Table 2.

A summary of nutrients and evidence for their association with prostate cancer risk and progression

Nutrient	Source examples	Preclinical data	Clinical data	References
Carbohydrates
Simple carbohydrates	Fruit, dairy products, table sugar, high- fructose corn syrup	Low- and no-carbohydrate diets slow tumor growth in mouse xenograft models	Low-carbohydrate diets are effective for weight loss and cause genetic changes in prostate epithelium	[10–12,15,16]
Complex carbohydrates	Whole grains, potatoes, legumes
Protein	Animal meat, soy, dairy products	Animal meat: N/A	Animal meat: data inconclusive	[17–24]
		Soy phytoestrogens inhibit cell proliferation and induce differentiation by blocking estrogens from binding to the receptors	Soy consumption may prevent cancer; conflicting results exist on soy consumption and established tumors	[26–28]
		Dairy products: N/A	Although contradictory, data suggest increased milk consumption may increase risk, but no effect on aggressive or lethal disease	[29–31]
Fat		Reduced fat intake slows tumor growth in mouse models	No association between overall fat intake and cancer risk	[32–37]
Saturated fat	Butter, lard, animal meats	N/A	May be associated with biochemical recurrence but not overall risk	[38,39]
ω-6 PUFAs	Vegetable oils such as corn, olive, and sunflower	Increased concentrations lead to increased inflammation and cellular growth through the conversion of molecules by cytochrome P450 oxygenases	High consumption may lead to increased risk of overall and high-grade cancer	[41,42]
ω-3 PUFAs	Oils found in tuna, salmon, and herring; flaxseed oil	Increased concentrations lead to the induction of antitumor pathways both in vitro and in vivo	Although inclusive, data suggest supplementation decreases tumor proliferation; it is unknown whether it prevents the disease	[43,45,46]
Cholesterol	Animal meat, cheese, egg yolks	Increased serum concentrations may lead to increased tumor cholesterol synthesis, activation of inflammatory pathways, and intratumoral steroidogenesis in vitro and in vivo; statin and ezetimibe treatments inhibit tumor growth in vitro and in vivo	Data suggest statins may prevent cancer progression but not overall incidence of the disease	[48,49,52–54]
Vegetables	Broccoli, cabbage, cauliflower, garlic, leeks, chives	Isothiocyanates within cruciferous vegetables inhibit cell growth by inhibiting androgen receptor transcription in vitro; sulfurous chemicals in allium vegetables boost immune response, inhibit tumor growth, and induce apoptosis in vitro and in vivo	Increased cruciferous and allium vegetable intake is associated with a decreased risk in overall PCa risk	[56–60]
Vitamins and minerals
Vitamin A	Cheese, eggs, oily fish, vegetables, fruit	N/A	Excessive vitamin supplementation (not vitamin A per se) was associated with higher PCa risk	[62,63]
B vitamins	Pork, chicken, salmon, potatoes, lentils, dairy products	In vivo, folate depletion slows tumor growth; supplementation has no effect on PCa growth but directly increases DNA methylation	Folate supplementation (specifically oxidized folate) may increase PCa risk	[64–66]
Vitamin C	Peppers, broccoli, brussels sprouts, citrus fruits	Supplementation slows tumor growth in both in vitro and in vivo models by acting as an antioxidant	Supplementation has no effect on PCa risk	[67–69]
Vitamin D	Eggs, butter, oily fish, whole-milk products	Increased concentrations inhibit proliferation and angiogenic pathways in both in vitro and in vivo models	Data suggest no association between supplementation and overall PCa risk; data investigating only aggressive PCa are contradictory	[6,70–73]
Vitamin E	Corn, soybean, sunflower, and palm oils	Data from in vitro and in vivo studies suggest treatment may inhibit DNA synthesis and induce apoptotic pathway signaling	Supplementation has no effect or may in fact increase PCa risk	[62,74–76]
Vitamin K	Spinach, kale, broccoli	In vitro, treatment dramatically slows tumor growth, in part by acting as a calcium chelator; in vivo, supplementation radiosensitizes tumors	One study to date showed an inverse relationship between supplementation and PCa incidence	[67,77]
Calcium	Milk, cheese, yogurt	N/A	Existing data are conflicting, with some studies suggesting increased PCa risk with increased consumption, no association between risk and calcium consumption, and others suggesting both calcium depletion and supplementation increase PCa risk (U shaped)	[78,79]
Selenium	Brazil nuts, mushrooms, fish, eggs	In vitro studies suggest increased concentrations inhibit angiogenesis and proliferation while inducing apoptotic pathways	Supplementation alone or in combination with vitamin E shows no association with PCa incidence	[6,76]
Phytochemicals
Curcumin	Turmeric	In vitro data suggest treatment inhibits NFκB signaling and induces apoptosis; in vivo, supplementation slows and radiosensitizes PCa tumors in mouse models	N/A	[25,80]
Ellagitannins	Pomegranates, walnuts	Data suggest treatment slows proliferation and inhibits angiogenesis while inducing apoptosis, particularly under hypoxic conditions	Increased consumption of pomegranate juice or supplementation with POMx increased PSA doubling time relative to the values prior to consumption or supplementation	[25,81–83]
Epigallocatechin gallate	Green teas	As an antioxidant, treatment induces both intrinsic and extrinsic apoptotic pathways and inhibits NFκB signaling, thereby inhibiting PCa growth	Consumption may be associated with decreased PCa incidence and possibly prevent the progression of HGPIN lesions; the effect of consumption on advanced disease is unknown	[25, 84,85]
Lycopene	Tomatoes, watermelon, grapefruit	In vitro, increased concentrations inhibit cell cycle progression, induce expression of IGF-1 binding proteins, and activate the PPARγ pathway; in vivo, tomato paste inhibits PCa growth in rats	Some studies suggest increased consumption is associated with lower PCa risk; others suggest an association between decreased PSA levels with increased consumption but no association with PCa incidence	[86–92]
Phenolic Compounds	Coffee	N/A	Increased coffee consumption may be associated with a decreased risk of PCa, independent of caffeine intake	[93,94]
Resveratrol	Fruit, in particular red grapes	In vitro data suggest treatment inhibits PCa growth, in part by activating SIRT1 and mimicking caloric restriction; data from in vivo studies are conflicting, with consumption slowing tumor growth in some mouse models but not in others	N/A	[25,96,97]

HGPIN = high-grade prostatic intraepithelial neoplasia; IGF = insulinlike growth factor; N/A = not applicable; NFκB = nuclear factor κB; PCa = prostate cancer; PPAR= peroxisome proliferator activated receptor.