An Open-Label Randomized Crossover Trial of Lyophilized Black Raspberries on Postprandial Inflammation in Older Overweight Males: A Pilot Study.

This study was a 14-day, outpatient, open-label randomized crossover trial of lyophilized black raspberries (BRBs) in older overweight or obese males to determine whether BRB consumption affects postprandial inflammation associated with consumption of a high-fat high-calorie (HFHC) meal. Ten study participants consumed 45 g/d of lyophilized BRBs for 4 days, followed by a HFHC breakfast plus BRBs on day 6 or consumed the HFHC breakfast on day 6 without previous consumption of BRBs and then crossed over to the other treatment after a 2-day washout period. Blood samples were obtained before and 1, 2, 4, 8, and 12 hours after consumption of the HFHC breakfast. The primary study outcomes were changes in area under the concentration-time curve (AUC) for interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). The secondary outcomes were safety and tolerability of lyophilized BRB powder. The chronology and values of measured serum concentrations for IL-6, TNF-α, and CRP were consistent with those described previously by other investigators. The AUC of serum IL-6 was lowered significantly (P = 0.03, n = 10) with BRB consumption (34.3 ± 7.6 pg·mL⁻¹·h⁻¹ compared with 42.4 ± 17.9 pg·mL⁻¹·h⁻¹ for consumption of the HFHC meal alone). However, no significant differences (change in AUC) were calculated for serum CRP and TNF-α. The findings of this pilot study suggest that consumption of lyophilized BRBs may attenuate postprandial inflammation in overweight or obese males consuming a HFHC meal. Further investigation of BRBs is warranted to better elucidate their inflammomodulatory potential.

Associations between vitamin D-binding protein isotypes, circulating 25(OH)D levels, and vitamin D metabolite uptake in colon cancer cells.

Vitamin D metabolites have been extensively studied as cancer chemopreventive agents. Gc-globulin (GC) isotypes, based on rs7041 and rs4588 diplotypes, have varying affinities for 1α,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25(OH)D), which may affect circulating metabolite concentration as well as delivery at the cellular level. We evaluated associations between GC isotype and circulating vitamin D metabolite concentrations in 403 ursodeoxycholic acid (UDCA) clinical trial participants. Metabolite uptake was evaluated in human colon cancer (HCT-116) cells treated with ethanol vehicle, 1,25(OH)2D, or 25(OH)D, and with plasma from individuals with known GC isotype. Mammalian-2-hybrid and vitamin D-responsive element-based luciferase assays were used to measure the vitamin D receptor pathway activation as a marker for metabolite uptake. Regression analysis demonstrated significantly lower serum 25(OH)D concentration for clinical trial participants with 1F_2, 1S_2, or 2_2 isotypes (P < 0.01) compared with 1S_1S. Consistent with these in vivo observations, cellular data revealed that 25(OH)D uptake varied less by GC isotype only at the higher concentration tested (P = 0.05), while 1,25(OH)2D uptake differed markedly by GC isotype across concentration and assay (P < 0.01). The 1F_1S and 1F_2 isotypes produced the greatest reporter gene induction with 1,25(OH)2D treatment and, while activation varied less with 25(OH)D, the 2_2 isotype demonstrated increased induction at the lower concentration. These results suggest that vitamin D metabolite concentration and delivery to colon cells may vary not only by GC isotype, but also that certain isotypes may more effectively deliver 1,25(OH)2D versus 25(OH)D. Overall, these results may help identify populations at risk for cancer and potential recipients of targeted chemoprevention.

Association between circulating concentrations of 25(OH)D and colorectal adenoma: a pooled analysis.

The relationship between the biomarker of vitamin D status, 25(OH)D, and the risk for colorectal neoplasia is suggestive but equivocal. Questions remain regarding whether there are differential associations between 25(OH)D and colorectal adenoma by gender, colorectal subsite or features of baseline and recurrent adenomas. We sought to investigate the relationship between 25(OH)D and both baseline and recurrent adenoma characteristics. Our study was conducted among 2,074 participants in a pooled population of two clinical intervention trials of colorectal adenoma recurrence. A cross-sectional analysis of 25(OH)D and baseline adenoma characteristics and a prospective study of recurrent adenomas and their characteristics were conducted. There was a statistically significant inverse association between the concentrations of 25(OH)D and the presence of three or more adenomas at baseline. Compared to participants with 25(OH)D levels of <20 ng/mL, the adjusted odds ratios (ORs) (95% condifdence intervals [CIs]) were 0.99 (0.70-1.41) for those with concentrations of ≥20 and <30 ng/mL, and 0.73 (0.50-1.06) among participants with levels of ≥30 ng/mL (p-trend = 0.05). Baseline villous histology was also significantly inversely related to 25(OH)D levels (p-trend = 0.04). Conversely, 25(OH)D concentrations were not associated with overall colorectal adenoma recurrence, with ORs (95% CIs) of 0.91 (0.71-1.17) and 0.95 (0.73-1.24; p-trend = 0.85). These findings support the concept that the relationship between vitamin D and colorectal neoplasia may vary by stage of adenoma development.