Nutrition in Hematological Cancers – From the Gut Microbiome to the Ketogenic Diet

The effects of diet and nutrition on the course of cancer have attracted increasing scientific interest. New findings presented at the 2024 American Society of Hematology (ASH) Annual Meeting drew attention to the relationship between food and hematological cancers such as leukemia and lymphoma, suggesting that dietary interventions may play a decisive role in disease progression. This article details findings from several studies and evaluates how nutritional strategies may contribute to treatment.

NUTRIVENTION: A High-Fiber Diet and Reduced Multiple Myeloma Risk

The NUTRIVENTION study, led by Dr. Urvi A. Shah at Memorial Sloan Kettering Cancer Center, showed that a high-fiber diet could make the progression of conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma, both precancerous conditions, to multiple myeloma slower.

Hypothesis: The researchers investigated whether the risk of developing myeloma could be reduced through weight control, blood sugar regulation, improved diet quality, and improvements in the microbiome and immune system.

Pilot Study Details:

• Number of Participants: 20 patients (body mass index, BMI > 25 kg/m²)

• Duration: 12 weeks (total follow-up of 52 weeks)

• Diet Type: Plant-based, high-fiber meals (meal kits delivered to participants' homes)

• Primary Endpoint: Feasibility (> 70% adherence) and a 5% reduction in BMI.

Results:

• Adherence rates of 91% at week 12 and 58% at week 52.

• Mean BMI reduction: 7% (maintained relative to baseline at the end of week 12).

• Improvements in insulin resistance, inflammation, and fecal microbiome diversity.

Key Findings: Dr. Shah noted that dietary intervention stabilized the disease course in two patients with progressive disease: “This is a rare example showing that diet and lifestyle changes can alter the course of disease.”

A larger follow-up study, NUTRIVENTION-3, has been launched and will include 150 patients. In addition to a high-fiber diet, participants will be assigned to supplement or placebo groups.

The Role of a High-Fiber Diet in Allogeneic Stem Cell Transplantation: Preventing GVHD

Dr. Jenny Paredes and colleagues at City of Hope National Medical Center observed that a high-fiber diet increased overall survival and reduced the incidence of graft-versus-host disease (GVHD) in patients undergoing allogeneic stem cell transplantation.

Data Details:

• Number of Participants: 173 patients

• Meals Tracked: 35228 meals (a total of 3837 days)

• GVHD Group: 29 patients who developed lower gastrointestinal GVHD and 29 patients who did not develop GVHD.

Findings:

• A high-fiber diet led to greater microbiome diversity, more butyrate-producing bacteria, and higher fecal concentrations of short-chain fatty acids.

• Preclinical Models: A diet containing 12% cellulose increased the Treg/conventional T-cell ratio and reduced GVHD mortality.

Implications: These findings suggest the potential to consider increased dietary fiber as a strategic measure to reduce GVHD severity. The City of Hope team plans to introduce new nutrition protocols for transplant patients.

The Importance of the Ketogenic Diet in CAR T-Cell Therapy

Dr. Shan Liu and colleagues at the University of Pennsylvania presented striking findings showing that a ketogenic diet (high in fat and low in carbohydrates) enhanced the effectiveness of chimeric antigen receptor (CAR) T-cell therapy.

Study Details:

• Five different diets were tested: ketogenic, high-fiber, high-fat, high-protein, and Western-style diets.

• Mice fed a ketogenic diet achieved the best tumor control and prolonged survival.

BHB and CAR T Cells: β-hydroxybutyrate (BHB), a molecule produced by fat breakdown during ketosis, fueled CAR T cells and enhanced their antitumor effects.

• Results: Supporting CAR T-cell functions with BHB increased metabolic resilience, gene expression, and cytokine release.

• Clinically, higher BHB levels in patients receiving CAR T-cell therapy for lymphoma were associated with greater CAR T-cell expansion.

Dr. Liu emphasized that these findings suggest a possible supportive role for a ketogenic diet in cancer treatment, and noted that a new clinical study of BHB supplementation had been launched in patients with non-Hodgkin lymphoma.

Expert Opinion: Bridging Diet and Cancer Treatment

Dr. Ciara L. Freeman of Moffitt Cancer Center stated that these studies were highly important for cancer prevention and treatment optimization:

• Gut Microbiome: “The NUTRIVENTION and City of Hope studies reveal the critical role of the gut microbiome in cancer prevention and recovery. Eating more plant-based, high-fiber foods has positive health effects, including reduced inflammation and stronger immunity,” she said.

• CAR T-Cell Therapy: “A ketogenic diet may be a promising strategy, particularly during immunotherapy. The ability of BHB to improve CAR T-cell metabolism suggests that nutritional strategies could be integrated into treatment protocols to optimize efficacy.”

Conclusion and Discussion

Although these are early findings, the studies reveal extensive connections between nutrition and cancer treatment and have the potential to significantly influence future clinical practice.

The findings presented at ASH 2024 emphasized that seemingly simple dietary changes could have transformative effects on cancer treatment and prevention strategies. A better understanding of how diet affects the microbiome and immune system may add a new dimension to individualized treatment plans.