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<title>
Salt, energy, metabolic rate, and longevity
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<h1>
Salt, energy, metabolic rate, and longevity
</h1>
<p></p>
<p>
In the 1950s, when the pharmaceutical industry was beginning to promote some new chemicals as diuretics to
replace the traditional mercury compounds, Walter Kempner"s low-salt "rice diet" began to be discussed in
the medical journals and other media. The diuretics were offered for treating high blood pressure, pulmonary
edema, heart failure, "idiopathic edema," orthostatic edema and obesity, and other forms of water retention,
including pregnancy, and since they functioned by causing sodium to be excreted in the urine, their sale was
accompanied by advising the patients to reduce their salt intake to make the diuretic more effective.
</p>
<p>
It was clear to some physicians (and to most veterinarians) that salt restriction, especially combined with
salt-losing diuresis, was very harmful during pregnancy, but that combination became standard medical
practice for many years, damaging millions of babies.
</p>
<p>
Despite numerous publications showing that diuretics could cause the edematous problems that they were
supposed to remedy, they have been one of the most profitable types of drug. Dietary salt restriction has
become a cultural cliché, largely as a consequence of the belief that sodium causes edema and hypertension.
</p>
<p>
Salt restriction, according to a review of about 100 studies (Alderman, 2004), lowers the blood pressure a
few points. But that generally doesn"t relate to better health. In one study (3000 people, 4 years), there
was a clear increase in mortality in the individuals who ate less salt. An extra few grams of salt per day
was associated with a 36% reduction in "coronary events" (Alderman, et al., 1995). Another study (more than
11,000 people, 22 years) also showed an inverse relation between salt intake and mortality (Alderman, et
al., 1997).
</p>
<p>
Tom Brewer, an obstetrician who devoted his career to educating the public about the importance of prenatal
nutrition, emphasizing adequate protein (especially milk), calories, and salt, was largely responsible for
the gradual abandonment of the low-salt plus diuretics treatment for pregnant women. He explained that
sodium, in association with serum albumin, is essential for maintaining blood volume. Without adequate
sodium, the serum albumin is unable to keep water from leaving the blood and entering the tissues. The
tissues swell as the volume of blood is reduced.
</p>
<p>
During pregnancy, the reduced blood volume doesn"t adequately nourish and oxygenate the growing fetus, and
the reduced circulation to the kidneys causes them to release a signal substance (renin) that causes the
blood to circulate faster, under greater pressure. A low salt diet is just one of the things that can reduce
kidney circulation and stimulate renin production. Bacterial endotoxin, and other things that cause
excessive capillary permeability, edema, or shock-like symptoms, will activate renin secretion.
</p>
<p>
The blood volume problem isn"t limited to the hypertension of pregnancy toxemia: "Plasma volume is usually
lower in patients with essential hypertension than in normal subjects" (Tarazi, 1976).
</p>
<p>
Several studies of preeclampsia or toxemia of pregnancy showed that supplementing the diet with salt would
lower the women"s blood pressure, and prevent the other complications associated with toxemia (Shanklin and
Hodin, 1979).
</p>
<p>
It has been known for many years that decreasing sodium intake causes the body to respond adaptively,
increasing the renin-angiotensin-aldosterone system (RAAS). The activation of this system is recognized as a
factor in hypertension, kidney disease, heart failure, fibrosis of the heart, and other problems. Sodium
restriction also increases serotonin, activity of the sympathetic nervous system, and plasminogen activator
inhibitor type-1 (PAI-1), which contributes to the accumulation of clots and is associated with breast and
prostate cancer. The sympathetic nervous system becomes hyperactive in preeclampsia (Metsaars, et al.,
2006).
</p>
<p>
Despite the general knowledge of the relation of dietary salt to the RAA system, and its application by
Brewer and others to the prevention of pregnancy toxemia, it isn"t common to see the information applied to
other problems, such as aging and the stress-related degenerative diseases.
</p>
<p>
Many young women periodically crave salt and sugar, especially around ovulation and premenstrually, when
estrogen is high. Physiologically, this is similar to the food cravings of pregnancy. Premenstrual water
retention is a common problem, and physicians commonly offer the same advice to cycling women that was
offered as a standard treatment for pregnant women--the avoidance of salt, sometimes with a diuretic. But
when women premenstrually increase their salt intake according to their craving, the water retention can be
prevented.
</p>
<p>
Blood volume changes during the normal menstrual cycle, and when the blood volume is low, it is usually
because the water has moved into the tissues, causing edema. When estrogen is high, the osmolarity of the
blood is low. (Courtar, et al., 2007; Stachenfeld, et al., 1999). Hypothyroidism (which increases the ratio
of estrogen to progesterone) is a major cause of excessive sodium loss.
</p>
<p>
The increase of adrenalin caused by salt restriction has many harmful effects, including insomnia. Many old
people have noticed that a low sodium diet disturbs their sleep, and that eating their usual amount of salt
restores their ability to sleep. The activity of the sympathetic nervous system increases with aging, so
salt restriction is exacerbating one of the basic problems of aging. Chronically increased activity of the
sympathetic (adrenergic) nervous system contributes to capillary leakage, insulin resistance (with increased
free fatty acids in the blood), and degenerative changes in the brain (Griffith and Sutin, 1996).
</p>
<p>
The flexibility of blood vessels (compliance) is decreased by a low-salt diet, and vascular stiffness caused
by over-activity of the sympathetic nervous system is considered to be an important factor in hypertension,
especially with aging.
</p>
<p>
Pregnancy toxemia/preeclampsia involves increased blood pressure and capillary permeability, and an excess
of prolactin. Prolactin secretion is increased by serotonin, which is one of the substances increased by
salt restriction, but prolactin itself can promote the loss of sodium in the urine (Ibarra, et al., 2005),
and contributes to vascular leakage and hypertension.
</p>
<p>
In pregnancy, estrogen excess or progesterone deficiency is an important factor in the harmful effects of
sodium restriction and protein deficiency. A deficiency of protein contributes to hypothyroidism, which is
responsible for the relative estrogen excess.
</p>
<p>
Protein, salt, thyroid, and progesterone happen to be thermogenic, increasing heat production and
stabilizing body temperature at a higher level. Prolactin and estrogen lower the temperature set-point.
</p>
<p>
The downward shift of temperature and energy metabolism in toxemia or salt deprivation tends to slow the use
of oxygen, increasing the glycolytic use of sugar, and contributing to the formation of lactic acid, rather
than carbon dioxide. In preeclampsia, serum lactate is increased, even while free fatty acids are
interfering with the use of glucose.
</p>
<p>
One way of looking at those facts is to see that a lack of sodium slows metabolism, lowers carbon dioxide
production, and creates inflammation, stress and degeneration. Rephrasing it, sodium stimulates energy
metabolism, increases carbon dioxide production, and protects against inflammation and other maladaptive
stress reactions.
</p>
<p>
In recent years, Weissman"s "wear-and-tear" theory of aging, and Pearl"s "rate of living" theory have been
clearly refuted by metabolic studies that are showing that intensified mitochondrial respiration decreases
cellular damage, and supports a longer life-span.
</p>
<p>
Many dog owners are aware that small dogs eat much more food in proportion to their size than big dogs do.
And small dogs have a much greater life expectancy than big dogs, in some cases about twice as long
(Speakman, 2003).
</p>
<p>
Organisms as different as yeasts and rodents show a similar association of metabolic intensity and
life-span. A variety of hamster with a 20% higher metabolic rate lived 15% longer than hamsters with an
average metabolic rate (Oklejewicz and Daan, 2002).
</p>
<p>
Individuals within a strain of mice were found to vary considerably in their metabolic rate. The 25% of the
mice with the highest rate used 30% more energy (per gram of body weight) than the 25% with the lowest
metabolic rate, and lived 36% longer (Speakman, et al., 2000).
</p>
<p>
The mitochondria of these animals are "uncoupled," that is, their use of oxygen isn"t directly proportional
to the production of ATP. This means that they are producing more carbon dioxide without necessarily
producing more ATP, and that even at rest they are using a considerable amount of energy.
</p>
<p>
One important function of carbon dioxide is to regulate the movement of positively charged alkali metal
ions, such as sodium and calcium. When too much calcium enters a cell it activates many enzymes, prevents
muscle and nerve cells from relaxing, and ultimately kills the cell. The constant formation of acidic carbon
dioxide in the cell allows the cell to remove calcium, along with the small amount of sodium which is
constantly entering the cell.
</p>
<p>
When there is adequate sodium in the extracellular fluid, the continuous inward movement of sodium ions into
the resting cell activates an enzyme, sodium-potassium ATPase, causing ATP to break down into ADP and
phosphate, which stimulates the consumption of fuel and oxygen to maintain an adequate level of ATP.
Increasing the concentration of sodium increases the energy consumption and carbon dioxide production of the
cell. The sodium, by increasing carbon dioxide production, protects against the excitatory, toxic effects of
the intracellular calcium.
</p>
<p>
Hypertonic solutions, containing more than the normal concentration of sodium (from about twice normal to 8
or 10 times normal) are being used to rescuscitate people and animals after injury. Rather than just
increasing blood volume to restore circulation, the hypertonic sodium restores cellular energy production,
increasing oxygen consumption and heat production while reducing free radical production, improves the
contraction and relaxation of the heart muscle, and reduces inflammation, vascular permeability, and edema.
</p>
<p>
Seawater, which is hypertonic to our tissues, has often been used for treating wounds, and much more
concentrated salt solutions have been found effective for accelerating wound healing (Mangete, et al.,
1993).
</p>
<p>
There have been several publications suggesting that increasing the amount of salt in the diet might cause
stomach cancer, because countries such as Japan with a high salt intake have a high incidence of stomach
cancer.
</p>
<p>
Studies in which animals were fed popular Japanese foods--"salted cuttlefish guts, broiled, salted, dried
sardines, pickled radish, and soy sauce"--besides a chemical carcinogen, showed that the Japanese foods
increased the number of tumors. But another study, adding only soy sauce (with a salt content of about 18%)
to the diet did not increase the incidence of cancer, in another it was protective against stomach cancer
(Benjamin, et al., 1991). Several studies show that dried fish and pickled vegetables are carcinogenic,
probably because of the oxidized fats, and other chemical changes, and fungal contamination, which are
likely to be worse without the salt. Animals fed dried fish were found to have mutagenic urine, apparently
as a result of toxic materials occurring in various preserved foods (Fong, et al., 1979).
</p>
<p>
Although preserved foods develop many peculiar toxins, even fresh fish in the diet have been found to be
associated with increased cancer risk (Phukan, et al., 2006).
</p>
<p>
When small animals were given a milliliter of a saturated salt solution with the carcinogen, the number of
tumors was increased with the salt. However, when the salt was given with mucin, it had no cancer promoting
effect. Since the large amount of a saturated salt solution breaks down the stomach"s protective mucus
coating, the stomach cells were not protected from the carcinogen. Rather than showing that salt causes
stomach cancer, the experiments showed that a cup or more of saturated salt solution, or several ounces of
pure salt, shouldn"t be ingested at the same time as a strong carcinogen.
</p>
<p>
Some studies have found pork to be associated with cancer of the esophagous (Nagai, et al., 1982), thyroid
(Markaki, et al., 2003), and other organs, but an experiment with beef, chicken, or bacon diet in rats
provides another perspective on the role of salt in carcinogenesis. After being given a carcinogen, rats
were fed meat diets, containing either 30% or 60% of freeze-dried fried beef, chicken, or bacon. Neither
beef nor chicken changed the incidence of precancerous lesions in the intestine, but the incidence was
reduced by 12% in the animals on the 30% bacon diet, and by 20% in rats getting the diet with 60% bacon.
Salt apparently made the difference.
</p>
<p>
Other protective effects of increased sodium are that it improves immunity (Junger, et al., 1994), reduces
vascular leakiness, and alleviates inflammation (Cara, et al., 1988). All of these effects would tend to
protect against the degenerative diseases, including tumors, atherosclerosis, and Alzheimer"s disease. The
RAA system appears to be crucially involved in all kinds of sickness and degeneration, but the protective
effects of sodium are more basic than just helping to prevent activation of that system.
</p>
<p>
A slight decrease in temperature can promote inflammation (Matsui, et al., 2006). The thermogenic
substances--dietary protein, sodium, sucrose, thyroid and progesterone--are antiinflammatory for many
reasons, but very likely the increased temperature itself is important.
</p>
<p>
A poor reaction to stress, with increased cortisol, can raise the body temperature by accelerating the
breakdown and resynthesis of proteins, but adaptive resistance to stress increases the temperature by
increasing the consumption of oxygen and fuel. In the presence of increased cortisol, abdominal fat
increases, along with circulating fatty acids and calcium, as mitochondrial respiration is suppressed.
</p>
<p>
When mice are chilled, they spontaneously prefer slightly salty water, rather than fresh, and it increases
their heat production (Dejima, et al., 1996). When rats are given 0.9 per cent sodium chloride solution with
their regular food, their heat production increases, and their body fat, including abdominal fat, decreases
(Bryant, et al., 1984). These responses to increased dietary sodium are immediate. Part of the effect of
sodium involves regulatory processes in the brain, which are sensitive to the ratio between sodium and
calcium. Decreasing sodium, or increasing calcium, causes the body"s metabolism to shift away from
thermogenesis and accelerated respiration.
</p>
<p>
Regulating intracellular calcium by increasing the production of carbon dioxide is probably a basic
mechanism in sodium"s protection against inflammation and excitatory cell damage and degeneration.
</p>
<p>
Cortisol"s suppression of mitochondrial respiration is closely associated with its ability to increase
intracellular calcium. Cortisol blocks the thermogenic effects of sodium, allowing intracellular calcium to
damage cells. With aging, the tissues are more susceptible to these processes.
</p>
<p>
The thermogenic effects of sodium can be seen in long-term studies, as well as short. A low-sodium diet
accelerates the decrease in heat production that normally occurs with aging, lowering the metabolic rate of
brown fat and body temperature, and increasing the fat content of the body, as well as the activity of the
fat synthesizing enzyme (Xavier, et al., 2003).
</p>
<p>
Activation of heat production and increased body temperature might account for some of the GABA-like
sedative effects of increased sodium. Increasing GABA in the brain increases brown fat heat production
(Horton, et al., 1988). Activation of heat production by brown fat increases slow wave sleep (Dewasmes, et
al., 2003), the loss of which is characteristic of aging. (In adult humans, the skeletal muscles have
heat-producing functions similar to brown fat.)
</p>
<p>
Now that inflammation is recognized as having a central role in the degenerative diseases, the fact that
renin, angiotensin, and aldosterone all contribute to inflammation and are increased by a sodium deficiency,
should arouse interest in exploring the therapeutic uses of sodium supplementation, and the integrated use
of all of the factors that normally support respiratory energy production, especially thyroid and
progesterone. Progesterone"s antagonism to aldosterone has been known for many years, and the synthetic
antialdosterone drugs are simply poor imitations of progesterone.
</p>
<p>
But the drug industry is interested in selling new drugs to block the formation and action of each of the
components of the RAAS, rather than an inexpensive method (such as nutrition) to normalize the system.
</p>
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