Cholesterol-lowering Sterols and Stanols

Sterols and stanols have a function in plants rather like cholesterol in humans. Stanols are saturated and sterols are not. A high intake of these substances impairs uptake of cholesterol from the gut. They reduce total and LDL cholesterol but have little or no effect on HDL cholesterol or triglycerides. They are most effective when taken with food.

They are ubiquitous in the plant world and are produced commercially to add to food .They are available commercially under various trade names, e.g. Benecol^TM andFlora Pro Active^TM. They are usually sold in the form of margarine but can occur in other forms like yoghurt. Rich natural sources include rice bran, avocado oil, original wheat germ and extra virgin olive oil.

The evidence shows that there is considerable variation between individuals in response to stanols and sterols.^1,2 They do tend to reduce LDL cholesterol and the effect is dose related. In general terms the reduction is between 10 and 20%. Two meta-analyses reported in Bandolier confirmed that 2g per day of stanols and sterols reduce LDL cholesterol by about 10%, or 0.3 to 0.5 mmol/L. This reduction should lower the risk of coronary heart disease (CHD) by about 25%.³

They have to be esterified or in emulsion form to have their full effect. This can make interpretation of the literature, especially some of the early work, very difficult as different forms are used. Another variable is the background diet. Some of the early work used vegetarians and found no significant change but vegetarians have a higher level of sterols in their diet than omnivores.⁴ Much of the early work was conducted on people with normal cholesterol. More recent work has found similar results in people with hypercholesterolaemia. In a recent study of 72 people with mildly raised cholesterol, taking 2g a day of sterol in orange juice reduced LDL cholesterol by an average of 12.4% over 8 weeks.⁵

The literature is very difficult to interpret because of a number of factors:

• The natural day to day variation in fasting lipids is up to 10% with significant variation for HDL cholesterol and triglycerides. A small decrease may thus be masked and yet offer very significant benefit.^6,7 A true reduction in LDL cholesterol of 10% is a very worthwhile achievement, reducing the risk of CHD by 50% at age 40, falling to 20% at age 70.
• There are many sources of stanols and much variation in bioactivity in terms of ability to impair cholesterol absorption. Therefore, even studies that state the number of grams per day of sterols may be meaningless in terms of comparing like with like, particularly when one adds the variation in normal dietary intake to the equation.. Many studies, especially the early ones, used quite small numbers. Therefore, although meta-analysis may seem appropriate, the variation in source of stanols may make the results invalid.
• Systematic reviews do seem to suggest a general trend that shows that stanols and sterols do reduce LDL cholesterol in people with normal and moderately raised cholesterol and that this effect is related to dose. They are also effective in reducing LDL cholesterol in more severe cases as in familial hypercholesterolaemia, including homozygous individuals.⁸
• The advent of powerful statins has led to neglect of dietary manipulation but sterols can be used in addition to statins to gain maximal effect.⁹ Although the response is dose dependent, the dictum of the more the better does not necessarily seem to apply. A diet containing over 1g a day of free sterols in full esterified or emulsion form seems to be the threshold and a higher intake is probably not deleterious but offers little further benefit.¹⁰
• It is likely that the ideal dose is about 0.8 to 1.0g a day of free sterol equivalent, in optimum form, taken with food in 2 or 3 servings but at this level not everyone will achieve a 5% reduction in LDL.¹¹

Sterols have been shown to have a beneficial effect in terms of prevention of cancer, especially carcinoma of colon, carcinoma of breast and carcinoma of prostate.¹² Not all studies have reported positive results and a number are based on samples of animals given carcinogens. Sterols appear to have antioxidant properties that would account for benefit with regard to both cancer. and atheroma.
There is some evidence that sterols have beneficial effects on the inflammatory response in HIV, stress induced immune suppression, rheumatoid arthritis, and allergic rhinitis.¹³ Much of the work has been based on animal studies.
There may be an antifungal effect.¹⁴ Sterols may even protect against peptic ulcer disease, even in areas with a high prevalence of Helicobacter pylori.¹⁵

Although sterols are natural products ubiquitous in food, their safety cannot be assumed.

• The ability to lower cholesterol is similar in both men and women but women seem to be much more susceptible to stanols causing impairment of the absorption of fat soluble vitamins.
• The greatest effect is on carotenoids but deficiency can be made up by increasing dietary intake.¹⁶
• Sterols are not recommended for pregnant or lactating women or for children under five. This both because of the fetotoxic effects of carotenoids and because the developing brain needs cholesterol.
• Sitosterolemia is a rare autosomal recessive inherited disorder which is known to be associated with high maternal absorption of plant sterol and cholesterol. It results in CHD at an early age.¹⁷

With such complexity it is dangerous to be dogmatic in terms of advice to patients. Sterols and stanols occur in a normal diet but there does seem to be good evidence that increasing the amount in the diet will reduce the risk of CHD and possibly some types of cancer. Food products that contain sterols are quite significantly more expensive than others and the extra cost of choosing them to obtain an adequate intake of stanols is probably around ?70 a year. To many people this is a small price to pay for a reduction of CHD risk that may be up to 25%.
Notwithstanding the cautions concerning pregnancy, lactation and children under five, stanols and sterols would seem to be a very valid addition to the changes in life style that are a benefit to health. The amount to recommend to take is very difficult. Bearing in mind the low incidence of adverse effects and the fact that not all sterol is in active form, the recommended dose of 0.8 to 1.0g is probably too low. 2 to 2.5g a day may be better.¹⁸