Cholesterol lowering margarine may not be useful in healthy fat modified diet
BMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7203.186 (Published 17 July 1999) Cite this as: BMJ 1999;319:186
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EDITOR- Non-pharmacological approaches, e.g. diet, increased physical
activity, constitute the first line treatment of elevated serum
cholesterol levels.
The main goals of dietary intervention are to lower
the intake of
saturated and transunsaturated fatty acids and dietary cholesterol, and to
increase the intake of dietary fibre. Weight reduction is recommended for
obese people and alcohol should be used in moderation. The cholesterol
lowering properties of plant sterols and plant stanol ester margarines are
well documented (1). Van Heyningen raised an important question of the
efficacy of stanol ester margarines when used as part of healthy fat
modified diet(2). His conclusion that these margarines may not be useful
in subjects following cholesterol lowering diet was based on Denke's study
(3).
Recently, we tested in a randomised controlled study the efficacy
of low-fat stanol ester margarine as part of cholesterol lowering diet in
55
subjects with slightly elevated serum total cholesterol levels(4). The
study included two low-fat stanol ester margarine groups (wood stanol
ester, vegetable oil stanol ester) and a control group (without added
stanols in
margarine).
During the first 4 weeks all three groups were on high-
fat diet (39.9-41.1 energy % from fat, 16.8-16.9 energy % from saturated
fatty acids), after that they followed for 8 weeks a low-fat, low-
cholesterol diet (fat
intake 25.6-26.5 energy %, saturated fatty acids 6.8-7.3 energy %).
The reduction in serum LDL cholesterol was 8.6-13.7% greater in the two
low-fat stanol ester margarine groups as compared to the control group;
the reductions
in serum LDL cholesterol were 23.6, 18.4 and 9.9% in wood stanol ester
margarine, vegetable oil stanol ester margarine and control margarine
groups, respectively, strongly indicating that these low-fat stanol ester
margarines offer an additional, clinically significant reduction in serum
cholesterol levels beyond that obtained with a low-fat diet alone.
Similar
results were obtained in another recent study using a sitostanol-
containing phytosterol mixture in hyperlipidaemic men on a prudent
diet(5). In our study the LDL cholesterol response to low-fat stanol
ester margarine was not dependent on the initial cholesterol level or the
main apolipoprotein E genotype groups. It is of note that the total
reduction of LDL cholesterol with a healthy diet and stanol ester
margarine is comparable to the effects of
many lipid-lowering drugs. Our view is that to achieve optimal
cholesterol-lowering effects with stanol-ester containing products, the
consumers should be counseled about the principles of healthy eating and
appropriate use of these new food products. In many persons with
moderately
elevated serum cholesterol levels fat modified diet with stanol ester
margarine can result in normalisation of LDL cholesterol.
Matti Uusitupa, M.D.
Professor of Clinical Nutrition and Metabolic Diseases
Maarit Hallikainen, M. Sc.
Nutritionist
1. Miettinen TA, Puska P, Gylling H, Vanhanen H, Vartiainen E.
Reduction
> of serum cholesterol with sitostanol-ester margarine in a mildly
> hypercholesterolemic population. N Engl J Med 1995; 333:1308-12
2. Van Heyningen C. Cholesterol lowering margarine may not be useful
in
> healthy fat modified diet. BMJ 1999; 319:186 (17 July 1999)
3. Denke MA. Lack of efficacy of low-dose sitostanol therapy as an
adjunct
> to cholesterol-lowering diet in men with moderate
hypercholesterolemia. Am
> J Clin Nutr 1995; 61:392-6.
4. Hallikainen MA, Uusitupa MIJ. Effect of 2 low-fat stanol ester
> margarines on serum cholesterol concentrations as part of a low-fat
diet
> in hypercholesterolemic subjects. Am J Clin Nutr 1999; 69: 403-10.
5. Jones PJH, Ntanios FY, Raeini-Sarjaz M, Vanstone CA.
> Cholesterol-lowering efficacy of a sitostanol-containing phytosterol
> mixture with a prudent diet in hyperlipidemic men. Am J Clin Nutr
1999;
> 69: 1144-50.
Competing interests: No competing interests
Editor-In his letter of July 17th Dr. Charles van Heyningen suggests
that the plant stanol ester-containing margarine, Benecol, may not lower
low density lipoprotein (LDL) cholesterol in subjects on fat modified
diets. He presents no evidence of his own for this assertion but cites a
study by Denke (1) which involved the administration of plant stanol in
gelatin capsules.
However, he fails to cite a more recent study where
plant stanol esters were dissolved in margarine and fed to subjects eating
a diet which provided only 26% of energy as fat and approximately 150 mg
of cholesterol daily (2). Reductions in LDL cholesterol in the 2 test
groups in this study were 8.6% and 13.7% respectively compared with
controls. In another recent study of subjects on a prudent diet plant
stanol dissolved in margarine lowered LDL cholesterol by 15.5% more than
did margarine without plant stanol (3).
As pointed out by Jones et al (3),
Denke's negative results probably reflect the fact that she administered
plant stanol in capsules instead of in margarine, which presumably
impaired its ability to inhibit cholesterol absorption in the small
intestine, rather than to it being given with a fat modified diet. Such a
diet has been shown to accentuate the extent to which LDL cholesterol is
lowered by Benecol, rather than the reverse (4).
Yours faithfully ,
Gilbert R. Thompson MD, FRCP
Emeritus Professor of Clinical Lipidology
References
1. Denke M.A. Lack of efficacy of low dose sitostanol therapy as an
adjunct to a cholesterol-lowering diet in men with moderate
hypercholesterolemia. Am.J.Clin.Nutr., 1995; 61: 392-396.
2. Hallikainen M.A. and Uusitupa M.I. Effects of 2 low-fat stanol ester-
containing margarines on serum cholesterol concentrations as part of a low
-fat diet in hypercholesterolemic subjects Am. J.Clin.Nutr., 1999; 69: 403
-410.
3. Jones P.J., Ntanios F.Y., Raeini-Sarjaz M. and Vanstone C.A.
Cholesterol-lowering efficacy of a sitostanol-containing phytosterol
mixture with a prudent diet in hyperlipidemic men. Am.J.Clin.Nutr.,1999;
69: 1144-1150.
4. Vessby B. Lipid-lowering effects of a stanol ester-containing margarine
when used as part of a strictly controlled lipid-lowering diet. Eur. Heart
J. Suppl. (in press).
Competing interests: No competing interests
Editor - We read with interest the letter by Dr Charles von
Heynsingen(1)suggesting that the plant stanol esters margarine
(BenecolTM) may not have a cholesterol-lowering effect in subjects
following a low-fat, low cholesterol diet. This conclusion is based on the
fact that in the landmark study with BenecolTM by Miettinen et al(2),
total fat intake (35% of calories), saturated fat intake (14% of calories)
and cholesterol intake (340 mg/day) were high. Furthermore, Dr van
Heynsingen cited one study that showed the lack of effectiveness of
sitostanol capsules in a group of men(3). Although it has been suggested
that the weak response may have been explained by a low dietary
cholesterol intake (<200 mg/dl), the sitostanol used in that study
was in an unesterified, crystalline, encapsulated form, in contrast to the
esterified stanols in a fat soluble form found in BenecolTM. This major
difference in the forms of stanols used may have explained the difference
in efficacy.
Indeed several studies have shown that the esterified form of
sitostanol is more efficient in lowering cholesterol than the crystalline
form (4 ,5) . This suggests that the process of esterification of plant
stanol and solubilization in a fat-soluble carrier is key in optimizing
the inhibitory effect on intestinal absorption not only of dietary
cholesterol but also of biliary cholesterol.
We have recently participated
in a multicenter study of the hypocholesterolemic effect of plant stanol
esters (BenecolTM) in a mildly hypercholesterolemic population of US men
and women. Preliminary results from our center at the Mayo Clinic (N=79)
showed that 3 g/d of plant stanol esters effectively reduced LDL-C by an
average of 14% in subjects following a lower total and saturated fat
intake (32% and 11% of calories respectively) as well as a lower
cholesterol intake (257 mg/day) than in most other studies .
Most
importantly, a recently published study (6)answered the question whether
plant stanols are effective in lowering cholesterol in the setting of an
even more restricted dietary cholesterol intake. In that study, subjects
had an average cholesterol intake of about 160 mg/d, total fat intake of
about 27% of calories, and saturated fat intake of about 7% of calories.
The data showed that 2.31 g/d of wood stanol esters containing margarine
significantly reduced total cholesterol by 10.6% and LDL-cholesterol by
13.7% compared to controls, in the setting of a diet similar to the
National Cholesterol Education Program (NCEP) step 2 diet.
These more recent data demonstrate that plant stanol esters can
effectively further lower total and LDL-cholesterol as part of a low fat,
low cholesterol diet.
Tu T. Nguyen M.D., Consultant in Endocrinology and Metabolism
Thomas E. Kottke M.D., Consultant in Cardiovascular Diseases and Clinical
Epidemiology
Mayo Clinic and Foundation
Rochester, Minnesota,
USA
References
1 Van Heynsingen C. Cholesterol lowering margarine may not be useful in
healthy fat modified diet BMJ 1999; 319: 186
2 Miettinen TA, Puska P, Gylling H, Vanhanen H, Vartiainen E. Reduction of
serum cholesterol with sitostanol-ester margarine in a mildly
hypercholesterolemic population. New England Journal of Medicine
1995;333:1308-12
3 Denke MA. Lack of efficacy of low-dose sitostanol therapy as an adjunct
to a cholesterol-lowering diet in men with moderate hypercholesterolemia.
American Journal of Clinical Nutrition 1995; 61:392-6
4 Vanhanen HT, Blomqvist S, Ehnholm C, Hyvonen M, Jauhiainen M, Torstila
I, Miettinen TA. Sitostanol ester in dietary oil reduces serum
cholesterol. Effect on serum plant sterols and cholesterol precursors. J
Lipid Res 1993;34:1535-44
5 Vanhanen HT, Kajander J, Lehtovirta H, Miettinen TA. Serum levels,
absorption efficiency, faecal elimination and synthesis of cholesterol
during increasing doses of dietary sitostanol esters in
hypercholesterolemic subjects. Clin Sci 1994; 87:61-7
6 Hallikainen MA, Matti Uusitupa MIJ. Effects of 2 low-fat stanol ester-
containing margarines on serum cholesterol concentrations as part of a low
-fat diet in hypercholesterolemic subjects Am J Clin Nutr 1999;69:403-10
Competing interests: No competing interests
Response
Editor,
It was interesting to read the responses referring to new studies
demonstrating that plant stanol ester margarines are effective
cholesterol lowering agents when used with lower fat and lower cholesterol diets.
The form of plant stanol used appears to be important in determining
efficacy. In the study by Hallikainen and Uusitupa (1) only the wood-based but not
vegetable oil-based stanols achieved significant lowering of LDL
cholesterol
after 8 weeks. There is likely to be a high degree of variability
between
subjects in response to therapy with functional foods. I agree with
the BMJ
editorial which points out a need for regulations on the advertising
of such
foods (2).
The British Dietetic Association has said that plant stanol ester
containing
products may have a place in lowering raised blood cholesterol, but
they
should not be viewed as ‘magic bullets’; the potential health
benefits of these
products must be kept in perspective, and affordability is another
important
consideration (3). A cover story article on eating smart for a
healthy heart in
Time magazine has recommended switching to a butter substitute, such
as
Benecol, that can boost good cholesterol (4). However most studies
report
no effect on good (HDL) cholesterol but show a reduction in bad (LDL)
cholesterol.
Two cholesterol lowering margarines have been made available in the
USA this year after approval by the FDA as foods. Concerns have been
expressed that they may decrease plasma antioxidant concentrations
and
increase plasma plant sterols. High plant sterol concentrations have
been
associated with premature coronary artery disease. These adverse
effects
may offset any benefits from cholesterol lowering (5). I therefore
believe that
some caution is called for in recommending the use of these
margarines for
the prevention of coronary artery disease.
Charles van Heyningen,
Consultant Chemical Pathologist,
Clinical Laboratories, University Hospital Aintree, Lower Lane,
Liverpool,
L9 7AL.
REFERENCES
(1) Hallikainen, MA and Uusitupa MIJ. Effects of 2 low-fat stanol
ester-containing margarines on serum cholesterol concentrations as
part of a
low-fat diet in hypercholesterolemic subjects. Am.J.Clin.Nutr.1999,
69, 403-10.
(2) Jacobson, MF and Silverlgade, B. Functional foods: health boon or quackery ? BMJ 1999, 319, 205-6.
(3) Benecol - New functional foods for the UK. Dietetics Today, May
1999, page 7.
(4) Lemonick, MD. Eat your heart out. Time, July 19, 1999, pages 54-
64.
(5) Cholesterol-lowering margarines. Med.Lett.Drugs.Ther. 1999, 41 (1055) 56-8.
Competing interests: No competing interests