Carnitine Improves Symptoms of Male Aging CME
News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD, FAAFP
To earn CME credit, read the news brief along with the CME information that follows and answer the test questions.
Release Date: April 14, 2004; Reviewed and Renewed: April 14, 2005; Valid for credit through April 14, 2006
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This activity was originally released on April 14, 2004. It was reviewed and renewed in its original form on April 14, 2005.
April 14, 2004 ï¿½?? Carnitine is more active than testosterone for improving symptoms of male aging such as sexual dysfunction, depressed mood, and fatigue, according to the results of a randomized study published in the April issue of Urology.
“Testosterone increases the tissue carnitine concentration,” write G. Cavallini, from the SocietÃ Italiana di Studi di Medicina della Riproduzione in Bologna, Italy. “Propionyl-L-carnitine and acetyl-L-carnitine proved active for diseases typical of aging.”
In this trial, 120 patients were randomized to receive testosterone undecanoate 160 mg/day, propionyl-L-carnitine 2 g/day plus acetyl-L-carnitine 2 g/day, or placebo for six months. Mean age was 66 years (range, 60-74 years).
Compared with baseline, testosterone and carnitines significantly improved the peak systolic velocity, end-diastolic velocity, and resistive index of cavernosal penile arteries, as well as nocturnal penile tumescence (NPT), International Index of Erectile Function score, Depression Melancholia Scale score, and fatigue scale score.
Compared with testosterone, carnitines were significantly more active in improving NPT and International Index of Erectile Function score.
Testosterone, but not carnitines, significantly increased the prostate volume and free and total testosterone levels and significantly lowered serum luteinizing hormone. Prostate-specific antigen (PSA) and prolactin did not change significantly in any group.
No symptoms or physiological markers improved in the placebo group. Adverse effects were negligible in all groups.
Carnitines and testosterone were effective for as long as they were administered, with reversal to baseline values when treatment was stopped. Six months after testosterone suspension, prostate volume remained significantly greater than baseline.
“Testosterone and, especially, carnitines proved to be active drugs for the therapy of symptoms associated with male aging,” the authors write. “At least one side effect of testosterone administration (i.e. prostate enlargement) will be avoided by carnitine administration.”
Two of the authors are patent inventors for use of carnitines in treating symptoms of male aging.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
* Describe the possible mechanisms of androgen replacement and carnitine in improving symptoms of male aging.
* Evaluate the efficacy of these two therapies in treating symptoms of male aging.
Both testosterone and carnitine metabolism have been implicated in contributing to the symptoms of sexual dysfunction, depressed mood, and fatigue in older men.
A decline of testosterone’s effects in the hypothalamic dopaminergic system, striated skeletal muscle, and corpus cavernosum may explain why older men suffer from the symptoms described above.
Both male and female sex hormones increase L-carnitine levels, in vivo carnitine-acetyl-transferase activity, and the activities of mitochondrial carnitine palmitoil-transferases.
Carnitines act as an antioxidant by promoting activity in the Krebs cycle, while also decreasing apoptosis via a reduction in ceramide levels along with insulin-like growth factor.
The authors of the current study sought to determine if the direct administration of carnitine could improve symptoms of male aging to a similar degree as androgen treatment. They also wanted to establish the safety of carnitine administration.
* Patients eligible for participation were men older than 60 years with symptoms of decreased libido and erectile quality, depressed mood and ability to concentrate, irritability, and fatigue. Patients with a free testosterone level less than 6 pg/mL were also included.
* Patients had to be generally healthy to participate in the study. Those with a history of obstructive urinary symptoms, alcohol or cigarette use, or cardiovascular disease were excluded.
* Subjects were randomized to receive 1 of 3 treatments: testosterone undecanoate 160 mg/day, propionyl-L-carnitine 2 g/day plus acetyl-L-carnitine 2 g/day, or placebo. All treatments were administered for 6 months.
* Participants were followed for PSA levels and prostate volume, measurements of penile blood flow, NPT, and serum levels of testosterone, luteinizing hormone (LH), and prolactin. They were also assessed for sexual function, mood, and fatigue.
All of these evaluations were performed at baseline, at 3 and 6 months after initiation of treatment, and 6 months after cessation of treatment. Although treatment was administered by blinded personnel, the authors did not comment whether subjects’ assessment was completed in a similarly blinded manner.
* 150 patients were randomized into the study, and 130 completed the study protocol. The authors did not perform an intent-to-treat analysis of their data.
* Baseline values for all study groups were similar. Mean age of subjects was 64 years.
* The testosterone group exhibited an increase in prostate volume as measured by ultrasonography at 3 and 6 months. The authors mention in their discussion that this increase prompted cessation of the study protocol at 6 months.
Prostate volume in the testosterone group had decreased 6 months after cessation of treatment but had not returned to baseline levels.
* Carnitine administration had no effect on prostate volume.
* Neither testosterone nor carnitine treatment changed PSA levels.
* Both carnitine and testosterone treatment improved penile blood flow at 3 and 6 months compared with placebo. There was no difference between the carnitine and testosterone groups in this outcome.
* NPT was improved to a similar degree in both active treatment groups at 3 months compared with placebo, and this improvement was stable at 6 months.
* Testosterone therapy caused an increase in serum testosterone levels and a decrease in LH levels at 3 months that remained stable at 6 months. Prolactin was unaffected by testosterone treatment. Carnitine did not significantly change any hormonal levels measured.
* Testosterone improved erectile dysfunction and sexual desire scores at 3 months, but it did not improve scores for orgasm or general sexual well-being at any point.
* Carnitine improved erectile dysfunction, sexual desire, orgasm, and general sexual well-being scores at 3 months, and these values either remained stable or improved slightly at 6 months.
* Carnitine was superior to testosterone in the 3- and 6-month erectile function domain, the 6-month orgasm domain, and the 6-month general sexual well-being domain.
* Both carnitine and testosterone improved depression scores compared with placebo, but carnitine was superior to testosterone in this variable.
* Fatigue was improved to a similar degree in both active treatment groups compared with placebo.
* Adverse events were similar among all treatment groups.
Pearls for Practice
* Both testosterone and carnitine can affect symptoms of male aging through multiple biochemical pathways in different tissues.
* Carnitine appears to improve symptoms of male aging to a similar or better degree than testosterone without causing an increase in prostate volume.