Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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COMPOSITION FOR MAINTAINING ANDROGEN AND
ANDROGEN-LIKE UPTAKE POTENTIAL BY CELLS
Field of the Invention
The present invention relates to a nutritional supplement for maintaining
androgen and androgen-like uptake potential in cells, via simultaneous
increase
in the availability of androgen receptors and improved availability of
androgen
and androgen-like molecules. More specifically, the present invention relates
to a
composition comprising a synergistic combination of L-carnitine fumarate and a
plant extract derived source of forskolin.
Background of the Invention
Androgen receptors (AR) are intracellular receptors that specifically bind
androgens, such as testosterone and dihydrotestosterone, but are also known to
be activated by growth factors, such as insulin-like growth factor-1 (IGF-1).
The
influence of testosterone on skeletal muscle protein synthesis is mediated by
the
AR. After an androgen binds to the AR, restructuring and dimerization of the
proteins occurs forming an activated receptor complex, which translocates to
the
nucleus and binds to DNA, thereby activating androgen-specific gene expression
in the nucleus.
Animal and clinical studies indicate that the AR signaling pathway is
required for the appropriate development of skeletal muscles, as it regulates
increases in lean muscle mass, muscle strength, and muscle protein synthesis.
The importance of AR for muscle protein accretion has been shown, since
muscle hypertrophy has been shown to be attenuated by AR blockade (Inoue K,
Yamasaki S, Fushiki T, Okada Y, Sugimoto E. Androgen receptor antagonist
suppresses exercise-induced hypertrophy of skeletal muscle. Eur J Appl Physiol
Occup Physiol. 1994;69(1):88-91).
The physiological importance of AR in exercise-induced muscle
hypertrophy has been investigated in a number of human and animal studies,
most of which emphasize the importance of increasing the AR content
(Deschenes MR, Maresh CM, Armstrong LE, Covault J, Kraemer WJ, Crivello JF.
Endurance and resistance expercise induce muscle fiber type specific responses
in androgen binding capacity. J Steroid Biochem Mol Biol. 1994 Aug;50(3-4):175-
9), in a muscle-fiber-specific manner. For example, resistance exercise
elicits
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significant decreases in AR content of slow oxidative skeletal muscle fibers,
and
a significant increase in fast glycolytic skeletal muscle fibers.
In untrained men, a single bout of heavy resistance exercise has been
shown to up-regulate AR mRNA 48 hours post-training (Bamman MM, Shipp JR,
Jiang J, Gower BA, Hunter GR, Goodman A, McLaffert CL Jr, Urban RJ.
Mechanical load increases musvle IGF-I and androgen receptor mRNA
concentrations in humans. Am J Physiol Endocrinol Metab. 2001
Mar;280(3):E383-90). While, repeated resistance exercise, having 48 hours
between sessions, has been shown to increase AR mRNA and protein
expression (Willoughby DS, Taylor L. Effects of sequential bouts of resistance
exercise on androgen receptor expression. Med Sci Sports Exerc. 2004
Sep;36(9):1499-506). Such augmentation has been correlated with elevated
serum testosterone levels and corresponded to significant increases in
myofibrillar protein.
In trained individuals, high-volume, high-intensity resistance exercise
appears to cause a decrease in AR protein content within 1 hour post-exercise
(Ratamess NA, Kraemer WJ, Volek JS, Maresh CM, Vanheest JL, Sharman MJ,
Rubin MR, French DN, Vescovi JD, Silvestre R, Hatfield DL, Fleck SJ,
Deschenes MR. Androgen receptor content following heavy resistance exercise
in men. J Steroid Biochem Mol Biol. 2005 Jan:93(1):35-42), almost certainly
due
to protein catabolism induced by exercise-related stress. However, this
negative
effect is mitigated by post-resistance exercise feeding, which has been shown
to
increase muscle AR content, resulting in increased testosterone tissue uptake
and enhanced luteinizing hormone release, via feedback mechanisms. These
observations provide a possible mechanism for increased protein synthesis
following post-resistance exercise food intake.
Summary of the Invention
The present invention relates to a nutritional supplement for maintaining
androgen and androgen-like uptake potential in cells, via simultaneous
increase
in the availability of androgen receptors and improved availability of
androgen
and androgen-like molecules. The effects of the present composition on
increasing and maintaining androgens and androgen-like substances in an
individual allows them to act upon an androgen receptor wherein they confer
their
respective endogenous effects. The nutritional supplement, comprising at least
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an effective amount of L-carnitine fumarate and an extract of Coleus
forskohlii. In
additional aspects of the present invention, one or more of N-acetyl L-
carninte,
melatonin, ubidecarenone (coenzyme Q10), idebenone, decylubiquinone, an
extract of Agaricus blazei Murill, and ginsenoside Rbl are added to the
composition to provide further synergistic benefits. Both a composition and a
method are provided by the present disclosure.
Detailed Description of the Invention
In the following description, for the purposes of explanations, numerous
specific details are set forth in order to provide a thorough understanding of
the
present invention. It will be apparent, however, to one of ordinary skill in
the art
that the present invention may be practiced without these specific details.
The present invention is directed towards a nutritional supplement, for
maintaining androgens and androgen-like uptake potential in a cell, via
simultaneous increase in the availability of androgen receptors and improved
availability of androgen and androgen-like molecules, comprising effective
sources of L-carnitine, and a plant extract providing forskolin. According to
various aspects, the present invention may further comprise combinations of N-
acetyl L-carnitine, melatonin, ubidecarenone (coenzyme Q10), idebenone,
decylubiquinone, an extract of Agaricus blazei Murill, and ginsenoside Rbl.
The term 'androgen-like' as used herein is understood to represent any
substance which behaves in a manner similar to that of an endogenous or
exogenous androgen with respect to its actions on a cell in the body of a
mammal.
The term 'uptake potential' as used herein is understood to define the
ability of a cell to interact with an extracellular substance, via membrane
proteins,
to produce intracellular signals and protein translocation to the nucleus
resulting
in gene expression. It is herein understood that uptake potential is enhanced
by
factors including, but not limited to the increased presence of extracellular
substances, increased presence of activated cell receptors as a result of
reduced
cell damage, enhancements of interactions between substances and receptors,
and increased ability to propagate intracellular signal cascades post-receptor-
substance interaction within a cell.
A used herein, the term 'nutritional composition' includes dietary
supplements, diet supplements, nutritional supplements, supplemental
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compositions and supplemental dietary compositions or those similarly
envisioned and termed compositions not belonging to the conventional
definition
of pharmaceutical interventions as is known in the art. Furthermore,
'nutritional
compositions' as disclosed herein belong to category of compositions having at
least one physiological function when administered to a mammal by conventional
routes of administration.
L-Carnitine and Functional Derivatives
Carnitine, referred to as L-carnitine, is a quaternary ammonium compound
synthesized from the amino acids lysine and methionine. L-carnitine plays a
role
in the transport of fatty acids across the mitochondrial matrix for the
subsequent
metabolism and energy production by beta-oxidation.
However, recent research in this area has mostly involved L-carnitine L-
tartrate (LCLT), a salt of L-carnitine, and has focused on a role separate
from
carnitine's originally hypothesized role in fat metabolism. LCLT
supplementation
has been evaluated on resistance exercise trained humans as an enhancer of the
hormonal responses to resistance exercise and as a recovery promoter. Three
weeks of supplementation with LCLT, providing the equivalent of 2 g of
elemental
carnitine per day, has been shown to reduce muscle damage produced by an
acute bout of high-intensity resistance exercise via cross-over, placebo
controlled
studies (Kraemer WJ, Volek JS, French DN, Rubin MR, Sharman MJ, Gomez AL,
Ratamess NA, Newton RU, Jemiolo B, Craig BW, Hakkinen K. The effects of L-
carnitine L-tartrate supplementation on hormonal responses to resistance
exercise and recovery. J Strength Cond Res. 2003 Aug;17(3):455-62). The
investigators conclude that less muscle damage may have resulted in more
hormonal receptors available for binding interactions with anabolic hormones.
This explains the reduced progression of muscle damage, as measure by MRI, in
the recovery days after resistance exercise (Volek JS, Kraemer WJ, Rubin MR,
Gomez AL, Ratamess NA, Gaynor P. L-carnitine L-tartrate supplementation
favorably affect markers of recovery from exercise stress. Am J Physiol
Endocrinol Metab. 2002 Feb;282(2):E474-82).
One study has shown that 21-days of L-carnitine supplementation, with 2 g
of carnitine per day, in weight-trained individuals induced significant up-
regulation
of pre-exercise skeletal muscle AR protein content (p<0.05) as compared to
placebo (Kraemer WJ, Spiering BA, Volek JS, Ratamess NA, Sharman MJ,
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Rubin MR, French DN, Silvestre R, Hatfield DL, Van Heest JL, Vingren JL,
Judelson DA, Deschenes MR, Maresh CM. Angrogenic responses to resistance
exercise: effects of feeding an L-carnitine. Med Sci Sports Exerc. 2006
Jul;38(7):1288-96). L-carnitine confers its function in this regard by
reducing
muscle damage associated with resistance exercise, therefore attenuating the
catabolism of muscle-specific proteins, such as AR, for example. It is
understood
that L-carnitine enhances testosterone uptake via offering a protective effect
resulting in a reduction in muscle damage and an increased availability of AR.
It
is understood the L-carnitine's effects are not conferred via direct
stimulation of
testosterone secretion. Based on these considerations, and on the fact that
post-
resistance exercise feeding stimulates increases in AR content, it is herein
understood by the inventors that L-carnitine and feeding independently yet
synergistically enhance the hormonal environments following resistance
exercise
and promote anabolism.
Furthermore, a study of the effects of L-carnitine supplementation on
delayed muscle soreness (Giamberardino MA, Dragani L, Valente R, Di Lisa F,
Saggini R, Vecchiet L. Effects of prolonged L-carnitine administration on
delayed
muscle pain and CK release after eccentric effort. Int J Sports Med. 1996
JuI;17(5):320-4), showed that L-carnitine has a protective effect against pain
and
damage from eccentric muscular effort. This result has been attributed to the
vasodilative properties of L-carnitine, which would increase the wash-out of
pain
inducing energy metabolites.
It is herein understood by the inventors that supplementation with the
equivalent of 2 g of L-carnitine per day, will reduce the catabolism of muscle-
specific proteins, resulting in enhanced testosterone uptake via the increased
availability of AR. Furthermore, it is understood that the vasodilative
properties of
the composition will improve energetic metabolism in hypoxic muscle tissue and
enhance the wash-out of pain generating energy metabolites, thus decreasing
muscle damage and pain and resulting in quicker recovery following resistance
exercise.
In an embodiment of the present invention, which is set forth in greater
detail in the examples below, the nutritional supplement comprises effective
sources of L-carnitine, such as, but not limited to, L-carnitine fumarate, L-
carnitine-L-tartrate, and N-acetyl L-carnitine HCI. In addition to the
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aforementioned derivatives, other effective and pharmaceutically acceptable
salts
or ester of carnitine may be employed in the practice of the invention.
By way of example, a serving of the nutritional supplement comprises from
about 0.5 g to about 5.0 g of L-carnitine fumarate, and from about 0.01 g to
about
1 g of N-acetyl L-carnitine. The preferred dosage of the nutritional
supplement of
the present invention, comprises about 1.25 g of L-carnitine fumarate and
about
0.375 g of N-acetyl L-carnitine per serving.
Coleus forskohlii
Plectranthus barbatus, also known as coleus forskohlii, is tropical
perennial plant, that is of scientific and medicinal interests since it is an
abundant
source of forskolin. Forskolin is a diterpene that is used to raise levels of
cyclic
adenosine monophosphate (cAMP) in cells, via a G-protein dependent
mechanism. cAMP is a second messenger, used for intracellular signal
transduction, such as transferring the effects of hormones like glucagon and
adrenaline, from cell-surface receptors to the nucleus.
It is well known in the literature that lipolysis in isolated fat cells in
vitro is
increased by administration of forskolin. Forskolin facilitates this improved
lipolysis by increasing levels of cyclic AMP (cAMP). The following other
biological effects of forskolin have been described as a result of the cAMP
mechanisms: increased chronotropic and inotropic effect on the heart,
hypotensive action, increased synthesis of body steroids, inhibition of
platelet
aggregation, potentiation of insulin secretion, increased release of
adrenocorticotropic hormone (ACTH), and decreased intraocular pressure.
Additionally, U.S. Patent No. 5,804,596 discloses a method of
administering forskolin to an individual in order to reduce body fat relative
to lean
body mass, by reducing body fat through increasing thermogenesis via increased
cAMP levels. However, U.S. Patent No. 5,804,596 does not disclose a method of
increasing the availability of androgen and/or androgen-like molecules with
concomitant increase in the availability of androgen receptors in skeletal
muscle,
thus providing for increased protein synthesis following post-resistance
exercise
food intake.
One study showed that, in overweight healthy male subjects,
supplementation, with 250 mg of 10% forskolin extract twice a day, caused
significant fat loss and lean body mass-sparing effects as compared to the
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placebo (Godard MP, Johnson BA, Richmond SR. Body composition and
hormonal adaptations associated with forskolin consumption in overweight and
obese men. Obes Res. 2005 Aug;13(8):1335-43). These effects are attributed to
significant increases in free testosterone levels and a tendency towards
increased endogenous total testosterone production.
Testosterone is a steroid hormone that is secreted in the testes, ovaries,
and in small amounts by the adrenal glands. Production and secretion of
testosterone by the Leydig cells of the testes is regulated by luteinizing
hormone
(LH) from the anterior pituitary. LH exerts its effects on Leydig cells
through the
use of a secondary messanger, cAMP. Thus, by increasing the accumulation of
cAMP, by use of forskolin, it is understood to lead to an increase in
testosterone
production and secretion. Increased levels of testosterone will result in
greater
stimulation of the AR signaling pathway, leading to increases in lean muscle
mass, muscle strength, and muscle protein synthesis.
In an embodiment of the present invention, which is set forth in greater
detail in the examples below, the nutritional supplement comprises an extract
of
Coleus forskohlii. A serving of the nutritional supplement comprises from
about
0.001 g to about 0.1 g of an extract of Coleus forskohlii. The preferred
dosage of
a serving of the nutritional supplement of the present invention comprises
about
0.025 g of an extract of Coleus forskohlii.
Simultaneous Increase in Androgen Receptors and Androgen
While, not wishing to be bound by theory, the present invention is
comprised of components for enhancing hormonal responses to resistance
exercise, reduce muscle damage associated with resistance exercise and
produce a protective effect against pain and damage from eccentric effort by
acting as a vasodilator.
According to one embodiment of the invention, the composition comprises
at least L-carnitine and Forskolin wherein the L-carintine will reduce the
catabolism of muscle-specific proteins, resulting in enhanced testosterone
uptake
via the increased availability of AR and the use of forskolin, will lead to an
increase in testosterone production and secretion. Thus the increased levels
of
testosterone along with the enhanced testosterone uptake will result in
greater
stimulation of the AR signaling pathway, leading to increases in lean muscle
mass, muscle strength, and muscle protein synthesis
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It is herein understood by the inventors that the above combination of
ingredients work synergistically to help mediate a faster recovery following
resistance exercise, reduce the catabolism of muscle-specific proteins,
resulting
in enhanced testosterone uptake via increased availability of AR than is
normally
observed in the absence of such supplementation.
In additional aspects of the present invention, one or more of N-acetyl L-
carninte, melatonin, ubidecarenone (coenzyme Q10), idebenone,
decylubiquinone, an extract of Agaricus blazei Murill, and ginsenoside Rbl are
added to the composition to provide further synergistic benefits relating to
maintaining androgen and androgen-like uptake potential in cells. The
additional
ingredients and synergistic benefits are disclosed hereinafter.
Melatonin
Melatonin, also known as Melatonine, Circadin, N-Acetyl-5-
methoxytryptamine, and 5-Methoxy-N-acetyltryptamine, is naturally produced in
the brain by the pineal gland and has been shown to stimulate the production
of
growth hormone as well as reduce free-radical damage. Evidence suggests that
melatonin plays a role in modulating pituitary gland secretions such as growth
hormone. Furthermore, melatonin follows a circadian rhythm and is thus
principally controlled by a shift from light to dark within the environment.
Exogenous oral melatonin administration of both 0.5 mg and 5.0 mg has
been shown to produce a significant increase in plasma GH concentrations with
peak values at 60 minutes being similar in amplitude. Moreover, both of the
aforementioned values share similar areas under the curve as detected by two
site immunoradiometric assay (Forsling ML, Wheeler MJ, Williams AJ. The effect
of melatonin administration on pituitary hormone secretion in man. Clin
Endocrinol (Oxf). 1999 Nov;51(5):637-42) indicating that 0.5 mg may be the
maximal dose for GH stimulation. Additionally, exogenous melatonin
administration was, however, shown to modulate the neurohypophysial response
to different stimuli (Forsling ML, Williams AJ. The effect of exogenous
melatonin
on stimulated neurohypophysial hormone release in man. Clin Endocrinol (Oxf).
2002 Nov;57(5):615-20), which could contribute to the night-time increase in
circulating concentrations of the hormones.
A release of GH has also been shown to occur in response to single bouts
of both cardiovascular and resistance exercise. At 85% of the weight of the
one
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repetition maximum for an individual, a single bout of weight lifting exercise
was
shown to significantly elevate the serum level of GH (Vanhelder WP, Goode RC,
Radomski MW. Growth hormone responses during intermittent weight lifting
exercise in men. Eur J Appl Physiol Occup Physiol. 1984;53(1):31-4.).
Additionally, the serum levels of GH where shown to be increased by a single
set
of low- and moderate-intensity (50% and 70% of one repetition maximum
respectively) resistance exercise following high intensity exercise (90% of
one
repetition maximum) (Goto K, Sato K, Takamatsu K. A single set of low
intensity
resistance exercise immediately following high intensity resistance exercise
stimulates growth hormone secretion in men. J Sports Med Phys Fitness. 2003
Jun;43(2):243).
Exogenous melatonin administered orally prior to bicycle exercise at 70%
VO2max was shown to cause significant increases in GH when compared to
placebo through a calculation of the area under the curve. In this case, 5.0
mg
was administered orally 60 minutes prior to exercise and GH levels were shown
to peak at 30 minutes following exercise, whereas the increase in GH levels in
the placebo group peaked at 15 minutes following exercise (Meeking DR,
Wallace JD, Cuneo RC, Forsling M, Russell-Jones DL. Exercise-induced GH
secretion is enhanced by the oral ingestion of melatonin in healthy adult male
subjects. Eur J Endocrinol. 1999 Jul;141(1):22-6). Since exercise-induced GH
secretion is thought to be mediated predominantly through a hypothalamic
pathway, it seems likely that melatonin facilitates GH secretion at the
hypothalamic level.
Additionally, a human study has reported that, in weight-trained young
males, 0.5 and 5.0 mg melatonin were significantly more effective than placebo
at
increasing serum free GH following a single bout of heavy-resistance exercise
(Nassar E, Mulligan C, Taylor L, Kerksick C, Galbreath M, Greenwood M,
Willoughby D. Effects of prophylactic N-Acetyl-5-methoxytryptamine (melatonin)
supplementation and resistance exercise on serum growth hormone levels and
the hypothalamus-pituitary-adrenal axis in young males and females. J Int Soc
Sports Nutr 2006;3(1):S1-29 (Poster 24)). This study also investigated the
effects of melatonin on IGF-1, IGFB-1 and IGFBP-3, and reported notable
increases in serum IGFBP-3 during both pre- and post-exercise periods. This
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suggests that melatonin may work by triggering a release of IGF-1 from IGFBP-3
in a manner different then GH-dependent release of IGF-1.
It is herein understood by the inventors that melatonin will act to increase
availability of free GH, resulting in increased binding to the extracellular
domain
of the GH receptor thus promoting the release of the anabolic insulin-like
growth
factor 1 (IGF-1), which is androgen-like and interacts with AR.
In an embodiment of the present invention, which is set forth in greater
detail in the examples below, the nutritional supplement comprises melatonin.
A
serving of the nutritional supplement comprises from about 0.00005 g to about
0.005 g of melatonin. The preferred dosage of a serving of the nutritional
supplement of the present invention comprises about 0.0005 g of melatonin.
Ubidecarenone (Coenzyme Q10), Idebenone and Decylubiquinone
Coenzyme Q10 (CoQ10, ubidecarenone) is found in the mitochondria of
all cells and is involved in energy production. It is found at its highest
concentrations in the heart, liver, kidney and pancreas. CoQ10 is a potent
antioxidant in human blood (Weber C, Sejersgard Jakobsen T, Mortensen SA,
Paulsen G, Holmer G. Antioxidative effect of dietary coenzyme Q10 in human
blood plasma. Int J Vitam Nutr Res. 1994;64(4):311-5) where it also acts to
preserve vitamin E, another major antioxidant (Thomas SR, Neuzil J, Stocker R.
Inhibition of LDL oxidation by ubiquinol-10. A protective mechanism for
coenzyme
Q in atherogenesis? Mol Aspects Med. 1997;18 Suppl:S85-103). As a result of
CoQ10's antioxidant activity it exerts a protective effect on mitochondrial
membranes, insuring the integrity of the membrane-receptor interface.
One study has shown that individuals suffering from angina were able to
exercise for longer periods when receiving CoQ10 (Kamikawa T, Kobayashi A,
Yamashita T, Hayashi H, Yamazaki N. Effects of coenzyme Q10 on exercise
tolerance in chronic stable angina pectoris. Am J Cardiol. 1985 Aug
1;56(4):247-
51) as compared to untreated groups. Moreover, myocardial function was
improved by CoQ10 in patients with disease conditions known to involve energy
production deficits (Folkers K, Wolaniuk J, Simonsen R, Morishita M,
Vadhanavikit S. Biochemical rationale and the cardiac response of patients
with
muscle disease to therapy with coenzyme Q10. Proc Natl Acad Sci U S A. 1985
Jul;82(13):4513-6) wherein these patients also reported a`subjective' improved
sense of well-being.
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Idebenone and decylubiquinone are synthetic CoQ10 derivatives. The
former being a potent antioxidant, with the ability to fight reactive oxygen
species
(ROS) under low oxygen tension situations (No authors listed. Idebenone -
Monograph. Altern Med Rev. 2001 Feb;6(1):83-6). As a result of this inhibition
of
lipid peroxidation, idebenone acts to protect cell membranes, especially those
of
the mitochondria, from oxidative damage. Decylubiquinone has been shown to
effectively block redox-dependent mitochondrial permeability transition
(Armstrong JS, Whiteman M, Rose P, Jones DP. The coenzyme Q10 analog
decylubiquinone inhibits the redox-activated mitochondrial permeability
transition.
J Biol Chem. 2003 Dec 5;278(49):49079-84), thereby reducing the loss of
mitochondrial transmembrane potential.
It is herein understood by the inventors that compounds comprising these
antioxidant quinones exert a protective effect on mitochondrial membranes (Liu
J,
Rone MB, Papadopoulos V. Protein-protein interactions mediate mitochondrial
cholesterol transport and steroid biosynthesis. J Biol. Chem. 2006 Dec
15;281(50):38879-93), thus ensuring the integrity of the membrane-receptor
interface and preserving the effect of hormones on mitochondrial cholesterol
transport and steroidogenesis.
In an embodiment of the present invention, which is set forth in greater
detail in the examples below, the nutritional supplement comprises
Ubidecarenone (Coenzyme Q10), Idebenone and Decylubiquinone. A serving of
the nutritional supplement comprises from about 0.0001 g to about 0.01 g of
Ubidecarenone (Coenzyme Q10), from about 0.00001 g to about 0.01 g of
Idebenone, and from about 0.000001 g to about 0.0001 g of Decylubiquinone.
The preferred dosage of a serving of the nutritional supplement of the present
invention comprises about 0.001 g of Ubidecarenone (Coenzyme Q10), about
0.0001 g of Idebenone, and about 0.00001 g of Decylubiquinone. Optionally, the
nutritional supplement of the present invention comprises about 0.0001 g of
Idebenone, and about 0.00001 g of Decylubiquinone.
Agaricus Genus Mushrooms
Agaricus blazei Murill is a gilled fungus which naturally occurs in Europe
and North America, and is commonly known as white and button mushroom,
amongst many others. The white mushroom is a source of unsaturated fatty acid
components such as linoleic, linolenic, and conjugated linoleic acids, that
are
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utilized by the body in the biosynthesis of many compounds, for example,
prostaglandins.
A study of the active components of an ethyl acetate extraction of white
mushrooms, linoleic, linolenic, and conjugated linoleic acids (Chen S, Oh SR,
Phung S, Hur G, Ye JJ, Kwok SL, Shrode GE, Belury M, Adams LS, Williams D.
Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus
bisporus). Cancer Res, 2006 Dec 15;66(24):12026-34 (Abstract)), showed that
these fatty acids are efficient suppressors of aromatase activity. Aromatase
is an
enzyme whose function is to increase the aromaticity of androgens, producing
estrogens from testosterone. Aromatase activity therefore acts to decrease
serum levels of testosterone, thereby inhibition of this enzyme's activitity
would
lead to a further increases in the levels of testosterone in the body.
Agaricus blazei, a mushroom providing an extract which nutritional
supplement of the of present invention may also comprise has been shown to
reduce blood glucose, blood pressure, cholesterol levels and the effects of
arteriosclerosis.
In an embodiment of the present invention, which is set forth in greater
detail in the examples below, the nutritional supplement comprises an extract
of
Agaricus blazei Murill. A serving of the nutritional supplement comprises from
about 0.0001 g to about 0.01 g of an extract of Agaricus blazei Murill. The
preferred dosage of a serving of the nutritional supplement of the present
invention comprises about 0.001 g of an extract of Agaricus blazei Murill.
In an additional embodiment of the present invention, the nutritional
supplement comprises and extract of Agaricus blazei. A seriving of the
nutritional
cupplement comprises from about 0.0001 to about 0.01 of an extract of Agaricus
blazei. The preferred dosage of a serving fo the nutritional supplement of the
present invention comprises about 0.001 g of an exrtract of Agaricus blazei.
Ginsenoside Rbl
Ginsenosides are a class of steroid-like compounds, found exclusively in
plants, Panax quinquefoius. Ginsenosides have been the target of research,
since they are viewed as the active compounds behind the claims of ginseng's
efficacy. Ginsenosides appear to affect multiple pathways, and so their
effects
are complex and difficult to isolate.
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Ginsenoside Rbl has been shown in animals to stimulate the secretion of
lutenizing hormone (LH) after exercise (Tsai SC, et al. Stimulation of the
secretion of luteinizing hormone by ginsenoside-Rbl in male rats. Chin J
Physiol.
2003 Mar;46(1): 1-7 (Abstract)). (LH) is a hormone that is synthesized and
secreted by the anterior pituitary gland and is responsible for the
stimulation of
Leydig cell production of testosterone. It is herein understood by the
inventors
that increased secretion of LH will result in a greater production of
testosterone,
thus greater levels of serum testosterone leading to more numerous
interactions
of testosterone with AR. This will lead to increases in lean muscle mass,
muscle
strength, and muscle protein synthesis.
In an embodiment of the present invention, which is set forth in greater
detail in the examples below, the nutritional supplement comprises ginsenoside
Rbl. A serving of the nutritional supplement comprises 0.000001 g to about
0.0001 g of ginsenoside Rbl. The preferred dosage of a serving of the
nutritional
supplement comprises about 0.00005 g of ginsenoside Rbl.
In an embodiment of the present invention, which is set forth in greater
detail Example 1, the nutritional supplement comprises L-carnitine fumarate,
an
extract of Coleus forskohlii, yohimbine HCI, N-acetyl L-carnitine, melatonin,
ubidecarenone (coenzyme Q10), idebenone, decylubiquinone, an extract of
Agaricus blazei Murill, and ginsenoside Rbl. The composition is provided in
any
acceptable and suitable oral dosage form as known in the art to maintain
androgen and androgen-like uptake potential of cells, and minimize muscle
damage associated with resistance exercise.
In another embodiment of the present invention, which is set forth in
greater detail Example 2, the nutritional supplement comprises L-carnitine
fumarate, idebenone, decylubiquinone, an extract of Agaricus blazei murill,
and
ginsenoside Rbl. The composition is provided in any acceptable and suitable
oral dosage form as known in the art to maintain androgen and androgen-like
uptake potential of cells, via simultaneous increase in the availability of
androgen
receptors and improved availability of androgen and androgen-like molecules,
as
well as to minimize muscle damage associated with resistance exercise.
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Additional Embodiments for Maintaining Androgen and Androgen-
like Uptake Potential in Cells
While, not wishing to be bound by theory, the present invention is
comprised of components that have been shown to enhance hormonal responses
to resistance exercise, reduce muscle damage associated with resistance
exercise and produce a protective effect against pain and damage from
eccentric
effort by acting as a vasodilator. It is herein understood by the inventors
that
inclusion of L-Carnitine fumarate in the claimed composition will act to
facilitate a
faster recovery following resistance exercise, reduce the catabolism of muscle-
specific proteins, resulting in enhanced testosterone uptake via increased
availability of AR than is normally observed in the absence of such
supplementation. Furthermore, it is understood that the vasodilative
properties
provided by the L-Carnitine fumarate will act to improve the energetic
metabolism
of the hypoxic muscle and enhance the wash-out of pain generating metabolites.
Furthermore, the present invention may additionally comprise melatonin
which has been shown to increase serum free GH after heavy-resistance
exercise, and induce a trend towards elevated levels of IGFBP-3. It is herein
understood by the inventors that the increased availability of GH will
increase
binding to the extracellular domain of the GH receptor and promote the release
of
the anabolic insulin-like growth factor 1(IGF-1), which is androgen-like and
is
known to interact with AR.
Additionally, the present invention comprises an extract of Coleus
forskolhii which has been shown to have a favorable effect on enhancing serum
testosterone levels, via cAMP-mediated LH effects on endogenous testosterone
production as well as increasing secretion of LH. It is herein understood by
the
inventors that increased testosterone will result in greater stimulation of
the AR
signaling pathway, leading to increases in lean muscle mass, muscle strength,
and muscle protein synthesis.
In addition, the present invention may additionally comprise
Ubidecarenone (Coenzyme Q10) and/or derivatives thereof,which exhibit
antioxidant activities and have protective effects on mitochondrial membranes
(Liu J, Rone MB, Papadopoulos V. Protein-protein interactions mediate
mitochondrial cholesterol transport and steroid biosynthesis. J Biol. Chem.
2006
Dec 15;281(50):38879-93). It is herein understood by the inventors that these
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protective effects will ensure the integrity of the membrane-receptor
interface and
preserve the effect of hormones on mitochondrial cholesterol transport and
steroidogenesis.
Further to the aforementioned functions, the present invention may
additionally comprise components, for example Agaricus blazei, which acts to
suppress aromatase activity and estrogen biosynthesis (Chen S, Oh SR, Phung
S, Hur G, Ye JJ, Kwok SL, Shrode GE, Belury M, Adams LS, Williams D. Anti-
aromatase activity of phytochemicals in white button mushrooms (Agaricus
bisporus). Cancer Res, 2006 Dec 15;66(24):12026-34 (Abstract)). It is herein
understood by the inventors that suppression of the activity of aromatase will
result in increased serum testosterone levels, yielding greater stimulation of
the
AR signaling pathway, leading to increases in lean muscle mass, muscle
strength, and muscle protein synthesis.
According to various embodiments of the present invention, the nutritional
supplement may be consumed in any form. For instance, the dosage form of the
nutritional supplement may be provided as, e.g., a powder beverage mix, a
liquid
beverage, a ready-to-eat bar or drink product, a capsule, a liquid capsule, a
tablet, a caplet, or as a dietary gel. The preferred dosage forms of the
present
invention are as a caplet or as a liquid capsule.
Furthermore, the dosage form of the nutritional supplement may be
provided in accordance with customary processing techniques for herbal and
nutritional supplements in any of the forms mentioned above. Additionally, the
nutritional supplement set forth in the example embodiments herein disclosed
may contain any appropriate number and type of excipients or additional
ingredients, as is well known in the art.
By way of ingestion of the composition of the present invention, a method
for substantially simultaneously reducing the catabolism of muscle-specific
proteins as well as stimulating the production of and inhibition of the
degradation
of androgen and androgen-like substances is provided. The increase of
androgen and androgen-like substances resulting from the method of the present
invention then confer their respective actions on androgen receptors. The
method of the present invention comprises at least the step of administering
to an
individual a therapeutically acceptable amount of the composition of the
present
invention.
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Although the following examples illustrate the practice of the present
invention in two of its embodiments, the examples should not be construed as
limiting the scope of the invention. Other embodiments will be apparent to one
of
skill in the art from consideration of the specifications and example.
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Examples
Example 1
A nutritional supplement comprising the following ingredients per serving is
prepared for consumption as a caplet to be consumed twice daily:
About 1.25 g of L-carnitine fumarate and about 0.025 g of an extract of Coleus
forskohlii standardized to 10% forskolin.
Preferably, the nutritional supplement is consumed in accordance with the
following directions:
Directions: The supplement should be consumed in 2 servings per day, one
taken with a main meal and the other with a pre-workout meal (generally
consumed 1 hr prior to commencement of exercise). On non-workout days, the
supplement should be taken with main meals, one of which is dinner.
Supplementation should last for a 21 day cycle, with a 7 to 10 day wash-out
period before commencement of another treatment round.
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Example 2
A nutritional supplement comprising the following ingredients per serving is
prepared for consumption as a caplet to be consumed twice daily:
About 1.25 g of L-carnitine fumarate, about 0.025 g of an extract of Coleus
forskohlii standardized to 10% forskolin, about 0.375 g of N-acetyl L-
carnitine,
about 0.0005 g of melatonin, about 0.001 g of ubidecarenone (coenzyme Q10),
about 0.001 g of Idebenone, about 0.00001 g of dexylubiquinone, about 0.001 g
of an extract of Agaricus blazei Murill, and about 0.00005 g of ginsenoside
Rbl.
Preferably, the nutritional supplement is consumed in accordance with the
following directions:
Directions: The supplement should be consumed in 2 servings per day, one
taken with a main meal and the other with a pre-workout meal (generally
consumed 1 hr prior to commencement of exercise). On non-workout days, the
supplement should be taken with main meals, one of which is dinner.
Supplementation should last for a 21 day cycle, with a 7 to 10 day wash-out
period before commencement of another treatment round.
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Example 3
A nutritional supplement comprising the following ingredients per serving is
prepared for consumption as a capiet to be consumed twice daily:
About 1.125 g of L-carnitine fumarate, about 0.0001 g og idebenone, about
0.00001 g of decylubiquinone, about 0.001 g of an extract of Agaricus blazei
murill, and about 0.00005 g of ginsenoside Rbl.
Preferably, the nutritional supplement is consumed in accordance with the
following directions:
Directions: The supplement should be consumed in 2 servings per day, one
taken with a main meal and the other with a pre-workout meal (generally
consumed 1 hr prior to commencement of exercise). On non-workout days, the
supplement should be taken with main meals, one of which is dinner.
Supplementation should last for a 21 day cycle, with a 7 to 10 day wash-out
period before commencement of another treatment round.
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Extensions and Alternatives
In the foregoing specification, the invention has been described with
specific embodiments thereof; however, it will be evident that various
modifications and changes may be made thereto without departing from the
broader spirit and scope of the invention.
