Review of the plant-based nutrition news March 2023: Haematological cancers

This month I cover the emerging role of plant-based lifestyle medicine for haematological cancers. This coincides with my preparation for the annual British Society of Haematology conference in April, where I will lead two sessions on lifestyle medicine along with fellow plant-based haematologists, Drs. Urvi Shah and Manmit Kaur.

We have known for decades that healthy habits can lower the risk of developing chronic conditions by around 80%. A seminal study titled ‘healthy living is the best revenge’ analysed data from 23,153 German participants aged 35 to 65 years from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study. The impact of four healthy lifestyle factors on the incidence of type 2 diabetes, myocardial infarction, stroke and cancer was analysed. The four factors were never smoking, having a body mass index (BMI) lower than 30, performing 3.5 hours/week or more of physical activity, and adhering to healthy dietary principles (high intake of fruits, vegetables, and whole-grain bread and low meat consumption). After almost 8 years of follow up, those with all four healthy lifestyle factors had a 78% reduction in the risk of developing a chronic condition compared with participants with no healthy lifestyle factors.

Haematology is a broad and diverse speciality with conditions that affect all blood cells, including genetic and acquired disorders and non-malignant and malignant conditions. I focus here on data relating to haematological cancers.

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BODY WEIGHT AND COMPOSITION: Overweight and obesity is associated with an increased risk of 13 different cancers, including plasma cell myeloma, a cancer of the bone marrow plasma cells. There is also an association, albeit less strong, between excess body weight and developing non-Hodgkin lymphoma and acute myeloid leukaemia. It may be that higher BMI in childhood and early adulthood is a stronger predictor for developing NHL later in life. A recent publication by Dr Urvi Shah has also shown that extremes of weight, both under and overweight can adversely impact outcomes in people living with myeloma. Therefore, weight management is a key aspect of preventing haematological malignancies.

The American Society of Clinical Oncology have published guidelines on weight management during cancer treatment. However, the review mainly highlights the lack of available good quality research to make recommendations for weight management during treatment.

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DIABETES AND RISK OF HAEMATOLOGICAL MALIGNANCIES: As the prevalence of type 2 diabetes continues to rise across the world, the impact on individual and population health is far-reaching. This is the largest population-based study to examine the association between diabetes and haematological malignancies, as well as the impact of diabetes on mortality risk. It included 1,003,276 individuals from Canada with diabetes and age and sex matched these to 2,006,552 individuals without diabetes. Compared with individuals without type 2 diabetes, those with the condition had a 10% increased risk of developing a haematological malignancy (leukaemia, lymphoma and multiple myeloma). When examining individual subgroups, type 2 diabetes was associated with an increased risk of acute and chronic leukaemia and aggressive lymphoma but not indolent lymphoma. Among those with haematological malignancies, diabetes was associated with a 36% higher risk of all-cause mortality and cause-specific mortality (13–29%).

There are several potential biological explanations underlying the relationship between diabetes and malignancies, including hyperinsulinaemia, hyperglycaemia, increase in inflammatory cytokines, IGF-1 (insulin-like growth factor-1) overproduction, up-regulation of IGF-1 receptors and suppression of the immune system. It may also be that obesity associated with type 2 diabetes is driving the increased risk of cancer.

The authors conclude ‘Greater efforts for lifestyle modification may not only reduce diabetes burden and its complications but may also potentially lower risk of malignancy and mortality.’

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NUTRITION AND CANCER: This is a fantastic summary of the current knowledge on diet and cancer. The following key points are highlighted.

•Plant-based diets are associated with a lower risk of developing cancer. This has been shown in a number of prospective cohort studies including the EPIC-Oxford, the Adventist Health Study-2 and the UK Biobank study, which all show that meat free diets, including vegan, reduce the risk of developing cancer by around 15%.

•Plant-based diets reduce the risk of metabolic disorders such as obesity and type 2 diabetes that increase the risk of cancer.

•Plant-based diets reduce the risk of chronic conditions after a diagnosis of cancer.

•Plant-based diets may positively impact response to anti-cancer treatments, but more studies are needed.

•Mechanisms involved include reduced inflammation, insulin and insulin-like growth factor 1 levels and healthier gut microbiome.

•These benefits are because plant-based diets are high in fibre, phytochemicals and support increased production of short chain fatty acids by gut microbes.

The article concludes: ‘The results of this review suggest that the collective evidence supports plant-enriched diets for the reduction of cancer risk and the improvement of metabolic disorders in survivors’.

When it comes to haematological cancers, studies that have assessed the impact of diet have shown an association with diet quality. For example, a Western style diet pattern was associated with a 63% increased risk of chronic lymphocytic leukaemia, the commonest chronic leukaemia in Western countries, when compared to healthier diet patterns such as the Mediterranean diet. One of the very few randomised dietary intervention studies in people with a haematological cancer has been reported in abstract form at the American Society of Haematology meeting in December 2022. The small study included people with myeloproliferative neoplasms and hypothesised that an anti-inflammatory diet would improve symptom burden in patients with these conditions. The results showed that adoption of a Mediterranean diet did improve symptoms.

For lymphoma, healthier eating patterns in line with the World Cancer Research Fund recommendations are associated with a reduced risk. Although the data are not as robust as for other cancer types, in general, higher consumption of red and processed red meat is associated with an increased risk of lymphoma, In the EPIC study, high intake of poultry was associated with an increased risk. Dairy consumption has been associated with an increased risk, but mainly in case-control studies rather than cohort studies. In contrast, fruit and vegetables consumption, specifically citrus fruit and cruciferous vegetables consumption has been associated with a reduced risk of lymphoma. In addition, organic food consumption has been associated with a reduced risk of lymphoma, presumably because of lower exposure to insecticides and herbicides that have been classified as probable causes of cancer, specifically lymphoma.

I summarised the available data of diet and non-Hodgkin lymphoma in this article from 2019. Interestingly, in the EPIC-Oxford study the risk of cancers of the lymphatic and haematopoietic tissues was 36% lower in vegetarians (including vegans) compared with meat eaters, and within this group of cancers, vegetarians had a significantly lower risk of myeloma (by 77%).

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PLANT-BASED DIET AND MYELOMA OUTCOMES: This is a pretty ground-breaking study as it is the first time that diet quality has been shown to impact outcomes in people living with myeloma.

Myeloma is a cancer of plasma cells that reside in the bone marrow. It is not conventionally thought of as a cancer that is influenced by diet and lifestyle factors, in part because extensive research into this area has not been conducted. However, it is one of the cancers that is associated with obesity, in part due to the inflammatory state associated with adiposity. In the EPIC-Oxford study, 65 of the 61, 647 participants developed multiple myeloma. Those following a vegetarian or vegan diet had a 77% reduction in the risk of developing myeloma. Diets associated with higher levels of inflammation may increase the risk of myeloma. An analysis from the Nurses’ Health Study and Health Professionals Follow-up Study that included 165,796 individuals with 423 multiple myeloma cases and 345 deaths, those with a healthier diet prior to diagnosis, based on the alternative healthy eating index 2010, had a longer survival than those with less healthy diets.

The top line summary of this new study is taken from the first authors’ social media (on IG urvishahMD, twitter UrviShahMD). The study hypothesis was that dietary factors impact the gut microbiome in people with myeloma and this may be associated with outcomes from treatment. The study analysed the impact of dietary factors, stool metabolites and the microbiome on sustained deep remission (MRD negative). It included 32 patients with sustained deep remission and 36 patients in which there remained evidence of residual disease. The results showed that higher stool butyrate (produced by healthy gut bacteria) and increased bacterial diversity were associated with a sustained deep remission. Healthier dietary protein (plant and seafood) correlated with butyrate levels and remission. Of note, seafood and plant proteins include seafood, nuts, seeds, soy products (excluding beverages), and legumes (beans and peas). Dietary flavonoids also correlated with butyrate levels. The authors conclude ‘this is the first study to show that dietary and microbiome factors may be associated with sustained MRD negativity in plasma cell disorders. Our study suggests that lifestyle modification in the form of dietary change may potentially contribute to multiple myeloma control’.

I look forward to the results of larger, longer interventional studies from Dr Shah.

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LYMPHOMA AND PHYSICAL ACTIVITY: Although the data are not as strong as for other cancer types, the information we do have suggests that regular physical activity may reduce the risk of developing lymphoma and support longer survival after a diagnosis. The study highlighted included 18 studies. Comparing highest vs. lowest activity categories suggested a small but significant reduction in the risk of lymphoma, although mainly in case-control studies rather than cohort studies. A prior study also suggested a benefit of physical activity for improving survival after a diagnosis of lymphoma.

For people living with myeloma, there is less data available and physical activity needs to be personalised because of the involvement of the skeletal system by the cancer. However, it does seem that patients are interested in being supported to increase levels of activity and based on data from other cancer types, this could lead to improvements in quality of life. A small feasibility study using an eHealth application to tailor physical activity interventions at home suggested that this was well received by patients, who reported benefits.

Extrapolating from data in breast cancer, it is likely that physical activity interventions may reduce the burden of chemotherapy-induced cognitive impairment, otherwise known as ‘chemo brain’.

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LIVING WELL AFTER A DIAGNOSIS OF CANCER: Not only does underlying chronic illness increase the risk of cancer, but there is an increased risk of cardiometabolic disease after a diagnosis of cancer. This makes lifestyle interventions for cancer survivorship increasingly important.

This paper reports finding from the UK biobank study and examines the impact of a healthy lifestyle on the risk for cardiovascular disease (CVD) and type 2 diabetes (T2D) before and after the onset of cancer. Two sub-groups were included. A cancer-free cohort of 397,136 individuals in the general population and a cancer-prevalent cohort of 35,564 individuals with cancer. All participants were aged 40 to 70 years, free of CVD and T2D at recruitment and then followed for median of 14 years. The healthy lifestyle index (HLI)was made up of 5 cardiometabolic disease–related healthy behaviours (smoking status, physical activity, diet, alcohol consumption, and sleep duration). If participants met the criteria for each healthy habit they received a score of 1 and if not a score of 0, so a maximum score of 5 could be obtained. A healthy diet was high in fruits, vegetables, whole grains, refined grains, fish and low in unprocessed meat and processed meat.

In the cancer-free cohort 40,097 individuals (10.1%) developed cancer during follow-up. Each 1-point increment in HLI was associated with an 8% lower risk of developing cancer. A 1-point increment in HLI was also significantly associated with a 10% lower risk for developing CVD in patients diagnosed with cancer and a 12% lower risk in those free of cancer. Each additional healthy lifestyle factor had a 17%-26% reduction in risk of death during follow up, with smoking having the strongest negative impact. A 1-point increment in HLI was also associated with a 19% reduction in risk of T2D and a 16% reduction in T2D following a cancer diagnosis.

In the cancer cohort, which included 1027 participants with haematological cancers, survivors with 5 healthy lifestyle factors had a 44% reduction in the risk of developing CVD and 38% reduction in the risk of T2D. A 1-point increment in HLI was associated with risk reductions of 10% and 13% in developing CVD and T2D, respectively.

Overall the findings confirm the importance of healthy lifestyle habits for prevention of cancer, CVD and T2D and also the benefits of these healthy habits after a diagnosis of cancer when the risk of chronic conditions is even higher.

Interestingly, there is growing recognition of what is termed clonal haemopoiesis, which occurs more frequently with ageing and in a minority of individuals can progress to a haematological cancer. What is significant is that clonal haemopoiesis is a major independent risk factor for cardiovascular disease and therefore an important intervention for these individuals is appropriate cardiovascular risk factor modification, which includes a heart healthy diet and lifestyle. It is thought that shared inflammatory pathways connect the two conditions and therefore reducing inflammation may be an effective therapeutic approach.

MY PREDICTION FOR THE FUTURE: The future of lifestyle intervention for haematological cancers I believe will focus on harnessing the power of the gut microbiome. We already know that a healthy gut microbiome predicts better responses and longer remissions when using immunotherapy. The health of the gut microbiome is predictive of outcomes after stem cell transplantation and Dr Urvi Shah’s research suggests it may be important for improving outcomes in people with myeloma. The gut microbiome is impacted by a number of factors including diet, physical activity, medication and antibiotic use, alcohol use, stress and sleep. Whilst waiting for further support data, we should focus on harnessing the numerous benefits up for grabs when addressing lifestyle habits in people living with and beyond a cancer diagnosis.

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