Pantetheine
WHAT
IS IT?
Pantethine
is the stable form of pantetheine, the active form of the vitamin Pantothenic
acid.
This
is the fundamental component of Coenzyme A (CoA) which transports fatty acids
into the
mitochondria
of cells. It is one of the most important enzymes in the body and is also
critical for
many
other functions ranging from antibody synthesis to maintaining blood sugar
levels. The
pathway
of pantethine is much shorter than pantothenic acid.
while
increasing the good HDL cholesterol. Pantothenic acid has no such activity.
In
studies, Pantethine reduced serum triglycerides by 32% (the most of any substance,)
total
cholesterol
by 19% and LDL cholesterol by 21%. It also raised HDL cholesterol by 23%!
source.
Niacin
impairs insulin action and is unsuitable for diabetics.
Although no studies have been done with it, the weight loss effects of
pantothenic
acid may be
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Comparison
of the efficacy of pantethine, acipimox, and bezafibrate on plasma lipids
and index of
cardiovascular
risk in diabetics with dyslipidemia
Atherosclerotic
manifestations are more common and precocious in diabetics than in the general
population. Due to the increased cardiovascular risk, a primary or secondary
(to diabetes mellitus) lipoprotein disorder in diabetics has to be carefully
considered. 27 diabetics (15 NIDDM and 12 IDDM) with dyslipidemia (14 type
IV, 8 type IIa and 5 type IIb) were divided in 3 groups and treated with 3
different hypolipemic drugs (Group A: pantethine 600 mg/day; Group B: acipimox
500 mg/day; Group C: bezafibrate 600 mg/day) to test their efficacy and acceptancy.
Body weight, Hb A1-c, serum lipoproteins have been measured before and during
the 6 months treatment. A significant variation of lipidemic pattern was observed
in Group C: a decrease of cholesterol (-20%), triglycerides (-40%), LDL (-24.4%)
and apo B (-26.8%) with an increase of HDL (+23.6%). Pantethine and acipimox
were more effective on triglycerides (-37.7% and -23.3% respectively). Cardiovascular
risk (CT tot/CT HDL) was significantly reduced with acipimox and normalized
with bezafibrate. Tonutti L, Taboga C, Noacco C. Comparison of the efficacy
of pantethine, acipimox, and bezafibrate on plasma lipids and index of cardiovascular
risk in diabetics with dyslipidemia. Minerva Med 1991;82:657-663.
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Preclinical
and clinical studies with cysteamine and pantethine related to the central
nervous
1.
Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin
(SS), prolactin and noradrenaline depletion in the brain and peripheral tissues.
2. Cysteamine influences several behavioral processes, like active and passive
avoidance behavior, open-field activity, kindled seizures, pain perception
and SS-induced barrel rotation. 3. Cysteamine has several established (cystinosis,
radioprotection, acetaminophen poisoning) and theoretical (HuntingtonÕs disease,
prolactin-secreting adenomas) indications in clinical practice. 4. Pantethine
is a naturally occurring compound which is metabolized to cysteamine. 5. Pantethine
depletes SS, prolactin and noradrenaline with lower efficacy compared to that
of cysteamine. 6. Pantethine is well tolerated by patients and has been suggested
to treatment of atherosclerosis. The other possible clinical indications (alcoholism,
ParkinsonÕs disease, instead of cysteamine) are discussed. Vecsei L, Widerlov
E. Preclinical and clinical studies with cysteamine and pantethine related
to the central nervous system. Prog Neuropsychopharmacol Biol Psychiatry 1990;14:835-862.
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Treatment
of hyperlipemia in diabetic patients on dialysis with a physiological substance
Hyperlipemia
is a very frequent complication of the diabetic patient on dialysis. There
is difficulty of treatment with the diet, because the dietary restriction
already imposed on these patients and the secondary effects and toxicity of
the available drugs in uremics aggravate the problem. We have treated 22 diabetic
patients on dialysis (8 on hemodialysis and 14 on continuous ambulatory peritoneal
dialysis) suffering from hyperlipemia with pantethine, a physiological substance
and coenzyme A precursor in the Krebs cycle. With the administration of an
oral dose of 900 mg/day we obtained a reduction of total cholesterol (275
+/- 72 vs. 231 +/- 54 mg/dl; p less than 0.001), very-low-density lipoprotein
(VLDL)-cholesterol (66 +/- 36 vs. 46 +/- 18 mg/dl; p less than 0.01) and triglycerides
(332 +/- 182 vs. 227 +/- 90 mg/dl; p less than 0.01) at 2 months. High-density
lipoprotein (HDL)-cholesterol did not change, but the total cholesterol/HDL-cholesterol
ratio decreased significantly (p less than 0.05). Total cholesterol, VLDL
and triglycerides showed a progressive and significant reduction at 4 and
6 months. No changes were observed in serum glutamic oxaloacetic transaminase,
serum glutamic pyruvic transaminase, uric acid, blood glucose and glycosylated
hemoglobin. Gastric discomfort in 2 patients and pruritus in another one were
the secondary effects related. Pantethine was shown to be a very effective
hypolipemic agent in diabetic patients on dialysis with a great tolerance.
Coronel F, Tornero F, Torrente J, et al. Treatment of hyperlipemia in diabetic
patients on dialysis with a physiological substance. Am J Nephrol 1991;11:32-36.
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Investigation
of the roles of the substances in serum lipids and their constitutive fatty
acids in
The
newly-generated lipid mediators include products of arachidonate metabolism,
prostaglandins and leukotrienes. In this study, serum lipids and fatty acids,
including arachidonic acid (C20:4) were examined in 12 normal subjects (6
males and 6 females) and 23 subjects with chronic urticaria (6 males and 17
females), including 17 who made an excellent or good recovery (4 males and
13 females). The results indicated a relationship between chronic urticaria
and serum lipids and fatty acids. The omega 6 (n-6) and omega 3 (n-3) series
of polyunsaturated fatty acids and lipid peroxidation were suggested that
may be one of the mediators in chronic urticaria. Pantethine, glutathione
and ascorbic acid were effective in controlling chronic urticaria. Kobayashi
S. Investigation of the roles of the substances in serum lipids and their
constitutive fatty acids in chronic urticaria. J Dermatol 1989;16:196-206.
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Lipoprotein
changes induced by pantethine in hyperlipoproteinemic patients: adults and
children
Following
a brief outline of current knowledge concerning atherosclerosis and its treatment,
the authors describe the results obtained by treating with pantethine (900-1200
mg daily for 3 to 6 months) a series of 7 children and 65 adults suffering
from hypercholesterolemia alone or associated with hypertriglyceridemia (types
IIa and IIb of FredricksonÕs classification). Pantethine treatment produced
significant reduction of the better known risk factors (total cholesterol,
LDL-cholesterol, triglycerides, and apo-B) and a significant increase of HDL-cholesterol
(signally HDL2) and apolipoprotein A-I. The authors conclude with a discussion
of these results and of the possible role of pantethine in the treatment of
hyperlipoproteinemia, in view of its perfect tolerability and demonstrated
therapeutic effectiveness. Bertolini S, Donati C, Elicio N, et al. Lipoprotein
changes induced by pantethine in hyperlipoproteinemic patients: adults and
children. Int J Clin Pharmacol Ther Toxicol 1986;24:630-637.
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Evaluation
of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal
age
Cardiovascular
diseases are the main cause of death also in women. Their incidence, rapidly
growing in the peri-menopausal period, is related to serum levels of total
cholesterol and its LDL fraction. It was also shown that the peroxidation
of LDL is an additional factor in the genesis of atherosclerotic vascular
disease. As long-term treatments with synthetic lipid-lowering drugs may cause
undesirable side effects, while pantethine is known to be well tolerated,
we treated 24 hypercholesterolemic women (total serum cholesterol greater
than or equal to 240 mg/dl), in perimenopausal age (range: 45-55 years, mean
+/- SD = 51.6 +/- 2.4) with 900 mg/day of pantethine. This is a precursor
of coenzyme A, with an antiperoxidation effect in vivo, and our aim was to
confirm its lipid lowering activity in this particular type of patients. After
16 weeks of treatment, significant reductions of total cholesterol, LDL-cholesterol
and LDL-C/HDL-C ratio could be observed. No remarkable changes of the main
laboratory parameters (fasting blood sugar, B.U.N., creatinine, uric acid)
were seen. Efficacy percentages of the treatment were about 80%. None of the
patients complained of adverse reactions due to the treatment with pantethine.
In conclusion, we suggest that pantethine should be considered in the long-term
treatment of lipid derangements occurring in the perimenopausal age. Binaghi
P, Cellina G, Lo Cicero G, et al. Evaluation of the cholesterol-lowering effectiveness
of pantethine in women in perimenopausal age. Minerva Med 1990;81:475-479.
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Pantethine,
diabetes mellitus and atherosclerosis. Clinical study of 1045 patients
After
a review of the clinical studies on the treatment of diabetic patients with
pantethine, the authors discuss the results obtained in a postmarketing surveillance
(PMS) study on 1045 hyperlipidemic patients receiving pantethine (900 mg/day
on average). Of these patients, 57 were insulin-dependent (Type I) and 241
were non insulin-dependent (Type II) diabetics. Beyond the epidemiological
considerations made possible by a PMS study, the authors show that pantethine
brought about a statistically significant and comparable improvement of lipid
metabolism in the three groups of patients, with very good tolerability. Pantethine
should therefore be considered for the treatment of lipid abnormalities also
in patients at risk such as those with diabetes mellitus. Donati C, Bertieri
RS, Barbi G. Pantethine, diabetes mellitus and atherosclerosis. Clinical study
of 1045 patients. Clin Ter 1989;128:411-422.
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Lowering
effect of pantethine on plasma beta-thromboglobulin and lipids in diabetes
mellitus
Pantethine
in a dosage of 600 mg for the first 3 months, and in a dosage of 1200 mg for
the second 6 months was given to 16 diabetics in whom plasma beta-thromboglobulin
was raised (greater than 50 ng/ml). Plasma beta-TG levels decreased significantly
with pantethine treatment for 9 months. Plasma triglyceride, total cholesterol,
apo E and apo CII levels decreased significantly after 9 months. Plasma LDL-C
and atherogenic index (LDL-C/HDL-C ratio or apo B/apo AI ratio) tended to
decrease with treatment. It is concluded that administration of pantethine
may be beneficial in the prevention of diabetic angiopathy because of its
lowering effect on plasma beta-TG, lipids and apolipoproteins. Eto M, Watanabe
K, Chonan N, Ishii K. Lowering effect of pantethine on plasma beta-thromboglobulin
and lipids in diabetes mellitus. Artery 1987;15:1-12.
Therapeutic
efficacy of pantothenic acid preparations in ischemic heart disease patients
The
therapeutic effectiveness of the pantothenic acid drugs: calcium pantothenate
and pantethine, was studied in 182 patients with coronary heart disease and
stable angina of effort. It is shown that both the drugs produce favourable
effects on certain parameters of hemodynamics, on the metabolism of lipids,
riboflavin and ascorbic acid. It is recommended that the administration of
calcium pantothenate in a dose of 300 mg/day, during 3 weeks, be included
into the combined treatment of coronary patients with no manifest disorders
of lipid metabolism. Patients with manifest hyperlipidemia should be administered
pantethine in a dose of 500 mg/day. Borets VM, Lis MA, Pyrochkin VM, et al.
Therapeutic efficacy of pantothenic acid preparations in ischemic heart disease
patients. Vopr Pitan 1987 Mar-Apr;(2):15-17.
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Effect
of oral treatment with pantethine on platelet and plasma phospholipids in
IIa hyperlipoproteinemia In a single-blind,
crossover, completely randomized study, the effects of oral treatment with
pantethine or placebo on fatty acid composition of plasma and platelet phospholipids
were investigated in 10 IIa hyperlipoproteinemic patients. A significant decrease
of total cholesterol and total phospholipids was observed both in plasma and
in platelets after a twenty-eight-day treatment. In plasma, pantethine induced
a decrease of the ratio sphingomyelin/phosphatidylcholine. Moreover, a relative
increase of n3-polyunsaturated fatty acids both in plasma and in platelet
phospholipids and a decrease of arachidonic acid in plasma phospholipids were
observed. These results indicate that pantethine can affect plasma and platelet
lipid composition with possibly favorable influences on the determinants of
cell membrane fluidity. Prisco D, Rogasi PG, Matucci M, et al. Effect of oral
treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia.
Angiology 1987;38:241-247.
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Hyperlipidemia,
diabetes and atherosclerosis: efficacy of treatment with pantethine
The hypolipidemizing effects of pantethine were investigated by the authors in 37 hypercholesterolemic and/or hypertriglyceridemic patients. Of these, 21 were also diabetic, in a satisfying glucidic compensation, in order to verify the action of this drug also in this metabolic condition. The study was carried out for three months and during this period the patients were given pantethine at the dose of 600 mg/day orally. At the 30th, the 60th, the 90th day of treatment the following parameters were controlled: cholesterolemia, HDL cholesterol, apolipoproteins A and B, triglyceridemia, systolic and diastolic arterial pressure, uricemia, body weight. Thirty days after suspending the treatment, the parameters were controlled again to detect a possible rebound effect. The results were analyzed on the whole case-record, subdividing the patients in dislipidemic and diabetic-dislipidemic, and on the basis of the FredricksonÕs classification. Pantethine induced in all groups a quick and progressive decrease of cholesterolemia, triglyceridemia, LDL cholesterol and Apolipoproteins B with increased HDL cholesterol and Apolipoproteins A. After suspending the treatment, there is a clear inversion of the state of these parameters. The authors conclude that the present work shows that pantethine, a natural and atoxic substance, an important component of Coenzyme A, is efficacious in determining a clear tendency towards normalization of the lipidic values. Arsenio L, Caronna S, Lateana Met al. Hyperlipidemia, diabetes and atherosclerosis: efficacy of treatment with pantethine. Acta Biomed Ateneo Parmense 1984;55:25-42.
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Effectiveness of long-term treatment with pantethine in patients with dyslipidemia
A
one-year clinical trial with pantethine was conducted in 24 patients with
established dyslipidemia of FredricksonÕs types II A, II B, and IV, alone
or associated with diabetes mellitus. The treatment was well tolerated by
all patients with no subjective complaints or detectable side effects. Blood
lipid assays repeated after 1, 3, 6, 9, and 12 months of treatment revealed
consistent and statistically significant reductions of all atherogenic lipid
fractions (total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein
B) with parallel increases of high-density lipoprotein cholesterol and apolipoprotein
A. The results were equally good in patients with uncomplicated dyslipidemia
and in those with associated diabetes mellitus. The authors conclude that
pantethine (a drug entity related to the natural compound, pantetheine) represents
a valid therapeutic support for patients with dyslipidemia not amenable to
satisfactory correction of blood lipids by diet alone. Arsenio L, Bodria P,
Magnati G, et al. Effectiveness of long-term treatment with pantethine in
patients with dyslipidemia. Clin Ther 1986;8:537-545.
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Pantethine
improves the lipid abnormalities of chronic hemodialysis patients: results
of a
In
the course of a post-marketing surveillance program on the effectiveness and
tolerability of pantethine in the treatment of hyperlipidemia, the effects
of the drug were explored in 31 patients with dyslipidemia undergoing chronic
hemodialysis. The mean duration of treatment was 9 months (min. 7 months,
max. 24 months), with oral doses of 600 to 1200 mg of pantethine daily (mean
daily dosage 970 mg). Improvement was noted in terms of total blood cholesterol
in the 7 patients with basal hypercholesterolemia (p less than 0.01) and highly
significant reduction of serum triglycerides. No variations of HDL-cholesterol
or total Apo-A were detected. None of the patients experienced any adverse
effects from the treatment. In the light of extensive experience with the
drug, plus the results of this study, the authors conclude by stressing the
importance of an effective and readily tolerated product, such as pantethine,
for the treatment of dyslipidemia in patients on chronic hemodialysis. Donati
C, Barbi G, Cairo G, et al. Pantethine improves the lipid abnormalities of
chronic hemodialysis patients: results of a multicenter clinical trial. Clin
Nephrol 1986;25:70-74.
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Changes
in fatty acid composition of the single platelet phospholipids induced by
pantethine treatment
In
a single-blind cross-over study the effect of oral treatment with pantethine
on plasma and platelet lipid composition was evaluated in 20 patients with
dyslipidaemia (7 IIa, 7 IIb and 6 Iv type). In plasma significant decreases
of total cholesterol and triglycerides with increase of high density lipoprotein-cholesterol
were observed. In platelets pantethine treatment significantly reduced phospholipid
and cholesterol content. In addition gas-chromatographic analysis showed a
reduction of saturated and monounsaturated and a relative increase of polyunsaturated
fatty acid content of platelet phospholipids. A selective relative increase
was observed of some n-3 polyunsaturated fatty acids like eicosapentaenoic
and docosahexaenoic acid whereas arachidonic acid decreased. The present study
indicates a favourable influence of pantethine not only on plasma but also
on platelet lipids which could be of value in delaying the development of
atherosclerosis in dyslipidaemic patients. Gensini GF, Prisco D, Rogasi PG,
et al. Changes in fatty acid composition of the single platelet phospholipids
induced by pantethine treatment. Int J Clin Pharmacol Res 1985;5:309-318.
Lowering of blood acetaldehyde but not ethanol concentrations by pantethine
following alcohol ingestion: different effects in flushing and nonflushing
subjects A rise in blood acetaldehyde concentrations
following alcohol ingestion was significantly inhibited when healthy nonflushing
subjects were administered a clinical dose of pantethine orally. However,
similar findings were not observed in flushing (alcohol-sensitive) subjects
lacking hepatic low Km aldehyde dehydrogenase (ALDH). The blood ethanol concentrations
were not altered by this treatment in either flushing or nonflushing subjects.
Acetaldehyde (45 microM) added in vitro to whole blood and plasma obtained
1 hr after pantethine administration disappeared as the incubation continued
similarly as with blood and plasma obtained prior to pantethine treatment.
Pantethine-related metabolites, such as taurine, pantetheine, coenzyme A,
and pantothenate, activated ALDH in vitro. Hepatic acetaldehyde levels following
ethanol loading of rats treated with pantethine were much lower than in untreated
rats. The pantethine action observed only in nonflushing subjects might be
due to an accelerated oxidation of acetaldehyde by the activation of low Km
ALDH by pantethine-related metabolites formed in the liver. Watanabe A, Hobara
N, Kobayashi M, et al. Lowering of blood acetaldehyde but not ethanol concentrations
by pantethine following alcohol ingestion: different effects in flushing and
nonflushing subjects. Alcohol Clin Exp Res 1985;9:272-276.
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Controlled
evaluation of pantethine, a natural hypolipidemic compound, in patients with
different forms of hyperlipoproteinemia
Pantethine
(P), the stable disulphate form of pantetheine, major component and precursor
of coenzyme A, was evaluated within a double-blind protocol (8 weeks for P
or for a corresponding placebo) in 29 patients, 11 with type IIB hyperlipoproteinemia,
15 with type IV, and 3 with an isolated reduction of high density lipoprotein
cholesterol (HDL-C) levels. In type IIB patients, P (300 mg t.i.d.) determined
a highly significant lowering of plasma total and low density lipoprotein
(LDL) associated cholesterol (-13.5% for both parameters). In the same patients,
HDL-C levels increased about 10% at the end of treatment. Switching from P
to placebo was associated with a rapid return to the baseline cholesterolemia.
Both in type IIB and type IV patients, plasma triglyceride levels were reduced
around 30%, when P was given as the first treatment; when it was preceded
by placebo, reductions were less striking (respectively, -17.8% for type IIB
and -13.0% for type IV, at the end of P treatment). HDL-C levels were not
increased by P, either in type IV, and in the patients with low HDL cholesterolemia.
In type IV, LDL cholesterol levels showed a variable response to P: they tended
to increase when below 132 mg/dl, prior to treatment, and to be reduced when
above this level. This study provides evidence for a significant hypocholesterolemic
effect of P, a natural compound free of overt side effects. It also indicates
that P may raise HDL-C levels in type IIB patients, while moderately reducing
triglyceridemia. Gaddi A, Descovich GC, Noseda G,et al. Controlled evaluation
of pantethine, a natural hypolipidemic compound, in patients with different
forms of hyperlipoproteinemia. Atherosclerosis 1984;50:73-83.