NHIOnDemand Health & Wellness Trade Site

St. John's Wort

(Hypericum perforatum)

Plant Part Used
Flowering buds
Active Constituents
This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.
Napthodianthrones (hypericin and pseudohypericin), flavonoids (including isoferulic acid, hyperoside, quercitin), phloroglucinols (hyperforin), melatonin.(1),(2)

Introduction
St. John’s wort has gained a great deal of attention for its use in minor depression. Its popularity has stemmed from its extensive use by physicians in Europe as an agent of choice in the treatment of mild to moderate depression. There are a variety of studies which are claimed to support the use of St. John’s wort in treating mild to moderate depression.(3),(4),(5) Also, sales of this herb in Europe, based on physician recommendation, outperform the popular pharmaceutical fluoxetine (Prozac). With approximately 18 million Americans potentially experiencing some level of depression in a given year from a variety of causes, it is attracting attention as a safe and natural alternative to current prescription therapies available in this country.

Article continues below

Advertisement | Advertise With Us

Recent results from two independent randomized controlled trials have indicated that St. John's wort is no more beneficial than placebo in individuals with major depression. However, one of these trials used sertraline (50 to 100 mg/day) as an active control and found no significant superiority of sertraline over placebo in this patient population as well. Though these two trials may indicate that St. John’s wort is not effective for major depression, they neither confirm nor deny the use of St. John's wort in mild to moderate depression.(6),(7) A recent study found that St. John's wort was effective in treating major depression.(8)

Interactions and Depletions
Dosage Info
Dosage Range
900mg (standardized extract) daily, in divided doses. (Some individuals may experience benefit with as little as 300-600mg daily.) Higher doses are used in viral infections, and should only be performed under the supervision of a doctor.

Topically: Apply oil extract as needed to affected area(s).

Liquid Extract: 1:1 in 25% ethanol - 2-4 milliliters, 3 times a day.(9)

Tincture: (1:10) in 45% ethanol - 2-4 milliliters, 3 times a day.(10)

Most Common Dosage
300mg (standardized extract), 3 times a day.

Topically: Apply oil extract as needed to affected area(s).

Liquid Extract: 1:1 in 25% ethanol - 2 milliliters, 3 times a day.

Tincture: (1:10) in 45% ethanol - 2 milliliters, 3 times a day.

Standardization
*Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.
The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 0.3-0.5% hypericin and/or 3-5% hyperforin per dose.
Uses
Frequently Reported Uses
  • Antiviral.
  • Depression
Other Reported Uses
  • Myalgia
  • Neuralgia
  • Fear
  • Genitourinary
  • Externally For Bruises, Sprains (Leaf)
  • HIV And Retroviruses
  • Nervous Symptoms Associated With Menopause And PMS
  • Wound Healing
Toxicities & Precautions
General
Although no real evidence has been presented to support it, there is theoretically a potential for an interaction with tyramine-containing foods, so these foods should be avoided.(11)

Based on evidence that St. John’s wort may cause changes in the need for certain medications, do not use St. John’s wort supplements if you are taking prescription and/or OTC medications without the advice of your doctor or pharmacist.

Allergy
Allergic reactions have occurred in a small percentage of individuals who use St. John's wort.
Health Conditions
Should not be taken in suicidal depression, psychosis or severe depression.

St. John's wort has affected the metabolism of certain medications via alteration of P-glycoprotein and cytochrome P-450 3A4 expression. Changes in cyclosporine levels have been confirmed. Based on human data, do not use St. John’s wort in transplant patients. Complications as well as transplant rejection have occurred with the use of this herb.(12),(13)

Photosensitivity

Based on pharmacology, animal data and human data, may cause photosensitivity.(14)

May cause photosensitivity in high doses such as those used by the AIDS population.(15)

Side Effects
Fatigue and GI distress may occur in about 0.5 percent of the individuals who take St. John’s wort.

Based on animal studies, it may induce liver enzymes in large doses, but these return to normal with discontinuation.(16)

Pregnancy/Breast Feeding
Based on animal studies, do not use in pregnancy.(17),(18)
Age Limitations
Do not use in children under 2 years of age unless recommended by a physician.
Pharmacology
St. John’s wort is a perennial flowering plant, which grows in many areas of the world, including Europe and the United States. The parts of the plant used are the portions above the ground. Studies with St. John’s wort have centered around the use of a 0.3 percent hypericin content standardized extract at a dose of 300mg, three times a day. It is viewed as safe and effective in Europe and its monograph is part of the Commission E Monographs for herbal medicines in Europe.

St. John’s wort is believed to have several possible effects on body chemistry. These include:

  • The inhibition of cortisol secretion and the blocking of catabolic hormones, such as interleukin 6 (IL-6).(19)

  • The inhibition of the breakdown of several central nervous system neurotransmitters, including serotonin. It may have mild MAO-inhibiting activity. This has not been clearly defined and cannot explain all the activity of St. John’s wort. Researchers do not consider this to be its major mechanism of action.(20),(21),(22)

  • St. John’s wort may amplify and improve the signal produced by serotonin once it binds to its receptor sites in the brain.(23), (24)

  • St. John’s wort contains the chemical melatonin (approximately 4.39 mcg/gm), which may also contribute to the antidepressant effects of the plant.(25)

Although the constituent hypericin was originally thought to have the antidepressant effects seen when using St. John’s wort, recent research has reported that the constituents pseudo-hypericin and hyperforin may enhance serotonin, catecholamines, and glutamine levels in the brain.(26)

Additionally, hypericum has been used as an antiviral agent, including HIV.(27) It has been reported that, in sufficient blood levels, it may decrease HIV titer and it may increase T-killer cell activity.(28) Hypericum and the xanthrones are thought to be responsible for the antiviral activity.(29) Although its antiviral action has been questioned, several studies report this potential action.(30),(31) The drawback is that large doses must be taken and this is where side effects related to St. John’s wort (such as phototoxicity) can occur. A recent study has reported no positive effect when using St. John’s wort as an antiretroviral agent.(32) If an individual is taking protease inhibitor medications do not use St. Johns wort as a therapy for HIV due to changes in liver metabolism of these agents.(33) Also, since anti-retroviral agents are hepatically metabolized, use extreme caution when taking these medications and St. John’s wort. Use only under the direction of a physician.

Recent literature has reported cytochrome P-450 enzyme-inducing activity of St. John’s wort in human studies. Interactions between St. John’s wort and anticoagulants, indinavir, cyclosporin, digoxin, ethinyloestradiol/desogestrel and theophylline have occurred.(34) The mechanism of action was believed to be liver enzyme induction and subsequent alterations of drug levels by the herb. Also, several reports have suggested that concurrent use of St. John’s wort and SSRIs may result in "serotonin syndrome," including sweating, tremor, confusion, flushing and agitation.(35),(36) Use St. John’s wort with caution if individuals are on these medications.

St. John’s wort has also been used topically to increase wound and burn healing, as well as for myalgia and neuralgia.(37) It has been used in dressing wounds, along with soluble collagen and gotu kola. St. John's wort was found to be effective in treating PMS symptoms.(38)

Many parents of children with attention deficit hyperactivity disorder (ADHD) seek out alternative therapies for treatment and one of the most commonly used herbal supplement is St. John's wort. In a recent study St. John's wort appeared to not have any additional benefit in comparison to a placebo in treating the symptoms of ADHD in children and adolescents.(39

References
  1. Derbentseva NA, et al. Action of Tannins from Hypericum perforatum L. on the Influenza Virus. Mikrobiol Zh. 1972;34(6):768-72.
  2. View Abstract:  Wagner H, et al. Pharmaceutical Quality of Hypericum Extracts. J Geriatric Psychiatry and Neurology. Oct1994;7(Supp 1):S65-68.
  3. View Abstract:  Volz HP. Controlled Clinical Trials of Hypericum Extracts in Depressed Patients--An Overview. Pharmacopsychiatry. 1997;30(Suppl 2):72-76.
  4. View Abstract:  Muller WE, et al. Effects of Hypericum Extract (LI 160) in Biochemical Models of Antidepressant Activity. Pharmacopsychiatry. 1997;30(Supp 2):102-07.
  5. View Abstract:  Linde K, et al. St. John's Wort for Depression--An Overview and Meta-analysis of Randomised Clinical Trials. BMJ. 1996;313m:253-58.
  6. View Abstract:  Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's Wort) in Major Depressive Disorder: A Randomized Controlled Trial. JAMA. Apr2002;287(14):1807-1814.
  7. View Abstract:  Shelton RC, Keller MB, Gelenberg A, Dunner DL, Hirschfeld R, Thase ME, et al. Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA. Apr2001;285(15):1978-86.
  8. View Abstract:  Linde K, et al. St. Johns wort for major depression. Cochrane Database of Systemic Reviews. Oct2008;4
  9. PDR for Herbal Medicines, 2nd edition. Montvale, NJ: Medical Economics Company; 2000:722.
  10. PDR for Herbal Medicines, 2nd edition. Montvale, NJ: Medical Economics Company; 2000:722.
  11. View Abstract:  Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. Nov1998;158(20):2200-11.
  12. View Abstract:  Ruschitzka F, et al. Acute Heart Transplant Rejection Due to St. John’s Wort. Lancet. Feb2000;355(9203): 548-49.
  13. View Abstract:  Ernst E. St John's Wort Supplements Endanger the Success of Organ Transplantation. Archives of Surgery. Mar2002;137:316-319.
  14. View Abstract:  Brockmoller J, et al. Hypericin and Pseudohypericin: Pharmacokinetics and Effects of Photosensitivity in Humans. Pharmacopsychiatry. 1990;30(Supp 2):94-101.
  15. View Abstract:  Gulick RM, et al. Phase I Studies of Hypericin, The Active Compound in St. John's Wort, As An Antiretroviral Agent in HIV-infected Adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med. Mar1999;130(6):510-14.
  16. View Abstract:  Brockmoller J, et al. Hypericin and Pseudohypericin: Pharmacokinetics and Effects of Photosensitivity in Humans. Pharmacopsychiatry. 1990;30(Supp 2):94-101.
  17. Grush LR, et al. St John's Wort During Pregnancy. JAMA. 1998;280(18):1566.
  18. View Abstract:  Ondrizek RR, et al. An alternative medicine study of herbal effects on the penetration of zona-free hamster oocytes and the integrity of sperm deoxyribonucleic acid. Fertil Steril. Mar1999;71(3):517-22.
  19. View Abstract:  Nordfors M, Hartvig P. St John's wort against depression in favour again. Lakrtidningen. 1997;94:2365-67.
  20. Bloomfield H, et al. Can Depression Be Successfully Treated with a Safe, Inexpensive, Medically Proven Herb Available Without a Prescription? Hypericum and Depression. California: Prelude Press; 1996:110-12.
  21. Suzuki O, et al. Inhibition of Monoamine Oxidase by Hypericin. Planta Medica. 1984;50:272-74.
  22. View Abstract:  Bladt S, et al. Inhibition of MAO by Fractions and Constituents of Hypericum Extract. J Geriatric Psychiatry and Neurology. 1994;7:S57-S59.
  23. Murray M. Natural Alternatives to Prozac. New York: William Morrow and Company, Inc; 1996:137.
  24. View Abstract:  Muller WEG, et al. Effects of Hypericum Extract on the Expression of Serotonin Receptors. J Geriatric Psychiatry and Neurology. 1994;7:S63-S64.
  25. Murch SJ, et al. Melatonin in Feverfew and Other Medicinal Plants. Lancet. Nov1997;350(9091):1598-99.
  26. View Abstract:  Kaehler ST, et al. Hyperforin Enhances the Extracellular Concentrations of Catecholamines, Serotonin and Glutamate in the Rat Locus Coeruleus. Neurosci Lett. Mar1999;262(3):199-202.
  27. View Abstract:  Degar S, et al. Inactivation of the Human Immunodeficiency Virus Uncoating. AIDS Res Hum Retroviruses. 1992;8(11):1929-36.
  28. View Abstract:  Dwyer JT, et al. The Use of Unconventional Remedies Among HIV-positive Men Living in California. J Assoc Nurses AIDS Care. 1995;6(1):17-28.
  29. View Abstract:  Lavie G, et al. Studies of the Mechanisms of Action of the Antiretroviral Agents Hypericin and Pseudohypericin. Proc Natl Acad Sci, USA. 1989;86:5963-67.
  30. View Abstract:  Meruelo D, et al. Therapeutic Agents with Dramatic Antiretroviral Activity and Little Toxicity at Effective Doses: Aromatic Polycyclic Diones Hypericin and Pseudohypericin. Proc Natl Acad Sci. 1988;85:5230.
  31. View Abstract:  Hudson JB, et al. Antiviral Activities of Hypericin. Antiviral Research. 1991;15:110-12.
  32. View Abstract:  Gulick RM, et al. Phase I Studies of Hypericin, The Active Compound in St. John's Wort, As An Antiretroviral Agent in HIV-infected Adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med. Mar1999;130(6):510-14.
  33. View Abstract:  Piscitelli SC, et al. Indinavir Concentrations and St. John's Wort. Lancet. Feb2000;355(9203):547-48.
  34. Ernst E. Second Thoughts About Safety of St John's Wort. Lancet. Dec1999;354(9195):2014-16.
  35. Gordon JB. SSRIs and St.John's Wort: Possible Toxicity? Am Fam Physician. Mar1998;57(5):950,953.
  36. View Abstract:  Lantz MS, et al. St. John’s Wort and Antidepressant Drug Interactions in the Elderly. J Geriatr Psychiatr Neurol. 1999;12:7-10.
  37. View Abstract:  Shipochliev T, et al. Anti-inflammatory Action of a Group of Plant Extracts. Vet Med Nauki. 1981;18(6):87-94.
  38. View Abstract:  van Die MD, et al. Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis. J Altern Complement Med. 2009;15(9):1045-8
  39. View Abstract:  Weber W, et al. Hypericum perforatum (St John's wort) for attention-deficit/hyperactivity disorder in children and adolescents: a randomized controlled trial. JAMA. Jun2008;299(22):2633-41