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Friday, August 9, 2013

British Heart Foundation does not want to engage with the troubling science on sterols - Briffa

The medical director of the British Heart Foundation does not want to engage with the troubling science on sterols

Last month, I wrote a blog post about how there was no evidence that cholesterol-lowering ‘stanols’ and ‘sterols’ (found in some margarines and other ‘functional foods’) have benefits for health. In fact, the National Institute for Health and Care Excellence explicitly states that they should not be used. Yet, the British Heart Foundation (BHF) recommends the use of stanols and sterols, though I wondered if this might have something to do with the fact that one of its corporate partners is Flora pro.activ (a brand of sterol-enriched foods made by Unilever).

On the 17th July, I emailed the BHF about this. Here’s my email to them:

The National Institute for Health and Care Excellence has this to say about dietary stanols and sterols: “People should not routinely be recommended to take plant sterols and stanols for the primary prevention of [cardiovascular disease].”
We are also advised by NICE that: “There is a need for trials to test both efficacy and effectiveness of plant sterols and stanols in people who are at high risk of a first CVD event.

 These trials should test whether plant sterols or stanols change lipid profiles and reduce CVD events under best possible conditions. Randomised controlled trials are needed to test the effectiveness of advising people who are at high risk of experiencing a first CVD event to include food items containing plant sterols or stanols in a low-fat diet. The trial should last for at least 2 years and should consider appropriate outcomes.”

Yet, I notice that the BHF advocates stanols and sterols. Can someone explain the discrepancy, and whether the BHF believes the fact that Flora pro-avtiv is a corporate partner of represents a financial conflict of interest?
 
On the 30th July, I got a reply from Professor Peter Weissberg, the medical director of the BHF. Here are the highlights from his email:
  • They are not suggesting that plant sterols/stanols can prevent a heart attack
  • They do help to reduce LDL cholesterol, which is a risk factor for heart disease
  • Their information reflects this and has not been altered by their fundraising partnership with Flora pro.activ.
  • The BHF  has a very clear set of principles on the basis of which they work with commercial organisations.
  • The amount of money they take from Flora pro.activ is a tiny percentage of their overall budget.
The same day, I emailed Professor Weissberg again, this time questioning the presumed benefit of LDL-cholesterol reduction, but also to draw his attention, should he not be aware of it already, of the considerable body of evidence which suggests sterols have the potential for harm. Here’s my email:
 
Dear Professor Weissberg
Thank you for getting back to me.

As you allude to, sterols/stanols have never been demonstrated to have clinical benefit, and it appears your support of them rests on their ability to reduce LDL-cholesterol levels (which you say is a risk factor for heart disease). Unfortunately, as I’m sure you’ll know, reduction of LDL-cholesterol most certainly does not assure clinical benefit. Ezetimibe – which has a similar mechanism of action to sterols/stanols – is a case in point.

Also, if arsenic and cyanide were found to be effective LDL-cholesterol reducing agents, it still would not make sense to recommend them for people for the reduction of cardiovascular disease risk, right?

The reason that I use this example is because, as you may know, there is a considerable body of evidence which suggests that sterols/stanols may have adverse effects on health. These are very well summarized in a paper published in the European Heart Journal in 2009 [Weingartner O, et al Controversial role of plant sterol esters in the management of hypercholesterolaemia. Europlean Heart Journal 2009;30:404-409]. If you have not already read it, I urge you to.

In this paper, the authors cite evidence linking the presence of sterols in the blood with an increased risk of cardiovascular disease. For example:

…there is evidence that elevated levels of plant sterols are associated with an increased cardiovascular risk. Glueck et al [Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives. Metabolism 1991;40:842–848] were the first to report that elevated plant sterols might be a risk factor for coronary heart disease. In a study with 595 hypercholesterolaemic patients, they found that slightly elevated plasma levels of plant sterols were a heritable marker for an increased cardiovascular risk.

Rajaratnam et al [Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women. J Am Coll Cardiol 2000;35:1185–1191]…found that in postmenopausal women, plant sterols were independently associated with coronary heart disease in a multivariate analysis. These findings were confirmed by Sutherland and his team in a study involving both sexes over all age groups [Association of plasma noncholesterol sterol levels with severity of coronary heart disease. Nutr Metab Cardiovasc Dis 1998;8:386–391].

The Scandinavian Simvastatin Survey Study (4S study) also identified a subpopulation of coronary artery disease patients with low endogenous synthesis of cholesterol and high absorption of cholesterol and plant sterols. The subjects of this subpopulation had the highest levels of plant sterols and the highest risk of recurrent coronary events despite lower levels of serum cholesterol due to simvastatin ingestion [Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Finnish 4S Investigators. BMJ 1998;316:1127–1130]

Larger epidemiological studies reported similar data. Results of the PROCAM-study showed that patients afflicted with myocardial infarction or sudden cardiac death had increased plant sterol concentrations [Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Munster (PROCAM) study. Nutr Metab Cardiovasc Dis 2006;16:13–21]. Upper normal levels of plant sterols were associated with a three-fold increase of risk for coronary events among men in the highest tertile of coronary risk according to the PROCAM-algorithm.

Similar data are available for the plant sterol campesterol from the MONICA/KORA-study. In this prospective study, campesterol correlated directly with the incidence of acute myocardial infarction [Abstract 4099: elevated campesterol serum levels–a significant predictor of incident myocardial infarction: results of the population-based MONICA/KORA follow-up study 1994–2005. Circulation 2006;114:II_884].

This is all epidemiological evidence, of course, but it supported by several animal, in vitro and clinical experiments that, I think, give us genuine cause for concern. Again, from the European Heart Journal paper [Weingartner O, et al Controversial role of plant sterol esters in the management of hypercholesterolaemia. Europlean Heart Journal 2009;30:404-409]:

Current experimental findings from our own research group show that a diet supplementation with plant sterol esters that is equivalent to a commercially available spread induces endothelial dysfunction and leads to an increase of ischaemic stroke size in wild-type mice [Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol 2008;51:1553–1561].

…in a clinical study, we demonstrated that patients who were consuming plant sterol ester enriched margarine had increased concentrations of plant sterols in cardiovascular tissue [Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol 2008;51:1553–1561].

Further mechanistic data suggest that vascular deposits of sterols, when compared with cholesterol, result in increased oxidation and release of oxygen radicals [Oxidized plant sterols in human serum and lipid infusions as measured by combined gas-liquid chromatography-mass spectrometry. J Lipid Res 2001;42:2030–2038].

…the induction of apoptosis is not limited to tumour cells, but extends also to vascular cells. Recent in vitro experiments demonstrated that the plant sterol sitosterol exerts a strong cytotoxic propensity inducing apoptosis in human endothelial cells, revealing detrimental effects on the vasculature [Beneficial or harmful influence of phytosterols on human cells? Br J Nutr 2008;100:1183–1191].
In fact, the first experimental study reporting negative cardiovascular effects dates back to the year 2000. Ratnayake et al.  [Vegetable oils high in phytosterols make erythrocytes less deformable and shorten the life span of stroke-prone spontaneously hypertensive rats. J Nutr 2000;130:1166–1178 reported that increased serum levels of plant sterols increase rigidity of erythrocytes and shorten the life span of stroke-prone spontaneously hypertensive (SHRSP) rats.

These findings were the reason for Health Canada, the federal department responsible for helping Canadians maintain and improve their health, to raise significant safety issues and not to allow functional foods enriched with plant sterol esters to be sold in Canada.

I am sure you must be very busy, but please take some time to consider this evidence. From what I can see from the research, we have no evidence at all that sterols/stanols improve clinical outcomes, and considerable evidence linking them with potential for harm. Until we have positive evidence regarding outcomes, wouldn’t the most prudent and safety-conscious thing be to not recommend sterols/stanols (as NICE does)?

Thank you for your explanation regarding your corporate partners. If the funds derived from this relationship are so low, why not sever the link and have no conflict of interest at all, here?
I look forward to hearing from you.
Kind regards
John Briffa
 
On the 6th August, I got this response from Professor Weissberg:
Dear Dr Briffa
Thank you for your further email on this subject. I am aware of a large number of publications, of varying quality and validity, on the subject of plant stanols and sterols and their potential benefits and harms. I would prefer not to enter into a debate on any one of them since they all have their strengths and weaknesses.

So, as with so much in science, interpretation of the data is not as straightforward as is sometimes presented. Nevertheless, we are agreed that, ideally, one would like to see appropriately designed outcome trials to test their role in protection against cardiovascular events. In the absence of such data (and I doubt they will ever be produced), it is a matter of judgement as to whether or not plant stanols should be included as part of a wider strategy to reduce cardiovascular risk, and different national bodies have come to different conclusions.

In drawing this correspondence to a close I would conclude by saying that the BHF only enters into partnerships after careful consideration of all the pros and cons of so doing. As discussed previously, the main objective of the partnership with Unilever is to utilise their considerable reach to help us highlight the risk of CVD to women.

I thank you for your interest in this project and assure you we take seriously all feedback we receive.
Yours
 
Notice here how Professor Weissberg makes no comment at all on the specifics of the studies, nor puts up one scrap of evidence to refute the concerns raised. And what are we to glean from his writing: “In drawing this correspondence to a close…” To me, that gives the impression Professor Weissberg wants to hear no more from me (or perhaps anyone else) on the matter. Case closed!
I think we deserve better to be honest. I genuinely believe that, based on the evidence, there is a case to answer regarding the health effects of sterols, and it’s simply not good enough for Professor Weissberg to dismiss the evidence based on rhetoric to do with, supposedly, the evidence being of ‘varying quality and validity’. This is true of all science, so is Professor Weissberg suggesting we just go back to the dark ages and believe what suits us?

How many people do you imagine look to the BHF as being a reliable and credible organisation dedicated to our heart health? Lots, I would imagine. How do you think they would feel to know that when legitimate concerns are raised about products they recommend (some of which are made by a company the BHF partners with), their medical director just flatly refuses to engage with the science?
There is absolutely no evidence that sterols benefit health, but it seems the BHF is going to recommend them anyway, even in light of significant evidence suggesting they have the potential for harm.

Professor Weissberg seems to claim that the BHF’s relationship with Unilever does not compromise them. In fact, Unilever is helping them raise awareness about the risk of cardiovascular disease in women! I wonder how many of these women will be concerned enough to put their faith in utterly bogus food products enriched with sterols?
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