Received: 2 July 2020 / Revised: 21 July 2020 / Accepted: 24 July 2020 / Published: 26 July 2020
(This article belongs to the Special Issue Nutrition for Cancer Survivors)
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Abstract
Cancer patients often ask which foods would be best to consume to improve outcomes. This is a difficult question to answer as there are no case-controlled, prospective studies that control for confounding factors. Therefore, a literature review utilizing PubMed was conducted with the goal to find evidence-based support for certain diets in specific cancer patients—specifically, we reviewed data for colon cancer, prostate cancer, breast cancer, malignant gliomas, and cancer patients on immunotherapy. Improved outcomes in colon cancer and patients on immunotherapy were found with high-fiber diets. Improved outcomes in malignant gliomas were found with ketogenic diets. Improved outcomes in prostate cancer and breast cancer were found with plant-based diets. However, the data are not conclusive for breast cancer. Additionally, the increased intake of omega-3 fatty acids were also associated with better outcomes for prostate cancer. While current research, especially in humans, is minimal, the studies discussed in this review provide the groundwork for future research to further investigate the role of dietary intervention in improving cancer outcomes. View Full-Text
Keywords: diet; cancer; carcinoma; colon cancer; colorectal cancer; prostate cancer; breast cancer; malignant gliomas; immunotherapy; cancer outcomes; cancer prognosis; western diet
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Prostate cancer is the most diagnosed cancer in men after skin cancer and has the second highest cancer-related mortality [36]. Historically, it was widely believed that fat intake was both a risk factor for the development of prostate cancer and likely a contributor for worse outcomes [37]. In fact, animal model studies have provided proof for this claim; Ngo et al., among others, showed that immunodeficient mice, engrafted with a prostate cancer xenograft, had a slower tumor progression and a longer life span if fed a fat-restricted diet.
Specifically, Ngo et al. stratified mice between a high-fat diet, in which 42% of the calories came from corn oil, and a low-fat group, in which 12% of calories came from corn oil. The diets were isocaloric. The mice were observed until the tumor progression was noted, upon which these mice were sacrificed. Of note, the mice fed a low-fat diet had a median survival of 20.8 weeks vs. 13.8 weeks for those fed a high-fat diet. Moreover, the mice fed a high-fat diet had a mean prostate specific antigen (PSA) of 75.2 vs. a mean PSA of 10.8 in the mice fed a low-fat diet, suggesting that the high-fat diet resulted in a higher tumor burden [14].
Similar to Ngo et al., other studies have also supported the idea that dietary fat may be linked to prostate tumor progression. Like the Ngo et al. group, mice in the high-fat diet group in other studies were predominantly fed a diet rich in corn oil and in turn had shorter life spans and faster prostate cancer growth rates compared to their low-fat diet counterparts [13,15].
There is no universally agreed upon proposed mechanism that explains the link between high dietary fat intake and prostate tumor growth. However, the results of the aforementioned studies could partly be explained by the fact that high-fat diets utilized corn oil, which is also widely used in western diets and processed foods. Corn oil composition is approximately 60% linoleic acid, an omega-6 fatty acid [38]. Linoleic acid, in turn, is converted into arachidonic acid and prostaglandin E2 (PGE2) via a cyclooxygenase enzyme [39]. In vitro studies have revealed that prostate cancer cells have a 5- to 10-fold higher concentration of arachidonic acid and PGE2 than benign neighboring cells.
In addition, much attention has recently been brought to the importance of the omega-3 to the omega-6 ratio in the diet [40]. In vitro studies by Bagga et al. utilizing fibroblasts have shown that omega-6 fatty acids promote IL-6 production and in turn increase the mitogenic activity of fibroblasts. Notably, this mitogenic activity was attenuated with the introduction of omega-3 or polyunsaturated fatty acids [19]. Cancer-associated fibroblasts make up the stromal component of prostate cancer; increased mitogenic activity of fibroblasts is suggestive of increased cancer aggressiveness [41].
Interestingly, recent literature utilizing the no-carbohydrate ketogenic (NCKD) and low-carbohydrate diets in mice models suggests that such high-fat diets could also be employed to slow prostate cancer progression. Unlike previous high-fat diet models that used corn oil as the primary source of calories, the NCKD and low-carbohydrate models utilized lard and milk fat as the primary source of calories [18]. These studies found that the prostate cancer mice models on the NCKD and low-carbohydrate diets vs. those on the western diet model in which calories were obtained in the following manner: 35% fat, 49% carbohydrates, and 16% protein kcals, had slower tumor growth [16]. In addition, NCKD and low-carbohydrate models also had a lower in vivo ratio of insulin growth factor-1 (IGF-1) to insulin growth factor binding protein-3 (IGFBP-3) [17]. It could be postulated that a decreased ratio of IGF-1:IGFBP-3 could result in anti-cancer properties as IGF-1 has been found to be pro-oncogenic and IGFBP-3 was found to be anti-oncogenic and pro-apoptotic in in vitro prostate cancer models by attenuating angiogenesis and vascular growth [42,43].
Though data from NCKD and low-carbohydrate diet models may seem contradictory of prior high-fat diet models, it should be kept in mind that a high-fat diet via corn oil ingestion vs. a high-fat diet via the ingestion of lard and/or milk fat are different in their micronutrient intake. Corn oil is predominantly rich in omega-6 fatty acids and the ratio of omega-3 to omega-6 is 1:50 [44]. Lard has an omega-3 to omega-6 ratio of approximately 1:10 [45]. As such, a lard diet has approximately five times the intake of omega-3. Such variance in micronutrients could possibly explain the difference in oncogenesis between the two different high-fat diets, as the aforementioned prior in vitro studies by Bagga et al. have revealed that diets with a low omega-3 to omega-6 ratio are pro-inflammatory, and as a result, could be more oncogenic.
Lastly, there is growing interest in the role of cruciferous vegetable intake and prostate cancer outcomes. One major bioactive compound found in cruciferous vegetables is sulforaphane, a compound that is a metabolite of phytochemical compounds known as isothiocyanates [46]. A double-blind, randomized, placebo-controlled multicenter trial with sulforaphane in 78 patients conducted by Cipolla et al. in patients with recurrent prostate cancer showed that individuals administered 60 mg of sulforaphane for six months had on average an 86% longer PSA doubling time [11]. Moreover, a phase II clinical trial with 20 patients with recurrent prostate cancer conducted by Alumkal et al. showed that the administration of 200 μmoles/day of sulforaphane-rich extract resulted in an approximate 50% reduction in PSA doubling time [12]. Though the effect of overall survival was not studied, the decrease in PSA doubling time does suggest that cruciferous vegetable intake could slow prostate tumor progression and thus improve outcomes. However, further studies are needed to determine the amount and ideal preparation of cruciferous vegetables to obtain maximum benefit.
As the authors speculate, corn oil might not be the best product to consume. Not only is the omega 6 to 3 ratio outside what is considered optimal by nutritionists(at the moment),high levels of omega 6's being associated with inflammation in general, also corn as it's produced in this country is largely a gmo product and that means consuming at least some of the downstream by products of Roundup. That both a high fat ,low carb diet and a plant based diet might slow down PCa growth also might support role of importance of anti-inflammatory diets in general. The only thing is, it's those d--n mice again- hard to keep em out of the kitchen!
Review of Sulphoraphane effects is great to read, really positive.
Yeah I agree that "corn oil" isn't a smart use of fats in this study. You need to inject chemicals into corn to extract the oil. It would have been smarter to use coconut oil, olive oil, or avocado oil.
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