Science has confirmed that exercise is good for the brain. It increases blood flow, inhibits stress hormones, and stimulates the release of “feel-good” endorphins. One way exercise is thought to yield these benefits for the brain is through a chain of processes that ultimately results in the release of the hormone brain-derived neurotrophic factor (BDNF). Produced by the liver, brain, skeletal muscle, and fat tissue, BDNF is known to promote the growth, survival, and maintenance of nerve cells.
Previous studies suggest that this physiological chain is triggered by high levels of lactate in the blood—a byproduct produced when carbohydrates are converted into energy in muscles, the liver, and the blood under low-oxygen conditions—for example, during high-intensity exercise. A study in human volunteers has now found that the physiological benefits of exercise may be partly mimicked by a simple IV infusion of lactate.
“Here we show for the first time that such an infusion leads to levels of lactate in the blood which are characteristic of medium to intense exercise,” said Marcus Moberg, PhD, a senior lecturer at the Swedish School of Sport and Health Sciences in Stockholm. “Ultimately, this boosts levels of the precursor molecule of BDNF, likely released by the skeletal muscle.”
Moberg is senior author of the team’s published paper in Frontiers in Cellular Neuroscience, titled “Lactate Infusion Increases Circulating pro-Brain-Derived Neurotrophic Factor Levels in Humans.”
“Brain-derived neurotrophic factor (BDNF) is a key mediator of neuroplasticity and responsive to acute physical exercise, providing a link between exercise and brain health,” the authors wrote. “Lactate, a metabolite related to exercise, has been proposed as a potential mediator of the BDNF exercise response; however, lactate’s role in isolation has not yet been determined.”
To further investigate this, the authors designed a trial that would investigate the potential effects of BDNF without the exercise stimulus. “At this point, it is uncertain whether lactate can affect plasma and serum mBDNF levels with no simultaneous exercise stimulus and whether lactate influences acute circulatory and/or muscle pro-BDNF levels in humans,” they noted.
Moberg and colleagues carried out a randomized crossover study involving 18 healthy volunteers (50% self-reported female) aged between 20 and 40 years. The volunteers were split into two groups: 12 in the experimental group (50% female), and six in the control group.
After fasting overnight, each participant in the experimental group lay down in a supine position for approximately four hours on two different occasions while receiving a 60-minute IV infusion of either sodium lactate (lactate trial) or isotonic saline (saline trial). The two experimental trials were separated by seven to 30 days.
Blood was taken from each volunteer every 10 minutes during both treatments, as well as 15, 30, 45, 60, 90, and 120 minutes afterwards. A leg muscle biopsy was taken before and immediately after each infusion with lactate, as well as 60 and 120 minutes later. The control group, six additional volunteers, exclusively underwent a treatment with saline solution, and likewise donated blood samples and four muscle biopsies.
The researchers measured the lactate concentration in each blood or muscle tissue sample. They further quantified the levels of pro-BDNF, a biologically active precursor molecule of BDNF, in addition to its mature molecular form, mBDNF, in blood plasma, serum, and platelet-poor plasma, which is plasma from which most platelets have been removed. “We asked if lactate in isolation could affect circulating levels of pro- and mBDNF, as well as muscle pro-BDNF levels,” the team stated.
As expected, the concentration of lactate in blood increased during infusion, peaking at values similar to those normally obtained after high-intensity exercise. Importantly, the concentration of the precursor protein pro-BDNF increased 15 min after the end of lactate infusion and stayed high for two hours afterwards. In contrast, neither the level of pro-BDNF in muscle nor that of mBDNF in plasma or serum changed during or after lactate infusion.
“Despite reaching markedly higher lactate levels during the one-hour infusion, mBDNF remained unaltered in both plasma and serum,” the investigators stated. “By contrast, lactate infusion increased plasma pro-BDNF levels, suggesting a differential regulation of the two BDNF isoforms in response to lactate when there is no simultaneous exercise stimulus.”
The authors concluded that IV infusion with lactate is sufficient to boost the levels of pro-BDNF in the bloodstream, but without affecting mBDNF levels. This indicates that lactate infusion alone is enough to mimic some, but not all, of the physiological effects of high-intensity exercise. It is expected that such an increase of pro-BDNF will have similar beneficial effects on brain health, irrespective of the mechanism behind it. “In conclusion, these results suggest that lactate in isolation affects circulatory pro-BDNF, but not mBDNF levels,” they stated.
Is this good news for those among us who loathe exercise? Possibly one day, but for now, the authors strongly caution against skipping the exercise step and relying on lactate infusion alone. “The present data support the notion that lactate is a molecule involved in the regulation of BDNF metabolism in humans,” the team concluded. “We propose that future human research should be directed to the importance of exercise-induced lactate-BDNF for peripheral nervous system function, as well as devotion to methods that can assess BDNF levels or effects directly in the CNS after an acute intervention.”
Moberg said, “We speculate rather that the intensity of exercise is important if brain health is the desired goal. High-intensity exercise a couple of times per week, thus exposing the brain to high levels of lactate, should be recommended for healthy neurological aging. In the future, these findings can aid in the targeted, individualized prescription of exercise in clinical settings, especially for populations with compromised brain health.”
Moberg continued, “Also, since lactate is known to exert hormonal-like effects, there is a potential for pharmacological interventions. This would require additional research to pinpoint the exact mechanism by which lactate controls BDNF metabolism in humans.”
