Deficiency of Carnitine in Cachectic Cirrhotic Patients

Abstract

A 3 S T RA C T Carnitine is synthesized from lysine and metlhionine. In the rat, inade(quiate intake of either of these essential amino acids cauises carnitinie depletioIn 14 of' 36 hospitalized cirrhotics hald subnormal valtues for seruim carnitine. The creatinine/height index, midarm munscle circumference, and triceps skin-fold thickness indicated protein-calorie starvation in the 14 hypocarnitinemic liver patients. In six of the hypocarnitinemic cirrhotics (average seruim level 50% of normal), spontaneouis dietary intakes of' carnitine, lysine, and methionine were measuired and foulnd to be only 5-15% as great as in six normocarnitinemiic, healthy controls. When these six cirrhotic anuI six normnal stil)jects were given the same lysine-rich, methioninle-ricl, and carnitine-free nultritionaitl intake, the normaiitls mnain tained n oi-'matl serumiii camr iti ne levels and exeretedl 100 tLmol/day, wvhereas the cirrlhoties' sertum level fell to 25% of noimatl, and(l uirinary excretion dec ined to 15 Lmol/day. Seven lhypocarniitiniemic cirrhotics dlie(l. P'ostmlortemn concentratioons of' carnitine in liver, musele, heart, kidney, and brain averagedl only one-fouirtlh to onethir(d those in corresponding tisstues of eight normally noutrished nonhepatic patients who died after an actute illness of a 1-3-day duiration.These data show that carn-itine depletion is common in pattients hospitalized for advanced cirrhosis, and that it resuilts from three factors: stubstandard intake of dietary carnitine; substandard intake of lysine and methionine, the prectursors ftor endlogenouis carnitine synthesis; acnd loss of' cappacity to syntlhesize carnitine from lysine and methiioniine.

Renal Handling of Carnitine in Secondary Carnitine Deficiency Disorders

“…Both plasma and urine total carnitine values remained slightly above the means of untreated control children at the end of the study, suggesting that the effect of high-dose carnitine supplements had not been entirely eliminated. This is consistent with observations that 6-8 d are required before reductions in carnitine intake are fully reflected by changes in urinary excretion rates (19). In contrast to this normal response to carnitine withdrawal, there was a rapid redevelopment of severe plasma total carnitine deficiency in the patient with a genetic defect in carni- tine transport affecting kidney and muscle (9) in whom renal conservation of carnitine is absent (Fig.…”

“…Because carnitine is not degraded, turnover is limited to input from endogenous synthesis plus dietary sources, such as meats and milk, and output through urinary excretion. Approximately 75% of new carnitine is usually provided from the diet, based on the differences in urinary total carnitine excretion rates between individuals on normal and on carnitine-free diets for prolonged periods (19,20). The remaining 25% comes from endogenous synthesis of carnitine from trimethyllysine residues released during protein turnover.…”

“…As noted above, like other Ntrimethylated substrates, such as trimethylhistidine, carnitine cannot be degraded in the body, but must be eliminated by excretion in the urine (I). Dietary carnitine deficiency, either acute (see Results) (19) or chronic (20), has little effect on plasma carnitine levels, except in very young infants (21), due to efficient renal conservation of carnitine. Dietary deficiency probably contributed to the very low plasma concentrations of carnitine seen in LCAD case 2 when first studied compared with the values noted at the end of the withdrawal study (Tables 1 and 2).…”

Hypoglycemia, Hepatic Dysfunction, Muscle Weakness, Cardiomyopathy, Free Carnitine Deficiency and Long-Chain Acylcarnitine Excess Responsive to Medium Chain Triglyceride Diet

“…He also had severe anorexia, recurrent infections, and developed postnecrotic cirrhosis. Although he had low liver carnitine levels, this could be readily explained by cachexia and severe hepatocellular injury (36). (2) The liver carnitine level in Patient 2 was only slightly below the lower normal level and it is difficult to explain how such a slight decrease could result in severe impairment of fatty acid oxidation.…”

Decreased carnitine biosynthesis in rats with secondary biliary cirrhosis

“…[21][22][23] In contrast, in cachectic patients with cirrhosis of diverse etiologies, urinary carnitine excretion and tissue and plasma carnitine concentrations were decreased as compared with control patients, suggesting impaired carnitine biosynthesis. 24 Rats with secondary biliary cirrhosis induced by long-term bile duct ligation (BDL) have increased hepatic carnitine content with a shift in the ratio of acylcarnitines/carnitine toward acylcarnitines in the fed state. 25,26 These changes in the hepatic carnitine pool are accompanied by an increase in urinary acylcarnitine excretion, whereas the total carnitine excretion is unchanged during feeding of a carnitinecontaining diet.…”