Just for a record - this is the original AA patent:
Use of arachidonic acid as a method of increasing skeletal muscle mass
United States Patent 6841573
This invention discloses a method of orally administering arachidonic
acid for the purpose of increasing the serum level of the
prostaglandin PGF2alpha and subsequently the level of retained
skeletal muscle mass.
A method for increasing muscle mass, which method comprises
administering orally to a human in need of such treatment an amount of
arachidonic acid between about 100 mg and 5,500 mg which is effective
in raising the level of the endogenous prostaglandin PGF2 alpha.
BACKGROUND OF THE INVENTION
Maintaining a healthy level of muscle mass can play an important role
in sustaining overall good health, with benefits such as increased
basal metabolic rate, better disposal of dietary fats and maintenance
of lower body fat levels, increased immune system health, and an
increase in one's overall vitality and sense of well-being compared to
maintaining lower than ideal levels of lean body mass. A number of
pathological conditions exist that make it difficult to maintain a
normal healthy level of muscle mass, including HIV (human
immunodeficiency virus), andropause or hypogonadism (subnormal
androgen levels), infection, trauma, burns, and spinal cord injury.
Some individuals also fail to gain or to maintain normal lean body
mass without definite pathophysiologic reasons. Many treatments are
offered that would help an individual in need of such treatment
promote the buildup of muscle tissue.
Skeletal muscle mass is increased or maintained in the body through a
number of separate and distinct mechanisms. Such mechanisms play a
role in the regulation of either skeletal muscle protein synthesis or
breakdown, and collectively control the total amount of accrued
protein present in the muscle cell. The actions of androgens are among
the most visibly tied to the regulation of skeletal muscle mass, as
these hormones are collectively responsible for the development and
maintenance of male sexual characteristics including external
virilization, sexual maturity at puberty, spermatogenesis, sexual
behavior/libido and erectile functioning and the support of bone and
muscle tissue growth. It is well documented in the prior art that
raising the level of androgenic hormones in the body can increase
skeletal muscle mass. A number of methods have similarly been
developed to increase the level of androgenic hormones in the body,
which ultimately can be used to offer the benefits of increased
skeletal muscle mass in humans.
In searching for ways to increase androgen levels in the body, the use
of androgen precursor hormones have been suggested. U.S. Pat. No.
5,578,588 to Mattem et al. relates a method of using a precursor
hormone, namely androstenedione, as a means of increasing testosterone
levels. Although the in-vivo conversion of endogenous androstenedione
to testosterone had been documented and cited in this patent, the use
of this compound as an external supplement for producing a stable and
effective increase in serum testosterone had never been investigated
before, and therefore represents a novel invention. The
pharmacokinetics of administering such a precursor is such that
hormone concentrations of active hormone (testosterone) peak within 90
minutes, and subsequently decline over a period of three to four
hours. This more closely resembles the natural pulsating pattern in
which the body releases testosterone, and avoids the prolonged peaks
and troughs noted with use of esterified injectable hormone
preparations.
Several other methods of using different androgen precursor hormones
have also been disclosed, including U.S. Pat. No. 5,880,117 to Patrick
Arnold, which relates a method of using 4-androstenediol as a means of
increasing testosterone levels in humans. This in-vivo conversion of 4-
androstenediol to testosterone, again, was well documented in the
prior art and this patent, however the use of this compound as an
effective oral medicament for raising testosterone levels was never
investigated prior, and therefore represents another novel invention.
U.S. Pat. No. 6,391,868 to Arnold similarly relates a method of using
5-alpha-androst-1-en-3-one for increasing levels of the anabolic/
androgenic steroid 17-beta-hydroxy-5-alpha-androst-1-en-3-one in
humans. Again the in-vivo bioconversion was known, however a formal
investigation of its oral use to increase serum androgen levels had
never been disclosed. U.S. Pat. No. 6,262,436 to Llewellyn further
discloses the method of using 5-alpha-androstanedione or 5-alpha-
androstanediol to increase levels of dihydrotestosterone in humans, a
hormone which also offers the benefit of regulating protein synthesis
and increasing skeletal muscle mass.
The use of androgenic hormones in general, however, is often thought
to entail some risk, as increasing the level of such hormones may also
be relevant to the development of undesirable side effects such as
gynecomastia, water retention (edema), unfavorable alterations in
cholesterol levels (increased heart disease risk) and increased blood
pressure to name just a few. If an individual is seeking solely to
increase skeletal muscle mass, and is not in need of androgen
replacement, then the methods regarding the use of androgen precursors
may be less than ideal. It therefore became to focus of this inventor
to find another distinct mechanism in the body that plays an important
role in the regulation of protein synthesis, and can be affected
externally by the similar use of a precursor compound to an active
constituent in said mechanism to enhance the buildup of skeletal
muscle tissue.
This invention relates a method of administering arachidonic acid for
the purpose of increasing the level of the prostaglandin PGF2alpha and
subsequently skeletal muscle mass. PGF2alpha is not an androgenic
steroid, but an endogenous prostaglandin. It is referred to commonly
as an inflammatory hormone, and is related to several biological
functions including immunity, response to allergens, intestinal
mobility and blood flow in various regions of the body. PGF2alpha is
also closely tied to skeletal muscle protein synthesis in the body
(Biochem J 1983 Sep. 15;214(3):1011-4), and represents an important
new target for the external modulation of skeletal muscle mass
distinct from the mechanisms involving male sex steroids. This method
of using arachidonic acid for increasing PGF2alpha and skeletal muscle
mass is an ideal solution for an individual in need of such treatment,
because PGF2alpha is non-steroidal, and can increase protein synthesis
and muscle mass without the potential undesirable side effects
associated with altering sex steroid levels with androgen precursor
hormones.
BRIEF SUMMARY OF THE INVENTION
Prior art relates several novel methods of using precursors to
hormones that regulate protein synthesis for the purpose of increasing
the levels of said hormones, which ultimately can increase skeletal
muscle mass. Although the suggested practice of using precursors to
physiologically active hormones seems quite sound, the target hormones
in the cited art, namely androgenic steroids, may be less than ideal
in many cases, particularly in those where increases in skeletal
muscle mass are desired but the potential side effects of androgens
contraindicates their use. The problem of the present invention is
therefore to provide a precursor to a target hormone that can also be
used to increase skeletal muscle mass when administered, but is
completely non-steroidal. According to the invention this problem is
solved by the oral use of arachidonic acid, a direct precursor to the
prostaglandin PGF2alpha. This method is ideal because it is natural,
non-toxic, quickly metabolized to active form after oral
administration, and can increase skeletal muscle mass without the
potential side effects of androgenic precursors.
DETAILED DESCRIPTION OF THE INVENTION
Arachidonic acid is a naturally occurring polyunsaturated fat,
belonging to the Omega-6 family of fatty acids. It is considered an
essential fatty acid (EFA), because it is an essential nutrient that
your body can't produce itself. The only way you can get arachidonic
acid is through the food you eat. It is obtained in small amounts in
the average human diet, coming from various plant and animal sources
including milk. Arachidonic acid has furthermore been identified as a
vital precursor to numerous hormones in the body including
prostaglandins, prostacyclin (PGI12), leukotrienes, and thromboxanes.
Studies by have fundamentally proven the in-vitro conversion of
arachidonic acid to the prostaglandin PGF2alpha. Experiments by Berlin
et al. (Acta Physiol Scand 1979 August;106(4):441-5) used 14C-labeled
arachidonic acid to chart the metabolism of this essential fatty acid
into various prostaglandins in human skeletal muscle and kidney
homogenates. Those prostaglandins produced during this incubation
include PGD2, PGE2, PGF2 alpha and 6-keto-PGF1 alpha. Further studies
with labeled arachidonic acid have fundamentally proven the in-vivo
conversion of this fatty acid into PGF2alpha (Acta Physiol Scand 1979
July;106(3):307-12). In this investigation the labeled metabolites of
arachidonic acid were measured in serum extracted from the forearm and
kidney of human volunteers after direct infusion into the brachial or
renal artery. PGD2, PGE2, PGF2 alpha, 6-keto-PGF1 alpha and 13,14-
dihydro-15-keto-PGE2 (Me) were all found in this experiment.
The prostaglandin PGF2alpha has also been proven to play a vital role
in skeletal muscle protein synthesis. In fact, it is one of the
prostaglandins most closely tied to protein synthesis, and therefore
the primary focus of this invention. Studies conducted by Smith et al.
(Biochem J 1983 July 15;214(1):153-61) have fundamentally proven the
importance of PGF2alpha in stimulating protein synthesis in-vitro, by
testing the effects of various arachidonic acid metabolites when
incubated with intact rabbit muscle that was intermittently placed
under stretch stimulus. In this study two prostaglandins, F2 alpha and
A1, increased rates of protein synthesis in unstimulated muscles, but
prostaglandins E2 and D2 and the leukotrienes C4 and D4 failed to do
so. Further studies with the cox-1 enzyme inhibitors
ibuprofen and
acetaminophen, which exhibit their anti-inflammatory actions by
inhibiting the synthesis of prostaglandins, suggest that these drugs
can profoundly diminish the anabolic response of muscle to resistance
exercise by inhibiting the normal post-exercise increase in levels of
PGF2alpha (Clin Endocrinol Metab 2001 October;86(10):5067-7). A search
of the prior art does not reveal any investigations into what effect
additional arachidonic acid in the diet would have on total protein
synthesis or skeletal muscle mass.
Prior art also does not disclose any investigations regarding the
effect oral arachidonic acid would have on the serum level of
PGF2alpha. Human tests carried out by Kelley et al. (Lipids 1998
February:33(2):125-30), however, did look at the effect of oral
arachidonic acid on in-vitro immune response as measured by the
secretion of different prostaglandins and immune system factors. In
this study, the in-vitro secretion of LTB4 and PGE2, as demonstrated
by influenza antibody titers determined on drawn blood, did seem to
measurably increase after oral administration of 200 mg and 1.5 g of
supplemented arachidonic acid per day. This suggested to this inventor
that a similar increase might be noted in-vivo with other
prostaglandins not measured in this experiment including PGF2alpha.
After learning of the in-vitro and in-vivo conversion of arachidonic
acid to PGF2alpha, plus the role PGF2alpha plays in the regulation of
skeletal muscle protein synthesis, it became the focus of this
invention that skeletal muscle mass can be increased by the oral
administration of arachidonic acid. In an effort to prove this theory
a clinical study was therefore undertaken by the inventor.
Specifically, it was the intention of this inventor to prove that
arachidonic acid would act as an effective in-vivo peroral PGF2alpha
precursor in man capable of raising and sustaining elevated PGF2alpha
levels, and that the resultant increases in levels of PGF2alpha would
result in increases in the level of skeletal muscle mass.
An effective oral daily dosage of arachidonic acid is between 100 mg
to 5,500 mg. It is ideally provided as a soft gelatin capsule or oral
liquid, due to the fact that arachidonic acid is in the form of free
flowing oil at room temperature. Due to the rapidity in which the
discussed compound is metabolized in the body, the total daily dosage
can be further subdivided for a more sustained blood hormone
concentration, with 2-3 applications per day being most preferred.
SOURCE:
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