It is commonly believed that “an ounce of prevention is worth a pound of cure.” But does this platitude ring true when it comes to diet and cancer prevention?
The hematology-oncology community has witnessed a surge of research examining the potential impact of dietary habits on blood cancer prevention, including multiple myeloma (MM). Blood Cancers Today spoke with several experts on the association between dietary patterns and blood cancer risk, the shortcomings of nutritional epidemiological studies, and how this contributes to the overall discourse about how dietary research in cancer is conducted.
Diet and Myeloma/MGUS Risk
Janine Joseph, MS, MBA, a Senior Research Specialist at Roswell Park Comprehensive Cancer Center, has been researching this question with Urvi Shah, MD, a Myeloma Specialist at the Memorial Sloan Kettering Cancer Center.
Their case-control study, “Dietary Risk Factors for Monoclonal Gammopathy of Undetermined Significance in a Racially Diverse Population,” evaluated data from the National Health and Nutrition Examination Survey (NHANES) to assess the health and nutritional status of the U.S. population. The study comprised of 373 patients with monoclonal gammopathy of undetermined significance (MGUS) and 1,406 matched controls.
NHANES administered a structured 24-hour recall, asking participants to report which foods they consumed over the past 24 hours. MGUS was inversely associated with whole-grain bread, oats, rice, fruits, and vegetables, and directly associated with sugar-sweetened beverages and artificially sweetened soft drinks.1 However, they found no association between MGUS risk and sugar-sweetened foods.
“There’s benefit to looking at dietary patterns,” Dr. Joseph said. “These findings are important for messaging regarding prevention.”
Another study led by Francesca Castro, MS, RDN, a Clinical Research Dietitian Nutritionist at Memorial Sloan Kettering Cancer Center, evaluated three dietary patterns: the healthy eating index, which compares an individual’s intake with how well they are meeting the U.S. Department of Agriculture dietary guidelines; the alternate Mediterranean diet (aMED) score, which compares intake with the Mediterranean diet score; and the plant-based dietary index, which evaluates vegetarian and vegan diets.
A healthy, plant-based diet had a “significant” association with reduced myeloma risk, which Castro attributed to the increased fiber intake in a plant-based diet.2
“Plant-based diets are higher in fiber and phytonutrients,” she emphasized. “There’s a huge fiber gap in the population, specifically in the American population.”
More than 90% of women and 97% of men do not meet recommended intakes for dietary fiber, according to the U.S. Department of Agriculture Dietary Guidelines for Americans.3
As senior author of the myeloma and MGUS studies, Dr. Shah noted that these findings are consistent with previously published dietary evidence. “We have summarized a lot of the nutrition information and dietary evidence that’s available before these two papers in a review article in Leukemia that looked at dietary and microbiome factors for myeloma,” she explained.
The World Cancer Research Fund (WCRF) and the American Association for Cancer Research (AACR) also recommend high consumption of plant-based foods and low consumption of sugary drinks to reduce the risk of several cancers.4,5
As Chief of Myeloma at the Roswell Park Comprehensive Cancer Center, Jens Hillengass, MD, PhD, is leading another study on how various lifestyle interventions—such as exercise, nutrition, and stress—impact quality of life and immune function in patients with MM.6
As Dr. Hillengass explained, the immune system has the job of killing cancer cells once they appear. “To fight the cancer, we have to strengthen the immune system,” he said. “Both solid and liquid tumors have developed certain capabilities to suppress the immune system.”
“Nutrition can affect so many different mechanisms, like the immune system,” Dr. Shah added. “For risk of progression, it’s a balance between the immune system and the genes. If we can modify the immune system through these different mechanisms, then we could maybe affect the disease in a different way.”
Shortcomings of Nutritional Epidemiology
Despite these findings, some hematologist-oncologists remain skeptical of observational studies linking cancer risk to dietary patterns.
“One of the main issues with nutritional epidemiology is that the studies don’t fully adjust for confounding, and there’s no way to do that because you can only adjust for the confounders that you can measure,” said Manni Mohyuddin, MBBS, an Assistant Professor at the University of Utah’s Huntsman Cancer Institute. “You can plug in a few different numbers and have a few different variables and assumptions, and you’ll get a different answer.”
Aaron Goodman, MD, an Associate Professor of Medicine at the University of California, San Diego, agrees. “There are too many things that confound with these data, and it’s very hard to tease apart in observational studies. You can really get any results you want,” he said.
Physical exercise and energy intake are variables that can confound the relationship between nutrient intake and disease risk. When studying dietary factors and myeloma risk, Castro and colleagues aimed to remove possible confounders and adjust for age, body mass index (BMI), education, and gender.2
“We used a residual method for adjusting for energy intake, which is important when using large cohorts because everyone eats differently, and somebody’s body size and activity level affect their energy intake. We also removed outliers of energy intake, [like] those who were eating extremely high or low caloric intakes,” Dr. Castro explained. “Everything is judged on the same wavelength.”
However, Dr. Mohyuddin believes that this method of excluding outliers in caloric intake from the overall dataset can be arbitrary. “Because you’ve thrown away so much of the data, what does that tell you about the data that’s left behind?” he questioned.
Dr. Mohyuddin also noted that the studies do not fully account for socioeconomic differences and that patients who adhere to a plant-based diet generally have higher socioeconomic status.
“This is the biggest shortcoming of most nutritional epidemiology,” he said.
When putting randomized, controlled trials of dietary interventions to the test, Dr. Mohyuddin and colleagues found that most trials measure non-clinical endpoints and that trials that did measure clinical endpoints (ie, progression-free survival, response rates) did not show an improvement in outcomes with dietary interventions for patients with cancer.7
“This is a stark contrast to the observational literature,” he noted. “There’s a right way of doing studies like this, and the right way is not doing retrospective, confounded, observational studies. We need high-quality, randomized trials that look at specific nutritional interventions, combine it with other therapeutic anti-cancer interventions, then measure endpoints that are actually looking at cancer.”
“There’s a lot of hesitation from oncologists, and doctors in general, when they look at epidemiologic studies,” Dr. Shah added. “Some of it is rightly so in the sense that we are looking at large populations, and that could be confounding in terms of whether the population is healthy overall. But we do the best we can with the data we have, and we adjust for all these things.”
Feasibility of Patient Self-Reporting and Adherence
The unreliability of patient adherence and self-reporting is another potential flaw of nutritional epidemiology. Is a time-limited dietary recall or fasting intervention enough to make accurate conclusions about a patient’s risk for cancer?
In Dr. Hillengass’ study, patients fast for 16 hours per day as researchers monitor their dietary diaries, microbiomes in stool, quality of life, and immune markers by flow cytometry to evaluate the effects of intermittent fasting intervention.6
However, Dr. Hillengass described the process of self-documenting food as “bothersome” for some patients. “Sometimes, [patients] are not perfect in their diary when it comes to dietary intake,” he said. “It’s a bit more challenging to assess because it’s not just a lab check. They document everything they eat, [but] they do it half an hour later or an hour later. For a research study, we need it to be very precise.”
“This issue is highly prevalent across nutritional epidemiology in how people fill out surveys,” Dr. Mohyuddin said. “You’re asking people what they remember eating in the last 24 hours, and you’re using that to draw firm conclusions about their lifestyle. You have not longitudinally followed people to see what they’re eating, how their dietary intake has stayed over time.”
“If you rely on people reporting what they ate, that’s not really controlled,” Dr. Goodman added.
Dr. Shah also noted that collecting data for nutritional studies poses a greater challenge than traditional clinical trials evaluating a specific drug or therapy.
“When you do a nutrition trial, you may want a person to eat a certain diet for a month, but people are human and they may follow it 50% or 70%,” she said. “That already reduces the effect of what we can see from that intervention. Whereas if it’s a drug or a therapy, it’s either 100% there or not there. It becomes much easier to study and quantify.”
In 2024, Laura F. Mendez Luque, MD, of the University of California, Irvine School of Medicine, and colleagues conducted a randomized, parallel-arm study to measure the feasibility of adhering to an education-focused Mediterranean diet among patients with myeloproliferative neoplasms (MPN). Patients were randomly assigned to either a Mediterranean diet or standard U.S. Dietary Guidelines for Americans (USDA) and received registered dietician counseling and written dietary resources.8
About 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of greater than or equal to 8 throughout the intervention period, while less than 50% of the USDA group achieved a score of greater than or equal to 8 at any time point.8
“With dietician counseling and written education, patients with MPN can adhere to a Mediterranean eating pattern,” wrote Dr. Mendez Luque and colleagues.8 “Diet interventions may be further developed as a component of MPN care and potentially incorporated into the management of other hematologic conditions.”
Growing Research
At the 66th Annual American Society of Hematology (ASH) Annual Meeting, Dr. Shah and colleagues took their research further. They conducted the first interventional clinical trial and in vivo study to show that a high-fiber diet may delay progression from MGUS to MM.
The single-arm trial consisted of 20 patients with MGUS or smoldering MM with a BMI of 25 or greater. Patients were given a controlled high-fiber plant-based dietary (HFPBD) intervention for 12 weeks and health coaching for 24 weeks.9
They found that the HFPBD intervention was safe, feasible, improved quality of life, and improved metabolic markers (BMI, insulin resistance, adiponectin leptin ratio), microbiome (increased alpha-diversity and butyrate producers), and immune response (decreased inflammation and increased anti-inflammatory classical monocyte).9
In transgenic Vk*MYC mice, the high-fiber diet also delayed the progression of smoldering MM to MM and increased the median progression-free survival from 12 weeks in the control arm to 30 weeks in the high-fiber diet intervention arm.9
Another study presented at ASH 2024 by Jenny Paredes, PhD, of the Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, explored the effects of a high-fiber diet on graft-versus-host disease (GVHD) risk after hematopoietic stem cell transplantation (HSCT).10
Dr. Paredes and colleagues collected dietary data from 173 patients who underwent allogeneic HSCT at the Memorial Sloan Kettering Cancer Center from 10 days before HSCT to 30 days after HSCT, totaling 3,837 patient days. They also collected 16S rRNA sequencing data of fecal samples and measured fecal short-chain fatty acids using gas chromatography-mass spectrometry (GC-MS) in a subset of patients with acute lower gastrointestinal (GI) GVHD and matched patients without GVHD.10
Increased fiber intake was associated with increased overall survival, lower incidence of acute GI-GVHD, higher microbial α-diversity, and increased butyrate. In a preclinical mouse model, mice receiving a fiber-rich diet had a lower rate of death from GVHD, higher microbial α-diversity, and a higher concentration of cecal butyrate.10
“These results suggest that dietary fiber could be used in the prevention of GVHD,” wrote Dr. Paredes and colleagues.10
Fate Versus Free Will
Dr. Hillengass noted that patients take a keen interest in altering their diet to improve their health.
“We give patients chemotherapy, we give them modern drugs. They often ask, ‘what else can I do right?’ Oftentimes, nutrition comes up fairly early in the discussion,” he said.
Patient adherence to dietary patterns raises a vital question: to what extent can patients become the pilots of their health?
“When a diagnosis of cancer happens, there’s a sense of loss of autonomy,” Dr. Mohyuddin said. “That is why [nutrition] is an immense interest to patients, and it’s a way of giving autonomy back to patients. It is a very relevant and hot question.”
Dr. Goodman pointed out that not only is preventative medicine difficult to execute, but it is unnecessary when considering MGUS.
“I think dietary interventions in a pre-cancer like MGUS where the majority of patients will never develop cancer is a low research priority,” he said.
According to the Weill Cornell Medicine Myeloma Center, 20% of patients with MGUS will progress to myeloma, and the risk for a patient’s progression from MGUS to myeloma is 1% per year.11
“The magnitude of benefit of a plant-restricted diet in MGUS would have to be so dramatic to do anything,” Dr. Goodman added.
However, others stress the importance of altering one’s diet and taking an active role in their health.
“I think it’s very helpful for patients to know that diet does play a role in overall cancer risk and myeloma risk and that even if they potentially move a little bit in the right direction, it can make a difference in outcomes,” Castro said.
In a Nutshell
The concept of dietary patterns is crucial to the larger conversation on diet and cancer risk, according to Dr. Shah. “Instead of only focusing on an individual food group, it’s important to think about the pattern that is consistent between these studies,” she explained. “The consistency I see across all these studies is showing that higher fiber and plant foods reduce risk, whether it’s MGUS or myeloma progression.”
While oncologists like Drs. Goodman or Mohyuddin take observational nutritional studies with a grain of salt, they do not discount the importance of keeping a healthy diet.
“I think that all of the general dietary advice still applies,” Dr. Mohyuddin emphasized. “There are far more compelling reasons to eat healthy and avoid obesity than to avoid MGUS.”
“We need no further study to suggest that exercising and eating healthy is a good thing to do,” Dr. Goodman agreed. “We need a very meticulous study with appropriately designed endpoints.”
Despite the reluctance from some oncologists, Dr. Shah and her team continue to spread awareness of the role of nutrition in myeloma and MGUS risk. This way, doctors can be better prepared to answer patients’ questions regarding diet and nutrition, she said.
“As doctors, we don’t get enough nutrition training,” she expressed. “I think that’s also why there’s a lot of hesitation from doctors because you assume that it doesn’t exist if you don’t know it. Often, doctors have not read enough about this topic and understand how these studies are done. Despite [the] adjustment, if we are seeing significance in not just one study, but in many studies and consistently over time, then as doctors it is our duty not to ignore this.”
References
1. Joseph J, et al. Blood Advances. 2024;8(3):538–548. Doi.org/10.1182/bloodadvances.2023011608
2. Castro F, et al. Leukemia. 2024;38(2):438-44. doi:10.1038/s41375-023-02132-3.
3. U.S. Department of Agriculture. Dietary Guidelines for Americans. Accessed May 1, 2025. https://www.dietaryguidelines.gov/sites/default/files/2020-12/Dietary_Guidelines_for_Americans_2020-2025.pdf
4. World Cancer Research Fund International. Accessed May 1, 2025. https://www.wcrf.org/diet-activity-and-cancer/cancer-prevention-recommendations/
5. American Association for Cancer. Accessed May 1, 2025. https://www.aacr.org/patients-caregivers/progress-against-cancer/reducing-cancer-risk-healthy-eating-alcohol/
6. Hillengass J. Non-chemotherapeutic interventions for the improvement of quality of life and immune function in patients with multiple myeloma. Accessed May 1, 2024. https://clinicaltrials.gov/study/NCT05312255
7. Ilerhunmwuwa NP, et al. J Natl Cancer Inst. 2024;116(7):1026-1034. doi:10.1093/jnci/djae051
8. Mendez Luque LF, et al. Cancer Res Commun. 2024;4(3):660-670. doi:10.1158/2767-9764.CRC-23-0380
9. 66th American Society of Hematology Annual Meeting &
Exposition. Abstract #671.
10. 66th American Society of Hematology Annual Meeting & Exposition. Abstract #671.66th American Society of Hematology Annual Meeting & Exposition. Abstract #259.
11. Weill Cornell Medicine Myeloma Center. Accessed May 1, 2025. https://www.myelomacenter.org/patients/other-
plasma-cell-disorders/precursor-conditions-multiple-myeloma
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