Increased sugar consumption is increasingly considered to be a contributor to the worldwide epidemics of obesity and diabetes and their associated cardiometabolic risks. As a result of its unique metabolic properties, the fructose component of sugar may be particularly harmful. Diets high in fructose can rapidly produce all of the key features of the metabolic syndrome. Here we review the biology of fructose metabolism as well as potential mechanisms by which excessive fructose consumption may contribute to cardiometabolic disease.

BACKGROUND: Soy foods possess both antiestrogenic and estrogen‐like properties. It remains controversial whether women diagnosed with breast cancer should be advised to eat more or less soy foods, especially for those who receive hormone therapies as part of cancer treatment.METHODS: The association of dietary intake of isoflavone, the major phytoestrogen in soy, with all‐cause mortality was examined in 6235 women with breast cancer enrolled in the Breast Cancer Family Registry. Dietary intake was assessed using a Food Frequency Questionnaire developed for the Hawaii‐Los Angeles Multiethnic Cohort among 5178 women who reported prediagnosis diet and 1664 women who reported postdiagnosis diet. Cox proportional‐hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).RESULTS: During a median follow‐up of 113 months (approximately 9.4 years), 1224 deaths were documented. A 21% decrease was observed in all‐cause mortality for women who had the highest versus lowest quartile of dietary isoflavone intake (≥1.5 vs < 0.3 mg daily: HR, 0.79; 95% confidence interval CI, 0.64‐0.97; P_trend = .01). Lower mortality associated with higher intake was limited to women who had tumors that were negative for hormone receptors (HR, 0.49; 95% CI, 0.29‐0.83; P_trend = .005) and those who did not receive hormone therapy for their breast cancer (HR, 0.68; 95% CI, 0.51‐0.91; P_trend = .02). Interactions, however, did not reach statistical significance.CONCLUSIONS: In this large, ethnically diverse cohort of women with breast cancer living in North America, a higher dietary intake of isoflavone was associated with reduced all‐cause mortality. Cancer 2017;123:2070–2079. © 2017 American Cancer Society.

Background: Limited data are available on the prospective relationship between beverage consumption and plasma lipid and lipoprotein concentrations. Two major sources of sugar in the US diet are sugar‐sweetened beverages ( SSBs ) and 100% fruit juices. Low‐calorie sweetened beverages are common replacements. Methods and Results: Fasting plasma lipoprotein concentrations were measured in the FOS (Framingham Offspring Study) (1991–2014; N=3146) and Generation Three (2002–2001; N=3584) cohorts. Beverage intakes were estimated from food frequency questionnaires and grouped into 5 intake categories. Mixed‐effect linear regression models were used to examine 4‐year changes in lipoprotein measures, and Cox proportional hazard models were used to estimate hazard ratios for incident dyslipidemia, adjusting for potential confounding factors. We found that regular (>1 serving per day) versus low (<1 serving per month) SSB consumption was associated with a greater mean decrease in high‐density lipoprotein cholesterol (β±standard error −1.6±0.4 mg/dL; P _trend <0.0001) and increase in triglyceride (β±standard error: 4.4±2.2 mg/dL; P _trend =0.003) concentrations. Long‐term regular SSB consumers also had a higher incidence of high triglyceride (hazard ratio, 1.52; 95% CI, 1.03–2.25) compared with low consumers. Although recent regular low‐calorie sweetened beverage consumers had a higher incidence of high non–high‐density lipoprotein cholesterol (hazard ratio, 1.40; 95% CI , 1.17–1.69) and low‐density lipoprotein cholesterol (hazard ratio, 1.27; 95% CI, 1.05–1.53) concentrations compared with low consumers, cumulative average intakes of low‐calorie sweetened beverages were not associated with changes in non–high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol concentrations, or incident dyslipidemias. Conclusions: SSB intake was associated with adverse changes in high‐density lipoprotein cholesterol and triglyceride concentrations, along with a higher risk of incident dyslipidemia, suggesting that increased SSB consumption may contribute to the development of dyslipidemia.

Metabolomics profiles were consistently associated with type 2 diabetes (T2D) risk, but evidence on long-term metabolite changes and T2D incidence is lacking. We examined the associations of 10-year plasma metabolite changes with subsequent T2D risk. We conducted a nested T2D case-control study (n=244 cases, n=244 matched controls) within the Nurses' Health Study. Repeated metabolomics profiling (170 targeted metabolites) was conducted in participant blood specimens from 1989/1990 and 2000/2001, and T2D occurred between 2002 and 2008. We related 10-year metabolite changes (Δ-values) to subsequent T2D risk using conditional logistic models, adjusting for baseline metabolite levels and baseline levels and concurrent changes of BMI, diet quality, physical activity, and smoking status. The 10-year changes of thirty-one metabolites were associated with subsequent T2D risk (false discovery rate-adjusted p-values [FDR]<0.05). The top three high T2D risk-associated 10-year changes were (odds ratio [OR] per standard deviation [SD], 95%CI): Δisoleucine (2.72, 1.97-3.79), Δleucine (2.53, 1.86-3.47), and Δvaline (1.93, 1.52-2.44); other high-risk-associated metabolite changes included alanine, tri-/diacylglycerol-fragments, short-chain acylcarnitines, phosphatidylethanolamines, some vitamins, and bile acids (ORs per SD between 1.31and 1.82). The top three low T2D risk-associated 10-year metabolite changes were (OR per SD, 95% CI): ΔN-acetylaspartic acid (0.54, 0.42-0.70), ΔC20:0 lysophosphatidylethanolamine (0.68, 0.56-0.82), and ΔC16:1 sphingomyelin (0.68, 0.56-0.83); 10-year changes of other sphingomyelins, plasmalogens, glutamine, and glycine were also associated with lower subsequent T2D risk (ORs per SD between 0.66 and 0.78). Repeated metabolomics profiles reflecting the long-term deterioration of amino acid and lipid metabolism are associated with subsequent risk of T2D.