Lactate Shuttle Analysis

Power Diagnostics based on the Lactate Shuttle Revolution

Feature by

CDeuker

 

 

1       Content

1     Content

2     Abstract

3     References

4     New Lactate Paradigm

5     Shuttles everywhere

6     Guessing Premise

2       Abstract

The Lactate Shuttle Hypothesis was first published by Brooks in the ’80 [s. Brooks, G. A.; 1985b] with a radical new insight into the concept of muscle physiology: the negation of lactate as a metabolic dead end product of gycolysis due to an oxygen lack during exercise. In experimental testing the appearance of lactate in cells showed very different performance than expected through the concentration in blood. Even in resting situations, oxidative metabolisms of lactate could be found inside cells, as well as in exercise with different loads [s. Brooks, G. A.; 1985a]. Not only had the concept of an anerobic threshold come into discourse with these findings, but more fundamentally the whole explanation of muscle physiology and energy consumption. In the contemporary physiological discourse, lactate shuttles play a central role as ‘cell-to-cell shuttles’ as well as ‘intra-cellular shuttles’ [s. Gladden, L. B.; 2008] and the connection to muscle fatigue and acidosis is discussed [s. Gladden, L. B.; 2004].

All these new insights changed the principle understanding of muscle physiology, setting lactate into a central role of exercise metabolisms [s. Cruz, R. S. d. O., et al.; 2012]. In this feature, these new findings are discussed with a scope to applied exercise physiology in training. Based on these radical new ideas an innovative technique for power diagnostics is proposed.

3       References

Allen, D. G.; Lamb, G. D.; Westerblad, H.; 2008; “Skeletal Muscle Fatigue: Cellular Mechanisms”; 287-332; Physiological Reviews; 88/1;

Brooks, G. A.; 1985a; “Anaerobic threshold: review of the concept and directions for future research”; 22-31; Medicine & Science in Sports & Exercise; 0195-9131; 17/1; http://journals.lww.com/acsm-msse/Fulltext/1985/02000/Anaerobic_threshold__review_of_the_concept_and.5.aspx

Brooks, G. A.; 1985b; “Lactate:Glycolytic End Product and Oxidative Substrate During Sustained Exercise in Mammals — The “Lactate Shuttle””; 208-218; In: Gilles, R.;”Circulation, Respiration, and Metabolism: Current Comparative Approaches”; Berlin, Heidelberg; Springer Berlin Heidelberg

Brooks, G. A.; 2007; “Lactate. Link Between Glycolytic and Oxidative Metabolism”; 341-343; Sports Medicine; 1179-2035; 37/4; http://dx.doi.org/10.2165/00007256-200737040-00017

Brooks, G. A.; 2009; “Cell–cell and intracellular lactate shuttles”; 5591-5600; The Journal of Physiology; 1469-7793; 587/23; http://dx.doi.org/10.1113/jphysiol.2009.178350

Cruz, R. S. d. O.; de Aguiar, R. A.; Turnes, T.; Penteado Dos Santos, R.; Fernandes Mendes de Oliveira, M.; Caputo, F.; 2012; “Intracellular Shuttle: The Lactate Aerobic Metabolism”; 420984; The Scientific World Journal; 1537-744X; 2012/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345575/

Gladden, L. B.; 2004; “Lactate metabolism: a new paradigm for the third millennium”; 5-30; The Journal of Physiology; 1469-7793; 558/1; http://dx.doi.org/10.1113/jphysiol.2003.058701

Gladden, L. B.; 2008; “A “Lactatic” Perspective on Metabolism”; 477-485; Medicine & Science in Sports & Exercise; 0195-9131; 40/3; http://journals.lww.com/acsm-msse/Fulltext/2008/03000/A__Lactatic__Perspective_on_Metabolism.12.aspx

Kindermann, W.; 2005; “Anaerobe Schwelle”; 161-162; Deutsche Zeitschrift für Sportmedizin; 0344-5925; 55/6;

Plowman, S. A.; Smith, D. L.; 2011; “Exercise physiology for health, fitness, and performance”; Philadelphia; Wolters Kluwer Health/Lippincott Williams & Wilkins; 9780781779760, 0781779766

Robergs, R. A.; 2011; “Nothing ‘evil’ and no ‘conundrum’ about muscle lactate production”; 1097-1098; Experimental Physiology; 1469-445X; 96/10; http://dx.doi.org/10.1113/expphysiol.2011.057794

Todd, J. J.; 2014; “Lactate: valuable for physical performance and maintenance of brain function during exercise”; hzu001-hzu001; Bioscience Horizons: The International Journal of Student Research; 7/http://dx.doi.org/10.1093/biohorizons/hzu001

image: LacShut by CDeuker

4       New Lactate Paradigm

The lactate shuttle revolution started with new analytical methods in physiology, indicating that lactate is active in resting muscles as well as in exercise [s. Brooks, G. A.; 1985b; 208]. These findings are in contrast to the classical explanation of lactate appearance because of a lack of oxygen forcing anerobe metabolisms.

Testing lactate appearance under fully oxidative conditions showed that lactate is not only a product of anerobic metabolic methods in contrast to energetically more efficient aerobe processes [s. Brooks, G. A.; 2007; 342] as the classical theory tells. These findings opened the door to a new understanding of power physiology in muscles and denied the dominant and strict separation between aerobic and anerobic metabolism.

Further research showed lactate usage as an energy source in rest as well as in exercise up to 75% of total lactate appearance [Brooks, G. A.; 2007; 342]. The classical explanation saw lactate as a dead end product of anerobe metabolisms in muscles instead. With this idea of lactate as a fuel for the muscle fiber mitochondrion, the classical system of physiological energy supply turned.

And last but not least, testing showed that acidosis and the claimed reduction in muscle work is not due to lactate [s. Robergs, R. A.; 2011; 1097]. All these findings together draw a very different light of lactate and energy physiology in exercise with a new paradigm: the lactate shuttle.

5       Shuttles everywhere

A quite well known cell-to-cell shuttle, that was accepted before the discussions of lactate pyruvate metabolisms as a central issue in muscle physiology, is the Cori Cycle [s. Plowman, S. A.; Smith, D. L.; 2011; 47]. In rest, the liver removes approximately 30% of total lactate concentration decline [s. Gladden, L. B.; 2008; 479] and during exercise the net lactate balance could not be raised due to decreased blood flow in liver reaching up to 25% [s. Brooks, G. A.; 2007; 342].

Lactate usage of the brain and nerves was also detected but in comparison to the whole body uptake of lactate it is negligible [s. Gladden, L. B.; 2008; 479].

Another cell-to-cell shuttle is the net lactate uptake of the myocardial fibers, not quantified in contrast to total lactate balance in the scientific discourse, but demonstrated as a prime example for intra-cellular shuttles. The fibers of the heart are oxidizing lactate up to 60% of total substrate metabolism [s. Gladden, L. B.; 2008; 479].

Also well known before is the lactate uptake of red blood cells. This transfer is proportional to exercise impact but limited with a maximal cap of total usage [s. Todd, J. J.; 2014; 4].

In the center of all these new findings was lactate appearance in muscle fibers. Net lactate turnover during exercise is reported to rise up to an 18 fold increase [s. Todd, J. J.; 2014; 3]. The way of metabolite lactate usage is discussed as the intra-cellular shuttle, the mitochondrial lactate oxidation. Another way of lactate is the cell-to-cell shuttle as the classical well-known directions of lactate but particularly as fueling other muscle tissues.

6       Guessing Premise

Now the thrilling question is how all these new insights affect training and physiological power diagnostics.

In this feature, only the lactate analysis is in focus.

The first and crucial insight is that lactate plays an active key role in muscle physiology and can give major information for training. As lactate is quite easily to detect in blood, this holds new opportunities for effective exercise planning.

The second quite radical finding is that the classical separation between aerobe and anerobe muscle metabolisms are inadequate. This is crucial for training but as well for power diagnostics. The latest scientific discourse tell us, that lactate is a ‘Link between Glycolytic and Oxidative Metabolism’ [Brooks, G. A.; 2007] with new interpretations to lactate concentration and appearance as well as usage in muscle physiology.

The third insight is that the information about lactate concentration in blood is insufficient for muscle physiology. Lactate Shuttles exists in different ways as intra-cellular shuttles and cell-to-cell shuttles. The intra-cellular shuttles are the expression of overturning the aerobe – anerobe separation with a new role of lactate in muscle physiology. The cell-to-cell shuttles indicate that the concentration of lactate in blood is a result of different simultaneous processes of lactate appearance and usage.

Because of these different and coexistent cell-to-cell shuttles, the blood concentration of lactate is not indicating a single process and the quantification is ambivalent. But still the blood lactate concentration is the total result of these different metabolisms, giving chances for analysis. Before describing these basic processes in exercise physiology and drawing relations to the resulting blood lactate level, again the aim of a Lactate Shuttle Analysis has to be emphasized:

With the admittance of lactate shuttles as the central metabolisms in exercise physiology, it is crucial to train these processes for improved performance [s. Brooks, G. A.; 1985a; 27]. Research with treadmill calorimetry and tracer infusion in rats showed little effect of training to lactate production but on oxidative usage [s. Brooks, G. A.; 2009; 5592]. A high quality training with enhanced effectiveness needs observable indications for specifying an improved lactate shuttle appearance.

Because the observation of lactate shuttles during exercise in vivo is only possible in the lab and not in field, the relations of different shuttle processes towards the resulting lactate concentration in blood is the only way to benefit from the contemporary scientific discourse in training.

Central to exercise physiological reasoning are processes in skeletal muscles and their different fiber types. For this purpose here, only the differentiation between slower type I and faster type II fibers is made. No doubt a simplification, but helpful for describing fundamental processes.

In rest, the net lactate balance of different fiber types were analyzed through labeled lactate perfusion showing a conversion of release to uptake at 2.5 mMol for type I fibers and 4 mMol for type II fibers [s. Gladden, L. B.; 2008; 477].

Similar in type but different in form is the net lactate balance of contracting fibers. Starting exercise, lactate is released from fibers, but with an ongoing contraction an increased uptake and a change to net balance clearing is detected [s. Gladden, L. B.; 2008; 478]. Type I fibers release lesser amounts of lactate and highly utilize it than type II fibers during exercise [s. Gladden, L. B.; 2008; 479]. In workloads of 75% VO2max tracer infusion analytics showed a lactate oxidation rate up to 80% [s. Brooks, G. A.; 2009; 5593].

The lactate turnover exceeds the oxidation rate [s. Brooks, G. A.; 1985a; 27] in different workloads and total lactate appearance is also higher than lactate clearance in muscle fibers [s. Brooks, G. A.; 1985a; 28]. This seems to be a universal characteristic for lactate metabolisms indicating the function of cell-to-cell shuttles: providing other tissues with a carbon source for oxidation [s. Cruz, R. S. d. O., et al.; 2012; 1].

With the acceptance of lactate shuttles, we can give new interpretations to the well-known blood lactate analysis in testing with rising workloads as argued in the past for example by Kindermann [s. Kindermann, W.; 2005; 161]. The typically blood lactate curve stays the same with a slight decrease for minimal workloads, a minimal increase for moderate exposures, followed by a medium and then a strong increase for high and highest intensities.

The activation of different fibers through their neuronal motor units is set appropriate to the demanded contractile efforts [s. Allen, D. G., et al.; 2008; 298]. Higher tetanic contraction is related with an extended metabolic rate in different fibers as well as increase in fiber frequentation. Prior to the Henneman’s principle to neuronal motor units, only few fibers are needed for weak contractions, which means vice versa that most fibers are in rest. Perfusion tests show a change to lactate uptake globally [s. Gladden, L. B.; 2008; 477] indicating a similar behavior locally. Besides the cell-to-cell shuttles in skeletal muscles, the Cori Cycle and the shuttles to the heart are active. For minimal workloads this means, that there is a lot of lactate clearance inside muscles because many fibers in rest and additionally the lactate clearance external to muscles. Together these shuttles can decrease the total blood lactate level slightly.

With rising workloads shuttles outside muscles stay constant in terms of relative clearing and the Cori Cycle is shrinking with higher impacts as already mentioned [s. Brooks, G. A.; 2007; 342]. Inside the muscles, more fibers are active and the local clearance through inactive fibers is shrinking. With ongoing activity, the cell-to-cell turnover inside muscles is reduced by 80% oxidation of active fibers. The result of these processes is a minimal increase of net lactate balance. With the distinction of type I and type II fibers, the initial cell-to-cell shuttle inside muscles is caused by type I due to a higher sensitivity to lactate concentration and Henneman’s principal of appropriate activation to contractile demands.

With ongoing workload the type I fiber shuttles characteristic changes from local clearance at rest to oxidation in contraction. As type I fibers are eagerly in lactate oxidation [s. Gladden, L. B.; 2004; 9] the result in total blood lactate concentration is a moderate increase. This blood lactate rise at this point is diminished by local clearance at rest of type II fibers, requiring higher lactate concentrations and it is increased by activation of motor units with a higher metabolic rate for enforced tetanic contractions.

At a specific point of workload, the local clearance in rest of type II fibers has reached a maximum as well as type I shuttles in action. From this point of performance, lactate clearance stays constant as further type II fibers with higher metabolic rates are recruited. The blood lactate increases highly at the rate of intracellular shuttles for oxidation of type II fibers until a maximum.

These are new explanations of blood lactate concentration during exercise and new conclusions for training. Again – with the admittance of lactate shuttles, increased performance is due to enhanced energy metabolisms achieved by training of shuttles. Blood lactate concentrations indirectly show the activity of different shuttles related with muscle fiber performance. This holds the opportunity of setting precise impacts for maximization of different shuttles in fibers. Analyzing the blood lactate development is the precondition for setting effective impacts in training with a lactate shuttle argumentation.