Study shows genetic link between instant coffee consumption and increased risk of dry AMD

(Image Credit: AdobeStock/Aleksey)

A new study from China revealed a genetic link between coffee consumption and age-related macular degeneration (AMD). Of particular note is that instant coffee may increase the risk of development of dry AMD. Reducing its intake could help prevent dry AMD. People at high‐risk for AMD should avoid instant coffee,¹ according to first author Qi Jia, MD,from theDepartment of Ophthalmology, Shiyan Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.

Investigators from other institutions in Hubei also participated in the study: the College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, and the Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.

Genetic factors have been reported to play a major role in the development of AMD, with many AMD‐related genetic loci, susceptibility genes, and risk factors identified, providing important clues for studying the mechanisms of AMD.^2-4 However, because the disease mechanisms are unclear and the treatment complex, slowing disease progression and timely prevention are particularly important,⁵ Jia and colleagues explained.

The effects of coffee on eye diseases and aging have been reported.^6-8 However, only a few studies have researched coffee and its association with AMD; previous cohort studies have shown that coffee can reduce the risk of AMD and slow its progression.⁹ However, cohort studies are often subject to biases due to confounding factors and reverse causation, leading to errors in the results.^10,11 Therefore, new methods to comprehensively assess the genetic association between coffee consumption and AMD are needed, they explained.

To conduct the study, the investigators obtained data on coffee consumption from genome‐wide association studies (GWAS) and the latest AMD‐related GWAS summary data from the Finngen consortium R11. The authors explained that they assessed the genetic correlation using linkage disequilibrium score regression, explored causal associations using Mendelian randomization, and identified shared genetic loci via colocalization. The investigations stated that combining the results of these three methods can provide more reliable evidence of the genetic variation and causal association between coffee consumption and AMD.¹²

Effects of instant coffee consumption

Jia and colleagues reported, “Our results revealed a genetic correlation between instant coffee consumption and dry AMD, with each standard deviation increase in instant coffee intake associated with a corresponding odds ratio of approximately 6.92 for dry AMD, indicating a 6.92‐fold increased risk. However, colocalization analysis did not show shared genetic variants between instant coffee consumption and AMD. Instant coffee may increase the risk of AMD, and reducing its intake could help prevent dry AMD. People at high‐risk for AMD should avoid instant coffee.”

Discussion of coffee effects

As noted, some studies have reported the beneficial effects of coffee against AMD,⁹ the current results, according to the investigators, provided a more detailed stratification of coffee types and yielded different results, indicating potential biases in previous research.

The linkage disequilibrium score regression results pointed to the potential genetic correlation between instant coffee consumption and both dry and wet AMD. Univariable Mendelian randomization analysis showed no causal relationship between overall coffee consumption and AMD.

“Interestingly, we found that instant coffee significantly increases the risk of AMD, with each standard deviation increase in instant coffee consumption corresponding to an odds ratio of approximately 6.92 for dry AMD, indicating a 6.92‐fold increased risk. This comprehensive analysis using various methods confirmed the reliable genetic link between coffee consumption and AMD,” they explained.

Coffee has been reported previously to improve liver steatosis and fibrosis and reduce their associated risks,¹³ and some reported both that decaffeinated coffee, ground coffee, and instant coffee might have protective effects on cardiovascular health and lower the risk of coronary heart disease and that excessive consumption was not associated with cardiovascular disease.^14-16

In contrast, coffee has been associated with an increased risk of primary open‐angle glaucoma age‐related cataracts.^7,17

They also noted that coffee seems to have a significant impact on age‐related diseases. “Although coffee consumption is positively correlated with longevity, instant coffee consumption is negatively correlated with the aging biomarker telomere length.^8,18 Similarly, we found no causal relationship between coffee and AMD, but a potential genetic and causal link between instant coffee and AMD. We speculate that the different effects of various types of coffee on AMD may be related to manufacturing processes, additives, and other factors,^19-21” they said.

Some studies have implicated the production of instant coffee to formation of potentially harmful substances such as acrylamide and advanced glycation end products (AGEs), which are involved in oxidative stress and inflammatory responses in retinal cells.

The manufacturing process of instant coffee involves brewing a concentrated extract and then spray‐drying or freeze‐drying the liquid; this intense heat and concentration generates high levels of Maillard reaction byproducts and often involves added ingredients (eg, sugar, creamer). Other types of coffee do not have similar additives, they pointed out.

The production process of other coffee types produces relatively few AGEs. Surveys of instant coffee chemistry show markedly elevated “neo‐formed” toxins.^22,23 AGEs activate multiple signaling pathways, leading to inflammation, apoptosis, and angiogenesis. AGEs also induce production of reactive oxygen species, which further exacerbates oxidative stress and inflammatory responses. AGEs also ultimately promote leukocyte adhesion to retinal endothelial cells, leading to disruption of the blood‐retinal barrier.²⁴

Jia and colleagues concluded, “Instant coffee may increase the risk of AMD, and reducing instant coffee intake can prevent dry AMD. People at high‐risk for AMD should avoid instant coffee intake.”

References

1. Jia Q, Zha Z, Li S, Zhang Y, Ke L, Liu S. Genetic correlation and mendelian randomization analyses support causal relationships between instant coffee and age‐related macular degeneration. Food Sci Nutr. 2025;13:e70439. doi:10.1002/fsn3.70439

2. Klein RJ, Zeiss C, Chew EY, et al. 2005. Complement factor H polymorphism in age‐related macular degeneration. Science. 2005;308: 385–389.

3. Fritsche LG, Fariss RN, Stambolian D, Abecasis GR, Curcio CA, Swaroop A. 2014. Age‐related macular degeneration: genetics and biology coming together. Annu Rev Genomics Human Genet. 2014;15:151–171.

4. Stahl A. The diagnosis and treatment of age‐related macular degeneration. Dtsch Ärztebl Int. 2020;117:513–520.

5. Deng Y , Qiao L, Du M, et al. Age‐related macular degeneration: epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy. Genes Dis. 2022;9:62–79.

6. Kim J, Aschard H, Kang JH, et al. Intraocular pressure, glaucoma, and dietary caffeine consumption: a gene‐diet interaction study from the UK Biobank. Ophthalmology. 2021;128:866–876.

7. Li X, Cheng S, Cheng J, Wang M, Zhong Y, Yu AY. Habitual coffee consumption increases risk of primary open‐angle glaucoma: a Mendelian randomization study. Ophthalmology. 2022; 129:1014–1021.

8. Wei Y, Li Z. Lai H, et al. Instant coffee is negatively associated with telomere length: finding from observational and Mendelian randomization analyses of UK Biobank. Nutrients. 2023;15:1354.

9. Chiu CJ, Chang ML, Li T, Gensler G, Taylor A. Visualization of dietary patterns and their associations with age‐related macular degeneration. Invest Ophthalmol Vis Sci. 2017;58:1404–1410.

10. Song JW, Chung KC. Observational studies: cohort and case‐control studies. Plast Reconstr Surg. 2010;126:2234–2242.

11. Vassy JL, Ho YL, Honerlaw J, et al. Yield and bias in defining a cohort study baseline from electronic health record data. J Biomed Inform. 2018;78:54–59.

12. Liu D, Cao M, Wang H, et al. Association between inflammatory bowel disease and cancer risk: evidence triangulation from genetic correlation, mendelian randomization, and colocalization analyses across East Asian and European populations. BMC Med. 2024;22:137.

13. Morisco F, Lembo V, Mazzone G, Camera S, Caporaso N. Coffee and liver health. J Clin Gastroenterol. 2014;48(Suppl 1): S87–S90.

14. O'Keefe JH, Bhatti SK, Patil HR, DiNicolantonio JJ, Lucan SC, Lavie CJ. Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all‐cause mortality. J Am Coll Cardiol. 2013;62:1043–1051.

15. Ding M, Bhupathiraju SN, Satija A, van Dam RM, Hu FB. 2014. Long‐term coffee consumption and risk of cardiovascular disease: a systematic review and a dose‐response meta‐analysis of prospective cohort studies. Circulation. 2014;129: 643–659.

16. Chieng D, Canovas R, Segan L, et al. The impact of coffee subtypes on incident cardiovascular disease, arrhythmias, and mortality: long‐term outcomes from the UK Biobank. Eur J Prev Cardiol. 2022;29:2240–2249.

17. Yuan S, Wolk A, Larsson SC. Metabolic and lifestyle factors in relation to senile cataract: a Mendelian randomization study. Sci Rep. 2022;12:409.

18. O'Keefe JH, DiNicolantonio JJ, Lavie CJ. Coffee for cardioprotection and longevity. Prog Cardiovasc Dis. 2018;61:38–42.

19. Moraes P, Bolini H. Different sweeteners in beverages prepared with instant and roasted ground coffee: ideal and equivalent sweetness. J Sens Stud. 2010;25:215–225.

20. FarahA, Farah A, eds. Coffee: production, quality and chemistry. Royal Society of Chemistry 2019; DOI: https://doi.org/10.1039/9781782622437

21. Neoh TL, Adachi S, Furuta T. Instant Coffee. In: Introduction to food manufacturing engineering. 2016;65–89. Springer, Singapore.

22. Zhang, F, Liu H, Wang Y. Production and inhibition of acrylamide during coffee processing. Food Sci Nutr. 2023;11:1305–1313. 10.1016/j.foodchem.2023.1305.

23. Moore TCB, Moore JE, Kaji Y, et al. 2003. The role of advanced glycation end products in retinal microvascular leukostasis. Invest Ophthalmol Vis Sci. 2003;44:4457–4464. 10.1167/iovs.02-1063.

24. Kang Q, Dai H, Jiang S, Yu L. Advanced glycation end products in diabetic retinopathy and phytochemical therapy. Front Nutr. 2022;9:1037186. 10.3389/fnut.2022.1037186.