Pomegranate

Pomegranate/Drug Interactions:

  • GeneralGeneral: Theoretically, concomitant oral administration may cause precipitation of some drugs, due to the high tannin content of pomegranate. It is recommended to separate the administration of oral drugs and tannin-containing drugs by the longest period of time practical.
  • AbortifacientsAbortifacients: Uterine-stimulant effects of pomegranate have been observed in animals (65), although the consumption of pomegranate as a food is likely safe during pregnancy.
  • Alzheimer's agentsAlzheimer's agents: In animal study, treatment with pomegranate juice decreased the accumulation of soluble Abeta42 and amyloid deposition in the hippocampus (119).
  • AnalgesicsAnalgesics: The use of ellagic acid, a pomegranate fruit extract, as an analgesic has been investigated (120; 121). Ellagic acid may exert analgesic effects through a non-anti-inflammatory pathway (120). Additional details are lacking.
  • Angiotensin-converting enzyme (ACE) inhibitorsAngiotensin-converting enzyme (ACE) inhibitors: Pomegranate juice may have additive ACE-inhibitor effects (52). Blood pressure and potassium levels should be monitored. ACE inhibitors include captopril (Capoten?), enalapril (Vasotec?), lisinopril (Prinivil?, Zestril?), and ramipril (Altace?). Pomegranate juice was shown to decrease serum ACE activity and lower blood pressure in elderly hypertensive patients (52).
  • AnthelminticsAnthelmintics: Pomegranate may have medicinal use as an anthelmintic, although reports conflict (5; 6).
  • AntibioticsAntibiotics: In vitro studies have shown P. granatum to have notable antimicrobial activity against Staphylococcus aureus (122; 123; 124; 125) (including methicillin-resistant strains (126; 127)), Pseudomonas aeruginosa (122; 128; 129; 130; 124), Clostridia (125), Candidaalbicans (122; 124; 131), Helicobacter pylori (78), Escherichia coli (132; 133; 134; 123; 124), 16 Salmonella strains (135) (including Salmonella enteritidis (133)), the Bacillus sp. (136), Aspergillus niger, Saccharomyces cerevisiae (137), Lactobacillus plantarum (138), Listeria monocytogenes (139; 123), Yersinia enterocolitica (123), and several other common pathogenic organisms (140).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Pomegranate juice may interact with warfarin (59; 60; 61), possibly through inhibition of cytochrome P450 enzymes involved in warfarin metabolism (60; 61), resulting in subtherapeutic international normalized ratios (INRs) in patients receiving warfarin (61). Collagen-induced platelet aggregation was significantly decreased in platelet-rich plasma obtained from healthy men consuming pomegranate juice for two weeks compared to baseline (reduction of 11%; p<0.02) (62).
  • AntidiabeticsAntidiabetics: Preliminary research in animals has involved the use of pomegranate parts to lower blood glucose levels (57).
  • AntidiarrhealsAntidiarrheals: Aqueous and alcoholic extracts of powdered pomegranate rind and seed decreased diarrhea in animal research (141; 142).
  • AntifungalsAntifungals: P. granatum has been used as a topical antifungal agent for the treatment of candidiasis associated with denture stomatitis in a randomized controlled trial (94). According to laboratory studies, pomegranate has exhibited antifungal activity (133; 143; 144; 145; 146; 147).
  • AntihypertensivesAntihypertensives: According to preliminary human and in vitro research, pomegranate juice may have hypotensive effects (52). However, in 2% of subjects in a clinical trial, the consumption of pomegranate juice resulted in hypertension (55).
  • Anti-inflammatoriesAnti-inflammatories: Pomegranate cold-pressed seed oil (5mcg total polyphenols) inhibited cyclooxygenase (COX) activity by 37% in vitro, and pomegranate fermented juice and cold-pressed seed oil inhibited lipoxygenase enzyme activity by 23.8% and 75%, respectively (6).
  • AntilipemicsAntilipemics: In humans, the consumption of pomegranate juice may decrease cholesterol (86; 87). In vitro, pomegranate extract increased the concentrations of short-chain fatty acids (148).
  • AntimalarialsAntimalarials: In vitro, ellagitannins of pomegranate fruit rind were found to antagonize the host inflammatory response mechanisms (22).
  • AntineoplasticsAntineoplastics: Flavonoid-rich polyphenol fractions from the pomegranate fruit exert antiproliferative, anti-invasive, antieicosanoid, and proapoptotic actions in breast (149) and prostate cancer cells (150), as well as antiangiogenic effects (151) in vitro and in vivo (152). Preliminary evidence suggests that pomegranate fruit extracts (PFEs) may enhance and sensitize tamoxifen action in estrogen receptor (ER)-alpha positive breast cancer cells (153). According to animal research, pomegranate seed extract (PSE) may protect against cisplatin toxicity (154; 155).
  • Antiobesity agentsAntiobesity agents: Pomegranate seed oil has been found to reduce weight gain in mice, and may reduce the risk for type 2 diabetes by improving insulin sensitivity (156). In animal research, pomegranate seed oil resulted in reduced body weight (decreased body fat); the mechanism of action did not include reduced food intake, energy expenditure, or liver insulin sensitivity but involved peripheral insulin sensitivity improvements (157).
  • Antiulcer agentsAntiulcer agents: Gastroprotective effects of pomegranate and its constituents have been shown in other animal studies, including ulcer models (158; 159).
  • AntiviralsAntivirals: According to laboratory research, pomegranate (Punica granatum) purified polyphenol extract may have a synergistic effect with oseltamivir in inhibiting influenza virus (160). In vitro tests have shown that tannins from the pericarp of pomegranate inhibit HSV-2 replication, kill the virus, and block its adsorption to cells (161). According to invitro research, pomegranate juice may be effective against several foodborne viruses, including feline calicivirus (FCV-F9), murine norovirus (MNV-1), and MS2 (ssRNA) (162). In laboratory research, polyphenols from pomegranate have been associated with activity against the influenza virus (160; 163).
  • BuspironeBuspirone: In in vitro intestinal research, pomegranate juice treatment of intestinal sacs affected transport of buspirone, perhaps by inhibiting CYP3A4 enzymes (164).
  • CarbamazepineCarbamazepine: According to animal research, pretreatment with pomegranate juice increased the transport of carbamazepine across the intestine, possibly through CYP3A4 induction (165). However, another study suggested that pomegranate may inhibit the metabolism of oral carbamazepine (166).
  • Cardiovascular agentsCardiovascular agents: In patients with ischemic coronary heart disease, pomegranate juice resulted in a decrease in stress-induced ischemia (81). In atherosclerotic patients, consuming pomegranate juice for up to three years resulted in a decrease in carotid intima-media thickness (167). Cardiovascular protective effects have also been shown in animal studies (62; 168).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Pomegranate inhibits CYP450 enzymes (169; 60; 61), including intestinal CYP3A4 (166; 170) and 2D6 (170). Despite its mechanism of action, pomegranate does not appear to alter the clearance of intravenous or oral midazolam or simvastatin. However, another study suggested that pomegranate juice may induce CYP3A4 enzymes (165).
  • Dermatologic agentsDermatologic agents: In vitro, pomegranate seed oil stimulated keratinocyte proliferation and a mild thickening of the epidermis without the loss of ordered differentiation (171). Furthermore, pomegranate peel extract, fermented juice extract, and seed cake extract stimulated type I procollagen synthesis and inhibited matrix metalloproteinase-1 production by dermal fibroblasts.
  • Drugs used for osteoporosisDrugs used for osteoporosis: According to laboratory research, pomegranate ethanol extract has been shown to stimulate osteoblastic differentiation and inhibit interleukin-6 and nitric oxide in MC3T3-E1 cells (172).
  • Fertility agentsFertility agents: In animal research, pomegranate juice increased epididymal sperm concentration, sperm motility, spermatogenic cell density, the diameter of seminiferous tubules, and germinal cell layer thickness, and decreased the abnormal sperm rate; mechanisms of action may include antioxidant effects (173; 23). Beneficial effects on sperm parameters were also noted in a lead toxicity animal model (174).
  • Gastrointestinal agentsGastrointestinal agents: In animal models, pomegranate was found to be effective in inflammatory bowel models (175; 176; 177; 178).
  • Heart rate regulating agentsHeart rate regulating agents: In animal research, the water extract of a pomegranate peel decreased heart rate (63). In animal research, the whole fruit extract of pomegranate increased heart rate (64).
  • Hormonal agentsHormonal agents: Despite traditional suggestions of estrogenic activity of pomegranate, no steroidal hormones were isolated from pomegranate in recent research (179).
  • ImmunostimulantsImmunostimulants: In male rabbits, pomegranate rind powder (100mg/kg) stimulated both humoral and cell-mediated immune responses in rabbits (180). In Paralichthys olivaceus, pomegranate increased innate immune parameters and improved survival against lymphocystis disease virus (LDV) (181) and Uronema marinum (182).
  • ImmunosuppressantsImmunosuppressants: In male rabbits, pomegranate rind powder (100mg/kg) stimulated both humoral and cell-mediated immune responses in rabbits (180). In Paralichthys olivaceus, pomegranate increased innate immune parameters and improved survival against lymphocystis disease virus (LDV) (181) and Uronema marinum (182).
  • Impotence agentsImpotence agents: In animal research, increased intracavernous blood flow, improved erectile response, and smooth muscle relaxation occurred following pomegranate juice consumption (183).
  • Memory agentsMemory agents: In animal research, pomegranate juice reversed the memory deficits induced by diazepam, scopolamine, and sodium nitrite (184).
  • MidazolamMidazolam: In a small Japanese adult volunteer population, pomegranate juice did not significantly alter the pharmacokinetic profile of single subtherapeutic doses of midazolam (166). In children, pomegranate juice masked the bitter taste of midazolam and improved drug ingestion (185).
  • Neurologic agentsNeurologic agents: In animal research, treatment with pomegranate juice decreased the accumulation of soluble Abeta42 and amyloid deposition in the hippocampus (119). When exposed to pomegranate juice in utero, mice had less brain damage than controls (116). In animal research, pomegranate seed extract had anxiolytic and antinociceptive effects, increased sleep latency, and reduced sleep time and immobility (186).
  • RosuvastatinRosuvastatin: Rhabdomyolysis has been associated with pomegranate juice consumption in an individual with a history of elevated creatine kinase levels (58). Pomegranate juice is known to inhibit intestinal cytochrome P450 3A4, although hepatic P450 3A4 does not appear to play an important role in rosuvastatin metabolism.
  • Uterine stimulantsUterine stimulants: Uterine-stimulant effects of pomegranate have been observed in animals (65). One animal study found pomegranate seed extract to be a potent stimulator of phasic activity the uterus, possibly due to beta-sitosterol inhibiting potassium channels and SERCA, thereby increasing contraction via calcium entry on L-type calcium channels and MLCK (115).

    • Pomegranate/Herb/Supplement Interactions:

  • GeneralGeneral: Theoretically, concomitant oral administration may cause precipitation of some herbs and supplements due to the high tannin content of pomegranate. It is recommended to separate the administration of oral agents and tannin-containing herbs/supplements by the longest period of time practical.
  • AbortifacientsAbortifacients: Uterine-stimulant effects of pomegranate have been observed in animals (65), although the consumption of pomegranate as a food is likely safe during pregnancy.
  • Alzheimer's agentsAlzheimer's agents: In animal study, treatment with pomegranate juice decreased the accumulation of soluble Abeta42 and amyloid deposition in the hippocampus (119).
  • AnalgesicsAnalgesics: The use of ellagic acid, a pomegranate fruit extract, as an analgesic has been investigated (120; 121). Ellagic acid may exert analgesic effects through a non-anti-inflammatory pathway (120). Additional details are lacking.
  • Angiotensin-converting enzyme (ACE) inhibitorsAngiotensin-converting enzyme (ACE) inhibitors: Pomegranate juice may have additive ACE-inhibitor effects (52). Blood pressure and potassium levels should be monitored. Pomegranate juice was shown to decrease serum ACE activity and lower blood pressure in elderly hypertensive patients (52).
  • AnthelminticsAnthelmintics: Pomegranate may have medicinal use as an anthelmintic, although reports conflict (5; 6).
  • AntibacterialsAntibacterials: In vitro studies have shown P. granatum to have notable antimicrobial activity against Staphylococcus aureus (122; 123; 124; 125) (including methicillin-resistant strains (126; 127)), Pseudomonas aeruginosa (122; 128; 129; 130; 124), Clostridia (125), Candidaalbicans (122; 124; 131), Helicobacter pylori (78), Escherichia coli (132; 133; 134; 123; 124), 16 Salmonella strains (135), (including Salmonella enteritidis (133)), the Bacillus sp. (136), Aspergillus niger, Saccharomyces cerevisiae (137), Lactobacillus plantarum (138), Listeria monocytogenes (139; 123), Yersinia enterocolitica (123), and several other common pathogenic organisms (140).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Pomegranate juice may interact with warfarin (59; 60; 61), possibly through inhibition of cytochrome P450 enzymes involved in warfarin metabolism (60; 61), resulting in subtherapeutic international normalized ratios (INRs) in patients receiving warfarin (61). Collagen-induced platelet aggregation was significantly decreased in platelet-rich plasma obtained from healthy men consuming pomegranate juice for two weeks compared to baseline (reduction of 11%; p<0.02) (62).
  • AntidiarrhealsAntidiarrheals: Aqueous and alcoholic extracts of powdered pomegranate rind and seed decreased diarrhea in animal research (141; 142).
  • AntifungalsAntifungals: P. granatum has been used as a topical antifungal agent for the treatment of candidiasis associated with denture stomatitis in a randomized controlled trial (94). According to laboratory studies, pomegranate has exhibited antifungal activity (133; 143; 144; 145; 146; 147).
  • Anti-inflammatoriesAnti-inflammatories: Pomegranate cold-pressed seed oil (5mcg total polyphenols) inhibited cyclooxygenase (COX) activity by 37% in vitro, and pomegranate fermented juice and cold-pressed seed oil inhibited lipoxygenase enzyme activity by 23.8% and 75%, respectively (6).
  • AntilipemicsAntilipemics: In humans, the consumption of pomegranate juice may decrease cholesterol (86; 87). In vitro, pomegranate extract increased the concentrations of short-chain fatty acids (148).
  • AntimalarialsAntimalarials: In vitro, ellagitannins of pomegranate fruit rind were found to antagonize the host inflammatory response mechanisms (22).
  • AntineoplasticsAntineoplastics: Flavonoid-rich polyphenol fractions from the pomegranate fruit exerted antiproliferative, anti-invasive, antieicosanoid, and proapoptotic actions in breast (149) and prostate cancer cells (150), as well as antiangiogenic effects (151) in vitro and in vivo (152).
  • Antiobesity agentsAntiobesity agents: Pomegranate seed oil has been found to reduce weight gain in mice and may reduce risk for type 2 diabetes by improving insulin sensitivity (156). In animal research, pomegranate seed oil resulted in reduced body weight (decreased body fat); the mechanism of action did not include reduced food intake, energy expenditure, or liver insulin sensitivity but involved peripheral insulin sensitivity improvements (157).
  • AntioxidantsAntioxidants: Pomegranate has demonstrated antioxidant activity in human, animal, and in vitro studies (62; 167; 88; 187; 188; 168; 189).
  • Antiulcer agentsAntiulcer agents: Gastroprotective effects of pomegranate and its constituents have been shown in other animal studies, including ulcer models (158; 159).
  • AntiviralsAntivirals: Tannins from pomegranate have shown antiviral activity against the herpes simplex 2 virus (HSV-2). In vitro tests have shown that tannins from the pericarp of pomegranate inhibit HSV-2 replication, kill the virus, and block its adsorption to cells (161). According to invitro research, pomegranate juice may be effective against several foodborne viruses, including feline calicivirus (FCV-F9), murine norovirus (MNV-1), and MS2 (ssRNA) (162). In laboratory research, polyphenols from pomegranate have been associated with activity against the influenza virus (160; 163).
  • Cardiovascular agentsCardiovascular agents: In patients with ischemic coronary heart disease, pomegranate juice resulted in a decrease in stress-induced ischemia (81). In atherosclerotic patients, consuming pomegranate juice for up to three years resulted in a decrease in carotid intima-media thickness (167). Cardiovascular protective effects have also been shown in animal studies (62; 168).
  • Cytochrome P450-metabolized herbs and supplementsCytochrome P450-metabolized herbs and supplements: Pomegranate inhibits CYP450 enzymes (169; 60; 61; 190), including intestinal CYP3A4 (166; 170) and 2D6 (170). Despite its mechanism of action, pomegranate does not appear to alter the clearance of intravenous or oral midazolam or simvastatin. However, another study suggested that pomegranate juice may induce CYP3A4 enzymes (165).
  • Dermatologic herbs and supplementsDermatologic herbs and supplements: In vitro, pomegranate seed oil stimulated keratinocyte proliferation and a mild thickening of the epidermis without the loss of ordered differentiation (171). In vitro, pomegranate peel extract, fermented juice extract, and seed cake extract stimulated type I procollagen synthesis and inhibited matrix metalloproteinase-1 production by dermal fibroblasts (171).
  • Fertility agentsFertility agents: In animal research, pomegranate juice increased epididymal sperm concentration, sperm motility, spermatogenic cell density, the diameter of seminiferous tubules, and germinal cell layer thickness, and decreased the abnormal sperm rate; mechanisms of action may include antioxidant effects (173; 23). Beneficial effects on sperm parameters were also noted in a lead toxicity animal model (174).
  • Gastrointestinal agentsGastrointestinal agents: In animal models, pomegranate was found to be effective in inflammatory bowel models (175; 176; 177; 178).
  • GrapefruitGrapefruit: Both grapefruit and pomegranate inhibited the CYP450 isoenzyme (190). Theoretically, concurrent consumption of both fruits may have synergistic effects.
  • Heart rate regulating agentsHeart rate regulating agents: In animal research, the water extract of a pomegranate peel decreased heart rate (63). In animal research, the whole fruit extract of pomegranate increased heart rate (64).
  • Hormonal agentsHormonal agents: Despite traditional suggestions of estrogenic activity of pomegranate, no steroidal hormones were isolated from pomegranate in recent research (179). In vitro, punicic acid inhibited estrogen receptor (ER)-alpha and ER-beta; alpha-eleostearic acid inhibited ER-alpha/ER-beta (191). The authors concluded that both linolenic acid isomers from pomegranate were selective estrogen receptor modulators (SERMs).
  • HypoglycemicsHypoglycemics: Preliminary research in animals has involved the use of pomegranate parts to lower blood glucose levels (57).
  • HypotensivesHypotensives: According to preliminary human and in vitro research, pomegranate juice may have hypotensive effects (52). However, in 2% of subjects in a clinical trial, the consumption of pomegranate juice resulted in hypertension (55).
  • ImmunomodulatorsImmunomodulators: In male rabbits, pomegranate rind powder (100mg/kg) stimulated both humoral and cell-mediated immune responses in rabbits (180). In Paralichthys olivaceus, pomegranate increased innate immune parameters and improved survival against lymphocystis disease virus (LDV) (181) and Uronema marinum (182).
  • Impotence agentsImpotence agents: In animal research, increased intracavernous blood flow, improved erectile response, and smooth muscle relaxation occurred following pomegranate juice consumption (183).
  • IronIron: The fruit husk and root/stem bark of pomegranate contain up to 28% and 25% tannins, respectively, compared to 12.9% in black tea and 22.2% in green tea. The tannin content of various herbs may interact with iron, forming nonabsorbable complexes (192; 193; 194).
  • Memory agentsMemory agents: In animal research, pomegranate juice reversed the memory deficits induced by diazepam, scopolamine, and sodium nitrite (184).
  • Metal saltsMetal salts: According to laboratory research, the addition of metal salts and vitamin C may enhance antimicrobial activity of pomegranate rind extracts (195).
  • Neurologic agentsNeurologic agents: In animal research, treatment with pomegranate juice decreased the accumulation of soluble Abeta42 and amyloid deposition in the hippocampus (119). When exposed to pomegranate juice in utero, mice had less brain damage than controls (116). In animal research, pomegranate seed extract had anxiolytic and antinociceptive effects, increased sleep latency, and reduced sleep time and immobility (186).
  • Osteoporosis agentsOsteoporosis agents: According to laboratory research, pomegranate ethanol extract has been shown to stimulate osteoblastic differentiation and inhibit interleukin-6 and nitric oxide in MC3T3-E1 cells (172).
  • PhytoestrogensPhytoestrogens: Despite traditional suggestions of estrogenic activity of pomegranate, no steroidal hormones were isolated from pomegranate in recent research (179). In vitro, punicic acid inhibited estrogen receptor (ER)-alpha and ER-beta; alpha-eleostearic acid inhibited ER-alpha/ER-beta (191). The authors concluded that both linolenic acid isomers from pomegranate were selective estrogen receptor modulators (SERMs).
  • ProbioticsProbiotics: In vitro, constituents of pomegranate, punicalagins, punicalins, and ellagic acid slightly inhibited the growth of Bifidobacterium animalis ssp. lactis; however, pomegranate extract increased the growth of Bifidobacterium breve and Bifidobacterium infantis (125).
  • Tannin-containing agentsTannin-containing agents: Theoretically, herbs that contain high percentages of tannins (such as pomegranate) may cause the precipitation of constituents of other herbs and supplements.
  • Uterine stimulantsUterine stimulants: Uterine-stimulant effects of pomegranate have been observed in animals (65). One animal study found pomegranate seed extract to be a potent stimulator of phasic activity the uterus, possibly due to beta-sitosterol inhibiting potassium channels and SERCA, thereby increasing contraction via calcium entry on L-type calcium channels and MLCK (115).
  • Vitamin CVitamin C: One pomegranate delivers approximately 40% of an adult's daily vitamin C requirement. According to laboratory research, the addition of metal salts and vitamin C may enhance antimicrobial activity of pomegranate rind extracts (195).

    • Pomegranate/Food Interactions:

  • GrapefruitGrapefruit: Both grapefruit and pomegranate inhibit the CYP450 isoenzyme (190). Theoretically, concurrent consumption of both fruits may have synergistic effects.
  • Tannin-containing foodsTannin-containing foods: The tannin content of pomegranate may interact with concomitantly administered iron, resulting in nonabsorbable, insoluble complexes and possibly in adverse sequelae on blood components.

    • Pomegranate/Lab Interactions:

  • AdiponectinAdiponectin: In animal research, pomegranate seed oil during high-fat feeding was associated with an increased concentration of leptin and a decreased concentration of adiponectin (156).
  • Antioxidant endpointsAntioxidant endpoints: In human research, pomegranate increased ferric reducing/antioxidant power (FRAP) assay (196; 79) and sulfhydryl groups (80; 77), and decreased plasma carbonyl (79) and thiobarbituric acid reactive substances (TBARS) (53; 77).
  • Blood glucoseBlood glucose: Preliminary research in animals has involved the use of pomegranate parts to lower blood glucose levels (57).
  • Blood lipidsBlood lipids: According to human research, the consumption of pomegranate juice may decrease cholesterol (86; 87). In vitro, pomegranate extract increased the concentrations of short-chain fatty acids (148).
  • Blood pressureBlood pressure: According to preliminary human and in vitro research, pomegranate juice may have hypotensive effects (52). However, in 2% of subjects in a clinical trial, the consumption of pomegranate juice resulted in hypertension (55).
  • Coagulation panelCoagulation panel: Collagen-induced platelet aggregation was significantly decreased in platelet-rich plasma obtained from healthy men consuming pomegranate juice for two weeks compared to baseline (reduction of 11%; p<0.02) (62).
  • Heart rateHeart rate: In animal research, the water extract of a pomegranate peel decreased heart rate (63). In animal research, the whole fruit extract of pomegranate increased heart rate (64).
  • Hematological measurementsHematological measurements: In animal research, pomegranate seed extract increased erythrocyte and leukocyte counts, hemoglobin, and hematocrit, and decreased percentage rates of total lymphocytes and ANAE positive lymphocytes (197).
  • Hormone panelHormone panel: Despite traditional suggestions of estrogenic activity of pomegranate, no steroidal hormones were isolated from pomegranate in a recent analysis (179).
  • LeptinLeptin: In animal research, pomegranate seed oil during high-fat feeding was associated with an increased concentration of leptin and a decreased concentration of adiponectin (156).
  • Probiotic bacteriaProbiotic bacteria: In vitro, pomegranate extract increased the growth of total bacteria, Bifidobacterium spp., and Lactobacillus spp. (148).
  • Salivary dental health markersSalivary dental health markers: In human research, pomegranate extract mouth-rinsing reduced total protein, activities of aspartate aminotransferase, and alpha-glucosidase activity, and increased activities of the antioxidant enzyme ceruloplasmin and radical-scavenging capacity, in saliva (198).