Dietary energy restriction (DER) inhibits mammary carcinogenesis, yet mechanisms accounting for its protective activity have not been fully elucidated. In this study, we tested the hypothesis that DER exerts effects on intracellular energy sensing pathways, resulting in alterations of phosphorylated proteins that play a key role in the regulation of cancer. Experiments were conducted using the 1-methyl-1-nitrosourea–induced mammary cancer model in which rats were 0%, 20%, or 40% energy restricted during the postinitiation stage of carcinogenesis. Parallel experiments were done in non–carcinogen-treated rats in which effects of DER at 0%, 5%, 10%, 20%, or 40% in liver were investigated. In a DER dose–dependent manner, levels of Thr¹⁷² phosphorylated AMP-activated protein kinase (AMPK) increased in mammary carcinomas with a concomitant increase in phosphorylated acetyl-CoA-carboxylase, a direct target of AMPK, the phosphorylation of which is regarded as an indicator of AMPK activity. Levels of phosphorylated mammalian target of rapamycin (mTOR) decreased with increasing DER, and down-regulation of mTOR activity was verified by a decrease in the phosphorylation state of two mTOR targets, 70-kDa ribosomal protein S6 kinase (p70S6K) and eukaryote initiation factor 4E binding protein 1 (4E-BP1). Coincident with changes in mTOR phosphorylation, levels of activated protein kinase B (Akt) were also reduced. Similar patterns were observed in mammary glands and livers of non–carcinogen-treated rats. This work identifies components of intracellular energy sensing pathways, specifically mTOR, its principal upstream regulators, AMPK and Akt, and its downstream targets, p70S6K and 4E-BP1, as candidate molecules on which to center mechanistic studies of DER. [Cancer Res 2008;68(13):5492–9]

Dietary energy restriction (DER) is a potent inhibitor of carcinogenesis, but chronic DER in human populations is difficult to sustain. Consequently, interest exists in identifying energy restriction mimetic agents (ERMAs), agents that provide the health benefits of DER without reducing caloric intake. The selection of a candidate ERMAs for this study was based on evidence that DER inhibits carcinogenesis by limiting glucose availability. The study objective was to determine if 2-deoxyglucose (2-DG), a glucose analogue that blocks its metabolism, would inhibit mammary carcinogenesis. Pilot studies were done to establish a dietary concentration of 2-DG that would not affect growth. For the carcinogenesis study, ninety 21-day-old female Sprague-Dawley rats were injected i.p. with 50 mg of 1-methyl-1-nitrosourea per kilogram of body weight. Following injection, animals were ad libitum fed AIN-93G diet containing 0.00%, 0.02%, or 0.03% (w/w) 2-DG for 5 weeks. 2-DG decreased the incidence and multiplicity of mammary carcinomas and prolonged cancer latency (P < 0.05). The 0.02% dose of 2-DG had no effect on circulating levels of glucose, insulin, insulin-like growth factor-I, IGF binding protein-3, leptin, or body weight gain. Using MCF-7 human breast cancer cells to investigate the signaling pathways perturbed by disruption of glucose metabolism, 2-DG reduced cell growth and intracellular ATP in a dose- and time-dependent manner (P < 0.01). Treatment with 2-DG increased levels of phosphorylated AMP-activated protein kinase and Sirt-1 and reduced phosphorylated Akt (P < 0.05). These studies support the hypothesis that DER inhibits carcinogenesis, in part, by limiting glucose availability and that energy metabolism is a target for the development of ERMA for chemoprevention.

Legume food crops can contribute to the solution of diet-related public health challenges. The rich diversity of the botanical family Fabaceae (Leguminosae) allows legumes to fill numerous nutritional niches. Pulses (i.e., a subgroup of legumes including chickpeas, cowpeas, dry beans, dry peas, and lentils) are a nutrient-dense food that could play a key role in eliminating the dramatic underconsumption of dietary fiber and potassium, two dietary components of public health concern, all while maintaining a caloric intake that promotes a healthy weight status. However, incorrect use of terminology—in the commercial and scientific literature as well as in publications and materials prepared for the consuming public—creates confusion and represents a barrier to dissemination of clear dietary guideline messaging. The use of accurate terminology and a simple classification scheme can promote public health through differentiation among types of legumes, better informing the development and implementation of nutritional policies and allowing health care professionals and the public to capitalize on the health benefits associated with different legumes. Although inconsistent grouping of legumes exists across countries, the recently released 2020–2025 Dietary Guidelines for Americans (DGA) were chosen to illustrate potential challenges faced and areas for clarification. In the 2020–2025 DGA, pulses are included in two food groups: the protein food group and ‘beans, peas, lentils’ vegetable subgroup. To evaluate the potential of pulses to contribute to intake of key dietary components within calorie recommendations, we compared 100 kilocalorie edible portions of pulses versus other foods. These comparisons demonstrate the unique nutritional profile of pulses and the opportunity afforded by this type of legume to address public health concerns, which can be greatly advanced by reducing confusion through global harmonization of terminology.

Background: Health benefits associated with diets rich in vegetables and fruit (VF) are often attributed to the antioxidant activity of their constituent phytochemicals. However, in vivo evidence that VF actually reduce markers of oxidative stress is limited. Objective: An 8-wk dietary intervention was conducted to test the hypothesis that increased VF consumption decreases oxidative stress. Urinary excretion of 8-isoprostane F_2α (8-iso-PGF_2α) was used as an index of whole-body lipid peroxidation. Design: The diets evaluated had comparable amounts of all macronutrients but varied in their content of VF. After a 2-wk low-VF (3.0 servings/d) run-in diet, 246 women were randomly assigned to receive either 3.6 (low) or 9.2 (high) servings VF/d. The low-VF group was switched to the high-VF diet during the final 2 wk of the study. Blood and first-void urine specimens were obtained at baseline and at 2-wk intervals thereafter. Results: The run-in diet reduced 8-iso-PGF_2α concentrations by 33% (P < 0.0001). The excretion of 8-iso-PGF_2α with the low-VF diet remained the same as that with the run-in diet, whereas urinary concentrations of 8-iso-PGF_2α were further reduced (P < 0.01) by the high-VF diet, either fed throughout the study or when the diet was switched from low to high VF (P = 0.05). The greatest reductions in 8-iso-PGF_2α were observed in subjects in the highest quartile of baseline concentrations of 8-iso-PGF_2α. Conclusions: A significant reduction in the excretion of 8-iso-PGF_2α was induced by the run-in diet and the high-VF diet. The degree of reduction was related to the subject’s baseline urinary concentration of 8-iso-PGF_2α.

Public health concerns are discussed so frequently that it is beginning to cause desensitization. And yet, rates of chronic disease remain alarmingly high worldwide—or are even increasing. Primary prevention is essential to reverse these trends. Indeed, the sustainable implementation of good health practices can promote human physical and psychological well‐being while simultaneously being more cost‐effective than the treatment of chronic disease. A healthy dietary pattern is a cornerstone of primary prevention. Pulses, or the dry seeds of non‐oilseed legumes (e.g., chickpeas, cowpeas, dry beans, dry peas, and lentils)—also called grain legumes—are widely recognized as a nutrient‐dense food and one of the richest sources of dietary fiber and plant protein. Combined with their affordable price point and contributions to sustainable food systems, they can be considered a prime example of a superfood. Historically, they also have a rich culinary history around the world, making them culturally relevant to many cuisines and cultures. The scientific literature supports the role of pulses in many health benefits, yet the quality of the evidence is often low. In this review, we explore the findings—and limitations—of research to date and conclude with suggestions for moving the field forward to investigate and establish robust support for a recommended serving size that is most beneficial for human health.