According to a new study by scientists at the University of Colorado Anschutz Medical Campus, acute amounts of lactate, such as those produced during exercise, are probably required for healthy cells, but chronic exposure causes cellular disruption, which can lead to cancer, heart failure, and type 2 diabetes.
The study was published last week in the journal Frontiers in Nutrition.
Type 2 diabetes is a condition in which the body’s ability to control and utilize sugar (glucose) as fuel is impaired. Too much sugar circulates in the bloodstream as a result of this long-term (chronic) disease. High blood sugar levels can eventually cause problems with the circulatory, neurological, and immunological systems.
“We know that lactate is not just a waste product,” said lead author Iñigo San Millán, Ph.D., assistant professor at the University of Colorado School of Medicine and associate professor at the University of Colorado Colorado Springs. “It has significant signaling and regulation properties at the cellular level.”
Lactate, a glucose byproduct, is a primary energy source for the cell, particularly the mitochondria. In the beating heart, muscles, and brain, it is a preferred fuel over glucose.
Cancer cells are producing glucose all the time and they are producing lactate all the time and it is never cleared out like it is during exercise. This lactate accumulation regulates the expression of many key genes involved in cancer as we have recently shown.
Iñigo San Millán
The chemical is also created during activity and quickly eliminated from the body by the mitochondria, which oxidize it quickly. However, when rats were exposed to lactate for up to 48 hours, San Millán and his colleagues discovered that they become more susceptible to disease.
“We know that when lactate is acutely exposed to cells, like during exercise, it is beneficial,” San Millán said. “But chronic exposure disrupts cellular metabolism entirely.”
Chronic lactate exposure was studied to see if it may reduce cardiac mitochondrial activity, produce cellular disruption, and contribute to metabolic inflexibility in the heart.
Long-term lactate exposure resulted in a significant drop in fatty acid transport, changes to a crucial component of mitochondrial membranes known as cardiolipin, and reductions in mitochondrial ATP or energy production, according to the researchers.
It also resulted in an increase in free radicals, which have been linked to heart failure and type 2 diabetes. Type 2 diabetes was previously referred to as adult-onset diabetes, however, both type 1 and type 2 diabetes can start in childhood or maturity. Although type 2 diabetes is more common in older persons, an increase in the number of obese youngsters has resulted in an increase in type 2 diabetes incidence among children.
“We found that dysregulated lactate is probably a major player in disease,” San Millán said. “This is a rat model but we believe the results would be similar in human cells.”
The next step is to figure out what’s causing the diminished ability to remove lactate.
San Millán has done a substantial study into the association between lactate and cancer, as well as the overall relevance of mitochondrial health, in addition to his research. He also coaches top cyclists, including last year’s Tour de France winner.
His research group previously discovered that lactate could be a master regulator of carcinogenesis, the process that transforms a healthy cell into a cancerous one.
“Cancer cells are producing glucose all the time and they are producing lactate all the time and it is never cleared out like it is during exercise,” he said. “This lactate accumulation regulates the expression of many key genes involved in cancer as we have recently shown.”
For San Millán, it comes down to mitochondrial health.
“We believe that a primary mitochondrial impairment or dysfunction could lead to excessive lactate accumulation leading to disease,” he said. “And right now, the only medication we have to fix mitochondrial function is exercise.”
