Effects of long-term supplementation with Centella asiatica (L.) Urb. extract (CA-HE50) on macular pigment optical density: a randomized, double-blind, placebo-controlled trial

Baek HI, Kim I, Bae J, Kwon JE, Kang SC. Nutrients. 2026 Mar;18(6):905.

Ageing is a major factor in the progressive vulnerability of the retina and the degenerative changes seen in the macula. This vulnerability is a result of cumulative oxidative stress, declining antioxidant defences and the gradual deterioration of retinal pigment epithelial (RPE) cells over time.

However, macular health appears to remain responsive to nutritional interventions during midlife, particularly prior to the development of advanced retinal pathology. Herbal and nutritional interventions have the potential to enhance the retinal antioxidant environment. One such example is Gotu Kola (Centella asiatica) which possesses antioxidant, anti-inflammatory, neuroprotective, and cytoprotective properties. Preclinical evidence exists to show that Gotu Kola extract can safeguard RPE cells from oxidative stress by activating endogenous antioxidant pathways (including Nrf2).

Study Design

A randomised, double-blind, placebo-controlled trial was performed in 80 men and women, aged between 45 and 65 years, with suboptimal baseline macular pigment optical density (MPOD) values (between 0.2 and 0.4) but without overt ocular disease. Macular pigment optical density (MPOD) is a nutrition-responsive biomarker that indicates the antioxidant status of the macula. Reduced MPOD levels have consistently been found in individuals with age-related macular degeneration (AMD).

Participants were randomly assigned to receive either Gotu Kola extract (300 mg/day) [n=40] or placebo (n=40) for six months. Efficacy was assessed by measuring MPOD at baseline and on days 60, 120 and 180. The primary endpoint was the change in MPOD from baseline to day 180. Safety was evaluated through monitoring adverse events, vital signs and clinical laboratory tests.

Key Findings

By day 180, Gotu Kola treatment significant increased MPOD compared to the placebo in the right eye, left eye and the average of both eyes (all p<0.001). Significant between-group differences were also observed at day 120, indicating a time-dependent improvement in MPOD.

The magnitude of MPOD increase observed in the present study (approximately 0.04 to 0.06 units) is comparable to the range reported in previous nutritional intervention studies, including clinical trials evaluating lutein and zeaxanthin supplementation.

Additionally, the proportion of responders was significantly higher in the Gotu Kola group compared to the placebo group (94.74% versus 32.43%; p<0.001), indicating a relatively consistent effect among individuals. This contrasts with the considerable inter individual variability often seen in carotenoid-based MPOD interventions.

Gotu Kola extract was well tolerated, with no serious adverse events or clinically relevant safety concerns identified during the trial.

Conclusion

This clinical trial suggests that long-term supplementation with Gotu Kola extract can improve macular antioxidant status in a consistent and sustained manner in middle-aged adults. Gotu Kola could be a valuable treatment option for enhancing macular resilience under oxidative stress and helping prevent AMD. This evidence expands our understanding beyond traditional carotenoid-based interventions.