If someone were to mention the word ‘lactate’ in conversation, you might be inclined to think about why people have stitches in their sides after running.
Classical secondary and tertiary education has taught us that lactate is a kind of muscle-cell waste product that may also be a marker of stress or illness. However, the study of this versatile biochemical product has experienced a considerable upheaval. This concern is due to the re-examining of some possibly faulty correlations made about the molecule and its roles in health and disease.
For example, when this event was first observed in conjunction with muscle cells following exertion, it was assumed that lactate was a waste product resulting from the use of glucose as fuel. Now, it seems that lactate may have been the actual fuel all along.
These new findings have opened many avenues for lactate in the arenas of emerging therapies and sports-performance optimization.
Lactate, Muscles and Exercise
Lactate in human biology often went along these lines: lactate has been observed to be the end-products of anaerobic exercise, which is carried out in conditions of reduced oxygen supply. Therefore, it may be a sign of activity in damaged or oxygen-starved muscle. In conclusion, lactate is deleterious and possibly even toxic to muscle tissue. It is true that lactate has been associated with stress in some studies.
Newer research has shown that lactate is produced as a result of glycolysis in healthy, functional tissues. This means that lactate is likely to be produced under aerobic conditions. It is also possible that this product has a role in mitochondria, the ‘power stations’ of cells.
It appears now that cells can convert pyruvate (a by-product of glucose metabolism) into lactate, which then passes into mitochondria and signals them to initiate gluconeogenesis, a process that converts a number of raw materials (lactate included) into new glucose molecules for energy.
Furthermore, lactate has been found to have a role in normal cellular signaling processes.
Lactate is also produced as a result of the breakdown of glycogen (the body’s medium-term energy stores), in addition to glucose. Finally, some of the lactate in mitochondria is metabolized to produce energy directly.
Lactate is thought to be produced and used by the body during exercise. (Source: Amanda Mills, USCDCP @ pixnio.com)
This new theory of lactate use is known as the Lactate Shuttle Theory of Cellular Energetics. The researcher most strongly associated with this new dimension of metabolism is George Brooks, a professor of integrative biology at the University of California (Berkeley). He produced the basis for the theory by conducting experiments that tracked the behavior and use of radio-labeled lactate in the bodies of animals and human subjects.
Brooks' research led to a vast improvement in the understanding of lactate’s role in physiology, and also cleared up some basic contradictions included in the older theories on the same subject. For example, some studies showed that lactate was being transferred between cells producing energy and other cells in need of it.
Why would this be, if lactate was a useless and potentially dangerous waste product? We now know this happens to confer more energy, as well as the means to make more of its own, on the ‘receptive’ cells.
Further research has found that dietary lactate can be absorbed into the bloodstream faster and more efficiently compared to dietary glucose. This work may result in a significant re-think for those who produce ‘sports’ and ‘energy’ products, which normally deliver glucose or other simple sugars such as fructose.
Other studies have resulted in a re-assessment of lactate’s role as a stress biomarker. It is also likely that elevated lactate levels indicate recent exertion rather than stress, and merely suggest that the body is being exerted or challenged in a training or conditioning context.
Lactate and the Brain
Glucose has also been seen as the main source of energy for the brain. This has been exploited to remarkable effect by sports-drinks manufacturers down the years. Therefore, when lactate was discovered to be present in brain tissue, it was (again) investigated in the context of possible biomarkers of injury or stress in the organ.
However, today, brain lactate has been found to be a probable source of energy, as well as a substance that acts as a cellular signaling molecule. For example, lactate may be exchanged between astrocytes (cells that support functional nerve cells) and other cell types in the brain in a preferential manner compared to glucose.
Some studies have even indicated that lactate may be neuroprotective and is released in order to protect injured or damaged brain tissue.
On the other hand, elevated lactate in the blood is also associated with reduced intestinal integrity. This biomarker has been detected in patients who have experienced an ischemic stroke and may suggest that the body’s responses to such an event may result in adverse effects for the gastrointestinal system.
Nevertheless, lactate is currently being considered as a new clinical intervention for patients with acquired brain damage.
Lactate Monitoring: The Health Metric of the Future?
Accordingly, new biosensors that test and track lactate levels may become more medically relevant in the future.
A team of researchers from a Beijing university has proposed their newly-developed sensor that measures this molecule, as well as glucose, in a recent issue of the journal Sensors (Basel).
This sensor is made of graphite and silver/silver chloride inks, into which enzymes that bind to glucose and lactate are also incorporated. This paintable sensor (which can also act as an electrode) can be applied to the inside of sample-collection tubes for convenient and accurate lactate sensing.
The graphite (a) and Ag/AgCl (b) lactate-sensing electrodes painted onto the insides of clear tubes. (Source: W. Shi, et al., 2018)
Lactate was once seen as a possible marker of tissue injury or stress. As a result, it had a negative reputation in areas such as biological research, sports science, and neurology.
However, a re-assessment of lactate's various roles in the body has led to its reimagining as a viable bio-energy source and metabolic regulator.
Lactate is also now under investigation as a putative, next-generation therapeutic, in disciplines such as post-brain injury rehabilitation. It may also be possible to track health – as well as the response to exercise – through lactate monitoring.
In other words, this simple molecule may have an important role in the future of medicine and athletic performance.
Top Image: Stick/vector model of the molecular structure of lactate. (Source: Naik M – Inkspace)
C. R. Camara-Lemarroy, et al. (2018) D-Lactate and intestinal fatty acid-binding protein are elevated in serum in patients with acute ischemic stroke. Acta Neurol Belg.
G. A. Brooks. (2018) The Science and Translation of Lactate Shuttle Theory. Cell Metabolism. 27:(4). pp.757-785.
W. Shi, et al. (2018) A Tube-Integrated Painted Biosensor for Glucose and Lactate. Sensors (Basel). 18:(5).
P. Bouzat, et al. (2014) Lactate and the injured brain: friend or foe? Curr Opin Crit Care. 20:(2). pp.133-140.
Rehabilitating lactate: from poison to cure, UC Berkerly News, http://news.berkeley.edu/2018/05/23/rehabilitating-lactate-from-poison-to-cure/ , (accessed 27 May 2018)