Thirty-one healthy, middle-aged adult males and females met the inclusion criteria between May 2019 and Jan 2020. The participants consumed either goji berries or the LZ supplement 5 days per week for 90 days. Twenty-eight individuals completed the intervention, after which two in the goji berry and one from the LZ group were excluded from the data analysis due to measurement errors. Furthermore, data from one was subsequently removed after learning of a major change in dietary patterns that included a low intake of macro-nutrients between days 45 and 90 .Reported protocol compliance was greater than 96% for both groups, and no adverse symptoms were noted other than minor intestinal gas from one participant in the goji berry group. Table 1presents the reported average intake of select nutrients in the habitual diet that may have affected eye health over the study period. No significant differences between groups were noted. The composition of the goji berries is presented in Table 2. A daily goji berry serving provided 28.8 mg of Z, hydroponic nft which was substantially higher than the 4 mg of Z present in the supplement.
Although sufficient extraction of L from our goji berry samples could not be obtained, previous work by others estimated a L content of 0.15 mg in 28 g of goji berries from six different goji berry samples collected in the Ningxia province of China, the same region from which the goji berries used in this study were obtained.Baseline MPOD measures were similar between the goji berry and supplement groups . No significant interaction effects for treatment and time were observed in any REs. A significant main effect of time was found for MPOD at 0.25 RE . In a sub-analysis, intake of gojiberries, but not LZ, significantly increased MPOD at 0.25 RE at day 90 compared to baseline . There was also a significant main effect of time for MPOD at 1.75 RE , with a significant increase at day 45 compared to the baseline , and again between day 90 . No significant MPOD changes were noted at any REs in the LZ group.Ninety days of 28 g of goji berry intake significantly increased the optical biomarker MPOD in healthy adults at 0.25 and 1.75 REs. These results suggest that even in a healthy population with no evidence of small drusen or early AMD, goji berry intake can improve eye health. Our results are consistent with data of improved MPOD after a similar amount and intake period of goji berry in a Chinese population at risk for intermediate AMD.
Moreover, our trial is consistent with reports of protection against macular hypopigmentation and drusen development in a population of generally healthy and older individuals who were provided Z at approximately a third of the amount of Z provided in the current trial. Our findings suggest that a higher intake of Z relative to L may be useful in reducing the risk of AMD. This is consistent with increased MPOD levels after 4 months of supplementation with 20 mg Z or 26 mg Z with 8 mg L plus 190 mg of mixed omega-3 fatty acids by young healthy adults. 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, which may increase the potential for improved MPOD in this peripheral area of the macula. Our results are also consistent with data from 11 randomized controlled trials where supplementation with at least 10 mg of the macular carotenoids was effective at increasing MPOD. Significant correlations were observed between the overall skin carotenoid score and MPOD, which is consistent with clinical results of carotenoid supplementation.
Further analysis demonstrated that L and Z, but not goji berry intake, was significantly influencing this trend. Previous work has shown an association between serum L and Z in skin and blood with macular pigment carotenoid accumulation. Data from the current trial are consistent with this observation as goji berry intake was significantly associated with the skin carotenoid score. However, in contrast to data with L and Z supplements, MPOD score was not correlated with changes in skin carotenoids with goji berry intake. The skin photometer detects overall carotenoid content, and as goji berries are also rich in β-carotene, neoxanthin, and cryptoxanthin, these carotenoids likely influenced the skin measurements, and would not reflect the selective carotenoid accumulation of L and Z in the macula. Other goji berry components such as taurine, vitamin C, zinc, and LBP may influence the results by lowering oxidant stress and improving eye health. For example, studies in animals and cell lines suggest that LBP can protect against AMD by reducing oxidative stress and cell apoptosis in retinal pigment epithelium. Taken together, under the conditions tested, it is reasonable that MPOD may not fully 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 levels, our findings suggest that even in populations with normal MPOD values, a significant increase can be detected after goji berry consumption at the most central part of the macula . 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 Z. The Age-Related Eye Disease Study 2 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 acid. The results showed a significantly reduced rate of progression from intermediate- to late-stage AMD after 5 years. Secondary analyses of the study indicated protective roles of L and Z. We did not use the AREDS2 supplement for the comparison group because this formula has only been shown to be effective for those with intermediate AMD, 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 the development of AMD. In the current study, the reported dietary intake of L plus Z, hydroponic channel 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 1.6–1.86 mg/d.Three to five mg/d of L and Z have been recommended to help support normal macular function, although no recommended dietary allowance values yet exist. Daily consumption of one Hass avocado containing 0.5 mg of L over 6 months was associated with a significant increase in MPOD in healthy adults. In contrast, no increase in MPOD was observed after consuming one Hass avocado daily for 3 months. 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 months. Another study giving older adults two egg yolks/day for 5 weeks, followed by four egg yolks/day for 5 weeks, reported increases in MPOD, but only among those with low baseline MPOD values. The addition of either spinach or corn , or the combination, for 14 months significantly increased the MPOD among the majority of healthy individuals. 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. The actual amount of L and Z in the supplement was not confirmed. A previous report noted that the carotenoid content of some powder-based supplements tested in 2017 did not meet label claims, while oil-based supplements did. Since L and Z are preferentially deposited at different eccentricities in the retina, the different amounts of Z in the goji berries and supplement may not be ideal. Volunteers were not screened for low MPOD as an inclusion criterion. Although the relatively modest number of participants in each group may raise some concerns, these numbers are similar to those reported by Obana et al. and are consistent with an initial probe study. Finally, although MPOD was the primary outcome measure, other ocular measurements such as contrast sensitivity and best corrected visual acuity were not assessed. Future studies on goji berry intake and eye health ideally should combine functional and anatomic measurements.Cardiovascular diseases have been the leading cause of death globally, with mortality estimated to be 17.9 million people in 2019, accounting for 32% of all deaths.1 Common modifiable risk factors for CVD include hypertension, hyperlipidemia, diabetes, harmful alcohol use, sedentary lifestyle, smoking, and male sex. In women, menopause is a risk factor for CVD due to the loss of the cardioprotective effects of estrogen and an increased likelihood of developing endothelial dysfunction, dyslipidemia, glucose resistance, and vascular inflammation. Endothelial dysfunction may also lead to an increased risk of cardiovascular events due to impaired control of vascular tone.5 Abundant consumption of fruits and vegetables is known to reduce the risk of CVD.6,7 Fruits and vegetables contain a variety of nutrients and bioactive compounds, many of which have vasculoprotective effects. Insights from traditional diets offer clues regarding which plant foods might confer vascular health benefits. For example, Kuna Indians living on their native islands off of the coast of Panama consuming a traditional diet rich in cocoa, fish, and fruits such as mangos showed virtually no CVD or hypertension. However, when they migrated to an urban environment and ate a diet rich in processed foods and fats, and low in their traditional fruits and vegetables, the incidence of vascular diseases increased significantly. While thesetrends helped to identify cocoa as a potentially vasculoprotective food, other foods with traditional use history for heart health, such as mango have been less studied. Mangos are abundant in β-carotene, and vitamins C and E, the intake of which are associated with reduced risk for CVD. Mango also contains numerous phenolic acids and polyphenols. Mangiferin, a unique xanthone polyphenol found in mango pulp, bark, and leaves has been shown to have bioactive properties such as anti-inflammatory and anti-diabetic effects. In hyperuricemic rats, mangiferin intake significantly reduced systolic blood pressure , serum uric acid and inflammatory markers, and increased the expression of endothelial nitric oxide synthase . In overweight individuals, mangiferin intake was associated with a reduction in serum triglycerides, free fatty acids, and the insulin resistance index.16 Moreover, insulin sensitivity was improved after mango fruit powder supplementation compared to a high fat control group in male C57BL/6 mice with early signs of metabolic syndrome. In overweight and obese individuals, the postprandial glucose and insulin levels after 100 kcal of fresh mango intake were significantly lower than the consumption of isocaloric low-fat cookies.18 These outcomes suggest that mango intake may have vasodilation and glucose control effects in humans. The vasodilation function of the vascular epithelium in response to reactive hyperemia is a useful measure of vascular function, and is measured non-invasively using flow mediated dilation or peripheral arterial tonometry . Reactive hyperemia is the shear stress induced from an increased blood flow caused by the release of occlusion of an artery. Using PAT, the changes in digital arterial pulse volume are assessed at baseline and after ischemia through digital probes placed on the fingertips, with the contralateral arm serving as the control. Although both methods may predict CVD events, a reduced reactive hyperemiavalue measured by FMD was associated with higher body mass index , age, and SBP, while PAT was associated with higher BMI, hypercholesterolemia, and diabetes.