Table 2.
Dietary supplements studied in ABCA4-associated Stargardt disease
| Class | Chemical compound [aliases] | Targeted pathway | Clinical Study | Design | Duration | Participant groups | Outcome measures | Safety | Key findings |
|---|---|---|---|---|---|---|---|---|---|
| Vitamin A (modified) | C20-D3-retinyl acetate [gildeuretinol acetate; ALK-001] | Kinetic isotope effect on retinoid condensation; photoreceptor/RPE preservation | NCT02402660 (TEASE) | Multicenter, randomized, double-masked, placebo-controlled clinical trial | 24 months | C20-D3-retinyl acetate (14 mg/day) and placebo; n = 50 | Primary: DDAF growth; Secondary: BCVA, LLVA, OCT exploratory structural measures | No unexpected safety signals reported | Efficacy to be determined; no published in peer-reviewed literature |
| Omega-3 Fatty Acids | Docosahexaenoic Acid (DHA) | Photoreceptor membrane integrity | NCT00060749 | Single-center, randomized, double-masked, placebo-controlled repeated crossover RCT | 12 months (four 3-month crossover periods) | DHA (2000 mg/day) ↔ placebo; n = 11 (crossover) | Primary: mfERG); Secondary: 30-Hz flicker ERG, Humphrey 10-2 visual field, BCVA (ETDRS), D-15 color vision, VFQ-25, serum DHA levels | No treatment-related adverse events | No statistically significant improvement on macular function or electrophysiologic outcomes (McDonald et al., 2008) [39] |
| NCT03297515 (MADEOS) | Multicenter, randomized, double-masked, placebo-controlled pilot RCT (mixed AMD/STGD1 cohort) | 6 months | Omega-3 (EPA+DHA ~3.6 g/day) and placebo; *STGD1 subset included but not analyzed separately | BCVA (ETDRS), systemic lipid biomarkers (AA/EPA ratio) | No major safety signals reported | No STGD1-specific efficacy conclusions can be drawn; outcomes reported for combined AMD/STGD1 cohort | |||
| NAT-3 study | Single-center, open-label, single-arm interventional pilot study | 6 months | DHA 840 mg/day; n = 20 | Primary: BCVA, mfERG; Secondary: FAF, OCT, serum and RBC membrane DHA | No adverse events or treatment-related toxicity reported | No statistically significant improvement overall; mild functional improvements observed in a small subset of patients | |||
| Apocarotenoids | Crocins and crocetin [saffron] | Retinal oxidative stress; upregulate antioxidant enzymes; activate anti-apoptotic signal pathway |
NCT01278277 (STARSAF02) | Single-center, randomized, double-masked, placebo-controlled crossover trial | 12 months (two 6-month crossover periods) | Saffron (20 mg/day) ↔ placebo in crossover; n = 31 | Primary: ffERG amplitude; Secondary: Visual function measures (per protocol) | No safety concerns reported | No significant improvement in ffERG or visual function compared with placebo (Piccardi et al., 2019) [41] |
| Carotenoids | Lutein (trace zeaxanthin from marigold extract) | Macular pigment augmentation; antioxidant; photo-oxidative protection | Academic | Single-center, open-label, uncontrolled pilot supplementation | 6 months | Lutein (20 mg/day); n = 17 total, n = 11 supplemented | Macular pigment optical density, serum lutein/zeaxanthin, BCVA, foveal sensitivity, retinal thickness (OCT) | No safety concerns reported | Increased serum lutein and macular pigment optical density in a subset of patients, but no improvement in BCVA or foveal sensitivity observed (Aleman et al., 2007) [42] |
BCVA, best-corrected visual acuity; DDAF, definitely decreased autofluorescence; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; ERG, electroretinography; ffERG, full-field electroretinography; mfERG, multifocal electroretinography; FAF, fundus autofluorescence; LLVA, low-luminance visual acuity; MPOD, macular pigment optical density; OCT, optical coherence tomography; RCT, randomized controlled trial; STGD1, Stargardt disease type 1; VFQ-25, 25-item National Eye Institute Visual Function Questionnaire.