Moussa, M.R., N. Fan, J. Birk, A.A. Provatas, P. Mehta, Y. Hatano, O.K. Chun, M Darooghegi Mofrad, A. Lotfi, A. Aksenov, V.N. Motta, M. Zenali, H. Vaziri, J.J. Grady, M. Nakanishi, D.W. Rosenberg, 2025. Systemic inflammation and the inflammatory context of the colonic microenvironment is improved by urolithin A. Cancer Prev Res (Phila). https://doi.org/10.1158/1940-6207.capr-24-0383
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 metabolomics 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 identifies 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 serological inflammatory markers, including C-peptide, sICAM 1, sIL6R, Ghrelin, TRAIL, sVEGFR2, PDGF and MCP2, alterations that are more pronounced in obese individuals for siCAM-1, ENA-78, Leptin, GLP-1 and MIP-1D. There is a significant increase in levels of PYY associated with urolithin A formation, whereas TNF-α levels show an opposite trend, recapitulated in an in vitro system with ionomycin/PMA-stimulated PBMCs. 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.
Carter, S., A.M. Hill, L.C. Mead, H.Y. Wong, C. Yandell, J.D. Buckley, S.Y. Tan, G.B. Rogers, F. Fraysse, A.M. Coates, 2023. Almonds vs. carbohydrate snacks in an energy-restricted diet: Weight and cardiometabolic outcomes from a randomized trial. Obesity 31(10):2467–2481.
Objective: This study evaluated weight and cardiometabolic outcomes after a 3-month energy-restricted diet (-30%) containing almonds (almond-enriched diet [AED]) or containing carbohydrate-rich snacks (nut-free control diet [NFD]) (Phase 1), followed by 6 months of weight maintenance (Phase 2). Methods: Participants (25-65 years old) with overweight or obesity (BMI 27.5-34.9 kg/m2 ) were randomly allocated to AED (n = 68) or NFD (n = 72). Results: Both groups lost weight during Phase 1 (p < 0.001) (mean [SE], -7.0 [0.5] kg AED vs. -7.0 [0.5] kg NFD, p = 0.858) and Phase 2 (p = 0.009) (-1.1 [0.5] kg AED vs. -1.3 [0.6] NFD, p = 0.756), with improvements in percentage lean mass after Phase 2 (4.8% [0.3%], p < 0.001). Reductions occurred in fasting glucose (-0.2 [0.07] mmol/L, p = 0.003), insulin (-8.1 [4.0] pmol/L, p = 0.036), blood pressure (-4.9 [0.8] mm Hg systolic, -5.0 [0.5] mm Hg diastolic, p < 0.001), total cholesterol (-0.3 [0.1] mmol/L), low-density lipoprotein (LDL) (-0.2 [0.1] mmol/L), very low-density lipoprotein (-0.1 [0.03] mmol/L), and triglycerides (-0.3 [0.06] mmol/L) (all p < 0.001), and high-density lipoprotein increased (0.1 [0.02] mmol/L, p = 0.011) by the end of Phase 2 in both groups. There were group by time interactions for lipoprotein particle concentrations: very small triglyceride-rich (-31.0 [7.7] nmol/L AED vs. -4.8 [7.9] nmol/L NFD, p = 0.007), small LDL (-109.3 [40.5] nmol/L AED vs. -20.7 [41.6] nmol/L NFD, p = 0.017), and medium LDL (-24.4 [43.4] nmol/L AED vs. -130.5 [44.4] nmol/L NFD, p = 0.045). Conclusions: An energy-restricted AED resulted in weight loss and weight loss maintenance comparable to an energy-restricted NFD, and both diets supported cardiometabolic health. The AED resulted in greater improvements in some lipoprotein subfractions, which may enhance reductions in cardiovascular risk.
Fan, N., J.L. Fusco, D.W. Rosenberg, 2023. Antioxidant and anti-inflammatory properties of walnut constituents: focus on personalized cancer prevention and the microbiome. Antioxidants. 12(5): 982. https://doi.org/10.3390/antiox12050982
Walnuts have been lauded as a ‘superfood’, containing a remarkable array of natural constituents that may have additive and/or synergistic properties that contribute to reduced cancer risk. Walnuts are a rich source of polyunsaturated fatty acids (PUFAs: alpha-linolenic acid, ALA), tocopherols, antioxidant polyphenols (including ellagitannins), and prebiotics, including fiber (2 g/oz). There is a growing body of evidence that walnuts may contribute in a positive way to the gut microbiome, having a prebiotic potential that promotes the growth of beneficial bacteria. Studies supporting this microbiome-modifying potential include both preclinical cancer models as well as several promising human clinical trials. Mediated both directly and indirectly via its actions on the microbiome, many of the beneficial properties of walnuts are related to a range of anti-inflammatory properties, including powerful effects on the immune system. Among the most potent constituents of walnuts are the ellagitannins, primarily pedunculagin. After ingestion, the ellagitannins are hydrolyzed at low pH to release ellagic acid (EA), a non-flavonoid polyphenolic that is subsequently metabolized by the microbiota to the bioactive urolithins (hydroxydibenzo[b,d]pyran-6-ones). Several urolithins, including urolithin A, reportedly have potent anti-inflammatory properties. These properties of walnuts provide the rationale for including this tree nut as part of a healthy diet for reducing overall disease risk, including colorectal cancer. This review considers the latest information regarding the potential anti-cancer and antioxidant properties of walnuts and how they may be incorporated into the diet to provide additional health benefits.
Fan, N., J.L. Fusco, D.W. Rosenberg, 2023. Antioxidant and anti-inflammatory properties of walnut constituents: focus on personalized cancer prevention and the microbiome. Antioxidants. 12(5):982. https://doi.org/10.3390/antiox12050982
Walnuts have been lauded as a ‘superfood’, containing a remarkable array of natural constituents that may have additive and/or synergistic properties that contribute to reduced cancer risk. Walnuts are a rich source of polyunsaturated fatty acids (PUFAs: alpha-linolenic acid, ALA), tocopherols, antioxidant polyphenols (including ellagitannins), and prebiotics, including fiber (2 g/oz). There is a growing body of evidence that walnuts may contribute in a positive way to the gut microbiome, having a prebiotic potential that promotes the growth of beneficial bacteria. Studies supporting this microbiome-modifying potential include both preclinical cancer models as well as several promising human clinical trials. Mediated both directly and indirectly via its actions on the microbiome, many of the beneficial properties of walnuts are related to a range of anti-inflammatory properties, including powerful effects on the immune system. Among the most potent constituents of walnuts are the ellagitannins, primarily pedunculagin. After ingestion, the ellagitannins are hydrolyzed at low pH to release ellagic acid (EA), a non-flavonoid polyphenolic that is subsequently metabolized by the microbiota to the bioactive urolithins (hydroxydibenzo[b,d]pyran-6-ones). Several urolithins, including urolithin A, reportedly have potent anti-inflammatory properties. These properties of walnuts provide the rationale for including this tree nut as part of a healthy diet for reducing overall disease risk, including colorectal cancer. This review considers the latest information regarding the potential anti-cancer and antioxidant properties of walnuts and how they may be incorporated into the diet to provide additional health benefits.
Key Area: Cancer
