Complex relationships exist between the gut microflora and their human hosts. Emerging evidence suggests that bacterial dysbiosis within the colon may be involved in the pathogenesis of the metabolic syndrome, type 2 diabetes and CVD. The use of dietary prebiotic supplements to restore an optimal balance of intestinal flora may positively affect host metabolism, representing a potential treatment strategy for individuals with cardiometabolic disorders. The present review aimed to examine the current evidence supporting that dietary prebiotic supplementation in adults has beneficial effects on biochemical parameters associated with the development of metabolic abnormalities including obesity, glucose intolerance, dyslipidaemia, hepatic steatosis and low-grade chronic inflammation. Between January 2000 and September 2013, eight computer databases were searched for randomised controlled trials published in English. Human trials were included if at least one group received a dietary prebiotic intervention. In the present review, twenty-six randomised controlled trials involving 831 participants were included. Evidence indicated that dietary prebiotic supplementation increased selfreported feelings of satiety in healthy adults (standardised mean difference 2 0·57, 95 % CI 21·13, 2 0·01). Prebiotic supplementation also significantly reduced postprandial glucose (20·76, 95 % CI 21·41, 2 0·12) and insulin (2 0·77, 95 % CI 2 1·50, 20·04) concentrations. The effects of dietary prebiotics on total energy intake, body weight, peptide YY and glucagon-like peptide-1 concentrations, gastric emptying times, insulin sensitivity, lipids, inflammatory markers and immune function were contradictory. Dietary prebiotic consumption was found to be associated with subjective improvements in satiety and reductions in postprandial glucose and insulin concentrations. Additional evidence is required before recommending prebiotic supplements to individuals with metabolic abnormalities. Large-scale trials of longer duration evaluating gut microbial growth and activity are required.

Advanced glycation end products (AGEs) formed via the Maillard reaction during the thermal processing of food contributes to the flavor, color, and aroma of food. A proportion of food-derived AGEs and their precursors is intestinally absorbed and accumulates within cells and tissues. AGEs have been implicated in the pathogenesis of diabetes-related complications and several chronic diseases via interaction with the receptor for AGEs, which promotes the transcription of genes that control inflammation. The dicarbonyls, highly reactive intermediates of AGE formation, are also generated during food processing and may incite inflammatory responses through 1) the suppression of protective pathways, 2) the incretin axis, 3) the modulation of immune-mediated signaling, and 4) changes in gut microbiota profile and metabolite sensors. In animal models, restriction of dietary AGEs attenuates chronic low-grade inflammation, but current evidence from human studies is less clear. Here, the emerging relationship between excess dietary AGE consumption and inflammation is explored, the utility of dietary AGE restriction as a therapeutic strategy for the attenuation of chronic diseases is discussed, and possible avenues for future investigation are suggested.

The benefits of advanced glycation end-product (AGE)-restricted diets in humans are unclear. This review aimed to determine the effect of dietary AGE restriction on the inflammatory profiles of healthy adults and adults with diabetes or renal failure. Eight computer databases were searched for controlled feeding trials published in English between January 1997 and December 2012. Human trials were included if at least one group received an AGE-restricted dietary intervention. A total of 12 trials reporting on 289 participants were included in the review. Five trials (42%) were of high methodological quality. Meta-analysis of two long-term (16 week) trials provided evidence favoring an AGE-restricted diet for the reduction of 8-isoprostanes (standardized mean difference 0.9; 95% confidence interval (CI): 0.3-1.5) and tumor necrosis factor-α (1.3; 95% CI: 0.6-1.9) in healthy adults. Intermediate-term dietary AGE restriction in adults with chronic renal failure reduced serum VCAM-1 (0.9; 95% CI: 0.1-1.7). Individual trials provided some evidence that long-term dietary AGE restriction reduces HOMA-IR (1.4; 95% CI: 0.3-2.6) and AGE-modified low-density lipoprotein (2.7; 95% CI: 1.6-3.9) in adults with type 2 diabetes. Generalisability is limited, as 75% of studies were of less than 6 weeks duration and more than half were of low methodological quality. Evidence quality ranged from low to very low, limiting the conclusions that can be drawn from this review. There is currently insufficient evidence to recommend dietary AGE restriction for the alleviation of the proinflammatory milieu in healthy individuals and patients with diabetes or renal failure. Additional long-term high-quality RCTs with larger sample sizes measuring patient-important outcomes are required to strengthen the evidence supporting the effects of AGE-restricted diets.

Vitamin D supplementation has been proposed as a potential strategy to prevent type 2 diabetes. Existing clinical trials have been limited by short duration, low doses of vitamin D, variability in participants' vitamin D-deficiency status, and the use of surrogate measures of body composition, insulin sensitivity, and insulin secretion. To address existing knowledge gaps, we conducted a double-blind, randomized, placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-standard methods. We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo. Sixty-five overweight or obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] concentration ≤50 nmol/L) adults were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and after the intervention, participants received gold-standard assessments of body composition (via dual X-ray absorptiometry), insulin sensitivity (via hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous-glucose-tolerance tests (IVGTTs)]. Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m): 30.9 ± 4.4]. 25(OH)D increased with vitamin D supplementation compared with placebo (57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L, respectively; = 0.02). Vitamin D and placebo groups did not differ in change in insulin sensitivity (0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg · min, respectively; = 0.9) or first-phase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; = 0.9). Results remained nonsignificant after adjustment for age, sex, percentage of body fat, sun exposure, physical activity, and dietary vitamin D intake ( > 0.1). Vitamin D supplementation does not improve insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults, despite using high-dose vitamin D supplementation and robust endpoint measures. Therefore, it is unlikely that vitamin D supplementation would be an effective strategy for reducing diabetes risk even in vitamin D-deficient populations. This trial was registered at clinicaltrials.gov as NCT02112721.