Clenbuterol's Other Benefit... Nerve Regeneration

[Goldy]

I ran across this on another board and along with muscle tissue accrual is one of the main reasons I use low dose clen (40 mcg eod), as a couple of years ago I had major issues with sciatica which is now completely cured since I began the clen therapy:
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Regeneration of peripheral nerves after clenbuterol treatment in a rat model.
Frerichs O, Fansa H, Ziems P, Schneider W, Keilhoff G.
Department of Plastic, Reconstructive, and Hand Surgery, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany. onno.frerichs@medizin.uni-magdeburg.de
Abstract

Clenbuterol is known to act as a neuroprotective substance in the central nervous system, and also reduces muscle atrophy after denervation. The aim of this study was to evaluate its influence on peripheral nerve regeneration. The rat sciatic nerve model was used in four groups (n = 8 per group). After complete nerve transection and microsurgical coaptation, two groups received a daily oral dose of 100 microg/kg clenbuterol and two served as controls. Regeneration was assessed clinically, histologically, and morphometrically after 4 and 6 weeks. The weight ratios of calf muscles were calculated. Histological examination showed significantly increased axon counts in the clenbuterol group and a better degree of myelination. Muscle weight ratios of the clenbuterol group were significantly increased after 6 weeks, and the animals showed improved function of the hindlimb. Thus, therapy with 100 microg/kg clenbuterol daily after coaptation of a sciatic nerve showed a positive influence on clinical, histological, and morphometrical parameters in the rat model. The underlying mechanism remains unclear.
Copyright 2001 John Wiley & Sons, Inc.

http://www.ncbi.nlm.nih.gov/pubmed/11745978

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The influence on nerve regeneration by the beta2-receptor agonist clenbuterol
[Article in German]
Frerichs O, Fansa H, Ziems P, Keilhoff G, Schneider W.
Klinik für Plastische, Wiederherstellungs- und Handchirurgie, Otto-von-Guericke-Universität Magdeburg, Germany. Onno.Frerichs@medizin.uni-magdeburg.de
Abstract

PURPOSE: Clenbuterol has shown a neuroprotective action in the central nervous system by induction of growth factors after cellular damage. Additionally, the atrophy of sceletal muscle is attenuated by the application of Clenbuterol after denervation. This experiment was performed to show the influence of Clenbuterol on regeneration of peripheral nerves. MEHOD AND MATERIAL: In a rat model, the sciatic nerve was transected and microsurgically coaptated. Eight animals in each group received a daily oral dosage of 100 microg/kg bodyweight during four, respectively six weeks. Two control groups received only drinking water under the otherwise same protocol. The assessment was done histologically, morphometrically and clinically. The weight ratio of the soleus and extensor digitorum muscles of the operated to the contralateral side was measured.
RESULTS: The groups treated with Clenbuterol showed histologically and morphometrically a significantly increased axon count and a better g-ratio. The muscle weight ratio was significantly higher in the Clenbuterol group after six weeks and more animals in this group were able to spread their toes.
CONCLUSION: The oral application of Clenbuterol in a rodent model shows a positive influence on nerve regeneration.

http://www.ncbi.nlm.nih.gov/pubmed/12073183

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Partial functional recovery after complete spinal cord transection by combined chondroitinase and clenbuterol treatment.
Bai F, Peng H, Etlinger JD, Zeman RJ.
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA.
Abstract

Spinal cord injury not only disrupts axonal tracts but also causes gliotic, fibrotic, and Schwannotic scarring with resulting deposition of chondroitin sulfate proteoglycans (CSPGs) which prevent axonal reconnection and recovery of locomotor function. Here, we determined whether recovery of locomotor function could be promoted after complete transection, by degrading CSPGs enzymatically within the injury site with chondroitinase ABC (chABC) together with treatment with the beta(2)-adrenoceptor agonist, clenbuterol, a neuroprotective agent which can promote regrowth of lower motoneurons. Partial recovery of locomotor function was observed 8-12 weeks postinjury only after combined chABC and clenbuterol treatment. The recovery of locomotor function coincided with the presence of axons caudal to the injury site arising from neurons of the reticular, vestibular, and red nuclei also only with combined chABC and clenbuterol treatment. Axons myelinated by Schwann cells were most prominent in the transection site in the combined treatment group. Clenbuterol treatment activated cAMP response element binding protein within retrogradely traced neurons which has been associated with axonal regrowth. ChABC treatment decreased scarring due to both CSPG and collagen deposition as well as the gap between intact regions of the spinal cord. ChABC also increased numbers of phagocytic cells which remove myelin debris as well as populations of astrocytes thereby aiding blood-spinal cord barrier reformation. Together the results suggest that chABC and clenbuterol can act synergistically to promote recovery of locomotor function.

http://www.ncbi.nlm.nih.gov/pubmed/20552220

 

[Goldy]

And this is the dosage equivalency from animals to humans:

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From, Dose translation from animal to human studies revisited, Shannon Reagan-Shaw, The FASEB Journal. 2008;22:659-661

Using BSA (Body Surface area:

Human Equivalent Dose (mg/kg) = Animal dose (mg/kg) x Animal km factor/ Human km factor

Table 1. Conversion of animal doses to HED based on BSA

Species Weight (kg) - BSA (m2) - Km factor

Human
Adult 60 ---- 1.6 ---- 37
Child 20 ---- 0.8 ---- 25
Baboon 12 ---- 0.6 ---- 20
Dog 10 ---- 0.5 ---- 20
Monkey 3 ---- 0.24 ---- 12
Rabbit 1.8 ---- 0.15 ---- 12
Guinea pig 0.4 ---- 0.05 ---- 8
Rat 0.15 ---- 0.025 ---- 6
Hamster 0.08 ---- 0.02 ---- 5
Mouse 0.02 ---- 0.007 ----3

So the rat dose was 100mcg/kg
Rat Km factor is 6
Human adult km factor is 37

Plug the numbers into the equation and get:


100mcg/kg x 6/37 = 16.22 mcg/kg

A 60kg adult equivalent dosing would be 16.22mcg x 60kg = 972mg

 

[Goldy]

Some other studies for posterity:
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Study 1: Dose: 720mcg -

Effect of clenbuterol on cardiac and skeletal muscle function during left ventricular assist device support.
J Heart Lung Transplant. 2006 Sep;25(9):1084-90.

Abstract
BACKGROUND: High-dose clenbuterol (a selective beta2-adrenergic agonist) has been proposed to promote myocardial recovery during left ventricular assist device (LVAD) support, but its effects on cardiac and skeletal muscle are largely unknown.
METHODS: 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 microg. The following procedures were performed at baseline and after 3 months of therapy: echocardiography at reduced support (4 liters/min); cardiopulmonary exercise testing; body composition analysis; and quadriceps maximal voluntary contraction (MVC). Myocardial histologic analysis was measured at device implantation and explantation.
RESULTS: There were no serious adverse events or arrhythmias. Creatine phosphokinase (CPK) was elevated in 4 subjects, with no clinical sequelae. No change in ejection fraction was seen. End-diastolic dimension increased significantly (4.73 +/- 0.67 vs 5.24 +/- 0.66; p < 0.01), despite a trend toward increased LV mass. Body weight and lean mass increased significantly (75.5 +/- 17.9 vs 79.2 +/- 25.1 kg, 21.1 +/- 8.9 vs 23.6 +/- 9.7 kg, respectively; both p < 0.05). Exercise capacity did not change, but MVC improved significantly from 37.0 +/- 15.7 to 45.8 +/- 20.6 kg (p < 0.05). No significant change in myocyte size or collagen deposition was seen.
CONCLUSIONS: Cardiac function did not improve in this cohort of LVAD patients treated with high-dose clenbuterol. However, clenbuterol therapy increased skeletal muscle mass and strength and prevented the expected decrease in myocyte size during LVAD support. Further study will clarify its potential for cardiac and skeletal muscle recovery.

Study 2: This is a follow-up study to the one above. Dose is not listed in the abstract but i found a review of this study that stated dosages (cannot vouch for its accuracy):

Patients were given oral clenbuterol or placebo for a total of 12 weeks in addition to their standard congestive heart failure therapy. Clenbuterol was initiated at a dose of 20 micrograms twice daily and uptitrated to 40 micrograms twice daily after seven days.

Clenbuterol Increases Lean Muscle Mass but Not Endurance in Patients With Chronic Heart Failure

J Heart Lung Transplant. 2008 Aug;27(8):934-5.

Abstract
Clenbuterol, a beta(2)-agonist with potent anabolic properties, has been shown to improve skeletal muscle function in healthy subjects, and in high doses, promotes cardiac recovery in patients with left ventricular assist devices. In a small, randomized controlled study, we investigated the effect of clenbuterol on skeletal muscle function, cardiac function, and exercise capacity in patients with chronic heart failure. Clenbuterol was well tolerated and led to a significant increase in both lean mass and the lean/fat ratio. 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.

Study 3: Dose not listed in abstract

Clenbuterol, a beta-adrenoceptor agonist, increases relative muscle strength in orthopaedic patients.
Rowett Research Institute, Bucksburn, Aberdeen, U.K.
Clin Sci (Lond). 1993 Jun;84(6):651-4.
Abstract
1. The sympathomimetic agent clenbuterol has a muscle-specific anabolic effect in normal and wasted muscles from animals. This trial was designed to examine the effect of the drug on the recovery of muscle strength and area after open medial meniscectomy. 2. 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. 3. 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. 4. It is concluded that the data lend support to the proposition that clenbuterol has therapeutic potential in the treatment of muscle-wasting conditions.