The optical biomarker, MPOD, was significantly increased in healthy adults at 0.25 and 1.75 REs in the goji berry group after 90 days of intake. This is consistent with a report that goji berry intake increased MPOD in a Chinese population at-risk for intermediate AMD19. Our results are similar to another study that reported consumption of a milk-based supplement containing 10 mg/d of Z derived from goji berries for 90 days protected against macular hypopigmentation and drusen development in a population of generally healthy males and females (65 to 70 years of age)21. Interestingly, we observed a significant increase in MPOD at 1.75 RE, but not at 0.5 or 1 RE, in the goji berry group. A possible explanation for this trend is the relatively low macular pigment at 1.75 RE compared to the other REs that may increase the potential for improved MPOD in this peripheral area of the macula.
Our results suggest that higher intake of Z relative to L may increase MPOD. This is consistent with a four-month intervention in healthy young adults (18 to 32 years of age) reporting significantly increased MPOD levels after daily intake of a supplement containing 20 mg Z, or 26 mg Z with 8 mg L plus 190 mg of mixed omega-3 fatty acids22. Our findings are also consistent with data from 11 randomized controlled trials where supplementation with at least 10 mg of the macular carotenoids is effective at increasing MPOD23.
Significant correlations were observed between the overall skin carotenoid score and MPOD, which is consistent with clinical results of carotenoid supplementation24. Further analysis demonstrated that LZ, but not goji berry intake, was significantly influencing this trend. Previous work has shown that the total carotenoid content in skin and blood is associated with macular pigment carotenoid accumulation24. In the current trial, goji berry intake was significantly associated with the skin carotenoid score, which is consistent with the recent observation by Obana et al. who reported a significant increase in skin carotenoid levels following the intake of 20 mg of L and 4 mg of Z along with modest amounts of vitamins and minerals for 16 weeks25. Improvements in macular pigment optical volume and MPOD for those with a BMI < 25 kg/m2 were also reported25. We did not collect BMI data in the current trial, so we are unable to assess the impact of BMI on MPOD and skin carotenoid score. The skin photometer detects overall carotenoid content, and since goji berries are also rich in β-carotene, neoxanthin, and cryptoxanthin26, these carotenoids likely influenced the skin measurements, which would not reflect the selective carotenoid accumulation of L and Z in the macula. Other components in goji berries may also have influenced the significant increase in MPOD, since the berries contain taurine, vitamin C, zinc, and LBP, which may lower oxidant stress and improve eye health27–29. Studies on animals and cell lines suggest that bioactive compounds in goji berries, such as LBP, can protect against AMD by reducing oxidative stress and cell apoptosis in retinal pigment epithelium30. Taken together, it is reasonable that MPOD may not correlate with skin carotenoids in the goji berry group.
To our knowledge, the impact of goji berry intake on MPOD in healthy middle-aged people has not been previously reported. While others have noted improved MPOD after LZ supplementation among people with low MPOD baseline levels31, our findings suggest that even in populations with high normal MPOD values, a significant increase can be detected after goji berry consumption at the most central part of the macula (0.25 RE). A meta-analysis regarding the effects of L, Z, and meso-Z supplementation noted that the MPOD at baseline was inversely associated with macular responses, suggesting individuals with a relatively lower macular pigment status may receive more benefit with higher amounts of L or Z32.
The Age-Related Eye Disease Study 2 (AREDS2) trial assessed the impact of dietary supplements containing 10 mg of L, 2 mg of Z, 500 mg of vitamin C, 400 IU of vitamin E, 80 or 25 mg of zinc, 2 mg of copper, and/or 350 mg of docosahexaenoic acid plus 650 mg of eicosapentaenoic acid33. The results showed a significantly reduced rate of progression from intermediate- to late-stage AMD after five years34,35. Secondary analyses of the study indicated protective roles of L and Z33. We did not use the AREDS2 supplement for the comparison group because this formula has only been shown effective for those with intermediate AMD35, and no clinical evidence exists for its efficacy in our study population of healthy people. In addition, we note that 80 mg of zinc in the AREDS2 supplement is twice the upper limit of recommended daily intakes for zinc.
In epidemiological studies, L and Z intakes have been inversely associated with development of AMD32,36. The reported dietary intake of L plus Z, not including the berries or supplement. was 3.1 and 1.9 mg/d in the goji berry and supplement groups, respectively, which is higher than the typical estimated intakes in the US of 1.58–1.76 mg/d37. Three to five mg/d of L and Z have been recommended to help support normal macular function8, although no Recommended Dietary Allowance values yet exist. Few studies have explored the effects of L and Z from a whole food on MPOD. Daily consumption of one Hass avocado containing 0.5 mg of L over six months was associated with a significant increase in MPOD in healthy adults38. In contrast, no increase in MPOD was observed after consuming one Hass avocado daily for three months39. Daily consumption of egg yolks providing 1.38 mg L and 0.21 mg Z resulted in a significant increase in MPOD and other measures of visual acuity in older adults with signs of early-stage AMD after 12 months40. Another study giving older adults two egg yolks/day for five weeks, followed by four egg yolks/day for five weeks reported increases in MPOD, in some subjects but only among those with low MPOD values at the start of the intervention41.
Our study has some limitations. Choice of a control is always a challenge in whole food studies, since masking is an issue. A commercially available LZ supplement was used, rather than an inert capsule, since our research design was intended to compare options available to consumers and explore the role of goji berries over and above the intake of purified L and Z. Volunteers were not screened for low MPOD as an inclusion criteria. Finally, although MPOD was the primary outcome measure in this study, other ocular measurements such as contrast sensitivity and best corrected visual acuity were not assessed. Future studies on goji berry intake and eye health should combine functional and anatomic measurements.
In conclusion, this study showed that 90 days of goji berry consumption was associated with an increase in MPOD in middle-aged healthy adults. In addition to L and Z, other bioactive compounds in goji berries may be involved in the increase in MPOD. Further research on goji berries is warranted as both a dietary strategy to help reduce the risk of AMD or to serve as part of an integrative approach to mitigate the consequences of this disorder.