Download Acetyl-L-carnitine and L-carnitine

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Harm reduction wikipedia , lookup

Diseases of poverty wikipedia , lookup

Syndemic wikipedia , lookup

HIV and pregnancy wikipedia , lookup

Epidemiology of HIV/AIDS wikipedia , lookup

Index of HIV/AIDS-related articles wikipedia , lookup

Transcript
FACTSHEET
Acetyl-L-carnitine and
L-carnitine
What is carnitine?
L-carnitine is an amino acid found in red meat
and acetyl-L-carnitine is another form of
this nutrient. Carnitine can be made in small
quantities by the brain, liver and kidneys.
Among other things, this amino acid plays a
role in helping to release energy from fat by
moving fats to power plants within cells where
fats can be burnt as fuel. These cellular power
plants, called mitochondria, are responsible
for making the energy a cell needs to survive
and function.
How does carnitine work?
Carnitine appears to have antioxidant
properties. According to at least one study,
people with HIV can have normal levels of
carnitine in their serum (the fluid part of the
blood) while still having very low levels in the
cells, where carnitine is needed.
In people with HIV whose health has improved
because of anti-HIV drugs (antiretroviral
therapy, or ART), carnitine levels may not
return to normal.
When taken orally as a supplement, only a
relatively small amount—between 5% and 18%—
of carnitine is absorbed.
Why do some people with HIV use
this supplement?
Carnitine may have several potential uses,
including the following:
• to help heal injured nerves (in cases of
peripheral neuropathy (PN))
• to decrease levels of lactic acid in the blood
• to reduce higher-than-normal levels of
triglycerides
1. To help heal injured nerves
Levels of carnitine in the blood are sometimes
lower in people who have HIV and PN (nerve
injury that causes tingling, numbness or a
burning sensation in the hands, feet and legs),
particularly under the following conditions:
• injury from viral infections such as HIV and
CMV (cytomegalovirus)
• past use of “d” drugs such as d4T
(stavudine, Zerit), ddI (didanosine, Videx)
and ddC (Hivid)
• the use of some anti-cancer drugs
and antibiotics
• drinking excess amounts of alcohol
• diabetes
What the medications in the above list
have in common is that they can injure the
energy-producing parts of nerve cells—the
mitochondria. Injured mitochondria cannot
ACETYL-L-CARNITINE AND L-CARNITINE
page 1 of 5
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 people with both HIV
and PN can develop abnormal sweating,
suggesting that nerves in sweat glands can also
be affected.
One formulation of carnitine, acetyl-Lcarnitine (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
and well-designed study of ALCAR in people
who have both HIV and PN. Their findings
revealed that most people with HIV showed
some degree of recovery from nerve damage
after taking 1.5 grams of ALCAR twice daily for
up to 4 years.
Seventy-six percent of participants had
significantly reduced pain. In the British
study, analyses of skin samples taken
during the clinical trial found that after six
months of ALCAR use, injured nerve fibres
were undergoing re-growth. The longer
participants took the supplement, the greater
the re-growth. Nerve fibres grow slowly so it
takes many months, perhaps even years, for
the injury from PN to heal. Such healing may
be incomplete.
There were no significant changes to CD4+
and CD8+ cells or viral load measures during
the study.
The research team speculates that ALCAR may
have helped nerves for the following reasons:
• Carnitine has antioxidant properties, which
may protect nerve cells from the toxicity
of the class of anti-HIV drugs known as
nucleoside analogues (or nukes).
ACETYL-L-CARNITINE AND L-CARNITINE
• By improving the transport of fats and
sugar, carnitine may have helped cells
become more energetic and active, perhaps
stimulating their recovery.
• Carnitine could have helped nerve regrowth
and repair by enhancing the effects of nerve
growth factor.
• People living with both HIV and PN have
been found to have decreased levels of
ALCAR in their blood and the supplement
may have reversed this.
Overall, this study goes a long way toward
helping researchers explore the role of
carnitine, particularly ALCAR, as part of the
management of PN.
Two randomized, placebo-controlled studies
for which participants took 500 mg/day
or 1,000 mg/day have also found it to be
beneficial in the management of PN in HIVnegative people with diabetes.
2. To help reduce levels of lactic acid in
the blood
A rare complication that can occur in users
of the anti-HIV drugs called nucleoside
analogues is the development of higher-thannormal levels of lactic acid in the blood. If
levels become very high, the following cluster
of signs/symptoms may occur as part of a
condition called lactic acidosis:
• unexpected tiredness
• abdominal pain
• swollen, fatty liver
• shortness of breath
• nausea and/or vomiting
The following blood tests help identify
lactic acidosis:
• lactate levels of 5 mmol/L or greater
• bicarbonate levels of 20 mmol/L or lower
page 2 of 5
If you think that you are experiencing lactic
acidosis, contact your doctor right away.
Anecdotal reports suggest that L-carnitine
may play a role in helping people with HIV to
recover from lactic acidosis. In a pilot study of
six people with HIV who were extremely ill and
who had high levels of lactic acid in their blood
from drug-related side effects, researchers
gave them intravenous L-carnitine at doses
between 50 mg and 100 mg/kg of body weight
per day. Despite this treatment, only three
of the participants survived and recovered
from lactic acidosis. Other researchers have
intervened at earlier stages of lactic acidosis
with oral supplements of B vitamins and
L-carnitine with successful results.
3. To reduce high levels of triglycerides in
the blood
In 2001, results of a pilot study in Montreal
were released. L-carnitine at a dose of 3 grams
daily was used by 16 people with HIV who were
also taking anti-HIV drugs. Triglyceride levels
decreased significantly within the first month
and by the end of the study had deceased by
about 35%. By the end of the study, 70% of
participants had their triglyceride levels return
to the normal range.
In that era, elevated levels of triglycerides in
the blood were common because most HIVpositive people taking ART were using a class
of drugs called protease inhibitors. Modern
protease inhibitors do not usually cause large
increases in triglyceride levels.
Side effects
1. Gastrointestinal
Nausea, vomiting and diarrhea may occur,
especially in people who take more than
4 grams per day.
2. Neurological
Seizures have been reported by some people
taking carnitine supplements, regardless of
ACETYL-L-CARNITINE AND L-CARNITINE
whether or not these people had seizures in
the past.
3. Thyroid hormones
The hormones produced by the thyroid gland
are called T3 (triiodothyronine) and T4
(thyroxine). Thyroid hormones help control
the body’s ability to produce energy and
regulate its temperature. In lab experiments,
L-carnitine blocks the ability of cells to
respond to these hormones by interfering with
the movement of these hormones within a cell.
In studies in HIV-negative people, L-carnitine,
at doses of 2 or 4 grams per day, reduced
thyroid hormone levels. Researchers are not
sure what effect lower doses of carnitine
might have on thyroid hormone levels. If
thyroid hormone levels fall below normal, a
range of symptoms may develop, including
the following:
• unexpected tiredness
• feeling cold
• dry skin
• muscle weakness
• forgetfulness and difficulty concentrating
• impaired hearing
If you are taking carnitine supplements, speak
to your doctor about monitoring the health of
your thyroid gland.
4. Pregnancy
Carnitine has not been studied in pregnant
women. Therefore, the manufacturer suggests
that carnitine be used by pregnant women only
if it is clearly needed.
Drug interactions
Always tell your doctor and other
members of your healthcare team about
all the medications (prescription and nonprescription), herbs and supplements that you
page 3 of 5
are taking. Carnitine may interfere with the
following drugs:
• drugs to treat or prevent blood clots—
acenocoumarol/nicoumalone (Sintrom)
• thyroid hormones
De Simone C, Famularo G, Tzantzoglou S et al. Carnitine
depletion in peripheral blood mononuclear cells from patients
with AIDS: effect of oral L-carnitine. AIDS. 1994;8:655-60.
Vilaseca MA, Artuch R, Sierra C et al. Low serum carnitine in
HIV-infected children on antiretroviral treatment. European
Journal of Clinical Nutrition. 2003;57(10):1317-22.
Dosage and formulations
Famularo G, De Simone C. Carnitine stands on its own in HIV
infection treatment. Archives of Internal Medicine. 1999
May;​159:1143-4.
Carnitine is produced by the Sigma-Tau
company, in Italy, in two formulations:
Evans AM and Fornasini G. Pharmacokinetics of L-carnitine.
Clinical Pharmacokinetics. 2003;42(11):941-67.
• L-carnitine
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.
• acetyl-L-carnitine
The dose usually used in clinical trials varies
from 500 mg to 3,000 mg (3 grams) a day. This
can be divided into several doses and taken
with food.
Availability
L-carnitine is sold under the brand name
Carnitor and is available by prescription in
North America. Acetyl-L-carnitine (ALCAR) is
sold under the brand name Nicetile in Italy
and some countries of the European Union. In
Canada and the United States, some health
food stores also sell different brands and
formulations of carnitine. All formulations
of carnitine are expensive. ALCAR is more
often used in studies of neuropathy. Both
formulations of carnitine have been used
in trials related to HIV, although some HIV
nutritional experts have suggested the acetyl
form may be more useful.
References
Carnitor (levocarnitine). Product Monograph. Compendium of
Pharmaceutical Specialties. 2015.
Cassol E, Misra V, Morgello S, et al. Altered monoamine and
acylcarnitine metabolites in HIV-positive and HIV-negative
subjects with depression. Journal of Acquired Immune
Deficiency Syndromes. 2015 May 1;69(1):18-28.
Vaz FM and Wanders RJ. Carnitine biosynthesis in mammals.
Biochemical Journal.2002;361(Pt 3):417-29.
Ilias I, Manoli I, Blackman MR et al. L-Carnitine and acetyl-Lcarnitine in the treatment of complications associated with
HIV infection and antiretroviral therapy. Mitochondrion. 2004
Jul;4(2-3):163-8.
Sima AA, Calvani M, Mehra M et al. Acetyl-L-carnitine
improves pain, nerve regeneration, and vibratory perception
in patients with chronic diabetic neuropathy: an analysis of
two randomized placebo-controlled trials. Diabetes Care.
2005 Jan;28(1):89-94.
Hart AM, Wilson AD, Montovani C et al. Acetyl-l-carnitine:
a pathogenesis based treatment for HIV-associated
antiretroviral toxic neuropathy. AIDS. 2004;18(11):1549-60.
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.
Vrouenraets SM, Treskes M, Regez RM et al. Hyperlactataemia
in HIV-infected patients: the role of NRTI-treatment.
Antiviral Therapy. 2002;7(4):239-44.
Brinkman K, Vrouenraets S, Kauffmann R et al. Treatment
of nucleoside reverse transcriptase inhibitor-induced lactic
acidosis. AIDS. 2000;14(17):2801-2.
Carter RW, Singh J, Archambault C and Arrieta A. Severe
lactic acidosis in association with reverse transcriptase
inhibitors with potential response to L-carnitine in a
pediatric HIV-positive patient. AIDS Patient Care and STDs.
2004;18(3):131-4.
Claessens YE, Cariou A, Monchi M et al. Detecting lifethreatening lactic acidosis related to nucleoside-analog
treatment of human immunodeficiency virus-infected
patients, and treatment with L-carnitine. Critical Care
Medicine. 2003;31(4):1042-7.
De Simone C, Tzantzoglou S, Jirillo E et al. L-carnitine
deficiency in AIDS patients. AIDS. 1992;6(2):203-5.
ACETYL-L-CARNITINE AND L-CARNITINE
page 4 of 5
Muller DM, Seim H, Kiess W et al. Effects of oral L-carnitine
supplementation on in vivo long-chain fatty acid oxidation in
healthy adults. Metabolism. 2002;51(11):1389-91.
De Simone C, Tzantzoglou S et al. High dose L-carnitine
improves immunologic and metabolic parameters in AIDS
patients. Immunopharmacology and Immunotoxicology. 1993
Jan;15(1):1-12.
Loignon M and 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.
Mingrone G. Carnitine in type 2 diabetes. Annals of the New
York Academy of Sciences. 2004 Nov;1033:99-107.
Day L, Shikuma C and Gerschenson M. Acetyl-L-carnitine for
the treatment of HIV lipoatrophy. Annals of the New York
Academy of Sciences. 2004;1033:139-46.
Dalakas MC, Leon-Monzon ME et al. Zidovudine-induced
mitochondrial myopathy is associated with muscle carnitine
deficiency and lipid storage. Annals of Neurology. 1994
April;35(4):482-7.
Georges B, Galland S, Rigault C et al. Beneficial effects
of L-carnitine in myoblastic C2C12 cells. Interaction
with zidovudine. Biochemical Pharmacology. 2003 May;​
65(9):​1483-8.
Mauss S and Schmutz G. L-Carnitine in the treatment of
HIV-associated lipodystrophy syndrome. HIV Medicine. 2001
Jan;2(1):59-60.
Benvenga S, Amato A, Calvani M and Trimarchi F. Effects of
carnitine on thyroid hormone action. Annals of the New York
Academy of Sciences. 2004 Nov;1033:158-67.
Bachmann HU and Hoffmann A. Interaction of food
supplement L-carnitine with oral anticoagulant
acenocoumarol. Swiss Medical Weekly. 2004 Jun 26;​
134(25-26):385.
Youle M. Acetyl-L-carnitine in HIV-associated antiretroviral
toxic neuropathy. CNS Drugs. 2007;21 Suppl 1:25-30;
discussion 45-6.
Kvetny J, Bomholt T, Pedersen P, et al. Thyroid hormone
effect on human mitochondria measured by flow
cytometry. Scandinavian Journal of Clinical and Laboratory
Investigation. 2009;69(7):772-6.
Credits
Author: Hosein SR
Published: 2016
Contact us
by telephone
1.800.263.1638
416.203.7122
by fax
416.203.8284
by e-mail
[email protected]
by mail
505-555 Richmond Street West
Box 1104
Toronto ON M5V 3B1
Disclaimer
Decisions about particular medical treatments should always
be made in consultation with a qualified medical practitioner
knowledgeable about HIV- and hepatitis C-related illness and the
treatments in question.
CATIE provides information resources to help people living with HIV
and/or hepatitis C who wish to manage their own health care in
partnership with their care providers. Information accessed through
or published or provided by CATIE, however, is not to be considered
medical advice. We do not recommend or advocate particular
treatments and we urge users to consult as broad a range of sources
as possible. We strongly urge users to consult with a qualified
medical practitioner prior to undertaking any decision, use or action
of a medical nature.
CATIE endeavours to provide the most up-to-date and accurate
information at the time of publication. However, information
changes and users are encouraged to consult as broad a range of
sources as possible. Users relying on this information do so entirely
at their own risk. Neither CATIE, nor any of its partners, funders,
employees, directors, officers or volunteers may be held liable
for damages of any kind that may result from the use or misuse of
any such information. The views expressed herein or in any article
or publication accessed or published or provided by CATIE do not
necessarily reflect the policies or opinions of CATIE nor the views of
its partners and funders.
Permission to reproduce
This document is copyrighted. It may be reprinted and distributed in
its entirety for non-commercial purposes without prior permission,
but permission must be obtained to edit its content. The following
credit must appear on any reprint: This information was provided
by the Canadian AIDS Treatment Information Exchange (CATIE). For
more information, contact CATIE at 1.800.263.1638.
Funding has been provided by the Public Health Agency of Canada.
CATIE fact sheets are available for free at www.catie.ca
ACETYL-L-CARNITINE AND L-CARNITINE
page 5 of 5