Lemon Balm Extract Reported Safe in Providing Beneficial Effects for Glycation-Associated Tissue Damage, Arterial Stiffness, and Skin Elasticity

  • Lemon Balm (Melissa officinalis, Lamiaceae)
  • Glycation-associated Tissue Damage
  • Arterial Stiffness
  • Skin Elasticity

Advanced glycation endproducts (AGEs) are generated by the nonenzymatic glycosylation of proteins, or glycation, and are associated with increased oxidative stress and inflammation. In patients with diabetes mellitus, cardiovascular disease, or Alzheimer’s disease, the tissue content of AGEs is much higher than in healthy individuals. The AGE pentosidine increases with age and correlates with the degree of skin and artery stiffness; yellowing skin associated with aging also may be due partly to glycation. Seeking to find a potent antiglycation food material, these authors studied plant extracts that inhibited the formation of pentosidine, selecting lemon balm (LB; Melissa officinalis, Lamiaceae) extract (LBE) and identifying its active components. In an open-label, parallel group, comparative trial, they examined the beneficial effects of LB on arterial stiffness, skin elasticity, and blood hematological and biochemical parameters.

A total of 681 plant extracts were screened and evaluated for antiglycation activity. Among the 22 possible candidate plants, 4 species were of the Lamiaceae family; 17 species exhibited higher activity against pentosidine than the antiglycation agent aminoguanidine. LB was selected from those plants because of its safety, taste, stable supply, and adaptability to beverage form.

Twenty-eight healthy Japanese subjects (14 males and 14 females) were enrolled in the trial, conducted at Yakult Central Institute in Tokyo, Japan, from late October 2010 to early December 2010. The subjects were instructed to continue their usual exercise regimens and diet, excluding herbal teas. The trial included a 1-week pre-intake phase and a 6-week intake phase. Measurements conducted during the pre-intake phase (baseline) and on the day after the last day of intake included brachial-ankle pulse wave velocity (baPWV) as a marker of arterial stiffness, blood pressure, skin elasticity of the left cheek, skin color, and hematological and biochemical parameters.

The subjects were randomly assigned to the LBE group or the control group, with 14 in each group. The beverages were prepared daily by the subjects for 6 weeks as follows: bags containing 3.3 g dried LB leaves (Charis Seijyo Co., Ltd.; Tokyo, Japan) in the LBE group or barley (Hordeum vulgare, Poaceae) tea grains (Nihon Seibaku Co., Ltd.; Kanagawa, Japan) in the control group were extracted for 5 minutes in 200 mL hot water before drinking. Fractionation of the LBE revealed that the polyphenol rosmarinic acid (RA) was the most abundant active component. The subjects recorded their daily intake of the beverages and any adverse effects.

Of the 14 subjects in the LBE group, 2 were excluded from the analysis because they had health problems, unrelated to the tea, for more than 10 days during the study period. Compliance rates were 100% in the control group and 99.5% in the LBE group.

Evaluations of the glycation-induced coloration of collagen fiber sheets and glycation-induced changes in the fibrous structure of elastin fiber sheets revealed that “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,” report the authors.

After 6 weeks of treatment, baPWV was reduced in the LBE group and unchanged in the control group, with a significant between-group difference in the change (P = 0.007). No significant between-group differences were observed for changes in systolic or diastolic blood pressure. Age of the subjects correlated strongly with baPWV at baseline (P < 0.001).

No significant between-group differences were observed in the changes in cheek skin elasticity during the trial. However, comparing the changes in male skin with female skin of both groups, the authors report that the only gender difference detected was a significant between-group difference in R7 value (total deformation) in only the female subjects; in females in the control group, the R7 value decreased by 0.044 ± 0.025 and in those in the LBE group, by 0.012 ± 0.018 (P = 0.027). The authors suggest that timing may have attributed to this finding, stating that because the trial was conducted during the autumn and winter, with frequent changes in humidity and temperature, and because female skin is thinner and drier than male skin, “the seasonal effects might be more severe in female subjects.”

In the LBE group compared with the control group, significant reductions were observed in both a* (red [asterisk is part of value name]; P = 0.017) and b* (yellow; P = 0.008) color values in forearm skin; the values did not change in the control group. Previously reported anti-inflammatory activity of RA1 may reduce a* value, say the authors. In one prior study, b* values increased through glycation in mouse skin,2 and such increases reportedly reflect the accumulation of AGEs.3,4 “Therefore, the decrease in b* values is presumed to be due to the anti-glycation effects of the daily intake of LB tea,” write the authors.

No significant between-group changes were observed for L* values (brightness of skin), which in earlier studies were found to be linked to antioxidation.5,6 “This observation indicates that the involvement of anti-oxidation in the anti-glycation effect of LB tea may be small,” state the authors.

No significant differences were seen in reported adverse effects between the 2 groups. Among the hematological and biochemical parameters, the serum glucose and uric acid levels after 6 weeks were significantly lower in the control group compared with baseline (P < 0.05 for both). Serum creatinine levels decreased significantly in both groups (P < 0.01 for the control group and P < 0.05 for the LBE group).

This study is limited by its small sample size; its lack of detection of AGE content in arteries and skin to clarify whether LB tea affects that content; and the study design, which did not include a placebo.

The authors conclude, “The hot water extract of LB leaves is considered a safe and potent food material to provide health benefits with regard to glycation-associated tissue damage and symptoms such as increased arterial stiffness and decreased skin elasticity.”


1Osakabe N, Takano H, Sanbongi C, et al. Anti-inflammatory and anti-allergic effect of rosmarinic acid (RA); inhibition of seasonal allergic rhinoconjunctivitis (SAR) and its mechanism. Biofactors. 2004;21(1-4):127-131.

2Yokota M, Tokudome Y. Permeation of hydrophilic molecules across the glycated skin is differentially regulated by the stratum corneum and epidermis-dermis. Biol Pharm Bull. 2015;38(9):1383-1388.

3Monnier VM, Cerami A. Nonenzymatic browning in vivo: a possible process for the aging of long-lived proteins. Science. 1981;211(4481):491-493.

4Ohshima H, Oyobikawa M, Tada A, et al. Melanin and facial skin fluorescence as markers of yellowish discoloration with aging. Skin Res Technol. 2009;15(4):496-502.

5Kim SB, Jo YH, Liu Q, et al. Optimization of extraction condition of bee pollen using response surface methodology: correlation between anti-melanogenesis, antioxidant activity, and phenolic content. Molecules. 2015;20(11):19764-19774.

6Ya W, Chun-Meng Z, Tao G, Yi-Lin Z, Ping Z. Preliminary screening of 44 plant extracts for anti-tyrosinase and antioxidant activities. Pak J Pharm Sci. 2015;28(5):1737-1744.

Yui S, Fujiwara S, Harada K, et al. Beneficial effects of lemon balm leaf extract on in vitro glycation of proteins, arterial stiffness, and skin elasticity in healthy adults. J Nutr Sci Vitaminol (Tokyo). 2017;63(1):59-68.


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