Christen William G, Rist Pamela M, Moorthy M Vinayaga, Smith Douglas C, Holman Beth, Clar Allison, Glynn Robert J, Mares Julie A, Sobrin Lucia, Shadyab Aladdin H, Allison Matthew A, Millen Amy E, Manson JoAnn E, Sesso Howard D
Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
JAMA Ophthalmol. 2025 May 1;143(5):429-437. doi: 10.1001/jamaophthalmol.2025.0353.
Abnormalities of choroidal blood flow in the eye are associated with occurrence of age-related macular degeneration (AMD). Cocoa flavanols show beneficial effects on vascular risk factors in small and short-term trials and may help reduce AMD risk.
To examine whether daily supplementation with cocoa extract, a source of flavanols, prevents the development or progression of AMD.
DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified ancillary study of the COSMOS (COcoa Supplement and Multivitamins Outcomes Study) trial, a double-blind, placebo-controlled, 2 × 2 factorial randomized clinical trial of a cocoa extract supplement and a multivitamin supplement in the prevention of cardiovascular disease and cancer among 21 442 US adults, including 12 666 women aged 65 years and older and 8776 men aged 60 years and older. The intervention phase was performed from June 2015 through December 2020; data analysis was completed in August 2024.
Cocoa extract supplement (500 mg/day cocoa flavanols, including 80 mg (-)-epicatechin) or placebo.
The primary end point was a composite of incident cases of AMD plus cases of progression to advanced AMD (geographic atrophy, neovascular membrane, retinal pigment epithelium detachment, or disciform scar) among participants with AMD at baseline, based on self-report confirmed by medical record review.
Mean (SD) participant age was 72.1 (6.6) years, and 12 666 participants (59.1%) were female. During a median (IQR) period of 3.6 (3.2-4.2) years of treatment and follow-up, 344 participants (1.6%) experienced a confirmed AMD event (316 incident AMD, 28 progression to advanced AMD). For the primary composite end point, there were 159 cases (1.5%) in the cocoa extract group and 185 cases (1.7%) in the placebo group (hazard ratio [HR], 0.87; 95% CI, 0.71-1.08; P = .21). Separate Cox models fitted because of evidence of nonproportional hazards (P = .048) indicated a 23% decreased risk in the cocoa extract group during the first 2 years of treatment (HR, 0.77; 95% CI, 0.59-1.01), with no added benefit for treatment beyond 2 years (HR, 1.06; 95% CI, 0.76-1.50). Similar time-dependent findings were observed for the secondary trial outcomes of incident visually significant AMD and advanced AMD.
In this ancillary study of the COSMOS randomized clinical trial, cocoa extract supplementation for a median period of 3.6 years among older women and men had no effect overall on occurrence of AMD. However, a possible modest treatment effect early in the trial could not be ruled out, which warrants further investigation to clarify whether cocoa extract may help reduce AMD risk.
ClinicalTrials.gov Identifier: NCT03205202.
眼部脉络膜血流异常与年龄相关性黄斑变性（AMD）的发生有关。在小型短期试验中，可可黄烷醇对血管危险因素显示出有益作用，可能有助于降低AMD风险。
研究每日补充可可提取物（一种黄烷醇来源）是否能预防AMD的发生或进展。
设计、地点和参与者：这是COSMOS（可可补充剂和多种维生素结果研究）试验的一项预先指定的辅助研究，COSMOS试验是一项双盲、安慰剂对照、2×2析因随机临床试验，研究可可提取物补充剂和多种维生素补充剂对21442名美国成年人预防心血管疾病和癌症的效果，其中包括12666名65岁及以上的女性和8776名60岁及以上的男性。干预阶段从2015年6月持续到2020年12月；数据分析于2024年8月完成。
可可提取物补充剂（每日500毫克可可黄烷醇，包括80毫克（-）-表儿茶素）或安慰剂。
主要终点是基线时患有AMD的参与者中，AMD发病病例与进展为晚期AMD（地图样萎缩、新生血管膜、视网膜色素上皮脱离或盘状瘢痕）病例的综合情况，基于病历审查确认的自我报告。
参与者的平均（标准差）年龄为72.1（6.6）岁，12666名参与者（59.1%）为女性。在中位（四分位间距）3.6（3.2 - 4.2）年的治疗和随访期间，344名参与者（1.6%）发生了确诊的AMD事件（316例新发AMD，28例进展为晚期AMD）。对于主要综合终点，可可提取物组有159例（1.5%），安慰剂组有185例（1.7%）（风险比[HR]，0.87；95%置信区间，0.71 - 1.08；P = 0.21）。由于存在非比例风险的证据（P = 0.048）而拟合的单独Cox模型表明，在治疗的前2年，可可提取物组的风险降低了23%（HR，0.77；95%置信区间，0.59 - 1.01），2年后治疗没有额外益处（HR，1.06；95%置信区间，0.76 - 1.50）。在新发有视觉意义的AMD和晚期AMD的次要试验结局中也观察到了类似的时间依赖性结果。
在这项COSMOS随机临床试验的辅助研究中，年龄较大的女性和男性补充可可提取物中位时间为3.6年，总体上对AMD的发生没有影响。然而，不能排除试验早期可能存在适度的治疗效果，这值得进一步研究以明确可可提取物是否有助于降低AMD风险。
ClinicalTrials.gov标识符：NCT03205202。
