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L-carnitine



Depletions

L-carnitine/Nutrient Depletion:
  • Adefovir dipivoxilAdefovir dipivoxil: According to a clinical trial, adefovir dipivoxil may reduce free carnitine levels (549).
  • AntibioticsAntibiotics: Acute encephalopathy occurred in a child with secondary carnitine deficiency due to pivalate-conjugated antibiotics (566; 567). Further details are not available . In two patients, use of pivalate-containing antibiotics resulted in the detection of pivaloyl-carnitine in the blood and reduced free carnitine levels (568). The effect of pivalic acid on carnitine levels has been reviewed (569; 570). In animal research, carnitine reduced renal oxidative damage associated with ceftriaxone treatment (571). In animal research, pivalic acid resulted in reduced carnitine levels (572). Mechanisms associated with pivalic acid-induced reduction of carnitine have been investigated in vitro (573; 574).
  • Anticonvulsants (phenobarbital, phenytoin, carbamazepine)Anticonvulsants (phenobarbital, phenytoin, carbamazepine): Reviews, systematic reviews, and case studies have concluded that valproic acid use lowers carnitine levels in some, but not all studies and that carnitine may be considered for valproic acid general toxicity; however, measurement of carnitine levels is warranted in order to determine the need (473; 474; 576; 577; 148; 578; 579; 580; 581; 582; 583; 584; 585; 586; 587; 588; 477; 589; 590; 591; 592; 593; 594; 206) and hepatotoxicity (595). Decreased serum carnitine has been noted in children using anticonvulsants, and in particular, phenobarbital, phenytoin, and carbamazepine (596). In some studies in children, new generation antiepileptic agents did not appear to decrease carnitine levels and decreases in carnitine related to anticonvulsants have not been shown in all studies (597; 585; 598).
  • Antineoplastics (general)Antineoplastics (general): Carnitine plasma levels were determined in children and adolescents receiving cisplatin, ifosfamide, or doxorubicin (626). It was determined that levels were increased in doxorubicin-treated patients vs. the other two. Decreased levels may be associated with fatigue. Further details are not available. Decreased levels of carnitine associated with chemotherapy have been shown in other human studies, but limited details available (627).
  • CarboplatinCarboplatin: In humans, carboplatin stimulated urinary loss of carnitine and acetyl-L-carnitine by inhibiting kidney reabsorption (643).
  • CefepimeCefepime: In animal research, an acute administration of cefepime lowered L-carnitine concentrations in rat milk in the early stage (662). This agent was found to complete with L-carnitine for transport.
  • CephalosporinsCephalosporins: Clinical studies with S-1108, a cephalosporin, suggest that this drug may reduce plasma carnitine levels (663; 664).
  • CholineCholine: According to a controlled trial, serum and urinary carnitine may decrease with choline supplementation (934).
  • CisplatinCisplatin: According to a case series, cisplatin may increase urinary excretion of carnitine, but the loss in the study did not exceed 3-5% and was easily replenished with food (666).
  • ClofibrateClofibrate: In animal research, use of clofibrate increased hepatic carnitine levels but decreased plasma carnitine levels (678). In vitro studies suggest that clofibrate stimulates carnitine cellular uptake and not synthesis (679).
  • DoxorubicinDoxorubicin: In children, doxorubicin treatment resulted in reduced carnitine levels; supplementation with carnitine did not improve carnitine levels or improve doxorubicin-induced changes on cardiac function (682). Negative effects of doxorubicin on carnitine levels have not been shown, but not in all human studies (687; 688). In vitro, carnitine did not reduce the anticancer effects of epirubicin (689).
  • GentamicinGentamicin: In animal research, gentamicin increased urinary loss of carnitine and decreased levels in blood; carnitine supplementation increased levels in plasma and prevented kidney damage (712).
  • GlucoseGlucose: Carnitine or its derivatives have shown blood glucose-lowering effects in animal models and humans, as well as protective effects against pathological states associated with diabetes in animal models (246; 247; 248; 249; 250; 251; 252; 253; 340; 240; 254; 600; 601; 602; 603). However, in separate study in human research, L-carnitine lacked effect on glucose levels (389) and in preterm infants, glucose levels increased (604). In patients with type 2 diabetes, the additional effects of carnitine over simvastatin alone resulted in decreased glycemia (p<0.001) (605). Carnitine had a lack of effect or resulted in a decrease of plasma glucose during exercise (606; 368).
  • IfosfamideIfosfamide: Increased urinary loss of carnitine has been noted (720). During one chemotherapy cycle, patients lost about 10% of their carnitine stores in a clinical trial.
  • InsulinInsulin: In patients with diabetes, insulin use was associated with lower carnitine levels in blood vs. oral antidiabetic use (983).
  • Ketogenic dietKetogenic diet: In patients on a ketogenic diet, asymptomatic carnitine depletion occurred (937). The effect of a ketogenic diet on carnitine metabolism was investigated in a separate study (938). Further details are limited .
  • LysineLysine: In animal research, a moderate excess of dietary lysine lowered plasma and tissue carnitine concentrations (912).
  • MildronateMildronate: In animal research, mildronate treatment resulted in reduced plasma and tissue levels of carnitine (744; 745; 746; 747; 748; 749; 750). The efficacy of mildronate is based on its ability to inhibit carnitine biosynthesis (752; 753; 746; 754), and mildronate is transported with the OCTN2 carnitine transporter (757; 758).
  • NatalizumabNatalizumab: Carnitine serum levels were examined in multiple sclerosis patients treated with natalizumab (760). Further details are not available .
  • Oxidized fatsOxidized fats: In animal research, oxidized fat resulted in increased hepatic carnitine and decreased plasma carnitine levels (946).
  • Penicillin derivatives (pivaloyloxymethyl-esterified; pivampicillin and pivmecillinam)Penicillin derivatives (pivaloyloxymethyl-esterified; pivampicillin and pivmecillinam): According to two clinical studies, penicillin derivatives may decrease in serum carnitine concentration, elevate excretion of acyl-carnitine, and reduce muscle carnitine concentration (813; 814). No clinical signs of carnitine deficiency were reported. In seven children, pivampicillin treatment reduced levels of total carnitine, free carnitine, and acyl-carnitines (815).
  • Phenylketonuric (PKU) dietPhenylketonuric (PKU) diet: In human research, the PKU diet was associated with decreased carnitine levels (948).
  • Plasma lipidsPlasma lipids: Carnitine was reported to reduce the level of serum triglycerides in patients with hyperlipidemia (612; 613), as well as in animals (614; 615), infants (616; 617), and other populations (257; 313; 618; 331; 619; 620; 478; 312; 266; 444; 445; 605). Decreased cholesterol has als been noted (257; 621; 618; 331; 614; 478; 265; 266; 312; 445). In pregnant women, carnitine reduced levels of free fatty acids and triglycerides (slightly) (503).
  • PropiconazolePropiconazole: In animal research, propiconazole altered levels of carnitine (820). Further details are not available.
  • Valproic acidValproic acid: Reviews, systematic reviews, and case studies have concluded that valproic acid use lowers carnitine levels in some, but not all studies and that carnitine may be considered for valproic acid general toxicity; however, measurement of carnitine levels is warranted in order to determine the need (473; 474; 576; 577; 148; 578; 579; 580; 581; 582; 583; 584; 585; 586; 587; 588; 477; 589; 590; 591; 592; 593; 594; 206) and hepatotoxicity (595). In children treated with valproic acid, a significant reduction was found in muscle carnitine content (833). The effects of valproic acid on carnitine status (muscle, serum) and associated adverse effects, as well as use of carnitine in valproate toxicity, have been discussed in reviews and other publications (142; 834; 835; 836; 837; 838) and human studies (839; 840; 841; 842; 843; 844; 845; 846), although decreases in free carnitine have not been shown in all human studies (848; 294).
  • Zidovudine (AZT)Zidovudine (AZT): In human research, AZT reduced muscle carnitine levels (858).
  • Zwitterionic drugs (levofloxacin and grepafloxacin)Zwitterionic drugs (levofloxacin and grepafloxacin): In vitro, in Caco-2 cells, zwitterionic drugs inhibited carnitine cellular uptake (859).

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