Diet, physical activity and energy balance and their impact on breast and prostate cancers

Abstract

Obesity, physical activity status and circulating levels of sex steroid hormones and growth factor proteins are intrinsically linked to energy balance. Epidemiological studies have previously reported associations between these factors and the risk of hormone-related cancers such as prostate and breast cancer in men and postmenopausal women. An increasing number of intervention studies in 'at-risk' populations and cancer survivors are now investigating the effects of lifestyle interventions that promote negative energy balance on circulating levels of sex hormones and growth factor proteins as surrogate markers of cancer risk. Evidence from these studies suggests that lifestyle interventions can improve insulin sensitivity, alter the balance of circulating sex steroid hormones and insulin-like growth factor (IGF) axis proteins (including IGF-1 and the IGF binding proteins 1 and 3) and change the functioning of immune cells in peripheral blood. Such changes could influence the risk of developing hormone-related cancers, as well as having the potential to improve disease-free survival in patients recovering from cancer treatment. However, despite promising results, the methodological quality of most intervention studies has been limited due to small subject numbers, lack of adequate control groups or nonrandomised designs and the absence of long-term follow-up measures. More intervention studies with randomised controlled designs, higher numbers of subjects and longer-term follow-up measures are needed to establish which combination of specific dietary and physical activity interventions work best for reducing risk in 'at-risk' populations and survivors, optimal doseresponse relationships and the magnitude of change in surrogate markers of cancer risk that is required to induce a protective effect.

Low-Carbohydrate Diets and Prostate Cancer: How Low Is “Low Enough”?

“…1). This is consistent with many clinical trials that show that low-carbohydrate diets are effective tools for weight loss (5, 26, 32, 33). All three diets also lowered serum glucose levels and increased urinary ketone production by the time of sacrifice compared with levels before randomization (Fig.…”

“…To test this hypothesis, we performed a xenograft study and found that mice consuming a no-carbohydrate ketogenic diet (NCKD; 84% fat–0% carbohydrate–16% protein kcal) had slowed tumor growth and an increase in overall survival compared with mice on a Western diet, whereas such a survival benefit was not seen for mice consuming a low-fat diet (19). Mice consuming NCKD were also found to have an increase in urinary ketones and decrease in signaling of the insulin-like growth factor (IGF) axis, a pathway known not only to be integral in the progression of prostate cancer but also well known to be highly controlled through dietary intake (10, 20–26). We confirmed these results in a second independent xenograft study using the LNCaP cell line (27).…”

The impact of physical activity on all-cause mortality in men and women after a cancer diagnosis

“…Furthermore, our data suggest that at least three weekly bouts of vigorous recreational activity are required for improved survival. Although body mass index was similar across physical activity tertiles and did not independently predict mortality, physical activity might have influenced all-cause mortality through its effects on insulin sensitivity or body composition, particularly central adiposity, and the impact this can have on putative risk factors for cancer, including circulating levels of sex steroid hormones, adipokines, and insulin-like growth factors [17,18]. Being overweight at the time of diagnosis and weight gain after diagnosis has been linked with poorer outcome in breast, colorectal, and prostate cancer patients [13,[19][20][21][22].…”

Exercise Does Not Counteract the Effects of a “Westernized” Diet on Prostate Cancer Xenografts

“…LNCaP cells treated with serum from men on a diet and exercise intervention displayed reduced growth correlating with alterations in the IGF-1 axis [24,36,37]. Lifestyle interventions have also been effective for breast and colorectal cancers [24,34]. Previously, our group reported significant increases in serum insulin and IGF-1 in mice on the high-fat diet [11], while saturated fat consumption has been associated with greater risk of advanced prostate cancer, possibly due to an IGF-1 related mechanism [25].…”

“…Insulin axis modifications are thought to contribute to diet and exercise's prostate cancer benefits, while increases in IGF‐1 are associated with increased cancer risk . Combining low‐fat diets with regular exercise has been shown to reduce insulin and IGF‐1 levels while increasing IGFBP‐1 and IGFBP‐3 levels . LNCaP cells treated with serum from men on a diet and exercise intervention displayed reduced growth correlating with alterations in the IGF‐1 axis .…”