Among the hundreds of dietary supplements currently receiving online media attention is the amino acid derivative L-carnitine. (Amino acids are essentially our body’s “building blocks” for making protein. L-carnitine is derived from the amino acid lysine.) Numerous claims have been made by “reputable” sources that it is effective for treatment of conditions such as “chronic fatigue syndrome” (C.F.S.), “age-related” fatigue and loss of memory, and even for male infertility. It has also been promoted online as a diet product, and as an ergogenic supplement that enhances athletic performance and speeds recovery from intensive sports participation. Among the lesser known claims is that dietary supplementation with L-carnitine can boost male sex drive and improve penile function in a safer and more effective manner than testosterone supplementation.
In our current segment, Spanking FIT examines carefully these claims including those of a sexual nature; but, first let’s explain exactly what L-carnitine is, and how it is believed to function in the human body:
What is L-carnitine & how does function?
In “Can Alpha-lipoic Acid Transform Your Body?” Jan. 2016, Spanking FIT, described the role enzymes play in production of Adenosine Triphosphate (A.T.P.) in those tiny “energy factories” within human body cells known as mitochondria. A.T.P. transports chemical energy within the cells for metabolism, and it is also required for the biochemical reactions involved in both brain function and muscle movement.
The amino acid derivative L-carnitine is responsible for transporting cellular fuel in the form of long-chain fatty acids across mitochondrial membranes to the oxidation sites where A.T.P. is produced. Since concentration of L-carnitine in body cells is known to decrease with age, the theory goes that it may be possible to increase energy metabolism through oral supplementation with it. This is similar to arguments made in favor of dietary supplementation with other natural products such as alpha-lipoic acid.
All scientific theories, no matter how appealing, need to be validated with well-designed experiments followed up with precise statistical data analysis. For that reason, Spanking FIT conducted a standard comprehensive evaluation of published research results purporting to support relevant L-carnitine efficacy claims. Here are the principal findings:
L-carnitine & age-related memory loss & fatigue
According to biochemical heavy weight Linus Pauling Institute (lpi.oregonstate.edu), studies have revealed that supplementing aged rats with acetyl L-carnitine (ALCAR) , an acetylated form of L-carnitine, and/ or alpha lipoic acid (A.L.), “improves” mitochondrial energy metabolism and memory in them. They refer to research in which aged rats receiving the combined treatment for three months allegedly showed improvement in both the total number of intact mitochondria, and mitochondrial ultra-structures of neurons in the hippocampus of their brains. (See: “Neuronal mitochondrial amelioration by feeding acetyl-L-carnitine and alpha lipoic acid to aged rats“ by G. Aliev, et al. published in Journal of Cellular and Molecular Medicine, 2009, Feb 13 (2), 320-33. The hippocampus of the brain is believed by neuroscientists to be its memory, emotion, and autonomic nervous system center. (The autonomic nervous system you will recall is responsible for non-conscious control of bodily function.) Among this study’s “findings” were that the number of intact mitochondria as a percent of total mitochondria in elderly 21 year old rats was not only increased by ALCAR (0.2% wt./vol.) plus A.L. (0.1% wt./wt.) supplementation, but the improved level actually approached that of the untreated four month old rats. This sounds like a “fountain of youth” discovery, at least for rodents!
These research “findings” would be extremely bullish were it not for flaws contained in statistical analyses. Upon examining the results, Spanking FIT uncovered that researchers made a common mistake of using parametric statistical tests (2-way ANOVA) and student t-test in lieu of non-parametric ones (e.g. Wilcoxon-Mann-Whitney) in analyzing the comparatively small sample sizes which they collected in each category. Furthermore, the authors did not provide raw data in an appendix which could have enabled Spanking FIT or others to perform independent analyses using the more appropriate non-parametric methods.
Another study which is frequently cited by L-carnitine advocates is: “Exploratory Open Label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome” by R. Vermeulen et al., published in Psychosomatic Medicine, March-April 2004, 66 (2) 276-82. In this study, 90 patients who had been diagnosed with Chronic Fatigue Syndrome (C.F.S.) and who were approximately age 40 on average, were randomly assigned to one of three treatment groups: 2 grams per day of acetylcarnitine (ACARN) for 24 weeks, 2 grams per day of propionylcarnitine (PCARN) for 24 weeks, or a combination of both treatments for same time period. (Propionylcarnitine is still another closely related form of L-carnitine.) After 24 weeks, a statistically significant proportion of patients in all groups showed improvement: 59% for ACARN, 59% for PCARN and 37% for the combination therapy. Clinical Global Impression of Change (C.G.I.C.) was the rather subjective measure of patient improvement which was utilized in this study. Researchers further reported significant improvements in “attention concentration” for all groups, based on a more objective Stroop test. (The Stroop test is a test of capacity to focus attention which relies on colors.) This study is unique in so far as relatively large samples were acquired and preferable non-parametric methods of analysis were used. Nevertheless, one serious weakness is the apparent absence of a “control or a placebo group” which would have enabled comparisons to be made with subjects not treated with L-carnitine. Moreover, the study contains a hint of conflict of interest because it was sponsored by Sigma-Tau Ethifarma, which Spanking FIT confirmed to be an L-carnitine maker. Still worthy of mention, nevertheless.
Among the many research studies which Spanking FIT reviewed, the one that made the strongest case for supplementation with L-carnitine for fatigue was:” L-carnitine treatment reduces severity of physical and mental fatigue and increases cognitive function in centenarians: a randomized clinical trial” by M. Malaguarnera and published in American Journal of Clinical Nutrition, 2007 Dec., 86(6) 1738-44. In this one, 66 female and male centenarians, ages 100-106 years, were randomly assigned to either treatment with 2 grams per day of L-carnitine for six months, or placebo. Based on the statistical test known as 2-way repeated measures ANOVA, it was inferred that total body fat significantly decreased in the treatment group, muscle mass significantly increased, and that treated patients were able to walk further in a six minute hospital corridor walking test. Subjective measures of both physical and mental fatigue were also improved in the group treated with L-carnitine.
A major limitation of this study is that it was conducted over a narrow age range (i.e. centenarians only) so that it is not known if L-carnitine supplementation would have a similar effect on a more general population, including the young. According to study authors, “plasma concentration of carnitine actually increases with the advancement of age until around seventy years, subsequently tending to diminish in parallel with the reduction in body mass index and muscle mass.”
Does L-carnitine supplementation enhance athletic performance?
As previously stated, L-carnitine supplementation is also being vigorously promoted online as an ergogenic substance that is capable of enhancing athletic performance and recovery from intense sports participation. To investigate these claims, Spanking FIT evaluated over fifty published experimental studies from universities and research institutes worldwide. We were disappointed to discover that in all cases, either inappropriate parametric statistical tests were employed for the analyses conducted, or that non-parametric tests yielded insignificant results possibly on account of the small sample sizes collected. Furthermore, so-called statistical meta-analyses, which involves combining results of numerous studies to make inferences, was not possible due to the inconsistency of parameters chosen by the researchers for estimation.
Just as the military serves as a testing ground for civilian products, the sporting arena can provide useful data for making improvements in human health. Consequently, Spanking FIT calls on major sports associations to finance large scale clinical trials on L-carnitine as an ergogenic agent.
L-carnitine & sexual performance
One of the most detailed studies conducted to date regarding a connection between L-carnitine supplementation and male sexual enhancement is “Carnitine versus androgen administered in the treatment of sexual dysfunction, depressed mood and fatigue associated with male aging” by G. Cavallini, et al. and published in Urology, 2004; 63:641-6. As the title implies, it also provides for comparative analysis of carnitine treatment versus standard testosterone supplementation. 130 male subjects in their 60’s and 70’s who had sought medical help for symptoms often attributed to androgen decline (decreased libido and erectile quality, depressed mood and intellectual concentration ability, fatigue, and free-t concentrations of less than 6 pg per mL) were assigned randomly to 160 mg. per day of testosterone supplementation for six months, a mixture of acetyl L-carnitine (2 gm. per day) and propionyl-L-carnitine (2 gm. per day) for six months, or a placebo. An impressive number of both objective and subjective measures of sexual fitness were implemented before therapy, three months after beginning therapy, six months after beginning and at therapy end, and six months after the therapy ended. Spanking FIT focused on the objective sexual measures including: total testosterone, free testosterone, prostate volume (P.V.), resistive index of cavernosal penile arteries (R.I.), and nocturnal penile tumescence (N.P.T.) or night erection. R.I. is an indication of bi-directional blood flow in the penile arteries as measured using doppler ultrasound equipment. N.P.T. is measured via a Rigiscan device, whereby an elastic band is placed around the penis before bedtime enabling measurements to be made.
As to be expected, the testosterone supplementation caused a statistically significant increase in serum free-t at end of six month therapy. No significant rise occurred in either the L-carnitine or the placebo group.
In “Male T-Replacement Should be the Last Resort“, Spanking FIT Jan. 2015, we reviewed some of the potential adverse side effects of T-replacement including stimulation of prostate tissue with increased prostate specific antigen (P.S.A.), increased risk of blood clots , decreased testicular size, etc. The Cavallini study confirmed that prostate volume (P.V.) increased significantly in the testosterone treated group by 66% on average. With L-carnitine, on the other hand, P.V. actually decreased by a non-significant 0.7%.
Regarding positive measures of sexual health, both R.I. and N.P.T. were increased significantly by both testosterone and L-carnitine treatment; however, outcomes were significantly better with L-carnitine. Study authors also reported similar improvements using more subjective measures based on questionnaire responses. They included improvements in erectile function, sexual satisfaction, orgasm, etc. with L-carnitine.
In the category of medical assessment, this study was very comprehensive; however, it contains weaknesses from a statistical perspective. Authors appear to have used the statistical tool of one-way ANOVA only when, in fact, factorial ANOVA was warranted. As is common with many research publications, authors presented summary stats only making it impossible for Spanking FIT or others to perform independent data analyses. This is the reason that Spanking FIT strongly favors making it mandatory that all journal publications provide a link to their raw data .
One final note: authors Cavallini and Biagiotti hold a patent on “the association of acetyl L-carnitine with propionyl L-carnitine for therapy of symptoms associated with partial androgen deficiencies of aging males.” Therefore, an appearance of conflict of interest also exists.
Biochemical principles support the hypothesis that L-carnitine dietary supplementation may be beneficial in decreasing physical and mental fatigue and may serve as an ergogenic aid for enhancement of athletic performance. Nevertheless, common problems exist in experimental efforts to date to validate such claims. They include: inadequate experimental sample sizes, inappropriately applied statistical tools, and apparent conflicts of interest on the part of some principal investigators.
The case that L-carnitine supplementation enhances male sexual performance and provides a safer alternative to testosterone replacement for the aging male, appears better made. However, results are still tainted by appearances of financial conflict.
A search on the website clinicaltrials.gov revealed that clinical trials with L-carnitine so far have been restricted primarily to its potential efficacy in treating diseases such as H.I.V., sepsis, etc. However, given L-carnitine’s potential as an important anti-aging agent, Spanking FIT recommends that large-scale clinical trials be funded and conducted for this purpose. (These trials also need to be gender-balanced so that females may benefit from research results equally with males.)
In the meantime. I personally consume 500 mg. of acetyl L-carnitine daily, and in the words of current Presidential candidate Donald Trump: “I guarantee you, there’s no problem!” Don’t forget to read “Can Alpha Lipoic Transform Your Body?” Spanking FIT, Jan. 2016. As usual, I look forward to your valuable input. Sincerely, Doc Garrett