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The effects of peanuts and tree nuts on lipid profile in type 2 diabetic patients: A systematic review and meta-analysis of randomized, controlled-feeding clinical studies.

Xia, J.Y., J.H. Yu, D.F. Xu, C. Yang, H. Xia, G.J. Sun, 2021. The effects of peanuts and tree nuts on lipid profile in Type 2 diabetic patients: A systematic review and meta-analysis of randomized, controlled-feeding clinical studies. Front. Nutr. https://doi.org/10.3389/fnut.2021.765571

Background: Type 2 diabetes mellitus was found to be associated with metabolic disorders, particularly abnormal glucose and lipid metabolism. Dietary food choices may have profound effects on blood lipids. The primary objective of this study was to examine the effects of peanuts and tree nuts intake on lipid profile in patients with type 2 diabetes. Methods: According to preferred reporting items for systematic reviews and meta-analysis guidelines, we performed a systematic search of randomized controlled clinical trials and systematic reviews published in PubMed, Web of Science, Embase, Scopus, and Cochrane library, from inception through June 2021. Studies in populations with type 2 diabetes, which compare nuts or peanuts to a controlled-diet group were included. We used the mean difference with 95% CIs to present estimates for continuous outcomes from individual studies. In addition, we used the GRADEpro tool to evaluate the overall quality of evidence. Results: Sixteen studies involving 1,041 participants were eligible for this review. The results showed that peanuts and tree nuts supplementation did not induce significant changes in low-density lipoprotein-cholesterol (LDL-C) (mean difference = −0.11; 95%CI: −0.25 – 0.03, p = 0.117) and high-density lipoprotein-cholesterol (HDL-C) (mean difference = 0.01; 95%CI: −0.01 – 0.04, p = 0.400) in patients with type 2 diabetics. In addition, we found that peanuts and tree nuts intake may cause a significantly reduction in total cholesterol (TC) (mean difference = −0.14; 95%CI: −0.26 – −0.02, p = 0.024) and triglyceride (TG) (mean difference = −0.10; 95%CI: −0.17 – −0.02, p = 0.010). In the subgroup analysis, a significantly greater reduction in TC was observed in studies which duration was <12 weeks (mean difference = −0.22; 95%CI: −0.37 – −0.08, p = 0.002). The quality of the body of evidence was “moderate” for TC and TG, the quality of evidence for LDL-C and HDL-C were “low.” Conclusion: Our findings suggest that consuming peanuts and tree nuts might be beneficial to lower TC concentration and TG concentration in type 2 diabetics subjects. Furthermore, peanuts and tree nuts supplementation could be considered as a part of a healthy lifestyle in the management of blood lipids in patients with type 2 diabetes. Given some limits observed in the current studies, more well-designed trials are still needed.

Quantitative determination of selected urolithin metabolites in human urine by simple sample preparation and UPLC-MS/MS analysis.

Provatas, A.A., S.A. Ayers, A.A. Callas, J.W. Birk, T.A. Lacson, D.W. Rosenberg, 2021. Quantitative determination of selected urolithin metabolites in human urine by simple sample preparation and UPLC-MS/MS analysis. Curr Top Anal Chem.  Vol 13, pg 69-80.

We report a simple, reliable, and validated method for the rapid screening and quantification of nine urolithin (UL) metabolites in human urine. Ultraperformance liquid chromatograph coupled with a tandem mass spectrometer (UPLC-MS/MS) was utilized for UL analysis following a simple sample preparation. Optimization of chromatographic and mass spectrometric conditions was performed to maximize the sensitivity and selectivity of the targeted analytes. A validation of the methodology was conducted to account for matrix interferences, linearity, method detection limits (MDLs), UL chemical stability, precision and accuracy of the ULs of interest. MDLs were achieved for the selected ULs ranging from 9.2-18.2 ng·mL-1. Excellent linear coefficients of determination were obtained for the range of calibration standards of 5.0-5,000 ng·mL-1, with R2 values between 0.9991 and 0.9998. The surrogate compound, 6,7-dihydroxycoumarin, was used to monitor the extraction efficiency and chrysin as the quantitative internal standard. The recoveries of the analytes were 88-99% with surrogate recoveries greater than 82%. This analytical method was developed and validated for processing samples associated with a human study, where it is hypothesized that walnut supplementation improves colonic health and lowers colorectal cancer risk, in part through enhancing UL formation.

The metabolomic-gut-clinical axis of Mankai plant-derived dietary polyphenols.

Yaskolka, M.A., K. Tuohy K, M. von Bergen, R. Krajmalnik-Brown, U. Heinig, H. Zelicha, G. Tsaban, E. Rinott, A. Kaplan, A. Aharoni, L. Zeibich, D. Chang, B. Dirks, C. Diotallevi, P. Arapitsas, U. Vrhovsek, U. Ceglarek, S.-B. Haange, U. Rolle-Kampczyk, B. Engelmann, M. Lapidot, M. Colt, Q. Sun, I., 2021. The metabolomic-gut-clinical axis of Mankai plant-derived dietary polyphenols. Nutrients. 13(6):1866. https://doi.org/10.3390/nu13061866.

Background: Polyphenols are secondary metabolites produced by plants to defend themselves from environmental stressors. We explored the effect of Wolffia globosa ‘Mankai’, a novel cultivated strain of a polyphenol-rich aquatic plant, on the metabolomic-gut clinical axis in vitro, in-vivo and in a clinical trial. Methods: We used mass-spectrometry-based metabolomics methods from three laboratories to detect Mankai phenolic metabolites and examined predicted functional pathways in a Mankai artificial-gut bioreactor. Plasma and urine polyphenols were assessed among the 294 DIRECT-PLUS 18-month trial participants, comparing the effect of a polyphenol-rich green-Mediterranean diet (+1240 mg/polyphenols/day, provided by Mankai, green tea and walnuts) to a walnuts-enriched (+440 mg/polyphenols/day) Mediterranean diet and a healthy controlled diet. Results: Approximately 200 different phenolic compounds were specifically detected in the Mankai plant. The Mankai-supplemented bioreactor artificial gut displayed a significantly higher relative-abundance of 16S-rRNA bacterial gene sequences encoding for enzymes involved in phenolic compound degradation. In humans, several Mankai-related plasma and urine polyphenols were differentially elevated in the green Mediterranean group compared with the other groups (p < 0.05) after six and 18 months of intervention (e.g., urine hydroxy-phenyl-acetic-acid and urolithin-A; plasma Naringenin and 2,5-diOH-benzoic-acid). Specific polyphenols, such as urolithin-A and 4-ethylphenol, were directly involved with clinical weight-related changes. Conclusions: The Mankai new plant is rich in various unique potent polyphenols, potentially affecting the metabolomic-gut-clinical axis.

Effects of walnut consumption for 2 years on lipoprotein subclasses among healthy elders: findings from the WAHA Randomized Controlled Trial.

Rajaram, S., M. Cofán, A. Sala-Vila, E. Haddad, M. Serra-Mir, E. Bitok, I. Roth, T.M. Freitas-Simoes, A. Kaur, C. Valls-Pedret, M. Doménech, K. Oda, D. Corella, J. Sabaté, E. Ros, 2021. Effects of walnut consumption for 2 years on lipoprotein subclasses among healthy elders: findings from the WAHA Randomized Controlled Trial. Circulation. 144(13):1083–1085.

Background: Frequent consumption of nuts, an important component of plant-based diets, is associated with 15% lower total cardiovascular disease (CVD) and 23% lower CVD mortality rates. Small, short-term randomized controlled trials (RCTs) indicate that diets supplemented with nuts have a consistent cholesterol-lowering effect; however, no trials of nut-enriched diets for lipid changes focused on elderly individuals, recruited participants from diverse geographical locations, or lasted 2 years. Also, there is little information concerning effects of nuts on lipoprotein subclasses. Objective: We hypothesized that incorporating walnuts into the usual diet would improve the lipid profile irrespective of differences in geographical and dietary background. Methods: The Walnuts and Healthy Aging (WAHA) study is a two-center (Barcelona, Spain and California, USA), 2-year, parallel-group RCT testing the effects of walnut supplemented diets in healthy elders. Lipoprotein changes were a pre-specified secondary outcome. Eligible candidates were cognitively healthy elders (63-79 years-old) without major comorbidities. Participants (n=708) were allocated to either a walnut-free (control) or walnut-supplemented diet (≈15% of energy, 30-60g/day). In 2-monthly visits, compliance, tolerance, medication changes, and body weight were recorded. At each visit, 8–week allotments of raw, pieced walnuts were delivered to the corresponding group. Results: 636 participants completed the study (90% retention rate) and 628 had full data for lipoprotein analyses (mean age 69 years, 67% women, 32% treated with statins). Mean baseline LDL-C and triglycerides were 117 and 105 mg/dL, respectively. The walnut diet significantly decreased (mg/dL) total cholesterol (mean -8.5 [95% CI, -11.2, -5.4]), LDL-C (mean -4.3 [-6.6, -1.6]), and intermediate-density lipoprotein (IDL)-C (-1.3 [-1.5, -1.0]), corresponding to reductions of 4.4%, 3.6%, and 16.8%, respectively, while triglycerides and HDL-C were unaffected (Figures-B, C). Total LDL particles and small LDL particle number decreased by 4.3% and 6.1%, respectively (Figure-D). Results were not different by study site. Lipid responses to the walnut diet differed by sex: LDL-C was reduced by 7.9% in men and by 2.6% in women (P-interaction=0.007). Conclusions: The results demonstrate that incorporating daily doses of walnuts (≈15% of energy) to the habitual diet of free-living elders with an essentially normal lipid profile resulted in a mean 4.3 mg/dL LDL-C reduction, which is modest, although greater responses have been observed among individuals with hypercholesterolemia. Our data also support a beneficial effect of the walnut diet on NMR-assessed lipoprotein subfractions, with reductions of IDL-C (a sizable contributor to remnant-C) and total LDL particles. Prospective studies have reported that LDL particle number consistently outperforms LDL-C in CVD risk prediction and that remnant-C causally relates to CVD independent of LDL-C. That lipid responses were not different in two cohorts consuming diverse diets strengthens the generalization of our results. WAHA is the largest and longest nut trial to date, overcoming the limitations of prior smaller and shorter nut studies. The novel finding of sexual dimorphism in LDL-C response to walnut supplementation needs confirmation. WAHA was conducted in free-living individuals, who chose their daily foods, which may be viewed as desirable since it is closer to real life than the situation in controlled feeding studies. On the basis of associations ascertained in cohort studies, the observed shift of the lipoprotein subclass phenotype suggests a reduction of lipoprotein-related CVD risk by long-term consumption of walnuts, which provides novel mechanistic insight for their potential cardiovascular benefit beyond effects on the standard lipid panel. Our data reinforce the notion that regular walnut consumption may be a useful part of a multi-component dietary intervention or dietary pattern to lower atherogenic lipids and improve CVD risk.