pure oxygen lowers the oxygen content of tissues; breathing rarefied
air, or air with carbon dioxide, oxygenates and energizes the tissues;
if this seems upside down, it's because medical physiology has been
taught upside down. And respiratory physiology holds the key to
the special functions of all the organs, and to many of their basic
Stress, shock, inflammation,
aging, and organ failure are, in important ways, respiratory problems.Definitions
Haldane effect: Oxygen displaces carbon dioxide from
hemoglobin, in proportion to its partial (specific) pressure.
Bohr effect: Carbon dioxide (or acidity) displaces oxygen
Lactic acidemia: The presence of lactic acid in the blood.
Alkalosis: A pH of the blood above 7.4.
Acidosis: A blood pH below 7.4.
Lactate paradox: The reduced production of lactic acid at
a given work rate at high altitude. Muscle work efficiency may
be 50% greater at high altitude. ATP wastage is decreased.
are some popular medical ideas that obstruct clear thinking about respiration.
One is that high altitude deprives you of oxygen, and is likely to be
bad for people with heart disease and cancer. Another is that
breathing pure oxygen helps sick people to oxygenate their tissues while
exerting less effort in breathing. These are both exactly wrong,
and the errors have been explored in quite a few publications, but the
ideas persist in the culture to such a degree that our perceptions
and intuitions have been misled, making closely related things
seem to be unrelated. In this culture, it is hard to see that
heart disease, cancer, and cataracts all involve a crucial respiratory
defect, with the production of too much lactic acid and too little carbon
dioxide, which leads to a "swelling pathology": A pathological
retention of water. The swollen heart beats poorly, the swollen
lens turns milky, other cells divide rapidly as a result of swelling.
who live at very high altitudes live significantly longer; they
have a lower incidence of cancer (Weinberg, et al., 1987) and heart
disease (Mortimer, et al., 1977), and other degenerative conditions,
than people who live near sea level. As I have written earlier,
I think the lower energy transfer from cosmic radiation is likely to
be a factor in their longevity, but several kinds of evidence indicate
that it is the lower oxygen pressure itself that makes the biggest contribution
to their longevity.
sickness" is a potentially deadly condition that develops in some
people when they ascend too rapidly to a high altitude. Edema
of the lungs and brain can develop rapidly, leading to convulsions and
death. The standard drug for preventing it is acetazolamide, which
inhibits carbonic anhydrase and causes carbon dioxide to be retained,
creating a slight tendency toward acidosis. This treatment probably
mimics the retention of carbon dioxide that occurs naturally in altitude
adapted people. The reasons for mountain sickness, and the reasons
for the low incidence of heart disease, cancer, cataracts, etc., at
high altitude, offer clues to the prevention of death and deterioration
from many other causes.
the weather in a particular place is cool, sunny and dry (which in itself
is very good for the health) the atmospheric pressure usually is higher
than average. Although sunny dry weather is healthful, periods
of higher pressure correspond to an increased incidence of death from heart disease and strokes.
The Haldane-Bohr effect describes the fact
that oxygen and carbon dioxide destabilize each other's binding to
hemoglobin. When oxygen pressure is high, the blood releases its
carbon dioxide more easily. In stormy weather, or at high altitude,
the lower oxygen pressure allows the body to retain more carbon dioxide.
Carbon dioxide, produced in the cells, releases oxygen into the tissues,
relaxes blood vessels, prevents edema, eliminates ammonia, and increases
the efficiency of oxidative metabolism.
breathing excessively and causing too much carbon dioxide to be lost,
is similar to being in the presence of too much oxygen; it's
similar to being at low altitude with high atmospheric pressure, only
worse. Therefore, the physiological events produced by hyperventilation
can give us an insight into what happens when the atmospheric pressure
is low, by looking at the events in reverse. Likewise, breathing
100% oxygen has known harmful consequences, which are very similar to
those produced by hyperventilation.
is defined as breathing enough to produce respiratory alkalosis from
the loss of carbon dioxide. Lactic acid is produced in response
to the alkalosis of hyperventilation.
too much oxygen displaces too much carbon dioxide, provoking an increase
in lactic acid; too much lactate displaces both oxygen and carbon
dioxide. Lactate itself tends to suppress respiration.
toxicity and hyperventilation create a systemic deficiency of carbon
dioxide. It is this carbon dioxide deficiency that makes breathing
more difficult in pure oxygen, that impairs the heart's ability to
work, and that increases the resistance of blood vessels, impairing
circulation and oxygen delivery to tissues. In conditions that
permit greater carbon dioxide retention, circulation is improved and
the heart works more effectively. Carbon dioxide inhibits the
production of lactic acid, and lactic acid lowers carbon dioxide's concentratrion
in a variety of ways.
carbon dioxide production is low, because of hypothyroidism, there will
usually be some lactate entering the blood even at rest, because adrenalin
and noradrenalin are produced in large amounts to compensate for hypothyroidism,
and the adrenergic stimulation, besides mobilizing glucose from the
glycogen stores, stimulates the production of lactate. The excess
production of lactate displaces carbon dioxide from the blood, partly
as a compensation for acidity. The increased impulse to breath
("ventilatory drive") produced by adrenalin makes the problem worse,
and lactate can promote the adrenergic response, in a vicious circle.
the 1920s when A. V. Hill proposed that the prolonged increase in oxygen consumption after a short
period of intense work, the "oxygen debt," was equivalent to the
amount of lactic acid that had entered the circulation from the muscles'
anaerobic work, and that it had to be disposed of by oxidative processes,
physiology textbooks have given the impression that lactic acid accumulation
was exactly the same as the oxygen debt. In reality, several things
are involved, especially the elevation of temperature produced by the
intense work. Increased temperature raises oxygen consumption
independently of lactic acid, and lower temperature decreases oxygen
consump-tion, even when lactic acid is present.
idea of the "oxygen debt" produced by exercise or stress as being
equivalent to the accumulation of lactic acid is far from accurate,
but it's true that activity increases the need for oxygen, and also
increases the tendency to accumulate lactic acid, which can then be
disposed of over an extended time, with the consumption of oxygen.
This relationship between work and lactic acidemia and oxygen deficit
led to the term "lactate paradox" to describe the lower production
of lactic acid during maximal work at high altitude when people are
adapted to the altiude. Carbon dioxide, retained through the Haldane
effect, accounts for the lactate paradox, by inhibiting cellular excitation
and sustaining oxidative metabolism to consume lactate efficiently.
loss of carbon dioxide from the lungs in the presence of high oxygen
pressure, the shift toward alkalosis, by the Bohr-Haldane effect increases
the blood's affinity for oxygen, and restricts its delivery to the
tissues, but because of the abundance of oxygen in the lungs, the blood
is almost competely saturated with oxygen.
high altitude, the slight tendency toward carbon dioxide-retention acidosis
decreases the blood's affinity for oxygen, making it more available
to the tissues. It happens that lactic acid also affects the blood's
oxygen affinity, though not as strongly as carbon dioxide. However, lactic acid doesn't vaporize as the blood passes through
the lungs, so its effect on the lungs' ability to oxygenate the blood
is the opposite of the easily exchangeable carbon dioxide's. Besides dissociating oxygen from hemoglobin, lactate also displaces
carbon dioxide from its (carbamino) binding sites on hemoglobin.
If it does this in hemoglobin, it probably does it in many other places
in the body.
to Meerson, ascending more than 200 feet per day produces measurable
stress. People seldom notice the effects of ascending a few thousand
feet in a day, but it has been found that a large proportion of people
have bleeding into the retina when they ascend to 10,000 feet without
adequate adaptation. Presumably, similar symptomless bleeding
occurs in other organs, but the retina can be easily inspected.
hypothyroid people, with increased adrenalin and lactate, are hyperventilating even at rest and at sea level, when
they go to a high altitude where less oxygen is available, and their
absorption of oxygen is impaired by lactic acidemia, their "oxygen
debt," conceived as circulating lactic acid, is easily increased,
intensifying their already excessive
"ventilatory drive," and in proportion to the lactic acid oxygen
debt, oxygen absorption is further inhibited.
lactic acid has to be disposed of, but their ability to extract oxygen
is reduced. The poor oxygenation, and the increased lactic acid
and free fatty acids cause blood vessels to become leaky, producing
edema in the lungs and brain. This is very similar to the "multiple
organ failure" that occurs in inflammatory conditions,
bacteremia, congestive heart failure, cancer, and trauma.
Warburg established that lactic acid production even in the presence
of oxygen is a fundamental property of cancer. It is, to a
great degree, the lactic acid which triggers the defensive reactions
of the organism, leading to tissue wasting from excessive glucocorticoid
hormone. The cancer's production of lactic acid creates the same kind
of internal imbalance produced by hyperventilation, and if we look at
the physiology of hyperventilation in the light of Warburg's description
of cancer, hyperventilation imitates cancer metabolism, by producing
lactic acid "even in the presence of oxygen." Lactate, a supposedly
benign metabolite of the cancer cells, which appears in all the other
degenerative conditions, including obesity, diabetes, Alzheimer's
disease, multiple sclerosis, is itself a central factor in the degenerative
out the mechanisms involved in susceptibility to altitude sickness will
clarify the issues involved in the things that cause most people to
die. At first, all of these changes occur in the regulatory systems,
and so can be corrected.
vitality of the mitochondria, their capacity for oxidative energy production,
is influenced by nutrition and hormones. In healthy people, mitochondria
work efficiently at almost any altitude, but people with damaged or
poorly regulated mitochondria are extremely susceptible to stress and
hyperventilation. Progesterone, testosterone, and thyroid (T3
and T2) are protective of normal mitochondrial function, by both local
and systemic effects. The
changes that occur in malnutrition and hypothyroidism affect the mitochondria
in a multitude of ways, besides the local effects of the thyroid and
progesterone deficiency. Increased
estrogen, nitric oxide, excitatory amino acids, cortisol, lactate, free
unsaturated fatty acids, prolactin, growth hormone, histamine, serotonin,
tumor necrosis factor and other pro-inflammatory cytokines and kinins,
and a variety of prostaglandins
and eicosanoids, have been identified as anti-mitochondrial, anti-respiratory agents. Edema
itself can be counted among these agents. (Carbon dioxide itself directly reduces tissue edema, as can be seen
in studies of the cornea.) Thyroid, progesterone, magnesium,
glucose, and saturated fatty acids are among the central protective
similarity of the changes occurring under the influence of estrogen
excess, oxygen deprivation, aging, and ionizing radiation are remarkable.
People who think that radiation's biological effects are mainly on
the DNA, and that estrogen acts through "estrogen receptors," aren't
interested in the parallels, but the idea of a common respiratory defect,
activating common pathways, suggests that there is something useful
in the perception that irradiation, hypoxia, and aging have estrogenic
by ultraviolet, gamma, or x-rays, and even by blue light, is damaging
to mitochondrial respiration. All of the ionizing radiations produce
immediate and lingering edema, which continues to damage metabolism
in a more or less permanent way, apart from any detectable mutagenic
actions. The amount of water taken up following irradiation can
be 20% to 30% of the normal weight, which is similar to the amount of
swelling that intense work produces in a muscle, and to the weight increase
under hormonal imbalances. The energy changes produced by irradiation
in, for example, the heart, appear to accelerate the changes produced
by aging. Since unsaturated fats accumulate in the respiratory
system with aging, and are targets for radiation damage, the involvement
of these fats in all sorts of antirespiratory degenerative processes
deserves more attention. Darkness, like irradiation, excess lactate,
and unsaturated fats, has the diabetes-like effect of greatly reducing
the ability of muscle to absorb sugar, while light stimulates respiration.
the ideas of "stress," "respiratory defect," and "hyperventilation"
are considered together, they seem practically interchangeable.
presence of lactic acid, which indicates stress or defective respiration,
interferes with energy metabolism in ways that tend to be self-promoting.
Harry Rubin's experiments demonstrated that cells become cancerous
before genetic changes appear. The mere presence of lactic
acid can make cells more susceptible to the transformation into cancer
cells. (Mothersill, et al., 1983.) The implications
of this for the increased susceptibility to cancer during stress, and
for the increased resistance to cancer at high altitude, are obvious.
the production of lactic acid can make cells more resistant (Seymour
and Mothersill, 1988); if lactic acid were merely a useful fuel, it's hard to see how poisoning
its formation could improve cell survival. But it happens to be
an energy-disruptive fuel, interfering with carbon dioxide metabolism,
among other things.
is present in hypothyroidism, and is driven by adrenalin, lactate, and
free fatty acids. Free fatty acids and lactate impair glucose
use, and promote edema, especially in the lungs. Edema in the
lungs limits oxygen absorption. Swelling of the brain, resulting
from increased vascular permeability and the entry of free fatty acids,
reduces its circulation and oxygenation; lactic acidemia causes
swelling of glial cells. Swelling of the endothelium increases
vascular resistance by making the channel narrower, eventually affecting
all organs. Cells of the immune system release tumor necrosis
factor and other inflammatory cytokines, and the bowel becomes more
permeable, allowing endotoxin and even bacteria to enter the blood.
Endotoxin impairs mitochondria, increases estrogen levels, causes Kupffer
cells in the liver to produce more tumor necrosis factor, etc..
Despite its name, tumor necrosis factor stimulates the growth and metastasis
of some types of cancer. Dilution of the body fluids, which
occurs in hypothyroidsim, hyperestrogenism, etc., stimulates tumor growth.
inflammatory factors that can promote cell growth can, with just slight
variation, deplete cellular energy to the extent that the cells die
from the energetic cost of the repair process, or mutate from defective
repairs. Niacinamide can have an "antiinflammatory" function,
preventing death from multiple organ failure, by interupting the reactions
to nitric oxide and peroxynitrile (Cuzzocrea, et al., 1999). The
cells' type, environment, and history determine the different outcomes.
cancer, congestive heart failure, seemingly such different degenerative
problems, have the same sort of metabolic problem, leading to the abnormal
absorption of water by cells, disrupting their normal functions.
same simple metabolic therapies,
such as thyroid, progesterone, magnesium, and carbon dioxide, are appropriate
for a great range of seemingly different diseases. Other biochemicals,
such as adenosine and niacinamide, have more specific protective effects,
farther downstream in the "cascade" effects of stress.
are many little cliches in the medical culture that prevent serious
thought about integral therapy: "Progesterone is the pregnancy
hormone," "thyroid makes your heart work too hard," "thyroid
uncouples mitochondrial phosphorylation," "magnesium has nothing
to do with thyroid or progesterone," "lactate provides energy,"
etc. But many of these minor cliches are held in place by deep
theoretical errors about the nature of cells and organisms. Once
those have been corrected, there should be progress toward more powerful