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Fats bolster sterols’ heart benefits

The ability of sterols derived from plants (beta-sitosterol, campesterol and stigmasterol), also known as phytosterols, to alter blood lipids in humans has been known since the 1950s.1 Their structural similarity to cholesterol and the sharing of an intestinal transport protein is indicative of their ability to blunt intestinal absorption of cholesterol.2

The advent of novel methods of producing phytosterols (and their esters) has offered a new vista directed at diet-mediated modulation of blood lipids. However, the ideal forms in which phytosterols can achieve clinically meaningful results remain a keen area of investigation.

Because of their poor solubility in water and oil, their incorporation into foods has centred on margarine-like spreads. The commercially available spread Take Control delivers phytosterol esters, while Benecol incorporates stanol esters (hydrogenated phytosterols). An expert review asserted that both are likely to reduce total and LDL cholesterol equally, although stanol esters produce a greater average reduction.4

Evidence with different food-delivery formats incorporating phytosterols has suggested that a reduction of fat in the vehicle may attenuate lipid-lowering effects.5 These results contrast with the recent findings of a clinical trial evaluating a (nonfat) commercial orange juice (Minute Maid, Coca-Cola) incorporating phytosterols (apparently unesterified) in a suspension.6

Men and women with mildly elevated total cholesterol were randomised to receive either placebo or phytosterol-enriched (1g/240ml serving; 40% beta-sitosterol, 25% campesterol and 20% stigmasterol) juice, consumed with breakfast and dinner for 10 weeks. Total cholesterol dropped 6.3% while LDL cholesterol by 8.8% (incorrectly reported in the article as 7.2% and 12.4%, respectively). It is plausible the absence of any appreciable amount of fat in the orange juice/phytosterol emulsion was supplemented by the fat contribution from foods, as the diets derived almost 33% of calories from fat.

A more recent study found that four weeks of drinking an unesterified phytosterol-enriched (1.2g or 1.6g/day sterol composition) low-fat milk (1.5% fat, excluding sterols) with added vegetable oils (Omega Milk, Nestlé) induced 10.2% and 12.7% decreases in LDL cholesterol in hyperlipidaemic men and women, compared to baseline.7 A different study assessed the effect of three weeks of consuming phytosterol ester-enriched (50% sitosterol, 20% stigmasterol, 20% campesterol; 1.6g/day) foods: 2% fat milk (7g fat/day), muesli (7.9g fat/day), yoghurt (3.2g fat/day), or white bread (3.4g fat/day).8 Total cholesterol and LDL fell the greatest with milk (9.7% and 15.9%, respectively).

Pairing with bioactives
Phytosterol formulation strategies have included combinations of bioactives. The union of 8g soy protein isolate and 2g beta-sitosterol (Inpharma SA),9 blended into lowfat yoghurt and consumed before the daily main meal for 40 days, following a 40-day Step 1 American Heart Association diet, produced 6.2% and 11.6% drops in total and LDL cholesterol in hypercholesterolaemic males.10

Several caveats merit discussion. There are no published long-term studies with phytosterol intervention demonstrating reduction in cardiovascular disease risk, with some one-year studies showing an erosion of shorter-term lipid changes. 11 Supranormal concentrations of plasma phytosterols promote the development of premature atherosclerosis. Preliminary case-control data suggest that modestly elevated plasma beta-sitosterol increases the risk of coronary events by 1.8-fold. 12 Because ingestion of phytosterols can lead to substantial increases in plasma phytosterols, 4,11 and statin drugs alone can augment gut phytosterol absorption, long-term safety is unknown. 13

Anthony Almada, MSc, is president and chief scientific officer of IMAGINutrition Inc. Respond:

1. Pollak OJ. Reduction of blood cholesterol in man. Circulation 1953; 7:702-6.
2. Davis HR, Jr., et al. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J Biol Chem 2004; 279:33586-92.
3. Ostlund RE, Jr. Phytosterols in human nutrition. Ann Rev Nutr 2002; 22:533-49.
4. Katan MB, et al. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 2003; 78:965-78.
5. Davidson MH, et al. Safety and tolerability of esterified phytosterols administered in reduced-fat spread and salad dressing to healthy adult men and women. J Am Coll Nutr 2001; 20:307-19.
6. Devaraj S, et al. Plant sterol-fortified orange juice effectively lowers cholesterol levels in mildly hypercholesterolemic healthy individuals. Arterioscler Thromb Vasc Biol 2004; 24:25-28.
7. Thomsen AB, et al. Effect of free plant sterols in low-fat milk on serum lipid profile in hypercholesterolemic subjects. Eur J Clin Nutr 2004; 58:860-70.
8. Clifton PM, et al. Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal. Eur J Clin Nutr 2004; 58:503-9.
9. Festo N. Dietary hypocholesterolaemic compositions comprising soya proteins and sitosterols. 1998, European patent 0 669 835.
10. Cicero AFG, et al. Effects of a new low dose soy protein/?-sitosterol association on plasma lipid levels and oxidation. Eur J Nutr DOI 10.1007/s00394-004-0478-y (in press).
11. Miettinen T and Gylling H. Plant stanol and sterol esters in cardiovascular diseases. Ann Med 2004; 36:126-34.
12. Assmann G, et al. Elevation in plasma sitosterol concentration is associated with an increased risk for coronary events in the PROCAM study. American Heart Association Scientific Sessions, November 2003, Abstr. 3300/P703.
13. Miettinen T, et al. Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins. J Lab Clin Med 2003; 141:131-7.

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