The Z and L content among dried goji berries ranges from 25 to 152 mg/100g, and 0.3 to 1.9 mg/100g, respectively, based on different cultivars. Additionally, the predominant form of Z in goji berries is a dipalmitate , connecting with a diester linkage, which has shown a significantly higher intestinal absorption than monoester and free Z due to the high efficacy of hydrolysis, mainly by carboxyl ester lipase. According to the National Health and Nutrition Examination Survey, the average L and Z intake among adults in the United States was 1.58 – 1.76 mg/d. Therefore, to increase dietary intake of these two xanthophylls, goji berry is an excellent source, which can complement other food sources such as green leafy vegetables, egg yolk, yellow corn products, and orange bell peppers. Recent clinical research on goji berry shows promising effects in protecting against AMD. Healthy older individuals who consumed 10 mg of Z extract from goji berries daily for 90 days showed no change in macular pigmentation or soft drusen, hydroponic nft system and significantly higher circulating Z levels, compared to a control group, which presented an increase in soft drusen.
In an uncontrolled trial, individuals with early stage AMD who consume a beverage daily for five months that contained 12 mg of L and 2 mg of Z derived from marigold flower and goji berry, respectively, showed lower interocular pressures, better best-corrected visual acuity scores and higher circulating levels of L and Z compared to their baseline levels. Unfortunately, the study lacked a control group, did not test the effect of Z separately, and did not clarify whether the form of Z extracted from goji berry was the dipalmitate. Another study investigating the effects of an herbal formula among healthy adults with dry eyes noted that those chewing tablets containing L , Z , combined with extracts from blackcurrant, chrysanthemum, and goji berry showed dose-dependent reductions in eye fatigue symptoms and tear secretion, as well as improved macular pigment optical density , a common non-invasive method to measure the total L and Z in the center of the macula, compared to those in a placebo group. The basis of this formula was derived from TCM, so the multi-component formulation could not directly assess the role of any single ingredient.
Another study in patients with early AMD reported that the MPOD was significantly higher in those consuming 25 g/day of goji berries for 90 days, compared to their baseline levels and to a habitual diet control group. The BCVA was also significantly improved in the goji berry group compared to their baseline values. We recently reported that MPOD and skin carotenoid scores were significantly increased in healthy middle-aged individuals consuming 28 g/day of goji berries five times a week for 90 days, compared to a group taking a dietary supplement with 6 mg of L and 4 mg of Z. These results illustrate that MPOD levels can increase in healthy individuals even without early signs of AMD. While these results are encouraging, longer intervention periods with a larger number of participants would be helpful to replicate and extend these initial observations. In addition to AMD, goji berries have also been studied as a therapy for retinitis pigmentosa, an inherited retinal disease. Patients who consume 0.35 g/d of Lycium barbarum polysaccharides for 12 months showed a significant improvement in visual acuity and macular thickness, compared to control subjects who did not consume L or Z.
Other bioactive compounds found in goji berries include flavonoids, vitamins, minerals, betaine, cerebrosides, phenolic acids, and certain amino acids which may also support the overall health of the eye, particularly when working synergistically. Based on preclinical evidence, potential benefits of goji berry intake on glaucoma and diabetic retinopathy have also been suggested. Goji berry extract ameliorated the high glucose-induced blood-retinal barrier disruption in human retinal pigment epithelial cells. Studies reported that LBP showed significant neuroprotective effects on retinal ganglion cells in male C57BL/6N mice and Sprague-Dawley rats with ocular hypertension. In db/db mice with thin retina, goji berry extract restored the thickness of the retina, the ganglion cell number, and the integrity of retinal pigment epithelium after daily intake for eight weeks.10Traditional uses of food in general, and fruits specifically, provide useful guides for modern research in both nutrition and pharmaceuticals. This literature review illustrates the evidence and certain proposed mechanisms of select fruits with a high phytonutrient profile on cardiovascular and eye health. The consumption of these fruits and bio-active compounds derived from them demonstrate great potential to protect against certain age-related diseases. Therefore, the objectives of this dissertation are i) to investigate the effects of mango consumption on markers of cardiovascular diseases, ii) to examine the effects of goji berry consumption on macular pigment accumulation in human eyes, and iii) to review evidence for L, Z, and goji berries on eye health throughout the lifespan, with an emphasis on clinical studies.Age-related macular degeneration is the leading cause of blindness among seniors in developed countries, and third worldwide after uncorrected refractive errors and cataracts. In early stages, the disease is characterized by small to intermediate drusen with pigmentary changes that may progress rapidly to more advanced forms such as choroidal neovascularization or central geographic atrophy with loss of central vision. Lutein , zeaxanthin , and the isomer meso-zeaxanthin are macular pigments that filter damaging blue light and provide oxidative defense in the macula. These pigments are found in plants as xanthophylls, with increased dietary intake proposed to reduce the development and progression of AMD. The relative concentration of xanthophyll carotenoids in the retina can be measured noninvasively by psychophysical and objective methods, expressed as macular pigment optical density. Numerous epidemiological studies report that individuals with a low MPOD level are at an increased risk of AMD. Dietary L and Z are found in certain fruits and vegetables with red, yellow, or orange color, egg yolk, and in some green leafy vegetables. The dietary intake of Z is lower than L in all age groups and ethnicities in the U.S.. Dietary intakes of L and Z are strongly associated with their serum levels, as well as with MPOD. Previous studies have shown that high intakes of these carotenoids from dietary sources or supplements can increase plasma L and Z, and MPOD. Once early AMD has progressed to the intermediate stage, dietary supplements are indicated, but no clinical evidence yet exists for interventions that can address the prevention of small-intermediate drusen with pigmentary changes, the initial clinical signs of macular disruption.Goji berry , also termed wolfberry or Go Chi Zi, has been used in traditional Chinese medicine for more than 2000 years. The bright red berry contains the highest amount of Z among all known dietary sources and is mainly present in a dipalmitate form. The intake of zeaxanthin dipalmitate extracts from goji berry increases plasma Z to a greater extent than non-esterified Z supplementation. The berries also contain unique carbohydrates that are present as conjugates with peptides or proteins, nft channel which are often referred to L. barbarum polysaccharides . These have shown anti-inflammatory and neuroprotective effects in animal and cell culture studies . The typical adult human eye has approximately 2.4 times more Z than L in the central fovea of the macula, making goji berry intake a prime candidate for increasing MPOD. Nevertheless, there is a paucity of clinical evidence on goji berry and MPOD particularly for the prevention or delay of progression from early to intermediate AMD.
In individuals from China with signs of early AMD, 25 g of daily consumption of goji berries for 90 days significantly increased both serum Z and MPOD. However, this study had a broad age range , some participants smoked, and others had certain pre-existing medical conditions. Additionally, the authors only reported central MPOD values up to 0.5 retinal eccentricity , whereas macular pathology and visual dysfunction in AMD may extend beyond that central region. Therefore, to provide a more complete understanding of the influence of goji berry intake on the progression AMD, data is needed on for different population groups that measures MPOD at eccentricities over the entirety of the macula. In the current study, we prospectively evaluated if the daily intake of 28 g of goji berries or a commercially available supplement providing 6 mg of L and 4 mg for 90 days can improve MPOD and skin carotenoid levels, an index of total carotenoid intake, among healthy middle aged adults, 45 to 65 years old, with no signs of drusen or early AMD.Eighty-eight volunteers, ages from 45 to 65 years old, were recruited from an online website and public advertisements in the area of greater Sacramento, California. Participants provided informed consent and were screened with a questionnaire. Inclusion criteria were being generally healthy , having a normal macular condition as verified by an optometrist, and if relevant, being prescribed the same medication regimen for at least 6 months that was not related to carotenoid metabolism and was approved by the study physician. Exclusion criteria were a dislike of, or allergy to goji berries, diseases of the eye, malabsorption problems, substance or alcohol abuse, smoking, drugs for management of lipids, glucose, or blood pressure, use of dietary supplements other than multivitamins and minerals that provided greater than 100% of the U.S. Dietary Reference Intake, or any supplement containing L or Z. The intervention was registered on ClinicalTrials.gov , with the first posted date of 6 December 2019, complied with the tenets of the Declaration of Helsinki, was approved by the Institutional Review Board of the University of California , Davis and was conducted at the UC Davis Ragle Human Nutrition Research Center.Qualified participants were randomized into a prospective, parallel-arm, unmasked study to consume either 28 g of goji berries or a commercially available supplement of L and Z five days per week for 90 days. Study measurements were collected at baseline , at 45 ± 2 days and 90 ± 2 days after intake. Twenty-eight grams of goji berries is considered a single serving size. The berries in this study were USDA-certified organic goji berries grown in the Ningxia region of northern China and provided by Navitas Organics, Novato CA, USA. The goji berries were portioned into clean, single-serving plastic bags and provided in 45-day allotments. The commercially available supplements were purchased online, contained 6 mg of L and 4 mg of Z per serving and were repackaged into 45-day supplies in clean plastic bottles. Compliance was monitored by a self-administered log. Habitual dietary information was collected with the Automated Self-Administered 24 h dietary assessment webbased tool once between day 0 and 45, and once again between day 45 and 90. The MPOD was assessed by the psychophysical method of customized heterochromatic flicker photometry using a macular densitometer . After participants viewed a 5-minute video detailing the measurement procedures, they were dark adapted for 7 minutes and then began the test. The flicker frequency was selected based on a preliminary test of the participant’s sensitivity. The task was to eliminate or minimize the flicker in the visual field three times by turning a dial that changed the intensity of a 460 nm light. Each participant performed the test while looking directly at the flickering light at 0.25, 0.5, 1, and 1.75 RE degrees, representing the MPOD level from the center to the periphery of the macula.Skin carotenoid content was measured by reflection spectroscopy . After cleaning, the tip of the right index finger was inserted into the spectrophotometer and three measurements were collected. A skin carotenoid score was calculated by the system software. Carotenoids that exist in human plasma, including β-carotene, lycopene, L, Z, and their isomers have been successfully detected in toto and quantified by this device , which has been validated to reflect fruit and vegetable consumption.Sample size was based on a study that assessed the impact of a Z supplement on MPOD in 24 healthy people. Statistical analyses were performed with JMP version 16 . Two-tailed t-tests evaluated potential between-group differences at baseline. The MPOD and skin carotenoid data were analyzed with mixed-effects models using time and treatment as the main factors, with age and sex as the covariates, and participant ID as the random effect. For main effects, student t-tests determined significance within group pairs. pValues of 0.05 or less were considered statistically significant. Correlation coefficients between the outcome measures were determined via Spearman’s method. The mean values of the dietary intake data were compared by two-tailed t-tests, which were log-transformed when necessary, and presented as the mean ± S.E.M. or the back-transformed mean with 95% confidence intervals .