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Background
Zinc has been used since ancient Egyptian times to enhance wound healing, although the usefulness of this approach is only partially confirmed by the clinical data of today.
Zinc is necessary for the functioning of more than 300 different enzymes and plays a vital role in an enormous number of biological processes. Zinc is a cofactor for the antioxidant enzyme superoxide dismutase (SOD) and is in a number of enzymatic reactions involved in carbohydrate and protein metabolism.
Its immune-enhancing activities include regulation of T lymphocytes, CD4, natural killer cells, and interleukin II. In addition, zinc has been claimed to possess antiviral activity. It has been shown to play a role in wound healing, especially following burns or surgical incisions. Zinc is necessary for the maturation of sperm and normal fetal development. It is involved in sensory perception (taste, smell, and vision) and controls the release of stored vitamin A from the liver. Within the endocrine system, zinc has been shown to regulate insulin activity and promote the conversion thyroid hormones thyroxine to triiodothyronine.
Based on available scientific evidence, zinc may be effective in the treatment of (childhood) malnutrition, acne vulgaris, peptic ulcers, leg ulcers, infertility, Wilson's disease, herpes, and taste or smell disorders. Zinc has also gained popularity for its use in the prevention of the common cold.
The role for zinc is controversial in some cases, as the results of published studies provide either contradictory information and/or the methodological quality of the studies does not allow for a confident conclusion regarding the role of zinc in those diseases.
Synonyms
Atomic number 30, Indian tin, pewter, polaprezinc, zinc acetate, zinc acexamate, zinc aspartate, zinc carbonate, zinc citrate, zinc chloride, zinc gluconate, zinc methionate, zinc methionine, zinc monomethioine, zinc oxide, zinc picolinate, zinc sulfate, Zink, ZN, Zn.
Brands used in clinical trials: A-84, Articulin-F®, Astra, Curiosin® (zinc and hyaluronic acid), Herpigon, Nels Cream®, Orazinc®, Solvezink®, Virudermin Gel®, Zeta N, Zicam® Nasal Gel, Zincolak, Zincomed, Zineryt®, Zinvit-C250.
Evidence
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
| When Treated to Use | Scientific Evidence Shows | Grade* |
|---|---|---|
| Depressive disorder (mild-to-moderate) | St. John's wort has been extensively studied in Europe over the last two decades, with more recent research in the United States. Short-term studies (1-3 months) suggest that St. John's wort is more effective than placebo (sugar pill), and equally effective as tricyclic antidepressants (TCAs) in the treatment of mild-to-moderate major depression. Comparisons to the more commonly prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine (Prozac®) or sertraline (Zoloft®), are more limited. However, other data suggest that St. John's wort may be just as effective as SSRIs with fewer side effects. Safety concerns exist as with most conventional and complementary therapies. | A |
| Anxiety disorder | Overall, there is currently not enough evidence to recommend St. John's wort for the primary treatment of anxiety disorders. | C |
| Atopic dermatitis | Early study of hypericum-cream in the topical treatment of mild to moderate atopic dermatitis shows positive results. Further studies are needed before a firm recommendation can be made. | C |
| Depressive disorder (severe) | Studies of St. John's wort for severe depression have not provided clear evidence of effectiveness. | C |
| Obsessive-compulsive disorder (OCD) | There are a few reported cases of possible benefits of St. John's wort in patients with obsessive-compulsive disorder (OCD). Currently there is not enough scientific evidence to recommend St. John's wort for this condition. | C |
| Peri-menopausal symptoms | There is currently not enough scientific evidence to recommend St. John's wort for this indication. | C |
| Premenstrual syndrome (PMS) | Further studies are needed before a recommendation can be made. | C |
| Seasonal affective disorder (SAD) | Despite some promising early data, there is currently not enough evidence to recommend St. John's wort for depressive disorder with seasonal pattern or Seasonal Affective Disorder (SAD). | C |
| Human immunodeficiency virus (HIV) | Anti-viral effects of St. John's wort have been observed in laboratory studies, but were not found in one human study. Multiple reports of significant adverse effects and interactions with drugs used for HIV/AIDS, including protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), suggest that patients being treated for HIV/AIDS should avoid this herb. Therefore, there is evidence to recommend against using St. John's wort in the treatment of patients with HIV/AIDS. | D |
| Social phobia | Results of early study fail to provide evidence for the efficacy of St. John's wort in social phobia. | D |
Key to Grades
- A: Strong scientific evidence for this use;
- B: Good scientific evidence for this use;
- C: Unclear scientific evidence for this use;
- D: Fair scientific evidence against this use;
- F: Strong scientific evidence against this use.
Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Abdominal discomfort or irritation, alcoholism, allergies, anti-inflammatory, antiviral, athletic performance enhancement, bacterial skin infections (topical), bedwetting, bruises (topical), benzodiazepine withdrawal, burns (topical), cancer, chronic bowel irritation, chronic ear infections, dental pain, diarrhea, diuretic (increasing urine flow), Epstein-Barr virus infection, fatigue, glioma, heartburn, hemorrhoids, herpes virus infection, influenza, insomnia, joint pain, liver protection from toxins, malaria treatment, menstrual pain, nerve pain, pain relief, rheumatism, skin scrapes, snakebites, sprains, ulcers, wound healing (topical).
Dosing
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Adults (18 years and older)
Clinical trials have used a range of doses, including 0.17-2.7 milligrams of hypericin by mouth, and 900-1,800 milligrams of St. John's wort extract daily by mouth.
1.5% hyperforin (verum) has been applied to the skin for treatment of atopic dermatitis.
Children (younger than 18 years)
There is not enough scientific data to recommend St. John's wort in children.
Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Allergies
Infrequent allergic skin reactions, including rash and itching, are reported in human studies.
Side Effects and Warnings
In published studies, St. John's wort has generally been well tolerated at recommended doses for up to 1-3 months. The most common adverse effects include gastrointestinal upset, skin reactions, fatigue/sedation, restlessness or anxiety, sexual dysfunction (including impotence), dizziness, headache, and dry mouth. Several recent studies suggest that side effects occur in one to three percent of patients taking St. John's wort, and that the number of adverse events may be similar to placebo (and less than standard antidepressant drugs). Animal toxicity studies have found only non-specific symptoms such as weight loss. One small study reported elevated thyroid stimulating hormone (TSH) levels to be associated with taking St. John's wort.
It has been reported that St. John's wort may cause psychiatric symptoms such as suicidal and homicidal thoughts.
Delayed ejaculation has been reported in animal studies.
Pregnancy & Breastfeeding
There is insufficient data available at this time to recommend use during pregnancy or breastfeeding.
Interactions
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.
Interactions with Drugs
St. John's wort interferes with the way the body processes many drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be increased in the blood in the short-term (causing increased effects or potentially serious adverse reactions), and/or decreased in the blood in the long-term (which can reduce the intended effects). Examples of medications that may be affected by St. John's wort in this manner include carbamazepine, cyclosporin, irinotecan, midazolam, nifedipine, birth control pills, simvastatin, theophylline, tricyclic antidepressants, warfarin, or HIV drugs such as non-nucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs). The U.S. Food & Drug Administration suggests that patients with HIV/AIDS on protease inhibitors or non-nucleoside reverse transcriptase inhibitors avoid taking St. John's wort.
Case reports exist of significant reductions in cyclosporine, tacrolimus, and mycophenolic acid drug levels, and possible organ rejections in people with transplants who are taking St. John's wort. Reports also exist of altered menstrual flow, bleeding, and unwanted pregnancies in women taking birth control pills and St. John's wort at the same time. St. John's wort may interact with digoxin or digitoxin, resulting in a decrease in digoxin blood concentration. In general, individuals should check the package insert and speak with a qualified healthcare professional including a pharmacist about possible interactions with St. John's wort.
Taking St. John's wort with other antidepressants may lead to increased side effects, including serotonin syndrome and mania. Serotonin syndrome is a condition defined by muscle rigidity, fever, confusion, increased blood pressure and heart rate, and coma. Mania is defined by symptoms of elevated or irritable mood, rapid speech or thoughts, increased activity, and decreased need for sleep. These interactions may occur in people taking St. John's wort with SSRI antidepressants such as fluoxetine (Prozac®) or sertraline (Zoloft®), or with monoamine oxidase inhibitors (MAOIs) such as isocarboxazid (Marplan®), phenelzine (Nardil®), or tranylcypromine (Parnate®). Using St. John's wort with MAOIs may also increase the risk of severely increased blood pressure.
St. John's wort may lead to increased risk of sun sensitivity when taken with other drugs such as antibiotics or birth control pills. St. John's wort may interact with anesthetic drugs. A possible interaction with loperamide (Imodium®) has been reported; confusion and agitation occurred in one patient taking St. John's wort, loperamide, and the herb valerian ( Valeriana officinalis ). St. John's wort may interact with triptan-type headache medications. Examples include naratriptan (Amerge®), rizatriptan (Maxalt®), sumatriptan (Imitrex®), and zolmitriptan (Zomig®). In theory, St. John's wort may also interact with certain chemotherapy drugs such as anthracyclines. St. John's wort may increase anti-inflammatory effects of COX2 inhibitor drugs like Vioxx®, or NSAIDS like ibuprofen (Motrin®).
St John's wort may increase imatinib clearance. Thus patients taking imatinib should avoid taking St John's wort. Concomitant use of enzyme inducers, including St John's wort, may necessitate an increase in the imatinib dose to maintain effectiveness.
In higher doses, St. John's wort has been shown to decrease the blood concentrations of omeprazole, tolbutamide, caffeine, dextromethorphan, fexofenadine, carbamazepine, and cimetidine, among other medications. No relevant interaction has been seen with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St. John's wort extract.
Coadministration of St. John's wort leads to a short-term but clinically irrelevant increase followed by a prolonged extensive reduction in voriconazole exposure. St. John's wort might put certain individuals at highest risk for potential voriconazole treatment failure.
Although cases of interaction are rare, caution is advised when taking St. John's wort and coumarin-type anticoagulants.
Caution is also advised when taking benzodiazepine tranquilizers, opioids or P-glycoprotein regulated drugs. In general, individuals should check the package insert and speak with a qualified healthcare professional including a pharmacist about possible interactions with St. John's wort.
Interactions with Herbs & Dietary Supplements
St. John's wort may interfere with the way the body processes certain herbs and supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be increased in the blood in the short-term, causing increased effects or potentially serious adverse reactions, or decreased in the blood in the long-term, which can reduce the intended effects.
Taking St. John's wort with herbs or supplements with antidepressant activity may lead to increased side effects, including serotonin syndrome, mania, or severe increase in blood pressure. There is a particular risk of these interactions occurring with agents that possess possible monoamine oxidase inhibitory properties.
St. John's wort may lead to increased risk of sun sensitivity when taken with capsaicin or other photosensitizing products. St. John's wort may interact with herbs that also possess cardiac glycoside properties and decrease blood levels.
A possible interaction with the herb valerian ( Valeriana officinalis ) has been reported: confusion and agitation occurred in one patient taking St. John's wort, loperamide (Immodium®) and valerian. However, St. John's wort and valerian are often used together, with few reported of adverse events. In theory, due to the presence of tannins, St. John's wort may inhibit the absorption of iron.
Although cases of interaction are rare, caution is advised when taking St. John's wort and coumarin-type anticoagulants.
Caution is also advised when taking red yeast rice or any herb or supplements that is P-glycoprotein regulated. In general, individuals should speak with a qualified healthcare professional including a pharmacist about possible interactions with St. John's wort.
Methodology
This information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): E-P Barrette, MD (Case Western Reserve University School of Medicine); Ethan Basch, MD (Memorial Sloan-Kettering Cancer Center); Samuel Basch, MD (Mt. Sinai School of Medicine); Steve Bent, MD (University of California San Francisco); Heather Boon, BScPhm, PhD (University of Toronto); Edzard Ernst, MD, PhD, FRCP (University of Exeter); Ivo Foppa, MD, ScD (Harvard School of Public Health); Paul Hammerness, MD (Massachusetts General Hospital); Adrianne Rogers, MD (Boston University); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Wendy Weissner, BA (Natural Standard Research Collaboration).
Selected References
- Behnke K, Jensen GS, Graubaum HJ, et al. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression. Adv Ther 2002;19(1):43-52.
- Donovan JL, DeVane CL, Lewis JG, et al. Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women: a pilot study.Phytother Res. 2005 Oct;19(10):901-6.
- Fava M, Alpert J, Nierenberg AA, et al. A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder.J Clin Psychopharmacol. 2005 Oct;25(5):441-7.
- Franklin M, Hafizi S, Reed A, et al. Effect of sub-chronic treatment with Jarsin (extract of St John's wort, Hypericum perforatum) at two dose levels on evening salivary melatonin and cortisol concentrations in healthy male volunteers.Pharmacopsychiatry. 2006 Jan;39(1):13-5.
- Hammerness P, Basch E, Ulbricht C, et al. St John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics 2003;44(4):271-282.
- Hicks SM, Walker AF, Gallagher J, et al. The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's wort (Hypericum perforatum L.) for premenstrual symptoms. J.Altern.Complement Med. 2004;10(6):925-932.
- Muller T, Mannel M, Murck H, et al. Treatment of somatoform disorders with St. John's wort: a randomized, double-blind and placebo-controlled trial. Psychosom.Med. 2004;66(4):538-547.
- Murphy PA, Kern SE, Stanczyk FZ, et al. Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding.Contraception. 2005 Jun;71(6):402-8.
- Pfrunder A, Schiesser M, Gerber S, et al. Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br.J.Clin Pharmacol. 2003;56(6):683-690.
- Philipp M, Kohnen R, Hiller KO. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. BMJ 12-11-1999;319(7224):1534-1538.
- Randlov C, Mehlsen J, Thomsen CF, et al. The efficacy of St. John's Wort in patients with minor depressive symptoms or dysthymia--a double-blind placebo-controlled study.Phytomedicine. 2006 Mar;13(4):215-21.
- Schempp CM, Windeck T, Hezel S, et al. Topical treatment of atopic dermatitis with St. John's wort cream--a randomized, placebo controlled, double blind half-side comparison. Phytomedicine. 2003;10 Suppl 4:31-37.
- Schulz V. Safety of St. John's Wort extract compared to synthetic antidepressants. Phytomedicine. 2006 Feb;13(3):199-204.
- Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA 4-18-2001;285(15):1978-1986.
- Szegedi A, Kohnen R, Dienel A, et al. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ 3-5-2005;330(7490):503.