Dietary Intervention Shows Promise in Blood Cancers

SAN DIEGO — Increased dietary fiber had a significant association with improved outcomes in blood cancers, according to studies reported here.

Patients undergoing allogeneic hematopoietic cell transplant (allo-HCT) had significantly better survival and a lower rate of graft-versus-host disease (GVHD) with higher levels of fiber intake. The outcomes were associated with changes in biomarkers linked to better outcomes. A second study showed improvement in biomarkers linked to progression of smoldering myeloma to the frank disease state in patients who consumed a plant-based, fiber-rich diet. Both studies were bolstered by laboratory data consistent with the clinical findings, as reported at the American Society of Hematology annual meeting.

“When someone is facing a diagnosis of cancer or some other blood disorder, the emotional response to that is to ask, ‘What did I do to be in this situation’ or ‘What can I do to resolve this situation,'” said Chancellor Donald, MD, of Tulane University School of Medicine in New Orleans, and moderator of a press briefing that included the fiber studies. “One of the things we have the greatest control over is our overall lifestyle and diet. This research speaks directly to the idea of ​​lifestyle modification as you face different issues.”

The makeup of gut microbiota can influence outcomes in allo-HCT. Previous studies have shown that high microbial diversity, high butyrate production, and a low abundance of Enterococci are associated with improved overall survival (OS) after allo-HCT, said Jenny Paredes, PhD, of City of Hope National Medical Center, in Duarte, California.

Dietary fiber promotes microbial growth, production of short-chain fatty acids (butyrate and acetate), and epithelial homeostasis, while reducing the abundance of opportunistic pathogens (such as Enterobacteriaceae ) and pro-inflammatory effector Th1 cells, she continued. Collectively, the evidence supported the hypothesis that dietary fiber increases microbial diversity and relative abundance of butyrate producers, which can reduce GVHD severity.

Dietary Fiber and Transplantation

Investigators collected dietary information of 173 patients who underwent allo-HCT. The data included 35,228 meals and 3,837 days of tracking, corrected for consumed portions and dry grams per nutrient. They separated fiber intake from various nutritional groups and further dissected fiber into the most common types. The resulting data were used to establish cohorts of high and low fiber intake.

The subsequent analyses showed that fiber intake had a positive correlation with Blautia (a butyrate producer) and negative correlation with Enterococcus. Paredes and colleagues also found a positive correlation between high fiber intake (as assessed on day 12 after allo-HCT) and OS (P =0.045) out to 24 months.

To examine associations between fiber intake and GVHD outcomes, investigators examined 101 non-T cell-depleted patients, and identified 29 who developed lower gastrointestinal (GI) GVHD and 29 who did not. They obtained more than 100 samples of small-chain fatty acids from both groups. Analyses showed that high fiber intake was associated with greater microbiome α-diversity (P =0.007) and β-diversity (P

Additionally, fecal butyrate (P P P =0.007, P = 0.008). Finally, the investigators found that high fiber intake had a significant negative association with acute GVHD incidence (P =0.034).

For validation of the findings, Paredes and colleagues examined varying dietary fiber intake in pre-clinical models of GVHD. They feed laboratory animals diets that contain 0%, 6%, or 12% cellulose. The highest fiber intake was associated with better GVHD survival. Increasing fiber intake was associated with greater microbial diversity (P =0.001) and butyrate production (P =0.065) and reduced abundance of enterococcus ( P =0.044).

Other favorable effects of the 12% cellulose diet included increased gene expression related to epithelial homeostasis, cecal butyrate, and ratio of regulatory T cells, reduced T cell-mediated inflammation, and prevention of gut barrier damage.

In response to a question, Paredes said investigators controlled for antibiotic use and type of conditioning regimen but not the indication for transplant and other potential confounders.

High Fiber Diet and Myeloma

The evolution of multiple myeloma from the precursor conditions, monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma, offer opportunities for secondary prevention, said Urvi A. Shah, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York City. Genomic alterations and progressive immune dysfunction occur during the transition to multiple myeloma, but many patients have modifiable risk factors that can affect the immune system, including diet/nutrition, obesity, diabetes, and microbiome diversity.

“Our hypothesis, or question, was ‘Can we tilt the scale and reduce risk for myeloma development if we normalize weight and blood sugar, improve diet quality, and improve the microbiome,'” she said.

Shah and colleagues designed the NUTRIVENTION study to determine whether a plant-based diet can affect the trajectory of MGUS and smoldering myeloma. They enrolled 20 patients who met diagnostic criteria for either of the two myeloma precursors and had a BMI >25.

Study participants consumed plant-based, high-fiber meals for 12 weeks, most of which were shipped to the participants. Patients could eat to satiety with no calorie restrictions. The primary endpoint of the pilot study was feasibility, defined as >70% adherence to the meals and BMI reduction >5% at 12 weeks. Follow-up continued for a total of 52 weeks.

During the first 12 weeks, adherence to the diet was 91%, and a majority of patients (58%) remained adherent at 52 weeks, as compared with 20% adherence before the study. Participants had a median BMI reduction of 7% at 12 weeks, and the improvement was maintained up to 52 weeks. In addition to meeting the adherence and BMI goals, the patients had favorable changes in a variety of biochemical markers, including insulation resistance, fecal microbiome diversity, and inflammation, as well as improved quality of life.

“We also saw that two patients with progressive disease had the progression stabilize and slow down on the intervention,” said Shah. “Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change the trajectory of the disease.”

Investigators at San Raffaele Hospital in Milan, Italy, conducted a companion study in a mouse model of smoldering myeloma. In the animals that consumed a high-fiber diet, progression to multiple myeloma slowed from a median of 12 weeks to 30 weeks. All of the animals in a control group progressed to multiple myeloma, whereas 40% of the animals that consumed a high-fiber diet did not progress to over myeloma.

Biochemical studies of the mice showed that consumption of the high-fiber diet was associated with increased microbiome diversity, reduced growth rate of abnormal plasma cells (suggesting an effect on disease progression), reduced inflammation, and improved immune function.

Shah said enrollment has begun in a follow-up trial (NUTRIVENTION-3) that will include 150 patients with MGUS or smoldering myeloma, randomized to the high-fiber diet with or without supplements or to a placebo group.