Transcript
[0:00] So, good morning to all of you. You can see my slides right? We certainly can. Thank you, yeah, great. So, I’m going to talk about our research on diet and microbiome and other modifiable risk factors in MGUS and Smoldering Myeloma, and how we’re studying to see if we could delay progression, at least for some patients.
These are my disclosures. Just some background: I grew up in India and went to medical school there. My training was very good but not very different from most medical schools across the world, with very little nutrition focus. I didn’t really think about this a lot when I was seeing patients in medical school or in residency in Boston, where I took care of a lot of very advanced medical conditions. It was the same thing there as well.
I went to Fellowship for hematology and oncology at Montefiore, and at that time, even for cancer patients, patients would ask, but I really didn’t know enough about the data available for most diseases and didn’t think much of it, as we don’t really focus on it in training. But in 2016, while I was in Fellowship, I was diagnosed with Hodgkin’s lymphoma, and that really opened my eyes to thinking about modifiable risk factors and things around it. I had family and friends telling you what to eat and what not. Sometimes it’s nice if we can find the evidence and know it ourselves, instead of others trying to tell us. When I started as faculty at Memorial Sloan Kettering, I decided that’s the area of research I’d like to focus on.
With that, we’ve developed a program to study nutrition, microbiome, and metabolism in myeloma and its precursor disorders.
[2:04] I’ll talk about lifestyle considerations. I’m sure all of you are familiar, but when we talk about MGUS and Smoldering Myeloma, they are the precursor, precancerous states to myeloma. A large number will never go on to develop myeloma, but there is a small proportion that may progress. The standard of care for these patients is observation. We tell them there’s nothing to do; you watch and wait. If it becomes myeloma, then we treat. That can be unnerving for many patients and bring on some anxiety because they feel like, “Why are we doing nothing?” The reason is because the majority of patients do not progress, and we don’t know that treating earlier really improves survival.
I’ll focus on looking at comorbidities and how that affects risk of myeloma, some research we’ve been doing, and some practical tips from what you see from our research. Some of my slides are related to myeloma, but I know that may not fully apply, but the same principles apply if somebody’s in a pre-cancerous stage. We also want to be the fittest in the rare situation that we do end up with cancer.
[3:44] Patients with myeloma are living longer than ever before because of new therapies. It’s quite encouraging as an oncologist to see. But as patients are living longer, many are living longer but not better, often because they are sick with many other medical conditions. It’s often important now more than ever to focus on helping patients live better and longer.
[4:12] I wanted to talk about genetic risks. Most people think about genes causing cancer. Yes, genes play a role, but they are not the complete picture. There’s genes, nutrition, the environment, and other factors. Nutrition is the only one we can really do something about; we can’t do something about our genes or maybe even the environment we live in.
When you think about this study looking at colorectal cancer (not myeloma), it’s quite interesting. They took over 300,000 participants and followed them. About 2,000 developed cancer. They went back and asked about lifestyle and looked at genetic risk. Those that had high genetic risk (bad genes) and an unhealthy lifestyle had the highest risk. But those that had bad genes but a good lifestyle had a risk almost a third less. Even patients with bad genes could benefit from lifestyle modification.
[6:27] This is a patient in clinic with so many medical conditions. To have myeloma means it’s going to be hard to treat well because we have to manage complexities. In green are things I believe could be avoided with a lifestyle change. Because of all these conditions, I could not offer them many treatments, and they lived a shorter life. So even if we do end up developing cancer, it is important that we are in our best health so we can manage to get all the treatments.
This is another patient who had myeloma, responded well, was in remission, but had medical conditions and unfortunately didn’t die of myeloma but of a cardiac arrest. People focus only on the cancer, but it’s important to focus on overall health.
The next part: common conditions linked to cancer, such as obesity and diabetes. Obesity is linked to 13 different types of cancer, including multiple myeloma. It doesn’t mean every obese person gets myeloma, but the risk increases. We know patients with MGUS who have an elevated BMI are twice as likely to progress to myeloma. We published a review on mechanisms. Patients with extreme BMIs tend to do worse overall in terms of survival after diagnosis.
Diabetes has also been linked to increased risk of blood cancers and myeloma. This study showed Leukemia, Lymphoma, and Myeloma were about 10 to 30% increased in those who had diabetes. We looked at myeloma patients; about 25% have diabetes. Patients who had diabetes tend to do worse. In a mouse model, myeloma progresses faster in mice with diabetes.
[11:21] What do patients want? We surveyed over 400 patients with MGUS, Smoldering Myeloma, and myeloma. Majority said yes to questions about nutrition, that their doctor didn’t address them, and those that got recommendations attempted to follow them. Most interestingly, patients self-reported that they increased intake of fruits, vegetables, whole grains, plant proteins, and seafood, and decreased consumption of unhealthy foods after their diagnosis. Patients are making changes on their own, so it’s important we give the right advice.
[12:09] This is the World Cancer Research Fund guidelines: 10 cancer prevention recommendations; six are related to diet. One is healthy weight and physical activity. On the American Institute of Cancer Research website, you can click on foods and see why they have anti-cancer properties. Most are plant foods that are unprocessed. Data shows about a third of common cancers could be prevented through healthy weight, physical activity, and nutrition. Foods to limit: alcohol, processed meats, red meat, sugar-sweetened drinks.
With myeloma specifically, what studies have been done? A 2014 UK study found vegans/vegetarians had a 77% lower risk of myeloma than meat eaters. Another study with over 400 cases found healthier dietary patterns (like Mediterranean) had a 15 to 24% lower likelihood of death after myeloma. An inflammatory or “Western” diet had higher risk.
We did a study with over a thousand myeloma participants, the largest to date. We found an association with a healthy plant food score; the highest score had a 15% lower risk. For MGUS, we studied over 300 MGUS and 1,400 controls. Eating whole grains, fruits, vegetables had about a 30% lower risk of developing MGUS, whereas sugar-sweetened beverages had a 30-50% increased risk.
[15:32] What about mechanisms? How does diet affect cancer reduction? Many mechanisms: improved weight, reduction in insulin, inflammation, plant chemicals (phytochemicals), and fiber. Fiber has many anti-cancer, anti-inflammatory properties. We published a review on how diet can affect the microbiome, immune system, and outcomes for patients with plasma cell disorders. We also looked at ketogenic diets. While they can improve weight and inflammation, the challenge is it’s not very physiologic, excludes fiber-rich foods, and is not very sustainable. Clinical trials on ketogenic diets often have trouble completing, whereas plant-based diet trials seem better.
[17:40] The microbiome and why it’s important. The number of bacterial cells in our body (38 trillion) is more than human cells (30 trillion). We are more bacterial cells than human cells. I think it’s important to be feeding the bacteria what they want. The microbiome needs fiber. It influences health and disease. Non-modifiable factors: age, gender, race. Modifiable factors: diet, exercise, antibiotics, etc.
One concept is diversity. Like a rainforest, we want variety of bacteria. Diversity is associated with better health. Some bacteria are butyrate producers; butyrate is an anti-inflammatory molecule with anti-cancer properties. These bacteria make chemicals that go into our bloodstream and affect the immune system.
[20:49] Can diet alter the microbiome, and how quickly? In a study, nine healthy people were given five days of an animal-based or plant-based diet. Fiber intake increased on the plant-based diet, and butyrate was higher. Just changing diet can start changing the microbiome.
Another study switched diets of healthy middle-aged Americans and Rural Africans for two weeks. With the Americans on the high-fiber African diet, a marker of cell division in the colon lining reduced, inflammatory cells changed, and the microbiome changed. Just two weeks can make a difference.
Another study had participants add 20g of fiber for four weeks. The microbiome function improved. Another group ate six servings of fermented food a day, showing a reduction in inflammation.
A good question: how many plant foods do you eat in a week? I encourage you to think about this. I’m talking about different plants: broccoli, spinach, kidney beans, chickpeas, seeds, nuts, herbs. You want more than 30 per week. That variety feeds different bacteria and improves diversity.
[24:15] Why care about diversity? Higher gut microbiome diversity is associated with better survival post-transplant and overall survival in myeloma, lymphoma, and other cancers. Those with higher diversity just do better overall.
Now, we’ve always talked about infection risk in MGUS and Smoldering Myeloma. A study with over 2,000 healthcare workers during the pandemic looked at diet and COVID severity. Plant-based diets had about a 73% lower odds of moderate to severe COVID. Low-carb, high-protein diets tended to have worse COVID. Another study with over 500,000 participants showed the same: more plant foods associated with lower risk and severity.
[26:05] How do we study diet? In prevention space (MGUS/Smoldering), treatment space (tolerating treatment), and survivorship (preventing relapse). We know the general trajectory of progression, with more genetic changes and immune function changes. We can affect the immune system by microbiome, diet, obesity, diabetes. Is it possible we can tilt the scale from increased risk to reducing risk with diet and lifestyle?
With that, we did the NUTRITION trial. Started a few years ago, finished this year. Three months where we shipped patients lunch and dinner, with coaching for six months. We didn’t calorie restrict; they could eat as much unprocessed plant-based foods as they wanted. We enrolled patients with MGUS/Smoldering and BMI over 25. Very few dropped out.
Before the study, healthy plant food consumption was about 20%. On the study, it went to 90% and stayed high after. Dietary fiber improved. Quality of life improved, especially shortness of breath and fatigue.
[30:34] What about weight and insulin resistance? High BMI is twice as likely to progress. Patients lost on average 8% of body weight by 3 months and maintained it at a year. A marker of insulin resistance (adiponectin/leptin ratio) improved. Cholesterol dropped 30 points on average without medication.
The microbiome: diversity improved. Healthy bacteria (butyrate producers) improved. This improvement was maintained up to a year.
[32:48] Two patient examples. One with MGUS had an M-spike rising slowly before the study. It seemed to slow down on the study. He was diabetic and was able to stop insulin after 30 years. Another, a Smoldering patient, lost weight, and the M-spike progression slowed. They also had advanced kidney disease, and its progression seemed to slow.
A patient shared before/after pictures and felt it was life-changing. We asked patients after the study about improvements (self-reported). Majority had improvement in self-confidence, diabetes, cholesterol, energy, diarrhea, arthritis, anxiety, depression. Patients reported the intervention easy to follow, and all would sign up again. Some had savings in medication expenditure. Patients felt more energy, less bloating.
[34:16] Given that, we started another study, a bigger one enrolling 150 patients with any BMI, looking at diet and supplements (omega-3, curcumin). Patients need to come to New York area over 12 months. This is another study open all over the US, looking at diet vs. supplements over two weeks and effect on microbiome.
[35:33] In the prevention setting, what about if somebody gets diagnosed with cancer? Can lifestyle improve survival? Early data in leukemia: newly diagnosed patients asked to eat a healthy diet. Insulin resistance improved, and likelihood of being in remission improved after a month.
In melanoma, those who ate adequate dietary fiber had best survival after immunotherapy. Another study in skin cancer showed healthier diet (whole grains, nuts, fruits, vegetables, fish) had higher likelihood of response and survival.
After cancer diagnosis, can it improve time to relapse? In myeloma, we published a study looking at patients on maintenance therapy. We didn’t intervene; we asked for diet survey and stool sample. Those in complete remission had higher microbiome diversity, higher butyrate producers, and higher butyrate concentration. Healthier proteins (beans, nuts, legumes, seafood) and dietary flavonoids (from plants) were associated with sustained remission. It’s a small study, but suggests links. We are studying this in an ongoing study with a dietary intervention.
[39:47] Data for Americans (likely similar elsewhere). How much added sugar do Americans eat on average? About 17 teaspoons. Recommended is max 6-9 teaspoons. Sugar is hidden in many things.
Dietary fiber: average is 10-15 grams. Target is 25 grams. Half the target. One cup of beans gives ~15g.
Salt: average 3,400 mg. Should be less than 2,000 mg. Most comes from prepared food.
Fruits: average 0.9 cups/day. Should be 1.5-2 cups.
Vegetables: average 1.4 cups. Should be 2.5-3.5 cups.
Protein: average 80-100g/day. Requirement is 50-70g. Almost double. One cup of beans gives ~15g.
The message: focus on getting enough fiber. If you eat enough fruits, vegetables, beans, you’ll get fiber. Sugar has many names (cane juice, sucrose, high fructose corn syrup); we want to avoid them.
[45:57] Survey: 67% of people think they get enough fibre. In reality, only 5% do. We are in a fibre deficiency. Fibre is important for gut lining and immune system.
Example of a Western diet: almost no fiber. Only ~1g from a slice of wheat bread. A high-fiber diet: every plant food has fiber; you can easily meet requirements.
Protein: plant foods have protein. High protein diets can be associated with increased kidney disease risk and potentially shorter lifespan. A study looked at animal vs. plant protein and risk of death. For all-cause, cardiovascular, and cancer death, plant protein was favored.
Plant proteins have all amino acids; the quantity is different. Eating a variety gives you what you need.
Whole grains: people focus on low-carb, but not all carbs are bad. Refined carbs/sugar are bad. Whole grains (buckwheat, quinoa, brown rice, barley, corn) are healthy and associated with reduced cancer risk. Recommendation: three servings a day.
[49:48] Shifting to high-fibre plant-rich foods. I’m not necessarily saying be vegetarian or vegan. Vegan/vegetarian diets can be driven by ethics/environment, but don’t have to be healthy. What I’m talking about is focusing on high-fibre plant foods for the majority of your diet. Like the Canadian food plate: half vegetables/fruits, quarter whole grains, quarter protein (mostly plant). You can be pescatarian, Mediterranean, etc. If you get 80-90% of calories from unprocessed plant foods, you’ll see benefits. The degree depends on health status.
[52:06] Calorie density: 500 calories of fruits/vegetables fills you up; 500 calories of cheese or oil does not. With calorie-dense foods, we tend to overeat.
[52:27] Organic foods? A study from France showed a 25% reduced cancer risk with organic food. But it’s possible these people were also healthier overall. You don’t need to focus only on organic. One could eat over 400 strawberries in a day without effect from the highest pesticide residue. If half the US increased fruit/vegetable by one serving a day, we could reduce 20,000 cancer cases per year. If someone stops eating them due to pesticide fears, that could lead to 10 additional cases. 20,000 vs. 10. I don’t think organic is necessary; getting fruits/vegetables is more important. If you want to buy organic, you can, but don’t have to.
[54:11] Vitamin D deficiency has been studied in myeloma, MGUS, Smoldering. It’s associated with reduced survival, increased inflammation. Trying to keep levels normal is probably beneficial, though we don’t have an intervention study proving benefit.
[54:50] To summarise: We have to individualise nutrition changes based on patient receptiveness and medical issues. Most patients will benefit from shifting to more high-fiber foods. Practical tips: three servings of whole grains, no sugary drinks, reduce refined carbs, improve fruit/vegetable diversity, prioritise plant proteins, eat fermented foods and unsaturated fats. Meal plan in advance; frozen fruits/vegetables are healthy. Read labels. Make it a lifestyle, not a diet. Pick one goal to begin with, then add others.
Example nutrition label: a cereal had 18g total sugar, fiber only 1g. Added sugars can be major. Avoid high sugar/sodium. For kidney disease, the National Kidney Foundation website has good info.
[57:00] Two surveys we are running: dietary patterns in MGUS/Smoldering/Myeloma (you get a nutrition report) and a supplement use survey. QR codes are available, or go to HealthTree Foundation website.
[57:36] It can be overwhelming to make changes, but we need to start somewhere. The first changes can be harder, but it becomes easier. Let’s change our focus from just living longer to living better and longer. Incorporating lifestyle changes is to improve quality of life and maybe reduce risk of progression for some (data is early). Future studies we hope to do. I thank the patients, colleagues, collaborators, funding agencies, and the myeloma service at MSK.
If you like more information, you can follow this link or follow me on these sites. Thank you.
