I calculate that the maximum plasma epicatechin concentration in the study of Serafini et al. is about 1 µM. Epicatechin metabolites are likely to be present at lower concentrations and to have reduced antioxidant activity compared with that of epicatechin itself, because of blocking of radical-scavenging hydroxyl groups by conjugation3. However, the total plasma antioxidant capacity (TPAC) measured by Serafini et al.2 rose by up to 18%. When measured by the ferric-reducing antioxidant-potential (FRAP) used by the authors, TPAC is usually 0.6–1.6 mM (ref. 4), of which 18% would be 108–288 µM. The rise in TPAC is therefore so large that it is unlikely to be due in significant part to the antioxidant action of epicatechin and its metabolites, or of other phenolics in chocolate.

The FRAP activity of human plasma is mainly attributable to ascorbate, α-tocopherol, bilirubin and urate4. Given normal plasma levels of these substances5, an increase in urate concentration is most likely to account for the results of Serafini et al., because urate is present in plasma at much higher levels than those of other antioxidants, and chocolate is unlikely to contain much ascorbate. Although α-tocopherol may be present in chocolate, even a high intake of this vitamin can increase its concentration in plasma by only a few micromolar at most5.

The mechanism and consequences of increased plasma urate levels following consumption of chocolate would be interesting to investigate, but should not necessarily be regarded as beneficial. Hyperuricaemia has been associated with stroke, cardiovascular and renal morbidity, and gout5,6,7,8.

Evidence is mounting regarding the potential importance of the overall redox network in disease prevention. It is crucial to our understanding to elucidate the mechanisms by which TPAC is modulated, and the effect of food on this important parameter.