When Urvi Shah was a hematology-oncology fellow, she was diagnosed with Hodgkin lymphoma, a cancer that affects the lymphatic system, which is vital for a healthy immune response. Shah received four months of intense chemotherapy that cured the disease, but she wondered what role, if any, diet played in eradicating her cancer.
“I heard a lot of advice from friends and family about what I should and shouldn’t eat, and I realized that in medical school we don’t learn anything about the role of nutrition in healing,” Shah says. “As a patient, I wanted to feel empowered to do something for my health.”
Intrigued by evidence that high-fiber plant foods reduce cancer incidence and risk of recurrence, Shah refocused her research on modifiable cancer risk factors, including nutrition, obesity, diabetes and the microbiome. Now a myeloma specialist and adjunct professor at Memorial Sloan Kettering Cancer Center in the United States, Shah is leading four dietary intervention studies (NUTRIVENTION trials) to provide nutritional guidance to cancer patients.
Shah’s work is part of a growing body of research suggesting that a constellation of metabolic diseases such as obesity, diabetes, hypertension, high cholesterol and high triglycerides (which affect more than 40% of Americans) could be a key factor in the onset and progression of many types of cancer. There is even a medical term — metabolic syndrome — to describe people who suffer from three or more of these conditions. The incidence of this syndrome has been rising for decades, and the Western diet combined with an inactive lifestyle are largely to blame.
Overindulging in alcohol, refined carbohydrates and high-fat foods, and spending most of your time on the couch or sitting at a desk, produces an inflammatory response that eventually damages DNA. Unfortunately, the more damaged the DNA, the more likely normal cells are to become cancerous.
“Our view of cancer as a genetic disease drove the development of therapies targeting specific genetic mutations,” said Stephen Freedland, director of the Center for Integrated Cancer and Lifestyle Research at Cedars-Sinai in California. “But we now know that cancer is a metabolic disease with unique metabolic requirements, and many of the genetic changes that occur in cancer regulate metabolism.”
According to estimates by the International Agency for Research on Cancer (IARC), there were nearly 20 million new cases of cancer and 9.7 million deaths from cancer in 2022. In many high-income countries, cancer has overtaken heart disease as the leading cause of death. And while genetic sequencing has advanced our understanding of the genomic changes that occur in cancer, it has not led to many effective therapeutic targets.
Because cancer cells have millions of genetic alterations, developing tumor-specific drugs is a daunting task. What scientists do know is that faulty metabolism (the process by which cells generate and use energy) is a hallmark of cancer. This suggests that metabolic reprogramming of cancer cells could be a viable treatment strategy.
Only 5 to 10 percent of cancers are linked to a specific genetic mutation, and no single mutation is associated with all cancers. Instead, metabolic changes occur in nearly all cancers. So it makes sense that cancer rates are rising along with the growing epidemic of metabolic diseases.
A study conducted in 2024 with more than 44,000 people in China, published in Cancerreported that people who had at least three of the five components of metabolic syndrome had a 30 percent increased risk of developing all types of cancers over the nine-year study period, compared with those who had fewer than three of these risk factors. The researchers found that the risk of breast, endometrial, kidney, colorectal and liver cancers among people in the group with the highest metabolic syndrome scores was two to four times higher than among those with the lowest scores.
Obesity, one component of metabolic syndrome, is associated with high levels of inflammation that damage healthy tissue and contribute to at least 13 types of cancer. For example, studies show that obese women have a three-fold increased risk of endometrial cancer and a 2.5-fold increased risk of kidney cancer compared to their metabolically healthy, normal-weight counterparts.
“Excess body fat, especially around the midsection, drives increased inflammation, blood sugar, and insulin-like growth factor-1 (IGF-1) production, all of which are linked to certain cancers,” Freedland says; “The mechanisms may be different for different cancers, but metabolic dysfunction is the common denominator.”
But what we eat and what we weigh aren’t the only factors at play. Research shows that even normal-weight people with metabolic syndrome have a higher risk of developing cancer. Lifestyle, for example, can alter the body’s response to insulin and ability to convert energy from food into fuel.
The theory that cancer is a metabolic disease dates back to the 1920s, when German scientist Otto Warburg reported that cancer cells have a metabolic peculiarity. Unlike normal cells, cancer cells use glucose almost exclusively as an energy source, even when there is sufficient oxygen to break down other fuel sources, such as fatty acids and proteins.
This feature allows for early detection of cancer using positron emission tomography (PET) with fludeoxyglucose-18 (FDG), a noninvasive imaging test that tracks glucose consumption by cells and allows the identification of cancerous cells (those that consume more glucose).
The question is: can cancer cells be starved by cutting out sugar?
Most scientists aren’t ready to make that leap, but several studies link excessive glucose consumption through sugary drinks and refined carbohydrates (aka sugar) to an increased risk of cancer. Research suggests that diabetic patients who take metformin, a blood sugar-stabilizing drug, are less likely to develop cancer than those who don’t take it.
Poorly controlled blood sugar is like candy for cancer. Unlike normal cells, which stop growing in response to hormonal signals, cancer cells’ faulty metabolism interferes with these messaging systems. In fact, two key hormones produced by adipose tissue (adiptin and adiponectin) can contribute to turning normal cells into cancer cells when their balance is disrupted.
Low adiponectin and high leptin levels are associated with obesity and metabolic syndrome, Shah explains. This altered ratio “is associated with increased cancer risk through insulin resistance and inflammation, two key drivers of cancer.”
However, what remains uncertain is whether genetic alterations lead to dysregulated metabolism in cancer or whether dysregulated metabolism is what gives rise to the genetic changes seen in cancer.
“Metabolic syndrome causes genetic changes that predispose people to cancer,” says Suresh T. Chari, a gastroenterologist at the University of Texas MD Anderson Cancer Center, who is investigating whether certain metabolic biomarkers could help detect cancer earlier. “But cancer itself also causes many metabolic alterations in the years before diagnosis, probably for its own survival.”
This link, Chari says, suggests an opportunity: Metabolic disorders, such as diabetes, and factors such as lipid levels and C-reactive protein (a measure of inflammation) could help detect elusive cancers earlier. And because the two processes are so intertwined, tools that combat metabolic disorders could also combat all types of cancer.
Scientific knowledge about the metabolic basis of cancer continues to evolve. According to Shah, controlling parameters such as sugar, blood pressure and cholesterol and taking steps to reprogram metabolic dysfunctions can help doctors detect cancer earlier or even prevent it.
“There is skepticism that these modifiable risk factors confer only modest risk, so we shouldn’t overwhelm patients with this information,” Shah says. “But in my experience, patients are hungry for information about how they can prevent or slow the disease process, and there is strong data to suggest that monitoring and managing metabolic syndrome is an important prevention and treatment strategy.”
In one of Shah’s trials, sugary drinks were associated with a 40 to 60 percent increased risk of abnormal blood proteins linked to multiple myeloma risk. In contrast, whole grains, fruits and vegetables were associated with a 30 to 50 percent reduced risk of this precancerous condition. Research also suggests that achieving a healthy metabolism through lifestyle strategies can improve your chances of survival if you already have cancer.
Thanks to the many ways to improve metabolic risk factors, patients can take charge of their health, at least to some extent. They should know that how much, when and what they eat makes a difference. That going to the gym instead of watching Netflix can reduce the risk of developing cancer and improve outcomes if they have already been diagnosed and that swapping soda for water with a squeeze of lime is the best cancer prevention strategy.
“Patients have tremendous power,” Freedland says. “The choices they make every day can make a dramatic difference in their risk of developing cancer and other diseases.”