All cancers are ultimately driven by metabolic disruption. If that is the case, can Metabolic Engineering® be used slow down tumor growth? If so, this would be a welcome addition to the usual clinical triad of cut (i.e., surgery), burn (i.e., radiation), and poison (i.e., chemotherapy) that have been the mainstays of cancer treatment for more than 80 years.
A new study suggests that two dietary components of Metabolic Engineering® (the Zone diet and high-dose fish oil) may offer that possibility, especially in the treatment of prostate cancer.
Prostate cancer is the second leading cause of cancer mortality in American males, with approximately 35,000 dying annually, and approximately 300,000 new cases of prostate cancer diagnosed in 2024. It is estimated that 1 in 8 American males will eventually develop prostate cancer (1). Of these new cases, about 50 percent opt for active surveillance rather than immediate surgery or radiation, but ultimately 50 percent will need to undergo surgery or radiation treatment within five years (2).
Some studies suggest that eating more vegetables is beneficial (3). Also, a detailed analysis indicated that omega-3 fatty acid supplementation is not associated with increased progression of prostate cancer (4); obviously, minimal dietary insight to be gleaned from these reports.
With this as background, a new trial has taken these dietary observations to a new level of sophistication (5). This trial took 100 males with either grade 1 or grade 2 prostate cancer who were practicing active surveillance and split them into two groups. The control group received no dietary counseling and was told not to take any fish oil supplementation for 1 year. The dietary advice to the active group was two-fold. First, supplement their diet with omega-3 fatty acids (2.2 grams of EPA and DHA) daily. Second, was to reduce their calorie intake by consuming no more than 30 percent of total calories—basically a poor man’s version of the Zone diet.
What was unique in this study was that, in addition to measuring standard markers of prostate cancer progression, the investigators looked at the level of the Ki-67 index derived from a prostate biopsy. The Ki-67 index is a very sensitive marker of the aggressiveness of prostate cancer and its future likelihood of patient mortality (6).
Well, what did the study indicate? First, patients in both groups had an initial AA/EPA ratio of 19, indicating that all subjects had significant chronic low-grade inflammation that drives tumor growth (7). In other words, they were all on thin ice given inflammation’s prominent role in promoting the tumor aggressiveness. The active group consuming EPA and DHA reduced their AA/EPA ratio from 19 to 7 in the first six months, and this reduced AA/EPA ratio was maintained at 12 months. There was no change in the AA/EPA ratio in the control group during the one-year study period. The active group participants also significantly reduced their calorie intake by more than 300 calories daily by simply decreasing their fat intake to less than 30% of total calories. Thus, they were following a poor man’s version of a calorie-restricted Zone diet.
What about the results? Although there were no changes in standard markers such as tumor grade, tumor length, or PSA levels at one year, the Ki-67 index, a precise marker of tumor aggressiveness, showed a striking change. The Ki-67 index increased by 25% in the control group and decreased by 14% in the active group. Thus, two relatively simple dietary changes had dramatically reduced the likelihood of existing prostate cancer from spreading.
Could the results have even been better? I believe that they would have been if they had employed Metabolic Engineering®. Metabolic Engineering is a more aggressive dietary approach to alter metabolic pathways that are disrupted in cancer. First, the Zone diet would have provided a better macronutrient composition to reduce further insulin resistance, which was only slightly reduced in the study. What decreases insulin resistance is an increase in AMPK activity that reduces cytokine-induced inflammation (8). Second, Metabolic Engineering® would have used a higher level of EPA and DHA supplementation to further reduce the AA/EPA ratio to 1.5-3. This would have required at least doubling their omega-3 fatty acid supplementation to 4.4 grams of EPA and DHA daily to reach that desired AA/EPA ratio (9). Third, Metabolic Engineering® would have provided additional polyphenol supplementation, which would have reduced oxidative stress, which also drives prostate tumor growth (10). So, as good as the results in reducing the aggressiveness of the existing tumor were in the study, I feel they could have been even greater if the patients had been following Metabolic Engineering® guidelines.
Bottom line is that if dietary interventions, especially Metabolic Engineering®, can provide potential improved outcomes in existing prostate cancer, it likely has equal potential in all types of cancer that ultimately result from a damaged metabolism.
References
1. American Cancer Society. American Cancer Society Launches the National Prostate Cancer Roundtable to Address an Alarming Rise in Diagnoses. 2024
2. Simpkin AJ, Tilling K, Martin RM, Lane JA, Hamdy FC, Holmberg L, Neal DE, Metcalfe C, Donovan JL. Systematic Review and Meta-analysis of Factors Determining Change to Radical Treatment in Active Surveillance for Localized Prostate Cancer. Eur Urol. 2015 Jun;67(6):993-1005. doi: 10.1016/j.eururo.2015.01.004. Epub 2015 Jan 21. PMID: 25616709.
3. Parsons JK, Pierce JP, Marshall JR. Vegetable Consumption and Progression of Prostate Cancer-Reply. JAMA. 2020 Jun 23;323(24):2530. doi: 10.1001/jama.2020.6732. PMID: 32573663.
4. Schenk JM, Liu M, Neuhouser ML, Newcomb LF, Zheng Y, Zhu K, Brooks JD, Carroll PR, Dash A, Ellis WJ, Filson CP, Gleave ME, Liss M, Martin FM, Morgan TM, Wagner AA, Lin DW. Dietary Patterns and Risk of Gleason Grade Progression among Men on Active Surveillance for Prostate Cancer: Results from the Canary Prostate Active Surveillance Study. Nutr Cancer. 2023;75(2):618-626. doi: 10.1080/01635581.2022.2143537. Epub 2022 Nov 7. PMID: 36343223; PMCID: PMC9974882.
5. Farrell SW, DeFina LF, Tintle NL, Leonard D, Cooper KH, Barlow CE, Haskell WL, Pavlovic A, Harris WS. Association of the Omega-3 Index with Incident Prostate Cancer with Updated Meta-Analysis: The Cooper Center Longitudinal Study. Nutrients. 2021 Jan 26;13(2):384. doi: 10.3390/nu13020384. PMID: 33530576; PMCID: PMC7912448.
6. Aronson WJ, Grogan T, Liang P, Jardack P, Liddell AR, Perez C, Elashoff D, Said J, Cohen P, Marks LS, Henning SM. High Omega-3, Low Omega-6 Diet With Fish Oil for Men With Prostate Cancer on Active Surveillance: The CAPFISH-3 Randomized Clinical Trial. J Clin Oncol. 2025 Mar;43(7):800-809. doi: 10.1200/JCO.24.00608.
7. Kammerer-Jacquet SF, Ahmad A, Møller H, Sandu H, Scardino P, Soosay G, Beltran L, Cuzick J, Berney DM. Ki-67 is an independent predictor of prostate cancer death in routine needle biopsy samples: proving utility for routine assessments. Mod Pathol. 2019 Sep;32(9):1303-1309. doi: 10.1038/s41379-019-0268-y. Epub 2019 Apr 11. PMID: 30976102; PMCID: PMC8647491.
8. Tewari AK, Stockert JA, Yadav SS, Yadav KK, Khan I. Inflammation and Prostate Cancer. Adv Exp Med Biol. 2018;1095:41-65. doi: 10.1007/978-3-319-95693-0_3. PMID: 30229548.
9. Burzinskis E, Janulaityte I, Jievaltas M, Skaudickas D, Burzinskiene G, Dainius E, Naudziunas A, Vitkauskiene A. Inflammatory markers in prostate cancer: potential roles in risk stratification and immune profiling. J Immunotoxicol. 2025 Dec;22(1):2497776. doi: 10.1080/1547691X.2025.2497776. Epub 2025 Apr 28. PMID: 40296239.
10. Borja-Magno A, Guevara-Cruz M, Flores-López A, Carrillo-Domínguez S, Granados J, Arias C, Perry M, Sears B, Bourges H, Gómez FE. Differential effects of high-dose omega-3 fatty acids on metabolism and inflammation in patients with obesity: eicosapentaenoic and docosahexaenoic acid supplementation. Front Nutr. 2023 May 5;10:1156995. doi: 10.3389/fnut.2023.1156995. PMID: 37215211; PMCID: PMC10196397.
11. Khandrika L, Kumar B, Koul S, Maroni P, Koul HK. Oxidative stress in prostate cancer. Cancer Lett. 2009 Sep 18;282(2):125-36. doi: 10.1016/j.canlet.2008.12.011. Epub 2009 Jan 30. PMID: 19185987; PMCID: PMC2789743.
2 comments
Interesting. I’ve been following The Zone since ’96 (about 80% of the time), and started taking about 5,000 mg of highly purified Fish Oil (Nordic Naturals) every day (mitigating some autoimmune issues). I’m 62 and in great health (or so I thought), w/ great blood pressure and fine grades on two Colonoscopies. I wasn’t getting my blood work done, however, and last April scored an 18 on my PSA. Of note, I’ve been doing intermittent and long term fasts for many years and have loved the benefits, especially higher HGH and feeling confident about autophagy’s reported effects on precancerous cells. I did a lot fasting while waiting three months for a second PSA, including a 5 day fast, feeling confident that the 18 was anomalous and/or would be reduced, but it rocketed to 23 in 90 days. I had the full radical prostatectomy in November, and appear to be good to go and not need radiation (still, one hell of a tough operation and recovery… not easy). My surgeon acknowledged the benefits of fasting for other cancers and congratulated me on my fine colon, but mentioned a meta analysis paper looking at diets of athletes and non athletes (I didn’t catch the citation). He said there was less than a 1% difference in cancer outcome according to diet, and that prostate cancer was fed by testosterone. As I delved deeper I found some disturbing papers about fasting and autophagy being beneficial to curbing some tumor growth, but also making some tumors more resilient (damn!). I fear the latter might have been what happened to me (especially because I have no family hx. of prostate cancer). I’m cutting back on the fasting–which, BTW, Sears endorsed in his first book–and going back to my mainstay of broccoli and chicken. Moral: don’t assume a low inflammation diet and positive markers for other cancers will preclude the need for regular testing.
Actually all tumors are driven by the gene transcription factor, mTOR. Testosterone activates mTOR, and AMPK inhibits mTOR. The Zone diet is not about fasting per se, but controlled calorie restriction with a defined macronutrient balance to alter the balance of mTOR to AMPK. This can be enhanced by the use of high-dose fish oil to further reduce inflammation. Relative to prostate cancer, the recent Capfish study (doi: 10.1200/JCO.24.00608) indicated that the combination of high-dose fish oil and a quasi-Zone diet reduced the aggressiveness of existing prostate tumors. Broccoli and chicken is far more in line with the Zone diet than is fasting. It is keeping the balance of protein-to-glycemic load of each meal that controls your metabolism for the next five hours. To get the latest information on the continuing evolution of my earliest concepts of Metabolic Engineering, I would urge you to visit http://www.DrSears.com.