High Nitrate and Thiocyanate Levels Tied to Early AMD Risk

A new NHANES-based study of 4,727 adults found that higher urinary nitrate and thiocyanate levels were linked to increased risk of AMD, and demonstrated a dose-response. Photo: Jeffry Gerson, OD. Click image to enlarge. Thyroid dysfunction has been associated with age-related macular degeneration (AMD). However, some of these relationships have controversial findings or lack significant evidence, prompting a group of researchers from China to investigate whether urinary thiocyanate, perchlorate and nitrate increase a person’s risk of AMD. Their results were published last week in PLOS One.Data was obtained from the US National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008, ultimately including a total of 4,727 participants aged ≥40 years, of which 362 were AMD and 4,365 were non-AMD individuals. The mean age was 55.9 and 52% of participants were women. The prevalence of AMD was 7.7%. Among 362 AMD patients, 88.1% had early AMD and the remaining 11.9% were deemed to have advanced disease. According to the results, nitrate exposure was positively associated with any AMD risk, with an odds ratio (OR) of 1.19. Subgroup analyses showed higher OR relationships as well. Those with the highest levels of nitrate and thiocyanate showed odds ratios of 1.94 and 1.70, respectively. Significant interaction between nitrate and hypertension on AMD risk was detected, and thiocyanate level was positively associated with AMD risk among the diabetes subgroup at an OR of 1.48. Significant interaction between thiocyanate and diabetes on AMD risk was detected. Summarizing their results in their paper, the authors wrote, “The results indicated that high nitrate and thiocyanate concentrations were significantly correlated with a higher AMD risk especially early AMD risk, while perchlorate was not correlated with AMD risk.”In the context of existing literature, the researchers say it is hard to assess the effect of single nutrient intake on AMD risk because an individual usually takes in hundreds of nutrients per day. “Our findings were consistent with a study assessing the relationship of nitrate-nitrogen levels in drinking water with AMD incidence,” they wrote. Few studies have explored the mechanism linking nitrate and thiocyanate exposure to retinal function and AMD risk. According to the authors, high levels of nitrate can generate elevated amounts of reactive nitrogen species such as peroxynitrite, a reactive tissue impairing substance, which can cause the accumulation of abnormal proteins and then lead to RPE damage and degeneration of photoreceptors. “The main routes of thiocyanate exposure are intake of cruciferous vegetables and cigarette smoking,” they wrote. “It is reported that high levels of thiocyanate could easily cross the basolateral membrane of RPE and impact the electrophysiological function of the retina.”Despite limitations such as its cross-sectional design, reliance on single-spot urine samples, potential for confounding and the small number of late AMD patients, the authors concluded that this study provides epidemiological evidence that high levels of nitrate and thiocyanate are associated with an increased risk of AMD. “These exploratory findings are hypothesis-generating and highlight the need for further longitudinal and laboratory studies to clarify potential mechanisms and clinical implications,” wrote the authors.Click here for the journal source. Jia S, Liu Q, Liu P, Zhao W, Li S. Association of perchlorate, nitrate, and thiocyanate with age-related macular degeneration in the United States. PLoS One. October 29, 2025. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.