New UC Berkeley Study Challenges Traditional Views on Lactate and Carbohydrate Metabolism

Over the years, many biology and sports science textbooks have mentioned that the human body mainly generates energy through anaerobic glycolysis during high-intensity exercise, producing lactic acid (lactate) that lowers muscle tissue pH, subsequently hindering muscle contraction and causing fatigue and soreness. However, there has been increasing research evidence in recent years that the idea of “lactic acid buildup after intense exercise leads to fatigue” no longer seems to hold water. 

Inspired by his journey from a high school track and field athlete to UC Berkeley doctoral student, Robert Leija, alongside his mentor Prof. George Brooks and their team, recently presented new evidence that lactate serves as a vital component in managing carbohydrate metabolism. Published in Nature Metabolism, their study unveils how lactate serves as a vital energy source, particularly after consuming carbohydrates, debunking the myth that lactate formation signals oxygen deprivation in muscles. 

Related article: Scientists Unlocked the Secret of Genetic Impact of Time-restricted Eating in Mice 

Lactate as a Vital Player in Carbohydrate Metabolism

In their study, 15 healthy, physically active young adults aged 21–35 years participated in an oral glucose tolerance test after a 12-hour overnight fast. Then the researchers closely monitored the participants’ blood glucose and lactate levels following carbohydrate ingestion by infusing them with lactate and glucose tracers, where lactate labeled with carbon-13, a stable, non-radioactive isotope of carbon, and glucose labeled with deuterium, a heavier isotope of hydrogen. The results demonstrated that lactate production begins in the intestines, preceding the appearance of glucose in the bloodstream, suggesting that lactate works in tandem with insulin to buffer the release of dietary glucose into the bloodstream. 

These findings redefine lactate as a key player in carbohydrate metabolism of humans, challenging the notion that it is solely a byproduct of anaerobic metabolism or oxygen deprivation. Dr. Brooks, UC Berkeley’s Professor of Integrative Biology who has long been working on the research on the lactate shuttle hypothesis, pointed out that “Instead of a big glucose surge, we have a lactate and glucose surge after eating. And the more of it that is converted into lactate from glucose, the better it is to manage glucose. Lactate is a carbohydrate buffer.”

Debunking the Bad Name of Lactate as a Harmful Metabolite

The study of Prof. Brooks’ team provides evidence that supports his hypothesis on the existence of postprandial lactate shuttle (PLS), where dietary glucose is metabolized into lactate in the gut before being transferred to the liver for glycogen storage. “We could see that because of lactate clearance and oxidation and because carbon-13 from the lactate tracer appeared in blood glucose. This shows that lactate is just a major energy highway for distributing carbohydrate — carbon energy flux,” he said.

On the one hand, the team established lactate’s constructive role in both aerobic and anaerobic metabolism instead of being a harmful metabolite through this study. On the other hand, they also found that lactate serves as an essential energy source when performing non-exercise activities or resting. This is similar to how lactate functions during high-intensity exercise, which the team has previously confirmed, in which human skeletal muscle, heart muscle, and brain cells prefer lactate over glucose as a fuel source. Lactate also signals fat tissue to cease burning fat for fuel.

Significant Implications for Medicine and Athletic Performance

As the first author of the study, which constitutes a part of his doctoral dissertation, Leija highlighted that lactate should be a critical fuel for tissues requiring sustained physiological performance rather than a waste product from oxygen-limited metabolism. He also admitted that Prof. Brooks’ theory of lactate shuttle has radically transformed his understanding of the relationship between lactate, often referred to as lactic acid, and athletic performance. “I had always associated lactic acid with exercising so hard that I was running out of oxygen and I wasn’t putting anything together in terms of physiology. Then it started to make a lot more sense.” 

In fact, these research findings hold significant implications for both athletic training and further exploration of metabolic disorders. Athletes and coaches can benefit from this knowledge by optimizing training regimens to utilize lactate as a beneficial fuel source during exercise, rather than viewing it as a hindrance. For researchers and medical professionals, the study sheds light on the misconceptions surrounding lactate and its role in carbohydrate metabolism. Contrary to popular belief, high levels of lactate in the blood may not indicate a problem but rather signal disruptions in the lactate shuttle cycle. This paradigm shift in understanding lactate may offer valuable insights into the intricate mechanisms of lactate metabolism, potentially leading to more informed healthcare approaches and breakthroughs in the management of various metabolic conditions such as diabetes. 

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Author

Richard Chau