Plasma carnitine insufficiency and effectiveness of <scp>L</scp>‐carnitine therapy in patients with mitochondril myopathy

Campos, Yolanda; Huertas, Rosa; Lorenzo, Gustavo; Bautista, Juan; Gutiérrez, Eduardo; Aparicio, Manuel; Alesso, L.; Arenas, Joaquı́n

doi:10.1002/mus.880160205

Cited by 89 publications

(50 citation statements)

References 18 publications

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“…Similar normal values were reported in an article describing patients suffering from mitochondrial myopathy based on the clinical findings of muscle weakness and specific histopathologic features found on muscle biopsy [19]. That article indicated that carnitine levels below their normal range were associated with cardiomyopathy, muscle weakness and related muscle pathology that improved with carnitine supplementation [19]. Low free carnitine was found in (11/40) 28% of our study subjects.…”

Section: Resultssupporting

confidence: 88%

“…These results were compared to values established for healthy adults in the clinical laboratory of All Children's Hospital, which is CAP certified and participates in their Proficiency Testing program. These results are similar to those reported in the literature [19]. None of these subjects had any clinical evidence of cardiovascular, renal or liver disease.…”

Section: Methodssupporting

confidence: 92%

“…The mean level for the entire group of subjects with diabetes (40.8 ± 8.8 nmol/ml) was just above the low end of the normal range (40 nmol/ml). An E/F ratio of 0.25 has been reported to indicate "carnitine insufficiency" [19]. The mean (20 -42) E/F ratio for this group of patients was 0.25 ± 0.09 supporting the general observation of carnitine insufficiency in this entire group of patients.…”

Section: Discussionsupporting

confidence: 66%

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Diabetic Cardiovascular Risk and Carnitine Deficiency <br/>—Carnitine Deficiency in Clinical Diabetes Mellitus

Malone¹,

Malone²,

Morrison³

2014

JDM

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Background: Type 1 diabetes mellitus increases the risk of coronary heart disease. The Pittsburgh IDDM morbidity and mortality study reported greater than 10 fold coronary heart disease mortality compared with US national data [1]. Adults with diabetes have heart disease death rates 2 to 4 times higher than adults without diabetes [2]. Diabetic cardiomyopathy explains much of this survival difference and carnitine deficiency is a cause of cardiomyopathy. Research Design and Methods: Adult subjects (40) with type 1 diabetes mellitus were seen for a routine annual visit having no clinical complaints. Fasting serum samples were collected for annual chemistries and the measurement of carnitine. Results: The mean total (40.8 ± 8.8) [40 -80 nmol/ml] and free (32.9 ± 7.9) [30 -60 nmol/ml] carnitine levels for this group included 43% low total and 28% low free carnitine. The mean esterified/free (E/F) carnitine ratio (0.25 ± 0.09) for this group was elevated indicating carnitine insufficiency. Conclusions: Fatty acids are the primary energy source for diabetic heart muscle, and carnitine is essential for intracellular fatty acid transport and ATP production. Therefore, mild carnitine deficiency can compromise fatty acid energy production in a failing heart. Carnitine deficiency in subjects at high risk for cardiovascular failure is a possible unrecognized reason for the 4 fold increased death rate in patients with type 1 diabetes. Supplementation with oral carnitine could reduce that increased risk of heart failure, in patients with type 1 diabetes. Intravenous carnitine may be life saving when managing acute cardiac failure in patients with diabetes mellitus. Normal carnitine levels in patients with type 1 diabetes may provide a biochemical environment that prevents the long recognized idiopathic heart failure that occurs in insulin requiring diabetics as first reported in the 1974 Framingham Study.

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Section: Resultssupporting

confidence: 88%

Section: Methodssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 66%

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Diabetic Cardiovascular Risk and Carnitine Deficiency <br/>—Carnitine Deficiency in Clinical Diabetes Mellitus

Malone¹,

Malone²,

Morrison³

2014

JDM

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“…It was found that daily administrations of 2 -3 g of LC led to blood carnitine concentrations superior to normal levels (Bach et al, 1983;Baker et al, 1993;Brass et al, 2001). Rapid recovery of symptomatic plasma carnitine deficiency is obtained within 10 days by either oral high-dose treatment (3 -4 g) in a single administration or by more prolonged therapy (Bizzi et al, 1978;Campos et al, 1993). Mucosal absoption of LC is saturated by 2 g doses and oral fractioned treatment for higher doses is required (Farper et al, 1988).…”

Section: Treatment Plan With Lcmentioning

confidence: 99%

Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients

Graziano

Bisonni²,

Catalano³

et al. 2002

Br J Cancer

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Ifosfamide and cisplatin cause urinary loss of carnitine, which is a fundamental molecule for energy production in mammalian cells. We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients. Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry. Patients were excluded if they had anaemia or other conditions thought to be causing asthenia. Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life questionnaire. Treatment consisted of oral levocarnitine 4 g daily, for 7 days. Fifty patients were enrolled; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients. In the whole group, baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 (±6.4; standard deviation) and the mean plasma carnitine value was 20.9 μ M (±6.8; standard deviation). After 1 week, fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 (±5.4; standard deviation) ( P <.001). All patients achieved normal plasma carnitine levels. Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy. In selected patients, levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue. This compound deserves further investigations in a randomised, placebo-controlled study. British Journal of Cancer (2002) 86 , 1854–1857. doi: 10.1038/sj.bjc.6600413 www.bjcancer.com © 2002 Cancer Research UK

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“…Carnitine regulates the transport of fatty acids across the inner mitochondrial membrane and modulates the intracellular acy1CoA:free CoA ratio (2,3) ( Figure 1). It also enhances P-oxidation of longchain fatty acids, stimulates the respiratory chain, and interacts with membrane phospholipids (2)(3)(4)(5)(6)(7). Thus, carnitine insufficiency could produce wide metabolic derangement and impairment of muscle function.…”

mentioning

confidence: 99%

Abnormal carnitine distribution in the muscles of patients with idiopathic inflammatory myopathy

Arenas

Gonzalez-Crespo

Campos

et al. 1996

Arthritis & Rheumatism

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Objective. To analyze the levels of free carnitine and carnitine esters in the muscles of patients with inflammatory myopathies.Methods. Six men and 7 women with inflammatory myopathy and 25 age-matched healthy controls were studied. Free carnitine and carnitine esters in muscle homogenates were measured by a radiochemical procedure. Muscle histochemical staining and measurement of respiratory chain enzyme activity were also performed.Results. Eleven patients had muscle carnitine insufficiency. Five of them had subsarcolemmal oxidative accumulations, 5 had lipid droplets, and 4 had defects of the respiratory chain enzyme complexes.Conclusion. Abnormal distribution of muscle carnitine is present in patients with inflammatory myopathies and could impair muscle function. Coexistent mitochondrial dysfunction may contribute to carnitine insufficiency.Idiopathic inflammatory myopathies are a heterogeneous group of chronic inflammatory muscle disorders characterized by proximal muscle weakness, increased serum concentrations of creatine kjnase (CK), typical clectromyographic (EMG) changes, and mononuclear cell infiltration, with necrosis and regeneration of myocytes seen on muscle biopsy (1). Carnitine (p- hydroxy-y-trimethylammonium butyrate) is an intracellular constituent with essential metabolic functions, mainly for skeletal muscle, which uses fatty acids for its energy needs. In plasma and tissues, carnitine is present in free and esterified forms. Long-chain acylcarnitines and short-chain acylcarnitines result from the esterification of free carnitine with acyl-and acetyl-coenzyme A (CoA) groups. Carnitine regulates the transport of fatty acids across the inner mitochondrial membrane and modulates the intracellular acy1CoA:free CoA ratio (2,3) (Figure 1). It also enhances P-oxidation of longchain fatty acids, stimulates the respiratory chain, and interacts with membrane phospholipids (2-7). Thus, carnitine insufficiency could produce wide metabolic derangement and impairment of muscle function.In patients with primary mitochondrial myopathies (5,8,9) or zidovudine-induced mitochondrial myopathy (lo), muscle carnitine insufficiency is associated with mitochondrial dysfunction. We have previously reported histochemical signs of mitochondrial proliferation and respiratory chain defects in patients with inflammatory myopathies. It was proposed that these and perhaps other metabolic derangements could contribute to muscle weakness (11). To further explore other relevant metabolic alterations in patients with inflammatory myopathies, we have now studied the levels of free carnitine and carnitine esters in muscle from 13 patients. PATIENTS AND METHODSThirteen consecutive patients who were seen at the Hospital Doce de Octubre and for whom muscle biopsy specimens were available were studied. The group consisted of 7 women and 6 men, with a mean age at biopsy of 43 years (range 16-72 years). All met the Bohan and Pcter criteria for the diagnosis of polymyositis (PM) or dermatomyositis (DM) (12). Clinically, all had proxi...

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Plasma carnitine insufficiency and effectiveness of L‐carnitine therapy in patients with mitochondril myopathy

Cited by 89 publications

References 18 publications

Diabetic Cardiovascular Risk and Carnitine Deficiency <br/>—Carnitine Deficiency in Clinical Diabetes Mellitus

Diabetic Cardiovascular Risk and Carnitine Deficiency <br/>—Carnitine Deficiency in Clinical Diabetes Mellitus

Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients

Abnormal carnitine distribution in the muscles of patients with idiopathic inflammatory myopathy

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Plasma carnitine insufficiency and effectiveness of L‐carnitine therapy in patients with mitochondril myopathy

Cited by 89 publications

References 18 publications

Diabetic Cardiovascular Risk and Carnitine Deficiency &lt;br/&gt;—Carnitine Deficiency in Clinical Diabetes Mellitus

Diabetic Cardiovascular Risk and Carnitine Deficiency &lt;br/&gt;—Carnitine Deficiency in Clinical Diabetes Mellitus

Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients

Abnormal carnitine distribution in the muscles of patients with idiopathic inflammatory myopathy

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Resources

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Diabetic Cardiovascular Risk and Carnitine Deficiency <br/>—Carnitine Deficiency in Clinical Diabetes Mellitus

Diabetic Cardiovascular Risk and Carnitine Deficiency <br/>—Carnitine Deficiency in Clinical Diabetes Mellitus