Mediterranean Diet Intervention in Patients with Myeloproliferative Neoplasm

Reasoning that a Mediterranean diet intervention is a low-risk, low-cost approach to reduce inflammation, we set out to test whether MPN patients can adopt a Mediterranean style eating pattern. We completed two randomized clinical trials to address the feasibility of a Mediterranean diet intervention in MPN patients. The primary objective of the 1st study was to test whether MPN patients can adopt a Mediterranean diet eating pattern with registered dietician (RD) counseling. We enrolled 28 patients with MPN (14 PV, 6 ET, 8 MF) into a 15 week interventional study. After a two-week observation period, patients were randomized to either a Mediterranean diet (MED) or the United States Dietary Guidelines for Americans (USDA) diet groups. Participants received active intervention for 10 weeks, comprising of weekly educational curriculum and personalized RD visits at weeks 3, 5, and 7 geared toward their assigned diet. Participants were observed for an additional 3 weeks post intervention.

Adoption of a Mediterranean style eating pattern was quantified using the 14-Item Mediterranean Diet Adherence Screener (MEDAS), with a score of ≥8 regarded as highly adherent to a Mediterranean eating pattern. Over 75% of the participants in the MED group maintained a MEDAS score of ≥8 over the entire active intervention period demonstrating that MPN patients can successfully adopt a Mediterranean diet eating pattern with RD counseling and written curriculum.

Symptom burden was assessed using the MPN-Total Symptom Score (MPN-TSS) measured at baseline, weeks 3, 6, 9, 12, and 15. Approximately half of the Mediterranean diet cohort enjoyed a ≥ 50% reduction in MPN-TSS at weeks 9-15 compared to baseline, whereas the maximum percentage of participants in the USDA arm achieving ≥ 50% reduction in their MPN-TSS was 31% at 15 weeks.

Exploratory biological correlates included CBC, CMP, lipid, hsCRP, cytokine panel, and fecal microbiome analysis at weeks 1, 6, 9, and 15. Blood counts, electrolytes, kidney and liver function remained stable throughout the intervention period for both groups. We found no significant changes in cytokines (TNFα, IL-6, IL-8, IL-10, IL-22) or hsCRP in either diet group.

Shotgun sequencing of fecal samples found no significant changes in microbial diversity, composition, or function associated with a MED diet intervention over time. Instead, we found the MPN subtype played a greater role in determining microbiome diversity, composition, and function. Individuals with Essential Thrombocythemia and Polycythemia Vera were more similar to each other, while those with Myelofibrosis (MF) were more disparate. This difference in the MF microbiome composition was associated with an increase in TNFα. Notably, members of the Bacteroidaceae family were positively associated with high TNFα levels.

In a second randomized trial we tested the feasibility of an online diet intervention, with zoom based dietician counseling, electronic curriculum, and online based questionnaires. We recruited 28 symptomatic MPN patients not already adherent to a MED diet and randomized them to either a MED arm or DASH diet. Participants received written curriculum and attended zoom one-on-one RD sessions at weeks 3, 4, 8, and 12. Participants completed an online MPN-TSS survey.

Participants attended most dietician visits, with only a 3.5% and 7.5% no show rate in the MED and DASH diet groups respectively. Participants were also compliant with online based daily surveys, with an average completion rate of 93.2% in the MED group and 69.3% in the DASH group. At week 16, 43% of participants in the MED group had a ≥50% reduction in MPN-TSS compared with 29% of participants in the DASH group.

Taken together, these two studies demonstrate that MPN patients can adopt a Mediterranean diet eating pattern if given written curriculum and RD counseling. Moreover, a remotely administered intervention is feasible in this patient population. Although patients in all diet groups had a ≥50% reduction in MPN-TSS, the percentage achieving the ≥50% benchmark was higher in the MED arm for both diet studies. These data suggest that a Mediterranean diet, which is rich in anti-inflammatory foods, may be particularly beneficial to manage symptom burden in MPN. We are now moving on to larger randomized studies to rigorously test the impact of a MED diet intervention on symptom burden in MPN patients.

Mesa:Novartis: Consultancy; AOP: Consultancy; CTI: Research Funding; Promedior: Research Funding; Genotech: Research Funding; Samus: Consultancy, Research Funding; AbbVie: Research Funding; Incyte: Consultancy, Research Funding; Celgene: Research Funding; Constellation Pharmaceuticals, Inc., a MorphoSys Company: Consultancy, Research Funding; LaJolla Pharmaceutical: Consultancy; Sierra Oncology: Consultancy, Research Funding; Roche: Consultancy; Bristol Myers Squibb: Consultancy; Blueprint: Consultancy; Geron: Consultancy; Gilead: Research Funding; Imago: Research Funding. Scherber:Incyte: Ended employment in the past 24 months; Blueprint Medicines: Current Employment. Fleischman:CTI: Speakers Bureau; BMS: Speakers Bureau; Pharmaessentia: Speakers Bureau; Incyte: Consultancy, Honoraria.