This is an abbreviation of unit 9 from the Advanced Equine Nutrition course. The complete text, a video, and quiz questions are available with The Horse’s Advocate membership. You can also purchase them separately. Note: Passing the Basic Equine Nutrition Course is required before starting the Advanced Course.

Unit 9 – Lactate: The Universal Fuel

A quick search on the Internet will yield conflicting information about lactate, often improperly interchanging lactate and lactic acid. Lactate is not lactic acid, and lactic acid is not part of cellular metabolism. Also, you may have heard of aerobic (with oxygen) and anaerobic (without oxygen) exercise and glucose metabolism. The old thinking was that with oxygen, glucose becomes pyruvate. In a low-oxygen state, glucose becomes lactate. People thought this caused lactic acidosis and muscle pain. Again, this needs to be corrected. No acid is formed with glucose metabolism, and glucose always becomes lactate.

I always promise to give you the latest information. However, I still needed more information and clarification about some parts of glucose metabolism. I discovered that what had been taught for 100 years was wrong! Lactate is the molecule that fuels everything in the body, not glucose.

I feel your confusion. Veterinarians and medical doctors learned correct information in school. However, this information was only accurate until about 30 years ago. This was a decade after I graduated from veterinary school. Like everything else, change is uncomfortable for many. Corrected information needs to be better welcomed, but many prefer to maintain what they know, even when wrong. But with your dedication and the collective effort of the scientific community, we can challenge and update existing knowledge. 

The information provided here is reliable, as far as I know. Let’s explore what is now known to be more accurate. Once the clutter is removed, we can better understand how to feed horses. I apologize for using glucose as the primary fuel in the past units. 

Once you discover this truth about glucose, everything about metabolism will make more sense. Glucose is primarily a carrier molecule of two smaller molecules called lactate. These molecules make most of the energy.

Lactate Preserves Glucose

Lactate is the preferred substrate over all other substrates during regular activity for cell energy production; therefore, glucose is preserved. How? Glucose is stored as glycogen or body fat. Lactate from glucose splitting in the enterocytes travels freely to all cells. It then enters into all cells as the primary fuel for daily cell functions. This preference for readily available lactate preserves the stored glucose for emergencies. More lactate can be produced on demand within muscle cells. This occurs by metabolizing glucose stored as glycogen. However, this happens only when there is not enough lactate available. Glycogen levels are restored when at rest via food and gluconeogenesis. So, glucose will remain as glycogen whenever there is lactate, thus preserving it.

Excess lactate produced in any cell can travel anywhere in the body for use in another cell. It travels between muscle fibers using the cell-cell lactate shuttle. It also moves from the enterocytes to cells throughout the body. It needs no hormone. It uses a specific transport mechanism in the cell wall, called the MonoCarboxylate Transporter (MCT). It enters independently of any hormone. Using lactate made in other cells preserves glucose stored as glycogen and fat. Glucose and lactate from a current meal are used mainly in the brain. The brain requires the most significant and continuous need for energy to maintain life. Without the glycogen storage system in the muscles, sudden and extreme muscle use would quickly deplete glucose in the blood. This depletion would occur immediately. The brain would stop working. The body would collapse in front of the threat.

Excess lactate formed in strenuous exercise returns to the liver via the Cori Cycle. There, it combines into a new glucose molecule. This process is called gluconeogenesis. The conversion of two lactate molecules into one glucose molecule preserves lactate’s potential energy. Excess lactate from newly eaten glucose is also converted back to glucose. Gluconeogenesis ensures glucose availability at all times. It works even when no glucose is found in food, and the BMR is lowered, such as in winter.

Key Points:

1. Lactate does not create an acid environment within exercising muscles but does keep them slightly basic. There is no evidence of lactic acidosis or a low oxygen state; therefore, all metabolism is aerobic.
2. Much dietary glucose is metabolized in the enterocytes, broken into 2 lactate molecules, and distributed throughout the body. Glucose not metabolized attaches to insulin. It is transported to cells needing more glucose or to the liver. There, it is stored as glycogen or body fat.
3. Glycolysis of glucose produces lactate, which maintains a basic pH in the cell and produces net 2 ATP.
4. Glucose is more of a storage molecule for 2 lactate molecules.
5. Storing glucose as glycogen in muscle and the liver spares blood glucose for use in the brain.
6. Lactate enters the mitochondria, producing considerable cellular energy (34 to 38 ATP) through the Krebs Cycle, releasing CO2 and H2O. For this reason, it is the preferred fuel in all cells.
7. Excess lactate in cells can be used for energy production in the mitochondria. It can move between muscle fiber types. Lactate can travel freely in the blood. It serves as the primary fuel for neurons. Lactate can recombine with another lactate molecule to make glucose in the liver. Excess lactate is also excreted through the kidneys.
8. High cellular ADP signals lactate to move into the mitochondria. This action produces and increases ATP and reduces ADP. This prevents lactate uptake by mitochondria. It also reduces glycolysis (glucose metabolism) and increases glycogenesis (glycogen creation).
9. Lactate becomes acetyl Co-A in the mitochondria., competing with acetyl Co-A produced from fatty acid metabolism. This blocks fat metabolism. The result is that when glucose is present, fat will not be metabolized.
10. When lactate serves as the predominant long-term cellular fuel, the mitochondria cannot efficiently create energy. This inefficiency is due to increased ROS and inflexibility between fuel substrates.
11. Rest is essential to reduce ROS and improve the efficiency of the mitochondria.
12. Lactate freely moves into neurons and may be essential to repairing an injured brain. Beta-hydroxybutyrate shares the same transport mechanism with lactate: MCT.
13. The Cori Cycle returns excess lactate to the liver to form glucose (gluconeogenesis). This process assures a steady supply of glucose for survival.
14. Exercise increases lactate production. It also increases the number of muscle fibers and the density of mitochondria. It increases the number of inner folds, which raises the surface area for greater lactate metabolism. Exercise also increases MCT sites and the enzymes required for all metabolic processes.
15. Increased lactate from exercise suppresses the appetite via ghrelin.
16. The mitochondria in all muscle cells create an energy grid. This network shares lactate via the cell-cell lactate shuttle. It helps mitochondria communicate with each other.
17. Fast-twitch fibers have fewer mitochondria, lower blood flow, and less myoglobin. They are used for rapid movement. These fibers make more lactate than they can consume. They share the excess with neighboring fibers and fatigue quickly (equipment limited).
18. Slow-twitch fibers have more mitochondria, blood flow, and myoglobin. They are used for endurance movement. They make less lactate than is required. They use lactate made from neighboring fibers. They can sustain contraction (fuel limited).
19. Muscle fatigue occurs when muscle fibers run out of available lactate. This situation may cause flexor tendon injuries in horses.
20. All metabolism occurs and changes moment by moment. However, when cells are not metabolically rested, they become stressed and fail. This reduced metabolism decreases energy flux, leading to illness and breakdowns.