Acetyl-L-carnitine

L-carnitine/Drug Interactions:

  • GeneralGeneral: In psychiatric inpatients, the use of polypharmacy and valproic acid, individually, were associated with low serum carnitine levels (537). Diao et al. discussed the quantitative structure activity relationship for inhibition of the human organic cation/carnitine transporter (OCTN2) (538). Sinicropi et al. examined the behavior of acetyl-L-carnitine injections (Nicetile fiale) in combination with different drugs used for combined therapy (539). The authors concluded that the content of all the active drugs after mixing remained optimal, within 10% of their nominal values. Diao et al. discussed novel inhibitors of OCTN2 based on computational modeling and in vitro testing (540). It was determined that compounds were more likely to cause rhabdomyolysis if the C(max):K(i) ratio was higher than 0.0025.
  • 2,3-Dimercapto-1-propanesulfonic acid2,3-Dimercapto-1-propanesulfonic acid: In animal research, 2,3-dimercapto-1-propanesulfonic acid prevented mercuric chloride-induced increases in urinary excretion of carnitine (541).
  • 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy)3,4-Methylenedioxymethamphetamine (MDMA; ecstasy): In animal research, MDMA increased heart tissue carnitine levels (542).
  • AcetaminophenAcetaminophen: In animal research, carnitine had hepatoprotective effects, based on improvement in liver enzymes and histopathologic changes, against acute acetaminophen toxicity (543). In animal research, carnitine also reduced ototoxic effects of acetaminophen with or without hydrocodone (544). In animal research, carnitine deficiency was associated with paracetamol use and was thought to play a role in hepatotoxicity associated with paracetamol (545). Carnitine supplementation improved biochemical markers and mitigated histologic alterations induced by paracetamol.
  • Acetylcholinesterase (AChE) inhibitorsAcetylcholinesterase (AChE) inhibitors: In children, 100mg/kg of carnitine daily for three months showed evidence of benefit over regular therapy alone (digoxin, diuretics, ACE inhibitors) (546). In animal research, galantamine antiacetylcholinesterase activity was increased (although not statistically significantly) by carnitine (547). In animal research, carnitine both increased and decreased the intestinal absorption of 7-methoxytacrine, depending on length of treatment of the individual agents (548).
  • Adefovir dipivoxilAdefovir dipivoxil: According to a clinical trial, adefovir dipivoxil may reduce free carnitine levels (549).
  • AdriamycinAdriamycin: According to animal studies, carnitine may prevent arrhythmias provoked by Adriamycin (550) and offer benefits against Adriamycin toxicity (551).
  • AlcoholAlcohol: In animal research, carnitine had a lack of effect on body weight, diet consumption, urinary nitrogen excretion, plasma free fatty acids, or lysine, methionine, and glycine levels in alcoholic malnourished rats (552).
  • Alpha-interferonAlpha-interferon: In a randomized trial, the addition of 2g of carnitine daily to alpha-interferon and ribavirin treatment reduced steatosis in 70 patients with chronic hepatitis C (553). The addition of carnitine resulted in significantly (p<0.05) greater reductions of alanine transaminase (ALT), total cholesterol, and triglycerides, with greater reductions in aspartate transaminase (AST) and ALT at follow-up.
  • Alzheimer's agentsAlzheimer's agents: Although evidence of benefit of acetyl-L-carnitine is mixed in human research (316), beneficial effects of acetyl-L-carnitine have been observed in various Alzheimer's disease animal models, as well as in vitro, either alone or in combination with other agents (554; 555; 556; 557; 558). In animal research, carnitine reduced acetylcholinesterase activities in the plasma and some tissues (559). Some change in acetylcholinesterase and butyrylcholinesterase activities in the brain and peripheral tissues occurred with carnitine, but specific details are not available (560).
  • AmiodaroneAmiodarone: In vitro, carnitine and acetyl-L-carnitine reversed amiodarone-induced injury in cultured lung cells by reducing mitochondrial membrane depolarization and cellular ATP depletion (561).
  • AnalgesicsAnalgesics: In an animal diabetic model, acetyl-L-carnitine improved hypoalgesic effects (562). In vitro, analgesic effects of acetyl-L-carnitine were shown (563; 564). The role of acetyl-L-carnitine in neuropathic pain was discussed in a review (565).
  • 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; 575).
  • AnticoagulantsAnticoagulants: According to a clinical trial of patients with angina, L-carnitine may decrease the need for anticoagulants (257). In vitro, carnitine decreased platelet aggregation (258; 259).
  • AnticonvulsantsAnticonvulsants: 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).
  • AntidepressantsAntidepressants: In human and animal research, antidepressant effects of acetyl-L-carnitine were shown (599; 316).
  • AntidiabeticsAntidiabetics: 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). Increased triglycerides, increased Apo B 100, increased Apo A1, and decreased glucose were observed in individuals with diabetes using L-carnitine (253). Carnitine levels did not change in diabetics with insulin or sulfonylurea therapy (607). In an animal diabetic model, carnitine reduced tissue ACE activity, possibly due to increased nitric oxide production (608).
  • AntihypertensivesAntihypertensives: Use of carnitine resulted in decreased blood pressure during exercise (239) or in patients with insulin sensitivity (240) and increased blood pressure in patients with congestive heart failure (242). In animal research, carnitine reduced blood pressure levels (236; 237; 238). Hypertension was reported in three subjects using oral carnitine (241).
  • Anti-inflammatoriesAnti-inflammatories: In hemodialysis patients, carnitine reduced levels of C-reactive protein and fibrinogen (609; 454). In vitro, a mixture of carnitine, thioctic acid, and saw palmetto decreased induced inflammation in keratinocytes by suppressing genes activated during the inflammatory response, such as CCL17, CXCL6, and leukotriene B4 (610). In an animal arthritis model, carnitine reduced malondialdehyde (MDA) levels and increased glutathione levels, resulting in reduced inflammation (611).
  • AntilipemicsAntilipemics: According to a clinical trial of angina patients, L-carnitine decreased the need for antilipidemic drugs (257). Carnitine was reported to reduce the level of serum triglycerides in patients with hyperlipidemia (612; 613). In patients with type 2 diabetes, the additional effects of carnitine over simvastatin alone resulted in decreased triglycerides (p<0.001), apo B (p<0.05), Lp(a) (p<0.05), and apo(a) (p<0.05), and significant increases in HDL cholesterol (p<0.05) (605). 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). Increased triglycerides, Apo B100, and Apo A1 were found in individuals with diabetes on glyburide or metformin (253) and in uremic patients on hemodialysis (255). Decreased cholesterol has been noted (257; 621; 618; 331; 614; 478; 265; 266; 312; 445). Increased HDL has been noted (621; 622; 623; 618; 619; 312). A decreased ratio of total cholesterol to HDL cholesterol has been noted (622; 623). No changes in Apo A1 or Apo B were noted in hypertensive individuals (618), but they were reduced in elderly individuals and other studies (312; 266; 624). No changes in triglycerides, total cholesterol, HDL cholesterol, ApoA, or Apo B were noted in other studies (497; 619; 351; 455; 389; 472). In pregnant women, carnitine reduced levels of free fatty acids and triglycerides (slightly) (503). In a high-fat diet animal model, carnitine normalized the lipid profile (625).
  • AntineoplasticsAntineoplastics: 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. Decreased levels of carnitine associated with chemotherapy have been shown in other human studies, although limited details are available (627). Acetyl-L-carnitine may have protective effects against chemotherapy-induced pain (628), and a review suggests the promise of carnitine for adverse effects of antineoplastics (189). The anticancer effects of carnitine have been shown in various in vitro studies (629; 630; 631).
  • Antiobesity agentsAntiobesity agents: In animal research using a neonatal model, carnitine resulted in reduced food intake in later life but did not affect body weight (632). In an animal model, propionyl-L-carnitine reduced body weight, food intake, and adiposity (633).
  • AntiretroviralsAntiretrovirals: According to a review, acetyl-L-carnitine use is associated with reduced HIV-associated antiretroviral toxic neuropathy (634). In vitro, carnitine protected against the oxidative effects of antiretrovirals (635) and prevented impaired fatty acid oxidation and lipid export, as well as liver abnormalities, due to stavudine (636; 637).
  • Aristolochic acidAristolochic acid: In animal research, aristolochic acid resulted in reduced levels of carnitine in the renal cortex of rats (638).
  • AzithromycinAzithromycin: In human research, azithromycin resulted in reduced symptoms in individuals with chronic fatigue syndrome who were already being treated with carnitine, but with inadequate benefits and inadequate acetyl-carnitine status (639).
  • Beta-blockersBeta-blockers: According to a clinical trial of patients with angina, L-carnitine may decrease the need for beta-blockers (257).
  • BupivacaineBupivacaine: In a case series, carnitine deficiency was found to increase susceptibility to bupivacaine toxicity of the heart (640). In animal research, addition of carnitine to carnitine-deficient animals reduced the cardiotoxicity of bupivacaine (641).
  • Calcium-channel blockersCalcium-channel blockers: According to clinical trials of patients with angina, L-carnitine may decrease the need for calcium channel blockers (256; 257).
  • CarboplatinCarboplatin: In animal research, carnitine deficiency aggravated carboplatin nephropathy, and carnitine supplementation ameliorated the negative effects of this deficiency (642). In humans, carboplatin stimulated urinary loss of carnitine and acetyl-L-carnitine by inhibiting kidney reabsorption (643). Carnitine showed no cytotoxicity on carboplatin in vitro (644).
  • Cardiovascular agentsCardiovascular agents: Results from human research are indicative of the efficacy of propionyl-L-carnitine and L-carnitine in treatment of peripheral vascular disease (424; 469; 269; 293; 422; 468; 466; 467; 465; 421; 645; 416; 417; 418; 419; 420; 646; 647; 648; 649; 650; 651; 652; 275; 653; 423; 654; 464; 655; 656). The cardiovascular protective effects of L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine have also been shown in animal or organ models (657; 633; 658; 659; 660; 661).
  • 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).
  • CinnoxicamCinnoxicam: L-carnitine plus acetyl-L-carnitine plus cinnoxicam were more effective in improving sperm parameters than L-carnitine plus acetyl-L-carnitine alone (665).
  • CisplatinCisplatin: According to a case series, cisplatin may increase urinary excretion of carnitine, but the loss did not exceed 3-5% and was easily replenished with food (666). Cisplatin, oxaliplatin, and carboplatin resulted in increased renal excretion of carnitine in patients (667). According to a case series, carnitine may reduce neuropathy symptoms associated with cisplatin use (274), as well as diminish fatigue (668). In animal studies, acetyl-L-carnitine improved cisplatin-induced auditory impairments, perhaps due to its antioxidant and antiapoptotic effects (669). In animal research, propionyl-L-carnitine reversed cisplatin-induced carnitine deficiency and improved renal and hepatic parameters (670; 671). In animal research, carnitine protected against cisplatin-induced nephrotoxicity in some (672), but not all (673), studies. In combination with alpha-lipoic acid and silymarin, carnitine protected against cisplatin-induced cardiotoxicity, based on biochemical measurements (674). In animal research, cisplatin-induced urinary excretion of carnitine was due to downregulation of OCTN2 (675). In vitro, acetyl-L-carnitine protected against cisplatin cytotoxicity and oxidative stress in neuroblastoma cells (676) and improved the chemotherapeutic effects of cisplatin (677).
  • 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). In animal research, clofibrate increased intestinal absorption of carnitine (680).
  • CyclophosphamideCyclophosphamide: Carnitine was associated with evidence of benefit in a subgroup of patients with fatigue due to interferon-beta and cyclophosphamide (270).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: In vitro, the combination of carnitine and methanol stimulated CYP2E1 (681).
  • DigoxinDigoxin: According to a clinical trial of patients with congestive heart failure, L-carnitine may decrease the need for digoxin (331). In children, 100mg/kg of carnitine daily for three months showed evidence of benefit over regular therapy alone (digoxin, diuretics, ACE inhibitors) (546).
  • DiureticsDiuretics: According to a clinical trial of patients with angina, L-carnitine may decrease the need for diuretics (257). In a study of patients with left ventricular dysfunction, no adverse effects were noted when diuretics were used with carnitine (332). In children, 100mg/kg of carnitine daily for three months showed evidence of benefit over regular therapy alone (digoxin, diuretics, ACE inhibitors) (546).
  • 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). In animals, the protective effect of carnitine against doxorubicin toxicity was shown (683; 684), and it was determined to be due to its antioxidant effects (685). The protective effects of carnitine against doxorubicin toxicity have also been shown in vitro (686). Negative effects of doxorubicin on carnitine levels have been shown, but not in all human studies (687; 688). In vitro, carnitine did not reduce the anticancer effects of epirubicin (689).
  • Drugs used for osteoporosisDrugs used for osteoporosis: In animal research, carnitine improved bone mineral density (690).
  • ErythropoietinErythropoietin: In hemodialysis patients, there was a negative correlation between erythropoietin (EPO) levels and carnitine levels (691). In human research, combined therapy with carnitine and EPO for anemia in chronic kidney failure patients undergoing hemodialysis resulted in a reduced dosage of EPO (692; 693; 351) and increased hemoglobin levels (693; 694). In a animal model, a carnitine-mediated improved response to EPO was found to involve the induction of heme oxygenase-1 (695), and decreased carnitine levels were associated with a decreased response to EPO-stimulating agents (696). According to a review, nutrient deficiencies, including carnitine, resulted in EPO-stimulating agent hyporesponsiveness (697). The effect of carnitine administration on EPO use in thalassemic minor hemodialysis patients was discussed (698). Further details are not available.
  • Exercise performance agentsExercise performance agents: In human research, a change in performance was related to changes in acetyl-L-carnitine (699). In human athletes, total antioxidant status was unaltered and enzyme activities (acetylcholinesterase and ATPases) were reduced following exercise in a carnitine-supplemented population (700). In animal research, the addition of nutrients, including acetyl-L-carnitine (as well as alpha-lipoic acid, vitamins, CoQ10, etc.), increased mitochondrial biogenesis and performance in exhaustively exercised rats; the antioxidant effects of this nutrient mixture were implicated (701). In animal research, carnitine attenuated intermittent hypoxia-induced oxidative stress and delayed muscle fatigue (702). In vitro, carnitine restored acetylcholinesterase activity (703).
  • Fertility agentsFertility agents: In human research, although L-carnitine increased the percentage of grade a + b sperm, significant changes in sperm concentration, sperm motility, and rate of sperm deformity were lacking (272). In animal research, L-carnitine enhanced oocyte maturation as well as the development of parthenogenetic embryos in pigs (514) and improved oocyte developmental competence in mice (515). In animal research, oral L-carnitine reduced the negative effects of oxidative stress on structure and functions of ovary and oocytes during repeated ovulation (526). In vitro, carnitine promoted meiotic resumption in mouse oocytes (704). In the presence of carnitine, human testis sperm cultured from azoospermic patients increased in motility (% motile sperm increase and % forward moving), with a lack of change in normal morphology (705). In human research, the level of free carnitine in the seminal plasma of fertile men was increased vs. infertile men, and the level of free carnitine in the semen was positively correlated with sperm concentration (706).
  • FluoroquinolonesFluoroquinolones: In vitro, fluoroquinolones inhibited carnitine transport in the placental cell line BeWo (707).
  • Gastrointestinal agentsGastrointestinal agents: In a randomized clinical trial there was a small increase in clinical and endoscopic response in patients treated with oral colon-release propionyl-L-carnitine tablets (311). Although gastrointestinal symptoms are associated with supplemental carnitine use (263; 264; 265; 266; 267; 268; 269; 270; 271; 272; 273; 274; 275; 276; 241; 277; 278; 279; 280; 278; 281; 282; 283; 284; 285; 286; 287; 288; 289; 290; 291; 292; 293; 294; 295; 296; 297), in animal research, carnitine protected against damage to the intestine or symptoms of gastrointestinal pathology (708; 709; 710; 711).
  • 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).
  • GlycosidesGlycosides: According to a clinical trial of angina patients, L-carnitine may decrease the need for glycosides (257).
  • Hair agentsHair agents: In vitro, carnitine-L-tartrate promoted human hair growth in cultured hair follicles; potential mechanisms of action include downregulation of apoptosis and induced proliferation by prolonged duration of anagen VI and reduced TGFbeta2 and caspase-3 and -7 (713).
  • HepatotoxinsHepatotoxins: Evidence from randomized controlled trials suggests that L-carnitine may be of benefit to individuals with hepatic encephalopathy, in terms of bilirubin, ammonia, urea, and liver enzymes (384; 292; 383; 277; 458; 382; 381; 291; 411; 377; 406). In human research, acetyl-L-carnitine reduced levels of AST, ALT, and hepatitis C viremia; significant between-group difference in levels of bilirubin and albumin were lacking (385; 280; 384). In animal research, carnitine protected against liver injury (714; 715; 716; 717; 718).
  • Heart rate-regulating agentsHeart rate-regulating agents: According to a clinical trial of patients with angina, L-carnitine may decrease the need for antiarrhythmics (257). In animal research, carnitine worsened injury and recovery of contractile function after transient ischemia in perfused rat heart (487). The authors indicated that carnitine resulted in a slower increase in heart rate (hr) and contractile force, as well as contracture of the heart after reperfusion.
  • HydroxyureaHydroxyurea: In a clinical trial, a combination of hydroxyurea plus carnitine resulted in changes in echocardiographic studies with respect to significant decreases in left ventricular end-diastolic diameter over hydroxyurea alone (p=0.032), and the authors suggested that a combination with hydroxyurea and carnitine may be more effective than hydroxyurea alone (719).
  • IfosfamideIfosfamide: Increased urinary loss of carnitine has been noted. During one chemotherapy cycle, patients lost about 10% of their carnitine stores in a clinical trial (720). Carnitine has been suggested to reduce fatigue associated with ifosfamide (668) and in animal research, ifosfamide-induced Fanconi syndrome was reduced (721; 722),
  • ImmunostimulantsImmunostimulants: In a clinical study, high-dose carnitine resulted in an increase in lymphocyte proliferation responsiveness to mitogens (723). In a clinical study, carnitine treatment resulted in a strong reduction in the percentage of CD4 and CD8 cells undergoing apoptosis, which is involved in T cell depletion in AIDS (724). Acetyl-L-carnitine administered to patients with active pulmonary tuberculosis for 30 days upregulated T cell-dependent antibacterial activity, which decreased in patients receiving placebo only (725; 726). An influence on the serum level of tumor necrosis factor was lacking.
  • ImmunosuppressantsImmunosuppressants: In a clinical study, high-dose carnitine resulted in an increase in lymphocyte proliferation responsiveness to mitogens (723). In a clinical study, carnitine treatment resulted in a strong reduction in the percentage of CD4 and CD8 cells undergoing apoptosis, which is involved in T cell depletion in AIDS (724). Acetyl-L-carnitine administered to patients with active pulmonary tuberculosis for 30 days upregulated T cell-dependent antibacterial activity, which decreased in patients receiving placebo only (725; 726). An influence on the serum level of tumor necrosis factor was lacking.
  • IndomethacinIndomethacin: In animal research, carnitine reduced gastric mucosal injury due to indomethacin (727).
  • Insulin preparationsInsulin preparations: High-circulating insulin (?90mU/L) was capable of stimulating skeletal muscle carnitine accumulation (728). In animal research, propionyl-L-carnitine reduced serum levels of insulin and insulin resistance (633). In human research, carnitine decreased plasma insulin (340).
  • Interferon-alphaInterferon-alpha: Biochemical and clinical improvements occurred in carnitine-treated patients with chronic hepatitis C being treated with pegylated interferon-alpha 2b (Peg-IFN-alpha 2b) plus ribavirin (RBV) (385; 280). L-carnitine also reduced fatigue associated with IFN-alpha (729).
  • Interferon-betaInterferon-beta: Carnitine was associated with evidence of benefit in a subgroup of patients with fatigue due to interferon-beta and cyclophosphamide (270).
  • InterleukinsInterleukins: According to a randomized controlled trial of cancer patients, L-carnitine supplementation may reduce side effects associated with IL-2 (730)
  • IrradiationIrradiation: In animal research, carnitine protected growing bone against single-dose irradiation damage (731).
  • IsotretinoinIsotretinoin: According to a clinical study, supplementation with carnitine may improve liver and muscular side effects associated with isotretinoin in acne patients (732). In human research, isotretinoin lacked effect on levels of serum carnitine (733).
  • LeupeptinLeupeptin: In animal research, a leupeptin-based inhibitors (leupeptin bound to carnitine) was not found to improve the mdx phenotype (animal model for Duchenne muscular dystrophy) (734).
  • LevamisoleLevamisole: In vitro, carnitine uptake in BeWo cells was decreased by levamisole (735).
  • LevofloxacinLevofloxacin: In vitro, the apical uptake transporter of levofloxacin was inhibited by carnitine (736). In human intestinal epithelial LS180 cells in vitro, the uptake of levofloxacin was only slightly inhibited by carnitine (737).
  • Lymphoblastoid interferon-alphaLymphoblastoid interferon-alpha: In humans, serum carnitine levels increased following lymphoblastoid interferon-alpha treatment in hepatitis C patients (738).
  • Memory agentsMemory agents: In animal research, acetyl-L-carnitine improved spatial memory (739).
  • MethamphetamineMethamphetamine: In vitro, acetyl-L-carnitine suppressed the effects of methamphetamine in primary human brain endothelial cells on glucose update and blood-brain barrier function (740). In animal research, acetyl-L-carnitine prevented methamphetamine-induced behavioral sensitization in mice (741), and protective effects against toxicity and withdrawal symptoms have been shown in other animal studies (742; 743).
  • MildronateMildronate: In animal research, mildronate treatment resulted in reduced plasma and tissue levels of carnitine (744; 745; 746; 747; 748; 749; 750; 751). The efficacy of mildronate is based on its ability to inhibit carnitine biosynthesis (752; 753; 746; 754; 755; 756), and mildronate is transported with the OCTN2 carnitine transporter (757; 758).
  • MitoxantroneMitoxantrone: In animal research, mitoxantrone-L-carnitine combination therapy had a lack of potentiating effect on the efficacy of mitoxantrone on an experimental solid form of Ehrlich tumor (759). In animal research, acetyl-L-carnitine in addition to mitoxantrone increased metastases (489).
  • NatalizumabNatalizumab: Carnitine serum levels were examined in multiple sclerosis patients treated with natalizumab (760). Further details are not available.
  • NephrotoxinsNephrotoxins: In animal research, carnitine, acetyl-L-carnitine, and propionyl-L-carnitine protected against renal toxicity in various models (761; 762; 763; 764; 765; 766; 767; 768; 769).
  • Neurologic agentsNeurologic agents: In animal research, carnitine, acetyl-L-carnitine, and palmitoyl-L-carnitine had neuroprotective effects (770; 771; 772; 773; 774; 775; 776; 777; 778; 779; 780; 781; 782; 783; 784; 785; 786; 787; 788; 789; 790; 791; 792; 793; 794; 795).
  • Nipecotic acidNipecotic acid: Napolitano et al. discussed carnitine conjugation of nipecotic acid as a new example of dual prodrug (796). Its capacity to antagonize pentylenetetrazol (PTZ)-induced convulsions was investigated, but further details are not available.
  • Nitro derivativesNitro derivatives: According to a clinical trial of angina patients, L-carnitine may decrease the need for nitro derivatives (257).
  • NortriptylineNortriptyline: According to a study in rabbits, carnitine may prevent widening of PQ and QRS intervals in electrocardiogram (ECG) caused by nortriptyline (797).
  • Nucleoside analogsNucleoside analogs: In a clinical trial, subjects suffering from neuropathy induced by nucleosides had significantly reduced levels of acetyl-carnitine compared to the control group (798).
  • OCTN2 inhibitorsOCTN2 inhibitors: In a review, Diao et al. discussed the synthesis and in vitro characterization of drug conjugates of L-carnitine as potential prodrugs that target human OCTN2 (799).
  • Ophthalmic agentsOphthalmic agents: Benefits were observed in clinical trials investigating eye drops containing carnitine and other ingredients (800; 801). In experimental glaucoma, carnitine reduced the lipoperoxidative damage of the membrane and apoptosis after induction of cell stress (802). In animal research, acetyl-L-carnitine protected against selenite-induced cataractogenesis (803; 804; 805; 806; 807).
  • Opioid antagonistsOpioid antagonists: In animal research, carnitine had a lack of effect on the blood brain-barrier transport of naloxone (808).
  • OrlistatOrlistat: In human research, carnitine reduced body weight (p<0.05), HbA1C (p<0.05), fasting plasma glucose (p<0.05), postprandial glucose (p<0.05), LDL cholesterol (p<0.05), and HOMA-IR (p<0.05), and increased adiponectin (p<0.01) over orlistat alone (809).
  • Otic agentsOtic agents: In animal research, acetyl L-carnitine had a lack of effect on age-related hearing loss (810).
  • OxiplatinOxiplatin: Acetyl-L-carnitine decreased pain associated with oxiplatin (811). Further details are lacking.
  • PaclitaxelPaclitaxel: According to a case series, carnitine may reduce neuropathy symptoms associated with paclitaxel use (274). In animal research, acetyl-L-carnitine reduced paclitaxel-induced pain, potentially by protecting C-fiber mitochondria (812). Carnitine had a lack of effect of cytotoxicity of paclitaxel in vitro (644).
  • PenicillinsPenicillins: According to two clinical studies, penicillin derivatives may cause a decrease in serum carnitine concentrations, elevate excretion of acyl-carnitine, and reduce muscle carnitine concentrations (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).
  • PhenazopyridinePhenazopyridine: According to a case report, carnitine was part of a conservative treatment plan in renal toxicity associated with phenazopyridine overdose (816).
  • Phosphodiesterase inhibitorsPhosphodiesterase inhibitors: In a systematic review, the authors indicated that following prostate cancer treatments, there was some evidence that PDE5 inhibitors are more effective for sexual dysfunction in combination with acetyl-L-carnitine and propionyl-L-carnitine (817).
  • PioglitazonePioglitazone: In human research, pioglitazone treatment increased fasting free, total, and propionyl carnitine levels in serum (818).
  • Potassium chloridePotassium chloride: According to a case study, L-carnitine chloride and KCl may minimize rhabdomyolysis associated with licorice ingestion (819).
  • ProgesteroneProgesterone: In vitro, carnitine uptake in BeWo cells was decreased by progesterone (735).
  • PropafenonePropafenone: According to a randomized controlled trial, carnitine plus propafenone may improve arrhythmia better than propafenone alone (440).
  • PropiconazolePropiconazole: In animal research, propiconazole altered levels of carnitine (820). Further details are not available.
  • Radioactive pharmaceuticalsRadioactive pharmaceuticals: In animal research, carnitine when given adjuvant to radioactive iodine treatment resulted in decreased asymmetric dimetilarginine (ADMA) levels in cardiac and gastrocnemius muscles (821).
  • Respiratory agentsRespiratory agents: In vitro, carnitine inhibited the majority of 4-[4-(dimethylamino)-styryl]-N-methylpyridinium (ASP+) uptake in human airway epithelia, suggesting a role of OCTN2 in human airway epithelia (822).
  • RibavirinRibavirin: Biochemical and clinical improvements occurred in carnitine-treated patients with chronic hepatitis C being treated with pegylated interferon-alpha 2b (Peg-IFN-alpha 2b) plus ribavirin (RBV) (385; 280). In a randomized trial, the addition of 2g of carnitine daily to alpha-interferon and ribavirin treatment reduced steatosis in 70 patients with chronic hepatitis C (553). The addition of carnitine resulted in significantly (p<0.05) greater reductions of ALT, total cholesterol, and triglycerides, with greater reductions in AST and ALT at follow-up.
  • SildenafilSildenafil: According to a randomized controlled trial, sildenafil and propionyl-L-carnitine may be more effective than sildenafil alone (281).
  • SimvastatinSimvastatin: In human research, the addition of carnitine to simvastatin therapy resulted in a significant decrease in glycemia (p<0.001), triglycerides (p<0.001), total cholesterol (p<0.05), small LDL (p<0.001), Apo B (p<0.05), Lp(a) (p<0.05), and apo(a) (p<0.05), while HDL, large-size LDL, and glycosylated hemoglobin significantly increased (p<0.05) over simvastatin alone (605; 291). Patients treated with propionyl-L-carnitine showed statistically significant increases in ankle-brachial index from baseline after six and 12 months of treatment (p<0.001), as well as decreased malondialdehyde, 4-hydroxynonenal (4-HNE), and the ratio of plasma nitrite to nitrate (NO2:NO3), over simvastatin alone (645).
  • TacrolimusTacrolimus: In animal research, tacrolimus induced a decrease in cauda epididymis carnitine levels, perhaps due to reduced carnitine transport from the bloodstream (823).
  • TadalafilTadalafil: In a clinical trial, the effects of tadalafil were maintained for six months in the group treatd with antioxidants including L-carnitine vs. three months in the other groups (824).
  • Tetradecylthioacetic acid (TTA)Tetradecylthioacetic acid (TTA): In animal research, TTA use resulted in reduced carnitine levels (825).
  • Thyroid hormonesThyroid hormones: In human research, L-carnitine preveted and treated symptoms of hyperthyroidism (390). In vitro, carnitine inhibited the T4 stimulation of membrane potential in human mitochondria in the human breast cancer cell line (826). In vitro, carnitine uptake was increased by thyroid hormones (827). According to a review, L-carnitine inhibits the entry of T3 and T4 into the nuclei (390).
  • TilisololTilisolol: In rabbit corneal epithelium, carnitine reduced the transcellular permeability of tilisolol (828).
  • TilmicosinTilmicosin: In animal research, the antioxidant effects of carnitine resulted in cardioprotective effects against tilmicosin (829).
  • TriheptanoinTriheptanoin: In an animal seizure model, triheptanoin increased levels of propionyl-carnitine in the blood (830).
  • Valproic acidValproic acid: In animal studies, free valproic acid concentrations in the brain were significantly increased by carnitine, potentially increasing effects associated with valproic acid (831). In humans, treatment with carnitine returned the prolonged half-lives of valproic acid, associated with carnitine deficiency, close to the normal range (832). In clinical studies, plasma carnitine concentrations were lower and blood ammonia values were higher in patients treated with valproic acid than in the untreated patients and control subjects (590; 591; 592). L-carnitine supplementation reduced levels of plasma ammonia in valproate-treated patients (589). 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; 847), although decreases in free carnitine have been shown, but not in all human studies (848; 588). Treatment with carnitine improved carnitine levels in children treated with valproate and had no effect on plasma valproic acid levels (849). 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). One case study suggested that carnitine supplementation had no effect on valproate-related hepatotoxic effects (850), and another reported a severe disabled case of incomplete Fanconi syndrome following discontinuation of carnitine use during valproate therapy (851). Carnitine was added to valproic acid treatment for spinal muscular atrophy in a clinical trial; the effect of carnitine alone was not examined (587). Mechanisms associated with valproate-induced reduction of carnitine have been investigated in vitro (573; 574; 852). In animal research, decreased carnitine stores were associated with increased valproic acid toxicity (853). However, in children using valproic acid, there was an increase in levels of free carnitine (294) and in patients with epilepsy although plasma and urinary free and total carnitine levels decreased levels of acyl-carnitine increased (593).
  • VasodilatorsVasodilators: Vasodilation and enhanced blood flow may be the basis for some physiological phenomena caused by carnitine (854; 298).
  • Wound-healing agentsWound-healing agents: Beneficial effects of carnitine have been observed in animal models of skin healing (855; 856).
  • Zidovudine (AZT)Zidovudine (AZT): In myotubes of human muscle in tissue culture, AZT induced depopulation of myotubes and destructive changes in mitochondria. L-carnitine used concurrently with AZT prevented all these effects (857). 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).

    • L-carnitine/Herb/Supplement Interactions:

  • AcupunctureAcupuncture: In animal research, manual acupuncture, but not electroacupuncture, increased muscle carnitine levels (860).
  • Alpha-ketoglutarateAlpha-ketoglutarate: In vitro, alpha-ketoglutarate led to the recovery of carnitine production following oxidative stress (861).
  • Alpha-lipoic acidAlpha-lipoic acid: In combination with alpha-lipoic acid and silymarin, carnitine protected against cisplatin-induced cardiotoxicity, based on biochemical measurements (674). Antiaging, antidiabetic, adipose metabolic, cardiovascular protective, cognitive protective, neuroprotective, and antioxidant, etc., effects of a combination of carnitine and alpha-lipoic acid have been shown in animal models (862; 863; 864; 865; 866; 867; 868; 869; 870; 871; 872; 873). In animal research, dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocholine, docosahexaenoic acid, and phosphatidylserine reduced oxidative damage to the brain and improved cognitive performance (874). In vitro, the combination of alpha-lipoic acid and acetyl-L-carnitine exerted preventative effects in a cellular model of Parkinson's disease (40). Decreases were noted with both agents alone, as were increased effects when the agents were used together. In an animal diabetic model, a combination of alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin improved mitochondrial biogenesis and function in skeletal muscle (875) and immune function (876).
  • Alpha-tocopherolAlpha-tocopherol: In animal research, alpha-tocopherol deficiency resulted in increased liver carnitine levels (877).
  • Alzheimer's agentsAlzheimer's agents: Although evidence of benefit of acetyl-L-carnitine is mixed in human research (316), beneficial effects of acetyl-L-carnitine have been observed in various Alzheimer's disease animal models, as well as in vitro, either alone or in combination with other agents (554; 555; 556; 557; 558). In animal research, carnitine reduced acetylcholinesterase activities in the plasma and some tissues (559). Some change in acetylcholinesterase and butyrylcholinesterase activities in brain and peripheral tissues occurred with carnitine, but specific details are lacking (560).
  • AnalgesicsAnalgesics: In an animal diabetic model, acetyl-L-carnitine improved hypoalgesic effects (562). In vitro, the analgesic effects of acetyl-L-carnitine were shown (563; 564). The role of acetyl-L-carnitine in neuropathic pain was discussed in a review (565).
  • AntibacterialsAntibacterials: 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; 575).
  • AnticoagulantsAnticoagulants: According to a clinical trial of patients with angina, L-carnitine may decrease the need for anticoagulants (257). In vitro, carnitine decreased platelet aggregation (258; 259).
  • AnticonvulsantsAnticonvulsants: 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).
  • AntidepressantsAntidepressants: In human and animal research, antidepressant effects of acetyl-L-carnitine were shown (599; 316).
  • Anti-inflammatoriesAnti-inflammatories: In hemodialysis patients, carnitine reduced levels of C-reactive protein and fibrinogen (609; 454). In vitro, a mixture of carnitine, thioctic acid, and saw palmetto decreased induced inflammation in keratinocytes by suppressing genes activated during the inflammatory response, such as CCL17, CXCL6, and leukotriene B4 (610). In an animal arthritis model, carnitine reduced malondialdehyde levels, and glutathione levels were higher, resulting in reduced inflammation (611).
  • AntilipemicsAntilipemics: According to a clinical trial of angina patients, L-carnitine decreased the need for antilipidemic drugs (257). Carnitine was reported to reduce the level of serum triglycerides in patients with hyperlipidemia (612; 613). In patients with type 2 diabetes, the additional effects of carnitine over simvastatin alone resulted in decreased triglycerides (p<0.001), apo B (p<0.05), Lp(a) (p<0.05), and apo(a) (p<0.05), and significant increases in HDL cholesterol (p<0.05) (605). 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). Increased triglycerides, Apo B100, and Apo A1 were found in individuals with diabetes on glyburide or metformin (253) and in uremic patients on hemodialysis (255). Decreased cholesterol has been noted (257; 621; 618; 331; 614; 478; 265; 266; 312; 445). Increased HDL has been noted (621; 622; 623; 618; 619; 312). A decreased ratio of total cholesterol to HDL cholesterol has been noted (622; 623). No changes in Apo A1 or Apo B were noted in hypertensive individuals (618), but they were reduced in elderly individuals and other studies (312; 266; 624). No changes in triglycerides, total cholesterol, HDL cholesterol, ApoA, or Apo B were noted in other studies (497; 619; 351; 455; 389; 472). In pregnant women, carnitine reduced levels of free fatty acids and triglycerides (slightly) (503). In a high-fat diet animal model, carnitine normalized the lipid profile (625).
  • AntineoplasticsAntineoplastics: The anticancer effects of carnitine have been shown in various in vitro studies (629; 630; 631).
  • Antiobesity agentsAntiobesity agents: In animal research using a neonatal model, carnitine resulted in reduced food intake in later life but did not affect body weight (632). In an animal model, propionyl-L-carnitine reduced body weight, food intake, and adiposity (633).
  • AntioxidantsAntioxidants: Carnitine, acetyl-L-carnitine, and propionyl-L-carnitine have demonstrated antioxidant effects in animal and in vitro research (878; 879; 880; 881; 882; 883; 884; 885; 886; 887; 888; 889; 890; 891; 7). The effect of dietary antioxidant supplementation on semen quality in pony stallions was investigated (892). Further details are not available . Acetyl-L-carnitine, as part of an antioxidant mixture, showed benefits as an antioxidant in an animal model of acoustic trauma (893). In an animal chronic valvular disease model, a combination of antioxidants, omega-3 fatty acids, taurine, carnitine, and arginine, resulted in various changes in the blood (fatty acid status, cholesterol, triglycerides), but the effect of carnitine itself is not clear (894).
  • AntiviralsAntivirals: According to a review, acetyl-L-carnitine use was associated with reduced HIV-associated antiretroviral toxic neuropathy (634). In vitro, carnitine protected against the oxidative effects of antiretrovirals (635) and prevented the impaired fatty acid oxidation and lipid export, as well as liver abnormalities, due to stavudine (636; 637).
  • ArginineArginine: In animal research, a combination of soy isoflavones, caffeine, arginine, and carnitine reduced adipose tissue weight (895). In an animal chronic valvular disease model, a combination of antioxidants, omega-3 fatty acids, taurine, carnitine, and arginine resulted in various changes in the blood (fatty acid status, cholesterol, triglycerides), but the effect of carnitine itself is not clear (894).
  • Athletic performance enhancersAthletic performance enhancers: In human research, a change in performance was related to changes in acetyl-L-carnitine (699). In human athletes, total antioxidant status was unaltered and enzyme activities (acetylcholinesterase and ATPases) were reduced following exercise in a carnitine-supplemented population (700). In animal research, the addition of nutrients, including acetyl-L-carnitine (as well as alpha-lipoic acid, vitamins, CoQ10, etc.), increased mitochondrial biogenesis and performance in exhaustively exercised rats; the antioxidant effects of this nutrient mixture were implicated (701). In animal research, carnitine attenuated intermittent hypoxia-induced oxidative stress and delayed muscle fatigue (702).
  • BetaineBetaine: In humans attending a lipid disorder clinic, carnitine affected betaine homeostasis (896).
  • BiotinBiotin: In an animal diabetic model, a combination of alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin improved mitochondrial biogenesis and function in skeletal muscle (875) and immune function (876). Levels of the carnitine metabolite in plasma and urine, 3-hydroxyisovaleryl carnitine, may be used as an early indicator of biotin deficiency (897; 898).
  • Branched-chain amino acidsBranched-chain amino acids: In animal research, carnitine protected against the oxidative stress induced by branched-chain amino acids (899).
  • ButyrateButyrate: In vitro, a combination of butyrate and carnitine inhibited human colon carcinoma cell proliferation and induced apoptosis (630). Butyryl-L-carnitine inhibited carnitine uptake in vitro (900).
  • CaffeineCaffeine: In animal research, a combination of soy isoflavones, caffeine, arginine, and carnitine reduced adipose tissue weight (895).
  • CalciumCalcium: In Rahmani ewes, a combination of calcium and L-carnitine improved the number and size of ovarian preovulatory follicles and the ovulation rate (901). L-carnitine alone did not have this effect.
  • Cardiovascular agentsCardiovascular agents: According to a clinical trial of patients with congestive heart failure, L-carnitine may decrease the need for digoxin (331). In children, 100mg/kg of carnitine daily for three months showed evidence of benefit over regular therapy alone (digoxin, diuretics, ACE inhibitors) (546). According to a clinical trial of angina patients, L-carnitine may decrease the need for glycosides and antiarrhythmics (257). Results from human research are indicative of the efficacy of propionyl-L-carnitine and L-carnitine in treatment of peripheral vascular disease (424; 469; 269; 293; 422; 468; 466; 467; 465; 421; 645; 416; 417; 418; 419; 420; 646; 647; 648; 649; 650; 651; 652; 275; 653; 423; 654; 464; 655; 656). The cardiovascular protective effects of L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine have also been shown in animal or organ models (657; 633; 658; 659; 660; 661).
  • CholineCholine: According to a clinical study of healthy humans, choline supplementation may reduce excretion, renal clearance, and fractional clearance of nonesterified carnitine (902).
  • Coenzyme Q10Coenzyme Q10: In an animal cardiomyopathy model, the combination of coenzyme Q10, omega-3 fatty acids, and propionyl-L-carnitine improved papillary muscle force-frequency responses (903). Also in animal research, a combination of carnitine, taurine, and coenzyme Q10 improved survival, infarct size, and cardiac function following myocardial infarction (904).
  • Conjugated linoleic acid (CLA)Conjugated linoleic acid (CLA): Li et al. reported on the lipase-catalyzed esterification of CLA with L-carnitine in a solvent-free system with acetonitrile (905). Further details are lacking.
  • CopperCopper: In animal research, carnitine protected against the detrimental effects of very high copper intakes (800mg/kg of copper proteinate) (906). In vitro, a dinuclear copper (II) complex of carnitine had enhanced cytotoxic effects over carnitine or copper chloride dehydrate (907).
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: In vitro, the combination of carnitine and methanol stimulated CYP2E1 (681).
  • DiureticsDiuretics: According to a clinical trial of patients with angina, L-carnitine may decrease the need for diuretics (257). In a study of patients with left ventricular dysfunction, no adverse effects were noted when diuretics were used with carnitine (332).
  • Fertility agentsFertility agents: In human research, although L-carnitine increased the percentage of grade a + b sperm, significant changes in sperm concentration, sperm motility, and rate of sperm deformity were lacking (272). In animal research, L-carnitine enhanced oocyte maturation as well as the development of parthenogenetic embryos in pigs (514) and improved oocyte developmental competence in mice (515). In animal research, oral L-carnitine reduced the negative effects of oxidative stress on structure and functions of ovary and oocytes during repeated ovulation (526). In vitro, carnitine promoted meiotic resumption in mouse oocytes (704). In the presence of carnitine, human testis sperm cultured from azoospermic patients increased in motility (% motile sperm increase and % forward moving), with a lack of change in normal morphology (705). In human research, the level of free carnitine in the seminal plasma of fertile men was increased vs. infertile men, and the level of free carnitine in the semen was positively correlated with sperm concentration (706).
  • Garcinia cambogiaGarcinia cambogia: In animal research, a mixture of the aqueous extract of Garcinia cambogia, soy peptide and carnitine reduced the accumulation of visceral fat mass and body fat following a high-fat diet (908). Other benefits were improved levels of blood and hepatic lipid concentrations and serum glucose, insulin, C-peptide, and leptin levels. In human research carnitine and Garcinia cambogia extract reduced lipid peroxidation and physical symptoms, such as "tired eyes," "blurry eyes," "muscle pain/stiffness," "early satiety," "epigastralgia," "dizziness," "arthralgia" and "easily breaking into a sweat" (6).
  • Gastrointestinal agentsGastrointestinal agents: In a randomized clinical trial there was a small increase in clinical and endoscopic response in patients treated with oral colon-release propionyl-L-carnitine tablets (311). Although gastrointestinal symptoms are associated with supplemental carnitine use (263; 264; 265; 266; 267; 268; 269; 270; 271; 272; 273; 274; 275; 276; 241; 277; 278; 279; 280; 278; 281; 282; 283; 284; 285; 286; 287; 288; 289; 290; 291; 292; 293; 294; 295; 296; 297), in animal research, carnitine protected against damage to the intestine or symptoms of gastrointestinal pathology (708; 709; 710; 711).
  • GenisteinGenistein: In vitro, carnitine uptake in BeWo cells was increased by genistein (735). In animal research, the addition of carnitine to genistein altered expression of genes potentially involved in obesity (909).
  • GlycerophosphocholineGlycerophosphocholine: In animal research, dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocholine, docosahexaenoic acid, and phosphatidylserine reduced oxidative damage to the brain and improved cognitive performance (874).
  • Hair agentsHair agents: In vitro, carnitine-L-tartrate promoted human hair growth in cultured hair follicles; potential mechanisms of action include downregulation of apoptosis and induced proliferation by prolonged duration of anagen VI and reduced TGF-beta2 and caspase-3 and -7 (713).
  • HepatotoxinsHepatotoxins: Evidence from randomized controlled trials suggests that L-carnitine may be of benefit to individuals with hepatic encephalopathy, in terms of bilirubin, ammonia, urea, and liver enzymes (384; 292; 383; 277; 458; 382; 381; 291; 411; 377; 406). In human research, acetyl-L-carnitine reduced levels of AST, ALT, and hepatitis C viremia; significant between-group difference in levels of bilirubin and albumin were lacking (385; 280; 384). In animal research, carnitine protected against liver injury (714; 715; 716; 717; 718).
  • HypoglycemicsHypoglycemics: 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). Increased triglycerides, increased Apo B 100, increased Apo A1, and decreased glucose were observed in individuals with diabetes using L-carnitine (253). Carnitine levels did not change in diabetics with insulin or sulfonylurea therapy (607). In an animal diabetic model, carnitine reduced tissue ACE activity, possibly due to increased nitric oxide production (608).
  • HypotensivesHypotensives: Use of carnitine resulted in decreased blood pressure during exercise (239) or in patients with insulin sensitivity (240) and increased blood pressure in patients with congestive heart failure (242). In animal research, carnitine reduced blood pressure levels (236; 237; 238). Hypertension was reported in three subjects using oral carnitine (241).
  • ImmunomodulatorsImmunomodulators: In a clinical study, high-dose carnitine resulted in an increase in lymphocyte proliferation responsiveness to mitogens (723). In a clinical study, carnitine treatment resulted in a strong reduction in the percentage of CD4 and CD8 cells undergoing apoptosis, which is involved in T cell depletion in AIDS (724). Acetyl-L-carnitine administered to patients with active pulmonary tuberculosis for 30 days upregulated T cell-dependent antibacterial activity, which decreased in patients receiving placebo only (725; 726). An influence on the serum level of tumor necrosis factor was lacking.
  • IronIron: In children, decreased carnitine levels were associated with iron-deficiency anemia (910). In vitro, carnitine uptake was decreased by iron (827).
  • LicoriceLicorice: In a case study, L-carnitine chloride and KCl minimized rhabdomyolysis associated with licorice ingestion (819).
  • Lotus leaf extractLotus leaf extract: In vitro, the combination of lotus leaf extract and carnitine reduced triglyceride accumulation in adipocytes to a greater extent than carnitine or lotus leaf extract alone (911).
  • LysineLysine: In animal research, a moderate excess of dietary lysine lowered plasma and tissue carnitine concentrations (912).
  • MagnesiumMagnesium: Although use of L-carnitine resulted in decreased migraine frequency, severity, and index, it was less effective than magnesium, and the combination of L-carnitine and magnesium was less effective than magnesium alone (295).
  • Medium-chain triglyceridesMedium-chain triglycerides: In animal research the effect of pre-exercise application of medium-chain triglycerides (MCT) on free carnitine was investigated, but further details are not available (913).
  • Memory agentsMemory agents: In animal research, acetyl-L-carnitine improved spatial memory (739).
  • N-acetyl cysteineN-acetyl cysteine: In animal research, a combination of N-acetyl cysteine, acetyl-L-carnitine, and S-adenosyl methionine improved cognitive performance and aggression in normal mice and mice expressing human ApoE4 (914).
  • NephrotoxinsNephrotoxins: In animal research, carnitine, acetyl-L-carnitine, and propionyl-L-carnitine protected against renal toxicity in various models (761; 762; 763; 764; 765; 766; 767; 768; 769).
  • Neurologic agentsNeurologic agents: In animal research, carnitine, acetyl-L-carnitine, and palitoyl-L-carnitine had neuroprotective effects (770; 771; 772; 773; 774; 775; 776; 777; 778; 779; 780; 781; 782; 783; 784; 785; 786; 787; 788; 789; 790; 791; 792; 793; 794; 795).
  • NickelNickel: In vitro, the antioxidant effects of carnitine were found to protect against the neurotoxic effects of nickel (915).
  • NicotinamideNicotinamide: In an animal diabetic model, a combination of alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin improved mitochondrial biogenesis and function in skeletal muscle (875) and immune function (876). In a similar model, the combination of carnitine and nicotinamide improved weight, plasma glucose, and plasma insulin (916).
  • Ocular agentsOcular agents: Benefits were observed in clinical trials investigating eye drops containing carnitine and other ingredients (800; 801). In experimental glaucoma, carnitine reduced the lipoperoxidative damage of the membrane and apoptosis after induction of cell stress (802). In animal research, acetyl-L-carnitine protected against selenite-induced cataractogenesis (803; 804; 805; 806; 807).
  • Omega-3 fatty acidsOmega-3 fatty acids: In rat hepatocytes in vitro, carnitine increased the beta-oxidation of the fatty acid eicosapentaenoic acid (EPA) as well as reduced the competitive inhibition of arachidonic acid-dependent prostaglandin E2 synthesis and cyclooxygenase-2 expression by EPA (917). In animal research, dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocholine, docosahexaenoic acid, and phosphatidylserine reduced oxidative damage to the brain and improved cognitive performance (874). In an animal cardiomyopathy model, the combination of coenzyme Q10, omega-3 fatty acids, and propionyl-L-carnitine improved papillary muscle force-frequency responses (903). In an animal chronic valvular disease model, a combination of antioxidants, omega-3 fatty acids, taurine, carnitine, and arginine resulted in various changes in the blood (fatty acid status, cholesterol, triglycerides), but the effect of carnitine itself is not clear (894).
  • Osteoporosis agentsOsteoporosis agents: In animal research, carnitine improved bone mineral density (690).
  • Otic agentsOtic agents: In animal research, acetyl L-carnitine had a lack of effect on age-related hearing loss (810).
  • PhosphatidylserinePhosphatidylserine: In animal research, dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocholine, docosahexaenoic acid, and phosphatidylserine reduced oxidative damage to the brain and improved cognitive performance (874).
  • ProgesteroneProgesterone: In vitro, carnitine uptake in BeWo cells was decreased by progesterone (735).
  • Respiratory agentsRespiratory agents: In vitro, carnitine inhibited the majority of 4-[4-(dimethylamino)-styryl]-N-methylpyridinium (ASP+) uptake in human airway epithelia, suggesting a role of OCTN2 in human airway epithelia (822).
  • S-adenosyl methionineS-adenosyl methionine: In animal research, a combination of N-acetyl cysteine, acetyl-L-carnitine, and S-adenosyl methionine improved cognitive performance and aggression in normal mice and mice expressing human ApoE4 (914).
  • SeleniumSelenium: In patients with phenylketonuria, a combination of carnitine and selenium reduced lipid and protein oxidation, and restored activity of glutathione peroxidase (918).
  • Sesame lignansSesame lignans: In animal research, sesame lignans (sesamin, episesamin, and sesamolin) affected gene expression profile, possibly resulting in changes of carnitine concentrations in the liver (919). In animal research, sesame lignans modified mRNA levels of proteins involved in regulation of hepatic carnitine levels (920). Further details are not available .
  • SilymarinSilymarin: In combination with alpha-lipoic acid and silymarin, carnitine protected against cisplatin-induced cardiotoxicity, based on biochemical measurements (674).
  • SoySoy: In premature infants, soybean oil based lipid emulsion (Intralipid?) resulted in increased acylcarnitine levels and decreased free carnitine levels (921). In animal research, a mixture of the aqueous extract of Garcinia cambogia, soy peptide and carnitine reduced the accumulation of visceral fat mass and body fat following a high-fat diet (908). Other benefits were improved levels of blood and hepatic lipid concentrations and serum glucose, insulin, C-peptide, and leptin levels. The expression levels of leptin, TNF-alpha, and sterol regulatory element binding protein-1c (SREBP1c) genes were reduced in the epididymal fat tissue, and expression of the uncoupling protein-2 (UCP2) gene was increased. In animal research, a combination of soy isoflavones, caffeine, arginine, and carnitine reduced adipose tissue weight (895).
  • Stevia rebaudiana Bertoni extractStevia rebaudiana Bertoni extract: In animal research Stevia rebaudiana Bertoni extract supplementation improved carnitine profiles during high-fat feeding, based on increases in the ratio of acyl-carnitine to free carnitine (922).
  • St. John's wortSt. John's wort: In human and animal research, antidepressant effects of acetyl-L-carnitine were shown (599; 316).
  • TaurineTaurine: In vitro, the combination of carnitine and taurine synergistically inhibited the proliferation and osteoblastic differentiation of vascular smooth muscle cells over carnitine alone (923). Mechanisms of action included increased uptake of taurine and the taurine transporter. In animal research, a combination of carnitine, taurine, and coenzyme Q10 improved survival, infarct size, and cardiac function following myocardial infarction (904). In an animal chronic valvular disease model, a combination of antioxidants, omega-3 fatty acids, taurine, carnitine, and arginine resulted in various changes in the blood (fatty acid status, cholesterol, triglycerides), but the effect of carnitine itself is not clear (894).
  • Thyroid agentsThyroid agents: In human research, L-carnitine preveted and treated symptoms of hyperthyroidism (390). In vitro, carnitine inhibited the T4 stimulation of membrane potential in human mitochondria in the human breast cancer cell line (826). In vitro, carnitine uptake was increased by thyroid hormones (827). According to a review, L-carnitine inhibits the entry of T3 and T4 into the nuclei (390).
  • VasodilatorsVasodilators: Vasodilation and enhanced blood flow may be the basis for some physiological phenomena caused by carnitine (854; 298).
  • Vitamin B12Vitamin B12: In animal research, carnitine reduced the urinary excretion of methylmalonic acid excretion in cobalamin-deficient animals (924). In newborns, vitamin B12 deficiency is a common cause of elevated propionyl-carnitine levels (925).
  • Vitamin CVitamin C: In animal research, vitamin C was not essential for carnitine (926). However, other authors suggested that vitamin C is necessary for carnitine biosynthesis (927; 928). Hudspeth et al. hypothesized that a response to ascorbic acid may be related to the making of ferrous iron available as a cofactor in carnitine synthesis (929).
  • Wound-healing agentsWound-healing agents: Beneficial effects of carnitine have been observed in animal models of skin healing (855; 856).
  • Wuzi Yanzong liquidsWuzi Yanzong liquids: Cui et al. conducted a study to compare the individual and additive effects of Wuzi Yanzong liquids and carnitine on oligospermia and asthenospermia (404). All the patients showed improvement in sperm parameters and had increased testosterone levels, although the authors indicated that the greatest improvements were observed in the combination group.

    • L-carnitine/Food Interactions:

  • GeneralGeneral: In patients with type 2 diabetes, there was a lack of difference in carnitine levels between the fasted and postprandial state (930).
  • AlcoholAlcohol: In animal research, carnitine had a lack of effect on body weight, diet consumption, urinary nitrogen excretion, plasma free fatty acids, or lysine, methionine, and glycine levels in alcoholic malnourished rats (552).
  • Breast milkBreast milk: According to a clinical trial, breastfed infants may have higher carnitine plasma levels and, as a consequence, higher ketone body production than formula-fed infants (931).
  • CarbohydratesCarbohydrates: In human research, a carbohydrate-induced insulin release augmented carnitine retention by the kidneys (932). In human research, perturbations in carnitine metabolism common during operation were attenuated by preoperative carbohydrate consumption (933).
  • CholineCholine: According to a controlled trial, serum and urinary carnitine may decrease with choline supplementation (934).
  • FructoseFructose: In animal research, carnitine reversed the negative effects of fructose on hepatic gluconeogenesis (935).
  • High-fat dietHigh-fat diet: In animal research, a combination of grape extract, green tea extract, and carnitine improved obesity, high blood lipids, and fatty liver following a high-fat diet (936). In a high-fat diet animal model, carnitine normalized the lipid profile; improved negative effects on various biochemical endpoints determining the health of the kidney, liver, and heart; and decreased hepatic malondialdehyde levels and lipid peroxidation (625).
  • 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. A review has been published on the need for carnitine and micronutrient supplementation when the ketogenic diet is implemented in intractable epilepsy (939).
  • LicoriceLicorice: According to a case study, L-carnitine chloride and KCl may minimize rhabdomyolysis associated with licorice ingestion (819).
  • Lipid preparationsLipid preparations: According to a clinical trial, lipid preparations administered intravenously to malnourished patients may strongly depress urinary carnitine excretion (940). According to a clinical trial, urinary excretion of acyl-carnitine may be significantly higher and the free:total carnitine ratio may be lower in infants ingesting formula containing medium-chain fatty acids (triglycerides) (941). In human research, lipid emulsions containing long-chain fatty acids resulted in higher plasma and urine levels of L-carnitine vs. lipid emulsions containing mixtures of medium and long chain fatty acids (942). A review has been published on intravenous lipid administration; however, conclusions related to carnitine are lacking (943).
  • Low-protein dietLow-protein diet: According to a crossover clinical study, the rates of carnitine excretion and reabsorption may be lower after a low-protein diet than after a high-protein diet, because of the lower glomerular filtration rate (944).
  • MeatMeat: Carnitine status may be used as a biomarker of meat intake (945).
  • Oxidized fatsOxidized fats: In animal research, oxidized fat resulted in increased hepatic carnitine and decreased plasma carnitine levels (946).
  • Persimmon-vinegarPersimmon-vinegar: In alcohol-fed rats, persimmon-vinegar resulted in increased hepatic carnitine levels (947).
  • Phenylketonuric (PKU) dietPhenylketonuric (PKU) diet: In human research, the PKU diet was associated with decreased carnitine levels (948).
  • SoySoy: In premature infants, soybean oil based lipid emulsion (Intralipid?) resulted in increased acylcarnitine levels and decreased free carnitine levels (921). In animal research, a mixture of the aqueous extract of Garcinia cambogia, soy peptide, and carnitine reduced the accumulation of visceral fat mass and body fat following a high-fat diet (908). Other benefits were improved levels of blood and hepatic lipid concentrations and serum glucose, insulin, C-peptide, and leptin levels. The expression levels of leptin, TNF-alpha, and sterol regulatory element binding protein-1c (SREBP1c) genes were reduced in the epididymal fat tissue, and expression of the uncoupling protein-2 (UCP2) gene was increased. In animal research, a combination of soy isoflavones, caffeine, arginine, and carnitine reduced adipose tissue weight (895).
  • Stevia rebaudiana Bertoni extractStevia rebaudiana Bertoni extract: In animal research Stevia rebaudiana Bertoni extract supplementation improved carnitine profiles during high-fat feeding, based on increases in the ratio of acyl-carnitine to free carnitine (922).

    • L-carnitine /Lab Interactions:

  • 3-Hydroxybutyrate3-Hydroxybutyrate: Increases have been noted in infants (949; 950; 616; 951; 479; 484).
  • 8-Oxo-deoxyguanosine (8-oxo-dG)8-Oxo-deoxyguanosine (8-oxo-dG): In human research, carnitine decreased levels of 8-oxo-dG (406; 465).
  • AcetoacetateAcetoacetate: Carnitine increased acetoacetate levels in infants (479).
  • AdiponectinAdiponectin: In hemodialysis patients, carnitine supplementation increased adiponectin levels (952).
  • Alpha-tocopherolAlpha-tocopherol: In animal research, carnitine significantly increased liver, but not plasma, brain, lung, or retroperitoneal fat, levels of alpha-tocopherol (615).
  • AmmoniaAmmonia: In humans, carnitine suppressed exercise-induced increases in ammonia (953).
  • Amprolium analysis (hydrophilic interaction liquid chromatography-tandem mass spectrometry)Amprolium analysis (hydrophilic interaction liquid chromatography-tandem mass spectrometry): In a study, carnitine was added as an interfering compound to standards and samples to allow the use of the external calibration method (954).
  • Anabolic hormonesAnabolic hormones: According to a study of 10 healthy, recreationally weight-trained men, L-carnitine L-tartrate may significantly increase IGFBP-3 concentrations prior to and at 30, 120, and 180 minutes after acute supplementation (955).
  • AntioxidantsAntioxidants: In human and animal research, carnitine had antioxidant effects (956; 457; 365; 5; 472; 266; 775; 889; 890; 702; 5). Carnitine had a lack of effect on oxidative stress in response to forearm ischemia-reperfusion, as evidenced by a lack of change in lactate, malondialdehyde, hydrogen peroxide, xanthine oxidase, hypoxanthine, glutathione, and other markers of oxidative stress (957).
  • Blood cell countBlood cell count: In animal research, carnitine-L-tartrate plus dehydroepiandrosterone sulfate (DHEAS) decreased red blood cells and increased platelets in the blood of aged Sprague-Dawley rats (958). In animal research, carnitine decreased packed cell volume (959). In pregnant women given carnitine during pregnancy, there were no significant differences for whole blood count at delivery, including leukocyte, erythrocyte, mean corpuscular volume, and thrombocyte levels (505).
  • Blood pressureBlood pressure: Use of carnitine resulted in decreased blood pressure during exercise (239) or in patients with insulin sensitivity (240) and increased blood pressure in patients with congestive heart failure (242). In animal research, carnitine reduced blood pressure levels (236; 237; 238). Hypertension was reported in three subjects using oral carnitine (241).
  • Bone turnoverBone turnover: In patients on hemodialysis, carnitine resulted in decreased bone-specific alkaline phosphatase and increased osteoprotegerin (960).
  • C-peptideC-peptide: In animal research, carnitine reduced C-peptide levels (602).
  • C-reactive proteinC-reactive protein: In human research, carnitine reduced levels of C-reactive protein in hemodialysis patients (609; 444; 348) and cancer patients (323; 961).
  • Cardiac markersCardiac markers: In human research, the addition of carnitine to percutaneous coronary intervention for non-ST elevation myocardial infarction resulted in reduced levels of the cardiac markers creatine kinase-MB and troponin-1 (962). In human research, L-carnitine use in patients being treated for acute carbon monoxide poisoning resulted in decreased levels of myoglobin, MB isozyme of creatine kinase, and cardiac troponin 1 (markers of myocardial injury) (462).
  • CarnitineCarnitine: In rats, treatment with L-carnitine restored levels of plasma carnitine (601), and increased carnitine levels in other tissues have been shown in other animal models (528). According to a clinical trial, muscle carnitine concentration at rest may not change due to carnitine supplementation (963). In a study of healthy vegans and lacto-ovo vegetarians, carnitine supplementation increased plasma free and total carnitine concentrations by 30 and 25%, respectively (964). Increase in blood carnitine and acyl-carnitine, blood and urinary acetyl-carnitine, and red blood cell and muscle carnitine have been shown by other authors in various populations, including preterm and term infants (949; 965; 966; 313; 967; 968; 497; 416; 934; 950; 969; 616; 970; 617; 971; 972; 973; 455; 322; 294). A decrease in free and total carnitine has been noted in premature infants (972). According to a study of newborn infants on total parenteral nutrition for the first seven days of life, Intralipid? may increase the plasma concentration of total carnitine, free carnitine, and acyl carnitine (974); however, in human research, lipid emulsions containing long-chain fatty acids resulted in higher plasma and urine levels of L-carnitine vs. lipid emulsions containing mixtures of medium and long chain fatty acids (942)
  • Chromogranin AChromogranin A: In human research, L-carnitine had a lack of effect on salivary chromogranin A (375).
  • Coronary flow velocity reserveCoronary flow velocity reserve: In human research, a single intravenous administration of propionyl-L-carnitine significantly increased the mean coronary flow velocity reserve (CFVR) in patients with systemic sclerosis, as determined by adenosine infusion and transthoracic Doppler examination (975).
  • CortisolCortisol: In young healthy females, carnitine decreased salivary cortisol levels (976).
  • Creatine kinaseCreatine kinase: In animal research, carnitine resulted in decreased creatine kinase levels (702). Increased creatine kinase was indicated in a study examining carnitine in simvastatin-treated patients, although it is unclear whether it was due to carnitine or simvastatin (291).
  • CreatinineCreatinine: According to a randomized controlled study in hemodialysis patients, creatinine levels may be decreased (977; 452). In an animal kidney transplantation model, propionyl-L-carnitine reduced serum creatinine levels (768).
  • CytokinesCytokines: In human research, carnitine reduced IL-6 and TNF-alpha levels (961).
  • Cytosolic proteinsCytosolic proteins: According to a study in resistance-trained men, exercise-induced increases in circulating cytosolic proteins (myoglobin, fatty acid-binding protein, and creatine kinase) may be significantly attenuated by L-carnitine L-tartrate supplementation (978).
  • Echocardiographic measurementsEchocardiographic measurements: In human research, echocardiographic measurements determined that carnitine resulted in a statistically significant difference in E wave velocity (p=0.024) and E wave:A wave ratio (p=0.001) (431). In patients with heart failure, carnitine resulted in statistically significant improvements in left atrial size, isovolemic relaxation time (IVRT), and annulus velocities (335).
  • FibrinogenFibrinogen: In human research, carnitine reduced fibrinogen levels in hemodialysis patients (609).
  • Free fatty acidsFree fatty acids: An increase in free fatty acids in premature infants has been noted (971). An increase was noted in full-term infants (617). A decrease has been noted in patients with coronary artery disease, patients on hemodialysis, and athletes (979; 620; 478; 374).
  • 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).
  • GlutamateGlutamate: Breitkreutz reported that carnitine use in cancer patients may increase plasma glutamate levels (980).
  • GlycerolGlycerol: An increase in glycerol in premature infants has been noted (971).
  • Heart rateHeart rate: Carnitine use resulted in increased heart rate (438). An acute dose of carnitine resulted in significant changes in the exercise maximum heart rate in elite badminton players (371). Further details are not available. During exercise, carnitine resulted in decreased heart rate (358; 239; 368; 457).
  • HematocritHematocrit: Carnitine in increased hematocrit in hemodialysis patients (344).
  • HomocysteineHomocysteine: In animal research, carnitine increased homocysteine levels in a period immediately after methionine loading (981).
  • HormonesHormones: In human research, L-carnitine L-tartrate resulted in increased pre-exercise androgen receptor and decreased levels of luteinizing hormone (LH) (982). In women with stress-induced functional hypothalamic amenorrhea, LH (p<0.01) and LH pulse amplitude (p<0.001) increased in women with decreased levels at the start of treatment (317). In infertile men, testosterone increased following carnitine use (404).
  • HypoxanthineHypoxanthine: In human research, carnitine decreased hypoxanthine levels postexercise (370; 365).
  • ImmunoglobulinsImmunoglobulins: In animal research, carnitine improved serum IgG content (959).
  • InsulinInsulin: In patients with diabetes, insulin use was associated with lower carnitine levels in blood vs. oral antidiabetic use (983). In rats, treatment with L-carnitine had no effect on insulin levels (601). In healthy subjects, a decrease in insulin levels with L-carnitine was noted (250). Decreased levels of insulin and homeostasis model assessment of insulin resistance (HOMA-IR) occurred in animal and human research (602; 340). In animal research, propionyl-L-carnitine reduced serum levels of insulin and insulin resistance (633).
  • Insulin-like growth factor (IGF-1 and IGF-II)Insulin-like growth factor (IGF-1 and IGF-II): In animal research, carnitine increased IGF-1 (602; 517) and its mRNA (984).
  • Iron statusIron status: In pregnant women given carnitine during pregnancy, significant differences were lacking for hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), MCH concentrations, and ferritin (505). In hemodialysis patients, carnitine increased hemoglobin and hematocrit (445; 452; 351).
  • Ketone bodiesKetone bodies: An increase in ketone bodies in premature infants has been noted (971).
  • LactateLactate: Both an increase and decrease have been noted after exercise (361; 985; 457; 239; 366; 457; 372). A lack of change in lactate has also been noted (979; 606). A decrease was noted in septic patients on parenteral nutrition (968). In human research, intravenous carnitine during a period of hyperinsulinemia resulted in decreased muscle lactate (986).
  • Left ventricular mass indexLeft ventricular mass index: Left ventricular mass index showed a significant decrease in carnitine-treated patients (349).
  • LeptinLeptin: In animal research, carnitine increased plasma leptin levels (254). According to a review, carnitine increased leptin levels in an animal model (220).
  • Lipoprotein (a)Lipoprotein (a): In human research, carnitine decreased lipoprotein (a) levels (279; 446). According to a review, carnitine may decrease lipoprotein (a) (987).
  • Liver enzymesLiver enzymes: Evidence from randomized controlled trials suggests that L-carnitine may be of benefit to individuals with hepatic encephalopathy, in terms of bilirubin, ammonia, urea, and liver enzymes (384; 292; 383; 277; 458; 382; 381; 291; 411; 377; 406). In human research, acetyl-L-carnitine reduced levels of AST, ALT, and hepatitis C viremia; significant between-group difference in levels of bilirubin and albumin were lacking (385; 280; 384).
  • Markers of purine catabolismMarkers of purine catabolism: Exercise-induced increases in plasma markers of purine catabolism (hypoxanthine, xanthine oxidase, and serum uric acid) were significantly attenuated by L-carnitine L-tartrate supplementation (978).
  • MyoglobinMyoglobin: In human research, carnitine use resulted in decreased levels of myoglobin postexercise (370).
  • Nitric oxideNitric oxide: In human research, carnitine increased nitric oxide (465).
  • PhosphorusPhosphorus: A decrease in phosphorous levels was noted in hemodialysis patients (977).
  • Plasma lipids and lipoproteinsPlasma lipids and lipoproteins: In patients with type 2 diabetes, the additional effects of carnitine over simvastatin alone resulted in decreased triglycerides (p<0.001), apo B (p<0.05), Lp(a) (p<0.05), and apo(a) (p<0.05), and significant increases in HDL cholesterol (p<0.05) (605). 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). Increased triglycerides, Apo B100, and Apo A1 were found in individuals with diabetes on glyburide or metformin (253) and in uremic patients on hemodialysis (255). Decreased cholesterol has been noted (257; 621; 618; 331; 614; 478; 265; 266; 312; 445). Increased HDL has been noted (621; 622; 623; 618; 619; 312). A decreased ratio of total cholesterol to HDL cholesterol has been noted (622; 623). No changes in Apo A1 or Apo B were noted in hypertensive individuals (618), but they were reduced in elderly individuals and other studies (312; 266; 624). No changes in triglycerides, total cholesterol, HDL cholesterol, ApoA, or Apo B were noted in other studies (497; 619; 351; 455; 389; 472). In pregnant women, carnitine reduced levels of free fatty acids and triglycerides (slightly) (503).
  • Plasma fatty acidsPlasma fatty acids: Carnitine supplementation did not affect eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content (964). Use of a new lipid emulsion containing carnitine, in infants, resulted in a decrease in DHA and arachidonic acid (AA) (969).
  • Plasma nitrate/nitritePlasma nitrate/nitrite: In resistance trained men, glycine propionyl-L-carnitine increased plasma nitrate/nitrite (988). In human research, oral acetyl-L-carnitine arginate increased plasma nitrate/nitrite (600).
  • Plasminogen activator inhibitor-1Plasminogen activator inhibitor-1: A decrease in plasminogen activator inhibitor-1has been noted with clinical use of propionyl-L-carnitine (417; 417)
  • Platelet aggregationPlatelet aggregation: An increased in platelet aggregation ex vivo was noted in uremic patients on hemodialysis (255).
  • ProteinProtein: In human research, carnitine increased plasma protein and albumin (444; 452).
  • Prothrombin timeProthrombin time: In human research on patients with minimal hepatic encephalopathy, carnitine decreased prothrombin time (277).
  • PyruvatePyruvate: A decrease in pyruvate was noted in septic patients on parenteral nutrition (968).
  • Red blood cell superoxide dismutase (SOD)Red blood cell superoxide dismutase (SOD): In humans, carnitine increased red cell SOD activity (333).
  • Red blood cell velocityRed blood cell velocity: In human research, propionyl-L-carnitine resulted in increased red blood cell velocity (464).
  • Serum amyloid ASerum amyloid A: In human research, carnitine resulted in decreased serum amyloid A (989).
  • Serum myoglobinSerum myoglobin: A decrease in serum myoglobin was noted in a clinical trial of L-carnitine (990).
  • Sperm parametersSperm parameters: According to a meta-analysis and systematic review, carnitine and/or acetyl-L-carnitine resulted in improvements in total sperm motility, forward sperm motility, sperm concentration, and atypical sperm cells (991; 402). In human research, although L-carnitine increased the percentage of grade a + b sperm, significant changes in sperm concentration, sperm motility, and rate of sperm deformity were lacking (272).
  • TNF-alphaTNF-alpha: A decrease in TNF-alpha has been noted in HIV patients (313).
  • TransferrinTransferrin: In human research, carnitine increased plasma transferrin (444).
  • TryptophanTryptophan: In animal research, carnitine increased plasma levels of tryptophan (889).
  • Urea nitrogenUrea nitrogen: A slight decrease in urea nitrogen has been noted in hemodialysis patients (977), and a decrease occurred in animal research (602).
  • White blood cell countsWhite blood cell counts: Increased CD4 and CD8 lymphocyte counts have been noted in some individuals with HIV-1 infection treated with L-carnitinge, but not been treated with antiretroviral therapy (992). In separate human research, there was a lack of effect on white blood cell count (472).