St. John's Wort

Synonym(s): hyperforin, hypericin, hypericum perforatum, Johanniskraut-Extrakt

Nutrient group: plant extracts & active ingredients, Neurotropic agents

Sources and physiological effects

Occurrences in food
St. John's Wort is a plant from the family of hard hay plants (Hypericaceae) and originally native to Europe, West Asia and North Africa. St. John's Wort is cultivated for industrial use in Germany and Austria, but also in Poland and South America. The extract is used in medicines and food supplements, but there are also St. John's wort oils for external application and as St. John's Wort tea.
Physiological effects
Nervous system	Anxiety-solving and antidepressive effects due to a direct effect on the pyramid neurons of the hippocampus
Pain	Pain reduction by activation of opioid and GABA receptors Pain reduction by activation of opioid and GABA receptors Pain reduction by activation of opioid and GABA receptors Pain reduction by activation of opioid and GABA receptors
Hormone metabolism	Increase in melatonin levels by inhibiting serotonin reuptake

Detailed information

John's Wort as a therapeutic for depression, anxiety and sleep disorders

Hypericum perforatum achieves its therapeutic efficiency through the interaction of several classes of active ingredients. Especially the group of hypericins, hyperforin and other flavonoids support each other and seem to be responsible for the antidepressive, anxiolytic and thymoleptic effects of St. John's wort (1)(2). St. John's Wort extract mainly influences the accompanying symptoms of mild and moderate depression such as nervousness, anxiety, restlessness or sleep disturbances and has a mood-lifting effect without making you tired (3). In a Cochrane Review of 29 studies involving about 5000 patients, the efficacy of St. John's Wort in depression was comparable to synthetic antidepressants, with better tolerability and lower abortion rates (4). Due to its compatibility it can also be used over a longer period of time (5).

Mechanism of St. John's Wort extract

St. John's Wort extract intervenes in the neurovegetative process through various mechanisms. The anxiolytic and antidepressive effect of St. John's Wort is due to a direct effect on the pyramid neurons of the hippocampus. By binding to TRPC6 channels and subsequently increasing the permeability of Ca and Na ions, it reduces the reabsorption rate of serotonin. According to a recent study, St. John's Wort has a mechanism of action similar to the neuroprotective, endogenous growth factor BDNF (brain-derived neurotrophic factor) (6). This explains the antidepressant, anxiety-dissolving and memory-improving properties (7). Sleep disorders can also be positively influenced by the increase in serotonin and the associated increase in nocturnal melatonin secretion. The pain-inhibiting effect of St. John's Wort extracts results from the activation of opioid receptors, the effect on the GABA(A) receptor complex (8) and the inhibition of protein kinase C (9).

Indications

Effect	Indication	Dosage
Physiological effects with low Nutrient dosages	For light to moderate depressions	500 – 1000 mg/d
	For psychovegetative disorders	500 – 1000 mg/d
	For anxiety	500 – 1000 mg/d
	For nervous restlessness and exhaustion	500 – 1000 mg/d
	For sleeping disorders	500 – 1000 mg/d

Administration

General income mode
When	St. John's Wort should be taken with meals. Hint: Application duration: 6 – 8 weeks. If no improvement of the symptoms occurs after 2 – 4 weeks, a specialist should be consulted. Hypericin may lead to increased sensitivity to sunlight. Although recent studies have shown that photosensitivity reactions to extracts are less frequent than with pure hypericin preparations (10), people with light skin should avoid intensive sun exposure or solarium visits if St. John's Wort extract is taken. There is an interaction between St. John's Wort and some groups of drugs through the activation of cytochrome P450. St. John's Wort must not be used, especially when taking cytostatic drugs, cyclosporins, antiretroviral drugs or antidepressants (11). It cannot be excluded that St. John's Wort impairs the effect of oral contraceptives (“pill“) (11). Due to the hyperincin-induced increased degradation of calcitriol, vitamin D should be added while taking St. John's Wort extract (12).
Side effects
In rare cases gastrointestinal complaints (nausea, diarrhea) or allergic skin reactions (itching, redness) may occur.
Contraindications
Pregnancy, lactation, children and adolescents. The simultaneous intake of St. John's Wort extract with medication should always be avoided, especially when using immunosuppressants, asthma medication and anticoagulants.

Interactions

Interactions with drugs

Estrogens/Gestagene
(oral contraceptives)

Low doses of oral contraceptives may cause spotting and reduced contraceptive effects if taken simultaneously.

Anticoagulants
(phenprocoumone)

If taken simultaneously, plasma levels of phenprocoumone may decrease significantly.

Asthmic mean
(theophylline)

Accelerated degradation of theophylline with simultaneous ingestion.

Sedativa
(e.g. alprazolam, triazolam, brotizolam)

When the sedative is added to St. John's Wort, lower sedative levels are expected. When St. John's Wort is added to the sedative, the plasma levels of the sedative are expected to increase.

Immunsuppressiva
(tacrolimus, cyclosporine)

A combined intake leads to significantly lower levels and therapy failure of cyclosporine and tacrolimus.

Interactions with other nutrients

5-HTP

Do not combine St. John's Wort and Griffonia. When taking 5-HTP and St. John's Wort (main ingredient hyperforin) at the same time, the effect is enhanced. The risk of toxic serotonin concentration increases significantly (serotonin syndrome).

References

1) Wagner, H., Wiesenauer, M. 2003. Phytotherapie. Phytopharmaka und pflanzliche Homöopathika.
2) Deutsche Kommission E. 1984. Monographie Hyperici herba (Johanniskraut). Bundesanzeiger.
3) Laakmann, G. et al. 2002. Hypericum perforatum extract in treatment of mild to moderate depression. Clinical and pharmacological aspects. Nervenarzt. 73(7):600-12.
4) Linde, K. et al. 2008. St John's wort for major depression. Cochrane Database Syst Rev. (4):CD000448.
5) Sarris, J. et al. 2012. St John's Wort (Hypericum perforatum) versus Sertraline and Placebo in Major Depressive Disorder: Continuation Data from a 26-Week RCT. Pharmacopsychiatry.
6) Leuner K, Li W, Amaral MD, Rudolph S, Calfa G, Schuwald AM, Harteneck C, Inoue T, Pozzo-Miller L. 2012. Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca (2+)-permeable TRPC6 channels. Hippocampus.
7) Laakmann, G. et al. 1998. St. John’s wort in mild and moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry. 3(Suppl 1):54-9.
8) Yaşar, S. N. et al. 2012. Central Nervous System Activities of Hypericum origanifolium Extract via GA-BAergic and Opioidergic Mechanisms. Phytother Res.
9) Galeotti, N. et al. 2012. St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase Cgamma and epsilon activity. Biochem Pharmacol. 79(9):1327-36.
10) Schmitt LA, Liu Y, Murphy PA, Petrich JW, Dixon PM, Birt DF: Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds. J Photochem Photobiol B. 2006 Nov 1; 85 (2): 118-30.
11) Davis, S. A. et al. 2014. Use of St. John's Wort in Potentially Dangerous Combinations. The Journal of Alternative and Complementary Medicine. 20(7):578-579.
12) Gröber, U. 2011. Mikronährstoffe. Metabolic Tuning – Prävention – Therapie. Wissenschaftliche Verlagsgesellschaft.

References Interactions
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3.
Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.