Almond Consumption Improves Inflammatory Profiles Independent of Weight Change: A 6-Week Randomized Controlled Trial in Adults with Obesity
Background: Obesity is characterized by chronic low-grade systemic inflammation that contributes to metabolic dysfunction. Diet is a modifiable factor that can help reduce this inflammation. Nuts such as almonds are rich in unsaturated fats, and antioxidant and anti-inflammatory micronutrients, which may work synergistically to attenuate obesity-related inflammation. Hence, the objective of this study was to investigate whether daily almond consumption improves systemic inflammatory and immune markers in adults with obesity. Methods: In this randomized controlled parallel-arm trial (ClinicalTrials.gov ID NCT05530499), 69 adults (age 30-45 years) with obesity (BMI 30-45 kg/m2) were assigned to consume either 57 g/day of almonds (n = 38) or an isocaloric snack (cookie; n = 31) for six weeks. Fasting serum inflammatory cytokines, innate immune cell counts, body weight, serum glucose, insulin, lipid profile, and alpha-tocopherol were measured at baseline and week six. Dietary intake, compliance, palatability, acceptance, and appetite ratings were also assessed. Primary outcomes were analyzed using linear mixed models and baseline-adjusted linear models. Results: Subjective compliance was high in both groups, with greater acceptance of almonds (p < 0.05); however, serum alpha-tocopherol did not change. Almond consumption significantly decreased serum IL-6, TNF-α, and IFN-γ over 6 weeks compared with the cookie group (p < 0.05). No significant group differences were observed for innate immune cell counts, body weight, appetite ratings, blood pressure, or serum fasting glucose, insulin, total cholesterol (C), LDL-C, and triglycerides over six weeks. The almond group also increased intakes of monounsaturated fat, fiber, alpha-tocopherol, magnesium, zinc, and manganese, and improved diet quality indices relative to the cookie group (p < 0.05). Conclusions: Daily almond consumption for six weeks improved inflammatory cytokine profiles in adults with obesity, without changes in body weight under free-living conditions. These findings support recommending almonds as part of healthy dietary patterns to help attenuate obesity-related inflammation.
https://doi.org/10.3390/nu18050875
Nuts about pemphigus? A cross-sectional investigation into the role of nuts intake in modulating disease severity
Background Given the anti-inflammatory properties of nuts, their consumption might play a role in reducing inflammation and the severity of pemphigus vulgaris (PV). However, limited evidence exists regarding the association between nut intake and PV severity. Thus, this cross-sectional study investigates the relationship between PV severity and the consumption of total nuts as well as specific nut varieties. Methods This study included 138 PV patients, of whom 108 had a Pemphigus Disease Area Index (PDAI)<15 and 30 had a PDAI≥15. Dietary intake was evaluated using a validated 168-item food frequency questionnaire, and consumption of total nuts and subtypes (peanuts, hazelnuts, almonds, walnuts and pistachios) was categorised into quartiles. Results While no significant association was found between individual nut types and PV severity, individuals with the highest total nut intake (including peanuts, hazelnuts, almonds, walnuts and pistachios) were 92% less likely to experience increased PV severity compared with those with the lowest intake (OR: 0.08; 95% CI 0.01 to 0.38). This association remained significant after adjusting for age, sex and energy intake (OR: 0.072; 95% CI 0.01 to 0.36). Further adjustments for corticosteroid use and physical activity did not alter the strength or significance of the association (OR: 0.08; 95% CI 0.01 to 0.42). Conclusion Our findings suggest that higher total nut consumption is inversely associated with PV severity, though no such link was observed for specific nut subtypes. Prospective cohort studies are needed to validate these results.
https://doi.org/10.1136/bmjnph-2025-001368
Systemic Inflammation and the Inflammatory Context of the Colonic Microenvironment Are Improved by Urolithin A
Diet affects cancer risk, and plant-derived polyphenols exhibit cancer-preventive properties. Walnuts are an exceptional source of polyphenolic ellagitannins, converted into urolithins by gut microflora. This clinical study examines the impact of urolithin metabolism on inflammatory markers in blood and colon polyp tissue. We evaluate the effects of walnut consumption on urinary urolithins, serum inflammatory markers, and immune cell markers in polyp tissues obtained from 39 subjects. Together with detailed food frequency data, we perform integrated computational analysis of metabolomic data combined with serum inflammatory markers and spatial imaging of polyp tissues using imaging mass cytometry. LC/MS-MS analyses of urine and fecal samples identify a widely divergent capacity to form nine urolithin metabolites in this patient population. Subjects with higher urolithin A formation exhibit lower levels of several key serologic inflammatory markers, including C-peptide, soluble form of intracellular adhesion molecule 1, sIL-6R, ghrelin, TRAIL, sVEGFR2, platelet-derived growth factor (PDGF), and MCP-2, alterations that are more pronounced in obese individuals for soluble form of intracellular adhesion molecule 1, epithelial neutrophil-activating peptide 78, leptin, glucagon-like peptide 1, and macrophage inflammatory protein 1δ. There is a significant increase in levels of peptide YY associated with urolithin A formation, whereas TNFα levels show an opposite trend, recapitulated in an in vitro system with ionomycin/phorbol 12-myristate 13-acetate-stimulated peripheral blood mononuclear cells (PBMC). Spatial imaging of colon polyp tissues shows altered cell cluster patterns, including a significant reduction of vimentin and CD163 expression associated with urolithin A. The ability to form urolithin A is linked to inflammation, warranting further studies to understand the role of urolithins in cancer prevention. Prevention Relevance: We evaluate cancer-protective effects of walnuts via formation of microbe-derived urolithin A, substantiating their functional benefits on serum inflammatory markers and immunologic composition of polyps in normal/obese subjects. Our approach incorporates personalized nutrition within the context of colonic health, providing the rationale for dietary inclusion of walnut ellagitannins for cancer prevention.
https://doi.org/10.1158/1940-6207.CAPR-24-0383
Brazil Nut (Bertholletia excelsa H.B.K.) Consumption in Energy-Restricted Intervention Decreases Proinflammatory Markers and Intestinal Permeability of Women with Overweight/Obesity: A Controlled Trial (Brazilian Nuts Study)
Background: Obesity is associated with low-grade inflammation and increased intestinal permeability (IP). The Brazil nut (BN) (Bertholletia excelsa H.B.K.) appears to be a promising dietary intervention to control inflammation by enhancing antioxidant defenses. Objectives: We aimed to assess the effect of daily BN consumption on inflammatory biomarkers and IP in the context of an energy-restricted intervention. Furthermore, we evaluated the correlation between the changes in these inflammatory markers and the changes in serum selenium and IP. Methods: In this 8-wk nonrandomized controlled trial, 56 women with overweight or obesity were allocated into 2 groups, both following an energy-restricted diet (-500 kcal/d). The control group (CO) consumed a nut-free diet, while the BN group consumed 8 g BN/d, providing 347.2 μg selenium (Se). Inflammatory cytokines were analyzed in plasma and Se in serum. IP was assessed using the lactulose/mannitol test (LM ratio). Results: Forty-six women completed the intervention. Both groups achieved similar energy restriction (CO Δ= -253.7 ± 169.4 kcal/d; BN Δ= -265.8 ± 141.8 kcal/d) and weight loss (CO Δ= -2.5 ± 0.5 kg; BN Δ= -3.5 ± 0.5 kg). The BN group showed lower values of C-reactive protein, tumor necrosis factor, interleukin (IL)1-β, IL-8, percentage lactulose excretion, and LM ratio than the CO group. Additionally, changes in serum Se concentration were predictive of changes in IL-8 concentration (β: -0.054; adjusted R2: 0.100; 95% confidence interval [CI]: -0.100; -0.007; P = 0.025), and changes in IL-8 were predictive of changes in the LM ratio (β: 0.006; adjusted R2: 0.101; 95% CI: 0.001, 0.011; P = 0.024). Conclusions: Regular intake of BNs can be a promising complementary dietary strategy for controlling low-grade inflammation and improving IP in women with overweight/obesity undergoing energy-restricted treatment. However, the effects of BNs seem to be Se status-dependent. This trial was registered at the Brazilian Registry of Clinical Trials (ReBEC: https://ensaiosclinicos.gov.br/rg/RBR-3ntxrm/). https://doi.org/10.1016/j.tjnut.2024.07.016
Regulation of Intestinal Inflammation by Walnut-Derived Bioactive Compounds
Walnuts (Juglans regia L.) have shown promising effects in terms of ameliorating inflammatory bowel disease (IBD), attributed to their abundant bioactive compounds. This review comprehensively illustrates the key mechanisms underlying the therapeutic potential of walnuts in IBD management, including the modulation of intestinal mucosa permeability, the regulation of inflammatory pathways (such as NF-kB, COX/COX2, MAPCK/MAPK, and iNOS/NOS), relieving oxidative stress, and the modulation of gut microbiota. Furthermore, we highlight walnut-derived anti-inflammatory compounds, such as polyunsaturated fatty acids (PUFA; e.g., ω-3 PUFA), tocopherols, phytosterols, sphingolipids, phospholipids, phenolic compounds, flavonoids, and tannins. We also discuss unique anti-inflammatory compounds such as peptides and polysaccharides, including their extraction and preparation methods. Our review provides a theoretical foundation for dietary walnut supplementation in IBD management and provides guidance for academia and industry. In future, research should focus on the targeted isolation and purification of walnut-derived anti-inflammatory compounds or optimizing extraction methods to enhance their yields, thereby helping the food industry to develop dietary supplements or walnut-derived functional foods tailored for IBD patients. https://doi.org/10.3390/nu16162643
The role of intestinal microbiota and microRNAs in the anti-inflammatory effects of cranberry: from pre-clinical to clinical studies
Cranberries have known anti-inflammatory properties, which extend their benefits in the context of several chronic diseases. These benefits highly rely on the polyphenol profile of cranberries, one of few foods rich in A-type proanthocyanidin (PAC). A-type PAC comprises flavan-3-ol subunits with an additional interflavan ether bond in the conformational structure of the molecule, separating them from the more commonly found B-type PAC. PACs with a degree of polymerization higher than three are known to reach the colon intact, where they can be catabolyzed by the gut microbiota and biotransformed into lower molecular weight organic acids that are available for host absorption. Gut microbiota-derived metabolites have garnered much attention in the past decade as mediators of the health effects of parent compounds. Though, the mechanisms underlying this phenomenon remain underexplored. In this review, we highlight emerging evidence that postulates that polyphenols, including ones derived from cranberries, and their metabolites could exert anti-inflammatory effects by modulating host microRNAs. Our review first describes the chemical structure of cranberry PACs and a pathway for how they are biotransformed by the gut microbiota. We then provide a brief overview of the benefits of microbial metabolites of cranberry in the intestinal tract, at homeostasis and in inflammatory conditions. Finally, we discuss the role of microRNAs in intestinal health and in response to cranberry PAC and how they could be used as targets for the maintenance of intestinal homeostasis. Most of this research is pre-clinical and we recognize that conducting clinical trials in this context has been hampered by the lack of reliable biomarkers. Our review discusses the use of miRNA as biomarkers in this context. https://doi.org/10.3389/fnut.2023.1092342