To understand the unique metabolism of the heart and its role in keeping the heart healthy, we first have to discuss some background information. Humans, as well as all mammals, have what is called an Autonomic Nervous System (ANS). It is the aspect of our nervous system that is monitoring our external environment to determine if we are in a safe or threatening situation. Depending on which it is, it will tell your body to have the appropriate reaction. Rest/relax or run away/defend yourself.
There are two aspects to the mammalian ANS, the sympathetic and parasympathetic, and dominant stimulation of one or the other tells your body which response to have in a given situation. The sympathetic is the “fight or flight” aspect that is used to helps us fight off or flee from a threatening situation, while the parasympathetic is the “rest and digest” aspect that takes over when everything is “safe” and we can focus on digestion, metabolism, sleeping, socializing, etc.
The information for the ANS is communicated in the nervous system through one of the cranial nerves called the vagus nerve. The part of the vagus nerve associated with the sympathetic signal is called the dorsal motor nucleus (DMN) and the part associated with the parasympathetic aspect is called the nucleus ambiguous (NA) (1). Below is a cross section of the spinal cord showing the different areas of the nerve.
But this dual vagus nerve system wasn’t always this way. Most reptiles, and anything that evolved before reptiles, had a single vagus nerve tract. The dorsal motor nucleus was the only aspect of the vagus nerve in these animals. Because the animals were very metabolically slow (think cold blooded like reptiles) this was all they needed. If they had an extreme stress response that overstimulated the vagus nerve it would cause their body to severely slow down. They would have slowed breathing and slowed heart rate (bradycardia). It was almost like a play dead defense mechanism for them.
Now, fast forward to higher evolved reptiles, like crocodiles and some turtles, and we start to see evidence of a split in the vagus nerve. This began to happen because these animals were becoming more active and metabolically demanding. If you tried to slow down bodily systems during a stress response in these animals, it would not end up well for them. This is because in these more active animals slowing down metabolism and blood flow would result in decreased oxygen to tissues, or hypoxia.
When mammals finally appear on the evolutionary scene (about 225 million years ago), we now see the complete split of the vagus nerve into the dorsal motor nucleus and the nucleus ambiguous, like we humans have today. Mammals are much more metabolically demanding than any living thing that evolved before them. This split of the vagus nerve into two pathways is what allowed mammals to become so metabolically demanding (running, quick movements, warm blooded) while retaining the ability of our Autonomic Nervous System to trigger a stress response to get away from something threatening without overstimulating metabolism and shutting down our very metabolically demanding organ systems.
If mammals had maintained the single dorsal motor nucleus pathway of the vagus nerve while evolving higher metabolically demanding organ systems, then when they had an overstimulating stress response the single tract dorsal motor nucleus would have tried to slow the metabolism of the organ systems just like it did in the reptiles and pre reptile animals. The highly metabolically active organ systems of mammals would not tolerate this, and it would likely cause shut down of organ systems and likely death.
Those older evolved species, without a split pathway, had a physiology that allowed them, in certain situations, to severely slow metabolism and blood flow (creating oxygen deprivation, or hypoxia, and metabolite deprivation) without cause harm to their tissues. In order to become more metabolically active, higher evolved reptiles, and then mammals, lost this ability in exchange for being faster, stronger, warmer, and bigger. However, there are a few species, that we know of, that seem to have held on to the ability to severely slow metabolism and not cause damage. A look into their metabolic physiology can help us understand what goes wrong with ours in chronic disease.
One animal that can do this is the common goldfish. It has been observed that during the winter, when water temperatures are very cold, goldfish can survive several days without any oxygen at all. Without oxygen, the fish are forced to use anaerobic glycolysis to produce energy. If done for too long this would usually cause an increase in lactic acid production causing damage. How does the fish get around this? While the complete mechanisms by which it does this are not completely fleshed out, scientists believe that the ability to do this comes from the ability of these fish to convert lactate into ethanol and excrete is very easily through their gills. It has also been observed that they do not always produce the acidic product of lactate during anaerobic glycolysis but instead produce other neutral substances. (2)
Another species of fish (carp), displays similar metabolic characteristics. When scientist put carp in a no oxygen environment they survived for 6 hours, and potentially longer because when they stopped the test the fish were still doing fine. It was determined that these fish also did this by easily converting lactate to ethanol and efficiently excreting it through their lungs into the water. They also made less lactate by instead making more neutral by-products of metabolism. (3)
Another example is North American freshwater turtles. In a low or no oxygen environment that requires these turtle to rely on anaerobic glycolosis, instead of being able to convert the excess lactic acid to ethanol like the fish, these turtles have mechanisms that buffer that lactic acid in the blood by releasing very alkaline calcium bicarbonate from their shells. (4)
That’s pretty fascinating! All these animals have evolved mechanisms that allow them to survive in low oxygen conditions. But the first three were two fish and a reptile, which evolved 530 million years ago, well before mammals. So, it is understandable that some fish would have these evolved characteristics to survive long bouts of time in without oxygen. However, one last example is a mammal.
That mammal is the naked mole rat. When faced with environments of very low or no oxygen, mammals can make a few physiologic adaptations to help them survive, one of them is anerobic glycolysis. However, since ATP is used up so quickly, most vertebrates can only live a few minutes in an anoxic environment. The fish previously discussed severely lowered their body temperature and had slight alterations in their metabolism that allowed them to do this, but a warm-blooded mammal, like a naked mole rat, theoretically cannot lower their body temperature too much without problems. Yet naked mole rats are able to withstand low oxygen environments, as is summarized by this quote from a research article:
“Park et al. observed that naked mole-rats can tolerate an atmosphere of 5% oxygen for 5 hours without undue stress, whereas mice (Mus musculus) died of asphyxiation in <15 min. Under complete anoxia (0% oxygen), mice and naked mole-rats both quickly lost consciousness. However, whereas mice quickly passed the point of no return and could not be resuscitated even when reexposed to ambient air (21% oxygen) within a minute of the initial anoxia exposure, the naked mole rats fully recovered from 18 min of complete anoxia.” (5)
One mechanism by which they do this is that rather than using glucose for fuel in anerobic glycolysis the mole rats evolved a way to use fructose instead. The advantage to this is that by using fructose it can by-pass certain steps in metabolism that serve as negative feedback loops that signal to the physiology that too much anerobic glycolysis is being done and lactate acid is in danger of being in excess. This allows the mole rats to keep making energy. As far as how mole rats deal with the increased lactate that is produced, the best researchers have to offer is that mole rats can severely depress their metabolism:
“We found that NMRs exhibit robust metabolic rate depression in acute hypoxia, accompanied by declines in all physiological and behavioral variables examined. However, blood and tissue pH were unchanged, and tissue concentrations of ATP and phosphocreatine were maintained. NMRs increased their reliance on carbohydrates in hypoxia, and glucose was mobilized from the liver to the blood.” (6)
Now, how does this information help us determine what causes chronic disease. For one thing, humans, and other mammals, do not have the unique capabilities of the mole rat. But humans and other mammals also do not live in the low oxygen environments of subterranean dwellings that the mole rat does either. Most mammals don’t experience issues resulting from excess lactic acid production, but humans seem to.
I have discussed in previous blogs how when the series of events that happen due to not being fat adapted, oxidative stress that depletes Nitric Oxide, and an imbalanced autonomic nervous system then a heart attack can occur. This is ultimately the result of altering metabolism of the heart tissue that results in an increase in lactic acid production that causes damage. Considering that the most metabolically active organs in the body are the kidney, brain, and heart (7) and these are the most common places to see infarction in the body (renal infarction, stroke, and heart attack), I think that ischemia from infarction in many cases is a metabolic issue where certain tissues in the body become too reliant on glucose for fuel.
There is something called The Metabolic Theory of Blood Flow Regulation. This suggests that when we have increased metabolism to an area, we will also have increased waste products from that metabolism. These waste products (carbon dioxide, hydrogen ions, and lactate) need to be evacuated from the area in a timely manner. (8) However, when too many are present this can result in the dilation of blood vessels, this slows blood flow tremendously and can cause a swelling of “dirty” blood in the area. This blood is low in oxygen which forces the area into anerobic glycolysis. Since anerobic glycolysis is less efficient and produces more waster products than oxidative phosphorylation (9), the tissue is unable to maintain proper physiologic function.
Since humans do not have any of the protective mechanisms that the other species we discussed have, then this situation can often result in tissue death. This is seen superficially in poorly control diabetics when the tissue of their limbs starts to die and they require amputation. Or it can happen in the organs, especially the very metabolically active organs like the kidney, brain, and heart that are very dependent on proper and efficient metabolism.
The increase in waste products in tissue is initiated by a carbohydrate-based metabolism. (10) This is evident because burning primarily carbohydrates for fuel results in more waste products than burning fatty acids or ketones. (11,12) While I don’t know too much about how this happens in the kidney or the brain (though I believe there is a reason that ketones can cross the blood brain barrier and supply the brain with a fuel source) I do think that I have worked out how this can happen in the heart.
It is well known that heart cells do not have the ability to divide and repair themselves when damaged. It is thought that they lose their ability to do this as a sort of trade-off for being so metabolically active. Because of this, I think that while the heart in mammals did not evolve the mechanisms to cope with increased lactate production when it happened like the other animals we discussed, instead the body developed mechanisms to ensure that the heart never had to rely primarily on glucose. These are the, more or less, direct delivery of fatty acids that we eat to the heart through chylomicrons in the lymphatic system. As well as a direct means of communication between the heart and fats cells so that the signal to mobilize fats can be given on a moment’s notice. (13)
As much as evolution tried, however, the mechanism to keep the heart burning primarily fat has proven to not be enough to protect the heart. The rapid change in way of life over the recent history of humans that have bypassed these mechanisms and resulted in the physiologic imbalances that can cause a heart attack. Again, those are a carbohydrate-based metabolism, oxidative stress that depletes Nitric Oxide, and an imbalance in the Autonomic Nervous System. I discuss in detail how the mechanisms that those imbalances cause result in a heart attack in my post “It’s Not Blockages, So What Really Causes Heart Attacks?”
Bringing this back to what we started off talking about. I think metabolically the heart is well evolved to ensure it doesn’t use too much glucose for fuel. However, the heart is unavoidably tied to our emotions and I do not think the heart was prepared for the sudden imbalance in our Autonomic Nervous System that so many people experience within our modern-day, unnaturally stressful world. Therefore, unbalanced stress responses to our emotion sensing organ can trigger a sudden surge in glucose metabolism in the heart and lead to the metabolic and blood flow issues we have discussed in this post.
The way to prevent this is to restrict carbohydrates enough to have a fatty acid and ketone base metabolism (at least most of the time), reduce oxidative stress to preserve Nitric Oxide by avoiding toxins and sticking to a fat based metabolism, and finding ways to balance your autonomic nervous system like contact with nature, community, hot and cold therapy, mediation, and loving relationships.
Stay healthy out there!
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