Nutrient-gene interactions: Coffee and Caffeine

By Nutritank Writing Team

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Nutritional genomics, ‘nutrigenomics’, ‘is the study of how nutrients interact with our genes and the nutritional control of gene expression’ (Bender, 2021). Epigenetics is how behaviours and interactions with our environment can switch genes on and off, without any changes being made to the base sequence of DNA (Bender, 2021).

Coffee and Histone Acetylation

As well as being antioxidants and anti-inflammatories, polyphenols, such as caffeine, may interact with our genes and alter gene expression (Felisbino et al., 2021). Studies show that polyphenols can reduce risks of non-communicable diseases, such as obesity and cardiovascular disease, through gene transcription regulation (Dall’Asta et al., 2022). For example, coffee contains hydroxycinnamic acid, which inhibits histone deacetylases to induce histone hyperacetylation (Dall’Asta et al., 2022); an epigenetic modification whereby chromatin structure is altered to become accessible or inaccessible to transcription factors, resulting in gene expression (Lee et al., 2020). Furthermore, studies suggest that polyphenols have anti-cancer properties by modulating transcription activity to regulate inflammation; thus, reducing oxidative stress and inhibiting cancer progression (Zhou et al., 2016; Kim et al., 2023; Tehami et al., 2023).

Coffee and DNA Methylation

A study by Chuang et al., (2017), using animal models, identified that coffee may benefit health by altering DNA methylation levels in the blood. DNA methylation regulates gene expression and has a role in ‘cell-proliferation, genomic imprinting, normal development and ageing’ (Alam et al., 2019). Furthermore, Ding, Xu and Lau (2023) found that ‘habitual coffee consumption’ altered DNA methylation sites located at 11 genes; with the majority linked to immune response and lipid metabolism, which can reduce risks of pathogen infection and lipid accumulation in non-alcoholic fatty liver disease (NAFLD).

 Epigenetic Effects of Coffee

There are three essential active ingredients in coffee with epigenetic effects: caffeine, chlorogenic acid (CGA), and caffeic acid (CA) (Ding, Xu and Lau, 2023). According to Ding, Xu and Lau, (2023) coffee affects the genome by ‘modulating DNA methylation and demethylation, histone modifications, and ncRNA expression’. Examples include:

  • Cancer: Studies suggest that coffee consumption can regulate ncRNA expression of colon carcinoma, which inhibits cancer proliferation (Ding, Xu and Lau, 2023). In vitro studies have shown CGA to inhibit the miR-31 oncogene, which is involved in promoting the cell-cycle progression (Ding, Xu and Lau, 2023).
  • Neurological function: Nutrigenomic studies have found coffee to be neuroprotective against Parkinson’s Disease (PD) and Alzheimer’s Disease (AD) (Ding, Xu and Lau, 2023; Lee and Mhd Rodzi, 2022).
    • According to Lee and Mhd Rodzi (2022), neuroprotective actions of caffeine include:
      • Antagonising the adenosine A2A receptor to regulate dopaminergic transmission.
      • Modulates VMAT-2 gene expression preventing neurotoxicity and brain damage by regulating neurotransmitters like dopamine, serotonin and noradrenaline.
      • Upregulating cytochrome oxidase (Cox) expression for striatal neuron survival (learning and memory).
    • Kidney function: In animal models, caffeine was found to be improve diabetic nephropathy by restoring autophagic activity by suppressing the gene expression of miR-133b, -342, and –30a and downregulating expression of miR-636 (Ding, Xu and Lau, 2023).

Nutrigenetics: the effect genetic variations can have on the food and nutrients we consume and how this can affect health (Ramos-Lopez et al., 2017).

The cytochrome P450 1A2 (CYP1A2) gene is responsible for 95% metabolism of caffeine in the liver, which can affect individuals differently; some people are fast metabolisers, and some are slow metabolisers (Mullins et al., 2020). For example, single nucleotide polymorphisms (SNP) of the CYP1A2 gene can lead to hypersensitivity to caffeine whereas carriers of the Heterozygous (Adenine/Cytosine) gene metabolise caffeine more slowly (Mullins et al., 2020).

Reference List

  • Alam, I. et al. (2019) ‘Relationship of nutrigenomics and aging: Involvement of DNA methylation’, Journal of Nutrition & Intermediary Metabolism, 16, p. 100098. Available at:
  • Bender, D.A. (2021) Introduction To Nutrition And Metabolism. S.L.: Crc Press.
  • Chuang, Y.-H. et al. (2017) ‘Coffee consumption is associated with DNA methylation levels of human blood’, European Journal of Human Genetics, 25(5), pp. 608–616. Available at:
  • Dall’Asta, M. et al. (2022) ‘Nutrigenomics: an underestimated contribution to the functional role of polyphenols’, Current Opinion in Food Science, 47, p. 100880. Available at:
  • Ding, Q., Xu, Y.-M. and Lau, A.T.Y. (2023) ‘The Epigenetic Effects of Coffee’, Molecules, 28(4), p. 1770. Available at:
  • Felisbino, K. et al. (2021) ‘Nutrigenomics in Regulating the Expression of Genes Related to Type 2 Diabetes Mellitus’, Frontiers in Physiology, 12. Available at:
  • Kim, K.H. et al. (2023) ‘Advanced Delivery System of Polyphenols for Effective Cancer Prevention and Therapy’, Antioxidants, 12(5), p. 1048. Available at:
  • Lee, H.-T. et al. (2020) ‘The Key Role of DNA Methylation and Histone Acetylation in Epigenetics of Atherosclerosis’, Journal of Lipid and Atherosclerosis, 9(3), pp. 419–434. Available at:
  • Lee, L.K. and Mhd Rodzi, N.A.R. (2022) ‘Addressing the Neuroprotective Actions of Coffee in Parkinson’s Disease: An Emerging Nutrigenomic Analysis’, Antioxidants, 11(8), p. 1587. Available at:
  • Mullins, V.A. et al. (2020) ‘Genomics in Personalized Nutrition: Can You “Eat for Your Genes”?’, Nutrients, 12(10), p. 3118. Available at:
  • Tehami, W. et al. (2023) ‘New Insights Into the Anticancer Effects of p-Coumaric Acid: Focus on Colorectal Cancer’, Dose-Response, 21(1), p. 155932582211507. Available at:
  • Zhou, Y. et al. (2016) ‘Natural Polyphenols for Prevention and Treatment of Cancer’, Nutrients, 8(8). Available at:



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