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Research Area: Cancer

The effect of nut consumption on cancer is a relatively new area of research. Tree nuts contain a wide range of nutrients with recognized benefits to human health including unsaturated fats, protein, vitamins (i.e., vitamin E, folate and niacin), minerals (i.e., magnesium, calcium and potassium) and phytochemicals—all of which may offer anticarcinogenic, anti-inflammatory and antioxidant properties.

In a recent study, researchers concluded that there was an inverse association of dietary nut consumption with cancer risk, especially for cancers of the digestive system[i].  A number of studies have been conducted to date looking at the effect of nuts on colorectal cancer, which affects both men and women, and is the second leading cause of cancer-related deaths in the United States and third most common cancer worldwide. In one study, researchers found an association between high frequency of nut consumption and reduced risk of colorectal cancer[ii]. In another study[iii], colon cancer patients who consumed nuts had a significant decrease in cancer recurrence and death.

While nut consumption is associated with reduced total and certain cause-specific mortality in general populations, its association with cancer outcomes among long-term breast cancer survivors remains unknown. Researchers in one study[IV] examined the associations of nut consumption (including tree nuts and peanuts) at 5-years postdiagnosis, with overall survival and disease-free survival among 3,449 long-term breast cancer survivors from the Shanghai Breast Cancer Survival Study. The data showed that nut consumption was associated with better survival, particularly disease-free survival, among long-term breast cancer survivors.

At Harvard, researchers looked at the association between nut consumption and prostate cancer risk and mortality among 47,299 men. While nut consumption was not associated with a reduced risk of prostate cancer, men who had prostate cancer and consumed tree nuts five or more times per week after diagnosis, had a significant 34 percent lower risk of overall mortality than those who consumed nuts less than once per month[iv].

While more research on tree nuts and cancer is needed, the research that has been done to date is very promising.

[i]Long, J., Z. Ji, P. Yuan, T. Long, K. Liu, J. Li, L. Cheng, 2020. Nut consumption and risk of cancer: A meta-analysis of prospective studies. Cancer Epidemiol Biomarkers Prev. 29(3):565-573.

[ii] Lee, J., A. Shin, J.H. Oh, J. Kim, 2018. The relationship between nut intake and risk of colorectal cancer: a case control study. Nutrition Journal. 17:37 https://doi.org/10.1186/s12937-018-0345-y.

[iii] Fadelu, T., S. Zhang, D. Niedzwiecki, X. Ye, L.B. Saltz, R.J. Mayer, R.B. Mowat, R. Whittom, A. Hantel, A.B. Benson, D.M. Atienza, M. Messino, H.L. Kindler, A. Venook, S. Ogino, K. Ng, K. Wu, W. Willett, E. Giovannucci, J. Meyerhardt, Y. Bao, C.S. Fuchs, 2018. Nut consumption and survival in patients with stage III colon cancer: results from CALGB 89803 (Alliance). J Clin Oncol. 36(11):1112-1120.

[iv] Cong, W., K. Gu, F. Wang, H. Cai, W. Zheng, P. Bao, X.-O. Shu, 2022. Nut consumption in association with overall mortality and recurrence/disease-specific mortality among long-term breast cancer survivors. International Journal of Cancer.doi.org/10.1002/ijc.33824.

[v]Wang, W., M. Yang, S.A. Kenfield, F.B. Hu, M.J. Stampfer, W.C. Willett, C.S. Fuchs, E.L. Giovannucci, Y. Bao, 2016. Nut consumption and prostate cancer risk and mortality. Br J Cancer. 115(3):371-374.

The effects of a Mediterranean diet intervention on cancer-related fatigue for patients undergoing chemotherapy: a pilot randomized controlled trial.

Kleckner, A. S., J.E. Reschke, I.R. Kleckner, A. Magnuson, A.M. Amitrano, E. Culakova, M. Shayne, C.S. Netherby-Winslow, S. Czap, M.C. Janelsins, K.M. Mustian, L.J. Peppone, 2022. The effects of a Mediterranean diet intervention on cancer-related fatigue for patients undergoing chemotherapy: a pilot randomized controlled trial. Cancers. 14(17):4202. https://doi.org/10.3390/cancers14174202

Cancer-related fatigue is a common, burdensome symptom of cancer and a side-effect of chemotherapy. While a Mediterranean Diet (MedDiet) promotes energy metabolism and overall health, its effects on cancer-related fatigue remain unknown. In a randomized controlled trial, we evaluated a rigorous MedDiet intervention for feasibility and safety as well as preliminary effects on cancer-related fatigue and metabolism compared to usual care. Participants had stage I–III cancer and at least six weeks of chemotherapy scheduled. After baseline assessments, randomization occurred 2:1, MedDiet:usual care. Measures were collected at baseline, week 4, and week 8 including MedDiet adherence (score 0–14), dietary intake, and blood-based metabolic measures. Mitochondrial respiration from freshly isolated T cells was measured at baseline and four weeks. Participants (n = 33) were 51.0 ± 14.6 years old, 94% were female, and 91% were being treated for breast cancer. The study was feasible, with 100% completing the study and >70% increasing their MedDiet adherence at four and eight weeks compared to baseline. Overall, the MedDiet intervention vs. usual care had a small-moderate effect on change in fatigue at weeks 4 and 8 (ES = 0.31, 0.25, respectively). For those with a baseline MedDiet score <5 (n = 21), the MedDiet intervention had a moderate-large effect of 0.67 and 0.48 at weeks 4 and 8, respectively. The MedDiet did not affect blood-based lipids, though it had a beneficial effect on fructosamine (ES = −0.55). Fatigue was associated with mitochondrial dysfunction including lower basal respiration, maximal respiration, and spare capacity (p < 0.05 for FACIT-F fatigue subscale and BFI, usual fatigue). In conclusion, the MedDiet was feasible and attenuated cancer-related fatigue among patients undergoing chemotherapy, especially those with lower MedDiet scores at baseline.

Nut consumption in association with overall mortality and recurrence/disease-specific mortality among long-term breast cancer survivors.

Cong, W., K. Gu, F. Wang, H. Cai, W. Zheng, P. Bao, X.-O. Shu, 2022. Nut consumption in association with overall mortality and recurrence/disease-specific mortality among long-term breast cancer survivors. International Journal of Cancer.doi.org/10.1002/ijc.33824.

High nut consumption is associated with reduced total and certain cause-specific mortality in general populations. However, its association with cancer outcomes among long-term breast cancer survivors remains unknown. We examined the associations of nut consumption (including peanuts and tree nuts), assessed at 5-year postdiagnosis, with overall survival (OS) and disease-free survival (DFS) among 3449 long-term breast cancer survivors from the Shanghai Breast Cancer Survival Study, applying Cox regression analysis. During a median follow-up of 8.27 years post dietary assessment, there were 374 deaths, including 252 breast cancer deaths. Among 3274 survivors without previous recurrence at the dietary assessment, 209 developed breast cancer-specific events, that is, recurrence, metastasis or breast cancer mortality. At 5-year post dietary assessment (ie, 10-year postdiagnosis), regular nut consumers had higher OS (93.7% vs 89.0%) and DFS (94.1% vs 86.2%) rates. After multivariable adjustment, nut consumption was positively associated with OS (Ptrend = .022) and DFS (Ptrend = .003) following a dose-response pattern, with hazard ratios (95% confidence interval) of 0.72 (0.52-1.05) for OS and 0.48 (0.31-0.73) for DFS, for participants with greater than median nut intake compared with nonconsumers. The associations did not vary by nut type. Stratified analyses showed that the associations were more evident among participants with a higher total energy intake for OS (Pinteraction = .02) and among participants with early stage (I-II) breast cancers for DFS (Pinteraction = .04). The nut-DFS associations were not modified by estrogen receptor/progesterone receptor status or other known prognostic factors. In conclusion, nut consumption was associated with better survival, particularly DFS, among long-term breast cancer survivors.

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.

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.