Diet and supplements in cancer prevention and treatment: Clinical evidences and future perspectives.

In recent years, calorie-restricted dietary regimens and compounds such as vitamins, curcumin, green tea extracts and omega-3 fatty acids have attracted attention for their potential anticancer effects. While definitive conclusions cannot be drawn in this field, many patients adopt complementary antitumor therapies aiming to improve efficacy or reduce toxicity of chemotherapy, with uncertain benefits and the risk of additional toxicities or antagonistic interactions with standard therapies. In this manuscript, we review the different levels of available evidence to suggest or discourage specific dietary changes or supplement use in the context of cancer prevention, reduction of tumor recurrences and survival prolongation in advanced cancers. Preventing or treating obesity, as well as adhering to healthy dietary patterns, should be recommended to both the general population and cancer survivors because they are convincingly associated with reduced risk of primary or second cancers and, in some cases, with reduced cancer recurrences. On the contrary, the role of specific interventions or supplements in patients with advanced malignancies is much more uncertain and actually a highly debated topic. With some exceptions, such as melatonin, the use of most complementary therapies cannot be encouraged, or should be discouraged, because of the lack of sufficient safety and efficacy data.

Protective Effect of Aerobic Physical Activity on Sleep Behavior in Breast Cancer Survivors.

HYPOTHESES: Sleep disorders are associated with an increased risk of cancer, including breast cancer (BC). Physical activity (PA) can produce beneficial effects on sleep. STUDY DESIGN: We designed a randomized controlled trial to test the effect of 3 months of physical activity on sleep and circadian rhythm activity level evaluated by actigraphy. METHODS: 40 BC women, aged 35-70 years, were randomized into an intervention (IG) and a control group (CG). IG performed a 3 month of aerobic exercise. At baseline and after 3 months, the following parameters were evaluated both for IG and CG: anthropometric and body composition measurements, energy expenditure and motion level; sleep parameters (Actual Sleep Time-AST, Actual Wake Time-AWT, Sleep Efficiency-SE, Sleep Latency-SL, Mean Activity Score-MAS, Movement and Fragmentation Index-MFI and Immobility Time-IT) and activity level circadian rhythm using the Actigraph Actiwatch. RESULTS: The CG showed a deterioration of sleep, whereas the IG showed a stable pattern. In the CG the SE, AST and IT decreased and the AWT, SL, MAS and MFI increased. In the IG, the SE, IT, AWT, SL, and MAS showed no changes and AST and MFI showed a less pronounced change in the IG than in the CG. The rhythmometric analysis revealed a significant circadian rhythm in two groups. After 3 months of PA, IG showed reduced fat mass %, while CG had improved weight and BMI. CONCLUSION: Physical activity may be beneficial against sleep disruption. Indeed, PA prevented sleep worsening in IG. PA can represent an integrative intervention therapy able to modify sleep behaviour.

Pre-diagnostic polyphenol intake and breast cancer survival: the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status.

Life style prevention of cancer recurrence: the yin and the yang.

There is increasing evidence that lifestyle after the diagnosis of cancer may affect prognosis. Several studies have shown that a Western dietary pattern, obesity, weight gain, a sedentary lifestyle, metabolic syndrome, high serum levels of insulin, growth factors, and inflammatory cytokines after the diagnosis of cancer are associated with an increased incidence of recurrences. Most studies have been on breast and colon cancer. However, in the clinical management of cancer, little attention is presently paid to improving lifestyle and controlling body weight. Lifestyle intervention trials are needed to corroborate or confute the observational results on cancer recurrences, but, even now, there is no contraindication to promoting moderate physical exercise, moderate calorie restriction (CR), and a Mediterranean dietary pattern. In fact, the AICR/WCRF 2007 systematic literature review recommends cancer patients to adopt the lifestyle recommended for the prevention of cancer. Interestingly, the evidence-based AICR/WCRF recommendations coincide with traditional rules, based on far Eastern philosophy, of avoiding extremely yin food, such as sugared beverages and calorie-dense foods, and extremely yang food, such as processed meat, and relying on the equilibrium of slightly yang food, such as whole-grain unprocessed cereals, eaten with slightly yin food, such as legumes and vegetables.

Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition.

The association between menopausal hormone therapy (HT) and risk of ovarian cancer was assessed among 126,920 post-menopausal women recruited into the European Prospective Investigation into Cancer and Nutrition. After an average of 9-year follow-up, 424 incident ovarian cancers were diagnosed. Cox models adjusted for body mass index, smoking status, unilateral ovariectomy, simple hysterectomy, age at menarche, number of full-term pregnancies, and duration of oral contraceptives were used. Compared with baseline never use, current use of any HT was positively associated with risk (HR [hazard ratio], 1.29; 95% CI [confidence interval], 1.01-1.65), while former use was not (HR, 0.96; 95% CI, 0.70-1.30). Current estrogen-only HT was associated with a 63% higher risk (HR, 1.63; 95% CI, 1.08-2.47), while current estrogen plus progestin was associated with a smaller and non-significant higher risk (HR, 1.20; 95% CI, 0.89-1.62). Use of tibolone was associated with a twofold greater risk (HR, 2.19; 95% CI, 1.06-4.50), but was based on small numbers. In conclusion, women who currently use HT have a moderate increased risk of ovarian cancer, and which may be stronger for estrogen-only than estrogen plus progestin preparations.

Menopausal hormone therapy and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Menopausal hormone therapy (HT) may influence colorectal cancer risk. A total of 136,275 postmenopausal women from the European Prospective Investigation into Cancer and Nutrition were followed for an average of 9 years, during which time 1,186 colorectal cancers were diagnosed. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by center and age, and adjusted for body mass index, smoking, diabetes, physical activity and alcohol consumption. Compared to never use of HT at study enrollment, current use of estrogen-only (HR, 1.02; 95% CI, 0.79-1.31) or estrogen plus progestin (HR, 0.94; 95% CI, 0.77-1.14) was not significantly associated with the risk of colorectal cancer, and these associations did not vary by recency, duration, route of administration, regimen or specific constituent of HT. Our results show no significant association of estrogen-only or estrogen plus progestin therapy with colorectal cancer risk.

Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into Cancer and Nutrition.

Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country-specific self-administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow-up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country-specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person-years of follow-up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23-1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40-2.24; p = 0.02 for combined vs. estrogen-only). Continuous combined regimens conferred a 43% (95% CI: 19-72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen-only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component.

A prospective study of dietary selenium intake and risk of type 2 diabetes.

BACKGROUND: Growing evidence raises concern about possible associations of high selenium exposure with diabetes in selenium-replete populations such as the US. In countries with lower selenium status, such as Italy, there is little epidemiological evidence on the association between selenium and diabetes. This study examined the prospective association between dietary selenium intake and risk of type 2 diabetes. METHODS: The ORDET cohort study comprised a large sample of women from Northern Italy (n = 7,182). Incident type 2 diabetes was defined as a self-report of a physician diagnosis, use of antidiabetic medication, or a hospitalization discharge. Dietary selenium intake was measured by a semi-quantitative food-frequency questionnaire at the baseline examination (1987-1992). Participants were divided in quintiles based on their baseline dietary selenium intake. RESULTS: Average selenium intake at baseline was 55.7 µg/day. After a median follow-up of 16 years, 253 women developed diabetes. In multivariate logistic regression analyses, the odds ratio for diabetes comparing the highest to the lowest quintile of selenium intake was 2.39, (95% CI: 1.32, 4.32; P for linear trend = 0.005). The odds ratio for diabetes associated with a 10 µg/d increase in selenium intake was 1.29 (95% CI: 1.10, 1.52). CONCLUSIONS: In this population, increased dietary selenium intake was associated with an increased risk of type 2 diabetes. These findings raise additional concerns about the association of selenium intake above the Recommended Dietary Allowance (55 µg/day) with diabetes risk.

Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer.

Experimental studies suggest detrimental effects of omega-6 polyunsaturated fatty acids (PUFA), and beneficial effects of omega-3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow-up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with alpha-linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between omega-6 and long-chain omega-3 PUFAs, with breast cancer risk inversely related to long-chain omega-3 PUFAs in women belonging to the highest quintile of omega-6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk.

Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Plasma phospholipid fatty acids have been correlated with food intakes in populations with homogeneous dietary patterns. However, few data are available on populations with heterogeneous dietary patterns. OBJECTIVE: The objective was to investigate whether plasma phospholipid fatty acids are suitable biomarkers of dietary intakes across populations involved in a large European multicenter study. DESIGN: A cross-sectional study design nested to the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted to determine plasma fatty acid profiles in >3,000 subjects from 16 centers, who had also completed 24-h dietary recalls and dietary questionnaires. Plasma fatty acids were assessed by capillary gas chromatography. Ecological and individual correlations were calculated between fatty acids and select food groups. RESULTS: The most important determinant of plasma fatty acids was region, which suggests that the variations across regions are largely due to different food intakes. Strong ecological correlations were observed between fish intake and long-chain n-3 polyunsaturated fatty acids (r = 0.78, P < 0.01), olive oil and oleic acid (r = 0.73, P < 0.01), and margarine and elaidic acid (r = 0.76, P < 0.01). Individual correlations varied across the regions, particularly between olive oil and oleic acid and between alcohol and the saturation index, as an indicator of stearoyl CoA desaturase activity. CONCLUSIONS: These findings indicate that specific plasma phospholipid fatty acids are suitable biomarkers of some food intakes in the EPIC Study. Moreover, these findings suggest complex interactions between alcohol intake and fatty acid metabolism, which warrants further attention in epidemiologic studies relating dietary fatty acids to alcohol-related cancers and other chronic diseases.

A dietary pattern rich in olive oil and raw vegetables is associated with lower mortality in Italian elderly subjects.

Dietary habits play an important role in healthy ageing. We have investigated the role of dietary patterns on overall mortality in a large series of Italian elderly, recruited in five EPIC cohorts in Northern (Varese and Turin), Central (Florence) and Southern Italy (Naples and Ragusa).A total of 5611 subjects (72.6 % women) aged 60 years or older, enrolled in 1993-1998, were prospectively followed (median 6.2 years), with 152 deaths (98 women). Four major dietary patterns were identified by using an exploratory factor analysis based on dietary information collected at enrollment. The associations between these dietary patterns and overall mortality were evaluated by Cox models adjusted for potential confounders. The 'Olive Oil & Salad' pattern, characterised by a high consumption of olive oil, raw vegetables, soups and poultry, emerged as being inversely associated with overall mortality in both crude and adjusted models. After adjustment for gender, age and caloric intake, overall mortality was reduced by approximately 50 % in the highest quartile and a significant trend emerged (P = 0.008). This association persisted after adjusting for several additional confounders (hazard ratio (HR) 0.50; 95 % CI 0.29, 0.86; P for trend = 0.02). An association of the 'Pasta & Meat' pattern (characterised by pasta, tomato sauce, red meat, processed meat, added animal fat, white bread and wine) with increased overall mortality was also suggested, but only for the highest quartile in a multivariate model. Dietary recommendations aimed at the Italian elderly population should support a dietary pattern characterised by a high consumption of olive oil, raw vegetables and poultry.

Erythrocyte membrane phospholipid composition as a biomarker of dietary fat.

BACKGROUND/AIMS: In a cross-sectional study, we investigated the relationship between erythrocyte membrane phospholipid fatty acid composition and dietary fat; we also investigated roles of menopausal status, age, body mass index (BMI) and waist-to-hip ratio (WHR) in interindividual variation of the biomarker. METHODS: Study participants were 204 women, aged 39-65 years, drawn from the ORDET cohort and selected as controls in a study of breast cancer. Membrane composition was assessed using capillary gas chromatography. Dietary fat composition was evaluated using a food frequency questionnaire. RESULTS: In pre- and postmenopausal women, erythrocyte membrane phospholipid levels of linoleic acid, oleic acid, and mono-unsaturated fatty acids were significantly associated with corresponding dietary measures (partial correlation coefficients: 0.23 and 0.39; 0.45 and 0.47; 0.40 and 0.48; respectively, in pre- and postmenopausal women). Among postmenopausal women, membrane poly-unsaturated fatty acids were correlated with the corresponding dietary measure (r=0.39, p<0.001). Membrane eicosapentanoic and docosahexanoic acid levels were significantly correlated with intake of fish/shell fish : r=0.21 and r=0.43 (premenopausal), and r=0.41 and r=0.44 (postmenopausal). Age, BMI and WHR had independent effects on membrane lipid composition. Age was associated with delta-6 desaturase activity in postmenopausal women (r=0.25, p<0.05). BMI was negatively associated with delta-9 desaturase activity in both pre- and postmenopausal women (r=-0.29, p=0.01 and r=-0.22, p<0.01, respectively). WHR was negatively associated with delta-5 desaturase activity in pre-menopausal women (r=-024, p<0.05). CONCLUSIONS: Erythrocyte membrane levels of some specific fatty acids can be used as biomarkers of these fatty acids as proportions of dietary fat.

Toenail selenium as biomarker: reproducibility over a one-year period and factors influencing reproducibility.

We assessed the reproducibility of selenium levels in toenails, comparing concentrations in two sets of specimens collected about a year apart, from 80 women (40 pre-menopausal and 40 post-menopausal) in the period October 1990 to February 1992. The women were participants in a prospective study on hormones and diet in relation to prediagnostic breast cancer (the ORDET study) conducted in northern Italy. Toenail selenium was determined by electrothermal atomic absorption spectrometry. The data were log-transformed as they were not normally distributed. To assess reproducibility Pearson correlation coefficients (r) for the two selenium determinations were calculated in pre- and post-menopausal women, according to smoking status and acetone treatment. A weighted kappa statistic (k) assessed inter-quintile agreement between the two sets of measures. Toenail selenium levels were highly reproducible (r = 0.57, p < 0.001), especially in pre-menopausal women (r = 0.66, p <0.001). Smoking lowered selenium levels (mean difference of 0.24 microg/g, p < 0.05 between smokers and non smokers) but did not significantly influence reproducibility. Acetone treatment to remove nail polish did not modify selenium levels but affected inter-quintile agreement, with moderate agreement (k = 0.58, p < 0.001) when acetone was used at both or neither samplings; and fair non significant agreement (k = 0.39, p = 0.06) when acetone was used at one sampling but not the other. As selenium levels in toenails are highly reproducible, notwithstanding variation in selenium levels in food and long-term changes in individuals' food choices, toenail selenium may be a useful biomarker of selenium exposure, particularly since toenail samples provide a measure of long-term exposure. However age, smoking status and acetone treatment are possible causes of misclassification.

Common and country-specific dietary patterns in four European cohort studies.

The association between diet and cancer, predominantly investigated univariately, has often been inconsistent, possibly because of the large number of candidate risk factors and their high intercorrelations. Analysis of dietary patterns is expected to give more insight than analysis of single nutrients or foods. This study aimed to develop and apply a common methodological approach to determine dietary patterns in four cohort studies originating in Finland, the Netherlands, Sweden and Italy. Food items on each of the food frequency questionnaires were aggregated into 51 food groups, defined on the basis of their position in the diet pattern and possible relevance to cancer etiology. Exploratory factor analysis was used to analyze dietary patterns. Using a standardized approach, 3-5 stable dietary patterns were identified, explaining 20-29% of total variance in consumption of the food groups. Two dietary patterns, which explained most of the variance, were consistent across the studies. The first pattern was characterized by high consumption of (salad) vegetables, the second by high consumption of pork, processed meat and potatoes. In addition, a few specifically national food patterns were identified. Sensitivity analyses showed that the identified patterns were robust for number of factors extracted, distribution of input variables and energy adjustment. Our findings suggest that some important eating patterns are shared by the four populations under study, whereas other eating patterns are population specific.

A plant food-based diet modifies the serum beta-sitosterol concentration in hyperandrogenic postmenopausal women.

Plant sterols or phytosterols are common components of plant foods, especially plant oils, seeds and nuts, cereals and legumes. The most common phytosterols are campesterol, beta-sitosterol and stigmasterol. Phytosterols have anticarcinogenic properties. Previous studies have suggested that populations with low breast cancer incidence often consume diets high in phytosterols. The present study evaluated whether consumption of a plant food-based diet, low in animal fat, may increase serum phytosterol levels in postmenopausal women. One hundred and four women volunteers were randomized to dietary intervention or control groups. The dietary intervention included intensive dietary counseling to replace animal products with plant-based foods. Subjects in the dietary intervention group participated twice a week for 18 wk in workshops about the preparation and consumption of a plant food-based diet. The absolute change in serum total phytosterol concentration was greater in the dietary intervention group than in the control group. The percent change tended to differ between groups (P = 0.06). However, only for beta-sitosterol did the absolute and percent changes within a group differ significantly between groups (P = 0.0017). The decrease in serum total cholesterol in the dietary intervention group (-14%) was greater than that in the control group (-4%; P = 0.0005). The results of this study show that circulating levels of phytosterols can be affected by dietary modification. These findings indicate that phytosterols, in particular beta-sitosterol, can be used as biomarkers of exposure in observational studies or as compliance indicators in dietary intervention studies of cancer prevention.

[Western diet and Alzheimer's disease]. / La dieta occidentale e la demenza di Alzheimer.

Alzheimer Disease, characterised by a global impairment of cognitive functions, is more and more common in Western societies, both because of longer life expectancy and, probably, because of increasing incidence. Several hints suggest that this degenerative disease is linked to western diet, characterised by excessive dietary intake of sugar, refined carbohydrates (with high glycaemic index), and animal product (with high content of saturated fats), and decreased intake of unrefined seeds--cereals, legumes, and oleaginous seeds--and other vegetables (with high content of fibres, vitamins, polyphenols and other antioxidant substances, phytoestrogens) and, in several populations, of sea food (rich in n-3 fatty acids). It has been hypothesised, in fact, that AD, may be promoted by insulin resistance, decreased endothelial production of nitric oxide, free radical excess, inflammatory metabolites, homocysteine, and oestrogen deficiency. AD, therefore, could theoretically be prevented (or delayed) by relatively simple dietary measures aimed at increasing insulin sensitivity (trough reduction of refined sugars and saturated fats from meat and dairy products), the ratio between n-3 and n-6 fatty acids (e.g. from fish and respectively seed oils), antioxidant vitamins, folic acid, vitamin B6, phytoestrogens (vegetables, whole cereals, and legumes, including soy products), vitamin B12 (bivalve molluscs, liver), and Cr, K, Mg, and Si salts. This comprehensive improvement of diet would fit with all the mechanistic hypotheses cited above. Several studies, on the contrary, are presently exploring monofactorial preventive strategies with specific vitamin supplementation or hormonal drugs, without, however, appreciable results.