(May 2017) For decades, lactate has been studied largely in the context of
exercise, painted as a nagging metabolic byproduct that accumulates in
the tissues and blood during workouts, stiffening muscles and hindering
Now a new paper, published in February in the journal
Carcinogenesis, paints the complex, often misunderstood, molecule in a
more sinister light—as a key driver in the development and spread of
Its authors say the paper could help explain why people
who exercise tend to have lower rates of cancer—because their bodies are
able to more effectively process the lactate we all produce when we
metabolize sugar. It also could lead to new treatments.
paper, we open a whole new door for understanding cancer, showing for
the first time that lactate is not only present, but mandatory for every
step in its development,” said lead author Iñigo San Millán, director
of the sports performance department and physiology laboratory at the CU
Sports Medicine and Performance Center at CU Boulder.
also an assistant professor in the School of Medicine’s Department of
Physical Medicine and Rehabilitation, spent two years working on the
paper with University of California Berkeley professor and renowned
lactate researcher George Brooks. The team applied lessons learned from
dozens of exercise physiology and muscle metabolism studies conducted
at CU Boulder, the CU Anschutz Medical Campus, the University of
California and elsewhere to try to answer a century-old question: How
does a normal cell become a cancer cell and then what happens?
far back as 1923, German Nobel laureate Otto Warburg observed that
cancer cells take in exponentially more sugar, or glucose, than normal
cells. They also inefficiently convert far less of it into ATP, or
energy, converting about 70 percent of it to lactate as a byproduct. The
phenomenon—the first sign of a normal cell turning cancerous through
abnormal cell metabolism—is known as the “Warburg effect.” The paper
seeks to explain why it happens.
With a heightened focus on
genetics in recent decades, many researchers moved away from studying
cancer metabolism, and the role of lactate became overshadowed, San
Millan said. He hopes to help swing the pendulum back.
illuminates the role lactate plays in fueling angiogenesis (the
formation of new blood vessels in tumors); how it interferes with the
body’s immune response to cancer; and how it creates an acidic
micro-environment (the space outside the cancer cell) supportive of
cancer metastases, or spread. The paper also theorizes how three
major transcription factors, or proteins, involved in most cancers
(HIF-1,cMYC, and p53) kick-start and perpetuate lactate deregulation in
The paper draws parallels between what happens in the
muscles of an athlete in training, and what happens in a developing
“During high-intensity exercise, working muscles display
many of the same metabolic characteristics as cancer cells,” explains
San Millán, a former pro cyclist and physiologist to Tour de France
cyclists. Muscles take up large amounts of glucose, turning it to energy
inside the mitochondria and churning out more lactate than the body can
In a healthy person, Brooks’ research has
shown, the body then recycles that lactate for beneficial use—turning it
into a key source of fuel for the brain, muscles, and organs,
preventing it from building up.
In cancer, the authors suggest, that recycling system breaks down.
Millán hypothesizes that while people who exercise regularly are at
less risk of cancer—in part due to their body’s ability to clear lactate
more efficiently—a sedentary lifestyle, combined with excess sugar
intake may fuel lactate accumulation and kick-start the metabolic
misfiring that can lead to cancer.
The authors hope cancer
researchers will use the paper as a starting point for further studies.
Already, San Millán is studying breast cancer cell lines, and this
summer he will team up with University of Colorado Hospital to study the
impact of personalized exercise programs on cancer patients.
he hopes the paper could lead to new exercise and dietary prescriptions
for cancer patients, new diagnostic tools that could use deregulated
lactate signaling as a marker of a brewing cancer, or new drugs which
target MCT Transporters, which are responsible for transporting lactate
from cell to cell.
“We hope to sound the alarm for the research
community that to stop cancer you have to stop lactate,” he said. “There
are many ways to do that.”