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American hellebore


Zinc/Nutrient Depletion:
  • ACE inhibitorsACE inhibitors: In human research, ACE inhibitors such as captopril (Capoten®) and enalapril (Vasotec®) had the potential to increase urine zinc excretion, resulting in zinc deficiency (272).
  • AntibioticsAntibiotics: According to expert opinion, tetracyclines forms complexes with zinc in the gastrointestinal tract, thereby decreasing the absorption and serum levels of tetracyclines, including demeclocycline, minocycline, and tetracycline (273). However, in human research, doxycycline lacked an interaction with zinc (662; 663). Similarly, quinolones (e.g., ciprofloxacin) may also form complexes with zinc in the gastrointestinal tract and decrease the absorption of these antibiotics (274).
  • Anti-hypertensivesAnti-hypertensives: According to human research, both captopril and enalopril increased renal zinc loss; however, captopril had the greatest effect on increased zinc excretion, and decreased plasma and erythrocyte zinc levels (275). In a patient being treated with captopril, zinc supplementation was able to reverse symptoms of zinc deficiency (676).
  • Anti-seizure agentsAnti-seizure agents: In human research, valproate treatment was associated with a reduction in erthryocyte, but not plasma or urinary, levels of zinc (277). The clinical significance of reduced manganese and zinc levels in treated epileptic patients was the topic of discussion (667). Valproate, birth defects, and zinc have also been the topic of discussion (668). Further details are lacking for these two publications.
  • CaffeineCaffeine: According to secondary sources, caffeine may decrease zinc concentrations.
  • Calcium saltsCalcium salts: A decrease in zinc absorption following calcium supplementation has been observed (20); increased calcium levels were observed in children following zinc supplementation (691).
  • CaroteneCarotene: In human research, zinc decreased carotene levels (162).
  • CisplatinCisplatin: In human research, cisplatin was shown to increase urinary zinc excretion and reduce plasma zinc levels (276).
  • CorticosteroidsCorticosteroids: In human research, large doses or prolonged use of corticosteroids were found to potentially reduce zinc levels, as the pituitary-adrenal axis may play a role in controlling zinc levels (278; 279). Increased urinary excretion of zinc has also been reported (280).
  • Deferoxamine (Desferal®)Deferoxamine (Desferal®): Deferoxamine increased urinary zinc elimination (281; 282; 283).
  • DexrazoxaneDexrazoxane: In human research, dexrazoxane has been shown to increase zinc excretion (284).
  • DisulfiramDisulfiram: In animal research, disulfiram has been shown to decrease intestinal absorption of zinc (285). According to expert opinion, disulfiram may act as a chelator of zinc (286).
  • DiureticsDiuretics: It has been suggested that in humans, thiazide diuretics (e.g., hydrochlorothiazide) and thiazide-like diuretics (e.g., chlorthalidone) may increase the urinary excretion of zinc (287; 288; 289; 290). In human research, hydrochlorothiazide increased urinary zinc excretion (291). Loop diuretics (e.g., furosemide) have been shown to reduce zinc concentrations and increase zinc excretion to a lesser extent than thiazide diuretics (287). However, in human research, the potassium-sparing diuretic amiloride (Midamor®) was also shown to reduce urinary zinc excretion (292). In other research, administration of diuretics lacked an effect on serum zinc levels (705).
  • Ethanol (alcohol)Ethanol (alcohol): Alcohol may decrease serum zinc concentrations (293).
  • Folic acidFolic acid: In human research, folic acid supplementation was suggested as interfering with intestinal absorption of zinc (303; 304). However, in other human and animal research, impairment was lacking (756).
  • GlucoseGlucose: In humans, zinc has been reported to improve glycemic control, shown by decreasing HbA1c concentration, as well as decrease fasting and postprandial blood sugar (234). In human research, zinc resulted in improved glucose disappearance and glucose effectiveness in a glucose challenge (236).
  • H2 blockersH2 blockers: Administration of the histamine-2 (H2) blocker cimetidine (Tagamet®) was suggested to alter zinc levels (295).
  • Hormonal agentsHormonal agents: In human research, estrogens have been shown to reduce zinc excretion (716; 717) and plasma zinc levels (308); however, effects on plasma zinc levels were lacking in some studies (718; 719).
  • IronIron: In human research, zinc supplementation in children lacked an effect on hemoglobin concentrations (792). Zinc use decreased serum hemoglobin in pregnant women (313). In human research, zinc has had negative effects on iron bioavailability at higher doses (11mg) (311); resulted in decreased serum iron, hemoglobin levels, and transferrin saturation (312; 313); decreased plasma ferritin and the percentage of transferrin saturation (314); and resulted in anemia or reduced iron levels (195; 136). Effects of iron on zinc levels or absorption or effects of zinc on erythrocyte incorporation of iron were lacking in further human research (761; 762; 763; 764; 765), and iron, zinc, and vitamin A have been used in combination to increase hemoglobin values most effectively in anemic women (766)
  • LipidseLipidse: Zinc had mixed effects on lipid levels in human research. In individuals with low baseline cholesterol levels, zinc resulted in increased total and LDL cholesterol levels and lacked an effect on HDL cholesterol levels (377). In human research, zinc lacked effects on total cholesterol levels, decreased LDL cholesterol, and had mixed effects on HDL cholsterol types, with increased HDL2 and a slight decrease in HDL3 (378). In a separate clinical trial, zinc decreased total cholesterol and lacked effects on triglycerides (171; 379). According to a review, at nontoxic lower levels but still above the RDA (from close to the RDA up to 100-300mg), reported adverse effects included an increased LDL:HDL cholesterol ratio (134), and reduced HDL:total cholesterol ratios were shown in other clinical trials (135). According to reviews, long-term, high-dose administration of zinc may result in decreased HDL cholesterol levels (1). Reduced levels of HDL cholesterol were observed in other clinical trials (137; 138; 136). The mixed effect of zinc on these parameters may be due to dosing, the age and/or sex of the participant, or baseline zinc and/or plasma lipid levels (379). In animal research, cholestyramine, a bile acid sequestrant, decreased urinary zinc excretion (679). In in vitro research, treatment with HMG-CoA reductase inhibitors resulted in an active zinc signal in peripheral blood mononuclear cells (PBMCs) from low-grade atherosclerotic patients (680).
  • Magnesium supplementsMagnesium supplements: In postmenopausal women, zinc supplementation increased excretion of magnesium, resulting in a magnesium imbalance (307).
  • Nicotinic acidNicotinic acid: Zinc supplementation has been shown to increase excretion rates of N'metylnicotinamide, a metabolite of nicotinic acid, and N'methyl-2-pyrodine-5-carboximide, an end product of nicotinamide-adenine dinucleotide (NAD) degradation, in alcoholic patients (728).
  • Penicillamine (Cuprimine®)Penicillamine (Cuprimine®): In human and in vitro research, penicillamine chelated zinc and was therefore suggested to reduce its supplemental effects (296; 202). Dosing times should be separated by at least two hours. Seelig et al. suggested the potential for a role of zinc depletion in autoimmune complications of penicillamine (further details are lacking) (732), and the possible interaction between penicillamine and zinc was discussed by other authors (136).
  • PhenytoinPhenytoin: In human research, phenytoin use has been associated with reduced zinc levels (297). In human research and according to expert opinion, phenytoin acted as a chelator of zinc (297; 286).
  • PropofolPropofol: Propofol in fusion contains EDTA, a chelator of zinc. In human research, concurrent use increased the urinary excretion of zinc and reduce zinc levels (298).
  • Proton pump inhibitorsProton pump inhibitors: In human research, gastric acid suppression of omeprazole was shown to reduce the intestinal absorption of zinc (299).
  • ZidovudineZidovudine: According to secondary sources, zidovudine may play a role in reducing zinc levels in individuals with AIDS. In human research, zinc supplementation as an adjunct to zidovudine therapy in AIDS patients appeared to restrict opportunistic infections caused by Pneumocystis carinii and Candida, but not cytomegalovirus or toxoplasma infections (260).
  • Specific patient populationsSpecific patient populations: Zinc deficiencies have been reported in various populations, including children (801; 802; 803; 582; 804), pregnant women (590; 591; 592), patients on home enteral feeding (805), patients with short bowel syndrome (14), and the elderly (806; 807). While available information about various biochemical and molecular genetic functions of zinc has increased, the exact mechanisms by which zinc actions or deficiencies result in the observed symptoms remain unclear and need to be elucidated.
  • Mononuclear cell metallothionein mRNA levels have been used as a marker to indicate poor zinc nutrition (808); however, it was shown in one study that such levels were not indicative of plasma zinc levels in humans (809). In vitro, interleukin-2 and interleukin-2 receptor-alpha may be useful to test for zinc deficiency (251). Some correlations of increased toenail zinc concentrations include increased dietary zinc intake, decreased vegetable intake, and increased body mass index (810).
  • Acne: In one study, patients with severe acne had significantly lower serum zinc levels than healthy individuals (811).
  • Acute respiratory tract infection: Hair and serum zinc levels in malnourished Bangladeshi children correlated with the occurrence of acute respiratory tract infection (812).
  • Alcoholism: According to secondary sources, excessive consumption of alcohol may lead to impaired zinc absorption and increased urinary excretion of zinc.
  • Anemia: In pregnant women, those presenting with anemia have significantly lower zinc concentrations compared with nonanemic pregnant women (637). A relationship between zinc deficiency and anemia has also been observed in low-income African-American and Hispanic children in the United States (59).
  • Arsenic-related disease: Low dietary intake of zinc has correlated with increased monomethyl arsenic (MMA) and dimethyl arsenic (DMA) in individuals in arsenic-exposed regions in the United States (813).
  • Beta-thalassemia: Beta-thalassemia is a genetic disorder that causes anemia that is so severe that chronic blood transfusions are often necessary, which may result in iron overload and, therefore, a zinc deficiency (814). Zinc deficiency has been correlated with insulin resistance in thalassemic patients (815).
  • Cancer: In a high-risk area, patients with TP53 mutations (a common mutation observed in cancer cells) in esophageal squamous cell carcinoma had lower zinc levels than those without mutation (816). According to a review, normally high prostate levels of zinc may be decreased during prostate cancer (83)
  • Cardiovascular disease: In diabetic patients, low serum zinc levels (?14.1mcM/L) may increase the risk of cardiovascular disease, as evidenced by a higher risk for death from coronary heart disease and myocardial infarction (817). Low zinc concentrations have been shown to negatively correlate with markers of inflammation in patients scheduled for coronary angiography (818). Zinc deficiency may be a risk factor for carotid stenosis (CS) development (819).
  • Cellular effects: Zinc deficiency has been shown to decrease transepithelial electrical resistance and to induce alterations to tight and adherens junctions in vitro (820). Furthermore, zinc deficiency led to a disruption of other cellular markers of cell infiltration.
  • Cognitive impairment: In human research, zinc levels were not associated with impaired cognitive function in adults (821), the elderly (822; 823), or children (824). Based on a review article, zinc supplementation may not improve cognitive function in zinc-deficient school-aged children (825).
  • Critical illness: According to a review, zinc is often depleted in critical illness (826). In critically ill children, plasma zinc levels have been observed to be low (mean: 0.43; range: 0.26-0.66mcg/dL), and levels were associated with organ failure (827). Patients in intensive care units typically require parenteral feeding, which has been shown to improve plasma zinc levels in these patients (828).
  • Degenerative lumbar stenosis: Zinc was decreased in samples of ligament flava from patients with degenerative lumbar stenosis or ossification of the ligamentum flavum (829).
  • Delayed wound healing: Low zinc levels may be a predictive factor in delayed wound healing following total hip replacement (830).
  • Eating disorders: According to secondary sources, zinc deficiency has been reported in individuals with eating disorders. In one study, a high zinc intake correlated with higher scores on the Eating Attitudes Test (EAT-26) and bulimia scale, compared to those with lower zinc status (107).
  • Exercise performance: Low levels of zinc have been reported in a population of gymnasts (831).
  • Febrile convulsions: Serum and cerebrospinal fluid (CSF) zinc levels were lower in children suffering from febrile convulsions, compared with those who were not (832; 833).
  • Gastrointestinal disorders: Zinc deficiency may result in gastrointestinal inflammation (7). A relationship between serum zinc levels and the progression of gastroenteritis in children was lacking in one study (834).
  • Goiter: According to a cross-sectional study in school children in Iran, serum zinc levels in goitrous vs. nongoitrous children were lacking in significance, nor was the prevalence of zinc deficiency between the two groups (835).
  • Growth: In one study, zinc deficiency was not correlated with a stunting of growth among primary school-aged children in China (836); however, in another study, stunted males demonstrated lower mean serum zinc levels and lower mean intakes of zinc than nonstunted males in a population in Thailand (837).
  • Hemodialysis: In patients with acute renal failure requiring hemodialysis, zinc supplementation may be required (838).
  • Hormonal effects: Zinc deprivation has been shown to enhance thyroid hormone induction of growth hormone mRNA in vitro (839).
  • Human immunodeficiency virus (HIV): In human research, zinc supplementation was associated with poor survival (840).
  • Infection: A correlation was lacking between zinc levels and infection with Trichinella britovi (841). According to a review, low zinc status in the elderly may increase the risk for pneumonia, possibly through a lowered immune status (842). In patients with reactive thrombocytosis, zinc concentrations decreased significantly upon discharge from the hospital (843). Patients with schistosomiasis infection displayed below-normal levels of zinc; a correlation between plasma zinc and vitamin A, retinol binding, and prealbumin concentrations was also observed (774).
  • Inflammation: It is hypothesized that low levels of plasma zinc may be one of the nonspecific features of inflammation (844).
  • Iron: In premenopausal women without anemia, lower serum ferritin concentrations were associated with smaller zinc pools; smaller zinc pools correlated (negatively) with bleeding through menstrual pads and positively with frequency of beef consumption (845).
  • Liver disease: A low intake of zinc has been observed in patients with steatohepatitis (846). In cirrhotic patients, plasma zinc levels lacked difference between those with hepatitis B and hepatitis C; however, zinc levels in both groups were less than half the normal range (847).
  • Malabsorption syndromes: According to secondary sources, individuals with malabsorption syndromes may be deficient in zinc.
  • Metabolic disease: Baseline zinc concentrations have been positively associated with the risk of developing metabolic syndrome in adults (848).
  • Premature birth: Exchangeable zinc pool size at birth is smaller in small-for-gestational-age than in appropriate-for-gestational-age preterm infants (849).
  • Rheumatoid arthritis: In human research, zinc absorption was reduced in individuals with rheumatoid arthritis (850). However, other research found that patients with rheumatoid arthritis lacked a demonstration of zinc deficiency (851).
  • Sickle cell anemia: Patients with sickle cell anemia had decreased serum zinc levels compared with controls (852; 435).
  • Stress: A negative correlation between perceived stress and zinc ingestion was observed in a population of college students (853).
  • Taste impairment: Zinc deficiency may cause taste impairment (854).
  • Vegetarian diet: In adults following a lactovegetarian diet, intakes of zinc were lower in those who reported mild health complaints compared with those that lacked a report of any complaints (855; 856).
  • Wound healing: Zinc concentrations surrounding venous leg ulcers have been shown to be lower than those observed in the surrounding skin (857).

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