Tuesday, June 11, 2024



PSA, or prostate-specific antigen, is a protein produced by prostate cells. It can be elevated when these cells increase in number and is a common screening test for prostate cancer. Studies have shown that up to 75% of men with elevated PSA levels do not have prostate cancer on biopsy, however, and up to 50% of prostate cancers are overdiagnosed. [1]

This means that most of the time, an elevated PSA is due to other causes not related to cancer, including normal aging and benign prostatic hypertrophy (BPH). Inflammation caused by prostatitis, trauma, or vigorous exercise, as well as sexual activity, can also impact PSA levels. In addition, PSA levels can vary with ethnicity, weight, diabetes, and certain medications. [1, 2]

Because the consequences of elevated PSA levels in the absence of prostate cancer can include increased surveillance and unnecessary biopsies, anxiety, and can even impact the ability to get life insurance, there is a need for more information on how to lower PSA levels and, indeed, whether this correlates with improved health.

Many supplements, dietary, and lifestyle choices have been promoted to lower PSA levels. However, the research is often contradictory and often linked together with prostate cancer risk; thus, knowing which strategies to reduce PSA are based on science can be challenging. Genetic expression is helping us untangle the complexity.

While a small number of cases of prostate cancer are due to rare genetic mutations, most are related to more common errors in genes called SNPs. These SNPs create small alterations in biochemistry and biology linked to the risk of prostate cancer, but this risk is modifiable by dietary and lifestyle choices and environmental exposures over that person’s lifetime. [3]  It turns out this holds true for PSA levels as well. 

Researchers evaluating PSA levels in men without prostate cancer found that up to 30-40% of the variation in PSA levels could be attributed to underlying SNPs in multiple biological systems including hormone metabolism, DNA repair, inflammation, cancer promotion and suppression, and oxidative stress. [3,4]

(L) Image source: Kachuri L et al. PSA-associated variants identified on GWAS.

Asian men have the lowest rate of prostate cancer, followed by Native and Latin American men, then Caucasian men, with African American men having the highest. Risks associated with elevated PSA also vary with ethnicity. Second-generation Japanese men in the U.S. will have the same rate of prostate cancer as Caucasian men, indicating that a combination of genetics and diet/lifestyle plays a role. [5]

Epigenetics gives us the ability to change how our genes express in response to our environment. As with our DNA, epigenetic changes can be inherited. But unlike our DNA, these epigenetic changes are dynamic. This is one of the key mechanisms by which changes in diet, lifestyle, and environment can create changes in health and well-being.

Epigenetic alterations associated with diet, exercise, smoking, trauma, or stress have been linked to elevated PSA levels as well as to prostate cancer. These can potentially be reversed by interventions addressing these factors. [6] Epigenetic testing may also be effective as a future screening tool, as it has been shown to reduce false positives of PSA tests in initial research.  [7]

Oxidative stress and chronic inflammation are linked to most chronic diseases including prostate cancer. [8] They are also linked with elevated PSA and are influenced by numerous factors, including diet, exercise, and stress – all of which “talk” to genes, influencing gene expression that can promote health or disease.

Early childhood stress and chronic stress are linked to increased inflammation and oxidative stress by altering gene expression, which can increase both PSA levels and prostate cancer. Combining mindfulness-based stress reduction (MBSR) and a plant-based diet has been shown to lower PSA levels [9] as has regular exercise. [10]

Plant-based diets, such as the Mediterranean Diet, include an abundance of foods rich in nutrients, antioxidants, and anti-inflammatory compounds, which are associated with beneficial gene expression that supports health. These include colorful fruits and vegetables, cruciferous vegetables, healthy fats, legumes, and whole grains, along with minimal amounts of processed foods and sugar. Conversely, diets low in these healthy foods but rich in saturated fats, processed foods, alcohol, and sugar are associated with adverse changes in gene expression that promote disease.

While research has shown the impact of various foods and diets on inflammation and oxidative stress, translating this into specific recommendations for reducing PSA is more challenging. One reason is that foods contain many different components that are often synergistic, and untangling these to isolate specific components often proves difficult. Another reason is that we are often looking at the wrong measurement.

Designing studies to evaluate the role of diet, supplements, and lifestyle in specific health issues, including PSA levels, is often fraught with challenges. This often translates into contradictory results that can be quite confusing, especially without knowing how to interpret the research. 

Evaluating multiple studies, one review found no evidence that intake of individual nutrients or supplements containing lycopene, vitamin E, cruciferous vegetables, soy/isoflavones, green tea, polyphenols, fish/marine omega-3, coffee, or vitamin D were significantly associated with PSA levels. [6] Another found that levels of Vitamin A, B2, C, D, E, alpha-carotene, selenium, lycopene, lutein + zeaxanthin, beta-cryptoxanthin, and folate were not associated with PSA levels, although low Vitamin D and low serum albumin were associated with elevated PSA levels. [10]

These results may reflect the limitations of applying the pharmaceutical model to nutritional supplements, as they often work synergistically. Consistent with this, the Pomi-T study showed that a specific supplement combining pomegranate, green tea, broccoli, and curcumin reduced PSA among men with prostate cancer. [11]

Antioxidants are not limited to vitamins and minerals. The most powerful antioxidants are phytonutrients. Phytonutrients, also known as polyphenols, can also have anti-inflammatory activity, affect epigenetics, and influence gene expression. Resveratrol, curcumin, sulforaphane, EGCG, quercetin, apigenin, genistein, silymarin, and anthocyanins are all examples. When evaluating the impact of antioxidants on oxidative stress, DNA damage provides a better assessment than individual nutrient status. Research shows that as these phytonutrients restore normal antioxidant status, they lower PSA levels along with inflammation. [12]

(L) Image source: Li, W., Chen, H., Xu, B., et al. (2023). Research progress on classification, sources and functions of dietary polyphenols for prevention and treatment of chronic diseases. Journal of Future Foods, 3(4), 289-305. https://doi.org/10.1016/j.jfutfo.2023.03.001

Putting this all together, reducing PSA levels needs to incorporate multiple elements to have the best effect. The combination of a Mediterranean-type Diet, regular exercise, and stress management, along with the incorporation of specific supplements, can beneficially affect gene expression to reduce PSA levels and potentially prevent progression to prostate cancer.


1) Bernal-Soriano, M. C., Parker, L. A., López-Garrigos, M., et al (2019). Factors associated with false negative and false positive results of prostate-specific antigen (PSA) and the impact on patient health: Cohort study protocol. Medicine, 98(40). https://doi.org/10.1097/MD.0000000000017451

2) Grammatikopoulou, M. G., Gkiouras, K., Papageorgiou, S. Τ., et al (2020). Dietary Factors and Supplements Influencing Prostate-Specific Antigen (PSA) Concentrations in Men with Prostate Cancer and Increased Cancer Risk: An Evidence Analysis Review Based on Randomized Controlled Trials. Nutrients, 12(10), 2985. https://doi.org/10.3390/nu12102985

3) Karunasinghe, N., Minas, T. Z., Bao, B., et al. (2022). Assessment of factors associated with PSA level in prostate cancer cases and controls from three geographical regions. Scientific Reports, 12(1), 1-16. https://doi.org/10.1038/s41598-021-04116-8

4) Kachuri, L., Hoffmann, T. J., Jiang, Y., et al (2023). Genetically adjusted PSA levels for prostate cancer screening. Nature Medicine, 29(6), 1412-1423. https://doi.org/10.1038/s41591-023-02277-9

5) Hinata, N., & Fujisawa, M. (2022). Racial Differences in Prostate Cancer Characteristics and Cancer-Specific Mortality: An Overview. The World Journal of Men's Health, 40(2), 217-227. https://doi.org/10.5534/wjmh.210070

6) Labbé, D. P., Zadra, G., Ebot, E. M., et al (2015). Role of diet in prostate cancer: The epigenetic link. Oncogene, 34(36), 4683-4691. https://doi.org/10.1038/onc.2014.422

7) Pchejetski, D., Hunter, E., Dezfouli, M., et al. (2023). Circulating Chromosome Conformation Signatures Significantly Enhance PSA Positive Predicting Value and Overall Accuracy for Prostate Cancer Detection. Cancers, 15(3), 821. https://doi.org/10.3390/cancers15030821

8) Rago, V., & Di Agostino, S. (2023). Novel Insights into the Role of the Antioxidants in Prostate Pathology. Antioxidants, 12(2), 289. https://doi.org/10.3390/antiox12020289

9) Dovey, Z., Horowitz, A., & Waingankar, N. (2023). The influence of lifestyle changes (diet, exercise and stress reduction) on prostate cancer tumour biology and patient outcomes: A systematic review. BJUI Compass, 4(4), 385-416. https://doi.org/10.1002/bco2.237

10) Lin, Y., Zhu, X., Aucoin, A. J., Fu, Q., Park, J. Y., & Tseng, S. (2023). Dietary and Serum Antioxidants Associated with Prostate-Specific Antigen for Middle-Aged and Older Men. Nutrients, 15(15). https://doi.org/10.3390/nu15153298

11) Thomas, R., Williams, M., Sharma, H., et al. (2014). A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer—The UK NCRN Pomi-T study. Prostate Cancer and Prostatic Diseases, 17(2), 180-186. https://doi.org/10.1038/pcan.2014.6

12) Naghii MR, Hedayati M, Mofid M (2015) Antioxidants therapy: An alternative for androgen deprivation therapy (ADT) to decrease prostate-specific antigen (PSA) level. 2: DOI: 10.15761/ICST.1000132


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