Guest guest Posted January 22, 2005 Report Share Posted January 22, 2005 ST. JOHN'S WORT EXTRACT JoAnn Guest Jan 21, 2005 19:06 PST by Michael T. Murray, N.D. http://www.doctormurray.com/articles/worteditorial.htm The fastest rising star in herbal medicine in Germany and now the United States is the St. John's wort extract standardized to contain 0.3% of hypericin. A total of 66 million daily doses of St. John's wort extracts were prescribed by German physicians in 1994 are expected to be dramatically higher when tallied for 1995, 1996, and beyond. In fact, these German doctor's now prescribe St. John's wort extract 8 times more often than Prozac. These doctors are knowledgeable about both medicines, but clearly favor St. John's wort extract. Why? The simple answer is that St. John's wort produces equal or better results in relieving depression, but has far fewer side effects. Over 25 double-blind randomized trials involving a total of 1,757 outpatients with mild to moderately severe depression have shown St. John's wort extracts standardized for hypericin to yield excellent results in the treatment in depression with virtually no side effects. What is St. John's wort? St. John's Wort (Hypericum perforatum) is a shrubby perennial plant with numerous bright yellow flowers. The term wort is an old English term for plant. Its naming after St. John was based on the claim that red spots, symbolic of the blood of St. John, appeared on the leaves of the plant on the anniversary of the saint's beheading. St. John's wort is cultivated worldwide, but grows quite well in Northern California and Southern Oregon. How can I be assured I will benefit from St. John's wort extract? If you want to see the same sort of results noted in the clinical trials in Europe, it is absolutely essential that you use the same extract used in the studies. This extract is a specially-prepared extract produced via an extraction with 80% methanol (subsequently the methanol is removed). The extract is standardized to contain 0.3% hypericin. Although hypericin is a key component, this extract is composed of a wide range of compounds constituting the remaining 99.7% of the extract. Distributors of this standardized extract employ HPLC techniques to identify not only the hypericin and pseudohypericin, but also related compounds, flavonoid components, xanthones, cinnamic acid, and several other key components. The point is that although the dosage is based upon hypericin levels (2.7 mg per day), assuring appropriate levels of these other constituents is also vitally important. How does St. John's extract work? Originally it was thought that the action of St. John's wort extract as an antidepressant was due to hypericin acting as an inhibitor of the enzyme monoamine oxidase (MAO) - thereby resulting in the increase of CNS monoamines such as serotonin and dopamine. However, newer information indicates that St. John's wort possesses no in vivo inhibition of MAO. At least two other mechanisms have been proposed: modulation of interleukin-6 activity and inhibition of the re-uptake of serotonin. The modulating effects of St. John's wort extract on interleukin-6 (IL-6) is the most interesting as it proposes a mechanism by which St. John's wort interacts with the link between the immune system and mood. The immune system and the nervous system share many common biochemical features and regulatory interactions. In regards to IL-6, this cytokine is heavily involved in the communication between cells within and outside the immune system. In relationship to the nervous system, IL-6 is known to modulate hypothalamic-pituitary-end organ axes, especially the hypothalamic-pituitary-adrenal (HPA) axis. The hypothesis is that an elevation in IL-6 results in activation of the HPA axis leading to elevations in CRH and other adrenal regulatory hormones - hallmark features in depression. St. John's wort extract has shown an ability to reduce IL-6 levels, hence this action may explain the clinical effectiveness of St. John's wort extract. St. John's wort extract has also been shown to inhibit the re-uptake of serotonin similar in fashion to drugs like fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft). The study demonstrating a 50% serotonin re-uptake inhibition utilized the 0.3% hypericin content standardized extract at a concentration of 6.2 mcg/ml and did not attempt to identify the active inhibitors. Even though the authors of the study concluded " that the antidepressant activity of Hypericum extract is due to inhibition of serotonin uptake by postsynaptic receptors. " An important point must be made - until pharmacokinetic studies demonstrate that St. John's wort components pass across the blood-brain barrier a primary site of action outside the central nervous system cannot be ruled out. How effective is St. John's wort? Very. As stated above, there have been over 25 double-blind studies with St. John's wort extract in the treatment of depression. The methodological quality of this research, particularly the studies since 1989, has been judged as being acceptable by strict criteria. The overall results have also been judged as providing good documentation of antidepressant activity. Those studies with the highest methodological quality rating are listed in Table 1. Table 1 - Summary of Clinical Trials with St. John's wort Extract in Depression Trials comparing St. John's wort to placebo Trial # of patients HDS at baseline Total hypericin per day(mg) Duration (weeks) Reponder rate St. John's wort Responder rate Placebo --- Halama7 50 18.0 1.08 4 10/25 0/25 Hansgren8 72 20.4 2.7 4 27/34 9/38 Harrer9 120 20.9 0.75 6 22/58 9/58 Hubner10 40 12.4 2.7 4 14/20 9/20 Quandt11 88 17.3 0.75 4 29/44 3/44 Reh12 50 20.0 1.0 8 20/25 11/25 Schmidt (1993)13 65 16.4 1.08 6 20/32 6/33 Schmidt (1989)14 40 29.5 0.75 4 15/25 3/24 Sommer14 105 15.8 2.7 4 28/50 13/55 Totals 630 185/313 (59%) 63/322 (20%) Trials comparing St. John's wort extract to an antidepressant drug Trial # of patients HDS at baseline Total hypericin per day(mg) Duration (weeks) Responder rate St. John's wort Responder rate Drug Bergman16 (amitryptiline) 80 15.4 0.75 6 32/40 28/40 Harrer17 (maprotiline) 102 19.4 2.7 4 27/51 28/51 Vorbach18 (imipramine) 135 19.4 2.7 4 42/67 37/68 Totals 317 101/158 (64%) 93/159 (58%) * Responder rate - a decrease in the HAMD of greater than 50% or achieving a value less than 10 In the study with the highest methodological rating, 135 depressed patients were treated in 20 centers. Patients were given either St. John's wort extract (0.3% hypericin content, 300 mg t.i.d.) or imipramine (25 mg t.i.d.) for a period of six weeks. Inclusion diagnoses were typical depressions with single episode, several episodes, depressive neurosis, and adjustment disorder with depressed mood in accordance with DSM-III-R. Main assessment criteria were the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S) and the Clinical Global Impressions (CGI). In both treatment groups, there were significant decreases in the HAMD from 20.2 to 8.8 in the St. John's wort group and from 19.4 to 10.7 in the imipramine group. The D-S point value also dropped from 39.6 to 27.2 in the St.John's wort group and 39.0 to 29.2 in the imipramine group. The analysis of CGI revealed comparable results in both treatment groups. The main advantage, however, was not so much a difference in therapeutic outcome, but rather a significant advantage in terms of lack of side effects and excellent patient tolerance in the St. John's wort group. St. Johns Wort Imipramine Hamilton Depression Scale Initial measurement 20.2 19.4 Week 6 8.8 10.7 Depression Scale (von Zerssen) Initial measurement 39.6 39 Week 6 27.2 29.2 Can St. John's wort extract be used with other antidepressant drugs? Yes, I have used St. John's wort successfully without incident in patients taking SSRIs, Effexor, and various tricyclics. I have not used it in conjunction with MAO inhibitors. I have also used St. John's wort extract with 5-hydroxytryptophan (5-HTP). The real concern when mixing antidepressant drugs is producing what is referred to as the " serotonin syndrome. " It is characterized by confusion, fever, shivering, sweating, diarrhea, and muscle spasms. Although this syndrome has never been produced when St. John's wort extract has been given alone, it is theoretically possible that combining St. John's wort with standard antidepressant drugs could produce this syndrome. My recommendation is that when using St. John's wort in combination with standard antidepressant drugs that patients be monitored closely for any symptoms suggestive of the serotonin syndrome. If these symptoms appear, elimination of one of the therapies is indicated. What is your recommendation for tapering off the antidepressant drug? It really depends on the patient and the severity of the pre-treatment depression. First of all, I should state that I always try to work in conjunction with the prescribing physician to accomplish the patient's goal of getting off the drug. In mild cases, I will have the patients start the St. John's wort extract while reducing the drug to ½ the daily dosage for two weeks. After which, they will totally eliminate the drug. For more severe cases, they keep the dosage of their antidepressant as it is and add the St. John's wort extract. We then evaluate at the end of one month and begin tapering off the drug is sufficient mood-elevating effects have been noted. How long should a patient stay on St. John's wort extract? Again, it really depends upon the patient. In general, I view St. John's wort as a " crutch " until dietary, lifestyle, and attitude changes have had a chance to really take hold. My experience is that only about 25% of people really require prolonged therapy beyond six months. This patients typically have dysthymic personality traits and possibly a genetic predisposition to depression. Given St. John's wort excellent safety profile and the concern over the long-term safety of antidepressant drugs, I would much rather see patients using St. John's wort extract for an indefinite period than drugs like Prozac, Paxil, Zoloft, and others. Does St. John's wort extract negatively affect sleep like other antidepressant agents? No. While antidepressant drugs, particularly tricyclic antidepressants and MAO inhibitors, interfere with REM (rapid eye movement) sleep and reduce sleep quality, St. John's wort has been shown to not interfere with REM sleep and to actually improve sleep quality and well-being.19 The ability to improve sleep quality may turn out to be a key mechanism of action for St. John's wort extract. It does not act as a sedative (i.e., it does not reduce sleep onset) nor does it change total sleep duration. It simply improves sleep quality. St. John's wort accomplishes this when given in divided dosages throughout the day (e.g., 300 mg three times daily). How long does it take before its antidepressant effects are noted? Most patients begin reporting effects within the first two weeks. Like most antidepressant agents, maximum benefits are typically seen after six to eight weeks of continued use. What should be done if someone does not respond to St. John's wort extract? Depression requires a comprehensive treatment plan. St. John's wort extract will not be effective if there is an underlying nutrient deficiency or hormonal imbalance. For example, if some is deficient in folic acid or suffering from hypothyroidism it is unrealistic to expect St. John's wort extract to produce a dramatic improvement. In cases of depression that have not responded to St. John's wort extract alone where no other identifiable cause of depression could be found, I have used supportive therapy. If the patient is over the age of 50, supportive therapy consists of Ginkgo Phytosome (80 mg three times per day). Researchers began studying the antidepressive effects of Ginkgo biloba extract as a result of the improvement in mood noted by patients suffering from decreased blood flow to the brain (cerebrovascular insufficiency). Several studies were conducted to determine if Ginkgo biloba extract was, in fact, an antidepressant. In one of the more recent double-blind studies, 40 patients (ages ranged from 51 to 78 years) with depression who had not benefited fully from standard antidepressant drugs were given either 80 mg of Ginkgo biloba extract three times daily or a placebo. By the end of the 8th week study, the total score of the Hamilton Rating Scale for Depression in the Ginkgo biloba extract group had dropped from 14 to 4.5. In comparison, the placebo group dropped from 14 to only 13. This study indicated two things: (1) Ginkgo biloba extract can be used with standard antidepressants and/or St. John's wort extract and (2) it may enhance their effectiveness, particularly in patients over 50 years of age. I prefer the Ginkgo biloba extract bound to phosphatidylcholine (Ginkgo Phytosome) to un-bound ginkgo. In patients, under the age of fifty, I tend to favor 5-hydroxytryptophan (5-HTP) - the direct precursor to serotonin. 5-HTP has shown impressive results as an antidepressant agent in numerous double-blind studies including head-to-head comparison studies with standard antidepressant drugs. Currently, 5-HTP is only available through compounding pharmacists. To find a compounding pharmacist in your area, call the International Academy of Compounding Pharmacists 1-800-927-4227. Is St. John's wort extract effective in seasonal affective disorder? Yes, but best results are achieved when it is combined with light therapy. Seasonal affective disorder (SAD) represents a subgroup of major depression with a regular occurrence of symptoms in autumn/winter and full remission in spring/summer. Light therapy has become the standard treatment of this type of depression. Apart from this, St. John's wort extract also seems to provide an improvement of SAD symptoms. The aim of a controlled, single-blind study was to evaluate if St. John's wort could be beneficial in treating SAD patients and whether the combination with light therapy would be additionally advantageous. Patients who fulfilled DSM-III-R criteria for major depression with seasonal pattern were randomized in a 4-week treatment study with 900 mg of St. John's wort extract (0.3% hypericin content) per day combined with either bright (3000 lux, n = 10) or dim light (<300 lux therapy). The fact that there was a significant reduction in the Hamilton Depression scale in both groups (72% and 60%, respectively) indicates that St. John's wort extract may offer support to patients with SAD as a sole therapeutic agent as well as in combination with light therapy. Obviously, the best results were obtained in combination with bright light. Are there any other indications for St. John's wort extract? One of the key indications for St. John's wort extract in my clinical practice is in the treatment of fibromyalgia. Fibromyalgia is a recently recognized disorder regarded as a common cause of chronic musculoskeletal pain and fatigue. Although fibromyalgia may be the " pop " diagnosis of the 1990s, it is a real clinical entity estimated to affect about 4% of the general population. Although fibromyalgia is a disorder that has many facets, the central cause of the pain of fibromyalgia are low levels of serotonin. As a result of a chronic low level of serotonin, the sensation of pain is great exaggerated. Table - Diagnostic Criteria for Fibromyalgia Diagnosis requires fulfillment of all three major criteria and four or more minor criteria. Major criteria Generalized aches or stiffness of at least three anatomic sites for at least three months. Six or more typical, reproducible tender points. Exclusion of other disorders which can cause similar symptoms. Minor criteria Generalized fatigue Chronic headache Sleep disturbance Neurological and psychological complaints Joint swelling Numbing or tingling sensations Irritable bowel syndrome Variation of symptoms in relation to activity, stress, and weather changes Although St. John's wort extract can certainly be effective on its own, in my clinical experience I have found that the combination of St. John's extract (300 mg, 0.3% hypericin content), magnesium (200 to 250 mg), and 5-HTP (100 mg) three times daily seems to work better than using any of these three supplements alone. Low magnesium levels are a common finding in patients with fibromyalgia as well as in chronic fatigue syndrome. Magnesium supplementation has produced very good results in both conditions part of which may be due to its importance to serotonin function.27,28 One of the primary benefits with St. John's wort as well as 5-HTP relates to their ability to improve sleep quality. One of the key findings in patients with fibromyalgia is a reduced REM sleep and an increased non-REM sleep. In addition, the deeper levels (stage III and IV) are not achieved for long enough periods. As a result people with fibromyalgia wake up feeling tired, wornout, and in pain. The severity of the pain of fibromyalgia correlates with the rating of sleep quality. What I mean by this statement is that when patients with fibromyalgia get a good night's sleep they have less pain. Conversely, when they sleep poorly, they feel terrible. The analogy I give my patients suffering from fibromyalgia is that sleep is like a battery re-charger. If the body, especially our muscles, is not being re-charged, it hurts. With a good, restful sleep the battery become fully charged and functions more optimally. The outcome is the body doesn't hurt anymore. What is the best dosage schedule for St. John's wort? The dosage of St. John's wort preparations are based upon the hypericin content. The overwhelming majority of the studies in depression have used the St. John's wort extract standardized to contain 0.3% hypericin at a dosage of 300 mg three times daily. Is St. John's wort extract safe? No significant side effects have been reported in the numerous double-blind studies, but perhaps the best demonstration of the excellent safety record of St. John's wort extract is a large scale study involving 3,250 patients conducted in Germany. Results were analyzed by means of a patient questionnaire. Pooled data indicated that symptoms of depression were reduced in frequency and intensity by approximately 50%. The frequency of undesired side effects were reported in 79 patients (2.43%) and 48 (1.45%) discontinued therapy. The most frequently noted side effects were gastrointestinal irritation (0.55%), allergic reactions (0.52%), fatigue (0.4%), and restlessness (0.26%). The frequency and severity of side effects with St. John's wort extract are clinically insignificant, especially when compared to the well-known side effects of tricyclics and other antidepressants. There have been no deaths due to St. John's wort toxicity, a stark contrast to the 31 deaths per one million prescriptions produced by synthetic antidepressants. What about phototoxicity? There is considerable evidence that St. John's Wort can cause severe photosensitivity in animals grazing extensively on the plant. In fact, the term " hypericism " has been used to describe a skin disease found in animals who graze on large quantities of St. John's Wort. Because of the possibility of photosensitivity, it is often recommend that individuals, especially those with fair skin, avoid exposure to strong sunlight and other sources of ultraviolet light when using St. John's Wort. However, while this recommendation may be appropriate it must be pointed out that the therapeutic dosage of 2.7 mg hypericin per day is about 30 to 50 times below the level required to produce phototoxicity. Reports of photosensitivity in humans have been rare and have been limited to those taking excessive quantities for HIV infection. St. John's Wort is unlikely to be toxic to humans when used at recommended medicinal doses. However, individuals with AIDS taking larger amounts of St. John's wort extracts (or hypericin) have developed photosensitivity. Should tyramine-containing foods be avoided? Initially it was also recommended that those taking St. John's wort should also avoid foods and medications that are known to negatively interact with MAO-inhibiting drugs such as tyramine-containing foods (cheeses, beer, wine, pickled herring, yeast, etc.) and drugs such as L-dopa and 5-HTP should be avoided. However, given more recent information on the lack of any in vivo MAO inhibition, this recommendation is not justified. References: Ernst E: St. John's wort, an antidepressant? A systematic, criteria-based review. Phytomed 2:67-71, 1995. Linde K, et al.: St. John's wort for depression - an overview and meta-analysis of randomised clinical trials. BMJ 313:253-8, 1996. Thiede HM and Walper A: Inhibition of MAO and COMT by hypericum extracts and hypericin. J Geriatr Psychiatry Neurol 7(Suppl. 1):S54-6, 1994. Bladt S and Wagner H: Inhibition of MAO by fractions and constituents of hypericum extract. J Geriatr Psychiatry Neurol 7(Suppl. 1):S57-9, 1994. Thiele B; Brink I and Ploch M: Modulation of cytokine expression by hypericum extract. J Geriatr Psychiatry Neurol 7(Suppl. 1):S60-2, 1994. Perovic S and Muller WEG: Pharmacological profile of hypericum extract. Effect of serotonin uptake by postsynaptic receptors. Arzneim Forsch 45:1145-8, 1995. Halama P: Efficacy of the Hypericum extract LI 160 in the treatment of 50 patients of a psychiatrist. Nervenheilkunde 10:305-7, 1991. HansgrenD, Vesper J and Ploch M: Multicenter double-blind study examining the antidepressant effectivenss of the hypericum extract LI 160. J Geriatr Psychiatry Neurol 7(Suppl 1):S15-8, 1994. Harrer G and Sommer H: Treatment of mild/moderate depressions with Hypericum. Phytomed 1:3-8, 1994. Hubner WD, Lande S and Podzuweit H: Hypericum treatment of mild depressions with somatic symptoms. J Geriatr Psychiatry Neurol 7(Suppl 1):S12-4, 1994. Quandt J, Scmidt U and Schenk N: Ambulante behandlung leichter und mittelschwerer depressiver verstiimmungen. Der Allgemeinarzt 2:97-102, 1993. Reh C, Laux P and Schenk N: Hypericum-extrakt bei depressionen - eine wirksame alternative. Therapeiwoche 42:1576-81, 1992. Schmidt U and Sommer H: St. John's wort extract in the ambulatory therapy of depression. Attention and reaction ability are preserved. Fortschr Med 111:339-42, 1993. Schmidt U, et al.: The therapy of depressive moods. Psycho 15:665-71, 1989. Sommer H and Harrer G: Placebo-controlled double-blind study examining the effectiveness of an hypericum preparation in 105 mildly depressed patients. J Geriatr Psychiatry Neurol 7(Suppl 1):S9-11, 1994. Bergman R, Nubner J and Demling J: Behandlung leichter gis mittelschwer depressionen. Therapiewoch Neurologie/Psychiatrie 7:235-40, 1993. Harrer G, Hubner WD and Podzuweit H: Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study. J Geriatr Psychiatry Neurol 7(Suppl 1):S24-8, 1994. Vorbach EU, Hubner WD and Arnoldt KH: Effectiveness and tolerance of the hypericum extract LI 160 in comparison with imipramine: randomized double-blind study with 135 outpatients. J Geriatr Psychiatry Neurol 7(Suppl 1):S19-23, 1994. Schulz H and Jobert M: Effects of hypericum extract on the sleep EEG in older volunteers. J Geriatr Psychiatry Neurol 7(Suppl 1):S39-43, 1994. Schubert H and Halama P: Depressive episode primarily unresponsive to therapy in elderly patients: Efficacy of Ginkgo biloba (Egb 761) in combination with antidepressants. Geriatr Forsch 3:45-53, 1993. van Praag HM and Lemus C: Monoamine precursors in the treatment of psychiatric disorders. In: Nutrition and the Brain, Vol. 7. Wurtman RJ and Wurtman JJ (eds.). Raven Press, New York, NY 1986 pp89-139. Byerley WF, et al.: 5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects. J Clin Psychopharmacol 7:127-37, 1987. Poldinger W, Calanchini B and Schwarz W: A functional-dimensional approach to depression: Serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 24:53-81, 1991. Martinez B, et al.: Hypericum in the treatment of seasonal affective disorders. J Geriatr Psychiatry Neurol 7(Suppl 1):S29-33, 1994. Romano TJ and Stiller JW: Magneisum deficiency in fibromyalgia syndrome. J Nutr Med 4:165-7, 1994/ Cox IM, Campbell MJ and Dowson D: Red blood cell magnesium and chronic fatigue syndrome. Lancet 337:757-60, 1991. Abraham G: Management of fibromyalgia: Rationale for the use of magnesium and malic acid. J Nutr Med 3:49-59, 1992. Hicks JT: Treatment of fatigue in general practice: a double blind study. Clin Med Jan:85-90, 1964. Affleck G, et al.: Sequential daily relations of sleep, pain intensity, and attention to pain among women with fibromyalgia. Pain 68:363-8, 1996. Woelk H, Burkard G and Grunwald J: Benefits and risks of the hypericum extract LI 160: drug monitoring study with 3250 patients. J Geriatr Psychiatry Neurol 7(Suppl 1):S34-8, 1994. Henry JA, Alexander CA and Sener EK: Relative mortality from overdose of antidepressants. Br Med J 310:221-4, 1995. Araya OS and Ford JH: An investigation of the type of photosensitization caused by the ingestion of St. John's Wort (Hypericum perforatum) by calves. J Comp Path 91:135-41, 1981. Siegers CP, Biel S and Wilhelm KP: Zur frage der phototoxizitat von hypericum. 12:320-2, 1993. Gulick R, et al.: Human hypericism: a photosensitivity reaction to hypericin (St. John's Wort). Int Conf AIDS 8:B90 (abstract no. PoB 3018), 1992. =============================================== Ten-year review of herbal psychiatric treatments. =============================================== Ten-year review of herbal psychiatric treatments. http://www.herbs.org/current/herbpsychtreatments.htm In a review article published in September 2000, researchers summarize and critique the findings of controlled clinical trials on St. John's wort, kava, ginkgo, and valerian published since 1991. Reviewers found the evidence for St. John's wort's efficacy the most convincing, with five of nine studies showing it to be superior to placebo, and the other four finding the herb to be as effective as prescription antidepressants. They believe that poorly defined patient populations, small sample sizes, short treatment duration, and nonstandard measures of symptoms make the positive results of many of the kava and ginkgo studies less credible. Thirty-nine of the 40 ginkgo trials reviewed found that the extract significantly improved memory, concentration, fatigue, anxiety, and depression in patients with dementia. Psychiatric Services, September 2000. _________________ JoAnn Guest mrsjo- DietaryTi- www.geocities.com/mrsjoguest/Genes AIM Barleygreen " Wisdom of the Past, Food of the Future " http://www.geocities.com/mrsjoguest/Diets.html The all-new My – What will yours do? Quote Link to comment Share on other sites More sharing options...
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