Thioctic acid
Alpha-lipoic acid/Drug Interactions:
AnalgesicsAnalgesics: In human research, alpha-lipoic acid reduced the pain from burning mouth syndrome (97; 98; 135). In human research, alpha-lipoic acid reduced pain caused by a herniated disk (148). Alzheimer's agentsAlzheimer's agents: In human research, alpha-lipoic acid potentially reduced progression of dementia (161). However, in other human research, a combination of vitamins E and C, and alpha-lipoic acid caused a decrease in Mini-Mental State Examination scores (104). Antianxiety agentsAntianxiety agents: Patients with burning mouth syndrome who had previously been treated with tranquilizers responded poorly to therapy with alpha-lipoic acid compared with those who had not received previous psychotropic therapy (162). Sleep disturbances were reported in a clinical trial, but both were also reported in the placebo group, and significance is unclear (83). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, supplementation with alpha-lipoic acid lacked an effect on fibrinolytic variables, including thrombin (prothrombin fragment 1 + 2, thrombin-antithrombin complexes) and fibrin formation (fibrinopeptide A), as well as markers of the fibrinolytic activity (tissue-plasminogen activator, plasmin-antiplasmin complexes, d-dimers) either at rest or in response to exercise (108). In human research, alpha-lipoic acid decreased platelet reactivity and the expression of CD62P in platelets ex vivo (31). The effect of alpha-lipoic acid has been examined on platelet reactivity in patients with type 1 diabetes; however, results were unclear (163). AntidiabeticsAntidiabetics: In human research, effects of alpha-lipoic acid on blood glucose levels and glucose hemostatis were mixed, with decreases or no effects occurring, alone or in combination with antidiabetic agents (8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 88; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 89; 90). In human research, alpha-lipoic acid improved steady state plasma insulin, glucose infusion rate, and insulin sensitivity index (13). In laboratory research, alpha-lipoic acid increased the overall glucose uptake (164; 165; 26; 166; 167; 15; 168; 169; 170). In human research, alpha-lipoic acid potentially reduced the need for antidiabetic medication, potentially causing short-term hypoglycemia (details regarding the placebo or alpha-lipoic acid group were lacking) (15). Anti-inflammatoriesAnti-inflammatories: In human research, alpha-lipoic acid reduced levels of cellular or blood tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-17, and IL-2 in most studies (171; 13; 125), but it lacked effect on IL-6, IL-1 beta, and TNF-alpha in another (147). Anti-inflammatory effects of alpha-lipoic acid have also been shown in vitro (2; 172). AntihypertensivesAntihypertensives: In human research, alpha-lipoic acid lacked effects on blood pressure in most studies (130; 15; 28; 124; 13); however, decreases were noted in others (82). AntilipemicsAntilipemics: In human research, alpha-lipoic acid has been shown to moderate cholesterol increases associated with use of atypical antipsychotic drugs (107). Improvements in plasma lipids (decreased total cholesterol, LDL cholesterol, and triglycerides, and/or increased HDL cholesterol) occurred in some (82; 118; 13) but not all (19; 17; 20; 27; 96; 126; 28; 30; 29) human studies. In HIV patients on antiretroviral therapy, changes in fat mass and lipid profile were lacking (173) AntineoplasticsAntineoplastics: In human research, a combination of alpha-lipoic acid, hydroxycitrate, cisplatin, and methotrexate was more effective than both alpha-lipoic acid and hydroxycitrate alone, and cisplatin and methotrexate alone (174). There is some preliminary evidence of benefit of alpha-lipoic acid in cancer patients in case reports (175; 176). According to secondary sources, alpha-lipoic acid antagonizes the action of cisplatin and may reduce cisplatin effectiveness. Anticancer effects of alpha-lipoic acid have been shown in vitro (177; 178). Antioxidants may influence the response to chemotherapy, as well as the development of adverse side effects that results from treatment with antineoplastic agents (179). Antiobesity agentsAntiobesity agents: In animal research, alpha-lipoic acid reduced body weight and food intake (180). In human research, alpha-lipoic acid has been shown to reduce weight gain associated with use of atypical antipsychotic drugs (107). In human research, alpha-lipoic acid increased weight loss in obese subjects (28) but lacked effect on body weight in other studies (15). Weight gain was reported in a clinical trial (84). In HIV patients on antiretroviral therapy, changes in fat mass and lipid profile were lacking (173). AntipsychoticsAntipsychotics: In human research, alpha-lipoic acid has been shown to reduce weight gain and cholesterol increases associated with use of atypical antipsychotic drugs (107). In vitro, alpha-lipoic acid prevented the antipsychotic induced dopamine D2 receptor upregulation and oxidative stress (181). AntiretroviralsAntiretrovirals: In HIV patients on antiretroviral therapy, changes in fat mass and lipid profile were lacking (173); however, alpha-lipoic acid improved lymphocyte function in patients with history of unresponsiveness to highly active antiretroviral treatment (123). In laboratory research, alpha-lipoic acid suppressed HIV transcription (182; 183; 184) and delayed replication of HIV (185; 186). In vitro, lipoic acid reduced the growth of vaccinia virus (187). AntiviralsAntivirals: In HIV patients on antiretroviral therapy, changes in fat mass and lipid profile were lacking (173); however, alpha-lipoic acid improved lymphocyte function in patients with history of unresponsiveness to highly active antiretroviral treatment (123). In laboratory research, alpha-lipoic acid suppressed HIV transcription (182; 183; 184) and delayed replication of HIV (185; 186). In vitro, lipoic acid reduced the growth of vaccinia virus (187). Cardiovascular agentsCardiovascular agents: In human research, antioxidants, including alpha-lipoic acid, were found to offer some improvements in patients undergoing cardiac surgery (188). In human research, alpha-lipoic acid reduced the pain associated with exercise in patients with peripheral artery disease (84). CNS depressantsCNS depressants: Patients with burning mouth syndrome who had previously been treated with tranquilizers responded poorly to therapy with alpha-lipoic acid compared with those who had not received previous CNS depressant therapy (162). Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Alpha-lipoic acid decreased NADPH-cytochrome P450 reductase activity in the human heart, liver, and lungs (189; 190). In vitro, alpha-lipoic acid was used as a reversible inhibitor of NADPH:cytochrome P450 reductase (191). Dermatologic agentsDermatologic agents: In human research, alpha-lipoic acid was found to have moderate antioxidative capability in terms of preventing oxidative damage to proteins in the human stratum corneum (192). In human research, DermaViteT, a preparation containing marine proteins, alpha-lipoic acid, pine bark extract, vitamins, and minerals, was found to be beneficial in aging symptoms of the skin (94). In human research, antioxidants containing alpha-lipoic acid before and during NB-UVB improved the clinical effectiveness of NB-UVB for vitiligo (193). Doxorubicin (Adriamycin?)Doxorubicin (Adriamycin?): In vitro, alpha-lipoic acid when given with doxorubicin provided a protective effect against cardiotoxicity (194). Drugs used for osteoporosisDrugs used for osteoporosis: Alpha-lipoic acid suppressed osteoclastogenesis in vitro (195). Erythropoietin-stimulating agentsErythropoietin-stimulating agents: In human research, a combination of antioxidants and vitamin D reduced the need for erythropoietin-stimulating agents in patients that were vitamin D deficient with anemic dialysis (196). GabapentinGabapentin: In human research, for burning mouth syndrome, one study reported better efficacy with a combination of alpha-lipoic acid and gabapentin (GABA) than either agent alone (98; 145). Glaucoma agentsGlaucoma agents: In human research, alpha-lipoic acid improved biochemical parameters and visual function in patients with glaucoma (122). Hematological agentsHematological agents: In human research, a combination of antioxidants and vitamin D reduced the need for erythropoietin-stimulating agents in patients that were vitamin D deficient with anemic dialysis (196). HepatotoxinsHepatotoxins: Alpha-lipoic acid has been advocated for liver disease; however, its use is anecdotal, and the mechanism of action remains unclear.ImmunosuppressantsImmunosuppressants: Alpha-lipoic acid supplementation was associated with an enhancement in glutathione levels and recovery of lymphocyte proliferative responsiveness in patients who previously failed antiretroviral treatment (HAART) (123). In vitro, alpha-lipoic acid and DHLA inhibited the migration of Jurkat cells, as well as matrix metalloproteinase (MMP)-9 activity in Jurkat cell supernatants (56). Neurologic agentsNeurologic agents: In animal research, alpha-lipoic acid scavenged very-long-chain fatty acid-dependent generation of reactive oxygen species, resulting in reduced oxidative stress to proteins, axonal degeneration, and locomotor impairment (197). In animal research, alpha-lipoic acid prevented nerve dysfunction, based on nerve conduction velocity (198). NitroglycerinNitroglycerin: In human research, alpha-lipoic acid before treatment prevented the inhibition of mitochondrial aldehyde dehydrogenase and nitrate bioactivation by nitroglycerin (199). Ophthalmic agentsOphthalmic agents: In human research, alpha-lipoic acid improved biochemical parameters and visual function in patients with glaucoma (122). Thyroid hormonesThyroid hormones: In animal research, alpha-lipoic acid interfered with the transformation of T4 to T3 (109). Tricyclic antidepressantsTricyclic antidepressants: The authors of a systematic review stated that the effect of alpha-lipoic acid treatment on neuropathy was comparable to the effects of carbamazepine, gabapentin, and tricyclic antidepressants (6). VasodilatorsVasodilators: In human research, alpha-lipoic acid improved endothelial dysfunction and flow-mediated dilation in most studies (124; 21; 82; 23; 153; 27). In vitro in vascular smooth muscle cells, alpha-lipoic acid up- or downregulated proteins involved in functioning of the cells (32). In laboratory research, alpha-lipoic acid was found to improve endothelial dysfunction and vasodilation (72; 200). VasopressorsVasopressors: In human research, alpha-lipoic acid improved endothelial dysfunction and flow-mediated dilation in most studies (124; 21; 82; 23; 153; 27). In vitro in vascular smooth muscle cells, alpha-lipoic acid up- or downregulated proteins involved in functioning of the cells (32). In laboratory research, alpha-lipoic acid was found to improve endothelial dysfunction and vasodilation (72; 200). Alpha-lipoic acid/Herb/Supplement Interactions:
AnalgesicsAnalgesics: In human research, alpha-lipoic acid reduced the pain from burning mouth syndrome (97; 98; 135). In human research, alpha-lipoic acid reduced pain caused by a herniated disk (148). Alzheimer's agentsAlzheimer's agents: In human research, alpha-lipoic acid potentially reduced progression of dementia (161). However, in other human research, a combination of vitamins E and C and alpha-lipoic acid caused a decrease in Mini-Mental State Examination scores (104). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In human research, supplementation with alpha-lipoic acid lacked an effect on fibrinolytic variables, including thrombin (prothrombin fragment 1 + 2, thrombin-antithrombin complexes) and fibrin formation (fibrinopeptide A), as well as markers of the fibrinolytic activity (tissue-plasminogen activator, plasmin-antiplasmin complexes, d-dimers) either at rest or in response to exercise (108). In human research, alpha-lipoic acid decreased platelet reactivity and the expression of CD62P in platelets ex vivo (31). The effect of alpha-lipoic acid has been examined on platelet reactivity in patients with type 1 diabetes; however, results were unclear (163). AntidepressantsAntidepressants: The authors of a systematic review stated that the effect of alpha-lipoic acid treatment on neuropathy was comparable to the effects of carbamazepine, gabapentin, and tricyclic antidepressants (6). Anti-inflammatoriesAnti-inflammatories: In human research, alpha-lipoic acid reduced levels of cellular or blood tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-17, and IL-2 in most studies (171; 13; 125), but it lacked effect on IL-6, IL-1 beta, and TNF-alpha in another (147). Anti-inflammatory effects of alpha-lipoic acid have also been shown in vitro (2; 172). AntilipemicsAntilipemics: In human research, alpha-lipoic acid has been shown to moderate cholesterol increases associated with use of atypical antipsychotic drugs (107). Improvements in plasma lipids (decreased total cholesterol, LDL cholesterol, and triglycerides, and/or increased HDL cholesterol) occurred in some (82; 118; 13) but not all (19; 17; 20; 27; 96; 126; 28; 30; 29) human studies. In HIV patients on antiretroviral therapy, changes in fat mass and lipid profile were lacking (173) AntineoplasticsAntineoplastics: In human research, a combination of alpha-lipoic acid, hydroxycitrate, cisplatin, and methotrexate was more effective than both alpha-lipoic acid and hydroxycitrate alone, and cisplatin and methotrexate alone (174). There is some preliminary evidence of benefit of alpha-lipoic acid in cancer patients in case reports (175; 176). According to secondary sources, alpha-lipoic acid antagonizes the action of cisplatin and may reduce cisplatin effectiveness. Anticancer effects of alpha-lipoic acid have been shown in vitro (177; 178). Antioxidants may influence the response to chemotherapy, as well as the development of adverse side effects that results from treatment with antineoplastic agents (179). Antiobesity agentsAntiobesity agents: In animal research, alpha-lipoic acid reduced body weight and food intake (180). In human research, alpha-lipoic acid has been shown to reduce weight gain associated with use of atypical antipsychotic drugs (107). In human research, alpha-lipoic acid increased weight loss in obese subjects (28), but it lacked effect on body weight in other studies (15). Weight gain was reported in a clinical trial (84). In HIV patients on antiretroviral therapy, changes in fat mass and lipid profile were lacking (173). AntioxidantsAntioxidants: Studies in humans have yielded mixed results, although the majority support the antioxidant effects of alpha-lipoic acid (116; 115; 17; 117; 118; 119; 121; 13; 192; 22). In laboratory research, alpha-lipoic acid and the metabolite DHLA had antioxidant activity and may interfere with other antioxidants (201; 202; 172; 73; 56; 54; 108). AntipsychoticsAntipsychotics: In human research, alpha-lipoic acid has been shown to reduce weight gain and cholesterol increases associated with use of atypical antipsychotic drugs (107). In vitro, alpha-lipoic acid prevented antipsychotic-induced dopamine D2 receptor upregulation and oxidative stress (181). AntiviralsAntivirals: In HIV patients on antiretroviral therapy, changes in fat mass and lipid profile were lacking (173); however, alpha-lipoic acid improved lymphocyte function in patients with history of unresponsiveness to highly active antiretroviral treatment (123). In laboratory research, alpha-lipoic acid suppressed HIV transcription (182; 183; 184) and delayed replication of HIV (185; 186). In vitro, lipoic acid reduced the growth of Vaccinia virus (187). BiotinBiotin: In human research, loss of taste due to a dietary supplement containing acyl-L-carnitine, alpha-lipoic acid, calcium, phosphorus, and biotin was treated with high-dose biotin (93). CalciumCalcium: In human research, loss of taste due to a dietary supplement containing acyl-L-carnitine, alpha-lipoic acid, calcium, phosphorus, and biotin was treated with high-dose biotin (93). Cardiovascular agentsCardiovascular agents: In human research, antioxidants, including alpha-lipoic acid, were found to offer some improvements in patients undergoing cardiac surgery (188). In human research, alpha-lipoic acid reduced the pain associated with exercise in patients with peripheral artery disease (84). Coenzyme Q10 (CoQ10)Coenzyme Q10 (CoQ10): In human research, alpha-lipoic acid lessened the increase in total CoQ10 plasma levels induced with hyperbaric oxygen (HBO) (150). Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Alpha-lipoic acid decreased NADPH-cytochrome P450 reductase activity in the human heart, liver, and lungs (189; 190). In vitro, alpha-lipoic acid was used as a reversible inhibitor of NADPH:cytochrome P450 reductase (191). Dermatologic agentsDermatologic agents: In human research, alpha-lipoic acid was found to have moderate antioxidative capability in terms of preventing oxidative damage to proteins in the human stratum corneum (192). In human research, DermaViteT, a preparation containing marine proteins, alpha-lipoic acid, pine bark extract, vitamins, and minerals, was found to be beneficial in aging symptoms of the skin (94). In human research, antioxidants containing alpha-lipoic acid before and during NB-UVB improved the clinical effectiveness of NB-UVB for vitiligo (193). Devil's clawDevil's claw: In human research, effects of alpha-lipoic acid on blood glucose levels and glucose hemostatis were mixed, with decreases or no effects occurring, alone or in combination with antidiabetic agents (8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 88; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29). Products that may raise blood sugar levels, such as devil's claw, may reduce the effectiveness of alpha-lipoic acid when used for a blood sugar-lowering effect. HepatotoxinsHepatotoxins: Alpha-lipoic acid has been advocated for liver disease; however, its use is anecdotal, and the mechanism of action remains unclear.Hyperglycemics and hypoglycemicsHyperglycemics and hypoglycemics: In human research, effects of alpha-lipoic acid on blood glucose levels and glucose hemostatis were mixed, with decreases or no effects occurring, alone or in combination with antidiabetic agents (8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 88; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 89; 90). In human research, alpha-lipoic acid improved steady state plasma insulin, glucose infusion rate, and insulin sensitivity index (13). In laboratory research, alpha-lipoic acid increased the overall glucose uptake (164; 165; 26; 166; 167; 15; 168; 169; 170). In human research, alpha-lipoic acid potentially reduced the need for antidiabetic medication, potentially causing short-term hypoglycemia (details regarding the placebo or alpha-lipoic acid group were lacking) (15). Hypertensives and hypotensivesHypertensives and hypotensives: In human research, alpha-lipoic acid lacked effects on blood pressure in most studies (130; 15; 28; 124; 13); however, decreases were noted in others (82). ImmunomodulatorsImmunomodulators: Alpha-lipoic acid supplementation was associated with an enhancement in glutathione levels and recovery of lymphocyte proliferative responsiveness in patients who previously failed antiretroviral treatment (HAART) (123). In vitro, alpha-lipoic acid and DHLA inhibited the migration of Jurkat cells, as well as matrix metalloproteinase (MMP)-9 activity in Jurkat cell supernatants (56). Neurologic agentsNeurologic agents: In animal research, alpha-lipoic acid scavenged very-long-chain fatty acid-dependent generation of reactive oxygen species, resulting in reduced oxidative stress to proteins, axonal degeneration, and locomotor impairment in an animal model (197). In animal research, alpha-lipoic acid prevented nerve dysfunction, based on nerve conduction velocity (198). Ophthalmic agentsOphthalmic agents: In human research, alpha-lipoic acid improved biochemical parameters and visual function in patients with glaucoma (122). Osteoporosis agentsOsteoporosis agents: Alpha-lipoic acid suppressed osteoclastogenesis in vitro (195). PhosphorusPhosphorus: In human research, loss of taste due to a dietary supplement containing acyl-L-carnitine, alpha-lipoic acid, calcium, phosphorus, and biotin was treated with high-dose biotin (93). SedativesSedatives: Patients with burning mouth syndrome who had previously been treated with tranquilizers responded poorly to therapy with alpha-lipoic acid compared with those who had not received previous psychotropic therapy (162). Sleep disturbances were reported in a clinical trial, but both were also reported in the placebo group, and significance is unclear (83). ThiamineThiamine: In animal research, thiamine deficiency has been reported with alpha-lipoic acid when taken in high doses (111; 112). Thyroid agentsThyroid agents: In animal research, alpha-lipoic acid interfered with the transformation of T4 to T3 (109). VasoconstrictorsVasoconstrictors: In human research, alpha-lipoic acid improved endothelial dysfunction and flow-mediated dilation in most studies (124; 21; 82; 23; 153; 27). In vitro in vascular smooth muscle cells, alpha-lipoic acid up- or downregulated proteins involved in functioning of the cells (32). In laboratory research, alpha-lipoic acid was found to improve endothelial dysfunction and vasodilation (72; 200). VasodilatorsVasodilators: In human research, alpha-lipoic acid improved endothelial dysfunction and flow-mediated dilation in most studies (124; 21; 82; 23; 153; 27). In vitro in vascular smooth muscle cells, alpha-lipoic acid up- or downregulated proteins involved in functioning of the cells (32). In laboratory research, alpha-lipoic acid was found to improve endothelial dysfunction and vasodilation (72; 200). Vitamin CVitamin C: Vitamin C levels may be increased when taken with alpha-lipoic acid (203). The reduced form of alpha-lipoic acid, DHLA, enhanced recycling of ascorbic acid and vitamin E (204; 205). Vitamin EVitamin E: The reduced form of alpha-lipoic acid, DHLA, enhanced recycling of ascorbic acid and vitamin E (204; 205). In human research, alpha-lipoic acid increased alpha-tocopherol plasma concentration (150). In rats, DHLA, in synergy with vitamin E, reduced oxidative damage to the hypoxic myocardium after reperfusion (206). Alpha-lipoic acid/Food Interactions:
GeneralGeneral: Theoretically, administration with food decreases the effects of alpha-lipoic acid, and therefore experts suggest that it be taken on an empty stomach.Alpha-lipoic acid/Lab Interactions:
AlbuminAlbumin: In human research, alpha-lipoic acid improved serum urinary excretion rates of albumin in some (22; 124), but not all (96), studies. In animal research, alpha-lipoic acid reduced albuminuria (207; 208; 209). Asymmetric dimethylarginine (ADMA)Asymmetric dimethylarginine (ADMA): In human research, alpha-lipoic acid reduced levels of ADMA (210; 96). Blood glucoseBlood glucose: In human research, effects of alpha-lipoic acid on blood glucose levels and glucose hemostatis were mixed, with decreases or no effects occurring, alone or in combination with antidiabetic agents (8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 88; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 89; 90). Blood lipidsBlood lipids: In human research, alpha-lipoic acid has been shown to moderate cholesterol increases associated with use of atypical antipsychotic drugs (107). Improvements in plasma lipids (decreased total cholesterol, LDL cholesterol, and triglycerides, and/or increased HDL cholesterol) occurred in some (82; 118; 13) but not all (19; 17; 20; 27; 96; 126; 28; 30; 29) human studies. Blood pressureBlood pressure: In human research, alpha-lipoic acid lacked effects on blood pressure in most studies (130; 15; 28; 124; 13); however, decreases were noted in others (82). cAMPcAMP: In multiple sclerosis patients, alpha-lipoic acid increased levels of cAMP in peripheral blood mononucleocytes (171). CD4+ lymphocyte countsCD4+ lymphocyte counts: In human research, alpha-lipoic acid reduced CD4+ lymphocyte counts in a nonclinically significant manner (105). Coagulation panelCoagulation panel: In human research, supplementation with alpha-lipoic acid lacked an effect on fibrinolytic variables, including thrombin (prothrombin fragment 1 + 2, thrombin-antithrombin complexes) and fibrin formation (fibrinopeptide A), as well as markers of the fibrinolytic activity (tissue-plasminogen activator, plasmin-antiplasmin complexes, d-dimers) either at rest or in response to exercise (108). In human research, alpha-lipoic acid decreased platelet reactivity and the expression of CD62P in platelets ex vivo (31). The effect of alpha-lipoic acid has been examined on platelet reactivity in patients with type 1 diabetes; however, results are unclear (163). Coenzyme Q10 (CoQ10)Coenzyme Q10 (CoQ10): In human research, alpha-lipoic acid lessened the increase in total CoQ10 plasma levels induced with hyperbaric oxygen (HBO) (150). C-reactive protein (CRP)C-reactive protein (CRP): In human research, an antioxidant containing alpha-lipoic acid lacked an effect on CRP levels in most studies (211; 196; 27; 96; 84; 29; 125; 147); however, it decreased in one study (126). Creatine kinaseCreatine kinase: In human research, alpha-lipoic acid lacked an effect on creatine kinase (117). CreatinineCreatinine: In human research, alpha-lipoic acid lacked effect on serum or urinary creatinine levels (17; 124). C-telopeptide (CTX)C-telopeptide (CTX): In human research, alpha-lipoic acid lacked effect on CTX levels (101). CytokinesCytokines: In human research, alpha-lipoic acid reduced levels of cellular or blood tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-17, and IL-2 in most studies (171; 13; 125; 13), but it lacked an effect on IL-6, IL-1 beta, and TNF-alpha in another (147). In human research, alpha-lipoic acid increased adiponectin levels (13). F2-isoprostaneF2-isoprostane: In human research, alpha-lipoic acid decreased cerebrospinal fluid F2-isoprostane levels (104). GlutathioneGlutathione: Alpha-lipoic acid supplementation improved HIV-caused glutathione deficiency (212; 213). Alpha-lipoic acid supplementation was associated with an enhancement in glutathione levels in patients who previously failed highly active antiretroviral treatment (HAART) (123). Glycated proteinsGlycated proteins: In human research, a combination of alpha-lipoic acid and benfotiamine reduced levels of advanced glycation end products (AGE) (214). DHLA prevented serum albumin glycation in vitro (215). Heart rateHeart rate: In human research, heart rate variability improved in some (87), but not all (130), studies. The effect of alpha-lipoic acid has been examined on heart rate variability in patients with type 1 diabetes; however, results are unclear (163). In human research, alpha-lipoic acid reduced (82) or had no effect (15) on heart rate. HomocysteineHomocysteine: In human research, alpha-lipoic acid lacked effect on homocysteine levels (101). InsulinInsulin: In human research, alpha-lipoic acid lacked effect on fasting insulin levels (15; 16). Liver function testsLiver function tests: In human research, alpha-lipoic acid reduced levels of aspartate and alanine transaminase (AST and ALT) in some (4), but not all (17), studies. Plasma troponin-1Plasma troponin-1: In human research, an antioxidant mixture containing alpha-lipoic acid increased plasma troponin-1 (188). Plasminogen activator inhibitor (PAI)-1Plasminogen activator inhibitor (PAI)-1: In human research, alpha-lipoic acid reduced levels of PAI-1 (125). Serum lactateSerum lactate: In human research, alpha-lipoic acid reduced serum lactate levels (9). Serum pyruvateSerum pyruvate: In human research, alpha-lipoic acid reduced serum pyruvate levels (9). ThiamineThiamine: In animal research, thiamine deficiency has been reported with alpha-lipoic acid when taken in high doses (111; 112). Thyroid panelThyroid panel: In animal research, alpha-lipoic acid interfered with the transformation of T4 to T3 (109). In human research, alpha-lipoic acid lacked an effect on free thyroxine (fT4), thyroid-stimulating hormone (TSH), and antithyroglobulin antibodies (Tg-Ab) (27). Trace elementsTrace elements: An overdose of alpha-lipoic acid has been hypothesized to cause trace element deficiency in those with diabetes mellitus (113). Uric acidUric acid: In human research, alpha-lipoic acid lacked effects on uric acid (13). Urinary radioactivityUrinary radioactivity: In human research, alpha-lipoic acid decreased urinary radioactivity levels (157). Vitamin CVitamin C: Vitamin C levels may be increased when taken with alpha-lipoic acid (203). The reduced form of alpha-lipoic acid, DHLA, enhanced recycling of ascorbic acid and vitamin E (204; 205). Vitamin EVitamin E: The reduced form of alpha-lipoic acid, DHLA, enhanced recycling of ascorbic acid and vitamin E (204; 205). In human research, alpha-lipoic acid increased alpha-tocopherol plasma concentration (150).