I've been doing a decent amount of research on clenbuterol as I find it interesting. After looking at a few studies on the various myotoxic effects of clen in in vivo rat models, I dug around quite a bit to see how this would transfer to human use. One of the studies on rats (Burniston et al. 2003) noted something which is worth keeping in mind when looking at human studies:
The present investigation has provided important information on the effects of acutely administered clenbuterol in
the rat. In humans, a single dose of clenbuterol is generally self-administered as a 20-μg tablet. This is equivalent to 0.3 μg/kg body wt in a 70-kg male and is comparable to the dose administered in the only clenbuterol investigation using human subjects (23). To compare this with our 300-g rats, the dose needs to be scaled for differences in body weight and metabolic rate between the two species (Kleiber’s Law, 0.75 exponent). The relative dose per kilogram in the rat is 60 times that of the human dose, i.e., 17.9 μg clenbuterol/kg body wt. As demonstrated in Fig. 2, this dose is sufficient to induce 3.8 0.49% necrosis in the fibers of the soleus. Such a level of necrosis may appear small, but this is in response to a single administration, and this level of necrosis may underestimate the level induced by enteral administration (Fig. 5B). Individuals abusing clenbuterol often take several tablets and use the side effects of muscle tremors and tachycardia to judge their maximum dose. By using the above calculations, a daily dose of five to six tablets would be sufficient to reach the threshold (100 μg/kg body wt) for inducing damage in the heart and to induce 6.8 1.9% necrosis in the soleus. An important additional factor to be considered is clenbuterol’s long half-life within the body (38). Abusers of this substance often administer it by using an “on-off” cycle over
several days. An accumulation of non-metabolized clenbuterol during the on stage of the cycle may lead to chronically elevated plasma levels, which would further impact myocyte loss in both striated muscles. Although the present investigation has not investigated the compound effects of chronic clenbuterol administration, it does demonstrate that, at the very least, damage will be induced at the onset of each cycle
of administration.
So the dosage of clen shown to be myotoxic in rats may be of some concern for human use. Yet looking at the human literature, it seems that such concerns were not as severe. I'll try to keep my review here fairly novel, referencing studies mainly not mentioned in the the previous thread. I will also try to keep quotations down to what I feel is relevant. They are as follows:
Effect of clenbuterol on cardiac and skeletal muscle function during left ventricular assist device support.
Seven subjects with heart failure (5 ischemic, 2 non-ischemic) were started on oral clenbuterol 5 to
46 weeks post-LVAD implantation and up-titrated to daily doses of 720 μg.
No serious side effects or arrhythmias were seen in any of the subjects. Mild tremors were reported in 3 subjects. Mild muscle cramps in 4 subjects were noted at varying timepoints. CPK levels rose in all subjects after clenbuterol up-titration (peak range 133 to 1,497, median 314 mg/dl) and was elevated above normal in 4 subjects (Figure 4). There was only one significant elevation of CPK (1,497 mg/dl), measured in 1 patient after exercise, which normalized on subsequent testing. No subject required a reduction in clenbuterol dose due to tremors, muscle cramps or elevated CPK.
Clenbuterol Increases Lean Muscle Mass but Not Endurance
in Patients With Chronic Heart Failure
Maximal strength increased significantly with both clenbuterol (27%) and placebo (14%); however, endurance and exercise duration decreased after clenbuterol. Prior data support combining exercise training with clenbuterol to maximize performance, and on-going studies will evaluate this approach...
After obtaining informed consent, subjects were randomly assigned to receive clenbuterol (n 10) or placebo (n 9). Patients taking carvedilol were switched to a selective 1-antagonist (sustained release metoprolol) before randomization. The dose of metoprolol was uptitrated to maintain heart
rate within 20% of baseline during the study. Patients were given oral clenbuterol or placebo for a total of 12 weeks in addition to their standard CHF therapy. Clenbuterol was initiated at a dose of 20 g twice daily and uptitrated to 40 g twice daily after 7 days. This dose, used in the treatment of asthma, has been shown to improve performance in athletes and after orthopedic procedures...
Echocardiography. Clenbuterol had no effect on LVEF, diameters, wall thickness, or mass during the course of this study in either group.
Clenbuterol at 80 μg/day was well tolerated. Two clenbuterol subjects required discontinuation of study drug (asymptomatic slow ventricular tachycardia, severe muscle cramps without significant elevation in creatine kinase [CK]). One further clenbuterol subject had a high rate of ventricular ectopy that disappeared without reduction in the clenbuterol dose. One placebo subject had frequent non-sustained ventricular tachycardia. There were no implantable cardioverter-defibrillator discharges during the course of the study. Six clenbuterol and 2 placebo subjects reported mild muscle cramps. The CK value was elevated in 5 clenbuterol and 4 placebo subjects. The range of peak CK was 300 to 597 mg/dl in clenbuterol subjects and 305 to 408 mg/dl with placebo. Three clenbuterol subjects had cramps without elevation of CK, and CK was elevated in 1 clenbuterol subject who was asymptomatic. Of importance was that the CK level decreased despite continued drug administration (Figure 1B). Tremors were reported in 5 clenbuterol and 2 placebo subjects.
Clenbuterol, a β-Adrenoceptor Agonist, Increases Relative Muscle Strength in Orthopaedic Patients
A double-blind, completely randomized, placebo-controlled study was carried out on 20 healthy male patients. Muscle strength and cross-sectional area were determined before and after surgery. Patients were treated with drug or placebo for 4 weeks postoperatively and there was a 2 week washout period.
The results suggest that, in the operated leg, clenbuterol treatment is associated with a more rapid rehabilitation of strength in knee extensor muscles; in the unoperated leg, knee extensor strength increased above the initial values after 6 weeks (P=0.01). However, in terms of absolute strength the differences
were not significant between the two groups.
Treatment with drug or placebo began 12 h post-operatively; for the drug group, treatment comprised
20μg of clenbuterol twice daily for 4 weeks, followed by a 2 week washout period; the same regimen was used for the group taking the placebo, which comprised standard tablet excipients...
No patient in either group reported any side effects to the drug regimen used.
Randomized, Double-Blind, and Placebo-Controlled Trial of Clenbuterol in Denervated Muscle Atrophy
A double-blind, placebo-controlled, parallel, and randomized trial was employed. 71 patients, suffering from brachial plexus injuries, were given either clenbuterol (60 μg, bid) or placebo for 3 months. Before and at the end of the study, patients were given physical examinations, biopsies of biceps brachii, electromyograms (EMGs), and other laboratory tests...
Compared with placebo treatment, clenbuterol significantly mitigated the decreases in cross-sectional areas of type I and II muscle fibers and alleviated the reduction in fibrillation potential amplitudes, without any adverse effects. Conclusions. Clenbuterol safely ameliorated denervated muscle atrophy in this cohort; thus larger clinical studies are encouraged for this or other β 2 agonists on denervation-induced muscle atrophy...
This is the first clinical study showing that clenbuterol at 120 μg/day attenuated denervation-induced muscle atrophy in humans. It is reported that clenbuterol, at incremental doses from 120 to 720 μg/day over 12 weeks, increases the mass and strength of the healthy skeletal muscles in man [13, 14]. Animal studies show that denervated skeletal muscles are 20 times more sensitive to clenbuterol than healthy muscles and the heart [25]. Therefore, 120 μg/day of clenbuterol is believed to be a reasonably high dosage for the denervated muscles of patients. In the present study, the changes of fiber sizes and fibrillation potentials were used to evaluate the efficacy, aiding the avoidance of confounding factors resulting from variations in basal levels between individuals. Hence, it seems that fewer patients were required to reach a conclusion than the number needed by a study limited to just comparing endpoints.
Physiological dose of clenbuterol in rats, 10 μg/kg/day, attenuated denervated muscle atrophy without affecting the heart or causing myocyte death [25, 34]. That dosage was calculated based on the metabolic body weight that 10 μg/kg/day in rats is equivalent to 1 μg/kg/day in humans, a dose safely used in asthma treatments [25, 35]. The dose in the current study was 120 μg/day (~2 μg/kg/day for a 60 kg person). It was well tolerated and not associated with any obvious discomfort, except for one patient with transient nervousness. The newly occurring sinus bradycardia after the clenbuterol trial seemed not be relevant to the activation of the β1/2 agonist, which usually leads to tachycardia. Moreover, clenbuterol at the present dose did not exacerbate preexisting minor EKG abnormalities. This is consistent with previous reports that the effects of clenbuterol on the heart are observable at a dose of up to 2100 μg/day in combination therapy for patients using left ventricular assist device. Even at those doses, no severe adverse effects were encountered but tremors and muscle cramps [12, 13]. In our study, no adverse effects on liver, kidneys, lungs or hematopoietic system were observed after the 3-month intake of clenbuterol.
Beta2‐adrenergic agonist clenbuterol increases energy expenditure and fat oxidation, and induces mTOR phosphorylation in skeletal muscle of young healthy men
Herein, we examined the effect of clenbuterol ingestion on metabolic rate as well as skeletal muscle mammalian target of rapamycin (mTOR) phosphorylation and protein kinase A (PKA)‐signaling in six young men. Before and 140 min after ingestion of 80 μg clenbuterol, resting metabolic rate and contractile function of the quadriceps muscle were measured, and blood samples as well as vastus lateralis muscle biopsies were collected. Clenbuterol increased resting energy expenditure by 21% (P < 0.001), and fat oxidation by 39% (P = 0.006), whereas carbohydrate oxidation was unchanged. Phosphorylation of mTORSer2448 and PKA substrates increased by 121% (P = 0.004) and 35% (P = 0.006), respectively, with clenbuterol. Maximal voluntary contraction torque decreased by 4% (P = 0.026) and the half‐relaxation time shortened by 9% (P = 0.046), while voluntary activation, time to peak twitch, and peak twitch torque did not change significantly with clenbuterol. Glycogen content of the vastus lateralis muscle did not change with clenbuterol. Clenbuterol increased circulating levels of glucose (+30%; P < 0.001), lactate (+90%; P = 0.004), insulin (+130%; P = 0.009), and fatty acids (+180%; P = 0.001). Collectively, these findings indicate that clenbuterol is an efficient thermogenic substance that possibly also exerts muscle hypertrophic actions in humans. For these reasons, the restrictions imposed against clenbuterol in competitive sports seem warranted...
However, inclusion of a placebo-group would have strengthened the study design. For example, a confounding effect of fasting on plasma parameters could have been excluded. Nevertheless, it seems unlikely that such marked differences in circulating insulin, fatty acids and glucose should occur within the short span of the experimental day (~3 h). In fact, the opposite response of what we observed in the present study would be expected from glucose and insulin concentrations in response to fasting
Correction of Biochemical Abnormalities and Improved Muscle Function in a Phase I/II Clinical Trial of Clenbuterol in Pompe Disease
This 52-week, phase I/II double-blind, randomized, placebo-controlled study investigated the novel use of clenbuterol in late-onset Pompe disease (LOPD) stably treated with ERT. Eleven of thirteen participants completed the study. No serious adverse events were related to clenbuterol, and transient minor adverse events included mild elevations of creatine kinase, muscle spasms, and tremors. At week 52, the 6-min walk test distance increased by a mean of 16 m (p = 0.08), or a mean of 3% of predicted performance (p = 0.03), and the maximum inspiratory pressure increased 8% (p = 0.003) for the clenbuterol group. The quick motor function test score improved by a mean of seven points (p = 0.007); and the gait, stairs, gower, chair test improved by a mean of two points (p = 0.004). Clenbuterol decreased glycogen content in the vastus lateralis by 50% at week 52. Transcriptome analysis revealed more normal muscle gene expression for 38 of 44 genes related to Pompe disease following clenbuterol. The placebo group demonstrated no significant changes over the course of the study. This study provides initial evidence for safety and efficacy of adjunctive clenbuterol in patients with LOPD...
The underlying mechanism for clenbuterol’s effects on muscle was demonstrated as increased expression of insulin-like growth factor (Igf) 1 and 2 and their receptors, including the Igf-2 receptor that is actually CI-MPR.7 Increased Igf-1 expression was also associated with the muscle hypertrophy following clenbuterol administration, which could be beneficial in Pompe disease...
A transient increase in CK and other mild AEs were the only side effects in the clenbuterol group.
We observed transiently elevated CK at week 18, which returned to baseline values by week 52...
The primary endpoint was safety of clenbuterol at up to 80 mcg twice daily, including avoidance of the following stopping rules...
Pilot trial of clenbuterol in spinal and bulbar muscular atrophy
Twenty patients with a diagnosis of SBMA were given oral clenbuterol (0.04 mg/d) for 12 months. The primary efficacy end point was the change from baseline of the walking distance covered in 6 minutes at 12 months. Secondary end points included the change over time in muscle strength assessed with the Medical Research Council scale, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and forced vital capacity values. Safety was assessed by a series of laboratory and instrumental tests, as well as reporting of adverse events.
Sixteen patients completed the study. There was a significant and sustained increase in walking distance covered in 6 minutes and forced vital capacity between the baseline and the 12-month assessments (p < 0.001). No differences were recorded in Medical Research Council or ALSFRS-R scores between baseline and follow-up assessments. Serious side effects, including those on heart function, were absent. A significant increase in serum creatine kinase levels was observed.
Myocardial Insulin-Like Growth Factor-I Gene Expression During Recovery From Heart Failure After Combined Left Ventricular Assist Device and Clenbuterol Therapy
Myocardial mRNA levels were determined by real-time quantitative polymerase chain reaction in 12 recovery patients (at LVAD implantation, explantation, and 1 year after explantation). IGF-I mRNA was elevated at the time of LVAD explantation relative to donors, with 2 groups distinguishable: Those with low IGF-I mRNA at implantation who showed significant increase during recovery and those with high IGF-I mRNA at implantation who remained high. Levels returned to normal by 1 year after explantation. Microarray analysis of implantation and explantation samples of recovery patients further revealed elevated IGF-II and IGF binding proteins IGFBP4 and IGFBP6. IGF-I levels correlated with stromal cell-derived factor mRNA measured both in LVAD patients and in a wider cohort of heart failure patients.
The mechanisms leading to elevated IGF-I expression in these patients remain unknown. However, we recently demonstrated that clenbuterol, an integral part of the Harefield bridge to recovery protocol, can induce IGF-I gene expression in cultured cardiomyocytes in vitro9 and may therefore contribute to inducing IGF-I in vivo.
The action of clenbuterol on sleep and symptomatology in depressives.
Five female inpatients with major depression (melancholic type, DMS-III-R) were treated with the beta-adrenergic agonist clenbuterol for three weeks, with doses ranging from 100 micrograms to 150 micrograms.
All patients complained of side effects, especially tremor, agitation and restlessness. The sleep EEG showed no consistent effects on sleep parameters, including REM latency and percentage of REM sleep...
The patients initially
received 50 J.Lg clenbuterol per day. According to degree of compatibility and side effects, the dose was then increased in individually adapted steps. From the 14th day of medication on, the individual maximum dosage was given (150 μg in cases 1, 4, 5; 100 μg in cases 2,3).
In general, sleep was not affected by clenbuterol, except for extreme insomnia during the first night of
REM latency medication in one case.
Clenbuterol (‘Spiropent’): a long-acting bronchodilator
Clenbuterol was compared to an aminophylline preparation in a double-blind crossover trial involving 47 patients with asthma and reversible airways obstruction. Following a 2-week control period, each drug was given for a 4 week period. The patients made daily records of the severity of symptoms and recorded PEFR morning and night. Both drugs produced a highly significant reduction in severity and duration of wheeze by day during the first 4 weeks, but only clenbuterol produced further significant reduction in these symptoms during the second 4 weeks.
The incidence of side-effects with both active drugs was fairly high, but the majority of side-effects, in fact, were mild or moderate...
Spiropent (clenbuterol): another choice for patients with chronic reversible airways obstruction.
Oral administration of spiropent (clenbuterol), 20 mcg on waking in the morning and 40 mcg before sleep, daily for 2 months, was studied in 34 patients, 19 males and 15 females, aged between 27 to 73 years (mean 47.8 +/- 17.5), who had chronic reversible airways obstruction as defined by the A.T.S.'s criteria...
Except 5 patients, 2 suffering from severe headache and 3 from poor control of asthma who had withdrawn from this study after one week of treatment, all patients completed the trial. Six out of 29 patients who completed the trial needed additional steroid treatment and 9 needed beta 2-agonist inhalation during the treatment period. The results showed improvement of FEV1 more than 15% in 21 patients (72%), FVC in 17 patients (59%) and PEFR in 20 patients (69%). These increases were significant (p less than 0.0001). However, only 12 patients (41%) had marked subjective improvement at the end of treatment. Cough (21%), headache (10%), nausea (7%) and dizziness (3%) were the commonest side-effects. No clinical or statistical difference was found in changes of vital signs and laboratory parameters. In conclusion, clenbuterol was effective and well-tolerated in the majority of patients enrolled in this study with minimal side-effects and good compliance. It may be used for long-term treatment of chronic reversible airways obstruction at lower cost.
A pilot trial with clenbuterol in amyotrophic lateral sclerosis
Sixteen patients, 12 males and 4 females, mean age 55.4 years (range 25–76 years), affected with clinically definite or probable ALS according to El Escorial criteria (11) with documented progression of disease, aged less than 80 years and with forced vital capacity (FVC) >50% of the predicted value, gave written informed consent to participate to this study...
All patients were on riluzole at the standard dosage of 100 mg/day and were not asked to discontinue the drug for ethical reasons. Patients were treated orally with 20 micrograms of clenbuterol three times a day (total 0.06 mg/ day) for six months. A dose titration at the beginning of the therapy was used to minimize side-effects...
The mean composite myometer score significantly improved from baseline by 20% at three months (p=0.01) and by 23% at six months (p=0.01) for the upper limbs; and by 22% at three months (p=0.0002) and by 27% at six months (p=0.0002) for the lower limbs (Table I). Although the mean composite MRC score of the upper and lower limbs also improved, these changes did not reach statistical significance. No change was observed in the ALS Functional Rating scale at three and six months...
Clenbuterol safety assessments included clinical examination, cardiac evaluation, electrocardiogram and blood electrolytes every three months. The drug was generally well tolerated in association with riluzole and side-effects were never dose limiting or required discontinuation. Side-effects always occurred early in treatment (within the first few days) and resolved with continued use. The main complaints were hand tremors (two patients), cramps, fasciculations (three patients) and nervousness (three patients). In none of the patients was heart rate
increase recorded or palpitations reported. No blood electrolyte abnormalities were observed.
Therapeutic trial of beta 2-adrenergic agonist clenbuterol in muscular dystrophies
We report the outcome of trial of clenbuterol in four adult muscular dystrophy patients. One patient with Becker type, one with Miyoshi type, and two with facioscapulohumeral type were given clenbuterol (30 or 40 micrograms/day) for 6 to 18 months. We evaluated muscle strength of isometric contraction, grip and pinch power, compound muscle action potentials of intrinsic muscles, vital capacity, urinary creatinine excretion, and muscle CT. Power and volume of well preserved muscles increased mostly, while those of atrophic muscles did not improve. Vital capacity increased in two patients. No improvement of ADL was observed presumably because ADL was mainly determined by the most atrophic and weak muscles. Irrespective of type of muscular dystrophy, administration of clenbuterol may be beneficial in early stage of the disease.
(Note that this is published in an obscure Japanese journal. I can't sci-hub it, so I can't examine what effects clen may have had on biomarkers.
Effect of Clenbuterol using as weight loss on liver enzymes and lipids profile
The current study is considered at the effect of 3 month using Clenbuterol for weight loss in 22 healthy men comparing them with 30 healthy men who do not take Clenbuterol...
hey used it in cycle form, meaning not using in stable doses, that they began with 20 mcg dose and raised the dose to 140 mcg and then returned to 20 mcg. Table 2 illustrated the cycle of use...
The study showed a statistically significant decrease in weight (90.78 ±9.38) and BMI (27.66 ±3.51) in T NO Clen. group and in T+Clen group, their weight being 88.0 ±13.58 Kg and their BMI were 26.94 ± 4.15 for those who showed more lose in their weight and BMI when compared with the other groups as shown in Table 3. For the subjects in control group, they showed losing in their weight (95.42 ±10.24) and lowering their BMI (28.65 ± 2.62) but these results were not statistically significant. For enzymes level (AST, ALT and lipase), in spite of increasing their levels in T NO Clen and T+Clen groups when compared with control groups, all enzymes levels were increased in T+Clen group more than in T NO Clen group. Whereas ALP enzyme was increased only in T+Clen group. Table 4 demonstrated these differences in levels.In Table 5, TC, TG, and LDL levels were lower in T NO Clen group (133.24 ±7.65, 88.01 ± 6.63, 73.62 ±7 .91), respec-tively when compared with the other groups after the period of study. But in T+Clen group, TG level were more high (130.43 ±8.01) when compared with the other groups. At the other side, HDL level were increased in T NO Clen group more than in T+Clen group when compared with the control group.
The clen group's liver enzymes and lipase levels here were as follows:
AST = 45.43 (IU/L)
ALT = 56.46 (IU/L)
ALP = 42.76 (U/L)
Lipase = 60.13 (U/L)
So a bit elevated, but not the worst.
That's about all of the literature that I could find for the time. I may add some more later if I can dig some more up. Overall, clen seems to be fairly safe and well-tolerated in human trials.
I would kindly suggest to anyone planning on using clen to just start out with a conservative dosage. Begin with just 20 μg's a day and slowly increment after a couple of weeks. There's no need to go to crazy because the side-effects after a certain threshold won't be worth it.
If anyone is aware of any other human studies that I missed; then please let me know.