Frontiers

2022; 2(1): 22-33

http://www.sciencepublishinggroup.com/j/frontiers
doi: 10.11648/j.frontiers.20220201.13

Review Article
Hossam (Y) Site Theory of Collagen Type I Decrypts the
Origin of Metabolic Syndrome (X) in the Elderly with a
Suggested Conjecture of Cure: Granted US Patent Review
Hossam Mohamed1, 2, *, Houda Almansour1, 2, Dalal Alsaadoun3, Mariam Almansour4,
Yasmin Almansour5, Sawsan Samy1, Sulaiman Alnassera6
1
Medical & Research Department, Huda Health INC, Ottawa, Canada
2
Medical & Research Department, Houda Almansour Global Medical Device & Designs INC, Ottawa, Canada
3
Internal Medicine Department, College of Medicine, King Faisal University, Alahsa, Saudi Arabia
4
Department of Endocrinology, AlFaisalia Hospital, Alhafouf City, Saudi Arabia
5
Department of Palliative Care, Specialized King Fahad Hospital, Dammam, Saudi Arabia
6
Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Qassim City, Saudi Arabia

Email address:

*
Corresponding author

To cite this article:

Hossam Mohamed, Houda Almansour, Dalal Alsaadoun, Mariam Almansour, Yasmin Almansour, Sawsan Samy, Sulaiman Alnassera.
Hossam (Y) Site Theory of Collagen Type I Decrypts the Origin of Metabolic Syndrome (X) in the Elderly with a Suggested Conjecture of
Cure: Granted US Patent Review. Frontiers. Vol. 2, No. 1, 2022, pp. 22-33. doi: 10.11648/j.frontiers.20220201.13

Received: December 27, 2021; Accepted: January 12, 2022; Published: January 20, 2022

Abstract: Collagen is the commonest protein in mammalian. Its function is thought to be only of structural support. New US
patents claimed that it has another very vital role in the human body which is piezoelectricity. Most of the chronic diseases in the
elderly are caused by the disturbance of this newly discovered function. The exact site of disturbance is defined as the site (Y) of
collagen. Profound molecular and biomechanical studies were done at the site (Y) to determine its mechanical disturbance from
the pathological point of view. As collagen is present all over the human body like bone, cartilage, the heart, brain, blood vessels,
skin, even the sclera of the eye, its correction would recover most of the tissues of the human body. This paper discusses the site
(Y) and its effect on piezo-electricity and its glycation. It discusses also all the factors that may affect the site (Y) either damaging
or recovery in the hope of avoidance of all the destructive factors and enhancing the repairing ones. It is believed that this new
method of thinking about the degenerative disease in the elderly could be treated perfectly, more physiological, and also at the
root level. This is much better than treating each disease as a separate entity. Lastly and for most, this group of degenerative
diseases has a great impact on the health care system and hospital resources of every nation. Thus, the recovery of these patients
would save a huge amount of money spent in the health care system for these chronic and almost long-lived diseases.
Keywords: Zero Holes, Gap Zone, Overlapping Zone, (Gly, X, Y), Piezo-electricity, Glycation, Visceral Fat

million. The collagen alone is about 30% & all remaining 2

1. Introduction million proteins are 70%. This percentage may denote the vital
1.1. Collagen Is the Commonest Protein in the Human importance of collagen. Moreover, the collagen itself is not
one type. It is more than 28 types. Collagen type1 is the
Collagen is the commonest protein in the mammalian. It commonest. It forms more than 90% of all the collagen of the
forms about 30% of all other proteins of the human. The human body. It is present in the bone, muscles, brain, heart,
number of known proteins in the human body is more than 2 blood vessels, skin, and sclera of the eye. Collagen is the main
 Frontiers 2022; 2(1): 22-33 23

building block of the skeleton of the animal kingdom. It is collagen acts as a transformer that converts the mechanical
analog to cellulose in the plant kingdom. As it is a fibrous stress into an electrical gradient difference (EGD) which could
protein, it is believed that its function is only of structural send messages to nearby cells to initiate the process of
support to nearby more vital structures. Therefore, it is present remodeling. The most fundamental property for the collagen,
in the capsules that support the vital organs like the liver and to do its proper job, is to be functional. This means it is not
kidney. It is also present in large amounts in tough structures glycated. Therefore, glycated collagen can not do its proper
like bone, muscle, cartilage, tendons, ligaments, and so on [1]. function in tissue remodeling. In other words, the normal
tissue damage by the wear and tear process of aging is not
1.2. Collagen and Piezoelectricity compensated by new tissue formation. Therefore, a gradual
Recently issued patent (US9801905) that profoundly tissue loss would occur leading, in the end, to complete tissue
studied the role of collagen in the vitality of the bone. dysfunction of the affected organ. If the condition is universal
Collagen is the prime mover for tissue remodeling including all over the body, the aging process occurs which is simply
bone, tendons, cartilage, ligaments, muscles, and so on. metabolic syndrome (X). This is the subject of this paper [2,
Collagen does this fundamental function through its 3].
piezoelectric (PZE) property. This simply means that the

Figure 1. The cross-section of collagen shows its 3 sites (gly, X, Y). The (Gly & X sites) are non-polar & and electrically neutral while the (Y) site is polar and
positively charged. Also, the (Y) site is the only site for the cross-linking of collagen.

amino acids are facing each other (figure 4). The site (X) is
2. The Molecular Mechanic of Collagen occupied by proline or hydroxy-proline. Proline is the only
amino acid in the collagen that has a ring that acts in the
2.1. The Hierarchy of the Collagen periphery to support the structure. The hydroxylation of
proline is an enzymatic process and needs (lysyl hydroxylase)
Collagen is formed of the triple helix which is 3 polypeptide and needs also iron and vitamin C as co-factors (figure 5). The
chains. They fold upon each other in the form of (α) folding. bonds between (Gly, X, Y) are peptide bonds. These strong
They are (2 α 1 & 1 α 2). The single thread is formed of about bonds can not yield under mechanical stress. The ones that
1050 amino acids. Therefore, each molecule that is formed of yield under the mechanical stress are the weaker hydrogen
3 threads is about 3150 amino acids. The length of each bonds [4, 7].
collagen molecule is 300nm & its cross-section is 1.5 nm.
These collagen molecules assemble via cross-linking at the (Y) 2.2. The Assembly of Collagen
site which is the subject of this paper. The cross-section of
collagen shows 3 sites of amino acids. These are (Gly, X, Y) Each collagen molecule (300nm) is assembled with the
as in figure 1. The (Gly) is always glycine and it is the smallest other nearby collagen to form collagen fibril (1-3um). The
and simplest amino acid ever. Therefore, it is always directed assembly occurs at the site (Y) if it is occupied by lysine
to the interior of the collagen. This means that the 3 (glycine) amino acids. This is an enzymatic connection that needs the
24 Hossam Mohamed et al.: Hossam (Y) Site Theory of Collagen Type I Decrypts the Origin of Metabolic Syndrome (X) in the
Elderly with a Suggested Conjecture of Cure: Granted US Patent Review

Lysyl oxidase enzyme (LOX) and copper. Many of the fibrils The same mechanism could occur in the valves of the heart
are connected to form the collagen fiber (10 um) [5]. [6].
2.3. The Importance of Zero Holes, Zero Channels 2.4. Folding of the Collagen

Zero holes are the sites between 2 collagen molecules. It is The collagen as a polypeptide chain (protein) can not do its
about 40 nm. This area goes up obliquely to form the zero proper function except if it is folded. This means the
channel 40 nm. These areas (zero holes & zero channels) have configuration of the shape of the protein. The folding of
a fundamental physiological role in the bone as they are the collagen is of (α) type which means it is helical in shape. This
site of calcification. This means that it starts in the zero holes occurs at the level of hydrogen bond between the glycine &
then proceeds obliquely to the zero channels. This is because proline in 2 different planes. The cut section of the same plane
the apatite chips are precipitated in the zero hole 1st then shows 3 amino acids (Gly, X, Y). The (Gly) site is always
proceed gradually to the zero channel. Each apatite chip has glycine. The (X) site is either proline or hydroxy-proline. The
the size of 5X20X50 nm. This means that the apatite chips are (Y) site is mostly lysine or to a lesser extent Arginine, and to
oriented vertically at the zero holes & horizontally at the zero the least extent histidine. The folding is done by the hydrogen
channels. Calcium ions would be deposited in the zero holes bonds at the different planes which are much weaker than the
1st then proceed to zero channels. The above mechanism is in peptide bonds between the amino-acid of the same plane (Gly,
the physiological situation in bone mineralization. The zero X, Y). This is the explanation of the hinge theory. This means
holes have a pathological role in soft tissue calcification. This that if the structure contains contain 2 types of bonds, the
is the site of phosphate precipitation in collagen. The source of weaker one can be stretched while the stronger one can not. If
the phosphate crystals is from the cell membrane of nearby the theory is applied here, the hydrogen bonds of folding are
structures as a result of tissue damage. The best example is the pliable and stretchable while the stronger peptide bonds
calcification of arteries as a result of hypertension that remain in their places (figure 3). This is the basis of collagen
damages the blood vessels that release the phosphate crystals conformation under the effect of the mechanical stress at the
to zero holes of the collagen with subsequent calcification. site (Y) [7].

Figure 2. The Zero Hole & Zero channels are the sites of phosphate precipitation and calcification.

1. It is positively changed.
3. The Sites (Y) of the Collagen 2. It is polar (surrounded by water) i.e it acts as the exterior
of the collagen.
The most important site of collagen is the site (Y) and this is 3. It is not connected with hydrogen (H) bonds of collagen
the subject of this paper. This is the site where collagen folding.
conformation occurs if mechanical stress is applied, provided 4. It is the site of cross-linking of collagen if lysine is the
that collagen is functional. The (Y) site is different from the occupying amino acid.
other 2 sites (Gly & X) in 4 main points: From the above, it is the site that can rotate under the effect
 Frontiers 2022; 2(1): 22-33 25

of mechanical stress and shift to the convex side of collagen arrangement is called protein folding. The change of water
(more capacious). Thus, the convex side becomes positive concentration around the protein under the effect of
while the concave side becomes relatively negative. This mechanical stress is associated with a change in the shape of
creates the electrical gradient difference (EGD) that can that protein. As the amino acids would re-arrange themselves
stimulate the nearby cells to modulate the tissues. in a new shape according to the new water concentration. This
is simply is the conformation of collagen. It must be noted that
3.1. The (Gly, X, Y) Sites of the Collagen on unloading, the water concentration returns to its original
These are the sites of one collagen thread at the percentage, and consequently, the collagen also returns to its
cross-section. They are connected by peptide bonds. The (Gly) original shape.
site is always occupied by glycine and this may be one 1/3 of This is because the amino acids regain their original shape.
sequences of collagen. The (X) site is occupied with either This is the basis of the theory that collagen has a memory
proline (or hydroxy-proline) each of them constitutes about 16% related to mechanical stress [29].
of the amino acid sequence. The site (Y) may be any amino 3.3. Lysine and Cross-linking of Collagen
acid but it has a predilection to Lysine, to lesser extent
Arginine, and the least extent histidine. It must be noted that This occurs only at the site (Y) provided it is occupied by
these 3 amino acids are the only polar (have an affinity to Lysine. It needs a very important enzyme called the lysyl
water) amino acids and also are positively charged. oxidase enzyme (LOX). This is activated by copper (Cu). The
cross-linking causes the collagen to be stronger. It does not
3.2. Collagen Conformation Under Mechanical Stress occur if the (Y) site is occupied by any amino acid other than
The conformation means a change of the shape of the (lysine). This explains the importance of supplementation of
protein under the effect of mechanical stress. This is exactly amino acid lysine in the performance of collagen. Recent
related to the change in the concentration of water around the studies show that this amino acid could be used to treat
protein structure. Mechanical stress causes some fluid to osteoporosis. It must be noted that Lysine is essential, polar,
escape. Thus, the water concentration would subsequently be and positively charged amino acid. Moreover, it is one of only
changed. The protein is formed of amino acids which are of a 2 ketogenic amino acids. This means it would not be
different polarity i.e few of them are polar (loving water) and converted to glucose like the other 18 glucogenic amino acids.
most of them are non-polar (hating water). Therefore, they The only 2 ketogenic amino acids are (Lysine & Leucine)
arrange themselves according to the surrounding water. This [30].

Figure 3. The mechanics of the conformation of the collagen shows that the (Y) site is shifted to the convex side. As the (Y) site is polar and positively charged, the
convex side becomes positively charged.
26 Hossam Mohamed et al.: Hossam (Y) Site Theory of Collagen Type I Decrypts the Origin of Metabolic Syndrome (X) in the
Elderly with a Suggested Conjecture of Cure: Granted US Patent Review

Figure 4. The glycine is the smallest amino acid and so it is always central. The proline is the only amino acid that has a ring to support the structure of collagen
and so it is peripheral. Lysine is the only polar and positively charged amino acid and is surrounded by water.

Figure 5. The hydroxylation of proline to hydroxyproline. This is an enzymatic process that needs Lysyl hydroxylase enzyme that needs vitamin C and iron as
co-factors.
 Frontiers 2022; 2(1): 22-33 27

Table 1. Comparison between the 3 sites of collagen (Gly, X, Y).

comparison Site (Y) Site (Gly) Site (X)

polarity Polar (dissolve in water) Non-polar (hates water) i.e not dissolve in water
Electrical charge Positively charged Neutrally charged
Lysine (commonest)
The type of amino Only glycine amino acid which forms 33% of
Arginine less common Proline 16% & hydroxyproline 16%
acid the collagen
Histidine very rare
Lysyl oxidase enzyme (LOX) that Lysyl hydroxylase is needed for the
Enzymes needed N/A
needs copper as co-factor conversion of proline to hydroxy-proline
The site of piezoelectricity They are needed in the folding of collagen. The (α) folding of collagen is a hydrogen bond
Importance
The site of cross-linking of collagen. between the glycine & proline (or hydroxyproline) that are not in the same ring

with excess visceral fat, hyperinsulinemia, and glycation.

4. The Glycation of Collagen Obesity is defined as the body mass index (BMI) is 30 or more.
The general guideline of the BMI is that a normal person is
The sulfur attaches non-enzymatically to collagen. In case from 18-25. The overweight is from25-29.9. More than that
of its deficiency, the empty sites of the sulfur on the collagen limit the patient is considered obese and would have excess
are occupied by glucose. This is known as glycation. This visceral fat, hyperinsulinemia, and glycation. Visceral fat is
process causes the collagen to be dysfunctional. In other present in the viscera like the liver, pancrease, omentum. This
words, the collagen can not do its proper function of tissue type of fat is metabolically active and secrets a large number
remodeling. It must be noted that the other 2 functions of of inflammatory cytokines namely tumor necrosis factors
cross-linking & conformation are also inhibited or may be (TNFs). These inflammatory cytokines are responsible for the
completely stopped. This shows the importance of the site (Y) initiation of chronic subclinical inflammation. This is the
in tissue regeneration & the effect of glycation in tissue starting point of metabolic (X) syndrome. This is the missing
damage. Moreover, recent studies show that glycation is link between glycation & metabolic syndrome. It is also
increased via the presence of obesity due to excess inaccessible for surgery. Its treatment needs to cut
inflammatory proteins like (NF-kB). Thus, the reversal of this carbohydrates and prolonged fasting.
process needs not only supplementation of sulfur but also
supplementation of antioxidants that block the (NF-kB) at the 4.4. Glycation and Senescent Cells
nuclear level. Alpha-Lipoic acid can do block the effect of The senescent cells are aged cells that similar to zombies
(NF-kB) at the transcription level [31]. that refuse to die and can not do their proper function as well.
4.1. Glycation Never Comes Alone These cells are very similar to visceral fat in the secretion of
inflammatory cytokines like tumor necrosis factors (TNFs).
As said earlier, glycation is the main process that causes the These cytokines can increase the glycation process of the
collagen to be dysfunctional. i.e it can not do its proper job as a collagen. These cells also secret products that convert the
tissue modulator except if it is not glycated. On the other hand, nearby healthy cells to become new senescent cells. In other
if glycation occurs, it needs a local factor as a sulfur deficiency words, they could infect the nearby cells to become senescent.
and root factors as visceral fat & hyperinsulinemia. The The hallmarks of these cells are the presence of
process is so complicated that all of these factors interact with senescence-associated heterochromatin foci (SAHF).
each other. Moreover, anyone of them exaggerates the others. Normally, the chromatin is present just under the nuclear
Therefore, it is a vicious cycle and is needed to be broken at all membrane but in the case of senescent cells, they are separated
its levels (figure 6) [32]. from the nuclear membrane to be seen as (SAHF) [8].
4.2. Sulfur Deficiency as the Starting Local Factor of the
Glycation 5. The Ingestion of Collagen
Sulfur deficiency in the elderly is the most important local Many studies have been done on the supplementation of
factor. It allows the glucose to attach to the empty sites that collagen to improve the internal collagen of the human body.
were previously occupied by sulfur. It is known sulfur is an The improvement is minimal because collagen is a very large
essential element for hair, nail, skin, and insulin. Moreover, particle. As said earlier, it is formed of 3150 amino acids.
the cooking causes sulfur to be damaged at and above 70°. Thus, it must be digested and broken down to its building
Furthermore, the elderly person usually has malabsorption for block amino acids. Then, they could be absorbed as single
sulfur. All these factors predispose to sulfur deficiency. units. They are rich in the most important amino acids needed
Subsequently, glycation could be predisposed for. for the manufacture of new collagen. As said earlier, collagen
is rich in glycine, proline, and hydroxy-proline. Despite all of
4.3. The Central Factors of the Glycation that collagen is not considered a super-food. Its ingestion has
many drawbacks.
Obesity usually does not come alone but it's also associated
28 Hossam Mohamed et al.: Hossam (Y) Site Theory of Collagen Type I Decrypts the Origin of Metabolic Syndrome (X) in the
Elderly with a Suggested Conjecture of Cure: Granted US Patent Review

Figure 6. The relation between hyperinsulinemia, Glycation, obesity (visceral fat) in the initiation of the metabolic syndrome (X).

Figure 7. The cross-linking of collagen occurs at the (Y) sites. via Lysyl oxidase enzyme (LOX). It needs copper as a co-factor.

supplemented. Therefore, it is considered semi-essential

5.1. The Drawbacks of Collagen Ingestion amino acid. Cysteine is critically important because it is the
It is deficient in tryptophan amino acid which is essential amino acid that is the only donor of the disulfide bonds. These
amino acid i.e the human body can not manufacture it and it are necessary for folding for many structural proteins of the
must be given with foods especially animal products. human body e.g hairs, nails, insulin, etc. In the case of
Tryptophan is needed for the manufacture of 3 vital products cysteine deficiency and it is not supplemented as in the case of
which are melatonin, serotonin, and niacin [9]. Collagen is chronic degenerative disease in the elderly, the body
also deficient in cysteine amino acid. However, this is not breakdown the muscles to get its requirement of the cysteine.
essential amino acid and can be manufactured inside the This explains the muscle wasting that could occur in chronic
human body. It can not be manufactured in the elderly or in the metabolic syndrome (X). It also explains the importance of
case of chronic debilitating conditions. Thus, it must be cysteine supplementation in chronic metabolic diseases in the
elderly. Recent studies show that the manufacture of collagen
 Frontiers 2022; 2(1): 22-33 29

consumes the cysteine component in the amino acid pool. As explains the enhanced collagen formation by the
cysteine is needed for the disulfide bond formation. This supplementation of N.actyl cysteine (NAC) [10].

Figure 8. The relation between visceral fat & glycation and metabolic syndrome (X) of aging {{DM, Alzheimer, coronary artery disease, arthritis, osteoporosis).

heart diseases, stroke, hypertension, DM II, fatty liver,

5.2. Collagen Ingestion Has a Neglected Effect on (Y) Site Alzheimer's, osteoarthritis, osteoporosis, and others. This
The collagen has a very small percentage of Lysine amino group of diseases can be reduced by cutting carbohydrates and
acid which is the key player of the (Y) site. Thus, the effect of increasing exercise and eating healthy non-processed foods.
collagen ingestion on the cross-linking of collagen is minimal. The exact mechanism was not clear but it is more common
Collagen is rich in glycine 33% which occupies the site (Gly). with an obese person especially with central obesity. It could
It is also rich in proline & hydroxyproline which occupy the be predicted if the waist size is more than 85 cm in women or
site (X). As said earlier, the percentage of each is 16%. 90 cm in men. The possible explanation is that eating excess
Moreover, the collagen must be broken down to its building carbohydrates and/or highly processed fast food leads to
block amino acids which enter the amino acid pool. They will excess fat in the liver. As the liver can store very little amount
not be directed specifically to collagen only because the of fat, it tries to export all the excess fat to the nearby organs
human body has more than 2 million proteins. i.e the pancrease, omentum, intestinal wall, kidney, and
Therefore, the ideal method of enhancing collagen is not via pericardium. This type of fat is metabolically active and
its ingestion but through its repair (deglycation). i.e removal secrets a large number of inflammatory products mainly TNFs
of the glucose that is attached to collagen. Removal of visceral & and subsequently NF-kB. These are the roots of all
fat via prolonged fasting and cutting of carbohydrates. Lastly, subclinical inflammations that are responsible for metabolic
adding certain anti-oxidants to block the effect of the syndrome (X) [22].
inflammatory products (NF-kB) of already present visceral fat. 6.1. The Root Causes of the Metabolic Syndrome
Certain amino acids like Lysine & cysteine also have a
beneficial effect on collagen better than ingestion of collagen As said earlier, visceral fat never comes alone, it almost
itself. This is a new method of thinking for the treatment of always comes with 2 of its sisters namely; glycation and
metabolic syndrome (X) syndrome via the deglycation hyperinsulinemia. These are known as biomechanical
process [11, 13]. metabolic triads. Therefore, for the treatment of all the
diseases of metabolic syndrome (X) to be optimal, it needs to
6. Metabolic (X) Syndrome be treated at all the 3 levels (figure 8). Osteoporosis would be
discussed as an example of metabolic disease in the elderly.
This is a group of diseases that have a high probability of
30 Hossam Mohamed et al.: Hossam (Y) Site Theory of Collagen Type I Decrypts the Origin of Metabolic Syndrome (X) in the
Elderly with a Suggested Conjecture of Cure: Granted US Patent Review

6.2. Idiopathic Osteoporosis Is an Example of Metabolic does not always come alone. It almost always comes with its 2
Syndrome (X) other sisters: hyperinsulinemia that is associated with visceral
fat. This is called above the metabolic triads.
Osteoporosis is a disease of bone weakness that could be Therefore, osteoporosis is considered a metabolic
broken with milder trauma than expected. It affects usually the disease. This new concept changes the lines of the treatment of
elderly. Its scientific definition is the reduction of bone mass osteoporosis. In other words, attention must be paid to treating
per unit volume. It has 2 main types: idiopathic and secondary. osteoporosis at all levels and not only at the bone level. The
The secondary type is out of the scope of this paper because it bone part of osteoporosis is considered as the tip of the iceberg
is caused by another causative disease. Therefore, the but beneath it, many other factors must be corrected. Special
treatment of secondary osteoporosis is via the treatment of attention is applied to the visceral fat.
causative diseases either fracture fixation, cancer, disability, As collagen is not only a protein of structural support as was
and so on [23]. By far, the commonest type of osteoporosis is thought. It has another very fundamental function as the
the (idiopathic) type. It is called the idiopathic because there is starting point of tissue remodeling. It can stimulate or inhibit
no apparent primary factor (s) that may predispose to this type nearby cells to remodel the surrounding tissues. This job can
of osteoporosis. It might be genetic, environmental, nutritional, be only done if the collagen is functional and not glycated
hormonal, occupational, or even lifestyle predispositions. The [12].
exact cause is not known. Therefore, it is called idiopathic The sulfur deficiency acts as an important point of collagen
which means with no known cause [24]. The US patent dysfunction. This is because the sulfur is non-enzymatically
(US9801905) discovered that osteoporosis's starting point is attached to collagen. In case of its deficiency, the glucose gets
the glycation of its bone collagen. The collagen forms 28% of access to the collagen and the glycation occurs [26].
the bone mass. Its main function was thought to be only
structural support. The above patent declared out that collagen 6.4. Hyperinsulinemia and Osteoporosis
is a reactive tissue. It acts as a transformer that converts the
mechanical stress into an electrical gradient difference (EGD). Hyperinsulinemia exaggerates osteoporosis. The recent
This is the most important function of collagen. This property studies that show the mitochondrial-nuclear axis could
is called piezo-electricity (PZE). This fundamental function of down-regulate the number of insulin receptors on the
the collagen necessitates it to be functional which means it is osteocytes. This is a simple negative feedback mechanism. In
not glycated. In other words, the glycated collagen is not the early stages, this would have a protective role for the
functional and it could not do its piezo-electric property. Thus, osteocytes to be saved from the high insulin level. Later, the
it could not start the bone remodeling and the new bone affected cells may suffer from starvation up to death. As the
formation [25]. osteocytes act as the maestro that controls all other bone cells
namely the activation of osteoblasts and/or inhibition of
6.3. Idiopathic Osteoporosis Is Not Idiopathic Anymore osteoclasts. The remodeling of the bone is greatly disturbed.
This means that new bone formation is reduced while bone
By the above explanation, the idiopathic type of resorption may be enhanced. This is because the osteoclasts
osteoporosis is not considered idiopathic anymore. This is are released from their inhibition. Thus, osteoporosis may
because the predisposing factor is known which is the issue [27].
glycation of collagen of the bone. As said earlier, glycation

Figure 9. Hyperinsulinemia down-regulates insulin receptors on the osteoblast (VDAC-Nuclear axis).

 Frontiers 2022; 2(1): 22-33 31

6.5. The Visceral Fat and Osteoporosis disease of known causes and its correction needs to deal with
all these factors to treat bone osteoporosis at the root levels.
Visceral fat is the 3rd limb of the metabolic syndrome. It
affects mainly the 3rd type of bone cells which are the
osteoclasts. Visceral fat secrets (TNFs) enhance the formation 7. Discussion
of (NF-kB) pathway. Subsequently, Reactive Activators of The (Y) site has a critical role in collagen function. It has
Nuclear factor (RANK)-(RANK-L) interaction (figure11). the following criteria:
These are the main stimulators of osteoclasts (bone-eating 1. The site of piezo-electricity.
cells). This exaggerates bone resorption with subsequent 2. It is a polar site (surrounded by water i.e loving water).
osteoporosis formation [28]. 3. It is the only positively charged site of collagen.
From the above, morbid obesity has 3 limbs namely; 4. The site of cross-linking of collagen (if lysine is the
visceral fat, hyperinsulinemia, and glycation. Every limb occupying amino acid).
could attack a certain part of the bone cells for osteoporosis to
occur. Therefore, idiopathic osteoporosis is a metabolic

Figure 10. The Functional collagen has an electrical gradient difference (EGD). This up-regulates the insulin receptors of the osteocytes.

Figure 11. The 3 limbs of morbid obesity could attack the bone at 3 levels. These are visceral fat, hyperinsulinemia, and glycation. Thus, Idiopathic osteoporosis
is considered as one of the metabolic syndrome (X).
32 Hossam Mohamed et al.: Hossam (Y) Site Theory of Collagen Type I Decrypts the Origin of Metabolic Syndrome (X) in the
Elderly with a Suggested Conjecture of Cure: Granted US Patent Review

5. It does not attach to hydrogen bonds of collagen folding. other 11 amino acids are non-essential and the body can
(it is not in the hinge of the rotation) manufacture them in case of their deficiency [19]. Regarding
As collagen is not only a protein of structural support as was collagen (Gly, X, Y) sites, the glycine & proline are
thought. It has another very fundamental function as the non-essential amino acids. Thus, the body can manufacture
starting point of tissue remodeling. It can stimulate or inhibit them in case of their deficiency. On the other hand, the site (Y)
nearby cells to remodel the surrounding tissues. This job can is occupied by Lysine mainly, and to lesser amount arginine,
be only done if the collagen is functional and not glycated and very rare histidine. Lysine & histidine are essential and
[12]. must be supplemented in the foods. Arginine is not essential
The sulfur deficiency acts as the starting point of collagen and can be manufactured by the human body. It must be noted
dysfunction. This is because the sulfur is non-enzymatically that arginine is the main source of nitric oxide for the body.
attached to collagen. In case of its deficiency, the glucose gets Arginine has some side effects on the gastrointestinal tract.
access to the same places i.e non-enzymatic attachment to Citrulline is the best alternative for arginine and is even more
collagen. Then, the collagen becomes dysfunctional and it can effective and has no side effects [20].
not do its role in the activation of nearby cells to remodel the Collagen supplementation has no or very minor effect on
surrounding tissues. thus, the supplementation of MSM as a the (Y) site of the collagen. Moreover, collagen has another
source of organic sulfur could be essential in the prevention of disadvantage of the deficiency of tryptophan amino acid that
this starting point [14, 15]. is essential and needed for melatonin, niacin, and serotonin. It
potent anti-oxidants have a very important role in the is also deficient in cysteine amino acids. Although cysteine is
prevention of the glycation process. e.g. Alpha-lipoic acid, N. non-essential, it is needed for supplying the body with
acetylcysteine, or taurine could prevent the glycation process disulfide bonds. In the elderly with chronic metabolic diseases,
via inhibition of the effect of (NF-kB) which is the main the body breakdown the muscles to get its requirement of
inflammatory product of the human body. Recent studies cysteine. This explains muscle wasting in chronic metabolic
show that (NF-kB) predisposes to the glycation process. Also, diseases. Therefore, collagen supplementation is not the ideal
from the (RANK)-((RANK-L) interaction pathway, the solution for the (Y) site diseases [21].
osteoclasts could be activated to aggravate the condition of
osteoporosis [16]. 8. Conclusion
As said earlier, visceral fat is the main source of (NF-kB).
This type of fat is present in the liver, omentum, intestinal wall, Collagen is a protein that means it is a polypeptide chain.
pancrease, kidneys, and even the pericardium. This fat is The cross-section of one collagen thread shows 3 amino
metabolically active and always manufactures the acids at 3 sites (Gly, X, Y). The (Y) site is different from the
inflammatory products that cause glycation of collagen with other 2 sites in being polar, positively charged, the site of
subsequent gradual tissue damage that leads at the end to the cross-linking of collagen, and the piezo-electricity.
chronic metabolic diseases of the elderly. This type of fat is Moreover, it is the site of the glycation of collagen. The
not accessible for surgical removal. It needs prolonged fasting group of amino acids that may occupy this critical site may
and completely cutting the intake of carbohydrates [17]. be Lysine, to a lesser extent arginine, and very rare to be
Hyperinsulinemia is a silent catastrophic disease. the histidine amino acids. It is known that Lysine & histidine are
patient has a false sense of security that he is not yet diabetic essential amino acids while arginine is not essential. It is
as blood sugar is still within the normal levels. The pancrease strongly believed that collagen as a fibrous protein has only a
can compensate to push sugar inside the tissues. high blood structural support function. Recently discovered that
sugar is dangerous but excess sugar inside the tissues is more collagen has another very fundamental function which is its
dangerous. Recent studies show that hyperinsulinemia is piezo-electricity (PZE). This means that collagen is the
associated down-regulation of insulin receptors. This is a prime mover for tissue remodeling. It acts as a transformer
protective mechanism at the early stages but later, the cells that converts some of the mechanical stress into an electrical
suffer from starvation. It must be noted that gradient difference (EGD). This is the very important
hyperinsulinemia does not come alone. It must be associated function of collagen depending on its (Y) site. Therefore, the
with obesity and excess visceral fat. Thus, there would be an recovery of the (Y) site could allow tissue repair to occur and
excess (NF-kB) of the visceral fat. Hyperinsulinemia is to compensate for the natural loss of the tissue as a result of
roughly 3 times more than that of DM II. In the US, the wear and tear. On the other hand, the dysfunctional (Y) site
percentage of hyperinsulinemia is about 36% of the stops the piezoelectric effect with subsequent loss of the
population which is about 86 million. On the other hand, DM repair of the damaged tissues. every effort is exerted in this
II in the US is about 11% of the population of about 31 paper to recover the site (Y) again to correct the metabolic
million [18]. syndrome (X). This could be done by certain materials which
Lastly, certain amino acids are very essential for collagen include organic sulfur, certain amino acids, some
function. the human body has 20 amino acids. Nine of them anti-oxidants, and change of the lifestyle of the patient, cut
are essential which means that they can not be manufactured carbohydrates especially refined sugar and grains.
by the human body. They must be supplemented by food. The
 Frontiers 2022; 2(1): 22-33 33

Article ID 976848, 10 pages.

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