Lactate-Not Guilty as Charged

Robergs, R.A., Ghiasvand, F., & Parker, D. 2004. Biochemistry of exercise-induced metabolic acidosis. American Journal of Physiology—Regulatory, Integrative and Comparative Physiology, 287, R502–16.

The muscle burn that accompanies intense exercise, generally referred to as acidosis, has traditionally been attributed to an increase in the body’s production of lactic acid. This concept of lactic acidosis is taught in many physiology, biochemistry and exercise physiology courses throughout the world and has been a topic of debate among fitness professionals for years. Many fitness specialists believe that the production of lactic acid—or, more accurately, lactate—is the cause of muscle fatigue, or “the burn,” during vigorous exercise. (See “Lactic Acid or Lactate?” on this page.)

Robergs and colleagues have recently completed an extensive re-examination of the biochemistry of exercise-induced metabolic acidosis. Their review includes a brief history of our understanding of lactic acid and provides an enlightening explanation of lactate production and acidosis. Following are some highlights.

Robergs and colleagues attribute the discovery of lactic acid in 1780 to Carl Wilhelm Scheele, a Swedish chemist. Scheele isolated an acid in sour milk samples (hence the term lactic acid). According to the Robergs account, by 1810 chemists had verified the presence of lactic acid in other organic tissues, such as fresh milk, meat and blood. In 1833 the actual chemical formula for lactic acid was determined, and by 1869 scientists had observed different isomers (atomic compounds with different energy states) of lactic acid and noted its formation in fermentation reactions. (Fermentation is an enzyme-driven chemical change in an organic compound whereby the substance is split into simpler compounds.) At that time, fermentation was the main direction of scientific inquiry into the biochemistry of lactic acid production.

Today’s prevailing understanding of lactic acidosis in humans (which is an extension of the understanding of lactic acid production in fermentation) can be attributed to some early research on skeletal muscle biochemistry during exercise. Otto Meyerhoff and Archibald V. Hill were two noted researchers who, in 1922, both received a Nobel Prize for their research on the energy capabilities of carbohydrate metabolism in skeletal muscle. Robergs and colleagues point out that it was Meyerhoff who elucidated most of the glycolytic pathway and suggested that lactic acid was produced in humans as a side reaction to glycolysis (the splitting of sugar to fuel rapid, intense muscle contractions) in the absence of oxygen.

Knowledge of acid-base chemistry and mitochondrial respiration (aerobic metabolism) was limited at the time. Most research on lactic acid production during fermentation, as well as the presence of lactic acid in numerous animal tissues, established a connection between lactic acid production and acidosis—and that connection was assumed to be cause-and- effect. The Robergs review contends that Hill and Meyerhoff’s research solidified the explanation of lactic acid production and acidosis in the mindset of academics in physiology and biochemistry—even though the early researchers’ commonsense explanation was based primarily on their (incomplete) observations of cell metabolism, not on experimental research. Robergs states, “It is easy to comprehend how the Nobel Prize quality of the work of Hill and Meyerhoff was proof enough to the scientific world at that time for the interpretation that lactate production and acidosis were cause-and-effect.”

This revealing and interesting history of acidosis and lactate exposes one important message: There was never any real experimental research demonstrating a cause-and-effect relationship between lactate production and acidosis. Yet the work of these early pioneers has been considered the absolute explanation of acidosis for more than 80 years.

Why do many educators and research-ers still believe that lactate production is the cause of acidosis? According to Robergs and colleagues, most textbooks simply do not thoroughly explain the chemically balanced reactions that occur during metabolic acidosis, and incomplete explanations have led to the acceptance of misconceptions.

During vigorous exercise, the ATP (adenosine triphosphate) demands of muscle contraction are considerable. Every time an ATP molecule is split to produce energy, it is broken down into an ADP (adenosine diphosphate) molecule and an inorganic phosphate molecule, and one hydrogen ion—or proton—is released. The increase in protons is what defines and causes acidosis.

When the ATP demands of exercise are being met by aerobic metabolism (mitochondrial respiration), the accumulated protons are used in important steps of cell metabolism. However, during very intense exercise (high-intensity resistance training or above steady-state endurance exercise), an accumulation of protons occurs in the muscle, owing to a much greater involvement of the phosphagen and glycolytic energy systems that provide ATP for muscle contraction. The Robergs study gives the biochemical explanation and illustrates (with chemical-structure reactions) that the ATP supplied from the phosphagen and glycolytic energy systems is the source of the increased proton accumulation in the cell—and thus the cause of acidosis (the burn).

During the demands of high-intensity exercise, muscle cells utilize a lot of glucose (from glycolysis) and muscle glycogen (the stored form of glucose). The final step of glucose breakdown results in the production of two molecules of pyruvate. The pyruvate molecules and the protons (from the splitting of ATP) begin to accumulate in the cells. To neutralize the soaring accumulation of pyruvate and protons, each pyruvate molecule absorbs two protons into its structure and converts to lactate. Thus, lactate production is a consequence, not the cause, of cellular acidosis. In fact, lactate production actually retards acidosis, acting as a temporary “neutralizer” or “buffer” to the elevated accumulation of protons in the muscle cells. Since increased lactate production coincides with acidosis, lactate measurement is an excellent indirect marker for the metabolic condition of the cell.

Lactate production is therefore good, not bad, for contracting muscle. Lactate has been given a bad rap for years, as it has been falsely accused of causing acidosis.

Fitness professionals can use this contemporary understanding of acidosis when designing exercise programs. For example, one modern endurance training method is lactate threshold training, a technique that capitalizes on the contribution of ATP from mitochondrial respiration, thus decreasing the reliance on glycolysis. (See “Optimize Endurance Training” in January 2003 IDEA Personal Trainer for a more thorough discussion of this type of training.) In addition, to optimize clients’ high-intensity resistance workouts, endurance exercise should be incorporated in the training design. Endurance training will improve clients’ proton-buffering capacity, thus inhibiting a major contributor to fatigue and allowing clients to participate in longer, more challenging resistance workouts.

Although the two terms are often used interchangeably, lactic acid and lactate are not the same compound. Lactic acid is, in fact, an acid, which by definition means that it can release a hydrogen ion, or proton, when pH conditions drop to less than 7.0. When lactic acid releases the hydrogen ion, the remaining compound (which is negatively charged) joins with a positively charged sodium ion (Na+) or potassium ion (K+) to form an acid salt (e.g., sodium lactate). Robergs and colleagues (2004) demonstrate through detailed chemical reactions that lactic acid is not produced in the body. Rather, it is lactate that is the product of a side reaction in glycolysis.

During high-intensity resistance training, the body’s more explosive fast-twitch motor units are recruited. The fuel for this energy demand comes primarily from anaerobic metabolism (the phosphagen and glycolytic energy systems). Fast-twitch muscle fibers have fewer mitochondria (where cell respiration and proton uptake occur) than slow-twitch, or aerobic- endurance, fibers. The extensive use of the fast-twitch fibers (with fewer mitochondria and less protein uptake) during high-intensity resistance training leads to a greater accumulation of protons, thereby causing acidosis, or “the burn.”