Can a low-inflammation diet alter prostate health?

Prostate cancer remains the most common neoplasm diagnosed in North American and Western European men. Furthermore, this disease appears to be on the rise throughout Asia, as well as many developing nations. Risk factors including age, family history, and ethnicity have been demonstrated to impact prostate carcinogenesis; however, recent molecular insights have implicated chronic inflammation as critical in early prostate cancer development (Int J Cancer 2016; 139:2398–404).

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As a consequence of these molecular insights into prostate health, a focus on the dietary components capable of triggering inflammation as well as those able to mitigate inflammation, thereby limiting cellular damage, have been postulated to play a role in prostate carcinogenesis (figure). The mechanisms through which lifestyle factors such as diet affect the endogenous inflammatory milieu, if better elucidated, may provide opportunities for improved prostate health and screening strategies for prostate cancer prevention, as well as opportunities for improved treatment outcomes.

Diet and prostatic epithelial injury

Inflammation resulting in prostatic epithelial injury has been primarily attributed to several factors, including dietary carcinogens, hormonal imbalance, and infection (Nat Rev Cancer 2007; 7:256–69). Presence of corpora amylacea as a result of neutrophil discharge was observed in response to prostate epithelial desquamation secondary to recurrent prostate inflammation. Microscopic examination of prostate tissues including glands containing prostate cancer demonstrated this innate immune phenomenon to be evident in prostate glands both during and after inflammatory insult, with numerous corpora amylacea containing myeloperoxidase, alpha-defensins, and calprotectins diffusely observed throughout such tissues (Proc Natl Acad Sci USA 2009; 106:3443–8). Over time, prostate epithelial injury results in focal atrophy lesions, as these cells favor an abnormal stress response pathway, thereby promoting a tissue-localized pro-inflammatory environment that may support its progression to prostate cancer.

Epidemiologic studies have demonstrated that prostate cancer incidence and mortality display distinct geographical patterns, with men residing in North America and Western Europe exhibiting the highest risk for disease development, while the lowest risk is noted in men residing in Asia. Furthermore, this geographic pattern of prostate cancer risk has been shown to change upon emigration by individuals from low- to high-risk geographies. This finding has been strongly attributed to changes in dietary practices, with the strongest dietary associations for prostate cancer appearing to be red meat intake and a diet high in dietary fats (HDF) of animal origin (Cancer Treat Res 2014; 159:51–68) (table).

With respect to red meat intake, cooking at high temperatures or barbecuing that results in charring creates carcinogens, including heterocyclic aromatic amines and polycyclic aromatic hydrocarbons. These cooking practices are also associated with pro-inflammatory cellular changes and may explain increased prostate cancer incidence among men of African-American ethnicity (Int J Cancer 2007; 121:1319–24). The most abundant carcinogen that occurs in charred meats is 2-amino-1-methyl-6-phenynlimidazopyridine (PhIP), and has been the best studied with respect to its impact upon prostate cancer development. Although non-toxic and non-carcinogenic in its parent form, upon metabolism by cytochrome p450 1A1/1A2 into its reactive metabolite, PhIP has been demonstrated to induce acute inflammation resulting in recurrent prostatic epithelial injury, a precursor to chronic inflammation and prostate cancer development (Cancer Treat Res 2014; 159:51–68).

Additionally, a diet rich in HDF has been closely associated with increased risk for benign prostatic hyperplasia as well as prostate cancer development (Eur Urol 2012; 61:560–70). Multiple studies in rodent models have demonstrated that HDF diets induce a prostatic pro-inflammatory milieu, increasing risk for both prostate cancer development and progression. A proposed mechanism for these observed phenomenon focuses upon adipocyte cytokine production resulting in subclinical chronic inflammation and subsequent prostate epithelial cell injury. HDF-induced prostate inflammation was demonstrated to promote immune cell infiltration into prostate tissues in conjunction with basal-to-luminal cell differentiation, a process essential for the initiation of prostate cancer of basal cell origin (Stem Cell Res 2016; 16:682–91).

Given basal cell-derived prostate cancers tend to be invasive, the interaction between HDF and aggressive prostate cancer may provide an alternative explanation for the close association between metabolic syndrome and increased risk for high-grade, invasive prostate cancer.

Next: Quantifying inflammatory potential of diet

Quantifying inflammatory potential of diet

The Dietary Inflammatory Index (DII), a validated and literature-derived scoring system developed to estimate the pro- and anti-inflammatory potentials of overall diet and its possible impact on chronic disease has been utilized to quantify potential inflammation resulting from dietary choices (J Nutr 2009; 139:2365–72). The association between DII and overall prostate cancer risk was assessed through a prospective cohort study of middle-aged men, and a positive association was noted between the pro-inflammatory potential of the diets with higher DII scores and increased prostate cancer risk. Furthermore, this phenomenon was statistically significant in three out of four stratified cohort quartiles, thus suggesting a threshold effect of chronic inflammation upon prostate cancer risk (J Nutr 2016; 146:785–91).

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Results of this study were consistent with additional epidemiologic studies that demonstrated correlations between DII and a pro-inflammatory background associated with increased cancer risk. DII validation has been associated with multiple reactive biomarkers, primarily IL-6, TNF-alpha, and high-sensitivity C-reactive protein.

The DII has also been investigated with respect to its impact on prostate cancer survival. Zucchetto et al conducted a retrospective cohort study in 726 men with histopathologically confirmed prostate cancer originally enrolled in a multicenter study exploring lifestyle factors and prostate cancer risk. DII was calculated by way of a retrospective food frequency questionnaire, and the study reported two main findings: DII scores were not significantly associated with all-cause mortality in prostate cancer patients, nor among patients with Gleason score 2-6. However, DII was noted to be directly associated with all-cause and prostate cancer-specific mortality in patients with Gleason score 7-10 disease. This finding implicates the potential impact of the DII on prognostication in patients with histopathologically proven aggressive prostate cancer.

Summary

Amassed evidence suggests that dietary inflammatory potential may play a significant role in the alteration of prostate health and development of prostate cancer. Although the precise molecular pathways potentiating diet-mediated prostate inflammation continue to be investigated, contemporary studies offer evidence supporting the association of dietary inflammatory potential in the alteration of prostate health. In response to dietary carcinogens secondary to cooking process, HDF, or both, the propensity for recurrent prostate inflammation induced by epithelial injury remains a potential mechanism in the progression of prostate carcinogenesis.

Ultimately, population-scale intervention with respect to diet modification and choice of cooking practice, with promotion of healthy food intake demonstrated to be anti-inflammatory, may prove to be an inexpensive intervention to improve prostate health and reduce the societal burden of prostate cancer.

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