Dietary blueberries and goji berries in the prevention of age-related macular degeneration: a narrative review of the evidence, mechanisms, and research gaps

Introduction

Background

Age-related macular degeneration (AMD) is a leading cause of vision loss in the developed world (1). As the name suggests, it particularly impacts individuals aged 55 years and above (2). The disease progresses from early AMD, characterized by medium drusen without pigmentary abnormalities, through to late AMD, characterized by either neovascular AMD and/or geographic atrophy (2).

Treatment for early and intermediate AMD focuses on lifestyle modifications, including dietary adjustments, to slow disease progression (3). The treatment approach changes once the disease develops into late AMD. For neovascular AMD, standard therapy involves repeated intraocular injections of anti-vascular endothelial growth factor (anti-VEGF), which has reduced the incidence of blindness by 50%. However, patient response to anti-VEGF injections cannot be predicted, and the injections carry inherent risks, such as ocular trauma. For geographic atrophy, intravitreal inhibitors of the complement cascade can slow disease progression, but these therapies do not halt the decline of visual function. Since many patients with advanced AMD experience significant vision loss, implementing early preventative measures to delay disease progression is essential.

Although its exact pathogenesis is not fully known, increasing dietary intake of specific antioxidants helps mitigate AMD progression (1,4,5). For example, the Age-Related Eye Disease Study (AREDS) found that those taking an antioxidant supplement that included vitamins C and E, beta-carotene, and zinc reduced their risk of progression to advanced AMD by about 25%, which reinforces the use of nutrition as a tool to manage this disease (5,6). For certain individuals, there can be some concerns related to supplement therapy. Recent evidence indicates that high-dose zinc supplementation can potentially increase AMD progression for those with high complement factor H (CFH) risk alleles and no age-related maculopathy susceptibility 2 (ARMS2) risk alleles (7).

Key micronutrients thought to be preventative for macular degeneration include the phytochemicals anthocyanins and xanthophylls, specifically lutein (L) and zeaxanthin (Z) (8). Anthocyanins are water-soluble pigments that provide the red, purple, and blue colors to fruits and vegetables (9). Berries are particularly rich in these compounds. Anthocyanins exhibit strong antioxidant and anti-inflammatory properties, allowing them to counteract oxidative stress. Specifically for the eye, anthocyanins can help increase blood supply to the retina, improve vision, and promote regeneration of rhodopsin (8,10,11). L and Z are both xanthophylls, which are oxygen-containing carotenoids that concentrate in the macula of the human retina (8). Along with their retinal metabolite meso-zeaxanthin, L and Z are collectively referred to as the macular pigment (MP) (12). Xanthophylls are common in green, red and yellow vegetables, including spinach, kale, and corn. The MP performs blue light filtration and acts as an antioxidant to protect retinal cells and reduce lipofuscin formation (13).

In clinical practice, patients frequently inquire about the potential benefits of consuming blueberries or goji berries (Lycium barbarum) as nutritional interventions for AMD. Although many fruits and vegetables contain high levels of anthocyanins, L, or Z, blueberries and goji berries were chosen for this review because of their high bioactive content and their relevance to common patient inquiries. Specifically, blueberries are rich in anthocyanins, while goji berries contain the highest known levels of Z for any food (14,15). This narrative review evaluates the evidence for these berries in AMD, helping provide clearer guidance for clinicians.

Understanding the pathophysiological mechanisms of this disease further highlights why dietary antioxidants may benefit patients. Oxidative damage and inflammation are recognized as major contributors to the development and progression of AMD (1,16,17). The retina and the retinal pigment epithelium (RPE) are particularly susceptible to oxidative damage because their high metabolic activity and constant light exposure cause the formation of reactive oxygen species (ROS) (18). An imbalance between the creation and neutralization of ROS is linked to the inflammatory pathways of AMD (19). There is also an accumulation of toxic byproducts, like lipofuscin, due to cell renewal process dysfunction (20).

Another hallmark of AMD relates to the formation of drusen (19,21). Drusen are lipid and protein-rich deposits that form between RPE cells and Bruch’s membrane (22). Some small drusen are associated with normal aging; however, an increase in their size or number is associated with an increased risk of developing this disease. Soft drusen contain pro-inflammatory factors, and their formation can cause retinal tissue atrophy, calcification of Bruch’s membrane, and even its potential rupture (23).

Researchers have also identified certain genetic factors associated with AMD (18). These include a variant of the CFH Y402H, the ARMS2, and the high-temperature requirement A serine peptidase 1 (HTRA1) (18,24,25).

Rationale and knowledge gap

Since current pharmacological treatments have limitations and can only slow down the progression to neovascular AMD, prioritizing both primary and secondary prevention strategies is essential (26). Modifications to lifestyle, such as smoking cessation and increasing dietary consumption of antioxidants, are currently used to mitigate disease progression (1,4,5). Anthocyanins, L and Z are antioxidants that can potentially reduce the ROS in the retina and influence cellular signaling pathways in ways that may benefit AMD (8,18). Blueberry anthocyanins appear to protect RPE cells by reducing ROS and lipid peroxidation, enhancing antioxidant enzymes, and inhibiting apoptosis by blocking cell signaling pathways (27). L and Z are believed to mitigate this disease by absorbing blue light, reducing the formation of ROS, and decreasing the formation of lipofuscin (28,29). Polysaccharides from goji berries help protect RPE cells in vitro by regulating the antioxidant enzymes catalase and superoxide dismutase, and by lowering matrix metalloproteinase-2 (MMP2) expression, which helps to reduce ROS (30).

Objective

Despite numerous preclinical studies suggesting that these berries could help with AMD, few human studies have been reported (16). We have therefore conducted a narrative review of the evidence for consuming blueberries, goji berries, or their products in AMD. We present this article in accordance with the Narrative Review reporting checklist (available at https://aes.amegroups.com/article/view/10.21037/aes-25-55/rc).

Methods

MEDLINE via Ovid, Embase via Ovid, Web of Science, Cochrane Database for Systematic Reviews, and Google Scholar were searched in June 2024 and updated in November 2025 to identify relevant articles. The search was limited to articles published in English. Initial screening was performed independently by the first author, which was deemed appropriate because this narrative review addresses a single clinical question (31). After removing duplicates and screening titles and abstracts, 29 full-text articles were assessed. All articles were retrieved through academic library or interlibrary loan. Of these, a total of five articles met the inclusion criteria. All authors reached consensus for final article selection.

In terms of the quality of selected articles, the risk of bias was assessed by using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) for nonrandomized studies, or the Cochrane Risk of Bias Tool for randomized trials (32,33). Risk levels of ‘unclear’, ‘low’, ‘moderate’, or ‘high’ were used during evaluation. Overall, these studies were deemed to have a predominantly low risk of bias, with no study rated as high risk. Publication bias was not assessed due to the limited number of studies. Additional details can be found in Appendix 1.

As shown in Table 1, search terms included ocular-health MeSH terms (“Macular degeneration”, “Retinal neovascularization”, “Macula lutea”, “Retinal degeneration”, and “Choroid”) with associated common keywords and abbreviations using the Boolean OR operator (“AMD”, “ArMD”, “CNVM”, “GA”, “Choroid neovascularization”, “Choroidal neovascular membrane”, and “Geographic Atrophy”), food-related MeSH terms (“Lycium” and “Blueberry plants”) and associated common keywords (“Goji berr*” and “Blueberr*”). Inclusion criteria then focused the review to studies relevant for evaluating the dietary intake of these berries (or their products) in adults for AMD. There was no exclusion based on the date of publication. Refer to Appendix 2 for a copy of the detailed search strategy. This strategy was adjusted for each database to identify all published systematic reviews, meta-analyses, cohort, case-control, and cross-sectional studies, and randomized controlled trials. Study populations included adult males and females. The exclusion criteria applied to conference presentations, grey literature, non-peer-reviewed articles, commentaries, editorials, studies that lacked AMD as a health outcome, non-English language papers, and non-human studies. A manual search of references included within original studies and relevant review articles was also performed.

Qualitative summary of blueberries, goji berries, and AMD

Our search identified five relevant studies published between 2011 and 2024 (14,34-37). The main study features and participant characteristics are summarized in Table 2, while measured outcomes are provided in Table 3. Studies varied in design, population, intervention, and comparator. Due to these variations, a qualitative synthesis follows.

During the screening process, three recent review articles were also identified that discussed natural products for treating AMD and included goji berries and/or anthocyanins in part of their analysis (18,28,38). While these articles fell outside the scope of this review, each found evidence suggesting that antioxidant-rich foods or supplements may benefit AMD. There was also a noted recent interest in the “gut-eye axis”, potentially linking gut microbiota to ocular health and AMD (39). A small randomized clinical trial is currently underway to assess the effects of consuming goji berries compared to fiber on visual health and the gut microbiome, with an expected completion date of 2026 (40). To our knowledge, this is the only relevant clinical trial currently in progress. No other trials were identified in a Cochrane Central search conducted in November 2025.

Preventive effects of anthocyanins and blueberries on AMD

This review confirms that there are few population studies examining anthocyanin intake in relation to ocular disease risk (41,42). Only one study examined the connection between blueberry and anthocyanin intake and AMD (14). This secondary analysis used data from the Women’s Health Study, a large randomized controlled trial that originally investigated low-dose aspirin and vitamin E for cardiovascular disease and cancer prevention in women ≥45 years in the United States. Blueberry intake was gathered via a semiquantitative food frequency questionnaire at baseline, where one serving was defined as 0.5 cup of fresh, frozen or canned blueberries. AMD cases were initially self-reported by participants and then confirmed through either medical record verification or completed questionnaires by ophthalmologists/optometrists. The study classified AMD exclusively by using total AMD (all confirmed diagnoses) and visually significant AMD [cases with best corrected visual acuity (BCVA) reduced to 20/30 or worse].

By using data from the Women’s Health Study, Sesso and colleagues found that consuming at least one serving of blueberries once per week reduced the total risk of AMD by 28% (14). There was a similar trend observed for a reduced risk of visually significant AMD, but this relationship was not statistically significant. No significant relationship between anthocyanin intake and AMD was found; thus, the role of anthocyanins in preventing AMD remains unclear.

The authors noted several important methodological limitations that temper these results (14). First, there was a potential misclassification bias because the study relied on a single baseline self-report of dietary factors. Second, blueberry and anthocyanin intake may have been susceptible to residual confounding from uncontrolled factors, such as baseline health status. Third, the study was also unable to determine a dose-response relationship because there was an insufficient intake of larger doses of blueberries. Finally, despite the observed relationship between blueberry consumption and a reduced risk of AMD, additional studies are needed to replicate these results across a more socioeconomically diverse population with a balanced gender profile. This would improve the generalizability of these findings and allow researchers to better understand the clinically relevant mechanisms at work.

Preventive and therapeutic effects of goji berries on AMD

The four remaining articles (34-37) focused on goji berry consumption and various visual health outcomes, as discussed below.

Changes to macular pigment optical density (MPOD)

As previously discussed, the MP is concentrated in the macula, the central region of the retina (43). It appears yellow due to its high concentration of three carotenoids: L, Z, and meso-zeaxanthin (12). These antioxidants help protect the retina from photochemical oxidative damage by filtering blue light (44). In vivo measurements of the MP are possible by examining the MPOD, which indicates the amount of L and Z present in the macula (43). MPOD follows a linear correlation with dietary intake of carotenoid-rich foods and circulating serum L and Z levels, and it can be measured using heterochromatic flicker photometry (HFP), fundus autofluorescence, or fundus reflectance. Although MPOD itself is not a reliable predictor of AMD progression, lower levels have been associated with disease risk factors, including obesity, tobacco use, and a positive family history (13,43,44). These levels are also typically lower for patients with AMD compared to healthy individuals (43).

Three of the four articles that examined goji berry intake and AMD reported on changes in MPOD using HFP (35-37). Each study reported a positive relationship between goji berry consumption and increased MPOD (Table 3). While MPOD was consistently measured using HFP, the areas of the macula included in the studies were inconsistently reported. Li et al. [2021] assessed MPOD at specific retinal eccentricities (0.25, 0.5, 1, and 1.75 RE) and multiple time points (36). Conversely, Li et al. [2018] stated that “MPODs of the fovea and the parafovea were measured” (p. 972), which provides a less precise indication of the areas studied (35). Peng et al. [2016] reported on improvements to MPOD, but did not specify the exact macula areas examined (37). Using HFP to measure MPOD also requires the patient to perceive and adjust to the light, which introduces subjectivity and variability across patients (45). Other techniques, such as autofluorescence imaging, are more objective and could facilitate meta-analysis of this type of data (28,46).

Changes to BCVA

Two of the four articles reported on changes to BCVA (35,37). While both studies noted an improvement, the evidence was inconsistent. Li et al. [2018] noted a statistically significant improvement in BCVA for the goji berry cohort (35). The study assumed that goji berry intake caused the increase in BCVA. However, there was a substantial discrepancy in baseline values between the two cohorts; thus, BCVA results were not a primary focus of their study. In contrast, Peng et al. [2016] reported a statistically significant improvement in BCVA for patients with early AMD (37). They hypothesized that the two-fold increase in serum L and Z levels from consuming the goji berry and marigold flower mixture would improve BCVA by forming a protective layer in macular retina and RPE, reducing initiation and progression of AMD (37,47). However, the authors note that further work is needed to investigate this hypothesis (37).

Indeed, high-energy light is selectively filtered by xanthophylls, and this filtering reduces light scattering and longitudinal chromatic aberration (28). Hu et al. [2023] theorize that higher levels of xanthophylls can improve BCVA by lowering dispersion and chromatic distortion from different light wavelengths (28). A positive correlation between MPOD and improved BCVA supports this theory and has been reported elsewhere (48). As well, L and Z are thought to scavenge ROS and help filter blue light, which would protect the retina and RPE from light-initiated oxidative damage and thus help protect against AMD disease progression (49).

Changes to drusen count

There is an established link between soft drusen number and risk of AMD (50). Only one of the included studies, by Bucheli et al. [2011], specifically reported on and assessed drusen count (34). At study onset, all subjects had baseline examinations to confirm the presence of zero or one soft drusen. Following the 90-day study period, those who consumed a proprietary Lacto-Wolfberry formulation (the LWB group) experienced no increase in macula pigmentation nor soft drusen accumulation. In contrast, soft drusen count significantly increased for eleven subjects in the placebo cohort (P=0.004). The LWB group also experienced a significant increase in plasma Z and antioxidant capacity (26% and 57%, respectively). Despite this, no significant relationship was observed between the change in plasma Z and the change in macular characteristics. Therefore, while this study indicates that goji berry supplementation can protect against macula hypopigmentation and drusen accumulation, the mechanism is unclear, which highlights the need for additional research to investigate this effect.

Strengths and limitations

Each study reported a positive relationship between goji berry or blueberry intake and a visual health outcome associated with AMD (Table 3). These results come from studies performed in different countries/regions and are generally consistent with other reports of L and Z supplementation and AMD (18,26,28,51). However, data interpretation can be nuanced, especially without any large-scale, high-quality and placebo-controlled studies on the topic. For this review, differences in study designs, interventions, and outcome assessments prevented a quantitative meta-analysis of MPOD or BCVA. The evidence our review has identified comes with important limitations that warrant further consideration, in addition to the items discussed previously.

Multi-component contributions of whole berries to AMD-related pathways

The Age-Related Eye Disease Studies (AREDS and AREDS2) demonstrated that a high-dose antioxidant vitamin and mineral combination formula can slow the progression of AMD (6,52). Key components of these formulations include vitamins C and E, and zinc. However, the independent contributions of these nutrients for AMD remain inconclusive (53). This highlights the potential importance of using multiple antioxidants for managing this disease.

Recent research suggests that multiple bioactive compounds found in a variety of berry types may offer synergistic effects against AMD (54). These compounds may influence a variety of biological pathways, which could enhance their overall impact. For example, vitamin C concentrates in the lens epithelium where it acts as a primary aqueous-phase antioxidant; L and Z accumulate in the MP and filter blue light (400–500 nm), blocking more than 90% of phototoxic wavelengths at the RPE; anthocyanins help preserve microvascular integrity; and dietary fiber metabolizes by gut microbiota into short-chain fatty acids, which can cross the blood-retina barrier to affect retinal signaling (5,54,55). Supporting this potential role of fiber, a study by Agron et al. found that insoluble dietary fiber was associated with a decreased risk of progression to large drusen for AREDS and AREDS2 participants (56).

Results from Sesso et al. may indirectly suggest the possibility of synergistic interactions (14). The authors reported no association between total dietary anthocyanin intake and AMD risk, yet blueberry consumption was associated with reduced AMD risk. These findings could suggest that components beyond anthocyanins may contribute to the protective effect observed with blueberry intake. Sesso and colleagues emphasized the need for further research to clarify the underlying mechanism.

Bioavailability differences between whole berries and extracts

The variations in sources and dosages of goji berries and blueberries across the studies complicated comparisons. Since no research-grade berry extracts are available on the market, researchers must purify their own supplements, which can introduce differences in the bioavailability of the bioactive compounds (57). For example, Peng et al. [2016] used a unique supplement in their study, prepared from goji berries, marigold flowers, and enriched with L, Z, and other phytocomponents to specifically improve bioavailability. This issue persists even with whole berries, since nutritional composition can change depending on berry genotype, geographic origin, growing conditions, harvesting time, and post-harvesting factors (58,59). Also, whole foods provide nutrition within a food matrix, and this can influence the bioavailability of compounds in ways that differ from isolated extracts (60). For example, current evidence suggests that the food matrix enhances anthocyanin stability and helps protect it from degradation until it reaches the intestine. In summary, there are bioavailability differences between whole berries, as well as between whole berries and their extracts. This represents an important area for standardization in future research.

Variability in nutritional analyses and bioavailability markers

Included articles varied in their nutritional analyses of the berries or berry products used. As well, the measurement and reporting of changes in serum L and Z levels, which provide insights into the bioavailability of L and Z from the ingested product, varied across included goji berry studies (see Table 3). Different assessments of visual parameters were also used. Taken together, these variations prevented the establishment of meaningful correlations between bioavailability markers and visual function outcomes. As a result, it is not currently possible to determine whether the measured changes in serum L and Z concentrations were associated with improvements in MPOD or BCVA.

Complicating this matter is the lack of reporting on dietary consumption patterns for study participants. This issue applies generally across much of the research investigating xanthophyll-rich food intake and visual health outcomes (28). Baseline dietary intake for fat, fiber, and antioxidants can affect the bioavailability of L and Z in foods (61). Yet of the included articles, only Li et al. [2021] and Sesso et al. [2024] provided a breakdown of select dietary nutrient intake for participants during the study period (14,36).

It is important to know the diet for study participants because their eating habits can directly affect their overall health and likelihood of AMD progression. For instance, a recent systematic review reported that following a Mediterranean diet, which is rich in vegetables and fruits—including berries—reduces the likelihood of disease progression from early to late AMD (26). In contrast, a Western diet, which involves a high consumption of red and processed meats, high-fat dairy, and refined grains, may be a risk factor in developing late AMD (62). Dietary consumption can directly affect AMD progression and should therefore be accounted for in analyses of dietary treatments for AMD.

Additionally, body fat loss can positively influence serum L concentrations (63). This suggests that physical features of study participants, like their body mass index and body fat, would be a useful metric to measure because they may influence bioavailability. However, this was inconsistently reported across the included studies.

Study populations

There were other notable limitations related to the study populations. Except for the work by Sesso et al. [2024] that examined data collected for the Women’s Health Study, all studies were relatively small and short in duration. Small sample sizes can reduce the statistical power to assess associations in the data (64). As well, the included studies took place in different regions, which could influence baseline dietary intake and genetic backgrounds. Genetics plays an important role in the development of AMD, and genetic variations may also affect how patients respond to dietary interventions for this disease (65,66). For example, it has been reported that some genetic variants associated with MPOD affected patient response to supplementation with L (66). Similarly, high-dose zinc supplementation may increase AMD progression for individuals with high CFH risk alleles and no ARMS2 risk alleles (7). Together, these findings suggest that genetic differences could influence individual responses to dietary interventions, and it would be worthwhile to collect genotyping data in future studies to assess these effects (67).

Exclusion criteria varied between studies, and some involved confounding factors. Li et al. [2018] included subjects across a broad age range, smokers, and those with preexisting health conditions, which can make it more difficult to interpret the effects of goji berry supplementation (35). Most of the included studies were relatively short in duration and focused on patients with no AMD or early AMD (Table 3). A previous review found that dietary L and Z is not significantly associated with a reduced risk of early AMD, but it may be protective against late AMD (68). Given this, it would be worthwhile for future studies to ensure confounding factors are eliminated, and to also investigate the effects of goji berry intake on late AMD.

Adverse outcomes and safety considerations

There is an unfortunate lack of literature exploring the long-term effects of blueberry and goji berry consumption on AMD. Although studies investigating the use of these berries to treat other conditions suggest both are generally well tolerated (41,58,69). From the studies included in this review, minor intestinal gas for one participant consuming 28 g/d of goji berries was the only reported adverse effect (36). A broader literature search identified a single case report of flecainide toxicity resulting from goji berry tea (70). Goji berries can strongly inhibit major CYP450 enzymes, which can cause serious, albeit uncommon, herb-drug interactions with medications such as flecainide and warfarin. Animal studies suggest that blueberry extract can cause hypoglycemia, though it is unclear how this could affect humans (71).

Reflecting on these results

This review identified only one relevant study related to blueberry consumption and AMD, confirming a gap in the published literature. Although the single study by Sesso et al. [2024] suggested blueberries may reduce the risk of developing AMD, there were several methodological limitations (14). Future studies are needed to reproduce these results and investigate the clinically relevant mechanisms at work.

This review also identified four studies examining the effects of goji berry intake and AMD (34-37). While each of these studies found potential benefits, there were inconsistencies in how they measured and reported on various visual outcomes, making it challenging to directly compare results. Using an objective technique to measure MPOD across the entire macula, such as autofluorescence imaging, could be useful in standardizing this measurement (28,46). Similarly, not all studies reported on changes in serum L and Z levels. Such measurements are indicators of bioavailability, and it would be useful to consistently include these measurements in future studies. The lack of reporting on dietary consumption patterns also complicated the ability to isolate the effects of goji berry consumption from the effects of the overall diet, and future studies would benefit from including this information. Other opportunities for improvement would be to perform genotyping on study participants, and report BMI and body fat information, since genetic variations can affect macula pigment and body fat levels can influence serum L concentrations (63,67).

To address heterogeneity in study designs, we propose standardizing outcome measurements, bioavailability assessments, participant characterization—including genotyping, BMI, and body fat—and documentation of dietary patterns. Future studies should also include balanced gender representation and focus on longer durations.

Conclusions

Overall, the current evidence that blueberries and goji berries are beneficial for preventing or delaying the progression of AMD is inconclusive. To better understand the mechanisms of action and the effects of blueberries and goji berries on AMD, larger, standardized studies are essential. Current research into the gut-eye axis for goji berry consumption and its effects on AMD may provide additional insights. This study may also help address patients’ questions regarding the use of blueberries and goji berries, as well as their over-the-counter products, in the management of AMD.

Until more robust data are available, clinicians should only consider mentioning blueberries and goji berries as part of a broader diet that is rich in antioxidants, as this may help contribute to overall eye health. Availability, accessibility, and affordability are key factors that influence household food purchasing decisions (72). Rather than focusing solely on blueberries or goji berries, patients and clinicians can work together to identify nutrient-rich food sources for anthocyanins, L and Z that the patient enjoys and is likely to purchase. These sources include, but are not limited to, green leafy vegetables and various fruits. This individualized approach may support successful long-term dietary changes while promoting overall eye health.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://aes.amegroups.com/article/view/10.21037/aes-25-55/rc

Peer Review File: Available at https://aes.amegroups.com/article/view/10.21037/aes-25-55/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aes.amegroups.com/article/view/10.21037/aes-25-55/coif). P.Y. serves as an unpaid editorial board member of Annals of Eye Science from July 2024 to December 2026. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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