Summary Glycation, a non-enzymatic glycosylation of proteins, induces tissue damage in association with various diseases and aging phenomena. Pentosidine, an advanced glycation end product, is involved in aging phenomena such as tissue stiffness. In this study, we aimed to find a potent anti-glycation food material and to verify its health benefits by clinical trial. From among 681 hot water plant extracts, lemon balm (Melissa officinalis; LB) leaf extract was selected and revealed to have more potent inhibitory activity for pentosidine formation than a representative anti-glycation agent, aminoguanidine. Rosmarinic acid (RA), a typical polyphenol in Lamiaceae plants, was identified as a major active component in LB extract (LBE). Furthermore, LBE or RA dose-dependently suppressed glycation-associated reactions such as increased fluorescence, yellowing of collagen fiber sheets, and degeneration of the fibrous structure of elastin fiber sheets. An open-label, parallel-group comparative trial was conducted in 28 healthy Japanese subjects aged 31-65 y who consumed LB tea (LB group) or barley tea (Control group) for 6 wk. The LB group showed significant reductions in brachial-ankle pulse wave velocity, reflecting arterial stiffness, and b* (yellow) color values in forearm skin compared with the Control group. A gender-stratified analysis revealed that cheek skin elasticity was significantly improved in the LB group compared with the Control group only in female subjects. It is concluded that the hot water extract of LB leaf has the potential to provide health benefits with regard to glycation-associated tissue damage in blood vessels and skin of healthy adults. Key Words lemon balm, glycation, pentosidine, arterial stiffness, skin elasticity Glycation, the non-enzymatic glycosylation of proteins, is known to be involved in the onset of various diseases and conditions of aging. The substances generated by this reaction are known as advanced glycation endproducts (AGEs). Since the tissue contents of AGEs in diabetic patients (1, 2) and diabetic animals (3) are known to be much higher than in their healthy counterparts, AGEs are considered to be involved in the progression of complications of diabetes such as diabetic nephropathy (4) and cataracts (5). Involvement of the accumulation of AGEs in cardiovascular diseases (6, 7) and Alzheimer's disease (8) has also been reported.However, the stiffness of tissues such as arteries and skin is known to increase with age (9, 10) and is especially high in patients with diabetes compared to healthy subjects (9, 11). Pentosidine, one of the crosslinking AGEs, has a structure in which the lysine and arginine residues of tissue protein are cross-linked by a pentose such as ribose (12). It has been reported that pentosidine content increases with age (2, 9, 12) and positively correlates with the degree of tissue stiffness (7,13,14). One of the causes of the deterioration of tissue elasticity in elderly or diabetic patients is considered to be the accumulation of crosslinking AGEs su...