Universal Principle of Cellular Energy

“I started my work with progesterone and related hormones in 1968. In papers in Physiological Chemistry and Physics (1971 and 1972) and in my dissertation (University of Oregon, 1972), I outlined my ideas regarding progesterone, and the hormones closely related to it, as protectors of the body’s structure and energy against the harmful effects of estrogen, radiation, stress, and lack of oxygen.

The key idea was that energy and structure are interdependent, at every level.

Since then, I have been working on both practical and theoretical aspects of this view. I think only a new perspective on the nature of living matter will make it possible to properly take advantage of the multitude of practical and therapeutic effects of the various life-supporting substances–pregnenolone, progesterone, thyroid hormone, and coconut oil in particular.”

“Life interposes itself between the “poles” of energy flow, and the flowing energy creates organization and structure, as it is dissipated into heat. Structures store some of the energy, and tend to increase in complexity, taking advantage of the flow of energy to create phase differences with expanded internal surfaces, like a finely mixed emulsion. Like a finely divided emulsion, the more highly energized the organism is, the stabler it is.”

“It seems that all of the problems of development and degeneration can be alleviated by the appropriate use of the energy-protective materials. When we realize that our human nature is problematic, we can begin to explore our best potentials.”

“A high level of respiratory energy production that characterizes young life is needed for tissue renewal. The accumulation of factors that impair mitochondrial respiration leads to increasing production of stress factors, that are needed for survival when the organism isn’t able to simply produce energetic new tissue as needed. Continually resorting to these substances progressively reshapes the organism, but the investment in short-term survival, without eliminating the problematic factors, tends to exacerbate the basic energy problem.”

“The biological idea of stress refers to the difficulty of adapting, and this involves energy, structure, and insight/orientation. Given enough energy, we can often adjust our structure to achieve full adaptation, and with insight, we can minimize the amount of energy and structural change needed, for example just by a change of pace or rhythm.”

“The metabolic interpretation of disease that had been making progress for several decades was suddenly submerged when government research financing began concentrating on genetic and viral interpretations of disease.”

“The availability of energy is central to our stable functioning, and the need for energy powerfully modifies our functioning.”

“Stress is an energy problem, that leads to the series of hormonal and metabolic reactions –lipolysis, glycolysis, increased serotonin, cortisol, estrogen, prolactin, leaky capillaries, protein catabolism, etc.”

“There is a repolarization of the cell after the production of ATP and CO2; the cell then gets ready to make more energy. Essentially the cell should be in a relaxed state as it gathers all of its forces to make energy. It then makes energy and goes back into its readiness state.”

“The intensity of oxidative metabolism is the basic factor that permits continuing coordination of activity, and harmonious renewal of all the components of the organism.”

“If we optimize the known factors which improve energy production (red light, short-chain and medium-chain saturated fats, and pregnenolone, for example), to the extent that our metabolism resembles that of a ten year old child, I don’t think there is any reason to suppose that we wouldn’t have regenerative, healing abilities which are common at that age.”

“In every type of tissue, it is the failure to oxidize glucose that produces oxidative stress and cellular damage.”

“Energy metabolism is the central biochemical issue.”

“Energy generates order and maintains it. Destruction of order degrades the ability of cells to produce energy.”

“Metabolic energy is fundamental to the development and maintenance of the body, and to the “ways in which living beings react to changed circumstances.” It’s an obvious first thing to consider when thinking about any “disease,” whether it’s cancer, radiation, sickness, dementia, depression, or traumatic injury.”

“The regulation of cell renewal probably involves all of the processes of life, but there are a few simple, interacting factors that suppress renewal. The accumulation of polyunsaturated fats, interacting with a high concentration of oxygen, damages mitochondria, and causes a chronic excessive exposure to cortisol. With mitochondrial damage, cells are unable to produce the progesterone needed to oppose cortisol and to protect cells.

Choosing the right foods, the right atmosphere, the right mental and physical activities, and finding the optimal rhythms of light, darkness, and activity, can begin to alter the streaming renewal of cells in all the organs. Designing a more perfect environment is going to be much simpler than the schemes of the genetic engineers. “

“Aging is an energy problem, and in the brain, which has extremely high energy requirements, interference with the energy supply quickly causes cells to die.”

“The balance between what a tissue needs and what it gets will govern the way that tissue functions, in both the short term and the long term. When a cell emits lactic acid and free radicals and the products of lipid peroxidation, it’s reasonable to assume that it isn’t getting everything that it needs, such as oxygen and glucose. With time, the cell will either die or adapt in some way to its deprived conditions.”

“The needs on the cellular level guide the organism’s adaptation.”

“Many of the anti-adaptive features of old blood can be reduced. Long daylight hours and high altitude (the altitude “lactate paradox” is an example of a cellular oxidative increase caused by lower oxygen pressure) shift the balance of some of the factors, and others can be improved by modifying the diet, and supplementing with things such as the protective steroids, thyroid hormone, aspirin, niacinamide (which can increase the oxidized state of NADH/NAD+), and caffeine. Providing the things needed for cellular energy while blocking some of the maladaptive factors approaches the problem of aging in a fundamental and holistic way.”

“In the excessively sensitive condition produced by hypoglycemia, several things happen that contribute to the maladaptive exaggerated inflammatory response. Adrenaline increases in hypoglycemia, and, if the adrenaline fails to convert glycogen into glucose, it will provide an alternative fuel by liberating free fatty acids from fat cells. If the liberated fatty acids are unsaturated, they will cause serotonin to be secreted, and both serotonin and the unsaturated fatty acids will suppress mitochondrial respiration, exacerbating the hypoglycemia. They will stimulate the release of cytokines, activating a variety of immunological and inflammatory processes, and they will cause blood vessels to become leaky, creating edema and starting the first stages of fibrosis. Both adrenaline and serotonin will stimulate the release of cortisol, which mobilizes amino acids from tissues such as the large skeletal muscles. Those muscles contain a large amount of cysteine and tryptophan, which, among other effects, suppress the thyroid. The increased tryptophan, especially in the presence of free fatty acids, is likely to be converted into additional serotonin, since fatty acids release tryptophan from albumin, increasing its entry into the brain. Free fatty acids and increased serotonin reduce metabolic efficiency (leading to insulin resistance, for example) and promote an inflammatory state.”

“When the available energy doesn’t meet the cell’s energy requirements, if the cell isn’t quickly killed by stress, it will use some adaptive mechanisms, stopping some repair processes to reduce energy expenditure, possibly stopping specialized functions to reduce energy needs. Fibrotic changes occur as a result of defensive reactions in stressed cells, usually following long periods of fatigue and inflammation.”

“When cells are in an energy deficient state, as in hypothyroidism, they are in the leaky edematous state.”

“Szent-Gyorgyi observed that, although ATP was involved in the contractions of muscles, its post-mortem disappearance caused the contraction and hardening of muscle known as rigor mortis. When he put hardened dead muscles into a solution of ATP, they relaxed and softened. The relaxed state is a state with adequate energy reserves.”

“Cells in their excited and exhausted state are increasingly open to penetration of toxins because of their own increased permeability and because of the increased leakiness of the blood vessels. Certain environmental toxins accumulate more rapidly as the cells lose their ability to destroy them. Several kinds of toxins, including unsaturated fats, inhibit the proteolytic enzymes that remodel tissue, and reduce the ability to dismantle and rebuild the cellular matrix.”

“Sugar can be used to produce energy with or without oxygen, but oxidative metabolism is about 15 times more efficient than the non-oxidative “glycolytic” or fermentive metabolism; higher organisms depend on this high efficiency oxidation for maintaining integration and normal functioning: If there is a small interference with respiration, the organism can adapt by increasing the rate of glycolysis, but there must be enough sugar to meet the demand. A response to stimulation is the production of more energy, with a proportional increase of oxygen and sugar consumption by the stimulated tissue; this produces more carbon dioxide. which enlarges the blood vessels in the area, providing more sugar and oxygen. If the irritation becomes destructive, efficiency is lost: oxygen is either consumed wastefully, causing blueness of the tissue (assuming circulation continues: blueness can also indicate bad circulation), or is not consumed. causing redness of the tissue. As more sugar is consumed in compensation, lactic acid also enlarges the blood vessels.

If the inflamed or exhausted tissue is small, the lactic acid can be consumed by other oxidizing tissues, sufficient sugar usually can be supplied, and repair occurs. But a large inflammation. or profound exhaustion, will lower the blood sugar systemically, and will deliver large amounts of lactic acid to the liver. The liver synthesizes glucose from the lactic acid, but at the expense of about 6 times more energy than is obtained from the inefficient metabolism – so that organismically, that tissue becomes 90 times less efficient than its original state. Besides this, an idle destruction of energy molecules (ATP or creatine phosphate) will increase the wastefulness even more.”

“The loss of control over water in the body is a result of energy failure…”

“As in other cells, ATP maintains the proper water content of cells.”

“…the essential element of stress is the inadequacy of energy to meet a challenge, and when energy is inefficient water is taken up.”

“When respiration is blocked tissues take up water.”

“Stress increases metabolic rate in a destructive, age accelerating way, with increased inflammation, and decreased resting oxidative metabolic rate. It’s the basic metabolic rate, with fast nerve conduction, quick cellular adaptation, etc., that’s biologically valuable.”

“The result of these passive and active processes is that each kind of ion has a characteristic concentration in each compartment, according to the metabolic energy state of the organism. 

Magnesium and potassium are mainly intracellular ions, sodium and calcium are mainly extracellular ions. When cells are excited, stressed, or de-energized, they lose magnesium and potassium, and take up sodium and calcium. The mitochondria can bind a certain amount of calcium during stress, but accumulating calcium can reach a point at which it inactivates the mitochondria, forcing cells to increase their inefficient glycolytic energy production, producing an excess of lactic acid. Abnormal calcification begins in the mitochondria. 

When cells are stressed or dying, they take up calcium, which tends to excite the cells at the same time that it inhibits their energy production, intensifying their stress. A cramp or a seizure is an example of uncontrolled cellular excitation. Prolonged excitation and stress contribute to tissue inflammation and fibrosis.

Gross calcification generally follows the fibrosis that is produced by inflammation.

Arteries, kidneys, and other organs calcify during aging. At the age of 90, the amount of calcium in the elastic layer of an artery is about 35 times greater than at the age of 20. Nearly every type of tissue, including the brain, is susceptible to the inflammatory process that leads through fibrosis to calcification. The exception is the skeleton, which loses its calcium as the soft tissues absorb calcium.

These observations lead to some simplifying ideas about the nature of aging and disease.

Some people who know about the involvement of calcium in aging, stress, and degeneration suggest eating a low calcium diet, but since we all have skeletons, dietary calcium restriction cant protect our cells, and in fact, it usually intensifies the process of calcification of the soft tissues. Statistics from several countries have clearly shown that the mortality rate (especially from arteriosclerotic heart disease, but also from some other diseases, including cancer) is lower than average in regions that have hard water, which often contains a very large amount of either calcium or magnesium.”

“Much of the intracellular magnesium is complexed with ATP, and helps to stabilize that molecule. If cellular energy production is low, as in hypothyroidism, cells tend to lose their magnesium very easily, shifting the balance toward the lower energy molecule, ADP, with the release of phosphate. ADP complexes with calcium, rather than magnesium, increasing the cells calcium content.”

“Degenerative diseases, especially cancer, heart disease, and brain diseases, are less prevalent in populations that live at a high altitude. When oxygen pressure is low, the lungs lose carbon dioxide more slowly, and so the amount of carbon dioxide retained in the body is greater. If the basic problem in hypothyroidism is the deficient production of carbon dioxide causing excessive loss of salt and retention of water, resulting in hypo-osmotic body fluids, then we would expect people at high altitude to have better retention of salt, more loss of water, and more hypertonic body fluids.”

“Since respiratory metabolism, governed by the thyroid hormone, is our main source of carbon dioxide, it’s obvious that thyroid deficiency should impair our ability to regulate water and solutes, such as salt.”

“The degenerative diseases can be seen as the cumulative result of stress, in which tissue damage results from the diabetes-like impairment of energy production.”

“Any stress or energy deficit that disturbs cellular structure or function disturbs the interactions among water, proteins, and other components of the cell. Excitation causes a cell to take up extra water, not by osmosis resulting from an increase in the concentration of solutes in the cell, or because the membrane has become porous, but because the structural proteins of the cell have momentarily increased their affinity for water.

This increased affinity is similar to the process that causes a gel to swell in the presence of alkalinity, and it is related to the process called electroosmosis, in which water moves toward a higher negative charge. Intense excitation or stress increases the cell’s electrically negative charges, and causes it to become more alkaline and to swell. Swelling and alkalinity cause the cell to begin the synthesis of DNA, in preparation for cell division.”

“The higher rate of metabolism produced by adequate thyroid function maintains a high rate of renewal of the cell’s systems, keeping the cell constantly adjusted to slight changes in the organism’s needs.”

“In hypothyroidism and diabetes, respiration is impaired, and lactic acid is formed even at rest, and relatively little carbon dioxide is produced. To compensate for the metabolic inefficiency of hypothyroidism, adrenalin and noradrenalin are secreted in very large amounts. Adrenalin causes free fatty acids to circulate at much higher levels, and the lactic acid, adrenalin, and free fatty acids all stimulate hyperventilation. The already deficient carbon dioxide is reduced even more, producing respiratory alkalosis. Free fatty acids, especially unsaturated fats, increase permeability of blood vessels, allowing proteins and fats to enter the endothelium and smooth muscle cells of the blood vessels. Lactic acid itself promotes an inflammatory state, and in combination with reduced CO2 and respiratory alkalosis, contributes to the hyponatremia (sodium deficiency) that is characteristic of hypothyroidism. This sodium deficiency and osmotic dilution causes cells to take up water, increasing their volume.”

“Thyroid, which opposes estrogen’s effects on cell energy, stimulates oxidative metabolism with the production of carbon dioxide, and reduces the water content of tissues.”

“Estrogen seems to work by blocking oxidative metabolism, and its first visible effect is to cause the stimulated tissue to take up water. Anything that causes cells to take up water seems to stimulate cell division.”

“This is where the issue of cell water comes in. Carbon dioxide, produced by oxidative cell metabolism, is associated with the high energy state of the cell. When something interferes with oxidative metabolism, lactic acid is produced instead of carbon dioxide. If the cell stays very long in this low oxygen state, it swells, taking up water. (The fatigued muscle, for example, can take up so much water in a short time that it weighs 20% more than before it began working so intensely that its energy needs far exceeded the availability of oxygen. This swelling is what causes the soreness and tightness of intense exercise. The swelling persists long after the liver has cleared the lactic acid from the blood.) This swelling from taking up water is involved in one type of “edema,” and in inflammation, or activation of the cells by hormones, as well as by simple oxygen deprivation.”

“Lactate formation from glucose is increased when anything interferes with respiratory energy production, but lactate, through a variety of mechanisms, can itself suppress cellular respiration. (This has been called the Crabtree effect.) Lactate can also inhibit its own formation, slowing glycolysis. In the healthy cell, the mitochondrion keeps glycolysis working by consuming pyruvate and electrons (or “hydrogens”) from NADH, keeping the cell highly oxidized, with a ratio of NAD+/NADH of about 200. When the mitochondrion’s ability to consume pyruvate and NADH is limited, the pyruvate itself accepts the hydrogen from NADH, forming lactic acid and NAD+ in the process. As long as lactate leaves the cell as fast as it forms, glycolysis will provide ATP to allow the cell to survive. Oxygen and pyruvate are normally “electron sinks,” regenerating the NAD+ needed to produce energy from glucose.

But if too much lactate is present, slowing glycolytic production of ATP, the cell with defective respiration will die unless an alternative electron sink is available. The synthesis of fatty acids is such a sink, if electrons (hydrogens) can be transferred from NADH to NADP+, forming NADPH, which is the reducing substance required for turning carbohydrates and pyruvate and amino acids into fats.”

“While Warburg was investigating the roles of glycolysis and respiration in cancer, a physician with a background in chemistry, W.F. Koch, in Detroit, was showing that the ability to use oxygen made the difference between health and sickness, and that the cancer metabolism could be corrected by restoring the efficient use of oxygen. He argued that a respiratory defect was responsible for immunodeficiency, allergy, and defective function of muscles, nerves, and secretory cells, as well as cancer. Koch’s idea of cancer’s metabolic cause and its curability directly challenged the doctrine of the genetic irreversibility of cancer that was central to governmental and commercial medical commitments.”

“A focus on correcting the respiratory defect would be relevant for all of the diseases and conditions (including heart disease, diabetes, dementia) involving inflammation and inappropriate excitation, not just for cancer.”

“Aging is characterized by loss of lean body mass, immunodeficiency, and a variety of autoimmune reactions. My perennial argument has been that decreased thyroid and progesterone, associated with increased estrogen and stress hormones, are largely responsible for those changes.”

“When respiratory energy production is blocked in stimulated cells, the cells are likely to die. (Cortisol, estrogen, polyunsaturated oils have this effect, especially on thymus cells.)”

“Thyroid is needed to keep the cell in an oxidative, rather than reductive state, and progesterone (which is produced elsewhere only when cells are in a rapidly oxidizing state) activates the processes that remove estrogen from the cell, and inactivates the processes that would form new estrogen in the cell.

Thyroid, and the carbon dioxide it produces, prevent the formation of the toxic lactic acid. When there is enough carbon dioxide in the tissues, the cell is kept in an oxidative state, and the formation of toxic free radicals is suppressed. Carbon dioxide therapy is extremely safe.”

“The organism can only be understood in its environments, and a cell can’t be understood without reference to the tissue and organism in which it lives. Although the geneticists were at first hostile to the idea that nutrition and geography could have anything to do with cancer, they soon tried to dominate those fields, insisting that mutagens and ethnicity would explain everything. But the evidence now makes it very clear that environment and nutrition affect the risk of cancer in ways that are not primarily genetic.”

“Substances such as PTH, nitric oxide, serotonin, cortisol, aldosterone, estrogen, thyroid stimulating hormone, and prolactin have regulatory and adaptive functions that are essential, but that ideally should act only intermittently, producing changes that are needed momentarily. When the environment is too stressful, or when nutrition isn’t adequate, the organism may be unable to mobilize the opposing and complementary substances to stop their actions. In those situations, it can be therapeutic to use some of the nutrients as supplements.”

“The movement of substances from blood to cell, and from cell to cell, is normally very tightly controlled, and when the systems that control those movements of water and its solutes are damaged, the tissues’ structures and functions are altered. The prevention of inappropriate leakiness can protect against the degenerative processes, and against aging itself, which is, among other things, a state of generalized leakiness.

When cells’ energy is depleted, water and various dissolved molecules are allowed to move into the cells, out of the cells, and through or around cells inappropriately. The weakened cells can even permit whole bacteria and similar particles to pass into and out of the blood stream more easily.

One of the earliest investigators of the effects of stress and fatigue on nerves and other cells was A.P. Nasonov, in the first half of the 20th century. A.S. Troshin (1956) has reviewed his work in detail. He showed that in cells as different as algae and nerve cells, fatigue caused them to take up dyes, and that the dyes were extruded, if the cells were able to recover their energy. When nerve cells are excited for a fraction of a second, they take up sodium and calcium, but quickly eliminate them. Prolonged excitation, leading to fatigue, can gradually shift the balance, allowing more substances to enter, and to stay longer.”

“If the cancer-productive field is taken into account, all of the factors that promote and sustain that field should be considered during therapy.

Two ubiquitous carcinogenic factors that can be manipulated without toxins are the polyunsaturated fatty acids (PUFA) and estrogen. These closely interact with each other, and there are many ways in which they can be modulated.

For example, keeping cells in a well oxygenated state with thyroid hormone and carbon dioxide will shift the balance from estradiol toward the weaker estrone. The thyroid stimulation will cause the liver to excrete estrogen more quickly, and will help to prevent the formation of aromatase in the tissues. Low temperature is one of the factors that increases the formation of estrogen. Lactic acid, serotonin, nitric oxide, prostaglandins, and the endorphins will be decreased by the shift toward efficient oxidative metabolism.

Progesterone synthesis will be increased by the higher metabolic rate, and will tend to keep the temperature higher.

Thyroid hormone, by causing a shift away from estrogen and serotonin, lowers prolactin, which is involved in the promotion of several kinds of cancer.

Vitamin D and vitamin K have some antiestrogenic effects. Vitamin D and calcium lower the inflammation-promoting parathyroid hormone (PTH).

Eliminating polyunsaturated fats from the diet is essential if the bystander effect is eventually to be restrained. Aspirin and salicylic acid can block many of the carcinogenic effects of the PUFA. Saturated fats have a variety of antiinflammatory and anticancer actions. Some of those effects are direct, others are the result of blocking the toxic effects of the PUFA. Keeping the stored unsaturated fats from circulating in the blood is helpful, since it takes years to eliminate them from the tissues after the diet has changed. Niacinamide inhibits lipolysis. Avoiding over-production of lipolytic adrenaline requires adequate thyroid hormone, and the adjustment of the diet to minimize fluctuations of blood sugar.”

“Failure to renew cells and tissues leads to loss of function and substance. Bones and muscles get weaker and smaller with aging. Diminished bone substance, osteopenia, is paralleled, at roughly the same rate, by the progressive loss of muscle mass, sarcopenia (or myopenia). The structure of aging tissue changes, with collagen tending to fill the spaces left by the disappearing cells. It’s also common for fat cells to increase, as muscle cells disappear.”

“Excitotoxicity, in its simplest sense, is the harmful cellular effect (death or injury) caused by an excitatory transmitter such as glutamate or aspartate acting on a cell whose energetic reserves aren’t adequate to sustain the level of activity provoked by the transmitter. Once an excitotoxic state exists, the consequences of cell exhaustion can increase the likelihood that the condition will spread to other cells, since any excitation can trigger a complex of other excitatory processes. As calcium enters cells, potassium leaves, and enzymes are activated, producing free fatty acids (linoleic and arachidonic, for example) and prostaglandins,”

“Simply getting outside the world of compartmentalized diseases, there is an abundance of evidence showing the variety of ways in which cells can fail. Energy is needed for cell maintenance and adaptation, and the type of fuel used to provide the energy is crucial. Fatty acids interfere with the oxidation of glucose, and this effect can be seen in heart failure, immunodeficiency, dementia, as well as in simple stress, diabetes, and many other simple situations (dementia: Montine and Morrow, 2005; Yaqoob, et al., 1994).”

“When a muscle or nerve is fatigued, it swells, retaining water. When the swelling is extreme, its ability to contract is limited. Excess water content resembles a partly excited state, in which increase amounts of sodium and calcium are free in the cytoplasm. Energy is needed to eliminate the sodium and calcium, or to bind calcium allowing the cell to extrude excess water and return to the resting state. Thyroid hormone allows cells’ mitochondria to efficiently produce energy, and it also regulates the synthesis of proteins (phospholamban and calcisequestrin) that control the binding of calcium. When the cell is energized, by the mitochondria working with thyroid, oxygen, and sugar, these proteins change their form, binding calcium and removing it from the contractile system, allowing the cell to relax, to be fully prepared for the next contraction. If the calcium isn’t fully and quickly bound, the cell retains extra water and sodium, and isn’t able to fully relax.”

“Older ways of understanding aging and degenerative disease are now returning to the foreground. The developmental interactions of the organism with its environment, and the interactions of its cells, tissues, and organs with each other, have again become the focus of biological aging research. In place of the old belief that “we are defined and limited by our genes,” the new perspective is showing us that we are limited by our environment, and that our environment can be modified. As we react to unsuitable environments, our internal environments become limiting for our cells, and instead of renewing themselves, repairing damage, and preparing for new challenges, our cells find themselves in blind alleys. Looking at aging in this way suggests that putting ourselves into the right environments could prevent aging.”

The end product of respiration is carbon dioxide, and it is an essential component of the life process. The ability to produce and retain enough carbon dioxide is as important for longevity as the ability to conserve enough heat to allow chemical reactions to occur as needed.

Carbon dioxide protects cells in many ways. By bonding to amino groups, it can inhibit the glycation of proteins during oxidative stress, and it can limit the formation of free radicals in the blood; inhibition of xanthine oxidase is one mechanism (Shibata, et al., 1998). It can reduce inflammation caused by endotoxin/LPS, by lowering the formation of tumor necrosis factor, IL-8 and other promoters of inflammation (Shimotakahara, et al., 2008). It protects mitochondria (Lavani, et al., 2007), maintaining (or even increasing) their ability to respire during stress.

The “replicative lifespan” of a cell can be shortened by factors like resveratrol or estrogen that interfere with mitochondrial production of carbon dioxide. Both of those chemicals cause skin cells, keratinocytes, to stop dividing, to take up calcium, and to begin producing the horny material keratin, that allows superficial skin cells to form an effective barrier. This process normally occurs as these cells differentiate from the basal (stem) cells and, by multiplying, move farther outward away from the underlying blood vessels that provide the nutrients that are oxidized to form carbon dioxide, and as they get farther from the blood supply, they get closer to the external air, which contains less than 1% as much CO2 as the blood. This normally causes their eventual hardening into the keratin cells, but when conditions are optimal, numerous layers of moist, translucent cells that give the skin the characteristic appearance of youth, will be retained between the basal cells and the condensed surface layers. (Wilke, et al., 1988)

In other types of tissue, a high level of carbon dioxide has a similar stabilizing effect on cells, preserving stem cells, limiting stress and preventing loss of function. In the lining of the mouth, where the oxygen tension is lower, and carbon dioxide higher, the cells don’t form as much keratin as the skin cells do. In the uterus, the lining cells would behave similarly, except that estrogen stimulates keratinization. A vitamin A deficiency mimics an estrogen excess, and can cause excessive keratinization of membrane cells.”