articles
This commit is contained in:
Daniel Ledda
964
raypeat-articles/processed/phosphate-activation-aging.html
Normal file
964
raypeat-articles/processed/phosphate-activation-aging.html
Normal file
@@ -0,0 +1,964 @@
|
||||
<html>
|
||||
<head><title></title></head>
|
||||
<body>
|
||||
<h1></h1>
|
||||
|
||||
<p></p>
|
||||
<blockquote>
|
||||
<h2>
|
||||
<strong><span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: large"
|
||||
><span style="font-style: normal">Phosphate, activation, and aging</span></span></span
|
||||
></span></strong>
|
||||
</h2>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Recent publications are showing that excess phosphate can increase inflammation, tissue atrophy,
|
||||
calcification of blood vessels, cancer, dementia, and, in general, the processes of aging. This
|
||||
is especially important, because of the increasing use of phosphates as food additives.</span
|
||||
></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>Previously, the complications of chronic kidney disease, with increased serum phosphate,
|
||||
were considered to be specific for that condition, but the discovery of a
|
||||
phosphate-regulating gene named klotho (after one of the Fates in Greek mythology) has
|
||||
caused a lot of rethinking of the biological role of phosphate. In the 19th century,
|
||||
phosphorus was commonly called brain food, and since about 1970, its involvement in cell
|
||||
regulation has become a focus of reductionist thinking. ATP, adenosine triphosphate, is
|
||||
seen as the energy source that drives cell movement as well as the "pumps" that maintain
|
||||
the living state, and as the source of the cyclic AMP that is a general activator of
|
||||
cells, and as the donor of the phosphate group that activates a great number of proteins
|
||||
in the "phosphorylation cascade." When tissues calcified in the process of aging,
|
||||
calcium was blamed (ignoring the existence of calcium phosphate crystals in the
|
||||
tissues), and low calcium diets were recommended. Recently, when calcium supplements
|
||||
haven't produced the intended effects, calcium was blamed, disregarding the other
|
||||
materials present in the supplements, such as citrate, phosphate, orotate, aspartate,
|
||||
and lactate.</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>I have a different perspective on the "phosphorylation cascade," and on the other functions of
|
||||
phosphate in cells, based largely on my view of the role of water in cell physiology. In the
|
||||
popular view, a stimulus causes a change of shape in a receptor protein, causing it to become an
|
||||
active enzyme, catalyzing the transfer of a phosphate group from ATP to another protein, causing
|
||||
it to change shape and become activated, and to transfer phosphate groups to other molecules, or
|
||||
to remove phosphates from active enzymes, in chain reactions. This is standard biochemistry,
|
||||
that can be done in a test tube.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Starting around 1970, when the involvement of phosphorylation in the activation of enzymes in
|
||||
glycogen breakdown was already well known, people began noticing that the glycogen phosphorylase
|
||||
enzyme became active immediately when the muscle cell contracted, and that phosphorylation
|
||||
followed the activation. Phosphorylation was involved in activation of the enzyme, but if
|
||||
something else first activated the enzyme (by changing its shape), the addition of the phosphate
|
||||
group couldn't be considered as causal, in the usual reductionist sense. It was one participant
|
||||
in a complex causal process. I saw this as a possible example of the effect of changing water
|
||||
structure on protein structure and function. This view of water questions the relevance of test
|
||||
tube biochemistry.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Enzymes are known which suddenly become inactive when the temperature is lowered beyond a certain
|
||||
point. This is because soluble proteins arrange their shape so that their hydrophobic regions,
|
||||
the parts with fat-like side-chains on the amino acids, are inside, with the parts of the chain
|
||||
with water-soluble amino acids arranged to be on the outside, in contact with the water. The
|
||||
"wetness" of water, its activity that tends to exclude the oily parts of the protein molecule,
|
||||
decreases as the temperature decreases, and some proteins are destabilized when the relatively
|
||||
hydrophobic group is no longer repelled by the surrounding cooler water. </span></span
|
||||
></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>In the living cell, the water is all within a very short distance of a surface of fats or
|
||||
fat-like proteins. In a series of experiments, starting in the 1960s, Walter
|
||||
Drost-Hansen showed that, regardless of the nature of the material, the water near a
|
||||
surface is structurally modified, becoming less dense, more voluminous. This water is
|
||||
more "lipophilic," adapting itself to the presence of fatty material, as if it were
|
||||
colder. This change in the water's properties also affects the solubility of ions,
|
||||
increasing the solubility of potassium, decreasing that of sodium, magnesium, and
|
||||
calcium (Wiggins, 1973).</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>When a muscle contracts, its volume momentarily decreases (Abbott and Baskin, 1962). Under
|
||||
extremely high pressure, muscles contract. In both situations, the work-producing
|
||||
process of contraction is associated with a slight reduction in volume. During
|
||||
contraction of a muscle or nerve, heat is given off, causing the temperature to rise.
|
||||
During relaxation, recovering from excitation, heat is absorbed (Curtin and Woledge,
|
||||
1974; Westphal, et al., 1999; Constable, et al. 1997). In the case of a nerve, following
|
||||
the heating produced by excitation, the temperature of the nerve decreases below the
|
||||
starting temperature (Abbot, et al., 1965). Stretching a muscle causes energy to be
|
||||
absorbed (Constable, et al., 1997). Energy changes such as these, without associated
|
||||
chemical changes, have led some investigators to conclude that muscle tension generation
|
||||
is "entropy driven" (Davis and Rodgers, 1995). </span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>Kelvin's description (1858) of the physics of water in a soap bubble, "…if a film such as a
|
||||
soap-bubble be enlarged . . . it experiences a cooling effect . . . ," describes the
|
||||
behavior of nerves and muscles, absorbing energy or heat when they are relaxing (or
|
||||
elongating), releasing it when they are excited/contracting. </span></span></span
|
||||
></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>Several groups of experimenters over the last 60 years have tried to discover what happens
|
||||
to the missing heat; some have suggested electrical or osmotic storage, and some have
|
||||
demonstrated that stretching generates ATP, arguing for chemical storage. Physical
|
||||
storage in the form of structural changes in the water-protein-lipid system, interacting
|
||||
with chemical changes such as ATP synthesis, have hardly been investigated.</span></span
|
||||
></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>Early studies of muscle chemistry and contraction found that adding ATP to a viscous
|
||||
solution of proteins extracted from muscle reduced its viscosity, and also that the loss
|
||||
of ATP from muscle caused its hardening, as in rigor mortis; if the pH wasn't too
|
||||
acidic, the dead muscle would contract as the ATP content decreased. Szent-Gyorgyi found
|
||||
that a muscle hardened by rigor mortis became soft again when ATP was added. </span
|
||||
></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>Rigor mortis is an extreme state of fatigue, or energy depletion. Early muscle studies
|
||||
described the phenomenon of "fatigue contracture," in which the muscle, when it reaches
|
||||
the point at which it stops responding to stimulation, is maximally contracted (this has
|
||||
also been called delayed relaxation). Ischemic contracture, in the absence of blood
|
||||
circulation, occurs when the muscle's glycogen is depleted, so that ATP can no longer be
|
||||
produced anaerobically (Kingsley, et al., 1991). The delayed relaxation of hypothyroid
|
||||
muscle is another situation in which it is clear that ATP is required for relaxation.
|
||||
(In the Achilles tendon reflex test, the relaxation rate is visibly slowed in
|
||||
hypothyroidism.) A delayed T wave in the electrocardiogram, and the diastolic
|
||||
contracture of the failing heart show the same process of delayed relaxation.
|
||||
Supplementing the active thyroid hormone, T3, can quickly restore the normal rate of
|
||||
relaxation, and its beneficial effects have been demonstrated in heart failure
|
||||
(Pingitore, et al., 2008; Wang, et al., 2006; Pantos, et al., 2007; Galli, et al.,
|
||||
2008).</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>A large part of the magnesium in cells is bound to ATP, and the magnesium-ATP complex is a
|
||||
factor in muscle relaxation. A deficiency of either ATP or magnesium contributes to
|
||||
muscle cramping. When a cell is stimulated, causing ATP to release inorganic phosphate,
|
||||
it also releases magnesium. Above the pH of 6.7, phosphate is doubly ionized, in which
|
||||
state it has the same kind of structural effect on water that magnesium, calcium, and
|
||||
sodium have, causing water molecules to be powerfully attracted to the concentrated
|
||||
electrical charge of the ion. Increasing the free phosphate and magnesium opposes the
|
||||
effect of the surfaces of fats and proteins on the water structure, and tends to
|
||||
decrease the solubility of potassium in the water, and to increase the water's
|
||||
"lipophobic" tendency to minimize its contacts with fats and the fat-like surface of
|
||||
proteins, causing the proteins to rearrange themselves. </span></span></span></span
|
||||
></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>These observations relating to the interactions of water, solutes and proteins in muscles
|
||||
and nerves provide a coherent context for understanding contraction and conduction,
|
||||
which is lacking in the familiar descriptions based on membranes, pumps, and
|
||||
cross-bridges, but I think they also provide a uniquely useful context for understanding
|
||||
the possible dangers of an excess of free phosphate in the body.</span></span></span
|
||||
></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>A few people (M. Thomson, J. Gunawardena, A.K. Manrai) are showing that principles of
|
||||
mass-action help to simplify understanding the networks of phosphorylation and
|
||||
dephosphorylation that are involved in cell control. But independently from the
|
||||
phosphorylation of proteins, the presence of phosphate ion in cell water modifies the
|
||||
cell's ion selectivity, shifting the balance toward increased uptake of sodium and
|
||||
calcium, decreasing potassium, tending to depolarize and "activate" the cell.</span
|
||||
></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>About 99% of the publications discussing the mechanism of muscle contraction fail to
|
||||
mention the presence of water, and there's a similar neglect of water in discussions of
|
||||
the energy producing processes in the mitochondrion. The failure of mitochondrial energy
|
||||
production leads to lipid peroxidation, activation of inflammatory processes, and can
|
||||
cause disintegration of the energy producing structure. Increased phosphate decreases
|
||||
mitochondrial energy production (Duan and Karmazyn, 1989), causes lipid peroxidation
|
||||
(Kowaltowski, et al., 1996), and activates inflammation, increasing the processes of
|
||||
tissue atrophy, fibrosis, and cancer.</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>For about twenty years it has been clear that the metabolic problems that cause calcium to
|
||||
be lost from bones cause calcium to increase in the soft tissues, such as blood vessels.
|
||||
The role of phosphate in forming calcium phosphate crystals had until recently been
|
||||
assumed to be passive, but some specific "mechanistic" effects have been identified. For
|
||||
example, increased phosphate increases the inflammatory cytokine, osteopontin
|
||||
(Fatherazi, et al., 2009), which in bone is known to activate the process of
|
||||
decalcification, and in arteries is involved in calcification processes (Tousoulis, et
|
||||
al., 2012). In the kidneys, phosphate promotes calcification (Bois and Selye, 1956), and
|
||||
osteopontin, by its activation of inflammatory T-cells, is involved in the development
|
||||
of glomerulonephritis, as well as in inflammatory skin reactions (Yu, et al., 1998).
|
||||
High dietary phosphate increases serum osteopontin, as well as serum phosphate and
|
||||
parathyroid hormone, and increases the formation of tumors in skin (Camalier, et al.,
|
||||
2010). Besides the activation of cells and cell systems, phosphate (like other
|
||||
ions with a high ratio of charge to size, including citrate) can activate viruses
|
||||
(Yamanaka, et al., 1995; Gouvea, et al., 2006). Aromatase, the enzyme that synthesizes
|
||||
estrogen, is an enzyme that's sensitive to the concentration of phosphate (Bellino and
|
||||
Holben, 1989).</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>More generally, increased dietary phosphate increases the activity of an important
|
||||
regulatory enzyme, protein kinase B, which promotes organ growth. A high phosphate diet
|
||||
increases the growth of liver (Xu, et al., 2008) and lung (Jin, et al., 2007), and
|
||||
promotes the growth of lung cancer (Jin, et al., 2009). An extreme reduction of
|
||||
phosphate in the diet wouldn't be appropriate, however, because a phosphate deficiency
|
||||
stimulates cells to increase the phosphate transporter, increasing the cellular uptake
|
||||
of phosphate, with an effect similar to the dietary excess of phosphate, i.e., promotion
|
||||
of lung cancer (Xu, et al., 2010). The optimum dietary amount of phosphate, and its
|
||||
balance with other minerals, hasn't been determined.</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>While increased phosphate slows mitochondrial energy production, decreasing its
|
||||
intracellular concentration increases the respiratory rate and the efficiency of ATP
|
||||
formation. A "deficiency" of polyunsaturated fatty acids has this effect (Nogueira, et
|
||||
al., 2001), but so does the consumption of fructose (Green, et al., 1993; Lu, et al.,
|
||||
1994).</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>In a 1938 experiment (Brown, et al.) that intended to show the essentiality of unsaturated fats, a
|
||||
man, William Brown, lived for six months on a 2500 calorie diet consisting of sucrose syrup, a
|
||||
gallon of milk (some of it in the form of cottage cheese), and the juice of half an orange,
|
||||
besides some vitamins and minerals. The experimenters remarked about the surprising
|
||||
disappearance of the normal fatigue after a day's work, as well as the normalization of his high
|
||||
blood pressure and high cholesterol, and the permanent disappearance of his frequent life-long
|
||||
migraine headaches. His respiratory quotient increased (producing more carbon dioxide), as well
|
||||
as his rate of resting metabolism. I think the most interesting part of the experiment was that
|
||||
his blood phosphate decreased. In two measurements during the experimental diet, his fasting
|
||||
plasma inorganic phosphorus was 3.43 and 2.64 mg. per 100 ml. of plasma, and six month after he
|
||||
had returned to a normal diet the number was 4.2 mg/100 ml. Both the deficiency of the
|
||||
"essential" unsaturated fatty acids, and the high sucrose intake probably contributed to
|
||||
lowering the phosphate.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>In 2000, researchers who were convinced that fructose is harmful to the health, reasoned
|
||||
that its harmful effects would be exacerbated by consuming it in combination with a diet
|
||||
deficient in magnesium. Eleven men consumed, for six months, test diets with high
|
||||
fructose corn syrup or starch, along with some fairly normal U.S. foods, and with either
|
||||
extremely low magnesium content, or with slightly deficient magnesium content. The
|
||||
authors' conclusion was clearly stated in the title of their article, that the
|
||||
combination adversely affects the mineral balance of the body. </span></span></span
|
||||
></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>However, looking at their results in the context of these other studies of the effects of
|
||||
fructose on phosphate, I don't think their conclusion is correct. Even on the extremely
|
||||
low magnesium intake, both their magnesium and calcium balances were positive, meaning
|
||||
that on average their bodies accumulated a little magnesium and calcium, even though men
|
||||
aged 22 to 40 presumably weren't growing very much. To steadily accumulate both calcium
|
||||
and magnesium, with the calcium retention much larger than the magnesium, the minerals
|
||||
were probably mostly being incorporated into their bones. Their phosphate balance,
|
||||
however, was slightly negative on the "high fructose" diet. If the sugar was having the
|
||||
same effect that it had on William Brown in 1938 (and in animal experiments), some of
|
||||
the phosphate loss was accounted for by the reduced amount in blood and other body
|
||||
fluids, but to continue through the months of the experiment, some of it must have
|
||||
represented a change in the composition of the bones. When there is more carbon dioxide
|
||||
in the body fluids, calcium carbonate can be deposited in the bones (Messier, et al.,
|
||||
1979). Increased carbon dioxide could account for a prolonged negative phosphate
|
||||
balance, by taking its place in the bones in combination with calcium and
|
||||
magnesium. </span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>Another important effect of carbon dioxide is in the regulation of both calcium and
|
||||
phosphate, by increasing the absorption and retention of calcium (Canzanello, et al.,
|
||||
1995), and by increasing the excretion of phosphate. Increased carbon dioxide (as
|
||||
dissolved gas) and bicarbonate (as sodium bicarbonate) both increase the excretion of
|
||||
phosphate in the urine, even in the absence of the parathyroid hormone. Below the normal
|
||||
level of serum bicarbonate, reabsorption of phosphate by the kidneys is greatly
|
||||
increased (Jehle, et al., 1999). Acetazolamide increases the body's retention of carbon
|
||||
dioxide, and increases the amount of phosphate excreted in the urine. </span></span
|
||||
></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Much of the calcium dissolved in the blood is in the form of a complex of calcium and bicarbonate,
|
||||
with a single positive charge (Hughes, et al., 1984). Failure to consider this complexed form of
|
||||
calcium leads to errors in measuring the amount of calcium in the blood, and in interpreting its
|
||||
physiological effects, including its intracellular behavior. Hyperventilation can cause cramping
|
||||
of skeletal muscles, constriction of blood vessels, and excitation of platelets and other cells;
|
||||
the removal of carbon dioxide from the blood lowers the carbonic acid, changing the state and
|
||||
function of calcium. Hyperventilation increases phosphate and parathyroid hormone, and decreases
|
||||
calcium (Krapf, et al., 1992).</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Since estrogen tends to cause hyperventilation, lowering carbon dioxide, its role in phosphate
|
||||
metabolism should be investigated more thoroughly. Work by Han, et al. (2002) and Xu, et al.
|
||||
(2003) showed that estrogen increases phosphate reabsorption by the kidney, but estrogen also
|
||||
increases cortisol, which decreases reabsorption, so the role of estrogen in the whole system
|
||||
has to be be considered. </span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>This calcium solubilizing effect of bicarbonate, combined with its phosphaturic effect,
|
||||
probably accounts for the relaxing effect of carbon dioxide on the blood vessels and
|
||||
bronchial smooth muscles, and for the prevention of vascular calcification by the
|
||||
thyroid hormones (Sato, et al., 2005, Tatar, 2009, Kim, et al., 2012). Distensibility of
|
||||
the blood vessels and heart, increased by carbon dioxide, is decreased in
|
||||
hypothyroidism, heart failure, and by phosphate. </span></span></span></span></span
|
||||
>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>While fructose lowers intracellular phosphate, it also lowers the amount that the intestine
|
||||
absorbs from food (Kirchner, et al.,2008), and the Milne-Nielsen study suggests that it
|
||||
increases phosphate loss through the kidneys. The "anti-aging" protein, klotho,
|
||||
increases the ability of the kidneys to excrete phosphate (Dërmaku-Sopjani, et al.,
|
||||
2011), and like fructose, it supports energy production and maintains thermogenesis
|
||||
(Mori, et al., 2000). </span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>Lowering the amount of phosphate in the blood allows the parathyroid hormone to decrease.
|
||||
While the parathyroid hormone also prevents phosphate reabsorption by the kidneys, it
|
||||
causes mast cells to release serotonin (and serotonin increases the kidneys'
|
||||
reabsorption of phosphate), and possibly has other pro-inflammatory effects. For
|
||||
example, deleting the PTH gene compensates for the harmful (accelerated calcification
|
||||
and osteoporosis) effects of deleting the klotho gene, apparently by preventing the
|
||||
increase of osteopontin (Yuan, et al., 2012).</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>Niacinamide is another nutrient that lowers serum phosphate (Cheng, et al., 2008), by
|
||||
inhibiting intestinal absorption (Katai, et al., 1989), and also by reducing its
|
||||
reabsorption by the kidneys (Campbell, et al., 1989). Niacinamide's reduction of free
|
||||
fatty acids by inhibiting lipolysis, protecting the use of glucose for energy, might be
|
||||
involved in its effect on phosphate (by analogy with the phosphate lowering action of a
|
||||
deficiency of polyunsaturated fatty acids). Aspirin is another antilipolytic substance
|
||||
(de Zentella, et al., 2002) which stimulates energy production from sugar and lowers
|
||||
phosphate, possibly combined with improved magnesium retention (Yamada and Morohashi,
|
||||
1986).</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>A diet that provides enough calcium to limit activity of the parathyroid glands, and that
|
||||
is low in phosphate and polyunsaturated fats, with sugar rather than starch as the main
|
||||
carbohydrate, possibly supplemented by niacinamide and aspirin, should help to avoid
|
||||
some of the degenerative processes associated with high phosphate: fatigue, heart
|
||||
failure, movement discoordination, hypogonadism, infertility, vascular calcification,
|
||||
emphysema, cancer, osteoporosis, and atrophy of skin, skeletal muscle, intestine,
|
||||
thymus, and spleen (Ohnishi and Razzaque, 2010; Shiraki-Iida, et al., 2000; Kuro-o, et
|
||||
al., 1997; Osuka and Razzaque, 2012). The foods naturally highest in phosphate, relative
|
||||
to calcium, are cereals, legumes, meats, and fish. Many prepared foods contain added
|
||||
phosphate. Foods with a higher, safer ratio of calcium to phosphate are leaves, such as
|
||||
kale, turnip greens, and beet greens, and many fruits, milk, and cheese. Coffee, besides
|
||||
being a good source of magnesium, is probably helpful for lowering phosphate, by its
|
||||
antagonism to adenosine (Coulson, et al., 1991).</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Although increased phosphate generally causes vascular calcification (increasing rigidity, with
|
||||
increased systolic blood pressure), when a high level of dietary phosphate comes from milk and
|
||||
cheese, it is epidemiologically associated with reduced blood pressure (Takeda, et al.,
|
||||
2012).</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>Phosphate toxicity offers some interesting insights into stress and aging, helping to
|
||||
explain the protective effects of carbon dioxide, thyroid hormone, sugar, niacinamide,
|
||||
and calcium. It also suggests that other natural substances used as food additives
|
||||
should be investigated more thoroughly. Excessive citric acid, for example, might
|
||||
activate dormant cancer cells (Havard, et al., 2011), and has been associated with
|
||||
malignancy (Blüml, et al., 2011). Nutritional research has hardly begun to investigate
|
||||
the optimal ratios of minerals, fats, amino acids, and other things in foods, and how
|
||||
they interact with the natural toxicants, antinutrients, and hormone disrupters in many
|
||||
organisms used for food.</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"><h3>REFERENCES</h3></span></span
|
||||
></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Physiology 1962; 161, 379-391. Volume changes in frog muscle during contraction. Abbott C &
|
||||
Baskin RJ.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Physiol. 1965 May; 178(2): 368–383. The initial heat production associated with the nerve impulse
|
||||
in crustacean and mammalian non-myelinated nerve fibbers. Abbott BC, Howarth JV, and Ritchie
|
||||
JM.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Fiziol Zh SSSR Im I M Sechenova. 1982 Jan;68(1):59-63. [Oxygen, carbon dioxide and calcium control
|
||||
of the mechanisms of relaxation in the cerebral artery smooth musculature]. [Article in Russian]
|
||||
Azin AL.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Biochem Biophys Res Commun. 1989 Jul 14;162(1):498-504. Placental estrogen synthetase (aromatase):
|
||||
evidence for phosphatase-dependent inactivation. Bellino FL, Holben L.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Neuro Oncol. 2011 Oct;13(10):1107-17. Elevated citrate in pediatric astrocytomas with malignant
|
||||
progression. Blüml S, Panigrahy A, Laskov M, Dhall G, Krieger MD, Nelson MD, Finlay JL,
|
||||
Gilles</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>FH.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Am J Physiol. 1956 Sep;187(1):41-4. Effect of corticoids on the resistance of the kidney to an
|
||||
excess of phosphates. Bois P, Selye H.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J. Nutrition 1938;16(6), Effects of prolonged use of extremely low-fat diet on an adult human
|
||||
subject. Brown WR, Hansen AE, Burr GO, & McQuarrie I. </span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Pharmacol Exp Ther. 1989 Oct;251(1):188-92. Specific inhibition of rat renal Na+/phosphate
|
||||
cotransport by picolinamide. Campbell PI, al-Mahrouq HA, Abraham MI, Kempson SA.</span></span
|
||||
></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Lab Clin Med. 1995 Jul;126(1):81-7. Effect of chronic respiratory acidosis on calcium metabolism
|
||||
in the rat. Canzanello VJ, Kraut JA, Holick MF, Johns C, Liu CC, Madias NE.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Clin J Am Soc Nephrol. 2008 Jul;3(4):1131-8. A randomized, double-blind, placebo-controlled trial
|
||||
of niacinamide for reduction of phosphorus in hemodialysis patients. Cheng SC, Young DO, Huang
|
||||
Y, Delmez JA, Coyne DW.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Physiol. 1997 Nov 15;505 ( Pt 1):205-15. Energetics of lengthening in mouse and toad skeletal
|
||||
muscles. Constable JK, Barclay CJ, Gibbs CL.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Am J Physiol. 1991 Jun;260(6 Pt 2):F921-8. Adenosine stimulates phosphate and glucose transport in
|
||||
opossum kidney epithelial cells. Coulson R, Johnson RA, Olsson RA, Cooper DR, Scheinman
|
||||
SJ.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Physiol. 1974 Apr;238(2):437–446. Energetics of relaxation in frog muscle. Curtin NA, Woledge
|
||||
RC. </span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10482-6. Indirect coupling of phosphate release to de
|
||||
novo tension generation during muscle contraction. Davis JS, Rodgers ME.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Cell Physiol Biochem. 2011;28(2):251-8. Downregulation of NaPi-IIa and NaPi-IIb Na-coupled
|
||||
phosphate transporters by coexpression of Klotho. Dërmaku-Sopjani M, Sopjani M, Saxena A,
|
||||
Shojaiefard M, Bogatikov E, Alesutan I, Eichenmüller M, Lang F.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Res Commun Chem Pathol Pharmacol. 1989 Mar;63(3):361-72. A rapid phosphate-induced depression of
|
||||
heart subsarcolemmal mitochondrial oxidative phosphorylation. Duan J, Karmazyn M.</span></span
|
||||
></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Med Princ Pract. 2011 Dec 16. Inflammatory Biomarkers in Patients with Asymptomatic Primary
|
||||
Hyperparathyroidism. Emam AA, Mousa SG, Ahmed KY, Al-Azab AA.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J of Dental Res. JDR January 2009 vol. 88 no. 1 39-44. Phosphate Regulates Osteopontin Gene
|
||||
Transcription. Fatherazi S, Matsa-Dunn D, Foster BL, Rutherford RB, Somerman MJ, Presland
|
||||
RB. </span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>J Clin Invest. 1968 May;47(5):983-91. The phosphaturic effect of sodium bicarbonate and
|
||||
acetazolamide in dogs. Fulop M, Brazeau P.</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Biochemistry. 2006 Oct 3;45(39):12083-9. Kosmotropic salt activation and substrate specificity of
|
||||
poliovirus protease 3C. Gouvea IE, Judice WA, Cezari MH, Juliano MA, Juhász T, Szeltner Z,
|
||||
Polgár L, Juliano L.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Am J Physiol. 1993 Sep;265(3 Pt 2):F440-8. Acute phosphate depletion inhibits the Na+/H+ antiporter
|
||||
in a cultured renal cell line. Green J, Foellmer O, Kleeman CR, Basic MM.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Am J Physiol. 1987 Jul;253(1 Pt 2):F34-40. Effect of acute hypercapnia on PTH-stimulated
|
||||
phosphaturia in dietary Pi-deprived rat. Guntupalli J, Matthews B, Carlin B, Bourke E.</span
|
||||
></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Exp Nephrol. 2002;10(5-6):355-64. Estradiol-17beta stimulates phosphate uptake and is mitogenic for
|
||||
primary rabbit renal proximal tubule cells. Han HJ, Lee YH, Park KM, Taub M.</span></span></span
|
||||
>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Biol Chem. 2011 Dec 23;286(51):44177-86. A dormant state modulated by osmotic pressure controls
|
||||
clonogenicity of prostate cancer cells. Havard M, Dautry F, Tchénio T.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Lab Clin Med. 1984 Jan;103(1):93-103. The effect of the bicarbonate anion on serum ionized
|
||||
calcium concentration in vitro. Hughes WS, Aurbach GD, Sharp ME, Marx SJ.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Am J Physiol. 1999 Jan;276(1 Pt 2):F46-53. Type II Na-Pi cotransport is regulated transcriptionally
|
||||
by ambient bicarbonate/carbon dioxide tension in OK cells. Jehle AW, Hilfiker H, Pfister MF,
|
||||
Biber J, Lederer E, Krapf R, Murer H.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Toxicol Sci. 2007 Nov;100(1):215-23. High dietary inorganic phosphate affects lung through altering
|
||||
protein translation, cell cycle, and angiogenesis in developing mice. Jin H, Chang SH, Xu CX,
|
||||
Shin JY, Chung YS, Park SJ, Lee YS, An GH, Lee KH, Cho MH.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Am J Respir Crit Care Med. 2009 Jan 1;179(1):59-68. High dietary inorganic phosphate increases lung
|
||||
tumorigenesis and alters Akt signaling. Jin H, Xu CX, Lim HT, Park SJ, Shin JY, Chung YS, Park
|
||||
SC, Chang SH, Youn HJ, Lee KH, Lee YS, Ha YC, Chae CH, Beck GR Jr, Cho MH.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Nephrol Dial Transplant. 1999 May;14(5):1195-201. Nicotinamide inhibits sodium-dependent phosphate
|
||||
cotransport activity in rat small intestine. Katai K, Tanaka H, Tatsumi S, Fukunaga Y, Genjida
|
||||
K, Morita K, Kuboyama N, Suzuki T, Akiba T, Miyamoto K, Takeda E.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Thyroid. 2012 May 24. Association between low serum free thyroxine concentrations and coronary
|
||||
artery calcification in healthy euthyroid subjects. Kim ES, Shin JA, Moon S, Shin JY, Han JH,
|
||||
Son HY.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Thyroid. 2012 Sep;22(9):870-6. Association between low serum free thyroxine concentrations and
|
||||
coronary artery calcification in healthy euthyroid subjects. Kim ES, Shin JA, Shin JY, Lim DJ,
|
||||
Moon SD, Son HY, Han JH.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Am J Physiol. 1991 Aug;261(2 Pt 2):H469-78. Ischemic contracture begins when anaerobic glycolysis
|
||||
stops: a 31P-NMR study of isolated rat hearts. Kingsley PB, Sako EY, Yang MQ, Zimmer SD, Ugurbil
|
||||
K, Foker JE, From AH.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Am J Clin Nutr. 2008 Apr;87(4):1028-38. Luminal fructose inhibits rat intestinal sodium-phosphate
|
||||
cotransporter gene expression and phosphate uptake. Kirchner S, Muduli A, Casirola D, Prum K,
|
||||
Douard V, Ferraris RP.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Biol Chem. 1996 Feb 9;271(6):2929-34.Effect of inorganic phosphate concentration on the nature of
|
||||
inner mitochondrial membrane alterations mediated by Ca2+ ions. A proposed model for
|
||||
phosphate-stimulated lipid peroxidation. Kowaltowski AJ, Castilho RF, Grijalba MT, Bechara EJ,
|
||||
Vercesi AE.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Kidney Int. 1992 Sep;42(3):727-34. Chronic respiratory alkalosis induces renal PTH-resistance,
|
||||
hyperphosphatemia and hypocalcemia in humans. Krapf R, Jaeger P, Hulter HN.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Nature. 1997 Nov 6;390(6655):45-51. Mutation of the mouse klotho gene leads to a syndrome
|
||||
resembling ageing. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y,
|
||||
Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R,
|
||||
Nabeshima YI.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Magn Reson Med. 1994 May;31(5):469-81. In vivo and in vitro 31P magnetic resonance spectroscopic
|
||||
studies of the hepatic response of healthy rats and rats with acute hepatic damage to fructose
|
||||
loading. Lu W, Locke SJ, Brauer M.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Undersea Biomed Res. 1979;6 Suppl:S57-70. Calcium, magnesium, and phosphorus metabolism, and
|
||||
parathyroid-calcitonin function during prolonged exposure to elevated CO2 concentrations on
|
||||
submarines. Messier AA, Heyder E, Braithwaite WR, McCluggage C, Peck A, Schaefer KE. "It is
|
||||
suggested that during prolonged exposure to low levels of CO2 (up to 1% CO2), calcium metabolism
|
||||
is controlled by the uptake and release of CO2 in the bones."</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Biochem Biophys Res Commun. 2000 Nov 30;278(3):665-70. Disruption of klotho gene causes an abnormal
|
||||
energy homeostasis in mice. Mori K, Yahata K, Mukoyama M, Suganami T, Makino H, Nagae T,
|
||||
Masuzaki H, Ogawa Y, Sugawara A, Nabeshima Y, Nakao K. "Uncoupling protein-1 gene expression of
|
||||
BAT and body temperature in klotho mice are lower than those in wild-type mice, suggesting that
|
||||
klotho mice have less energy expenditure than wild-type mice." "All these changes of parameters
|
||||
for energy homeostasis in klotho mice are very similar to those reported under food-restricted
|
||||
conditions.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Bioenerg Biomembr. 2001 Feb;33(1):53-61. Mitochondrial adaptation to in vivo polyunsaturated
|
||||
fatty acid deficiency: increase in phosphorylation efficiency. Nogueira V, Piquet MA, Devin A,
|
||||
Fiore C, Fontaine E, Brandolin G, Rigoulet M, Leverve XM.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>FASEB J. 2010 Sep;24(9):3562-71. Dietary and genetic evidence for phosphate toxicity accelerating
|
||||
mammalian aging. Ohnishi M, Razzaque MS.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Bone Miner Metab. 2012 Jan;30(1):10-8. Can features of phosphate toxicity appear in
|
||||
normophosphatemia? Osuka S, Razzaque MS.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Clin Sci (Lond). 2011 Feb;120(3):91-7. Phosphate toxicity: new insights into an old problem.
|
||||
Razzaque MS.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Circ Res. 1960 Jul;8:788-93. Distensibility and water content of heart muscle before and after
|
||||
injury. Salisbury PF, Cross CE, Rieben PA.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Circ Res. 2005 Sep 16;97(6):550-7. Thyroid hormone targets matrix Gla protein gene associated with
|
||||
vascular smooth muscle calcification. Sato Y, Nakamura R, Satoh M, Fujishita K, Mori S, Ishida
|
||||
S, Yamaguchi T, Inoue K, Nagao T, Ohno Y.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Gene Med. 2000 Jul-Aug;2(4):233-42. Improvement of multiple pathophysiological phenotypes of
|
||||
klotho (kl/kl) mice by adenovirus-mediated expression of the klotho gene. Shiraki-Iida T, Iida
|
||||
A, Nabeshima Y, Anazawa H, Nishikawa S, Noda M, Kuro-o M, Nabeshima Y.J </span></span
|
||||
></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Nutr Rev. 2012 Jun;70(6):311-21. Dietary phosphorus in bone health and quality of life. Takeda E,
|
||||
Yamamoto H, Yamanaka-Okumura H, Taketani Y.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"> <span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
><span style="font-style: normal"><span style="font-weight: normal"
|
||||
>Clin J Am Soc Nephrol. 2011 Sep;6(9):2240-6. Associations of triiodothyronine levels with
|
||||
carotid atherosclerosis and arterial stiffness in hemodialysis patients. Tatar E,
|
||||
Kircelli F, Asci G, Carrero JJ, Gungor O, Demirci MS, Ozbek SS, Ceylan N, Ozkahya M, Toz
|
||||
H, Ok E.</span></span></span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Int J Cardiol. 2012 May 26. Serum osteoprotegerin and osteopontin levels are associated with
|
||||
arterial stiffness and the presence and severity of coronary artery disease. Tousoulis D, Siasos
|
||||
G, Maniatis K, Oikonomou E, Kioufis S, Zaromitidou M, Paraskevopoulos T, Michalea S, Kollia C,
|
||||
Miliou A, Kokkou E, Papavassiliou AG, Stefanadis C. "Osteopontin (OPN) and osteoprotegerin (OPG)
|
||||
have recently emerged as </span></span></span>
|
||||
</blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>key factors in both vascular remodeling and development of atherosclerosis." "These preliminary
|
||||
results suggest that OPG and OPN levels are significantly correlated with vascular function
|
||||
contributing to the pathogenesis of atherosclerosis in CAD." </span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Science 2 July 1999: Vol. 285 no. 5424 pp. 93-96. Regulation of NMDA Receptors by an Associated
|
||||
Phosphatase-Kinase Signaling Complex. Westphal RS, Tavalin SJ, Lin JW, Alto NM, Fraser
|
||||
IDC, Langeberg LK, Sheng M, Scott JD.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Biophys J. 1973 Apr;13(4):385-98. Ionic partition between surface and bulk water in a silica gel. A
|
||||
biological model. Wiggins PM.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Am J Physiol Gastrointest Liver Physiol. 2008 Oct;295(4):G654-63. High dietary inorganic phosphate
|
||||
enhances cap-dependent protein translation, cell-cycle progression, and angiogenesis in the
|
||||
livers of young mice. Xu CX, Jin H, Lim HT, Kim JE, Shin JY, Lee ES, Chung YS, Lee YS, Beck G
|
||||
Jr, Lee KH, Cho MH.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Nutr Cancer. 2010;62(4):525-32. Low dietary inorganic phosphate stimulates lung tumorigenesis
|
||||
through altering protein translation and cell cycle in K-ras(LA1) mice. Xu CX, Jin H, Lim HT, Ha
|
||||
YC, Chae CH, An GH, Lee KH, Cho MH.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1317-24. Regulation of intestinal
|
||||
NaPi-IIb cotransporter gene expression by estrogen. Xu H, Uno JK, Inouye M, Xu L, Drees JB,
|
||||
Collins JF, Ghishan FK.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>"These studies demonstrate for the first time that estrogen stimulates intestinal sodium-dependent
|
||||
phosphate absorption in female rats. This stimulation is associated with increased NaPi-IIb mRNA
|
||||
and protein expression."</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Nihon Yakurigaku Zasshi. 1986 Nov;88(5):395-401. [Effect of sodium salicylate on renal handling of
|
||||
calcium, phosphate and magnesium]. [Article in Japanese] Yamada S, Morohashi T. "On the
|
||||
other hand, we observed increased urinary excretion of Pi and decreased Mg excretion, which
|
||||
resulted from the changes in tubular</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>reabsorption of Pi and Mg, respectively."</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Biol Chem. 1995 Dec 15;270(50):30168-72. Stimulation of the herpes simplex virus type I protease
|
||||
by antichaeotrophic salts. Yamanaka G, DiIanni CL, O'Boyle DR 2nd, Stevens J, Weinheimer SP,
|
||||
Deckman IC, Matusick-Kumar L, Colonno RJ.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>Proc Assoc Am Physicians. 1998 Jan-Feb;110(1):50-64. A functional role for osteopontin in
|
||||
experimental crescentic glomerulonephritis in the rat. Yu XQ, Nikolic-Paterson DJ, Mu W,
|
||||
Giachelli CM, Atkins RC, Johnson RJ, Lan HY.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>PLoS Genet. 2012;8(5):e1002726. Deletion of PTH rescues skeletal abnormalities and high osteopontin
|
||||
levels in Klotho-/- mice. Yuan Q, Sato T, Densmore M, Saito H, Schüler C, Erben RG, Lanske
|
||||
B.</span></span></span>
|
||||
</blockquote>
|
||||
<blockquote></blockquote>
|
||||
<blockquote>
|
||||
<span style="color: #222222"><span style="font-family: georgia, times, serif"><span
|
||||
style="font-size: medium"
|
||||
>J Pharm Pharmacol. 2002 Apr;54(4):577-82. Non-steroidal anti-inflammatory drugs inhibit
|
||||
epinephrine- and cAMP-mediated lipolysis in isolated rat adipocytes. de Zentella PM,
|
||||
Vázquez-Meza H, Piña-Zentella G, Pimentel L, Piña E.</span></span></span>
|
||||
</blockquote>
|
||||
<p></p>
|
||||
|
||||
© Ray Peat Ph.D. 2013. All Rights Reserved. www.RayPeat.com
|
||||
</body>
|
||||
</html>
|
||||
Reference in New Issue
Block a user