Why does creating a muscle burn make you stronger (I learned something!)

When a muscle is exercising strenuously, glycolytic  (breakdown of glucose in cytoplasm) and oxidative (breakdown of glucose in mitochondria) pathways lead to multiple metabolites. Some of those include lactate, succinate, and H+. 

With exercise, the pH of the cytoplasm of muscle cells becomes more acidic, thus, more muscle burn. This helps add an H+ (protonate) to lactate and succinate molecules. Protonation eases their transport across the cell membrane and into the surrounding tissues, carrying the proton with them. In effect, lactate and succinate help reduce the acid load in the cell. Once the protonated molecules are outside the muscle, lactate and succinate moieties are regenerated and the H+ ions are disposed of.

Interestingly, succinate and lactate are highly valuable molecules. Some of us think of lactic acid as a waste product of exercise. But lactate (the unprotonated form of lactic acid) and succinate are like gold. They have positive effects locally and throughout the body (4, 5, 6, 7). Let's see how.

Exercising muscle cells releases succinate from their mitochondria. However, the succinate is stuck within the cell unless one of its carboxylate groups is protonated. The excess acid in the cell produced in the cytoplasm protonates the molecule allowing it to be released to the outside of the muscle cell.

The released succinate then activates nerves and other non-muscle cells inducing both remodeling of the muscle as well as remodeling the matrix surrounding the cells. Succinate, in effect, is acting as a stimulant to the nerves and the muscles. This leads to increased muscle strength with exercise (4, 5).

Keep in mind that too much of a good thing can be bad. When there is too much acid - for example, with ischemic muscle - the cells' capacity to get rid of the excess acid is overrun and the cell dies (8).

How about lactate? Lactate has local effects on the tissues and the nerves (7, 9, 10, 11).  Thus, regular exercise when repeated will increase the production of new mitochondria within muscle (9).  

Lactate produced by the muscle is also used by major organs as a fuel energy source (for example, the heart muscle and the brain). During exercise, the lactate produced by skeletal muscle is taken up by multiple tissues, in addition to the endothelial cells lining the arteries. Interestingly, with continued exercise, skeletal muscles change from producers of lactate to consumers! They start using the serum lactate as an energy source.

In point of fact - and this is not a well-known fact - many major organs (liver, heart, brain) prefer using lactate as an energy source compared to glucose (11).

Lactate as a youth-promoting molecule

Lactate promotes the expression of a number of genes that  keep the body healthy, including preventing stem cell dysfunction. Keeping one's stem cells young and vibrant is critical to preventing aging (9, 12). The lactate produced through exercise also has positive effects on the brain (helping the hippocampal mitochondria, for example, as well as improving microcirculation) (10, 11).

Not only does lactate serve as a fuel source and a signaling molecule, it also regenerates glucose in the liver as well as other organs (7, 10). Given the positive effects on neurons and cardiac tissues, lactate solutions are being investigated as a means of reducing neuronal damage in traumatic brain injury as well as helping cardiac muscle cells in heart failure (13).

Muscle burn and producing lactate and H+ is a good thing. Lactate is a metabolic connection between exercising muscle and the rest of the body, nudging tissues and organs into healthier processes (9, 11). 

Let's look at exercise effectiveness. Should one maximize the muscle burn? Here are several factors that relate to effective exercising. 

The first has to do with stimulating the stem cells in muscle to proliferate. Studies have shown that using eccentric contraction (the action of relaxing the muscle slowly while still holding the weight) increases stem cell numbers. The second has to do with producing the high levels of lactate for a given exercise. High intensity endurance training cycle pushes those stem cells to differentiate into muscle cells ((6, 12).

Endurance training: The emphasis on shuttling lactate across membranes

Keep in mind that it is not only the level of lactate that is important, but rather the ability to mobilize lactate out of the muscle to the rest of the body. Thus, the third factor has to do with the efficiency of moving lactate in and out of the cells (14, 15). Exercise seems to increase the number of lactate protein transporters (MCTs) in skeletal muscle (14). However, what is likely more important is each transporter's inbuilt effectiveness at mobilizing lactate. 

Some people are born with lactate transporters that are highly efficient compared to others. When that is the case, they accumulate  lower blood lactate levels, even with intense exercise. Lower blood lactate levels translates into skeletal muscles being able to shuttle lactate and H+ more effectively out of the muscle, leading to delayed onset of muscle fatigue (15). In this regard, runners of African descent have a lactate transporter that is seemingly highly efficient at keeping the blood lactate levels lower during endurance-focused exercise (15). 

Exercise creates a positive web of connections between skeletal muscle and the rest of the body's organs. With exercise. skeletal muscle revs up production of multiple metabolites (lactate, succinate, and H+). The acid that is produced gives our familiar muscle burn. It also facilitates the release of succinate and lactate into the blood stream.

Those metabolites stimulate the muscle to become stronger; they also activate distant tissues to produce health-promoting genes. The result is improved muscle function and structure as well as a healthier circulation, heart muscle cells, brain neurons, and liver cells. 

Furthermore, with endurance training, cells become even more adept at producing, shuttling, and consuming lactate. The net effect is a stronger and more vibrant organism.

What can we learn?

I wasn't aware of the connections that lactate has with the brain and the heart and the liver. I didn't know that our major organs have a preference for lactate over glucose. I hope that reading the research will make you as motivated to amp up your exercise  as it has made me - particularly with the clear effect of lactate on the neurons.