may further attenuate the exercise-induced increase in HDL-C.
Statins are currently estimated at a global revenue of $22 billion and are the most-used pharmaceutical solution to hypercholesterolaemia.7 As previously mentioned, phytosterols have a similar action of cholesterol reduction. In recent years pharma is becoming more interested in combining nutraceutical applications to enhance their mechanism of action. In a recent study, researchers investigated the effect of plant sterols in patients already receiving a maximal dose of statins yet still not reaching target lipid levels.8 The control group was taking optimal doses of statins and received margarine without plant stanols and dietary advice. Both groups had cholesterol levels measured pre- and post-intervention.
In the plant-stanol group, LDL cholesterol decreased significantly by 15.6 per cent compared with a reduction of only 7.7 per cent in the control group. This demonstrates that dietary intervention with plant stanols results in a clinically relevant reduction of LDL cholesterol in patients optimally treated with statins, showing a clear additive/complementary effect beyond traditional statin therapy.
Weight loss is one of the largest markets in the natural-products industry, accounting for more than $1.9 billion per annum in the US alone.9 The weight-loss market is driven largely by novel ingredients; in 2006 a study examined the effects of the phytostanol analogue, disodium ascorbyl phytostanyl phosphate (DAPP), on energy homeostasis, body weight and intestinal energy absorption.
For five weeks, experimental diets varying in cholesterol and phytostanol content were given and included (1) noncholesterol (diet without added cholesterol); (2) cholesterol control (diet with 0.25 per cent cholesterol); (3) stanol (cholesterol-control with one per cent free phytostanols); (4) DAPP 0.7 per cent (cholesterol control with 0.71 per cent DAPP); or (5) DAPP 1.4 per cent (cholesterol control with 1.43 per cent DAPP).10
Those fed 1.4 per cent DAPP gained less weight than those fed noncholesterol and stanol diets. Diets had no effect on total food consumption or gross energy intake after five weeks, but lower weekly food consumptions in the 1.4 per cent DAPP group were observed at weeks one and two of the experiment.
In comparison to noncholesterol and cholesterol-control diets, DAPP 1.4 per cent increased faecal energy output by 47 and 46 per cent, respectively. In conclusion, stanol ascorbate (DAPP) decreases body-weight gain, likely due to lower energy absorption at the intestinal level, but longer trials specific to DAPP supplementation in humans are needed to fully understand any anorexic influence of this stanol analogue.
Cancer. Cancer-related disease states, although declining, are still responsible for 22 per cent of all US deaths, according to the Centers for Disease Control, and are the nation's second-leading cause of death.11 It has been suggested excessive free radical and oxidative stress can increase the incidence of cancerous cells.
Cocoa contains many different types of physiologically active components, including antioxidants such as flavonoids, catechins, epicatechins and proanthocyanidins. Additionally, beta-sitosterol (the most common phytosterol) may play a protective role in the development of cancer. The aim of one study was to evaluate the inhibitory effect of different concentrations of cocoa polyphenols, alone or combined with beta-sitosterol, on two human prostate cancer cells and normal human prostate cells.12
At the highest-tested concentration, cocoa polyphenol extracts induced a complete inhibition of growth of metastatic and nonmetastatic cancer cell lines. Moreover, at the highest-tested concentration, cocoa polyphenols extracts had no effect on normal prostate cell lines. Beta-sitosterol induced low-growth inhibition of both cancer-cell lines. Cocoa polyphenols extracts, however, were significantly more active, and showed a stronger and faster inhibition of cell growth than beta-sitosterol alone. These results show that cocoa polyphenols extracts have an antiproliferative effect on prostate cancer cell growth but not on normal cells with similar but lower levels of growth inhibition from beta-sitosterol. Clearly this in vitro work is just the beginning, and in vivo work is needed to confirm the anti-cancer properties of cocoa polyphenols and sitosterols.
Applications for the sterol market are changing and expanding into new fields emanating from novel research that goes beyond that of the traditional cholesterol domain. Weight loss, cancer, novel phytosterol forms and pharma-friendly combinations are likely to help keep the phytosterol market growing for the foreseeable future.
1. No author. Strategic analysis of the European phytosterols market. Frost and Sullivan research services.2006.
2. Conner AH, et al. Microbial conversion of tall oil sterols to C19 steroids. Appl Environ Microbiol.1976;32(2):310-1.
3. Hayes KC, et al. Free phytosterols effectively reduce plasma and liver cholesterol in gerbils fed cholesterol. J Nutr 2002; 132(7):1983-8.
4. Nissinen M, et al. Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion. Am J Physiol Gastrointest Liver Physiol 2002;282(6):G1009-15.
5. Thompson PD, et al. Acute effects of prolonged exercise on serum lipids. Metabolism 1980;29(7):662-5.
6. Alhassan S, et al. Blood lipid responses to plant stanol ester supplementation and aerobic exercise training. Metabolism 2006; 55(4):541-9.
7. No author. Statins and the anti-cholesterol market, market report. Lead Discovery Ltd. United Kingdom. 2004.
8. Castro Cabezas M, et al. Effects of a stanol-enriched diet on plasma cholesterol and triglycerides in patients treated with statins. J Am Diet Assoc 2006;106(10):1564-9.
9. No author. Weight control - US market report. Mintel International Group Ltd. USA0. 2005.
10. Ebine N, et al. Plant stanol ascorbate esters reduce body weight gain through decreased energy absorption in hamsters. Int J Obes (Lond) 2006; 30(5):751-7.
11. US Cancer Statistics Working Group. United States cancer statistics: 1999-2002 incidence and mortality Web—based report version. Atlanta: Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2005. Available at: www.cdc.gov/cancer/npcr/uscs/.
12. Jourdain C, et al. In-vitro effects of polyphenols from cocoa and beta-sitosterol on the growth of human prostate cancer and normal cells. Eur J Cancer Prev 2006;15(4):353-61.
Mark J Tallon, PhD, is chief science officer of OxygeniX, a London-based consultancy firm specialising in claims substantiation, product development and technical writing. www.oxygenix.com Dr Tallon is also co-founder of Cr-Technologies, a raw-ingredients supplier. www.cr-technologies.net Respond: [email protected]