Can Carnitine Reduce Diabetes Risk and Improve Body Shape?
Inside each cell are tiny power plants called mitochondria. Inside mitochondria, fats are burned to release energy to power a cell. When mitochondria are damaged, cells do not get sufficient energy and can become dysfunctional and, in some cases, even die.
Carnitine is a nutrient found in food of animal origin. Carnitine helps to move fatty substances into mitochondria, where they can be used to produce energy.
Some studies have found less-than-normal levels of carnitine in the blood of HIV positive people. Other studies have found that regular supplementation with carnitine can help to reduce abnormal levels of triglycerides, a fatty substance in the blood. Most of the studies focused on a formulation of carnitine called L-carnitine.
Long-term studies of a different formulation of carnitine -- acetyl-L-carnitine -- suggest that this substance can help damaged nerves recover from the toxicity of certain anti-HIV drugs such as d4T (Zerit, stavudine) and ddI (Videx EC, didanosine).
Now researchers in Milan, Italy, have conducted a small study with HIV positive volunteers and carnitine, to assess its effects on body composition and other related metabolic parameters. The results from this study suggest the possibility of a decreased risk for diabetes. Furthermore, the research team claims that carnitine supplements increased the fat content in the legs of volunteers. We urge readers to exercise caution when interpreting the results of this small study and we provide critical details later in this CATIE News bulletin.
Researchers at San Raffaele Hospital in Milan recruited nine HIV positive volunteers for this study. Their average profile was as follows:
- four females, five males
- age -- 35 years
- weight -- 66 kg (146 pounds)
- body mass index (BMI) -- 23 (This is a method of assessing the fatness of a person. A BMI that ranges between 18.5 and 24.9 is considered within the healthy range.)
- CD4+ cell count -- more than 400 cells
- viral load -- less than 50 copies
All participants were taking highly active antiretroviral therapy (HAART) and had stable CD4+ cell counts.
Researchers also enrolled nine healthy HIV negative volunteers of similar age and gender mix. This group was used for comparison.
No HIV positive participant had diabetes or serious heart, lung, liver or kidney dysfunction. All HIV positive participants had lost a moderate-to-severe degree of subcutaneous fat, the fatty layer just under the skin.
All participants ate a diet designed by the researchers that consisted of a similar amount of calories.
All participants received magnetic scans or MRIs (magnetic resonance imaging) of different parts of their body. They also received low-dose X-ray scans called DEXA (dual-energy x-ray absorptiometry) to assess changes in fat distribution.
HIV positive participants received carnitine formulated as L-acetyl-carnitine at a dose of 2 grams per day for eight consecutive months.
There was a trend for levels of fat in the upper body of participants to decrease. Perhaps this trend might have become statistically significant had the study continued for a longer period of time or had many more people participated. Still, according to a statistical analysis, there was no significant change in the fat content of the upper body or arms. However, according to the results of DEXA scans, the legs of HIV positive participants became a bit thicker as the amount of fat increased by about 500 grams (about a pound). This difference would probably not be noticed by participants as it likely happened gradually and was only detectable using high-tech instruments. Moreover, the increase in fat content of the legs of HIV positive people, although statistically significant, resulted in leg fat levels far below those seen in HIV negative people.
The hormone insulin helps cells absorb sugar from the blood. In cases of pre-diabetes, cells gradually lose their ability to respond to the effects of insulin. As a result, blood sugar levels can remain high for prolonged periods of time. The pancreas gland, which produces insulin, is forced to make ever-high amounts of this hormone to try to stimulate cells to reduce blood sugar. If this continues over a period of years, the pancreas gets exhausted and can eventually fail.
At the start of the study, the bodies of the HIV positive participants were somewhat insensitive to the effects of insulin. By the end of the study, insulin sensitivity improved among HIV positive people and reached the level detected in HIV negative people.
After eight months of carnitine supplementation, lipid -- cholesterol and triglyceride -- levels in the blood were only modestly affected, with small decreases in total cholesterol and "bad" (LDL-C) cholesterol and triglycerides.
In some previous studies, reduced levels of thyroid hormones were sometimes detected in carnitine users. However, in the present Italian study no reduction in thyroid hormone levels were seen.
Less-than-normal levels of growth hormone (GH) occur in HIV infection. At the start of the study, GH levels were about 67% below levels seen in HIV negative people. However, after eight months of carnitine supplementation, GH levels increased by 40% -- a significant difference.
Although the results of this study are promising, they should be viewed with caution for the following reasons:
- The trial was very small and should be considered a pilot study. Its findings therefore are not conclusive. It is noteworthy that another recent pilot study with 16 HIV negative volunteers has found that acetyl-L-carnitine (1 gram twice daily for 24 weeks) appears to help reduce high blood pressure and increase the body's sensitivity to insulin.
- The changes in body fat distribution were at best modest and only detectable with highly sensitive X-ray scans.
- A previous study of carnitine for HIV-related changes in body shape did not find any beneficial effect. However, this study lasted only three months.
- A previous study of carnitine provided hints that use of this nutrient might stimulate the release of GH. The finding of an increase in GH secretion in the present study is intriguing and requires further confirmation.
What Is to Be Done?
The results from the present Italian study with HIV positive volunteers are interesting, particularly the impact on insulin sensitivity and GH production. Now a larger and longer study is needed to confirm and extend the results seen so far. At a minimum, such a trial should consider a strategy of randomization and also a placebo-controlled phase, perhaps for the first six or eight months. These steps may be helpful in reducing bias when interpreting the results of such a trial.
L-carnitine is a prescription drug in North America for the treatment of carnitine deficiency, sold under the brand name Carnitor. Not all provincial/territorial formularies in Canada will pay for Carnitor in cases of HIV infection.
Acetyl-L-carnitine is available over the counter in Italy and some health food stores in the United States.
The carnitine formulation used in the present study was made by Sigma-Tau SpA, Italy.
- Herzmann C, Johnson MA, Youle M. Long-term effect of acetyl-L-carnitine for antiretroviral toxic neuropathy. HIV Clinical Trials. 2005 Nov-Dec;6(6):344-50.
- Youle M. Acetyl-L-carnitine in HIV-associated antiretroviral toxic neuropathy. CNS Drugs. 2007;21 Suppl 1:25-30; discussion 45-6.
- Youle M, Osio M; ALCAR Study Group. A double-blind, parallel-group, placebo-controlled, multicentre study of acetyl L-carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV-1 infection. HIV Medicine. 2007 May;8(4):241-50.
- Ferraresi R, Troiano L, Roat E, et al. Protective effect of acetyl-L-carnitine against oxidative stress induced by antiretroviral drugs. FEBS Lett. 2006 Dec 11;580(28-29):6612-6.
- Day L, Shikuma C, Gerschenson M. Acetyl-L-carnitine for the treatment of HIV lipoatrophy. Annals of the New York Academy of Sciences. 2004 Nov;1033:139-46.
- Hart AM, Wilson AD, Montovani C, et al. Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy. AIDS. 2004 Jul 23;18(11):1549-60.
- Mauss S, Schmutz G. L-Carnitine in the treatment of HIV-associated lipodystrophy syndrome. HIV Medicine. 2001 Jan;2(1):59-60.
- Loignon M, Toma E. L-Carnitine for the treatment of highly active antiretroviral therapy-related hypertriglyceridemia in HIV-infected adults. AIDS. 2001 Jun 15;15(9):1194-5.
- Di Marzio L, Moretti S, D'Alò S, et al. Acetyl-L-carnitine administration increases insulin-like growth factor 1 levels in asymptomatic HIV-1-infected subjects: correlation with its suppressive effect on lymphocyte apoptosis and ceramide generation. Clinical Immunology. 1999 Jul;92(1):103-10.
- Famularo G, Moretti S, Marcellini S, et al. Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. AIDS. 1997 Feb;11(2):185-90.
- Vilaseca MA, Artuch R, Sierra C, et al. Low serum carnitine in HIV-infected children on antiretroviral treatment. European Journal of Clinical Nutrition. 2003 Oct;57(10):1317-22.
- Benedini S, Perseghin G, Terruzzi I, et al. Effect of L-acetylcarnitine on body composition in HIV-related lipodystrophy. Hormone and Metabolic Research. 2009; in press.
- Ruggenenti P, Cattaneo D, Loriga G, et al. Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-L-carnitine therapy. Hypertension. 2009 Sep;54(3):567-74.