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Research Nut: Walnuts

Association of nut consumption with risk of total cancer and 5 specific cancers: evidence from 3 large prospective cohort studies.

Fang, Z., Y. Wu, Y. Li, X. Zhang, W.C. Willett, A.H. Eliassen, B. Rosner, M. Song, L.A. Mucci, E.L. Giovannucci, 2021. Association of nut consumption with risk of total cancer and 5 specific cancers: evidence from 3 large prospective cohort studies. Amer J Clin Nutr. 114(6):1925–1935. https://doi.org/10.1093/ajcn/nqab295

Background: The associations between nut consumption and cancer risk have not been extensively investigated. Objectives: We aimed to examine the associations between nut consumption, especially specific types of nuts (peanut, tree nut, walnut, and tree nut other than walnut), and cancer risk. Methods: Nut consumption was assessed by FFQ at baseline and updated every 2–4 y in the Nurses’ Health Study (1980– 2014), the Nurses’ Health Study II (1991–2015), and the Health Professionals Follow-up Study (1986–2018). We examined the associations between the intake of total and specific types of nuts and risk of total cancer and common cancers, including lung, colorectal, breast, bladder, and aggressive prostate cancer. Cox proportional hazards models were used to obtain the HRs and 95% CIs in each cohort as well as pooled. Results: During 5,873,671 person-years of follow-up in 180,832 women and 45,560 men, we documented 44,561 incident cancer cases. As compared with nonconsumers, the pooled multivariable HRs of total nut consumption for ≥5 times/wk were 0.99 (95% CI: 0.94, 1.04; P-trend = 0.54) for total cancer, 0.88 (95% CI: 0.74, 1.04; P-trend = 0.18) for lung cancer, 1.07 (95% CI: 0.92, 1.26; P-trend = 0.89) for colorectal cancer, 0.90 (95% CI: 0.71, 1.14; P-trend = 0.65) for bladder cancer, 0.96 (95% CI: 0.85, 1.08; Ptrend = 0.36) for breast cancer, and 1.18 (95% CI: 0.92, 1.51; Ptrend = 0.52) for aggressive prostate cancer Conclusions: In 3 large prospective cohorts, frequent nut consumption was not associated with risk of total cancer and common individual cancers.

Branched-chain amino acids in relation to food preferences and insulin resistance in obese subjects consuming walnuts: A cross-over, randomized, double-blind, placebo-controlled inpatient physiology study.

Tuccinardi, D., N. Perakakis, O.M. Farr, J. Upadhyay, C.S. Mantzoros, 2021. Branched-chain amino acids in relation to food preferences and insulin resistance in obese subjects consuming walnuts: A cross-over, randomized, double-blind, placebo-controlled inpatient physiology study. Clin Nutr. 40(5):3032-3036.

Background & aims: To assess whether the concentrations of circulating Branched-Chain Amino Acids (BCAAs) change after walnut consumption and, whether these changes are associated with alterations in markers of insulin resistance and food preferences. Methods: In a crossover, randomized, double-blind, placebo-controlled study, ten subjects participated in two 5-day inpatient study admissions, during which they had a smoothie containing 48 g walnuts or a macronutrient-matched placebo smoothie without nuts every morning. Between the two phases there was a 1-month washout period. Results: Fasting valine and isoleucine levels were reduced (p = .047 and p < .001) and beta-hydroxybutyrate levels were increased after 5-days of walnut consumption compared to placebo (p = .023). Fasting valine and isoleucine correlated with HOMA-IR while on walnut (r = 0.709, p = .032 and r = 0.679, p = .044). The postprandial area under the curve (AUC) of leucine in response to the smoothie consumption on day 5 was higher after walnut vs placebo (p = .023) and correlated negatively with the percentage of Kcal from carbohydrate and protein consumed during an ad libitum buffet meal consumed the same day for lunch (r = −0.661, p = .037; r = −0.628, p = .05, respectively). Conclusion: The fasting and post-absorptive profiles of BCAAs are differentially affected by walnut consumption. The reduction in fasting valine and isoleucine may contribute to the longer-term benefits of walnuts on insulin resistance, cardiovascular risk and mortality, whereas the increase in post-absorptive profiles with walnuts may influence food preference.

Dietary intake of walnut prevented Helicobacter pylori-associated gastric cancer through rejuvenation of chronic atrophic gastritis.

Park, J.M., Y.M. Han, Y.J. Park, K.B. Hahm, 2021. Dietary intake of walnut prevented Helicobacter pylori-associated gastric cancer through rejuvenation of chronic atrophic gastritis. J Clin Biochem Nutr. 68(1): 37–50.

The fact that Fat-1 transgenic mice producing n-3 polyunsaturated fatty acids via overexpressed 3-desaturase significantly mitigated Helicobacter pylori (H. pylori)-associated gastric tumorigenesis through rejuvenation of chronic atrophic gastritis (CAG) led us to study whether dietary intake of walnut plentiful of n-3 PUFAs can be nutritional intervention to prevent H. pylori-associated gastric cancer. In our model that H. pylori-initiated, high salt diet-promoted gastric carcinogenesis, pellet diet containing 100 mg/kg and 200 mg/kg walnut was administered up to 36 weeks. As results, control mice (24 weeks) developed significant chronic CAG, in which dietary walnuts significantly ameliorated chronic atrophic gastritis. Expressions of COX-2/PGE2/NF-κB/c-Jun, elevated in 24 weeks control group, were all significantly decreased with walnut (p<0.01). Tumor suppressive enzyme, 15-PGDH, was significantly preserved with walnut. Control mice (36 weeks) all developed significant tumors accompanied with severe CAG. However, significantly decreased tumorigenesis was noted in group treated with walnuts, in which expressions of COX-2/PGE2/NF-κB/IL-6/STAT3, all elevated in 36 weeks control group, were significantly decreased with walnut. Defensive proteins including HO-1, Nrf2, and SOCS-1 were significantly increased in walnut group. Proliferative index as marked with Ki-67 and PCNA was significantly regulated with walnut relevant to 15-PGDH preservation. Conclusively, walnut can be an anticipating nutritional intervention against H. pylori.

Transcriptome profiling analysis of the response to walnut polyphenol extract in Helicobacter pylori-infected cells.

Park, J.M., Y.M. Han, H.J. Lee, S.J. Hwang, S.J. Kim, K.B. Hahm, 2021. Transcriptome profiling analysis of the response to walnut polyphenol extract in Helicobacter pylori-infected cells. J Clin Biochem Nutr. doi.org/10.3164/jcbn.20-128.

Dietary intervention to prevent Helicobacter pylori (H. pylori)-associated gastric diseases seems to be ideal with no risk of bacterial resistance, safe long-term intervention, and correcting pathogenic mechanisms including rejuvenation of precancerous atrophic gastritis and anti-mutagenesis. A transcriptome as set of all RNAs transcribed by certain tissues or cells demonstrates gene functions and reveals the molecular mechanism of specific biological processes against diseases. Here, we have performed RNAseq and bioinformatic analysis to explain proof of concept that walnut intake can rescue from H. pylori infection and explore unidentified mode of actions of walnut polyphenol extract (WPE). As results, BIRC3, SLC25A4, f3 transcription, VEGFA, AZU1, HMOX1, RAB3A, RELBTNIP1, ETFB, INPP5J, PPME1, RHOB, TPI1, FOSL1, JUND.RELB, KLF2, MUC1, NDRG1, ALDOA, ENO1, PFKP, GPI, GDF15, and NRTN genes were newly discovered to be enriched with WPE, whereas CCR4, BLNK, CCR7, CXCR4, CDO1, KLSG1, SELE, RASGRP2, PIK3R3, TSPAN32, HOXC-AS3, HCG8, BTNL8, and CXCL3 genes as inhibitory targets by WPE in H. pylori infection. We identified additional genes what WPE afforded actions of avoiding H. pylori-driven onco-inflammation and rejuvenating precancerous atrophic gastritis. Conclusively, after applying RNAseq analysis in order to document walnut intake for precision medicine against H. pylori infection, significant transcriptomic profiling applicable for validation were drawn.