Very-long chain omega-3 fatty acids (EPA and DHA) have anti-inflammatory properties that may help reduce morbidity and mortality from COVID-19 infection. We conducted a pilot study in 100 patients to test the hypothesis that RBC EPA+DHA levels (the Omega-3 Index, O3I) would be inversely associated with risk for death by analyzing the O3I in banked blood samples drawn at hospital admission. Fourteen patients died, one of 25 in quartile 4 (Q4) (O3I ≥5.7%) and 13 of 75 in Q1-3. After adjusting for age and sex, the odds ratio for death in patients with an O3I in Q4 vs Q1-3 was 0.25, p = 0.07. Although not meeting the classical criteria for statistical significance, this strong trend suggests that a relationship may indeed exist, but more well-powered studies are clearly needed.

SUMMARYVery-long chain omega-3 fatty acids (EPA and DHA) have anti-inflammatory properties that may help reduce morbidity and mortality from COVID-19 infection. We conducted a pilot study in 100 patients to test the hypothesis that RBC EPA+DHA levels (the Omega-3 Index, O3I) would be inversely associated with risk for death by analyzing the O3I in banked blood samples drawn at hospital admission. To have adequate power (>80%) in this pilot study, we pre-specified a significance level of 0.10. Fourteen patients died, one of 25 in quartile 4 (Q4) (O3I ≥5.7%) and 13 of 75 in Q1-3. After adjusting for age and sex, the odds ratio for death in patients with an O3I in Q4 vs Q1-3 was 0.25, p=0.07. Thus, we have suggestive evidence that the risk for death from COVID-19 was lower in those with the highest O3I levels. These preliminary findings need to be confirmed in larger studies.

INTRODUCTION There is abundant interest in the potential therapeutic and supportive role of a ketogenic diet (KD) for glioblastoma patients. We conducted a single-arm phase 1 trial to assess the safety and feasibility of KD plus standard-of-care (SOC) in glioblastoma patients (NCT03451799). METHODS Adults within 3 months of diagnosis participated in a 16-week intervention of a classic 3:1 KD (grams fat : grams carbohydrate + protein) with dietitian support. Blood glucose and ketone levels were assessed twice daily (Keto-Mojo), with remote monitoring of daily weight and activity (Fitbit). The primary objective was to assess safety (weight stability, CTCAE) and feasibility (maintaining ketosis > 0.3mM for > 50% of study period). Secondary objectives included assessments of progression-free survival (PFS), overall survival (OS), health-related quality of life (HRQOL), and cognition (MoCA). RESULTS From 04/2018-02/2021, 14 patients were evaluable: female:male, 8:6, median age 55 years, KPS 80, BMI 24.5. MGMT promoter methylation: 6 present, 7 absent, 1 indeterminate. Adherence to KD was high, with all patients maintaining ketosis ( > 0.3mM) > 50% and 11 patients maintaining ketosis > 85% of study days. Adverse events (> Grade 2) potentially attributable to KD: appetite loss (Grade 2: 2); fatigue (Grade 2: 5); flu-like symptoms (Grade 2: 1); constipation (Grade 2: 5, Grade 3: 1). No patients were removed from study for safety reasons. HRQOL was stable, with improvements in role function (not statistically significant). MoCA score improved in 10/14 patients. Median PFS and OS from KD initiation were 11.7 and 29.1 months, respectively. CONCLUSION Our findings suggest that a supervised KD plus SOC is safe and feasible in glioblastoma patients. KD was well-tolerated with encouraging trends in HRQOL and cognition. PFS and OS in this small trial compare favorably to historical control. A multicenter phase 2 trial powered to assess efficacy is planned.

Objectives Prostate cancer (PC) is the most common non-skin cancer in men and the second leading cause of cancer death. Omega-3 fatty acids and polyphenols have bioactive properties that may alter tumor biology and reduce PC progression. Walnuts (Juglans regia L.) are one of the best sources of plant-based omega-3 s (2.5 g per oz) and polyphenols (total polyphenols 462 mg per oz). We propose to determine the effect of walnuts added to a typical diet on markers of PC progression in men scheduled for radical prostatectomy (RP). The primary objective of the study is to determine the effect of walnut intake on Ki67 expression in prostatic tissue. Secondary objectives are to determine the effect of walnuts on prostatic tissue oxidative stress and inflammation. Exploratory objectives include measuring the effect of walnuts on the gut microbiome, insulin/IGF signaling and gene expression. Methods 50 men with PC scheduled for RP are recruited from the Durham Veterans Medical Center and Cedars-Sinai Medical Center. Men are randomized to receive 2 oz. of walnuts added to a usual diet (intervention) or control (usual diet) using a 1:1 allocation during the 3–10-week pre-RP period. An experienced dietitian provides counseling and recipes to men in the intervention arm and monitor dietary compliance.  RP tissue is stained and scored for Ki67 by an experienced pathologist. Tumors are processed for RNA extraction and RNA-sequenced at the UCLA genomics core.  Fasting blood are collected at baseline and pre-RP visits, spun, separated into serum, plasma, and red blood cells and stored at −80°C. Serum are batch-analyzed for insulin, IGF-1, IGFBP-3, and IL-6. Stool samples for microbiota analyses are collected at baseline and pre-RP visits and undergo 16 s rRNA gene sequencing and statistical analyses to identify microbiome community content. Between-arm differences during the study are assessed by t-test for continuous variables and chi-square test for categorical variables. The study will be completed in 3 years. To date, 7 men have been recruited. Results N/A Conclusions If shown to be effective in improving PC outcomes in men diagnosed with early stage PC, this modest dietary change could provide a much needed feasible, low-cost, easily accessible, non-toxic option that could be sustained over the long-term. Funding Sources California Walnut Commission.

BACKGROUND Emerging evidence suggests that a ketogenic diet (KD) may limit neoplastic growth, but limited data exist regarding the effect of KD on daily activity, cognition, and health-related quality-of-life (HRQOL) for patients with glioblastoma. METHODS Newly diagnosed GBM patients participating in a single-arm phase 1 trial of a 16-week KD plus standard-of-care measured BID blood glucose and ketone levels (Keto-Mojo), captured continuous activity data (Fitbit), and completed quality-of-life (QLQ30) surveys and Montreal Cognitive Assessments (MoCA) at baseline, Week 8, and study end (up to 16 weeks). NCT03451799. RESULTS All patients (n = 14; 57% female; median age 55 years) maintained blood ketones above 0.3 mM > 50% of study duration (mean per-patient days in ketosis = 87%). Mean glucose (mg/dl) and ketone levels decreased through the study – Weeks 1/2: glucose 94.9 (SD:16.5), ketones 1.44 (SD:5.82); Weeks 3/4: glucose 94.1 (SD:12.9), ketones 1.34 (SD:0.9); Final two weeks: glucose 92.3 (SD:13.3), ketones 1.13 (SD:0.7). On average, patients walked 6,836 steps/day (SD:5,129), spending 14.3 hours sedentary (SD:6.45) and 43.6 minutes (SD:60.4) in high-intensity activity. Sleep duration was 6.8 hours (SD:2.26). Patients (n = 9) with OS > 14.6 mo from diagnosis demonstrated greater minutes of high-intensity activity (58.2 vs 20.7, p = 0.001), downtrending glucose (p = 0.001), and higher ketone levels (1.40 vs 1.11, p = 0.026). Activity data corroborated the tolerability of KD with stable-to-increased activity by study end. MoCA scores were stable from baseline (mean 23.4/30, SD:4.16) to study end (mean 24.8/30, SD:7.12; p = 0.38). When viewed as a composite score, HRQOL was stable-to-improving in 10/14 patients at Week 8 and EOS. CONCLUSION The use of wearable technology and at-home testing allowed for remote monitoring of activity and diet adherence. Good adherence and stable HRQOL and activity levels were observed in this phase 1 trial.