Can carnitine reduce diabetes risk and improve body shape?

We were interested to read about a recent study on carnitine, diabetes risk and body shape in people with HIV, as reported on the CATIE (Canadian AIDS Treatment Information Exchange) website:

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.

Read more information on the study at:
http://www.catie.ca/catienews.nsf/00a48c8905294f0b8525717f00661eb8/4c5c394577db43018525763f00731b34!OpenDocument

Read more background information at the NYBC entries:

Acetylcarnitine

and

L-Carnitine

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Multivitamin Antioxidant Combination (MAC-Pack): a K-Pax alternative available in no-iron formula for those with liver impairment

In 2007, NYBC began offering an alternative to the K-Pax multivitamin-antioxidant supplement, which was added to some ADAP and Medicaid formularies following publication in 2006 of Dr. Jon Kaiser’s study that found CD4 increases in people with HIV taking a micronutrient combination supplement. A first reason for the NYBC alternative, called the MAC-Pack, was price: for those without access to ADAP or Medicaid programs, the double strength K-Pax cost of about $140/month was rather high, and NYBC as a nonprofit co-op was able to present a close equivalent for only $62/month.

But another rationale for introducing the MAC-Pack was its flexibility. In fact, because MAC-Pack uses the AMNI/Douglas multivitamins Added Protection as its core, it can be configured as a formula with or without iron. Having the option of an iron-free MAC-Pack is important especially to people with elevated liver enzymes, liver impairment, or hepatitis co-infection. Taking iron supplements is generally not recommended for this group, since processing the iron puts an extra strain on liver function.

Also note that the MAC-Pack provides somewhat more acetylcarnitine than the K-Pax, which may not be a bad idea, especially if you believe, as we do, that acetylcarnitine is probably a key element in the multivitamin-antioxidant combination. (Two tabs/day is sufficient if you’re just interested in matching the K-Pax formula, but three/day may be better especially for those dealing with neuropathy.)

For more information, see the NYBC entry:

MAC-Pack

Acetylcarnitine for peripheral neuropathy, and as a component of a multivitamin/antioxidant combination

The UK-based information website http://www.aidsmap.com provides this succinct summary of evidence for use of acetylcarnitine (also “L-acetylcarnitine” or “acetyl-l-carnitine”) for HIV-associated antiretroviral toxic peripheral neuropathy:

A deficiency in L-acetyl carnitine may also play a role in neuropathy related to HIV treatment[4]. Taking L-acetyl carnitine supplements may reverse the nerve damage caused by HIV treatment, accompanied by an improvement of pain in most patients[5]. Similar studies have also shown improvements in pain with L-acetyl carnitine treatment, with one showing sustained benefit after more than four years[6][7][8]. Although the mechanism of L-acetyl carnitine’s action is unknown, it may counteract neuropathy by acting as an anti-oxidant, preventing the damage to mitochondria. Preliminary evidence suggests that carnitine may also be effective in treating other symptoms of mitochondrial toxicity, including elevated lactic acid levels[9].

(You can retrieve the references by going to the original web page,
at http://www.aidsmap.com/cms1235526.asp)

For more information, see the NYBC entry:

Acetylcarnitine

Also note that acetylcarnitine is a principal component of NYBC’s MAC-Pack (a low-cost alternative to the K-PAX):

MAC-Pack

Acetylcarnitine and Alzheimer’s Disease

The Journal of Neuroscience Research featured an article in 2006 on acetylcarnitine and Alzheimer’s Disease (AD)
that outlined the possible mechanism of this supplement in counteracting the effect of AD. Essentially, acetylcarnitine antioxidant workings may be able to prevent, or helpt to prevent, the deformations of brain structure associated with the development of Alzheimer’s. The authors of this NIH-funded research conclude that acetylcarnitine “may be useful as a possible therapeutic strategy for patients with AD.”

For more on this supplement, including its applications for neuropathy, see the NYBC entry Acetylcarnitine.

Acetyl-L-carnitine for diabetic neuropathy

Below we give the abstract of a recent (2005) assessment of acetyl-l-carnitine’s effectiveness in the management of neuropathy (tingling, pain due to nerve damage) in people with diabetes.

For additional information on the use of this nutrient for neuropathy and other conditions, see the NYBC entry on Acetylcarnitine.


Acetyl-L-Carnitine Improves Pain, Nerve Regeneration, and Vibratory Perception in Patients With Chronic Diabetic Neuropathy: An analysis of two randomized placebo-controlled trials

Anders A.F. Sima, MD, PHD, Menotti Calvani, MD, Munish Mehra, PHD and Antonino Amato, MD

OBJECTIVE—We evaluated frozen databases from two 52-week randomized placebo-controlled clinical diabetic neuropathy trials testing two doses of acetyl-L-carnitine (ALC): 500 and 1,000 mg/day t.i.d. [tid = 3 times per day]

RESEARCH DESIGN AND METHODS—Intention-to-treat patients amounted to 1,257 or 93% of enrolled patients. Efficacy end points were sural nerve morphometry, nerve conduction velocities, vibration perception thresholds, clinical symptom scores, and a visual analogue scale for most bothersome symptom, most notably pain. The two studies were evaluated separately and combined.

RESULTS—Data showed significant improvements in sural nerve fiber numbers and regenerating nerve fiber clusters. Nerve conduction velocities and amplitudes did not improve, whereas vibration perception improved in both studies. Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg ALC.

CONCLUSIONS—These studies demonstrate that ALC treatment is efficacious in alleviating symptoms, particularly pain, and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy.

Citation: Diabetes Care 28:89-94, 2005

Nutrients for Liver Toxicity: Practical Guide from the Canadian AIDS Treatment Information Exchange (CATIE)

CATIE provides an information sheet on liver toxicity as part of its “Practical Guide to Managing HIV Drug Side-Effects.” This info sheet suggests ways of coping with liver impairment, which is frequent in people with HIV, and may result from a variety of factors, including medication side-effects, hepatitis co-infection, repeated use of antibiotics, alcohol or drug use, or a nutrient-poor, chemically-rich diet.

Here’s an excerpt on some supplementation strategies to counteract liver impairment:


In addition to removing, as much as possible, anything that might be stressing the liver, it is very important to add the therapeutic agents that can help the liver to detoxify, repair and protect itself. There are a number of potentially useful agents, listed below:

Nutrients to Maintain Glutathione

Glutathione (GSH) is the most important intracellular antioxidant and is crucially important for protecting the liver against toxicity when it goes about its task of breaking down drugs and other toxins. Taking the following nutrients may help to maintain or increase levels of glutathione:

–vitamin C (2–6 grams per day, in divided doses)
–N-acetyl-cysteine, or NAC (500 mg, 3 times per day; always take with food because taking it on an empty stomach can cause gastrointestinal tract irritation)
–L-glutamine (5 grams per day, increased up to 30–40 grams in those who also have diarrhea or wasting). Note that anyone with seriously compromised liver or kidney function should not take glutamine without a doctor’s approval since it is an amino acid that must be processed by those organs.
–alpha-lipoic acid, or thioctic acid (300-500 mg, twice daily; take on an empty stomach with fluids). Alpha-lipoic acid is a naturally occurring fatty acid that acts as a cellular coenzyme. It is very important to the liver cell metabolic pathways and can be rapidly depleted when the liver is under stress. It appears to help boost repair when there has been either virally induced or drug-induced liver damage. Note that alpha-lipoic acid disappears from the bloodstream very rapidly, so products made in an extended-release form will last longer and work better.

For anyone with liver dysfunction or disease, the above nutrients may be very important as part of a total treatment approach.

For people with fatty livers, another important nutrient is the amino acid carnitine. Researchers say that it may help prevent mitochondrial toxicity, thus helping the body to handle fat better. Early studies of its use for non-HAART-related elevated triglycerides in PHAs did, indeed, show successful lowering of the blood fat levels. Research in animals has shown its successful use in reversal of fatty livers. The usual dosage is two capsules (500 mg each) twice daily. The alternative is Carnitor, the basic form of carnitine, available by prescription only. It is usually prescribed in doses of 3,000 mg daily (three 330-mg capsules, 3 times daily). Too-high doses can cause diarrhea, so watch for this. Doses of plain carnitine need to be higher because the acetyl-L-carnitine releases four times as much free carnitine into the bloodstream, using equivalent doses.

Note that in addition to the individual supplements mentioned above, NYBC also stocks its combination of N-acetyl-cysteine and alpha-lipoic acid, ThiolNAC.

Acetyl-l-carnitine and L-carnitine: Canadian AIDS Treatment Information Exchange Fact Sheet

Acetyl-l-carnitine (often shortened to acetylcarnitine) and L-Carnitine (aka carnitine) are among the most heavily investigated of dietary supplements for their applications to HIV/AIDS. In particular, acetylcarnitine has been studied for more than a decade for HIV-associated neuropathy, especially by Michael Youle in the UK (see other entries under “acetylcarnitine, this Blog). Acetylcarnitine is also a key component in the K-Pax (and NYBC’s low-cost K-pax equivalent, the MAC Pack). Meanwhile, carnitine is also much used by people with HIV, and the prescription form, Carnitor, is made available through some state-funded formularies.

For a very good overview on acetycarnitine and carnitine research and application to HIV/AIDS, see

Acetyl-l-carnitine and L-carnitine: Canadian AIDS Treatment Information Exchange Fact Sheet

A brief excerpt:

Why do PHAs use this supplement?
Carnitine has many potential uses, including the following:

1. helping to heal damaged nerves—peripheral neuropathy (PN)
2. helping to decrease levels of lactic acid in the blood
3. reducing higher-than-normal levels of cholesterol and/or triglycerides
4. helping to maintain muscle growth

1. To manage peripheral neuropathy (nerve damage causing tingling, numbness or burning in the hands, feet and legs)
Levels of carnitine in the blood are sometimes lower in PHAs with peripheral neuropathy, particularly under the following conditions:

• damage from viral infections such as HIV and CMV (cytomegalovirus)
• the use of “d” drugs such as d4T, ddI and ddC
• the use of some anti-cancer drugs and antibiotics
• alcohol abuse
• diabetes

What the medications in the above list have in common is that they can damage the energy-producing parts of nerve cells—the mitochondria. Injured mitochondria cannot supply sufficient energy and nerves begin to malfunction and can die. Nerves in the feet, legs and hands, particularly in the skin covering those body parts, appear to be especially susceptible to PN. Some researchers have noticed that PHAs with PN can develop abnormal sweating, suggesting that nerves in sweat glands can also be affected.

One formulation of carnitine, acetyl-L-carnitine (ALCAR), may play a role in the management of PN. This compound helps mitochondria function and also appears to enhance the effect of a chemical that helps nerves grow—nerve growth factor.

Researchers in England conducted an extensive study of ALCAR in PHAs with peripheral neuropathy. Their findings revealed that most PHAs showed some degree of recovery from nerve damage after taking ALCAR 1.5 grams twice daily for up to 2¾ years.

See also the NYBC entry on acetylcarnitine. Like its predecessor DAAIR, NYBC has this key supplement manufactured by pharmaceutical-grade producer Montiff; this allows for considerable cost savings for co-op buyers compared to commercially available products.