|
J
Nutr. 2007 Jun;137(6 Suppl 2):1646S-1649S.
Pharmacokinetics of arginine and related amino acids.
Arginine (ARG) and its related amino acids (AAs) ornithine (ORN)
and citrulline (CIT) find a range of applications as dietary supplements
in subgroups of healthy subjects (e.g., bodybuilders) and patients
with acute or chronic malnutrition. These AAs appear to be well utilized
in humans with, in general, a rapid return of blood concentrations
to basal values (i.e., within 5-8 h) and low absolute and relative
excretion in urine (<5% of administered dose). Based on published
data for the maximum observed plasma concentrations (Cmax) after
administration of doses in the range 5 to 10 g, CIT appeared to present
relatively
better absorption and systemic bioavailability than ARG and ORN.
The few relevant dose-ranging studies available include 1 limited
to a
single subject receiving 5- to 20-g doses of ornithine alpha-ketoglutarate
and another in which 8 subjects received from 5 to 15 g of CIT. Comparison
of these 2 studies further indicates that CIT has higher bioavailability
than ORN. The pharmacokinetics and metabolism of these AAs are modified
by the coadministration of a salt such as alpha-ketoglutarate that
modifies AA metabolism, as has clearly been demonstrated for ornithine
alpha-ketoglutarate. Concomitant administration of a meal leads to
a 15- to 30-min delay in Cmax. Finally, data from various pharmacokinetic
studies together with basic physiology and biochemistry indicate
that ARG is a net urea producer and ORN has a nitrogen-sparing effect,
whereas
CIT is neutral. However, most of the studies performed to date carry
methodological weaknesses and are difficult to compare because of
a number of confounding factors. To date, there have been no pharmacokinetic
studies on the long-term administration of these AAs in healthy subjects
despite the need to determine the safe upper limit of daily intake.
Physiol Res. 2008 Feb 13 [Epub ahead of print]
Hormonal aspects of the muscle-bone unit.
Osteoporotic fractures are the result of low density and especially
inferior bone quality (microarchitecture) caused by both internal
(genes, hormones) and external (life style) influences. Bone mechanosensors
are extremely important for the overall integrity of the skeleton,
because in response to mechanical load they activate its modeling,
resulting in an increase in bone density and strength. The largest
physiological loads are caused by muscle contractions. Bone mass
in adult men has a closer relationship to muscle mass than is case
in women. The sexual differences in the relationship between bone
and muscle mass are also apparent in children. Based on the mechanostatic
theory, the muscle-bone unit has been defined as a functional system
whose components are under the common control of the hormones of
the somatotropin-IGF-I axis, sexual steroids, certain adipose tissue
hormones and vitamin D. The osteogenic effects of somatotropin-IGF-I
system are based on the stimulation of bone formation, as well as
increase in muscle mass. Moreover, somatotropin decreases the bone
mechanostat threshold and reinforces the effect of physical stress
on bone formation. The system, via the muscle-bone unit plays a significant
role in the development of the childhood skeleton as well as in its
stability during adulthood. The muscle and bone are also the targets
of androgens, which increase bone formation and the growth of muscle
mass in men and women, independently of IGF-I. The role of further
above-mentioned hormones in regulation of this unified functional
complex is also discussed. This paper is scheduled for Physiological
Research, Vol. 57, Supplement 1 (2008).
Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):50-4
Growth hormone, arginine and exercise.
PURPOSE OF REVIEW: To describe the effect of an acute bout of exercise
on growth hormone responses and to discuss the effect of L-arginine
supplementation on growth hormone responses. RECENT FINDINGS: Recent
studies have shown that resting growth hormone responses increase
with oral ingestion of L-arginine and the dose range is 5-9 g of
arginine. Within this range there is a dose-dependent increase and
higher doses are not well tolerated. Most studies using oral arginine
have shown that arginine alone increases the resting growth hormone
levels at least 100%, while exercise can increase growth hormone
levels by 300-500%. The combination of oral arginine plus exercise
attenuates the growth hormone response, however, and only increases
growth hormone levels by around 200% compared to resting levels.
SUMMARY: Exercise is a very potent stimulator of growth hormone release
and there is considerable research documenting the dramatic growth
hormone rise. At rest oral L-arginine ingestion will enhance the
growth hormone response and the combination of arginine plus exercise
increases growth hormone, but this increase may be less than seen
with exercise alone. This diminished response is seen in both in
both younger and older individuals. Int J Sport Nutr. 1997 Mar;7(1):48-60.
Acute effect of amino acid ingestion and resistance exercise on plasma
growth hormone concentration in young men.
Sixteen
men completed four trials at random as follows: (Trial A) performance
of a single bout of resistance exercise preceded by
placebo ingestion (vitamin C); (Trial B) ingestion of 1,500 mg
L-arginine and 1,500 mg L-lysine, immediately followed by exercise
as in Trial
A; (Trial C) ingestion of amino acids as in Trial B and no exercise;
(Trial D) placebo ingestion and no exercise. Growth hormone (GH)
concentrations were higher at 30, 60, and 90 min during the exercise
trials (A and B) compared with the resting trials (C and D) (p < .05).
No differences were noted in [GH] between the exercise trials.
[GH] was significantly elevated during resting conditions 60
min after
amino acid ingestion compared with the placebo trial. It was
concluded that ingestion of 1,500 mg arginine and 1,500 mg lysine
immediately
before resistance exercise does not alter exercise-induced changes
in [GH] in young men. However, when the same amino acid mixture
is ingested under basal conditions, the acute secretion of GH
is increased. Curr Opin Clin Nutr Metab Care. 2007 Jan;10(1):46-51.
Effects of L-arginine supplementation on exercise metabolism.
PURPOSE OF REVIEW: To describe the influence of acute and chronic
administration of L-arginine on metabolism at rest and during exercise.
RECENT FINDINGS: There has been substantial examination of the effect
of infusion and ingestion of L-arginine at rest. It has been clearly
demonstrated that L-arginine administration improves endothelial
function in various disease states. In addition, L-arginine infusion
at rest increases plasma insulin, growth hormone, glucagon, catecholamines
and prolactin. Such hormonal changes affect metabolism. There has,
however, been very little examination of the effect of increases
in L-arginine availability during exercise. This is important to
study as there is preliminary evidence that L-arginine infusion,
probably via increases in nitric oxide (NO), alters skeletal-muscle
metabolism during exercise. There is a need for further research,
especially to understand the mechanisms of how L-arginine affects
exercise metabolism and also to determine whether the hormonal responses
that occur in response to L-arginine at rest are also present to
some extent during exercise. SUMMARY: This line of research may have
important therapeutic implications as there are indications that
L-arginine augments the effects of exercise training on insulin sensitivity
and capillary growth in muscles.
J
Cosmet Dermatol. 2008 Mar;7(1):2-7.
Anti-aging properties of resveratrol (compound found
in grapes and red wine): review and report of a potent new
antioxidant skin care formulation.
(Studies also suggest that Resveratrol may play a role in
calorie restriction and anti-aging.)
Resveratrol, an antioxidant polyphenol from red wine, has
been the subject of intense interest in recent years due to
a range of unique anti-aging properties. These include cardiovascular
benefits via increased nitric oxide production, down-regulation
of vasoactive peptides, lowered levels of oxidized low-density
lipoprotein, and cyclooxygenase inhibition; possible benefits
on Alzheimer's disease by breakdown of beta-amyloid and direct
effects on neural tissues; phytohormonal actions; anticancer
properties via modulation of signal transduction, which translates
into anti-initiation, antipromotion, and antiprogression effects;
antimicrobial effects; and sirtuin activation, which is believed
to be involved in the caloric restriction-longevity effect.
Here we report a resveratrol-based skin care formulation, with
17 times greater antioxidant activity than idebenone. The role
of resveratrol in prevention of photoaging is reviewed and
compared with other antioxidants used in skin care products.
Crit
Rev Clin Lab Sci. 2008;45(1):91-135.
FGF-1: from biology through engineering to potential medical applications.
Human fibroblast growth factor 1 (FGF-1) is one of the best
characterized members of the FGF superfamily. FGF-1 is a powerful
mitogen exhibiting strong action on numerous different cell
types. It plays a role in various stages of development and
morphogenesis, as well as in angiogenesis and wound healing
processes. Engineering of FGFs can bring many advantages. Design
and construction of different mutants can contribute to a better
understanding of the mechanism of action of protein growth
factors. Moreover, application of FGFs as recombinant polypeptides
in the treatment of wound and fracture healing, cardiovascular
diseases and neurodegenerative diseases seems to be a rational
medical approach. However, low thermal stability and high sensitivity
to proteases limit the potential pharmaceutical use of wild-type
FGFs. Thus, advanced protein design techniques and recombinant
protein production can help to obtain new variants of FGFs
with radically increased thermodynamic stability, prolonged
half-life and improved proteolytic resistance. Such studies
can provide a good starting point to convert short-lived and/or
sensitive growth factors to effective therapeutic proteins.
|
|
