Multi-biomarker approach demonstrates flavanol cardio benefits: Study

By Shane Starling

- Last updated on GMT

Related tags Nutrition European food safety authority

Multi-biomarker approach demonstrates flavanol cardio benefits: Study
An eight-week study of monomeric and oligomeric flavanols (MOPs) employing a “multi-biomarker approach” in a healthy population of smokers has shown cardiovascular benefits.

Mindful of the European Food Safety Authority’s (EFSA) tough stance on antioxidant science, the Maastricht University researchers tested a number of biomarkers and found a significant increase in cardiovascular-related measures when the results were combined.

The most significant change occurred in the ratio of glutathione to glutathione disulphide in erythrocytes. It was 22% higher in the supplemented subjects.

They also found OPCs reduced bacterial endotoxins and expression of inflammatory genes in leukocytes and reduced serum total cholesterol and LDL cholesterol.

But platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, and prostaglandin F2alpha were not significantly different.

“However, integrating all measured effects into a global vascular health index and taking into account that the trial was performed with healthy subjects,”​ the researchers, led by Dr. Antje Weseler concluded.

“a representative panel of markers”

They commented on some of the challenges the European Union nutrition and health claims regulation (NHCR) has presented to the field of nutrition science, especially in regard to biomarkers.

“Food scientists are facing the challenge to prove the clinical efficacy of nutrients that modulate human physiology in a subtle and non-specific manner,”​ the observed.

“In drug research, where the one-target-one-hit concept is imperative, randomized clinical trials with a well-defined single endpoint are the gold standard of efficacy testing. However, a single endpoint neither sufficiently reflects the multifarious nature of nutrients’ functions in humans nor the complexity of pathomechanisms underlying virtually all diseases.”

“Our study pioneered the implementation of a pragmatic solution for this problem: Carefully select a representative panel of markers that reflect the major relevant pathological aberrations and integrate all measured effects into a global health index.”


The researchers recruited smokers because they sought a healthy but slightly distressed group to test against the placebo group.

The double-blind, randomised, placebo-controlled intervention study was comprised of 28 middle-aged, smoking Dutch males to take either placebo or 200 mg per day of MOFs from grape seeds.

The meticulous selection of outcome parameters led to a spectrum of makers that comprised established as well as novel cardiovascular risk factors and systemic biomarkers reflecting the most essential pathomechanisms in the human vasculature on a functional and (sub)cellular level,”​ the researchers wrote.

“The integration of the changes in these biomarkers into a vascular health index enabled us to demonstrate the beneficial effects of MOF on vascular health in general. This is the first trial that applies an integrative biomarker approach in order to determine the health effects of a dietary supplementation in the human vasculature.”

The study was partially sponsored by the International Nutrition Company along with a Seventh Framework Programme European Union grant under the Flaviola project.

Source: PLoS ONE

6(12): e28460. doi:10.1371/journal.pone.0028460 (2011)

Pleiotropic Benefit of Monomeric and Oligomeric Flavanols on Vascular Health - A Randomized Controlled Clinical Pilot Study’

Authors: Weseler AR, Ruijters EJB, Drittij-Reijnders M-J, Reesink KD, Haenen GRMM, et al.

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1 comment

Thoughts on interpreting dietray intervention outcomes.

Posted by Leto Atreides,

The idea of integrating the assessment of various biomarkers in order to study health and disease is sound, but not novel! In the context of cardiovascular disease, the paper by Blankenberg and co-workers [1], and the various subsequent publications associated with it, are just a couple of examples of previously published work based on the same rationale.
In addition, the IOM Report [2] discusses this interesting topic in detail and provides various excellent perspectives. Moreover, and just as an example of the use of a multi-biomarker approach in the area of flavanol research you could review Curtis et al. 2012 [3]. Taken together your claim of novelty is actually rather more rhetoric than fact. What about the meaningfulness of your interpretation with regard to assessing the impact on cardiovascular health? Where is the support for the claim you make that your version of an integrated multi-biomarker assessment is in anyway related to cardiovascular morbidity, mortality, disease risk, or health?
The work described in the 3 reference examples given above is fundamentally concerned with exactly this questions, and thus with the validity and meaningfulness of any future recommendations with regard to treatment or prevention that are founded on biomarker-based clinical trial outcomes. Consequently, in the absence of an effect on the primary outcome measure [FMD] in your dietary intervention study, and without having sufficient supporting data that your version of a multi-biomarker assessment is actually enabling you to estimate an impact on disease risk or health, how can you conclude that your intervention demonstrated the “Pleiotropic Benefit of Monomeric and Oligomeric Flavanols on Vascular Health…”?
[1] Blankenberg S. et al. Circulation. 2010 Jun 8;121(22):2388-97. Epub 2010 May 24. Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project.
[2] IOM, 2010. Consensus report: evaluation of biomarkers and surrogate endpoints in chronic disease. Available from:
[3] Curtis et al. Diabetes Care 2012: Chronic Ingestion of Flavan-3-ols and Isoflavones Improves Insulin Sensitivity and Lipoprotein Status and Attenuates Estimated 10-Year CVD Risk in Medicated Postmenopausal Women With Type 2 Diabetes.

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