Rohrmann, S., D. Faeh, 2013. Should we go nuts about nuts? BMC Medicine. 11:165.
Since the beginning of the 1990s, increasing evidence supports beneficial effects of nut consumption on health. A new analysis of the Spanish PREDIMED trial, published in BMC Medicine, has expanded our knowledge. The study showed that individuals eating nuts more than three times per week died less often from cardiovascular disease and cancer than non-consumers. The study also adds an important finding that previous epidemiological studies could not provide: a protective effect on premature mortality was only seen in the intervention group in which nut consumption increased during the 4.8 years of follow-up, not in the intervention group with additional olive oil consumption or in the control group. Nut consumption actually decreased during follow-up in the latter two groups. Questions remain to be answered on the quantity of nuts to be consumed for health benefits, on possible mechanisms of action, and on whether some types of nuts should be favored.
Guasch-Ferré, M., M. Bulló, M.Á. Martínez-González, E. Ros, D. Corella, R. Estruch, M. Fitó, F. Arós, J. Wärnberg, M. Fiol, J. Lapetra, E. Vinyoles, R.M. Lamuela-Raventós, L. Serra-Majem, X. Pintó, V. Ruiz-Gutiérrez, J. Basora, J. Salas-Salvadó, on behalf of the PREDIMED study group, 2013. Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial. BMC Med. 11:164.
Background: Prospective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person. Methods: We evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED (‘PREvención con DIeta MEDiterránea’) study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality. Results: During a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend <0.05, all). Compared to non-consumers, subjects consuming nuts >3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts >3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66). Conclusions: Increased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk.
Moon, H.-S., X. Liu, J.M. Nagel, J.P. Chamberland, K.N. Diakopoulos, M.T. Brinkoetter, M. Hatziapostolou, Y. Wu, S.C. Robson, D. Iliopoulos, C.S. Mantzoros, 2012. Salutary effects of adiponectin on colon cancer: in vivo and in vitro studies in mice. Gut. doi:10.1136/gutjnl-2012-302092.
Background: Obesity and a high-fat diet are associated with the risk and progression of colon cancer. Low adiponectin levels may play an important role in the development of colon and other obesity-related malignancies. No previous studies have directly investigated the mechanistic effects of adiponectin on colon cancer in the settings of obesity, a high-fat diet and/or adiponectin deficiency. Objective: To investigate the effects of adiponectin on the growth of colorectal cancer in adiponectin-deficient or wild-type-C57BL/6 mice fed a low-fat or high-fat diet. Results: Mice fed a high-fat-diet gained more weight and had larger tumours than mice fed a low-fat-diet. Adiponectin administration suppressed implanted tumour growth, causing larger central necrotic areas. Adiponectin treatment also suppressed angiogenesis assessed by CD31 staining and VEGFb and VEGFd mRNA expression in tumours obtained from mice fed a high-fat diet and from adiponectin-deficient mice. Adiponectin treatment decreased serum insulin levels in mice on a high-fat-diet and increased serum-interleukin (IL)-12 levels in adiponectin-deficient mice. In vitro, it was found that adiponectin directly controls malignant potential (cell proliferation, adhesion, invasion and colony formation) and regulates metabolic (AMPK/S6), inflammatory (STAT3/VEGF) and cell cycle (p21/p27/p53/cyclins) signalling pathways in both mouse MCA38 and human HT29, HCT116 and LoVo colon cancer cell lines in a LKB1-dependent way. Conclusion: These new mechanistic and pathophysiology studies provide evidence for an important role of adiponectin in colon cancer. The data indicate that adiponectin or analogues might be useful agents in the management or chemoprevention of colon cancer.
Davis, P.A., V.T. Vasu, K. Gohil, H. Kim, I.H. Khan, C.E. Cross, W. Yokoyama, 2012. A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model. British Journal of Nutrition. doi:10.1017/S0007114511007288
Prostate cancer (PCa) has been linked to fat intake, but the effects of both different dietary fat levels and types remain inconsistent and incompletely characterised. The effects on PCa in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model of an elevated fat (20% of energy as fat) diet containing 155 g of whole walnuts were compared to those of an elevated fat (20% of energy as soyabean oil) diet with matched macronutrients, tocopherols as well as a low-fat (8% of energy as soyabean oil) diet. Mice, starting at 8 weeks of age, consumed one of the three different diets ad libitum; and prostates, livers and blood were obtained after 9, 18 or 24 weeks of feeding. No differences were observed in whole animal growth rates in either high-fat (HF) diet group, but prostate tumour weight and growth rate were reduced in the walnut diet group. Walnut diet group prostate weight, plasma insulin-like growth factor 1, resistin and LDL were lower at 18 weeks, while no statistically significant prostate weight differences by diet were seen at 9 or 24 weeks. Multiple metabolites in the livers differed by diet at 9 and 18 weeks. The walnut diet’s beneficial effects probably represent the effects of whole walnuts’ multiple constituents and not via a specific fatty acid or tocopherols. Moreover, as the two HF diets had dissimilar effects on prostate tumour growth rate and size, and yet had the same total fat and tocopherol composition and content, this suggests that these are not strongly linked to PCa growth.
Dalamaga, M., K.N. Diakopoulos, C.S. Mantzoros, 2012. The role of adiponectin in cancer: A review of current evidence. Endocrine Reviews. 33(4):547-94.
Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies.
Nagel, J.M., M. Brinkoetter, F. Magkos, X. Liu, J.P. Chamberland, S. Shah, J. Zhou, G. Blackburn, C.S. Mantzoros, 2012. Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis. Nutrition. 28(1):67-75.
OBJECTIVE: Animal studies have demonstrated that dietary supplementation with flaxseed oil inhibits colorectal cancer growth. Recent data indicate that walnuts have strong antiproliferative properties against colon cancer cells in vitro but no previous study has assessed the effects of walnuts in vivo or performed a joint evaluation of flaxseed oil and walnuts. The aim of the present study was to examine the effect of dietary walnuts on colorectal cancer in vivo and to comparatively evaluate their efficacy in relation to flaxseed oil. METHODS: HT-29 human colon cancer cells were injected in 6-wk-old female nude mice. After a 1-wk acclimation period, mice (n = 48) were randomized to diets containing ∼19% of total energy from walnuts, flaxseed oil, or corn oil (control) and were subsequently studied for 25 d. RESULTS: Tumor growth rate was significantly slower in walnut-fed and flaxseed-fed mice compared with corn oil-fed animals (P < 0.05) by 27% and 43%, respectively. Accordingly, final tumor weight was reduced by 33% and 44%, respectively (P < 0.05 versus control); the differences between walnut and flaxseed diets did not reach significance. We found no differences among groups in metabolic and hormonal profile, serum antioxidant capacity, or inflammation (P > 0.05). However, walnuts and flaxseed oil significantly reduced serum expression levels of angiogenesis factors, including vascular endothelial growth factor (by 30% and 80%, respectively), and approximately doubled total necrotic areas despite smaller tumor sizes (P < 0.05 versus control). Dietary walnuts significantly decreased angiogenesis (CD34 staining; P = 0.017 versus control), whereas this effect did not reach significance in the flaxseed oil group (P = 0.454 versus control). CONCLUSION: We conclude that walnuts in the diet inhibit colorectal cancer growth by suppressing angiogenesis. Further studies are needed to confirm our findings in humans and explore underlying mechanisms.
Hardman, W.E., G. Ion, J.A. Akinsete,T.R. Witte, 2011. Dietary walnut suppressed mammary gland tumorigenesis in the C(3)1 TAg mouse. Nutr Cancer. 63(6):960-70.
Walnuts contain multiple ingredients that, individually, have been shown to slow cancer growth, including omega-3 fatty acids, antioxidants, and phytosterols. In previous research, consumption of walnuts has slowed the growth of implanted breast cancers. We wanted to determine whether regular walnut consumption might reduce the risk for developing cancer. Homozygous male C(3)1 TAg mice were bred with female SV129 mice consuming either the control AIN-76 diet or the walnut-containing diet. At weaning, the female hemizygous pups were randomized to control or walnut-containing diets and followed for tumor development. Compared to a diet without walnuts, consumption of walnuts significantly reduced tumor incidence (fraction of mice with at least one tumor), multiplicity (number of glands with tumor/mouse), and size. Gene expression analyses indicated that consumption of the walnut diet altered expression of multiple genes associated with proliferation and differentiation of mammary epithelial cells. A comparison with another dietary intervention indicated that the omega 3 content alone did not account for the extent of tumor suppression due to the walnut. The results of this study indicate that walnut consumption could contribute to a healthy diet to reduce risk for breast cancer.
Bulló, M., M.R. Nogués, P. López-Uriarte, J. Salas-Salvadó, M. Romeu, 2010. Effect of whole walnuts and walnut-skin extracts on oxidant status in mice. Nutrition. 26(7-8):823-8.
Objective: To evaluate the effect of the intake of whole walnuts and walnut fractions on the oxidant status in mice. Methods: Thirty-six C57BL/6J male mice were randomized to be fed one of three diets: 1) a standard diet (control group), 2) a standard diet with 10% of whole walnuts (walnut-diet group), or 3) a standard diet with 2% of walnut skins (walnut-skin-diet group) for 8 wk. The plasma antioxidant capacity was measured by oxygen radical-absorbance capacity and plasma ferric-reducing antioxidant potential. Conjugated diene formation and reduced glutathione levels were also analyzed. Results: We observed no changes in plasma oxidation capability between the walnut and walnut skin groups with the exception of conjugated dienes. Plasma total antioxidant capacity and the ratio between reduced and oxidized forms of glutathione were lower in the walnut and walnut skin groups than in the control group. Conclusion: The decrease in the antioxidant burden observed in enzymatic and non-enzymatic antioxidant systems after sustained consumption of a whole-walnut or a walnut-skin diet in mice may be related to the plasma oxidation capability being maintained in the groups consuming the walnut diets.
Yang, J. 2009. Brazil nuts and associated health benefits: A review. LWT – Food Science and Technology.42:1573–1580.
Epidemiological studies have shown an inverse relationship between nut intakes and chronic diseases such as cardiovascular diseases and cancers. The composition of lipids, minerals, and phytochemicals, and their associated health functions in Brazil nuts are critically reviewed. The nuts have high nutritive food value containing 60–70% oil and 17% protein. Brazil nuts contain abundant dietary antioxidants, especially selenium (Se). One single Brazil nut provides 160% of the US Recommended Daily Allowance (RDA) of selenium – perhaps the best source of Se from plant-based foods. Brazil nuts possess phenolics and flavonoids in both free and bound forms and are rich in tocopherol, phytosterols, and squalene. These compounds’ possible beneficial effects are due to their antioxidant and antiproliferative activities, which are linked to a reduced risk for developing atherosclerosis and cance
Alasalvar, C., F. Shahidi, 2009. Natural antioxidants in tree nuts. Eur. J. Lipid Sci. Technol. 111:1056-1062
The levels of natural antioxidants and phytochemicals present in tree nuts are reported. Where possible, the health claims by Food and Drug Administration and European Food Safety Authority and health effects of tree nuts are provided. The content and recommended dietary allowances of nutrient antioxidants (such as vitamins A, C, E, and the mineral selenium) present in various tree nuts are compared. Antioxidant activity and phytochemicals present among tree nuts have been thoroughly reviewed. Research findings from over 65 references, many of which have been published within the last 10 years, have been compiled and reported.
