Precision Nutrition, Circadian Fasting, and Renal Cell Carcinoma

Author(s): Scott Douglas Jacobsen

Publication (Outlet/Website): The Good Men Project

Publication Date (yyyy/mm/dd): 2025/07/15

Dr. Tracy E. Crane, PhD, RDN, of the University of Miami, discusses the MAC-3 program, exploring how circadian fasting, body composition, and metabolomics impact renal cell carcinoma treatment outcomes. With over $30 million in research funding, Dr. Crane’s team combines mouse and human trials to investigate the obesity paradox, emphasizing behavioural science, dietary timing, and precision interventions. The research aims to improve cancer care through scalable, cost-effective methods by integrating wearable technologies, glucose monitoring, and advanced imaging. This multidisciplinary approach highlights how fasting duration and fat distribution might reshape clinical strategies in oncology.

Scott Douglas Jacobsen: Today, we are joined by Dr. Tracy E. Crane, PhD, RDN, Associate Professor of Medical Oncology, Public Health, and Kinesiology at the University of Miami Miller School of Medicine. She serves as Co-Leader of the Cancer Control Research Program and Director of Lifestyle Medicine, Prevention, and Digital Health at the Sylvester Comprehensive Cancer Center.

Dr. Crane is internationally recognized for her cancer prevention and survivorship work, focusing on integrating lifestyle interventions, such as nutrition and exercise, into cancer care. Her research emphasizes using digital health technologies to deliver personalized behavioural strategies to improve patient outcomes across the cancer continuum. Over the past five years, she has secured over $30 million in research funding, including multiple National Cancer Institute (NCI)-funded studies and a large Patient-Centred Outcomes Research Institute (PCORI)-funded trial. She has authored over 100 peer-reviewed publications, including co-authoring the latest American Cancer Society guidelines on nutrition and physical activity for cancer survivors.

Dr. Crane also serves as Vice Chair of the Cancer Prevention and Control Committee for NRG Oncology’s NCI Community Oncology Research Program (NCORP).

Dr. Crane, what inspired the development of the MAC-3 program, particularly about renal cell carcinoma?

Crane: The MAC-3 program was developed to explore the impact of dietary interventions on renal cell carcinoma outcomes. We recognized that a multidisciplinary approach—combining expertise from various scientific disciplines—was essential to address the complex questions surrounding cancer prevention and treatment. For instance, Dr. Scott Wellford leads preclinical studies using mouse models to investigate dietary effects in this project, while I oversee parallel human clinical trials. This collaborative approach allows us to align our studies closely, ensuring that findings from animal models can inform human interventions and vice versa.

In human trials, we face ethical and practical limitations in manipulating diets, but mouse models offer more control over dietary variables. By conducting these studies concurrently, we can synthesize our findings to generate comprehensive insights, leading to more effective and personalized dietary strategies for cancer patients. This synergy accelerates our research progress, so we named the program MAC-3—a nod to “Mach 3,” symbolizing high speed—reflecting our commitment to advancing cancer research swiftly through team science.

Jacobsen: So the other part of this involves Dr. Lombard. He is a pathologist who specializes in metabolomics—studying biological processes at the molecular level to understand what tissues, tumours, and blood samples are signalling. What are the cells doing? How are they communicating? Could you elaborate on his role?

Crane: Yes. Both the mouse and human studies send biological samples to Dr. Lombard. He analyzes those samples and helps conclude from a metabolomic perspective. By adding that layer—looking at what the cells are doing in real time, including things like sirtuin activity—we can move more quickly toward answering larger research questions. These are questions we would not be able to answer as quickly or thoroughly if we worked in isolated silos.

If you did everything independently, you might get the same answers. However, it would take much longer, and you would miss the insights that emerge when multiple scientific perspectives come together. That is the power of multidisciplinary science.

Jacobsen: Moving into the following research phase, how can you precisely predict disease risk or treatment outcomes? How early can these predictions be made, and how accurately can they become?

Crane: One of the primary motivations behind this work is addressing the obesity paradox in renal cell carcinoma. It is a fascinating and counterintuitive phenomenon. Obesity is a known risk factor for developing renal cell carcinoma. However, once a person has the disease and begins treatment, obesity appears protective. That paradox—how the same factor can increase risk yet offer a protective effect later—does not make intuitive sense, and we are trying to understand why that happens.

We are developing potential biomarkers not only from blood samples but also from body imaging. One of the aims of this trial is to analyze body composition through imaging. We want to see if something is changing or shifting—perhaps BMI, a crude, population-level measure of obesity, is not the right tool for assessing individual risk. Maybe the answers lie in specific aspects of body composition.

Precision would come from combining multiple tools, like imaging and metabolomics. By integrating advanced imaging, metabolomic profiling, and other biological markers, we aim to better analyze who is at higher risk and what interventions they need.

Jacobsen: So, theoretically, if someone with a high BMI develops renal cell carcinoma and then loses a significant amount of weight, would that correlate with a higher risk of mortality?

Crane: That is what our current epidemiological data suggest. Extensive cohort studies—epidemiological trials—show associations like this. However, those are not cause-and-effect studies. That is why our current project is a randomized controlled trial. We are not just looking at weight loss; we are specifically examining whether manipulating metabolism, without necessarily changing body weight, affects outcomes. It is about understanding whether the metabolic changes, not just the physical weight, influence cancer responses.

Jacobsen: When you say body composition, you mean total body fat, muscle mass, etc.?

Crane: Yes, and it is important to recognize that fat does not distribute evenly across people. Some individuals carry more visceral fat in the abdomen; others store fat in the hips or thighs. Moreover, some people may even shift fat stores on purpose. However, in general, this variability matters a lot.

Jacobsen: Are there particular fat or fat distribution types that seem more significant?

Crane: That is precisely what we are trying to determine. Not all adipose tissue is created equal. Visceral adipose tissue, for example, behaves very differently from subcutaneous fat. Understanding the role of different fat types and distributions could be crucial in predicting risk and tailoring treatment strategies. You have brown fat, and you have white fat. These different types of adipose tissue have distinct metabolic functions and responses.

When we talk about lean mass, that includes muscle and bone, it is important to understand what happens to these tissues when patients undergo treatment for renal cell carcinoma. Are there changes in response to the treatment contributing to this paradoxical outcome? We are still trying to investigate many unknowns. We hope to better understand the obesity paradox by looking at the whole picture, from whole-body imaging and body composition down to the smallest particles of cellular metabolism.

Jacobsen: Are there other methods that might be as coarse as body composition but still as accurate or predictive in identifying risk? Could something else serve that purpose just as well?

Crane: That is a good question. Honestly, I do not know yet. Body composition may or may not be the best predictor, which is precisely why we do science. Our current hypothesis is that it offers real potential.

Another important consideration is clinical translation. We aim to build on tools and resources already available in the healthcare system. For example, most patients undergo routine imaging as part of their standard care. These scans are not currently analyzed for body composition in clinical practice, but we can add that layer of analysis.

Suppose we use existing scans, layer on the body composition data, and combine that with biomarkers from blood samples, which we collect in large volumes. In that case, we can develop clinically useful prediction models. The point is to use what is readily available to avoid burdening the healthcare system and still generate valuable insights.

Could there be a completely different biomarker or a better method that works even more accurately? Absolutely. That is always a possibility. However, this approach—the one we developed as a team—offers a strong scientific rationale and the most significant translational potential.

Jacobsen: Really, it is what you said earlier—this is why we do science. It reminds me of a talk by Richard Dawkins a while back where he discussed different kinds of language, contrasting scientific talk with non-scientific language.

If I remember correctly, he made the point that there is a reason why writing in scientific journals often reads a certain way. It might seem dry or formulaic to some, but it reflects the precision required in scientific discourse. It is not about embellishment but clarity, evidence, and reproducibility.

Dawkins gave other examples, quoting what he called a “peer-reviewed journal”—though in that case, it was fictional. He said something like, “It has been privately revealed to Dr. So-and-so that…” to demonstrate how non-scientific language differs. So that scientific spirit you are pointing to is critical—it underscores the importance of method and discipline in getting accurate results.

Crane: There is a specific way of doing things in science. It is about getting to the truth through reproducible, evidence-based approaches, not intuition or anecdote.

Jacobsen: Now, shifting focus a bit—what about biological rhythms and dietary interventions? Suppose two individuals have the same body composition. One is vegan, another pescatarian, and another follows a fad like eating three steaks a day. Do we have preliminary findings on how diet types affect outcomes, or is that still theoretical? Are those relevant considerations?

Crane: That is a great question. One of the things we are exploring relates to what Dr. Scott Wellford is doing in the lab with mouse models. He has already been altering the mice’ diets—testing high-fat versus low-fat variations, for example. However, what he has not done yet is adjust for circadian alignment.

We are beginning to see metabolic shifts based on dietary composition that correlate with how well the mice do when they have renal cell carcinoma. We see real potential based on Scott’s findings and my research on prolonged overnight fasting and circadian rhythm alignment. The key is balancing what science shows us with what we can realistically ask human patients to do.

In my human trials, I have been studying how meal timing can help align circadian rhythms. One of the most effective ways to do that is adjusting when people eat relative to daylight after the sun comes up, when you break your fast, matters a lot.

Prolonging the overnight fasting window—from 7 PM to 9 AM the next day—can improve circadian alignment. People undergoing treatment have shown high adherence to this kind of intervention. Their metabolic profiles improve, their sleep quality improves, and they tolerate treatment better. This has been documented in other cancer types, not renal cell carcinoma, yet.

However, based on that data and the metabolic indicators Scott has observed in mice, we believe this is both scientifically valid and practical for patients newly diagnosed with advanced renal cell carcinoma.

In this study, we ask participants to shift to a 14-hour daily fast. We equip them with continuous glucose monitors and wearable devices to assess circadian alignment. The only change we ask for is when they eat, not what they eat.

This will lead to favourable metabolic changes that improve treatment outcomes and reduce side effects. Beyond glucose monitoring, we will also assess cellular metabolic changes through samples analyzed by Dr. Lombard, which may further illuminate protective mechanisms.

We also expect to observe changes in body composition due to this dietary timing intervention, which is part of what we are measuring.

Jacobsen: As always, at the end of every academic poster, presentation, or publication, there is that familiar line: “More research is needed.”

Crane: [Laughing] Yes, fill in the blank!

Jacobsen: Where do you see the next step in this line of research? We have been focusing on body composition and circadian alignment—what logically follows from here?

Crane: Once we run this first trial, the next step is to analyze the data and identify which variables responded well and which did not. We are not restricting what people eat during their 10-hour eating window, but monitoring their choices. Between Dr. Wellford’s trials in mice and what we observe in the human participants, we will better understand what the subsequent intervention should look like.

That next step would likely combine predictors from body composition data with tailored dietary guidance—essentially, figuring out not just when to eat, but what to eat based on individual characteristics.

I suspect that prolonged overnight fasting will have a favourable impact. The real question is, once we establish that, what do we do with food intake? We can prescribe specific interventions tailored to metabolic profiles if Dr. Lombard finds early signatures in the metabolomics data.

All these data—wearables, body composition, blood biomarkers—will come together. We also track things like sleep, daily step count, and overall activity through wearable devices. So we are looking for phenotypes—composite profiles of individuals—that respond best to specific interventions. The goal is to move toward precision interventions.

Jacobsen: Do you have any favourite facts or findings from the research papers?

Crane: That is a great question—and a tough one. There is so much to choose from.

However, one of my favourite findings is how well individuals can adopt circadian alignment strategies. The adherence rates from our studies are high. Moreover, this is in people undergoing treatment, which makes it even more impressive.

People do not usually think about their eating windows until you bring it to their attention. Once they become aware of how much they snack after dinner, it often leads to meaningful behavioural changes.

From a behavioural science perspective, that is a powerful takeaway. It does not cost any additional money. We are not asking them to buy different foods or follow a complicated regimen. It is accessible. Now, I should not say everyone finds it easy. However, our data shows that around 90% of participants can consistently follow the fasting window.

About ninety percent of the population would benefit from extending their time in a fasted state. When you are not constantly digesting, your body can rest, repair, and function more efficiently. Energy is not being diverted to digestion—it can be used elsewhere in the body for metabolic regulation, cellular maintenance, and recovery.

Jacobsen: I would love to interview a researcher on the Japanese school system. Their population is so healthy because every school employs professional nutritionists.

Crane: Yes, every single school has a nutritionist. The Japanese government made a deliberate effort to overhaul its school food system, which is paying off. The results are measurable.

Jacobsen: Have the Americans been bought off? I suggest adding sugar, in particular.

Crane: [Laughing] Yes… yes. Listen, we do not have to get into all of that here. Since January, I have given numerous interviews about food additives and what is happening. So we will see where that conversation goes.

Jacobsen: Tracy, thank you so much for your time and expertise.

Crane: You are welcome. It was nice to meet you.

Jacobsen: Thank you. It is nice to meet you as well. I will get to this later today.

Crane: That sounds good.

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