Chocolate is good for your funding

Chocolate is good for your health, scientists keep saying. This may sound counter-intuitive; given that chocolate is an extremely calorie-rich confectionery, which mostly contains industrially refined cocoa fat and huge quantities of added sugar, a substance finally about to be recognised as the prime cause for the obesity epidemics.

A recent clinical study from the Luxembourg Institute of Health, published in the British Journal of Nutrition (Alkerwi et al, 2016), discovered that “chocolate consumers (81·8 %) were more likely to be younger, physically active, affluent people with higher education levels and fewer chronic co-morbidities”. The authors used data from the nationwide Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX) survey to determine that “chocolate consumption may improve liver enzymes and protect against insulin resistance, a well-established risk factor for cardiometabolic disorders”. Basically, this paper advices hyperglycaemic and diabetic patients to eat sugar-rich confectionery, which may appear somewhat irresponsible or even dangerous. These alleged chocolate benefits on diabetes prevention present a new turn in a long history of bold claims about the medicinal magic inside the sweets wrapper. Moreover, the lead author Ala’a Alkerwi also determined that chocolate improves cognitive capacities (Crichton et al 2016).

A fresh editorial in the BMJ journal Heart simply asked: “Is life longer with a box of chocolates?”. The authors Donaldson et al present “the health benefits of eating chocolate” as a scientific fact, which only needs physiological and molecular elucidation. Clinical studies have allegedly proven that regular consumption of chocolate reduces risk of heart attack and heart failure. The authors, led by Phyo Kyaw Myint, Chair for Medicine of Old Age at University of Aberdeen, decree that “future studies will need to narrow down exactly how chocolate exerts its beneficial effects”.

There were however quite a lot of chocolate studies done for more than a decade, funded with millions from the public, but also from the chocolate industry. Reliable reports of people cured of any cardiovascular diseases by eating chocolate do not exist. Even the health benefits of the purportedly medicinal raw cocoa ingredients of the flavanol compound family are far from being conclusively proven.

Chocolate also is a huge industry. Giant food conglomerates make tremendous profits with confectionery produce alone, the US-based world leader Mars Inc made over $18Bio in sales in 2015, the 3^rd biggest manufacturer Nestlé SA from Switzerland sold $11Bio worth of chocolate. It is to be expected that the industry would be interested to see their tasty, but obesity-causing product, to be scientifically presented as beneficial for health. Indeed, Mars and Nestle invest heavily into basic and clinical research and collaborate with academic scientists and entire universities. At the Swiss EPFL, Nestle finances two professorships in energy metabolism and neurodevelopment, the chocolate giant also had a say and veto right on these appointments.

In 2005, Mars invited around 20 of their sponsored researchers to a conference in the Swiss town of Luzern, the agenda was “The Potential Use of Cocoa Flavanols in Preventing Cardiac and Renal Disease; Targeting the Individual Susceptible to Damage“. This was reported by the Washington Post, which also declared that Mars was

“holding ‘serious discussions with large pharmaceutical companies’ about the development of a line of cocoa-based prescription drugs that could help treat diabetes, some forms of dementia and other ailments”.

One of these participants was the Mars-funded researcher Norman Hollenberg, professor of medicine at Harvard Medical School. He originally established the alleged health benefits of raw chocolate and its natural flavanol substances on vasodilation in 27 healthy volunteers (Fisher, 2003), and on blood pressure (Hollenberg, 2006) in Kuna Indians, who lived separated from the civilisation at the Caribbean coast of Panama and regularly consumed beverages made of raw cocoa. Finally, Hollenberg’s collaborative publication in PNAS established “beneficial effects of flavanol-rich cocoa on vascular function in humans” (Schroeter et al, 2005. Science is indeed a village: one of the contributors, Helmut Sies, led a large lab just one floor below where I did my PhD at that exact time at the University Clinic of Düsseldorf; I even recall talking with his PhD students about their Mars-funded research). Two authors of that paper were employed by Mars, which also funded this study, as well as all other earlier and later chocolate-related research by Hollenberg. Mars Inc in turn patented the use of flavonol derivates. Another Hollenberg co-author from Düsseldorf, Malte Kelm, ran from 2009 to 2013 a huge international Flaviola study, to establish the health benefits of flavanols. It was funded by EU with €3Mio, another million Euros came from Mars. Yet after many millions of euros and dollars spent, we still do not really know if medical flavanols can really help any cardiovascular patients.

Originally, Mars probably thought to use their control over world cocoa production to establish collaborations with the pharma industry. Their goal was possibly less about convincing people to eat more sweets, but to produce hypertension drugs out of natural flavanols like epicatechin and their metabolites, to be taken in pill form. Apparently not much came out of it, which did not stop the chocolate industry from further research. Now however it was not about some mysterious natural substances of raw cocoa. It was simply about the life-saving industrial “dark” chocolate. Even despite the fact established by Hollenberg himself, that the supposedly cardiovascular-active flavanols in raw cocoa actually get almost completely degraded during the industrial preparation process of chocolate.

Certain cardiologists decided to simply use the commercial chocolate from their industrial sponsors, who in turn claimed to have developed secret technologies to preserve the flavanols inside their industrial chocolate and to properly measure their content afterwards (in case others fail to detect anything).

The example below may be representative, or exceptional. But it surely shows how questionable and conflict-of-interest-ridden research on the alleged health benefits of chocolate can receive the quality approval seal from some of the most respected medical journals.  By this virtue alone, it becomes quasi a medical fact.

Thomas Lüscher is professor and chairman of the cardiology centre at the University Hospital Zurich in Switzerland. The extremely influential cardiologist and highly successfully industrial fund-raiser is now close to retirement. His scientific legacy also includes evidence that Nestle chocolate is beneficial for patients with cardiovascular diseases. To a Swiss magazine NZZ Folio, Lüscher once said: “Only investigative journalists maintain the image of the evil industry, which seduces doctors and only wants shovels financial profits”. As the NZZ journalist had to learn, Lüscher’s own funding contracts with the industry are not available to public. As Lüscher rhetorically asked: “Is the public the right place to assess these contracts? Aren’t the university lawyers better qualified?”

In 2006, Lüscher’s lab published in the BMJ-journal Heart a paper by Hermann et al, titled: “Dark chocolate improves endothelial and platelet function”. Its last author (as well as on several other Lüscher papers) was his subordinate clinician Roberto Corti, who meanwhile quit academia to work in a hospital and did not reply to my email. The authors discovered that dark chocolate had a positive effect on blood coagulation “in healthy smokers 2–8 hours after ingestion”. No competing interests were declared, though not just any dark chocolate was tested, but in fact specifically Nestlé Noir Intense (which contains 30% added sugar). Also, at that time Lüscher was receiving funding from the world-biggest chocolate giant Mars, which Lüscher only admitted in his latter papers.

In 2007, Lüscher lab published in the journal Circulation a paper by Flammer et al, titled: “Dark Chocolate Improves Coronary Vasomotion and Reduces Platelet Reactivity”. The paper’s conclusions in regard to Nestlé Noir Intense specific health benefits were:

“Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration”.

Unlike with the BMJ’s Heart, Lüscher was now asked to declare his COI more thoroughly:

“Nestlé provided chocolate but was not involved in funding or in any part of the study, except in the analysis and interpretation of serum and chocolate polyphenol concentrations. Dr Cooper [co-author of the paper, -LS] is an employee of the Nestlé Research Center. Dr Lüscher has been a consultant for MARS Inc and has received research grants not related to the present study”.

Nestle therefore provided not only chocolate, but also the fully unbiased and balanced analysis of the research data. There was another interesting statement to assure the impartiality of analysis:

“Dark and control chocolates were prepared by Nestlé (Lausanne, Switzerland). Both were wrapped identically, and randomization was done by an organization independent of the study group (InterCorNet, Zürich, Switzerland)”.

However, InterCorNet, which belongs to the “Zurich Heart House”, is actually not really an independent institution in this context. It was founded by Lüscher himself. One of the industrial donators of the foundation is the chocolate giant Mars, through their research branch Mars Symbioscience.

The close collaboration with Nestle paid off for Lüscher quite handsomely. The 2007 research paper was followed two years later by a review in Circulation authored by Corti, Lüscher and the original chocolate-benefits discoverer Hollenberg, titled: “Cocoa and Cardiovascular Health”. The funding declared was:

“Drs Lüscher and Hollenberg received research grants from MARS Inc until 2007. Dr Lüscher received a research grant from Nestlé, Switzerland”.

Obviously, once the funding from one chocolate giant ran out, Lüscher had to find another benefactor. And Nestle proved in this regard the best choice possible. Lüscher was given an unrestricted industrial grant, i.e., this industrial funding is not attached to any particular research project and can be used freely (something most of his colleagues can only dream of). This was evidenced by the COI declaration in this 2011 follow-up paper by Flammer et al in the European Heart Journal, titled “Cardiovascular effects of flavanol-rich chocolate in patients with heart failure”:

“Partly supported by an unrestricted grant from Nestlé Research Center, Switzerland, as well as by funds of the Zurich Heart House—Foundation for Cardiovascular Research, Zurich, and a strategic alliance with Pfizer, Inc., New York, USA. Nestlé reviewed and approved the manuscript”.

The latter statement insinuates that Nestle received as the paying customer of these university clinicians the full control over their subsidised research and its outcome, a somewhat unusual constellation.  One of Nestle employees is co-author of this work, where Nestlé Noir Intense chocolate was used to prove that it “acutely improves vascular function in patients with CHF [congestive heart failure, -LS]. A sustained effect was seen after daily consumption over a 4-week period, even after 12 h abstinence”. The Zurich Heart House is once again presented as independent institution financing this research, while its founder Lüscher was actually deciding on awarding its grants to himself.

Finally, it is hardly surprising that this Flammer et al 2011 paper became “Editor’s choice” in the European Heart Journal, which is published by the European Society of Cardiology. It was “guest edited by Professor Stefano Taddei, Universita degli Studi di Pisa, Italy”, who as I was informed, used to be a former postdoc-colleague of Lüscher (they were trained in the same prestigious US lab, though not simultaneously).  Another minor detail, which may or may not have influenced the editorial process: Lüscher is Editor-in-Chief of the European Heart Journal.

From this case, one is well advised to look closely at open and hidden financial conflicts of interest of researchers proclaiming health benefits of chocolate. There surely are no good reasons whatsoever for patients with high blood pressure or diabetes to indulge themselves on chocolate, hoping for cure.