GEROVITAL (GH3) Articles (V)
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Gerovital
H3 (GH3) - Old Age Humoral Dysmetabolism
By Mircea Dumitru, M.D., Ph.D.
The
functions of an aging individual show in the totality of the changes
of the metabolic and neurohormonal modulation.
The
dominant feature in elderly people is a great liability under stressful
conditions', as a consequence there is a decrease in the total water
content of the body and hydroelectrolytic turnover, as well as cellular
and humoral dysmetabolisms. Advancing age brings about a general anabolic
deficit, a reduction of tolerance of carbohydrates, an increasing
in biochemical values of lipids and hemocoagulation components, and
a diminution of the cellular energetic potential. Each of the functions
having its own development and aging time-table.
Gerovital-H3®
has a positive effect on the cell metabolism and on the cell membrane.
There are studies where the emphasis was placed on Gerovital-H3®
intervention in the intermediate metabolism favoring ATP synthesis
(1). This hypothesis was based on the discrepancy between the favorable
trophic effect and the reduced O2 consumption. This finding seems
to point out procaine similarity with antioxidative abilities. Since
1962, Ficher and Klotz (2) insisted on procaine's antioxidative effect.
Other studies carried out on yeast (3) pointed out procaine action
on the enzymes involved in oxireduction. Research on liver homogenate
revealed procaine intervention on oxidative phosphorilation of glucidic
metabolism (4).
ENERGETIC
METABOLISM (EM)
EM
undergoes modifications during the life cycle at the level of energy
production, storage, transformation and liberation. The cell oxygen
consumption decreases progressively with age: At the age of 20: a
man's basal metabolism is of 42.5 1.6 cal/sq.m./h; A female's metabolism
is of 36.7 2.7 cal./sq. m./h. At the age of 40: a man's metabolism
is of 38 2.9 cal./sq.m./h and 35.9 2 cal./sq.m./h. in females.
However,
this diminution of the cellular oxygen consumption is neither regular
nor uniform; as a compensation, while tissular activity of oxidative
phosphorylation decreases, the glycolytic activity increases and some
anaerobic energy-generating processes are intensified.
The
reduction of the energetic potential is brought about by the diminution
in the number and volume of the mitochondria, of the oxidation substrate
and of respiratory enzymes. Unlike other structures, the heart tissue
shows an accentuation of oxidative and phosphorylating couplings.
The low capacity of an aging organism in pathological conditions reflects
the low energetic potential of the cells.
The
controversial results of the studies on basal metabolism in the elderly
depend on the normal and pathological factors that may influence it.
The elderly's physical state, the muscle activity one develops, as
well as one's bone pathology, neuromuscular coordination, psychological
state and integument's aging degree may influence on production or
loss of heat.
With
the advance in age, in parallel to the decrease of oxygen consumption,
we also may see modifications of the thermoregulation. In conditions
of average temperature, the body maintains constant temperature even
in advanced ages. However, it presents difficulties for its adaptation
to extreme temperatures. As the years pass by, as a consequence of
a poorer blood flow in the skin, temperature records has a tendency
to decrease, so that the response to the low environmental temperatures
will be slower. On the other hand, by the integument aging through
atrophy, dryness, reduced elasticity and modifications of the capillaries
structure, this diminishes the capacity of water elimination through
the skin, explaining the elderly's difficulty of adaptation to caloric
stress.
LIPID
METABOLISM
The
normal indicators of the lipids metabolism inscribe themselves on
a curve with maximum values in the 6th and 7th decades of life. In
long-lived people, biochemical constants are significantly equal to
those of young adults. Directly related to the quantity of cholesterol,
total blood lipids increase at the age of 70 as compared to the values
recorded at 30 years. The increase is especially on account of the
esterified cholesterol (low density) and of the cholesterol bound
to beta-lipoproteins (with a tropism to the vascular wall). The relation
of lecithin to cholesterol decreases. Kurth's studies (5) on procaine
action on the lipids metabolism recorded favorable results in atherosclerotic
subjects in whom the function of the cell membrane was corrected.
Also, the arteriosclerotic dysproteinemias became normal as a result
of procaine administration. The author noticed the clearing of serum
as well as the decrease of cholesterol levels.
In
order to point out the antiatherogenous action of Gerovital-H3®,
Aslan carried out a study on 25 subjects aged 72-90 to procaine treatment
for 4-11 years (1); an equal number of patients were used as controls.
The author studied lipoprotein lipase activity in vitro as well as
different lipids-fractions after both heparin injections and the activation
of the endogenous lipoprotein lipase. Lipoprotein lipase activity
reached the average values 13.01 2.01 in the treated subjects, as
against 8.75 1.77 in the controls (the normal value is 15 1.6). An
obvious dislocation of the lipoproteins fractions was noticd after
the heparin injection, with the modification of the beta/alpha-lipoprotein
gradient (80% in the treated subjects, as against 15% in the controls).
The modifications of the coefficient beta/alpha specific to the post-heparin
lipoproteins tallied with the lipoprotein lipase enzymatic activity
in vitro.
The
inference maybe thus drawn is that one of the important links in the
atherosclerotic dyslipoidosis chain is also subjected to the eutrophic
treatment with Gerovital-H3®. This data may be correlated with
the reduced number of trombotic accidents in aged subjects treated
with Gerovital-H3®.
Comparative
studies on Gerovital-H3® and procaine action carried out by Greppy
and Sgardigli (6) showed the higher efficiency of Gerovital-H3®.
Gordon and colleagues (7,8) conducted comparative studies on American
procaine and Gerovital-H3®.
The experiments revealed too the higher efficiency of Gerovital-H3®.
PROTEIN
METABOLISM
Enzymatic
structures and protein biochemistry undergo modifications in elderly
people. Quantitative modifications are noted in the activity of monoaminooxydase
(MAO), aldolase, myosin, adenosine-triphosphatase and phosphofructokinase.
Studies published (9,10) draw attention to the modification induced
by aging in the enzymatic activity of the nerve cell as well as to
the intervention of procaine at this level. The increased MAO activity
could play an important role in the biochemical modifications induced
by aging and depressive states. Depressive states have been correlated
with the reduction of central amines (11) which is due to the increase
of MAO. The anti depressive effect of Procaine (Gerovital-H3®)
has been pointed out by Bucci and Saunders (12), Siggelkow (13), Cambel
(14), MacFarlane (9,10), Zung (15) and other researchers.
The
total contents of seric proteins remain unchanged. A modification
in the ratio of albumin to globulin will be observed: from 1.38 0.03
at the age of 25 it becomes 1.02 0.02 at the age of 75.
Quantitative
modifications are observed in the protein contents of muscles, brain
and liver. The net muscle mass decreases. Cytoplasm proteins tend
to form inactive complexes, so that the fibrils protein structures
increase. A diminution of active protoplasmic mass, and along with
it, a reduction of the total potassium content of the body will be
observed.
CARBOHYDRATES
METABOLISM (CM)
CM
presents two important phenomena in the aged:
The
accentuation of the anaerobic phase of glycolyse, and in consequence
the diminution of oxidative phosphorilation processes;
The reduction of the tolerance to glucose.
The aspects related to the statement of a tolerance reduction to glucose
with the advance in age, and to the physiological or physiopathological
mechanisms which lead to this situation are not yet completely elucidated.
It was considered that there is a "real" decrease of the
tolerance to glucose with the advance in age, in both sexes, this
being shown by glycemia (fasting blood sugar) and by dynamic tests.
Some researchers consider that for each decade of age after 50, the
fasting blood sugar increases by 1 to 2mg./dl., and postprandial blood
sugar increases by 5 to 6 mg./dl.
There
are four age-related factors that are incriminated in bringing about
modifications in CM: (Carbohydrate Metabolism)
An
inadequate Insulin Input;
Decrease of the body net muscle mass;
Increase of the adipose mass tissue, and
Reduction of the cell sensitivity to Insulin independently of any
effect of adiposity.
It is considered that previous estimation as to the influence of age
upon the decrease of the tolerance to glucose have been exaggerated,
as it is not taking into account among other parameters, the correlation
of diabetes mellitus, overweight and other existing chronic diseases.
However,
the correlation between fasting blood sugar and advance in age was
statistically proved, considering the modifications due to overweight.
As
years pass by, a slight unbalance will be observed in the glucose
homeostasis. However, this is not an absolute rule and it is more
or less accentuated by the frequent association of chronic diseases
and obesity.
THE
INADEQUATE INSULIN INPUT
A
reduced insulin secretion has been initially considered as an important
factor in reducing the tolerance to glucose in the elderly. This opinion
is being revised today considering the following:
Most
of the studies show that the advance in age does not lead to reducing
the insulin liberation by a stimulation with glucose;
It has even been demonstrated that plasmatic insulin concentration
increase in the old, whence it may be deducted that their intolerance
to glucose could be determined by a diminished capacity of plasmatic
insulin to stimulate the utilization of plasmatic glucose. It is also
supposed that there may be a deficient insulin metabolization- a supposition
based on data showing a diminution with age of the plasmatic insulin
clearance.
REDUCTION
OF THE BODY NET MUSCLE MASS
With
the advance in age, a correlation has been stated between a reduction
of the muscle mass and the reduced tolerance to glucose.
INCREASE
OF THE ADIPOSE TISSUE
It
is known that the process of hypertrophy and hyperplasia at the adipocyte
level is accompanied by a reduced insulin-receptivity, but the inner
mechanism by which obesity is determining it is not explained. On
the other hand, during the aging process an increased frequency of
obesity is observed. However, replacement of the muscle-mass by adipose
tissue takes place even if the body weight remains unchanged. Specific
transformation in the adipose tissue, associated to above mentioned,
may cooperate in modifying the glucidic homeostasis.
DECREASE
OF THE CELL SENSITIVITY TO INSULIN
It
was emitted the hypothesis that, with age there might exist a decrease
of the cell sensitivity to insulin in the target organs, independently
of the degree of obesity.
However,
there is not sufficient proof to support this hypothesis which is
contradicted by the fact that it is a normal sensitivity to insulin
associated to a normal tolerance to orally administered glucose.
CONCLUSIONS
On
the basis of the above considerations it may be said that:
Glucidic
homeostasis is not necessarily modified by the aging process.
When glucidic homeostasis appears to be modified by the aging process,
a modification manifested by a reduced tolerance to glucose and apparition
of the age-related hyperglycemic syndrome, there may exist a loss
of the insulin normal action "in vivo".
A parallel drawn between diabetes mellitus and the aging process suggests
that diabetes mellitus could represent a model for the latter and
some common elements being observed:
-
The rigidity of the arterial wall;
- An increased incidence of coronary atherosclerosis;
- The thickening of the basal membrane of the capillaries;
- Anomalies of lipids metabolism.
- Gerovital-H3®, as
an intact molecule, and through diethylaminoethanol (DEAE) and paraaminobenzoic
acid (PABA) intervenes in the metabolic regulation.
According
to Laborit, substances having this type of action, play an important
role in the cellular reactivating, and thus we may deduce an enhancement
of activity at the cellular level leads to improved energy levels.
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