- Excerpt
Since Masquelier filed his free radical scavenging patent, 30 years have passed and claims for the beneficial effects of antioxidants on human health have come under fire from scientists and critics who think that the claims were overstated and overestimated. Indeed, a word of caution may be spoken. Without a doubt, antioxidants play a role in reducing the risk of developing degenerative diseases. But, do they cure degenerative diseases the way one expects medicines to cure diseases? In a 2013 issue of the scientific journal Cell, Dutch scientists Aalt Bast and Guido Haenen of Maastricht University take a balanced and thoughtful position. “Clear pharmacological responses,” they write, “should not be expected from antioxidants.” This is because “drugs act on a specific target, such as an enzyme, a receptor, or a transporter. The preferable action of a drug is specific, that is, it acts on a unique target and induces a strong effect.” […] “This is in contrast to food and food-derived compounds such as food supplements. These compounds have a multitude of actions. Their action is certainly not specific and their effects on human health are difficult to determine.”
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The food supplement used in the aforementioned multiple effects study was MASQUELIER’s OPCs. And indeed, integrating all measured effects into a global vascular health index revealed a significant improvement of overall vascular health compared to placebo. The study was performed by the Department of Toxicology of Maastricht University in 2013. The research team led by Dr. Antje Weseler faced a particular challenge. Not only was it looking for weak and subtle signals, it was also looking for such signals in healthy people. Obviously, it is more difficult to produce measurable beneficial effects in organisms that are functioning “at constancy and in equilibrium,” than in organisms whose constancy is upset or seriously challenged. “Food scientists,” so wrote Weseler and colleagues, “are facing the challenge to prove the clinical efficacy of nutrients that modulate human physiology in a subtle and non-specific manner. 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.”
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All biomarkers that were measured in this study were validated markers relevant to cardiovascular health. The study showed a significant decrease in serum total cholesterol and LDL. Additionally, after 8 weeks of supplementation, the ratio of glutathione to glutathione-disulphide in erythrocytes rose from baseline by 22% in the supplemented subjects. Glutathione is one of the enzymes that forms part of the body’s antioxidant defense shield. The researchers also observed that MASQUELIER’s OPCs exerts anti-inflammatory effects in blood towards ex vivo added bacterial endotoxin and significantly reduces expression of inflammatory genes in leukocytes. Conversely, alterations in biomarkers such as platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, and prostaglandin F2alpha, did not reach statistical significance.
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Epigenetics is a hot research topic, so, when the Maastricht University group that had studied Masquelier’s OPCs and developed the Cardiovascular Index had the opportunity to also investigate whether OPCs influence “gene expression,” they didn’t hesitate. Together with top notch research groups in France and Belgium, the Dutch researchers began an analysis of the data they had gathered in the Vascular Index study, this time to search for the genomic impact of OPCs, more specifically, to look for the impact of OPCs consumption on the gene expression profile of leukocytes that had been isolated from the blood of the people who had participated in the Vascular Index study. Gene expression profiles were determined using whole-genome microarrays. A microarray is an orderly arrangement of the genetic sample, so that one can check whether and how the genes express themselves. A typical microarray experiment can check the expression of thousands of genes. By determining in which part of the array the expression takes place, one can draw conclusions about the type of body functions that are being addressed.
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OPCs significantly modulated the expression of 864 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organization, suggesting lower immune cell adhesion to endothelial cells. This effect was confirmed by in vitro experiments showing that white blood cells that had been exposed to OPCs are less prone to adhere to endothelial cells that had been stimulated to develop an inflammatory response, so as to attract the white blood cells. Cardiovascular problems tend to occur most commonly when white blood cells attach themselves to the endothelium, or even move through the endothelium into the vascular wall. Adhesion of white blood cells to the endothelium often enhances inflammatory processes, which may eventually lead to serious cardiovascular complications. Apparently, OPCs influence gene expression in white blood - immune - cells in a way that significantly reduces their propensity to adhere to the endothelium. The discovery that Masquelier’s OPCs positively influence genomic expression in white blood cells confirms that the vascular-protective effects of OPCs also take place at the most fundamental level of biological action.
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The bioinformatic data produced in this study also revealed that over 30 genes are involved in different processes related to inflammation. The role of chronic inflammation in the promotion, initiation and development of chronic diseases, such as cancer, cardiovascular disease or osteoporosis has been described in numerous studies. Intake of OPCs resulted in “down-regulating” the expression of some of these pro-inflammatory genes. Interestingly, the nutrigenomic data also revealed an increase in the expression of the gene coding for the endogenous inhibitor of a protein complex that controls many genes involved in inflammation. This protein’s name is NF-kB (k as in kappa). It is active in most inflammatory diseases.
