Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 14 No. 1 • April 2011

There May Be a Lot More
Polyphenols in the Circulation
Than Just Those Found in the Plasma

One of the current beliefs concerning dietary (or supplemental) polyphenols is that they are not well absorbed, as reflected in the very low concentrations found in blood plasma. In a new paper,1 researchers propose that the proportion of total oxidant-scavenging capacity (TOSC) carried in the blood that is due to polyphenols cannot be adequately measured in just the plasma, but that the true TOSC can be derived only from including the red blood cells and plasma. They suggest that, “similar to microorganisms, blood cells (mainly red blood cells [RBC]) in the circulation might also avidly bind polyphenols to their surfaces resulting in enhanced TOSC.”1 Thus, they propose that studies in which polyphenols were only determined by measuring their content in plasma have provided deceptively low levels because they did not include the polyphenols in whole blood, which includes red blood cells and platelets that also carry polyphenols.

The authors note that red blood cells contain antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase/reductase and NADH-metHgb reductase, as well as nonenzymatic antioxidants such as lipophilic (fat soluble) vitamin E, carotenoids, ubiquinone, melatonin, etc. and water-soluble vitamin C, glutathione, uric acid, ceruloplasmin, transferrin, haptoglobulin, etc. Plasma is rich in albumin and in low molecular weight antioxidants such as glutathione, ascorbate, alpha-tocopherol, uric acid, and bilirubin. Thus, the researchers say, “... it stands to reason that the TOSC of whole blood is the sum of the intracellular antioxidants present in RBC [red blood cells] and in other blood cells, the antioxidants bound to their surfaces and those found in plasma.”1

The authors, on the basis of the studies described in their paper,1 argue that “since erythrocytes [red blood cells] can form stable complexes with polyphenols, they acquire the ability to act in concert with LMWA [low molecular weight antioxidants] and with albumin to enhance TOSC.” “The minute quantities of polyphenols detected in plasma do not reflect the true amount of polyphenols which gain access to the circulation, since these agents might also be complexed with circulating erythrocytes [red blood cells], removed and therefore not accounted for if TOSC is tested exclusively in plasma.” They further propose, on the basis of their findings concerning the binding of polyphenols to red blood cells that “human erythrocytes play a pivotal role in the distribution and bioavailability of circulating polyphenols and in protection against cell damage induced by ROS [reactive oxygen species].”

The analysis1 was done using freshly collected non-fasting human blood from 11 healthy volunteers. The researchers used a “cocktail” of substances to generate at room temperature a flux of hydrogen peroxide and of cobalt-catalyzed hydroxyl radicals, which were detected by luminol-dependent chemiluminescence assay. Using the luminescence assay, Figure 3a in the paper “shows that incubation of whole blood with eight antioxidant agents followed by removal of unbound materials by washing resulted in a decrease in luminescence. It indicated that RBC [red blood cells] in whole blood could bind polyphenols and that gallic acid, curcumin and resveratrol were the most potent polyphenols [of those tested by the authors] attached.” In a separate analysis using a different test (fluorescence confocal microscopy), polyphenols (morin, resveratrol, curcumin, and tannic acid) were exposed to washed erythrocytes. The most potent quenchers of luminescence were (in descending order) wine/tannic acid, curcumin, resveratrol, and morin. In addition, using a different method (differential pulse voltammetry), the authors confirmed that polyphenols remained attached to the washed erythrocyte surfaces. They hypothesize, therefore, that “erythrocytes and possibly other blood cells in the circulation might always be coated, in a cumulative manner, with polyphenols, which gain access to the circulation from nutrients.”1

These are very exciting findings that we hope will be followed up by further research. As the authors note, “the nature of the binding of polyphenols to erythrocyte surfaces is still not fully clear ...” but suggest that they might do so via hydroxyl groups, hydrophobic interactions, hydrogen bonding, or other mechanisms. The binding of polyphenols to red blood cells and possibly other blood cells could help explain the important protective effects of polyphenols (in cardiovascular disease, cancers, neurodegenerative diseases, and others) despite the very low concentrations previously reported in plasma.

The authors also promise more to be published on this line of research. They say that “[i]n recent observations (to be published) RBC were also shown to synergize strongly with washed platelets, lymphocytes, salivary antioxidants and with plasma to enhance TOSC.” They even propose that following destruction of red blood cells in the spleen, “higher levels of polyphenols might be accumulated in this organ” and say further that “[s]tudies along this line are now in progress.” Bravo!


  1. Koren, Kohen, Ginsburg. Polyphenols enhance total oxidant-scavenging capacities of human blood by binding to red blood cells. Exp Biol Med 235:689-99 (2010).

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