St. John’s Wort Supreme
St. John’s wort (Hypericum perforatum) is a flowering perennial native to temperate regions across Europe, Asia, and the northern parts of Africa. It has been introduced to East Asia, Australia, New Zealand, and parts of North and South America.
St John's wort (SJW) has been used in traditional medicine since at least the first century AD, often as a cure-all for many diseases. Today, it’s commonly known to be used as an antidepressant, immune system modulator, and hormonal influencer. It can also have a dramatic influence on the enteric nervous system due to the gut-brain axis relationship.
SJW and Mood:
Regarding mood and specifically depression, SJW appears to be more effective than a placebo and as effective as standard antidepressant medications for mild and moderate depression, often without the side-effects. (1) A 2015 meta-analysis review concluded that SJW has fewer adverse effects than other antidepressants. (2) Overall, there are countless studies proving the effectiveness of SJW to help improve serotonin levels in the body. Due to the gut-brain relationship, this can greatly influence the digestive track and specifically the microbiota.
SJW and the Digestive System:
The main metabolites of SJW, such as hypericin, hyperforin, quercitrin, isoquercitrin, quercetin, kaempferol, and rutin, are shown in traditional Persian medicine to be very beneficial in the management of chronic liver disorders and help with jaundice and as a choleretic medication. (3)
SJW can significantly reverse the pathological symptoms of body weight gain, serum lipid disorders and hepatic steatosis, and also reestablish gut microbial composition and metabolite profiles. (4) Probiotic yeast growth can be stimulated by extracts of medicinal herbs, specifically SJW, and suppress Candida yeasts suggesting a potential benefit of the treatment in diseases that are associated with fungal dysbiosis. One study also showed that the growth of the beneficial yeast S. boulardii was increased 130-fold with SJW. (5)
SJW and the Endocrine System:
St. John’s wort might be helpful for menopausal symptoms, wound healing, and somatic symptom disorder. (6) SJW can influence the testosterone to DHT ratio in both men and women which was consistent with the possible inhibition of 5alpha-reductase. (7) In women using oral contraceptive pills and SJW simultaneously, it appears that SJW does not interfere with the antiandrogenic properties of these BCPs. (8) Though some studies note that SJW can reduce the effectiveness of come birth control pills. (9)
SJW and the Immune System:
SJW has been found to increase Treg cell levels in the spleen, thus improving immune responses. (10) The administration of SJW significantly also has been shown to reduce stress-induced increases in TNF-alpha levels as well as help to mediate the interrelationship between the immune, oxidative defense, and neuroendocrine systems. (11)
RegardingSARS-CoV-2 infection, one study identifies SJW and its active compound hypericin as potent inhibitors of SARS-CoV-2 and its variants alpha, beta, delta, and omicron. The antiviral efficacy of this plant has also been shown to be beneficial against the herpes simplex virus, human cytomegalovirus, hepatitis B virus, influenza A virus, and human immunodeficiency virus. (12)
There is also a therapeutic potential of SJW with the management of sleep deprivation-induced anxiety-like behavior and oxidative damage. (13)
SJW Considerations and Precautions:
The most common side effects of SJW is stomach pain, fatigue, and restlessness, though this is uncommon if used correctly. Other more rare effects include photosensitivity and skin irritation, breakthrough bleeding when taking oral contraceptives, and decreased effectiveness of immunosuppressants in those who have had organ transplants. Available data from clinical studies and case reports suggests that St. John's wort is unlikely to inhibit cytochrome P450 (CYP) 3A4 or 2D6, but is likely an inducer of CYP 3A4 and possibly the P-glycoprotein transporter. Examples of conventional medications which may undergo significant CYP 3A4 induction by St. John's wort include cyclosporine, indinavir, and oral contraceptives. (14)
Certain studies link some St. John's wort products with reducing the effectiveness of medicines like birth control pills, heart medications, HIV drugs, cancer medications, and some anticoagulants. (9)
One major precaution to be aware of is the possibility of “Serotonin syndrome.” This can occur when a SSRI medication (e.g. Lexapro, Zoloft, Prozac) is given with a monoamine oxidase inhibitor (MAOI) drug (e.g. Marplan, Nardil), slowing the breakdown of serotonin. (MAOIs elevate levels of serotonin as well as norepinephrine and dopamine.) Headaches, confusion, agitation, cardiovascular symptoms, and digestive symptoms often occur in serotonin syndrome. St. John’s wort, 5-HTP, tryptophan, and high tyramine foods (smoked, pickled, and fermented meats, as well as seafood and many yeast products) can also increase the risk of serotonin syndrome if combined with an MAOI drug. (15)
Dosage: 1-2 capsules 3 times per day. This is our official recommendation.
Clinically, Dr Stephen Gangemi has found this dosing to work well for him:
1 capsule two times per day to start for those with mild serotonin imbalances or gut impairment. Sometimes up to 3 capsules three times per day is indicated for more extreme cases. Have the patient slowly increase the dose every 4-5 days.
Precautions: Do not take if pregnant or breastfeeding. Avoid excess exposure to UV radiation while taking. This herb can interact with antidepressants, oral contraceptives, and other prescription medication. Consult your physician before taking if on any prescription medicine.
1. Apaydin EA, Maher AR, Shanman R, Booth MS, Miles JN, Sorbero ME, Hempel S. A systematic review of St. John's wort for major depressive disorder. Syst Rev. 2016 Sep 2;5(1):148. doi: 10.1186/s13643-016-0325-2. PMID: 27589952; PMCID: PMC5010734.
2. Linde K, Kriston L, Rücker G, Jamila S, Schumann I, Meissner K, Sigterman K, Schneider A (February 2015). "Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis". Annals of Family Medicine. 13 (1): 69–79. doi:10.1370/afm.1687. PMC 4291268. PMID 25583895.
3. Mohagheghzadeh A, Badr P, Mohagheghzadeh A, Hemmati S. Hypericum perforatum L. and the Underlying Molecular Mechanisms for Its Choleretic, Cholagogue, and Regenerative Properties. Pharmaceuticals (Basel). 2023 Jun 15;16(6):887. doi: 10.3390/ph16060887. PMID: 37375834; PMCID: PMC10300974.
4. Chen L, Liu Y, Tang Z, Shi X, Song Z, Cao F, Wei P, Li M, Li X, Jiang D, Yan Y, Yang N. Improvements in estrogen deficiency-induced hypercholesterolemia by Hypericum perforatum L. extract are associated with gut microbiota and related metabolites in ovariectomized (OVX) rats. Biomed Pharmacother. 2021 Mar;135:111131. doi: 10.1016/j.biopha.2020.111131. Epub 2020 Dec 28. PMID: 33383372.
5. Milutinović M, Dimitrijević-Branković S, Rajilić-Stojanović M. Plant Extracts Rich in Polyphenols as Potent Modulators in the Growth of Probiotic and Pathogenic Intestinal Microorganisms. Front Nutr. 2021 Jul 30;8:688843. doi: 10.3389/fnut.2021.688843. PMID: 34409062; PMCID: PMC8366775.
6. "St. John's Wort". National Center for Complementary and Integrative Health, US National Institutes of Health. October 2020. Retrieved 3 September 2023.
7. Donovan JL, DeVane CL, Lewis JG, Wang JS, Ruan Y, Chavin KD, Markowitz JS. 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. doi: 10.1002/ptr.1755. PMID: 16261523.
8. Fogle RH, Murphy PA, Westhoff CL, Stanczyk FZ. Does St. John's wort interfere with the antiandrogenic effect of oral contraceptive pills? Contraception. 2006 Sep;74(3):245-8. doi: 10.1016/j.contraception.2006.03.015. Epub 2006 May 15. PMID: 16904419.
9. "St. John's Wort". National Center for Complementary and Integrative Health, US National Institutes of Health. October 2020. Retrieved 3 September 2023.
10. Nosratabadi R, Rastin M, Sankian M, Haghmorad D, Tabasi N, Zamani S, Aghaee A, Salehipour Z, Mahmoudi M. St. John's wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells. J Immunotoxicol. 2016 May;13(3):364-74. doi: 10.3109/1547691X.2015.1101512. Epub 2015 Dec 3. PMID: 26634391.
11. Grundmann O, Lv Y, Kelber O, Butterweck V. Mechanism of St. John's wort extract (STW3-VI) during chronic restraint stress is mediated by the interrelationship of the immune, oxidative defense, and neuroendocrine system. Neuropharmacology. 2010 Mar-Apr;58(4-5):767-73. doi: 10.1016/j.neuropharm.2009.12.014. Epub 2009 Dec 28. PMID: 20036263.
12. Mohamed FF, Anhlan D, Schöfbänker M, Schreiber A, Classen N, Hensel A, Hempel G, Scholz W, Kühn J, Hrincius ER, et al. Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2. Pharmaceuticals. 2022; 15(5):530. https://doi.org/10.3390/ph15050530
13. Kumar A, Singh A. Protective effect of St. John's wort (Hypericum perforatum) extract on 72-hour sleep deprivation-induced anxiety-like behavior and oxidative damage in mice. Planta Med. 2007 Oct;73(13):1358-64. doi: 10.1055/s-2007-990234. Epub 2007 Oct 4. PMID: 17918039.
14. Markowitz JS, DeVane CL. The emerging recognition of herb-drug interactions with a focus on St. John's wort (Hypericum perforatum). Psychopharmacol Bull. 2001 Winter;35(1):53-64. PMID: 12397870.
15. Gangemi, Stephen DC. Systems Health Care Manual V3.2. Self published, 2022.