Propionyl-L-Carnitine, Acetyl-L-Carnitine, and Lipoic Acid

Propionyl and acetyl carnitine derivatives beat sex hormone at its own game and enhance Viagra’s benefits By Will Block

I kissed my first woman and smoked my first cigarette on the same day. I have never had time for tobacco since. 
— Arturo Toscanini

Italians—you gotta love ’em. Warm, passionate, ebullient, and full of the joy of life and love. What fun they are to be with, and what a marvelous country and culture they have: the timeless beauty of the land and sea, the inspiring historical heritage, the magnificent art and architecture, the brilliant science and engineering, the glorious music, the fabulous food and wine, the sophisticated fashions, the sexy cars, … and Sophia Loren!

And, oh, the language—was there ever a more seductively beautiful tongue than Italian? It seems made for music and made for love. Madonna (full name: Madonna Louise Veronica Ciccone) once said, “You don’t have to have a language in common with someone for a sexual rapport. But it helps if the language you don’t understand is Italian.” Your partner could be reciting the tax code, for all you knew, and it would still sound deliciously sexy.

Men, Stand Up and Fight!

The Italians, it could be said, are in love with amore. Where there’s love, of course, there tends to be sex, so it seems fair to say that Italians have more than a passing interest in mankind’s favorite pastime. All of which may or may not have anything to do with the fact that some recent studies on the subject of sexual function (dysfunction, actually) were conducted by a team of Italian researchers in Ferrara, Bologna, Fermo (Ascoli Piceno), and Rome. Two of the scientists are the inventors of a patented process involving the combined use of two chemical compounds, propionyl-L-carnitine (PLC) and acetyl-L-carnitine (ALC), “for the therapy of symptoms associated with partial androgen deficiency of the aging male.”1

By androgen they mean the male sex hormones, especially testosterone. The primary symptoms in question are impotence, depressed mood, and fatigue. It’s no surprise that impotence (aka erectile dysfunction) does a man’s mood no good, and fatigue seems to be a natural part of aging in any case. But should a man simply accept all this as an inevitability of the aging process? Certainly not! He should stand up and fight for what is rightfully his: a degree of vigor that, while it might not match that of his youth, still far exceeds what a stingy Mother Nature doles out to those who fail to grab the bull by the horns.

In other words, a man should behave like an Italian—like Toscanini, for example, who clearly had his priorities straight. Whether the aging Maestro (he lived to be 89) ever felt the need for some pharmacological enhancement for his amorous pursuits, we do not know, and it’s none of our business anyway. What we do know is that today’s man has available a variety of prosexual boosters that men of earlier generations could only have dreamed about (some dreams do come true).

Prescription Remedies Carry Risks

Breathes there a man who hasn’t heard of Viagra®, Levitra®, and Cialis®? These are the Big Three sexual enhancers of the pharmaceutical world (they enhance performance, but not libido—that’s still the man’s responsibility). We hear about their benefits all the time, but what we seldom hear is that these wonder drugs have some less than wonderful side effects (especially in older men), including headache, flushing, dyspepsia, nasal stuffiness, painful urination, diarrhea, and visual disturbances. It’s even possible for users of these drugs to experience sudden blindness; this prompted the FDA to issue a warning about all three of them in 2005.

A more traditional therapy for male sexual problems is testosterone, which enhances both libido and performance, as well as muscle mass and strength, bone density, mood, and overall energy. Testosterone, however, is generally recommended only for men with unusually low levels of it, and, like most other steroid hormones, it is not without its dangers. It can, e.g., increase the risk for stroke, aggravate sleep apnea, increase PSA (prostate-specific antigen) levels, and cause enlargement of the prostate gland. Although it probably does not cause prostate cancer, it may enhance the growth of an existing prostate cancer. (Testosterone is also used, by the way, to treat women for breast cancer and low libido.)

Carnitine Derivatives—An Attractive Alternative

Is there anything that can simulate testosterone’s prosexual effects, but without the risks? The Italian researchers mentioned above think there is. Italy has long been in the forefront of studying and using the amino acid carnitine and its derivatives (see the sidebar) for boosting energy metabolism, as well as for other therapeutic purposes. Thus it was natural to think of these compounds as potential prosexual supplements. [For more information on this subject, see “Acetyl L-Carnitine Can Help Straighten Your Penis” (October 2001) and “Testosterone Is Life, If You’re a Man” (February 2002).]

Acetyl-L-Carnitine and Propionyl-L-Carnitine

Both acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) are natural substances that help boost our energy metabolism by acting as sources of their parent compound, carnitine, an unusual type of amino acid.* Carnitine in our cells facilitates the transport of fatty acid molecules across the mitochondrial membranes. Without these fuel molecules, our mitochondria (the cells’ chemical “powerhouses”) would sputter and die—and so would we. Our carnitine levels tend to decline with age, so maintaining a healthy supply of this compound is a good idea.

*Acetyl is pronounced ah·SEE·tl, and propionyl is pronounced PRO·pee·oh·neel. The acetyl group (CH3CO–) comes from acetic acid (CH3COOH), and the propionyl group (CH3CH2CO–) comes from propionic acid (CH3CH2COOH).

For energy metabolism, ALC is more important than PLC, because it acts as a delivery system for both carnitine molecules and acetyl groups. The latter are extremely important in many of life’s biochemical processes, such as the production of acetyl-coenzyme A (the most important intermediary in the generation of energy from amino acids, fats, and carbohydrates) and acetylcholine (the neurotransmitter whose depletion in the brain is a hallmark of Alzheimer’s disease).

ALC’s role in boosting energy metabolism may explain in part why it improves memory and other cognitive functions in people with mild cognitive impairment and early Alzheimer’s disease.  ALC also exerts a neuroprotective effect, which may help explain its tendency to inhibit the peripheral neuropathies that often accompany diabetes. And ALC’s methyl-group-donating action helps to prevent eye damage caused by a harmful, age-related process called glycation, which degrades the proteins in our lenses.

Cardioprotective properties have been attributed to ALC, and to PLC as well. There is evidence suggesting that PLC, in particular, may be helpful in treating such cardiovascular disorders as congestive heart failure, angina pectoris, and intermittent claudication (pain upon walking, owing to peripheral arterial disease). Whether for therapeutic purposes or as a nutritional supplement, it’s generally more effective to take PLC than carnitine itself; the same is true of ALC.

Contrary to some claims, ALC and PLC are not antioxidants. In fact, they tend to have an indirect pro-oxidant effect because of their enhancement of cellular energy metabolism, which is the primary source of free radicals in our bodies. This tendency can be offset, however, with the potent antioxidant lipoic acid, which should therefore always be taken along with ALC and PLC. [See “Can Acetyl L-Carnitine and Lipoic Acid Slow the Aging Process?” (October 2004).]

The researchers conducted a randomized, double-blind, placebo-controlled trial of the effects of propionyl-L-carnitine and acetyl-L-carnitine, taken together, versus those of testosterone undecanoate (a commonly used chemical derivative that we’ll refer to simply as testosterone).1 They recruited 150 generally healthy men, aged 60–74 (average 64), whose chief complaints were those typical of older men who feel that they’re “slowing down” in various ways. These symptoms include decreased libido, partial to complete impotence, depressed mood, and a reduced ability to concentrate, as well as irritability and fatigue. All the men had very low serum testosterone levels.

The carnitine derivatives PLC and 
ALC produced improvements in 
virtually all the measures used in this 
study, and greater improvements than 
testosterone in several of them.

Of the 150 men, 130 completed the 12-month trial. They had been divided into three groups: Group 1 received 160 mg/day of testosterone; Group 2 received 2 g/day of PLC and 2 g/day of ALC; and Group 3 received a placebo (a 500-mg starch tablet). The men were examined at the outset of the trial and again at 3 months and 6 months, after which the treatments were halted; the final examination was performed 6 months later. The following variables were measured:

  • Total PSA – PSA is a glycoprotein whose elevated levels in the blood can indicate prostate cancer. The PSA test routinely administered to aging men is useful but usually not definitive; it must be used in conjunction with the familiar digital rectal examination and any other tests the physician deems appropriate.
  • Prostate volume – This can be measured by ultrasonography (ultrasound). It provides a clue to testosterone activity, which tends to enlarge the prostate gland.
  • Peak systolic velocity – This is the maximum rate of blood flow, measured by Doppler ultrasonography (a special technique for measuring flow rates) within the cavernosal arteries of the penis during systole (the heart’s contraction).
  • End diastolic velocity – This is the minimum rate of blood flow, measured at the end of diastole (the heart’s resting period between contractions).
  • Resistive index (RI) – This is a useful number calculated from the two measured blood velocities. The higher the RI, the better, in terms of erectile function.
  • Nocturnal penile tumescence (NPT) – This is measured using an ingenious device that monitors the penis’s size and rigidity while the patient is asleep; it records the number and duration of erections that meet certain minimum criteria.
  • Total and free testosterone – Much of a man’s testosterone is chemically bound to proteins in the blood and is thus not bioavailable (free) for hormonal action. Thus the most important measure is that of free testosterone—especially in aging men, in whom it continually declines as a percentage of the total.
  • Lutropin – Also called luteinizing hormone, this pituitary hormone stimulates the production of testosterone by the testes; it also stimulates estrogen production and ovulation in women. (All the sex hormones, and the hormones that stimulate their production, have roles to play in both sexes.)
  • Prolactin – This is a pituitary hormone that stimulates and maintains the secretion of breast milk. Its relevance in men is that an age-related increase in prolactin can inhibit the release of gonadotropins, which are hormones that stimulate the growth and function of the gonads in both sexes. Thus, excessive prolactin levels would suppress testosterone production.

Testosterone Increased Prostate Volume

Regarding the results of this trial, let’s get the placebo group out of the way first: these men showed no significant changes in any measure—which is surprising, considering how strong the placebo effect usually is. In any case, it means that the effects found in the two treatment groups were real as measured and did not require the subtraction of a placebo effect.

Both Group 1 (testosterone) and Group 2 (PLC/ALC) benefited significantly from their respective treatments, with Group 2 faring better overall. First of all, neither treatment increased PSA levels (which is good). The testosterone group showed a significant increase in prostate volume (not good), which was to be expected. After 12 months (i.e., 6 months after treatment had ceased), prostate volume had decreased significantly, but not to the baseline level. By contrast with the testosterone group, the PLC/ALC group showed no increase in prostate volume.

Bigger and Better Things to Come with PLC/ALC

Both groups showed similar, significant increases in the resistive index at 3 months, and these improvements were maintained at 6 months. After 6 more months withouttreatment, however, the RI had reverted to baseline values in both groups. The same pattern was observed with nocturnal penile tumescence, except that here the PLC/ALC group had significantly better results: whereas the total duration of NPT increased by 48% in the testosterone group, it increased by 88% in the PLC/ALC group. (I know what you’re thinking: “Big deal—what good does more NPT do me? I sleep right through it anyway.” But it’s a sign of bigger and better things to come when you’re awake!)

The men who took PLC plus 
sildenafil had significantly better 
results in virtually all respects than 
the men who took only sildenafil.

As expected, testosterone treatment increased both total and free testosterone levels in Group 1, and it reduced the levels of lutropin (via a negative feedback mechanism); it had no effect on prolactin levels. In Group 2, by contrast, treatment with PLC/ALC produced no changes in any of the hormone levels—meaning no undesirable consequences from any such changes.

PLC/ALC Outperforms Testosterone

Leaving the realm of laboratory tests, the researchers also evaluated the men’s sexual function, using the International Index of Erectile Function (IIEF), a standardized set of questionnaires in five categories. Following are the categories and the results observed:

  • Erectile function – Both testosterone and PLC/ALC produced significant improvement at 3 months, with further improvement at 6 months. The improvement with PLC/ALC was significantly better than that with testosterone at both time points.
  • Satisfaction with sexual intercourse – With both treatments, there was significant improvement at 6 months.
  • Orgasm – There was no improvement with testosterone, but PLC/ALC produced significant improvement at 3 months, with further improvement at 6 months.
  • Sexual desire – Both treatments produced significant improvement at 3 months, but no further improvement at 6 months.
  • General sexual well-being – There was no improvement with testosterone, but PLC/ALC produced significant improvement at 3 months, with no further improvement at 6 months.

Depression and Fatigue Are Both Improved

Leaving no stone unturned, the researchers also evaluated the men’s mood, using a standardized test called the Hamilton Depression and Melancholia Scale. Both treatment regimens produced significant mood improvement at 3 months, with no further improvement at 6 months. At both time points, the scores for the PLC/ALC group were significantly lower—meaning better mood—than those for the testosterone group.

Finally, the researchers also measured the men’s fatigue level, again using a standardized test. The fatigue scores dropped significantly—meaning more energy—for both groups at both time points, by roughly the same amounts. Throughout the trial, there were no significant side effects in either group.

In summary, the combined carnitine derivatives, PLC and ALC, produced improvements in virtually all the measures used in this study, and greater improvements than testosterone in nocturnal penile tumescence, in three of the five measures of erectile function (per the IIEF questionnaires), and in mood—all without altering hormonal levels or enlarging the prostate gland.

PLC/ALC Enhances Benefits of Sildenafil

The prosexual benefits of PLC and ALC are supported by the results of another recent study by the same research group, this one on 96 men (average age 61) who had undergone a prostatectomy of the kind that largely spares the nerves required for erections to occur.2 Many such men experience erectile difficulties and find help in products such as Viagra (sildenafil). The researchers surmised that PLC and ALC would enhance sildenafil’s efficacy in restoring or improving sexual activity after the operation, and they found that this was true. The men who took PLC/ALC (2 g/day of each) in addition to sildenafil (as required) for 4 months had significantly better results in virtually all areas of sexual function than the men who took only sildenafil (as required).

Bottling up our emotions is 
bad for us in many ways. Now we 
have learned that this tendency is 
also associated with impotence.

Another Italian research group studied the effects of PLC in combination with sildenafil in 40 diabetic men (average age 64) who suffered from impotence, which is a common consequence of that disease.3 (To make matters worse, many of the drugs used to treat diabetes can, in certain cases, contribute to impotence, and they can reduce sildenafils efficacy.) In this 6-month study, the men who took PLC (2 g/day) plus sildenafil (twice weekly) had significantly better results in virtually all respects than the men who took only sildenafil (twice weekly).

Lipoic Acid Also Gives Men an Erectile Boost

It’s worth noting that another natural supplement found to be helpful for diabetic men with impotence is the potent antioxidant lipoic acid, a compound widely used in Europe for the treatment of diabetes. [See “Lipoic Acid, the ‘Antioxidant’s Antioxidant’” (July 2001), “Lipoic Acid Helps Fight Diabetes” (December 2003), and “Can Lipoic Acid Fight Diabetes-Induced Impotence?” (April 2006).] It’s advisable for those taking a carnitine derivative to take lipoic acid as well (see the sidebar).

Men, Let It All Hang Out (Emotionally, That Is)

No one ever accused the Italians of being shy about expressing themselves openly and volubly. Luckily for them, their unabashedly emotional nature may help to keep them healthy. Doctors have long known that bottling up our emotions—something that many men are accused of by their long-suffering wives or girlfriends—is bad for us in many ways. Now we have learned (from yet another group of Italian researchers, naturally) that this tendency is also associated with impotence.4

In studying 100 men (average age 40) with psychogenic impotence, i.e., impotence notcaused by organic disease, the researchers found an unusually high prevalence (34%) of alexithymia, the psychiatric term for a difficulty in recognizing, acknowledging, and communicating emotions openly (those men were not behaving like proper Italians!).

The lesson here is that, when it comes to love and sex, our emotions do not want to be bottled up—they want to be free, so that we can … well, you know. Bottles are good, however, for containing nutritional supplements—and if some of those might help revitalize your sex life, well then, hit the bottle!


  1. Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology 2004;63:641-6.
  2. Cavallini G, Modenini F, Vitali G, Koverech A. Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy. Urology 2005;66:1080-5.
  3. Gentile V, Vicini P, Prigiotti G, Koverech A, Di Silverio F. Preliminary observations on the use of propionyl-L-carnitine in combination with sildenafil in patients with erectile dysfunction and diabetes. Curr Med Res Opin 2004;20:1377-84.
  4. Michetti PM, Rossi R, Bonanno D, Tiesi A, Simonelli C. Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction. Int J Impot Res 2006;18:170-4.