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Herbs: Uses, Side effects | Tags: clinical-testing

CLINICAL TRIALS

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May 25, 2011 at 6:33 am

Impairment of Cerebral Function/Cerebral Insuffiency

Impairment of cerebral function and cerebral insuffiency are not well-defined syndromes (in contrast to dementia or major depression). These terms are mainly used for arbitrarily naming a cluster of symptoms associated with ageing and were characteristic for early to moderate dementia at times when commonly accepted criteria for dementia did not yet exist, or were not yet routinely applied by clinicians. Moreover, today’s clinical criteria do not apply for patients with very early dementia, since a certain degree of impairment is required in order to establish the diagnosis. It is however quite clear that the disease begins with mild impairment and then progresses until a diagnosis of dementia can be established. Taking these facts into account, it can be assumed that a substantial part of those patients included in these earlier trials under the diagnosis impairment of cerebral function really did suffer from dementia. This view is supported by a comparison of the trials involving such patients, and trials in well-defined dementia patients: the results of treatment with Ginkgo biloba special extracts are essentially the same.

Two groups of patients suffering from cerebral function impairment due to cerebrovascular disease were examined in a study by Moreau (1975). One group (n=60) was subjected to a double-blind comparison of Ginkgo Biloba Extract 761 and placebo. The other group (n=30) was treated with ergot alkaloid derivatives in an open part of the study. Treatment efficacy was evaluated by means of psychometric tests, the clinician’s global judgement, a scale of typical symptoms, and a general activities scale. The oral daily dose of Ginkgo Biloba Extract 761 was 120mg, the treatment period was 3 months. In 79.3% of patients Ginkgo Biloba Extract 761 led to a global improvement (physician’s assessment as “good” or “very good” results), whereas only 21.4% improved relevantly in the placebo group (p<0.001). Ginkgo Biloba Extract 761 treatment led to a more pronounced improvement than placebo application in functional symptoms (vertigo, headache, tinnitus), general activity, in 7 of 10 psychometric tests, and in the overall assessment. Treatment with ergot alkaloids was also of some benefit, in that 53.3% of global judgements were favourable after 3 months.

Twenty patients treated with Ginkgo Biloba Extract 761 (120mg/day) and 20 patients who received placebo during 60 days, all suffering from chronic impairment of cerebral function and being of an average age of 62 years, were compared in a trial by Dieli et al. (1981). Patients were selected using the geriatric assessment scale according to Plutchik et al. (1970) for proof of relevant impairment and the Hachinski ischaemic score (<7). Thus the majority of them may be presumed to have suffered from primary degenerative dementia of the Alzheimer type or mixed type dementia. Psychometric tests could be carried out in only 11 Ginkgo Biloba Extract 761-treated and 14 placebo-treated patients due to advanced severity of the disease. Active treatment was significantly superior (p<0.05) to placebo with respect to 11 items of the Plutchik assessment scale and both the Wechsler digit span and digit symbol test. Two adverse reactions of mild intensity and short duration were recorded in the Ginkgo Biloba Extract 761-treated group (1 case of nausea, 1 of water brash). The multitude of tests referring to items of the Plutchik scale justify their classification as descriptive. Evidence was nevertheless provided for the efficacy of Ginkgo Biloba Extract 761 on the psychopathological, the psychometric and the behavioural level.

Fifty patients with cerebrovascular insufficiency were studied by Eckmann and Schlag (1982). After random allocation, 25 patients were treated with oral daily doses of 120mg Ginkgo biloba special extract Ginkgo Biloba Extract 761 and 25 patients received placebo. Duration of treatment was 4 weeks. The outcome measures comprised psychological and neurological findings and typical symptoms (dizziness, headache, tinnitus, state of consciousness, anxiety, language function, sensibility, orientation, speech comprehension, motor behaviour, depressed mood). Except for frequency of tinnitus and hearing disorders both groups were comparable at baseline. Improvement of pathological symptoms began much earlier (median 12 days) in the patients treated with Ginkgo Biloba Extract 761 than in those treated with placebo, single symptoms had disappeared after 30 days in 91 to 100% of Ginkgo Biloba Extract 761 patients in whom they were present before treatment (p<0.0005 vs. placebo). In the placebo group, single symptoms disappeared in only 43 to 57% of patients. No adverse reactions and no significant changes in laboratory tests were observed. Distinct outcome differences in favour of Ginkgo Biloba Extract 761 allow to assume clinical efficacy in disturbances of cerebral function caused by cerebrovascular disease.

One hundred and sixty-six patients over 60 years of age and suffering from impairment of cerebral function, mostly due to mild primary degenerative dementia, vascular dementia, and mixed forms, were studied by Taillandier et al. (1986). They were treated for 12 months with either 160mg/day of Ginkgo Biloba Extract 761 or placebo. Eighty patients were included in the Ginkgo Biloba Extract 761 group, 86 patients in the placebo-group. With respect to demographic data and severity, the groups were well comparable. In the course of Ginkgo Biloba Extract 761 treatment, there was a steady decrease in the total score of the clinical geriatric evaluation scale EACG resulting in a statistically significant difference compared to the placebo group (p<0.05) from month 3 onward. Mean improvement in the actively treated group was 17% from baseline score after 12 months, but only 7% in the placebo group (p=0.05). Laboratory parameters showed no relevant changes during the trial. Patients suffering from impairment of cerebral function for more than 2 years had more benefit from Ginkgo Biloba Extract 761 treatment than those afflicted more recently. In conclusion, it could be demonstrated that the treatment with Ginkgo Biloba Extract 761 can significantly improve everyday behaviour and the social integration of patients with dementia syndrome.

Eighty patients (mean age 68.4 years) suffering from memory impairment affecting their daily life activities were enrolled in a trial by Israel et al. (1987). They were randomly assigned to 4 groups of 20. Mild cognitive impairment was verified by a score of 20 to 26 in the Mini-Mental State Examination. Patients were excluded if they had a depressive syndrome as defined by a score of 18 or more on the Geriatric Depression Scale. The first and the third group were treated with Ginkgo Biloba Extract 761 (160mg/day), the second and fourth group received placebo. Patients of groups 3 and 4 took part in a standardized memory training program in addition to the study medication. Treatment duration was approximately 3 months. Memory training sessions took place weekly. Four factors of memory as assessed by a comprehensive test battery developed by the authors were examined: general memory, immediate memory (attention/perception), learning factor, mental fluidity and control. The absolute difference in the scores of the 4 factors was comparatively tested by an analysis of variance. Significant improvements were observed in the Ginkgo Biloba Extract 761 group in the context of immediate memory and mental fluidity and control. Training had a positive effect on both general memory and immediate memory. The learning factor did not change in either treatment; there was, however, an additive improvement of immediate memory in patients who underwent Ginkgo Biloba Extract 761 treatment and training. Memory training by itself had an influence on general recall factors, but treatment with Ginkgo Biloba Extract 761 only was able to influence mental fluidity, which involves association speed. Eighty-eight percent of the patients treated with Ginkgo Biloba Extract 761 by itself considered their therapy to have been sufficiently effective, which was the case in only 23% of the placebo group (p<0.001). Of the patients who underwent both memory training and Ginkgo Biloba Extract 761 treatment, 100% experienced memory improvement. Three adverse events were observed: 2 occurred under treatment with Ginkgo Biloba Extract 761 (1 case of nausea, dyspepsia; 1 of dizziness), another one in the placebo-group (retrosternal chest pain). There were 5 further drop-outs (2 patients did not take the study drug, 3 refused to undergo the tests; they felt disadvantaged because they had not been assigned to the training sessions). In summary, treatment with Ginkgo Biloba Extract 761 was safe and turned out to be more effective in improving impaired memory function when combined with memory training than either treatment alone.

Forty outpatients suffering from mild to moderate impairment of cerebral function due to cerebrovascular disease (mostly vascular dementia), comprising a Hachinski Ischemic Score less than 7, were included in a study by Halama et al. (1988). According to random allocation, 20 patients received a daily dose of 120mg Ginkgo biloba special extract Ginkgo Biloba Extract 761 and 20 patients were given placebo. Patients with other neurologic, psychiatric, or severe somatic illness or taking other rheologically active or psychotropic drugs were excluded. Duration of treatment was 12 weeks. Primary outcome measure was the SCAG total score. In the group receiving Ginkgo Biloba Extract 761 the SCAG total score diminished by an average of 9 points, whereas it remained unchanged in the placebo group (p<0.005). Descriptive evaluation of the single items indicated particularly pronounced effects on disturbances of short-term memory, mental alertness and dizziness. Superior effects of Ginkgo biloba extract were also demonstrated as regards headache and tinnitus. Improvement of attention and memory was confirmed by an objective cognitive test (SKT). There were no drop-outs. A mild and temporary adverse event (headache) was observed in 1 patient of the active treatment group.

Out of 50 inpatients from a neurological ward (age 57 to 76 years) suffering from organic brain syndrome, Hofferberth (1991) treated 25 patients with oral daily doses of 150mg Ginkgo biloba special extract LI 1370 for 6 weeks. A further 25 patients were given placebo during the same time. Efficacy was assessed by two psychometric tests, the Vienna Determination Test and the digits connection test, functional dynamic investigations (saccadic eye movements, EEG analysis, measurement of evoked potentials), a symptom scale and global rating of change (e.g. “good”, “moderate” or “satisfactory” improvement). A significant superiority of LI 1370 compared to placebo could be demonstrated in 9 out of 11 typical symptoms of age-related cerebral impairment (p<0.01) as well as in the global rating of improvement (p<0.001) and in all of the functional dynamic measurements (p<0.001). No adverse reactions were reported.

Schmidt et al. (1991) randomly assigned 99 patients aged 50 to 70 years and suffering from impairment of cerebral function to treatment with Ginkgo biloba extract LI 1370 (150mg/day) or placebo (50 and 49 patients, resp.). Patients with neurologic or severe somatic conditions or taking medication that could possibly interfere with efficacy assessment had to be excluded. Therapeutic success was documented by a symptom scale comprising 12 typical symptoms of age-related cerebral impairment and by a global judgement. After 12 weeks of LI 1370 treatment 8 of the 12 symptoms were significantly more improved than after placebo treatment (p<0.05). This was confirmed by both the physician’s and the patient’s global assessment of therapy response (p<0.01). Three events of mild nausea which might have been related to the drug under study were recorded in the active treatment group.

Bruchert et al. (1991) enrolled 303 patients (age range 45-80 years) of 33 general practices into a multicentre trial with the Ginkgo biloba special extract LI 1370, administered at a daily dose of 150mg for 12 weeks. The inclusion diagnosis was a syndrome of impaired cerebral function as defined by a typical psychopathology not due to a somatic or psychiatric disease (other than dementia). Psychotropic or cognition-enhancing drugs were prohibited during participation in the study. Clinical efficacy was assessed on the psychopathological level by a symptom rating scale comprising 11 typical symptoms of age-associated impairment of cerebral function (concentration disturbances, forgetfulness, memory impairment, fatigue, loss of drive and capability, depressed mood, anxiety, dizziness, headache, tinnitus) and by the physician’s global judgement of therapy response. On the level of objective performance testing, the digits connection test (a sort of trail-making test); was chosen as an outcome measure. Because of major protocol violations, 94 patients had to be excluded from the efficacy analysis, which was therefore based on the data of 209 patients. After 12 weeks of treatment with LI 1370, improvements were significantly more pronounced in the actively treated group than in the placebo group regarding 8 out of 11 symptoms in the rating scale. This was confirmed by the physician’s global judgement as well as by the patient’s global self-assessment of well-being. In the digits connection test, there was a mean decrease in processing time in both groups, amounting to 25% of the pre-treatment values in the LI 1370 group and 14% in the placebo group (p<0.01). Adverse events were reported for 16 patients of the active-treatment group and for 32 patients in the placebo group. The only kind of event which might have been unfavourable for the Ginkgo biloba extract on account of its frequency was headache (4 events vs. 1 event in placebo; n=153 and 150, respectively). In particular, this trial reflects everyday therapeutic reality in general practices and, under such unfavourable conditions, the clinical efficacy of Ginkgo biloba extract was still noticeable. There was, however, one drawback in that the number of protocol violations was rather high.

The effect of Ginkgo biloba special extract Ginkgo Biloba Extract 761 on basic parameters of mental performance was studied by Gravel (1992). 72 outpatients (37 females, 35 males, mean age: 63.8±8.4 years) with impairment of cerebral function due to cerebrovascular disease were included in this 24-week clinical trial. The patients received either Ginkgo Biloba Extract 761 (160mg/day) or placebo. Diagnosis was verified by the patients’ medical history (indications of stenosing vascular process in the cranial area) and several computer-based psychometric tests requiring a simple patient-PC dialogue. Patients suffering from other neurologic, psychiatric, or relevant somatic diseases had to be excluded from the study. Treatment with psychotropic or vasoactive drugs or with drugs having an influence on the cell metabolism was not allowed during the study. The intelligence quotient (IQ) as calculated from short-term storage capacity steadily increased in the actively treated group from 93.5 at commencement to 107.5 after 24 weeks of treatment (mean values), where as only a slight improvement, most likely due to training effects, could be observed in the placebo group (from 93.8 to 95.8). Intra-group comparisons revealed statistically significant pre-post differences in the Ginkgo Biloba Extract 761 group from week 6 onwards, but at no time in the placebo group. Inter-group differences were statistically significant at week 24 (p<0.05). The memory quotient (MQ), derived from learning speed, basically showed the same development in the course of treatment. However, due to a difference in baseline values favouring the placebo group, inter-group differences did not reach statistical significance after treatment in spite of larger improvements in Ginkgo Biloba Extract 761 patients. Four adverse reactions were documented in the Ginkgo Biloba Extract 761 group and 6 in the placebo group. Seven patients dropped out of the Ginkgo biloba group and 12 from the placebo group. Dropout reasons appeared unrelated to the study drug. In summary, the findings of this study demonstrate that, in patients suffering from impaired cerebral function due to cerebrovascular disease, basic functions of information processing can be improved by Ginkgo Biloba Extract 761 treatment. It has to be mentioned here that this type of theory-guided testing has been explicitly recommended by the German Federal Health Authority’s expert committees.

Vesper and Hansgen (1994) tested the efficacy of Ginkgo biloba special extract LI 1370 versus placebo in 86 patients (aged 55 to 80 years) attending 11 practices run by neurologists, psychiatrists, general practitioners and internists. The diagnosis for inclusion was cerebral insufficiency according to ICD-9 criteria (290.X). Patients had a minimum IQ of 80 and suffered from distinct subjective troubles which were reflected by a minimum score of 19 in the cerebral insufficiency (C.I.) scale according to Weidenhammer and Fischer (1987). Patients suffering from any severe somatic or psychiatric illness (including pseudodementia) or using any nootropic, psychotropic or vasoactive agents had to be excluded. In accordance with random allocation, 42 patients were treated with Ginkgo biloba special extract LI 1370 (150mg/day) and 44 patients were given placebo for 12 weeks. Efficacy evaluation was based on self-rating symptom scales and a computerized test battery comprising 5 subtests: a) basic reaction time (required for accomplishing simple tasks); b) time/tenacity training test (reflecting qualitative aspects of attention and ability to learn); c) mental flexibility test (for qualitative attention to be determined from the patients mental flexibility); d) visual memory test; e) character discrimination test (measuring the ability to discriminate 2 different short-term stimuli counts). Additionally, a short test of general basic parameters of intelligence was carried out. This test accounts for the speed of information processing and the period for which the information is available in the short-term memory. As regards sociodemographic data and severity, the two treatment-groups were quite homogeneous at randomization. Superiority of active treatment already became obvious after 6 weeks when the groups were distinguishable by statistical means with respect to nearly all outcome variables. After 12 weeks of treatment significant inter-group differences in favour of LI 1370 were found in the self-rating symptom scale, in the C.I. total score and in the 5 subtests of the computerized battery. In the KAI there was a faster improvement of basic factors of information processing, although this could not be proven statistically at 12 weeks. No adverse side effects were observed under either treatment.

Dementia

Cerebral Insufficiency and Depressed Mood

Stocksmeier and Eberlein (1992) performed a trial on 60 patients aged between 51 and 71 years, and suffering from both impairment of cerebral function and depressed mood. Patients were required to score below 90% of the age-specific norm in the concentration-performance test and above 15 in the Hamilton Depression Scale. According to their random allocation, 30 patients each were treated with daily oral doses of 120mg Ginkgo Biloba Extract 761 and placebo respectively. After 12 weeks treatment, a significantly more pronounced decrease in the HAMD total score was observed in the Ginkgo Biloba Extract 761 group compared with the placebo group (45% vs. 31%; p<0.05). No significant inter-group differences were found with respect to the KLT.

Schubert and Halama (1993) included 40 patients aged 51 to 78 years and suffering from both mild impairment of cerebral function and depressive mood in a randomized trial. Cerebral impairment was assessed by the C.I. scale (total score at least 20 points). Depression had been treated with standard antidepressants for at least 3 months without achieving an acceptable improvement or remission. While continuing the antidepressive treatment at a stable dosage, 20 patients each were additionally administered 240mg/day of Ginkgo Biloba Extract 761 or placebo for 8 weeks. Concomitant medication possibly influencing depression or cerebral function was prohibited during study participation. In the actively treated patients, a decrease in the HAMD total score from 14 to 7 was observed after 4 weeks followed by a further drop to 4.5, thus reflecting a considerable alleviation of depressive symptoms. At the same time the HAMD total score decreased from 14 to 11 in the placebo group. The superiority of Ginkgo Biloba Extract 761 treatment was statistically confirmed (p<0.01). Cognitive performance as assessed by a short general intelligence test was also significantly improved by Ginkgo Biloba Extract 761 (p<0.05 vs. placebo).

It might be criticized that, in both trials, depression and impairment of cerebral function were not precisely defined as ICD or DSM diagnoses. This is exactly the problem when using this approach. In a considerable number of elderly patients appearing depressed and cognitively impaired, it is very difficult or even impossible to decide whether they are suffering from depression with concomitant disturbances of cognitive functions, or from dementia with concomitant depression. The American Psychiatric Association was aware of this problem when drawing up the DSM-III-R. They recommended first to assume a depression and, when antidepressant therapy proved ineffective, to change the diagnosis into that of dementia. An increase of antidepressant dosage as would be adequate in younger patients is often impossible in elderly as many antidepressants further aggravate cognitive impairment due to anticholinergic side effects. Therefore, it appears intriguing to have a drug that improves both impairment of cerebral function and depressive mood. There remain, however, questions that should be addressed in further studies: Can any predictors of treatment response be identified? Is there an advantage of combined (antidepressant) treatment over Ginkgo Biloba Extract 761 alone?

Herbs: Uses, Side effects | Tags: clinical-testing

DEMENTIA

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May 25, 2011 at 6:32 am

Weitbrecht and Jansen (1986) studied the effects of Ginkgo Biloba Extract 761 (120mg/day) compared with placebo and ergot alkaloids (5.94mg/day) in patients suffering from mild to moderate primary degenerative dementia. This randomized trial was double-blind with respect to Ginkgo Biloba Extract 761 and placebo, and the reference substance was given to a third treatment group under open conditions. Sixty patients (average age 72.4±4.6; Hachinski score<7) were treated for 3 months with Ginkgo Biloba Extract 761, placebo, or ergot alkaloids, 20 patients each. Efficacy was measured on the psychopathological level from the patient’s self-assessment, the physician’s global assessment and the Sandoz Clinical Assessment — Geriatric. Objective assessment of performance was carried out by applying the Wechsler digit symbol substitution test and the digit span test. Flicker fusion frequency and reaction time were tested to provide insight into functional-dynamic effects, and the Crichton scale was employed for assessment of behaviour closely related to activities of daily living. After only 4 weeks of treatment, the EGb 76 l-treated group showed statistically significant improvements in both psychometric test performance and clinical assessments. After 3 months of Ginkgo Biloba Extract 761 treatment, a mean improvement of 23.5% as compared to baseline was found on the Crichton scale. Pre/post differences were significantly higher in the active treatment group as compared with the placebo group after 3 months (p<0.0001; U-test). The SCAG total score improved by approximately 33% in comparison to baseline values (p<0.0001 for pre/post differences vs. placebo; Fig. 1). According to the physician’s global assessment and the patients’ self-assessment, the patients’ state of health improved significantly under Ginkgo Biloba Extract 761 treatment, but not under placebo. Both the digit span and digit symbol substitution test demonstrated significantly greater improvements in actively treated patients compared with placebo-treated patients. The same was true for flicker fusion frequency and reaction time. Treatment with ergot alkaloids gave also a significantly better outcome than placebo treatment. There were no significant differences at any time between the reference substance and Ginkgo Biloba Extract 761. No adverse reactions were reported (2 patients in the placebo-group dropped out for reasons unrelated to treatment). To summarize, the results of this study indicate the effectiveness of Ginkgo Biloba Extract 761 in treatment of mild to moderate primary degenerative dementia.

Wesnes et al. (1987) included 58 elderly patients (mean age 71 years) who were living at home and suffering from mild dementia manifesting itself as an impairment of everyday functioning (Crichton score >14). After a washout period of 1-3 weeks, 27 patients were treated with Ginkgo Biloba Extract 761 (120mg/day), and 27 were given placebo. Duration of treatment was 12 weeks. Efficacy was assessed by an extensive cognitive test battery comprising computerized as well as pencil and paper tests of memory function, attention, and information processing. Quality of life was measured by a behavioural questionnaire applied before and after the study. Improvements could be detected in both groups, but the improvement at week 12 was significantly more pronounced in the Ginkgo Biloba Extract 761-treated group than in the placebo group in most of the single tests, and also when the accuracy scores from all the 8 tests were combined (p<0.05). The most important finding in this study, however, emerged from the quality of life scale. While there was no difference between the treatment groups with respect to the number of activities still practised, the number of activities carried out with “high interest” increased significantly in the Ginkgo Biloba Extract 761-treated group (p<0.05) but not in the placebo group. One adverse event (constipation) was reported in the actively treated group which was not considered to be related to the treatment.

Figure 1 Development of SCAG Total Scores During 12 Weeks Treatment with Ginkgo Biloba Extract 761 and Placebo; mean values and standard deviations; *: p<0.0001 for inter-group comparison of pre/ post differences.

In 50 outpatients suffering from mild dementia (uncomplicated senile dementia, presenile dementia and arteriosclerotic dementia) according to ICD-9, Halama (1991) studied the effects of Ginkgo biloba special extract LI 1370 on cognitive functioning and psychopathology. Patients were treated for 12 weeks with 150mg/day of LI 1370 or placebo, 25 patients each. A symptom scale comprising 11 typical symptoms of early dementia, the SKT-test, the digit connection test ZVT and global ratings by patients and the physician were employed to measure the therapeutic outcome. LI 1370 was found to be significantly superior to placebo concerning 7 out of 11 typical symptoms and the SKT total score. There was also a more pronounced decrease in ZVT processing time on active treatment which did not reach statistical significance. Global ratings of therapeutic success by both the patients and the physician significantly favoured LI 1370. Three adverse events were reported in this study: 1 patient receiving placebo suffered from headache and nausea; out of 2 patients under active substance, 1 reported an allergic skin reaction, the other complained of a pain in the kidney region.

Twenty patients with dementia of the Alzheimer type according to DSM-III-R and NINCDS/ADRDA criteria were enrolled in a study by Ihl et al. (1992). Treatment duration was 3 months. As primary efficacy measure, the sum score of the SKT-test was defined. Secondary efficacy measures were further psychometric tests: the ZVT and the Alzheimer’s Disease Assessment Scale, the Clinical Global Impressions, and electrophysiological parameters (topographic EEG). During treatment, SKT-scores changed in the Ginkgo biloba group from 19.67 to 16.78 (mean values) and from 18.11 to 18.89 in the placebo group (p=0.013 for differences). The superiority of Ginkgo biloba was also observed in the secondary variables, CGI change (p=0.069) and EEG (increase of mean amplitudes). There were no adverse drug reactions. The most important finding in this study was that the efficacy of Ginkgo Biloba Extract 761 could be clearly demonstrated by objective cognitive testing and global rating in patients suffering from relatively severe cerebral impairment in moderately severe dementia of the Alzheimer type, which rapidly progressed in placebo-treated patients.

Forty inpatients (aged 50 to 75 years) with a clinical diagnosis of mild senile dementia of the Alzheimer type, were studied by Hofferberth (1994). Diagnosis was based on common clinical criteria together with a CT-scan and the Hachinski Ischemic Score. Patients received, after random allocation, either Ginkgo Biloba Extract 761 (240mg/day) or placebo for 3 months. Inclusion criteria were described as follows: Blessed Dementia Scale (Blessed et al., 1968): sum Part A: 0-16, sum Part B: 9.5-30.5; Ischemic Score according to Rosen et al. (1980) <4; normal or diffuse and possibly asymmetrically atrophic CT findings. The severity of the disease was determined by the SKT-test (a brief cognitive test battery for the measurement of memory and attention; Kim et al., 1993) the total score of which was 17 in the Ginkgo Biloba Extract 761 group and 15 in the placebo group, both consistent with a moderately severe cognitive impairment. Exclusion criteria were: advanced Alzheimer dementia, i.e. necessity of special accommodation and constant care; intellectual deterioration or state of confusion and/or dementia syndrome of another origin, pseudodementia; significant depression with a HAMD total score >15; pronounced sensory or motor disturbances; severe organic illness. Treatment with vasoactive agents, nootropics, psychotonics, tranquilizers and/or antidepressants was prohibited throughout the study. The SKT-test was predefined as the primary outcome measure. Secondary variables were the Saccade Test, Vienna Determination Test, the Sandoz Clinical Assessment — Geriatric and electroencephalography (particularly the theta/alpha quotient). Memory and attention, as measured by the SKT, improved significantly in the verum group already after 1 month (inter-group differences at p<0.001), as did psychopathology, psychomotoric performance, and functional dynamic variables as measured by the procedures mentioned above. After 3 months of Ginkgo Biloba Extract 761 treatment, the mean SKT total score had decreased by 5 points whereas an increase of 2 points was found in the placebo group, resulting in a highly significant inter-group difference in favour of the active treatment (p<0.001). This was confirmed on the psychopathological level by a mean decrease of 29 points in the SCAG total score after Ginkgo Biloba Extract 761, compared with a negligible change during placebo application. At month 3, the theta/alpha quotient in the active-treatment group had decreased from 79.4% to 61.9%, indicating enhanced vigiliance. Significant superiority of the Ginkgo biloba special extract was also demonstrated as regards choice reaction time and both latency and speed of saccadic eye movements. No adverse events were observed. In this methodologically adequate trial, again, the clinical relevance of treatment-selected effects could be demonstrated by highly consistent results on 3 levels of assessment. Improvement in test performance measured by objective procedures was in accordance with a decrease in psychopathology and changes towards normal in functional dynamic measures.

Haase et al. (1996) enrolled 40 patients, aged 68±12.5 years, suffering from moderate dementia of the Alzheimer type, vascular dementia, and mixed forms according to DSM-III-R criteria (American Psychiatric Association, 1987) into a short-term study. Psychopathology corresponded to stages IV or V of the Global Deterioriation Scale of Reisberg e£ a/. (1982); patients showing any signs consistent with another type of dementia or suffering from severe somatic disease had to be excluded. Treatment duration was 4 weeks. Patients received either intravenous infusions of Ginkgo Biloba Extract 761 (200mg active substance/250ml saline) on 4 days of each week or placebo infusions having the same appearance. Clinical efficacy was assessed by the Nuremberg Gerontopsychological Observation Scale for Activities-of-Daily-Living which reflects the patient’s ability to perform activities of daily living as observed by a relative or a caregiver; by the change in the patient’s overall condition as realized by the psychiatrist (CGI, Item 2; National Institute of Mental Health, 1976); and by objective cognitive testing. In the actively treated group, a mean decrease of 3.6 in the NAB total score was found after 4 weeks treatment, thus reflecting a meaningful improvement in patients with moderate dementia. Only a minimal decrease of 0.3 points was seen in the placebo group. The resulting inter-group difference was highly significant (p<0.01). According to the CGI, 85% of actively treated patients and 35% of those who received placebo were judged as having improved (p<0.0001). The cognitive test revealed an improvement in general IQ in 45% of the patients treated with Ginkgo Biloba Extract 761 and in 5 patients who were given placebo (p<0.05). No adverse events occurred during Ginkgo Biloba Extract 761 treatment. As this trial was designed in accordance with the most recent published recommendations of the German Federal Health Authority, efficacy was assessed — and established — on the psychopathologic and the psychometric plane, and the plane of activities of daily living. It was thus possible to demonstrate that treatment-related improvements of psychopathology and cognitive test performance do in fact result in a gain of competence in coping with the demands of everyday life.

A very convincing study has been published by Kanowski et al. (1996). The objective was to prove the clinical efficacy of Ginkgo biloba special extract Ginkgo Biloba Extract 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Diagnoses were established by DSM-III-R criteria with support from CT-scans and the Ischemic Score according to Rosen et al. (1980). Patients were included if they scored between 13 and 25 in the Mini-Mental State Examination and between 6 and 18 in the SKT-test , which is compatible with mild to moderate dementia. Patients suffering from any other significant psychiatric or somatic disease, or taking any drugs possibly interfering with efficacy assessment were excluded. 216 patients aged over 55 years were randomized to receive either Ginkgo biloba special extract Ginkgo Biloba Extract 761 (240mg/day) or placebo. A run-in period of 4 weeks was followed by a treatment period of 24 weeks. Three primary variables were selected according to the recommended multi-dimensional approach for proving the efficacy of nootropic and/or anti-dementia drugs; these were the CGI (Item 2) as a global rating on the psychopathological level, the SKT for objective assessment of syndrome-relevant cognitive performance, and the Nuremberg Gerontopsychological Observation Scale for Activities-of-Daily-Living (NAB; Oswald and Fleischmann, 1995). Per-protocol analysis was based on the data from 156 patients (Ginkgo Biloba Extract 761: 79; placebo: 77) and carried out as a multiple-responder analysis according to pre-specified rules. Only those improvements considered clinically meaningful were accepted as being a response, i.e. a judgement of “much improved” or “very much improved”, with respect to the patient’s condition, in the CGI; a decrease of at least 4 points in the SKT total score; and a decrease of at least 2 points in the NAB total score. A response in at least 2 of the three primary variables was considered a treatment response. After 24 weeks, 28% of the patients treated with Ginkgo Biloba Extract 761 were found to be treatment responders, whereas only 10% of placebo patients showed multiple response (p<0.005, Fisher’s Exact Test). When considering only those patients who showed response in all of the 3 primary variables, Ginkgo Biloba Extract 761 was again found to be significantly superior to placebo (p<0.05, descriptive). When reviewing the single variables, improvements in CGI-scores termed “better” or “much better” were found in 32% of Ginkgo Biloba Extract 761-treated patients and in 17% of patients in the placebo group (p<0.05). Decreases in SKT total scores by at least 4 points were documented in 38% of the actively treated patients and in 18% of the placebo patients (p<0.005). Improvements in the NAB of at least 2 points were found in 33% of cases in the Ginkgo Biloba Extract 761 group and 23 % of cases in the placebo group (p<0.1). An additional intent-to-treat analysis of the data from 205 patients led to noticeably similar results. Exploratory analyses of prospectively defined subgroups did not reveal any relevant differences in efficacy in the context of the dementia type (Alzheimer or vascular). There were 5 adverse events in the Ginkgo Biloba Extract 761 group which were judged as possibly treatment-related by the investigators (allergic skin reactions, gastrointestinal complaints, headache). A comparison of all adverse events observed in 216 patients exposed to study medication (Ginkgo Biloba Extract 761 or placebo) shows, however, that allergic skin reactions were the only type of event that occurred more frequently in the actively treated group. The opposite was the case for gastrointestinal complaints; and headaches were virtually equally distributed between the groups.

Herbs: Uses, Side effects

WILD YAM

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May 24, 2011 at 2:08 pm

Botanical name: Dioscorea villosa

Family name: Dioscoreacaea

Synonyms: Colic root, rheumatism root

Part used: Root and rhizome

MAJOR CHEMICAL CONSTITUENTS

Glycoside and steroidal saponins, including diosgenin and dioscin, alkaloids, tannins, phytosterols, and starch

PRINCIPAL USES

• Spasmolytic in the treatment of uterine cramping, dysmenorrhea, and chronic pelvic pain

• Spasmolytic in cases of urinary tract infection (UTI) and interstitial cystitis

• Antiemetic in nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum

• Antispasmodic for irritable uterus or threatened miscarriage with uterine contractions

• Intrapartum use for painful labor with dysfunctional uterine contractions

• Postnatally for afterbirth pains

• Proposed estrogenic effects owing to theoretical ability of steroidal saponins in the plant to bind to estrogen receptors, thus used in the treatment of a variety of perimenopausal and menopausal complaints.

TRADITIONAL AND HISTORICAL USES

Wild yam was used by Native Americans and Eclectic physicians for a wide variety of complaints relating to spasmodic contractions of the hollow viscera ranging from bilious colic to dysmenorrhea. It was included in the National Formulary (NF) from 1916 to 1942 as a diaphoretic and expectorant. In the past decade it has enjoyed a resurgence in popularity based on the erroneous assumption that because it contains steroidal saponins used in the manufacture of progesterone for oral contraceptive pills (OCPs), it could be taken as an herb to increase progesterone levels and thus treat a variety of gynecologic complaints. It is found in topical creams for vaginal dryness. Any increase in progesterone associated with using topical creams, was due to the inclusion of USP grade synthetic progesterone to these products. Its alleged hormonal activity has also led to the inclusion of this herb in breast-enhancing products.

CLINICAL INDICATIONS

Wild yam is reported by herbal practitioners to be a reliable spasmolytic herb in the treatment uterine cramping, dysmenorrhea, chronic pelvic pain (CPP), urinary tract infection (UTI) and interstitial cystitis, particularly as an adjunct in combination with other herbs specific to those complaints. It is also sometimes used by midwives as an antiemetic in the treatment of troublesome nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum, and as an antispasmodic for irritable uterus or threatened miscarriage with uterine contractions. It is also occasionally used as an adjunct antispasmodic herb painful labor with dysfunctional uterine contractions and in the post-partum period for afterbirth pains.There is a paucity of studies on the clinical effects of wild yam, and no studies evaluating antispasmodic activity were identified.

IN VITRO, ANIMAL, AND CLINICAL DATA

A 2001 double-blind placebo-controlled crossover study of the effects of a wild yam cream in 23 healthy women suffering from troublesome symptoms of menopause was conducted. After a 4-week baseline period, each woman was given active cream and matching placebo for 3 months in random order. Diaries were completed over the baseline period and for 1 week each month thereafter, and blood and saliva samples were collected at baseline and at 3 and 6 months, for measurement of lipids and hormones. The average age of the subjects was 53.3 *** 1.1 years and average time since last period 4.3 *** 0.9 years. At baseline, the average body mass index was 27.3 *** 0.8, cholesterol level 5.7 *** 0.2 mmol/L and follicle stimulating hormone (FSH) level 74.2 5.1 IU/L; estradiol levels were undetectable in the majority of cases. After 3 months of treatment, no significant side effects were reported with either active treatment or placebo, and there were no changes in weight, systolic or diastolic blood pressure, or levels of total serum cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, FSH, glucose, estradiol, or serum or salivary progesterone. Symptom scores showed a minor effect of both placebo and active treatment on diurnal flushing number and severity and total non-flushing symptom scores, and on nocturnal sweating after placebo, but no statistical difference between placebo and active creams. A randomized, controlled trial of 13 menopausal women given two capsules three times daily for 3 months of an herbal combination containing wild yam root in doses lower than recommended, along with burdock root (Arctium lappa), licorice root (Glycyrrhiza glabra), mother-wort (Leonurus cardiaca), and angelica root {Angelica arch-angelica) demonstrated statistically nonsignificant decreases in menopausal symptoms in the active treatment group. Diosgenin, a component of wild yam, has been shown in several studies to reduce total serum cholesterol levels, likely as a result of reduced intestinal cholesterol and an effect potentiated by taking the herb with vitamin C. No hormonal effects, including no changes in DHEA, estrogen, and progesterone levels, or FSH or LH levels, have been observed. In one study of ovariectomized mice receiving 20 to 40 mg/kg of diosgenin injected subcutaneously daily for 15 days, mammary gland epithelial stimulation was observed without progesteronic effects, however, the effects of oral wild yam on breast tissue have not been studied in animal or human trials.

Is Eating Yams Where the Where the Health Benefits for Women Occur?

Interestingly, in a study by Wu et al, 24 apparently healthy postmenopausal women were recruited to replace their staple food (rice for the most part) with 390 g of yam (Dioscorea alata) in two of three meals per day for 30 days and 22 completed the study. Fasting blood and first morning urine samples were collected before and after yam intervention for the analyses of blood lipids, sex hormones, urinary estrogen metabolites and oxidant stress biomarker. The design was a one arm, pre-post study. A similar study of postmenopausal women (n = 19) fed 240 g of sweet potato for 41 days was included as a control study. Serum levels of estrone, estradiol, and SHBG were analyzed for this control group. After yam ingestion, there were significant increases in serum concentrations of estrone (26%), sex hormone-binding globulin (SHBG) (9.5%), and near significant increase in estradiol (27%). No significant changes were observed in serum concentrations of dehydroepiandrosterone sulfate, androstenedione, testosterone, follicular stimulating hormone, and luteinizing hormone. Free androgen index estimated from the ratio of serum concentrations of total testosterone to SHBG decreased. Urinary concentrations of the genotoxic metabolite of estrogen, 16-hydroxyestrone decreased significantly by 37%. Plasma cholesterol concentration decreased significantly by 5.9%. The researchers concluded that ingestion of yams as a staple part of the diet might reduce the risk of breast cancer and cardiovascular diseases in postmenopausal women. This is quite different than using wild yam as an herbal supplement, but nonetheless, worthy of further research. And as yams are such a nourishing food, unless one is on a diabetic diet, they are a healthy inclusion in most diets.

MECHANISMS OF ACTION

The belief that wild yam acts as a precursor to human sex hormones was widely popularized in the early 1990s based on research John Lee, a proponent of the benefits of progesterone replacement for a variety of menopausal complaints. However, the steroidal saponins found in wild yam are not biologically converted to human sex steroids in the body, nor does the plant itself contain progesterone or estrogen, and claims of it having hormonal activity appear to be erroneous based on clinical research. Mechanisms for the anti-spasmodic effects of this herb have not been elucidated nor substantiated.

RATINGS

Botanical Safety Handbook class 1: Herbs that can be safely consumed when used appropriately.

• No significant adverse events in clinical trials

• No case reports with significant adverse events and high probability of causality [need to select causality assessment references

• No identified concerns for use during pregnancy or lactation

• No innately toxic constituents

• History of safe traditional use

• Toxicity associated with excessive use is not a basis for exclusion from this class

• Idiosyncratic, minor or self-limiting side effects are not bases for exclusion from this class.

PREPARATIONS USED CLINICALLY

• Dried root in capsules

• Tincture

DOSAGE

• Dried root in capsules: 250 mg one to three times daily

• Tincture: 2 to 4 mL three to five times daily

SAFETY INFORMATION: HERB-DRUG INTERACTIONS, TOXICITY, AND CONTRAINDICATIONS

Wild yam appears to be generally safe when used internally or topically, as recommended Topical application of wild yam extract in women suffering from menopausal symptoms appears to be free of side effects, but appears to have little effect on menopausal symptoms. The herb is sometimes contraindicated for those using hormonal contraception and those with hormone dependent cancers, but this is based on the supposition of hormonal activity of the herb, which is not currently supported by the scientific literature.

Anecdotal reports state that large doses (amounts unspecified) may result in emesis. Positive interactions may be found in association with added benefits of lipid reduction when combined with lipid-lowering medications.

USE IN PREGNANCY AND LACTATION

Wild yam was used by the Eclectic medical physicians for the treatment of NVP and by Native American tribes to ease childbirth, suggesting some historical expectation of its safety during pregnancy. It remains in contemporary use by midwives for use as an antiemetic in nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum, as an antispasmodic for irritable uterus or threatened miscarriage with uterine contractions [in combination with other herbs such as cramp bark (Viburnum opulus) and black haw (Viburnum prunifolium)], occasionally for intra-partum use for painful labor with dysfunctional uterine contractions, again with cramp bark and black haw or other herbs, and postnatally for afterbirth pains, often combined with motherwort. Although the Botanical Safety Handbook categorizes wild yam as a Class 1 herbs that can be safely consumed when used appropriately, no data exist on the safety of this herb during pregnancy or lactation. One limited report suggests the possibility of induction of uterine contractions associated with this herb, this is not a finding consistent with the traditional observations or contemporary literature on this herb. Although concerns of hormonal activity are unfounded based on the scientific literature, care should be taken when using any herb during pregnancy and lactation.

SUMMARY

Scientific data do not lend credibility to the popular use of wild yam as a hormonal precursor or supplement. There is no research into the traditional and contemporary use of this herb as an antispasmodic for the hollow viscera. The herb appears safe when used as recommended both internally and topically. Although no significant reports of adverse events in pregnancy and lactation are found in the literature, care should be taken when using any herbs in this context.

Herbs: Uses, Side effects

UVA URSI

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May 24, 2011 at 2:05 pm

Botanical name: Arctostaphylos uva ursi

Family: Ericaceae

Synonyms: Bearberry, Kinnikinnik

Part used: Dried leaf

MAJOR CHEMICAL CONSTITUENTS

The primary medicinally active constituent is arbutin, a phenolic glycoside that generates hydroquinone as a result of glycolysis. Tannins, and flavonoids are also present. A small amount of free hydroquinone is found in the leaves. P-coumaric acid and caffeic acid, compounds with known antibacterial properties, and salicylic acid, a known bacteriostatic and anti-inflammatory agent, may be of significance. Uva ursi contains the flavonoid quercetin and the triterpenes ursolic acid, among many other constituents.

PRINCIPAL USES

• Urinary tract antiseptic, bacteriostatic, anti-inflammatory, and astringent in the treatment of cystitis, urethri-tis, dysuria, and pyelonephritis.

• Topical astringent applied for postpartum vulvovaginal healing

TRADITIONAL AND HISTORICAL USES

Uva ursi was used by numerous native tribes of the northern United States and Canada as a diuretic or for treatment of inflammation of the genitourinary tract. It appears to have been introduced into European medical practice in the thirteenth century as a treatment for conditions of the bladder and kidney, and as such has remained in use since. Goethe is reported to have been prescribed and successfully treated for kidney stones with this herb. Early US medical botanists reported on its usefulness in the treatment of genitourinary disorders and by the late nineteenth century it was widely used by Eclectic physicians as an astringent tonic for chronic diarrhea, dysentery, and menorrhagia, as well as for genitourinary disorders and diabetes. It has had an official entry in pharmacopoeias of numerous western nations since the eighteenth century, including the British Herbal Pharmacopoeia, the National Formulary and the United States Dispensatory. It can still be found in the pharmacopoeias of numerous countries including Austria, Czechoslovakia, Egypt, France, Germany, Hungary, Japan, Russia, Switzerland, and others.

IN VITRO, ANIMAL, AND CLINICAL DATA

Uva ursi remains one of the most important and commonly used urinary tract disinfectants in modern herbal medicine, widely used in the treatment of uncomplicated acute and recurrent urinary tract infections. Midwives include the herb as an astringent anti-inflammatory in sitz baths and perineal rinses for postnatal perineal healing and as part of treatment of vaginitis and urethritis. There are few clinical trials or pharmacodynamic studies of uva ursi. In vitro studies using crude leaf preparations and extracts of uva ursi leaf have demonstrated mild antimicrobial activity against known UTI causing organisms, including but not limited to C. albicans, E. coli, S. aureus, and Proteus vulgaris, and others. Several studies have also demonstrated antiinflammatory activity of the herb, particularly enhanced when extracts are used in combination with anti-inflammatory pharmaceutical drugs, for example, prednisolone, indomethacin, or dexamethazone.

MECHANISMS OF ACTION

The mechanisms of action of uva ursi are not fully elucidated. It appears, however, that arbutin, and its agly-cone, hydroquinone — a urinary disinfectant — are primarily responsible for the herb’s antimicrobial activity. Hydroquinones are primarily hydrolyzed in the kidney because tannins prevent enzymatic activity that would normally lead to its conversion in the gut; it also appears that arbutin might be hydrolyzed in the urinary tract as a result of P-glucosidase activity stimulated by pathogenic infection. Arbutin is rapidly absorbed after consumption of tea and extract preparations, with urinary excretion of metabolites within a few hours and up to 24 hours. Antibacterial actions may be most prominent in an alkaline (pH urinary environment; however, activity is not necessarily dependent on elevated urinary pH.

RATINGS

• German Commission E: Approved for the treatment of inflammatory conditions of the urinary tract.

• Botanical Safety Handbook Class 2b and 2d rating: Not to be used in pregnancy, a caution that is reiterated by most authorities.

PREPARATIONS USED CLINICALLY

• Cold water infusion

• Hot water infusion

• Tincture

Uva ursi shows greater antibacterial activity in an alkaline environment; some authors suggest giving it along with sodium bicarbonate or substantially increasing fresh fruit and vegetable consumption during treatment to alkalinize the urine; others suggest avoiding the use of acidifying agents during treatment. Alkalinization of the urine seems not to be a prerequisite to the antiseptic properties of hydroquinone released from arbutin. Some amount of disagreement can be found in the literature regarding the requirement of an alkaline pH environment for the efficacy of this herb. Some authors postulate that a reduced urinary pH inhibits the efficacy of the herb; others argue that increasing the alkalinity of the urinary environment enhances the efficacy of the herb, while still others state that activity is not depend on urinary pH. Given the reliability of this herb generally, it is prudent to conclude that if uva ursi does not seem to be working, the addition of 2 “00″ capsules of sodium or potassium bicarbonate may be taken once or twice daily with uva ursi doses, to alkalinize the urine in such situations before making a final determination about efficacy. Some authors recommend discontinuing use of the herb after 7 days; however, the European Scientific Cooperative on Phytotherapy (ESCOP) recommends treatment be continued until complete disappearance of symptoms, up to a maximum of 2 weeks.

DOSAGE

Doses should provide the equivalent of 400 to 840 mg arbutin daily, divided over two to four doses.

• Hot or cold infusion: 1.5 to 4 g dried leaves to 150 mL water as a cold infusion steeped for 2 hours or as a hot infusion steeped 30 minutes, and taken up to four times daily.

• Tincture: 2 to 4 mL three to four times daily of a 1:5 preparation.

USE IN PREGNANCY AND LACTATION

Pregnancy

The Botanical Safety Handbook gives this herb a class 2b and 2d rating: Not to be used in pregnancy, a caution which is reiterated by numerous authorities. However, the reasons for contraindication are variable and not well supported, ranging from alleged uterotonic and oxytocic activity to “theoretical fetotoxicity.” The risk of oxytoxic effect is based on a single unreferenced anecdotal report by Brinker in Herb Contraindications and Drug Interactions, and has not been substantiated clinically. Limited evidence suggest that the herb has potentially fetotoxicity owing to its hydroquinone content. Studies using pure hydroquinone (i.e., not the herb in bulk or extract form) have produced microtubulin dysfunction in bone marrow, and exposure of human lymphocytes and cell lines and pure hydroquinone has been shown to cause genetic damage. Low potential for mutagenicity and negative Ames test have also been reported. In animals administered 100 and 400 mg/kg sc per day of arbutin, no signs of fetal toxicity were observed. Uva ursi has been used by midwives in the United States as a primary treatment of acute symptomatic cystitis in pregnancy for at least two decades, with no adverse reports associated with its use.

Lactation

The transfer to infants of arbutin/hydroquinone from uva ursi use during lactation has not been researched and therefore is not recommended; however, the risk remains speculative. It is recommended that this herb be used only in the lowest doses during lactation, observing the infant for side effects, and using under the guidance of a qualified health professional.

SAFETY INFORMATION: SIDE EFFECTS, CONTRAINDICATIONS, TOXICITY, AND HERB-DRUG INTERACTIONS

Used as per directed dose and duration, uva ursi appears to have a good safety profile.

Side Effects

• Nausea and vomiting have been reported with use, but are not common.

• Excessive ingestion of arbutin may cause tinnitus, delirium, convulsions, collapse, and death.

Contraindications

• Kidney disorders

• Pregnancy and lactation (discussed in the preceding)

• Children under 12 years old

• Bowel inflammation

No justification is given for the caution against use in children.

High tannin levels may interfere with iron absorption in the gut and may aggravate highly inflamed or ulcerated GI conditions.

Toxicity

Several authorities claim that arbutin-containing preparations should not be taken for longer than a consecutive week, nor should they be taken more than 5 times annually without medical consultation. No explanation for this recommendation is given though it is likely due to concern regarding hydroquinone consumption. Contrary to this, the European Scientific Cooperative on Phytotherapy (ESCOP) recommends treatment be continued until complete disappearance of symptoms, up to a maximum of 2 weeks. Uva ursi is a known inhibitor of melanin synthesis, and in excessive doses could result in retinal damage. Used acutely according to general dosing recommendations, this herb is expected to have very low carcinogenicity, though carci-nogenicity has been observed in mouse and rat models given pure hydroquinone.

Herb-Drug Interactions

• The only expected drug interaction is possible potentiation of prednisolone and related anti-inflammatory drugs by 50% methanolic extract.

Herbs: Uses, Side effects

ST. JOHN’S WORT

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May 24, 2011 at 2:03 pm

Botanical name: Hypercium perforation

Family name: Clusiacaea

Synonyms: St. Joan’s wort

Part used: Flowers, upper 6 to 8 inches of the aerial portion of the herb, including leaf and flower

MAJOR CHEMICAL CONSTITUENTS

Hypericin, pseudohypericin, isohypericin, hyperforin; flavonols including kaempferol and quercetin; flavones, glycosides, bioflavonoids, catechins; phenols including caffeic acid, p-coumaric acid, ferulic acid, and vanillic avid; volatile oils, carotenoids, nicotinic avid, isovalerinic acid, palmitic acid, and a number of volatile oils.

PRINCIPAL USES

• Mild to moderate depression

• Mild sedative and nerve tonic for excitability, anxiety, and nervous irritability

• Mild sedative/analgesic for neuralgia and sciatica

• Antiviral for both internal and topical prevention and treatment of Herpes simplex virus (herpes simplex virus)

• Neurovegetative menopausal complaints

• Topical wound healing, for example, postpartum perineal healing, hemorrhoids, sore, cracked nipples during lactation, and vaginal abrasions in vaginitis and perimenopausal vaginal atrophy and associate vaginal dryness

• Cystitis, urinary frequency and urgency, interstitial cystitis

TRADITIONAL AND HISTORICAL USES

St. John’s wort (SJW) has been a famed vulnerary and antidepressant herb since the Greco-Roman times. In ancient medical history, however, depression was not the likely diagnosis — a patient was said to have been afflicted by evil spirits or other psychic malady.

In our modern era, mounting evidence from clinical trials, especially those conducted in the 1980s and 1990s, established the efficacy and safety of standardized SJW extracts for treating mild to moderate depression, and practically overnight, SJW became a “household alternative” for the treatment of depression as well as a multi-million dollar boon for the natural products industry. Although SJW remains a top-selling herb, reports of potentially serious herb-drug interactions, as well as widely publicized but poorly conducted studies questioning its efficacy have led to some decline in its popularity as a treatment for depression.

CLINICAL INDICATIONS

SJW is indicated for mild to moderate depression. Herbalists also prescribe SJW as a mild sedative and nerve tonic for excitability, anxiety, and nervous irritability, for pain relief for neuralgia and sciatica, as an antiviral for both internal and topical prevention and treatment of Herpes simplex virus (herpes simplex virus), and for neurovegetative menopausal complaints, particularly anxiety and sleep difficulties, typically in combination with other herbs. It is commonly included as a vulnerary — or wound healing herb — in formulae for the treatment of cuts, scrapes, and puncture wounds, as well as to soothe and heal the perineum with or without perineal lacerations after childbirth, to soothe and reduce hemorrhoids, and for the treatment of vaginal abrasions in vaginitis and those that can occur with perimenopausal vaginal atrophy and vaginal dryness. Herbal practitioners may also include SJW in formulae for the treatment of cystitis, urinary frequency and urgency, and interstitial cystitis.

MECHANISMS OF ACTION

The precise mechanisms of action for the antidepressant effects of SJW are not understood. In vitro studies using hyperforin have demonstrated significant binding of GABA A and GABA B, adenosine, MAO, and benzodiazepine receptors. Only GABA A and GABA B receptor activity is likely to be achieved in concentrations to elicit a biological effect after oral administration in humans. Early studies focused on the inhibitory activity of hypericin on MAO receptors; however, most studies have demonstrated only weak binding if at all. It appears that there might be some effects in inhibition of synap-tosomal uptake of serotonin (5-HT), dopamine, and nor-adrenaline, with an upregulation of 5-HT in rat cortex, with some increase in dopamine and noradrenaline. Studies have shown possible decrease in tryptophan degradation; tryptophan is a 5-HT precursor. Another possible explanation for the antidepressant effect of SJW is via inhibition of interleukin-6 (IL-6) by hyperforin and via inhibition of substance P mediated effects on depression.

Antiviral effects of SJW are attributed in part to the flavonoid and catechin fractions of the herb. Both hypericin and psuedohypericin have demonstrated in vitro inhibition of herpes simplex virus Types 1 and 2, Varicella zoster virus, and HIV type 1 via a photoactivation process that is not yet elucidated.

Tannins in SJW have a mild astringent effect and may help to explain some of the vulnerary effects, as well as use in the treatment of hemorrhoids. A quercetin-like compound in SJW has been attributed with possible analgesic effects of the herb. SJW extract has also been observed to suppress inflammation and leukocyte infiltration in murine models. Hypericin has demonstrated in vitro ability to inhibit tumor necrosis factor induced activation of NF-kappa B and the release of arachadonic acid, as well as inhibition of 5-lipoxygenase and COX-1. SJW may have free-radical scavenging activity; however, this has not been a consistent finding in studies.

RATINGS

• Botanical Safety Handbook rating 2d: Not for use during phototherapy; interaction Class C. Herbs for which clinically significant interactions are known to occur

• German Commission E: Internal uses include the treatment of psychovegetative disturbances, depressive moods, anxiety and/or nervous unrest. External: Oil-based preparations for the treatment of acute and contused injuries, myalgia, and first-degree burns.

PREPARATIONS USED CLINICALLY

• Dried herb in tea and capsules

• Tincture

• Standardized extract

• Oil extract for topical use

DOSAGE

• Dried herb: 2 to 4 g as an infusion three times daily

• Tincture: 2 to 4 mL 3x daily

• Clinical trial doses: 240 to 1800 mg daily standardized to varying concentrations of hypericin and hyperforin for a minimum of 4 to 6 weeks. Dosing in depression clinical trials suggests a starting dose of 300 mg of SJW standardized to 0.3% hypericin (and possibly also to 2-5% hypericin) 3x daily with a maintenance dose of 300 to 600 mg per day.

• Topical use as needed

SAFETY INFORMATION: HERB DRUG INTERACTIONS, TOXICITY, AND CONTRAINDICATIONS

St. John’s wort is considered a generally well-tolerated herb, even when taken continuously for up to 8 weeks. Adverse reactions are usually mild and included skin reactions, GI symptoms, fatigue, sedation, restlessness, dizziness, dry mouth, and headache with few side effects, most notably photosensitivity and mania, reported in clinical trials. Studies of chronic toxicity in animals have shown only nonspecific symptoms such as weight loss. Rarely, skin reactions such as pruritus and rash have been reported, with a drug monitoring study of 3250 patients showing 17 allergic reactions.

A European review of adverse reactions from 1991 to 1999 involving nearly 8 million people documented only 95 adverse reactions. Three case reports in the literature suggest the possibility of phototoxicity; in patients taking SJW. Two of the cases involved patients receiving laser or UVB treatments. Phase 1 trials of IV and oral hypericin in adult patients with HIV demonstrated severe cutaneous phototoxic reactions in 11 of 23 subjects, and a variety photosensitivity reactions in 14 of 19 hepatitis C patients. Several additional studies have confirmed similar findings particularly at high doses of hypericin or high UVA light. One study did not find phototoxic effects. Patients receiving UV treatment are advised to avoid SJW use during treatment and those with fair skin are advised to avoid sun exposure of skin while taking SJW internally or topically.

Anorgasmia has been reported in 25% of patients taking 900 to 1500 mg SJW daily for 8 weeks versus 32% taking sertraline and 16% taking placebo, in additional to 2 published case reports of sexual dysfunction in patients taking the herb for mood disorders. Frequent urination was also seen in 27% of patients taking 900 to 1500 mg SJW daily for 8 weeks vs. 21% taking sertraline and 11% taking placebo.

SJW, through its actions on the hepatic metabolism of drugs, specifically via induction of the cytochrome system, may lead to changes in the plasma level of a number of drugs, preventing a patient from achieving appropriate therapeutic levels. There is evidence from clinical trials and case reports that SJW may interact with the following medications:

• Antiarrhythmics/calcium channel blockers: May lead to decreased plasma levels of digoxin, verapamil, and nifedipine

• Anticonvulsants: May lead to decreased plasma levels phenytoin

• Anticoagulants: May lead to decreased plasma levels warfarin

• Antidepressants: May lead to decreased plasma levels amitriptyline (a tricyclic antidepressant) and the SSRIs paroxetine, fluoxetine, and trazadone. Serotonin syndrome can result from reduced serum levels of SSRIs.

• Antihistamines: Fexofenadine (single dose may increase while continued use may decrease plasma level of drug)

• Antipsychotics and anxiolytics: May lead to decreased plasma levels of buspirone, quitazepam, midazolam, and alprazolam

• Antiulcer agents: May lead to decreased plasma levels of omeprazole

• Antivirals: May lead to decreased plasma levels of indinavir

• Chemotherapeutic agents: May lead to decreased plasma levels of irinotecan and imatinib

• Hormonal contraceptives: May lead to decreased plasma levels of hormonal birth control/oral contraceptives

• Immunosuppressants: May lead to decreased plasma levels of cyclosporine and tacrolimus

• Reverse transcriptase inhibitors: May lead to decreased plasma levels of nevirapine

• Skeletal muscle relaxants: May lead to decreased plasma levels of chlorzoxazone

• Statins: May lead to decreased plasma levels of simvastatin

WARNING

Patients taking cyclosporine for the prevention of transplant rejection or other medical reasons should avoid the concurrent use of SJW as it has been shown to interfere with immunosuppressant medications.

Patients taking medications metabolized by CYP450 should avoid SJW or consult with the physician prior to use.

Caution is advised with SJW use for patients with fair skin, receiving photosensitizing drugs, or receiving UV treatments. At recommended doses of whole plant extracts, the risk of photosensitization appears to be quite low.

Activation may occur in patients with a history of mania, bipolar disorder, and other mood disorders.

SJW is suggested for the treatment of patients with mild to moderate depression, not severe depression or suicidality.

Cases of possible serotonin syndrome has been reported in patients taking SJW.

USE IN PREGNANCY AND LACTATION

Herbs: Uses, Side effects

USE IN PREGNANCY AND LACTATION

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May 24, 2011 at 2:00 pm

Because of lack of clinical trials and safety data, SJW is not commonly recommended for the treatment of mood disorders during pregnancy. Its use is more often reserved for topical treatment of vaginitis, in the treatment of perineal tears, and for the treatment of sore, cracked nipples during lactation.

It is becoming increasingly well established that untreated depression in pregnant women and new mothers can have significant health and social consequences for their offspring. Comparative studies on the efficacy and safety of SJW compared to pharmaceutical antidepressants for the treatment of prenatal and post-partum depression are needed.

Murine and rat studies on the prenatal consumption of SJW have been generally associated with normal gestation and fetal development. In one study, male offspring in a SJW exposed group had a statistically significant lower birth weight than the placebo group, however, by three days after birth the difference was not statistically significant. The males in the SJW group also demonstrated a statistically significant temporary delay in the appearance of upper incisors. In another rat study females were given a methanol extract of SJW standardized to 0.3% hypericin at 100 or 1000 mg/kg or placebo by gavage for 2 weeks prior to conception, throughout gestation, and/or for 3 weeks during lactation. Histological evidence of hepatic and renal changes was seen in the SJW exposed group, with more severe lesions in the rat pups whose dams received higher doses and the offspring of those receiving both SJW in both pregnancy and lactation. No significant impact on cognitive behaviors have been seen in the offspring of mice given SJW throughout gestation. A slight increase in in vitro uterotonic activity has been reported with SJW use.

Overall there is a lack of toxicity studies conducted on SJW use during pregnancy. A limited number of human case reports indicated healthy pregnancies and infants when SJW was used prenatally. In a small prospective cohort safety study of breastfeeding women (n = 33) who took SJW products during pregnancy and who contacted a toxicology advise service, compared to 101 matched controls who had also contacted the service but had not taken SJW, there were no maternal adverse effects, no statistically significant differences in women reporting decreased breast milk volume, and no medical problems in the offspring. Two of the infants born to mothers taking SJW experience colic, drowsiness, or lethargy compared with the other group; a number of these infants were also reported to have been exposed to conventional antidepressant medications while breastfeeding. Limitations to this report include lack of product identification or quantification in this report, and the number of women taking SJW while pregnant was small.

Hyperforin was detected in low concentrations in the breast milk who took 300 mg of SJW three times daily starting at 5 months postpartum for the treatment of postpartum depression. No adverse effects were seen in her baby. The clinical significance to the infant of SJW in breast milk is unknown; no adverse effects have been reported. Use of topical applications of SJW oil or salve as treatment for sore, cracked nipples, particularly if well-absorbed with any excess wiped off prior to nursing does not appear harmful to the infant. See warnings in the preceding regarding interactions with immunosuppressant and other medications.

The safety of SJW taken internally during pregnancy and breastfeeding, both in terms of effects on the mother and her child, are unknown at this time. Because of this, the herb is generally not recommended for internal consumption during pregnancy and lactation. Given the widespread incidence of depression in society, and the relatively high incidence and serious consequences of postpartum depression on the health of mother, baby, and their relationship, as well as the family overall, research in to SJW for prophylaxis and treatment of depression during the childbearing years should be explored in carefully controlled studies.

Herbs: Uses, Side effects

RED CLOVER

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May 24, 2011 at 1:59 pm

Botanical name: Trifolium pratense

Family name: Leguminosae

Synonyms: Meadow clover, purple clover, trefoil

Part used: Flowering tops and leaf

MAJOR CHEMICAL CONSTITUENTS

Isoflavondoids including biochanin A, daidzein, formo-nonetin, genistein, and others; flavonoids including kaempferol, quercetin and others; coumarins; carbohydrates, saponins, salicylic acid, and trace vitamins and minerals.

PRINCIPAL USES

• Prevention and treatment of menopausal symptoms including hot flashes and vaginal dryness

• Hormone replacement therapy substitute

• Prevention and treatment of osteoporosis

• Hypercholesterolemia

• Acne and chronic skin disease

TRADITIONAL AND HISTORICAL USES

Red clover has been used traditionally as an alternative or “blood purifying” herb. As such, it has been included in the treatment of acute and chronic skin diseases, including acne, eczema, and psoriasis, and it is commonly found in herbal formulae for treating cancer, including the infamous Hoxsey formula. Numerous so-called “trifolium compounds” were marketed as blood purifiers to “help clear the body of toxins.” Red clover was listed in the National Formulary as a skin remedy until 1946. It has also been used traditionally for the treatment of upper respiratory conditions including acute and chronic cough, asthma, and pertussis. In recent years it has become an exceedingly popular herb for the treatment of menopausal complaints including hot flashes, vaginal dryness, and osteoporosis.

CLINICAL INDICATIONS

Red clover is one of the most popular herbal products in Europe and the United States for the prevention and treatment of menopausal complaints, particularly hot flashes. It is also used to prevent and treat vaginal dryness, osteoporosis, and hypercholesterolemia. Promensil, a commonly used red clover product, is used in many of the red clover clinical trials.

IN VITRO, ANIMAL, AND CLINICAL DATA

Results of human clinical trials to date are conflicting. High-quality human clinical trials supporting the use of red clover (for any conditions) are limited. A small number of positive trials suggest a reduction in menopausal symptoms, particularly hot flashes; improved bone density; reduction in serum lipids; and improvement in arterial compliance. However, study designs have often been weak or contain methodologic flaws including lack of power calculations, unclear statistical significance versus placebo, small sample sizes, lack of control groups, and lack of dietary records to account for other dietary isoflavones that might confound study results.

MECHANISMS OF ACTION

The basis of action of this herb is its phytoestrogen constituents, which exhibit both agonist and antagonist binding with endogenous estrogen receptors.

RATINGS

• Botanical Safety Handbook Class 2b and 2d rating: Not to be used in pregnancy

PREPARATIONS USED CLINICALLY

• Dried blossoms and aerial parts

• Tincture

• Isoflavone extracts

DOSAGE

• Dried blossoms: 4 g in infusion 3x daily

• Tincture: 1.5 to 3 mL 3x daily

• Red clover isoflavones: 40 to 160 mg red clover isoflavones daily

SAFETY INFORMATION: HERB DRUG INTERACTIONS, TOXICITY, AND CONTRAINDICATIONS

Red clover is widely used in Europe and the United States for the prevention and treatment of menopausal complaints with a very high safety profile. Although there are a limited number of human clinical trials using this herb, even those looking at effects up to a year show excellent tolerance and no significant adverse effects. It is theoretically contraindicated for women taking HRT due to possible competition with the drugs. Red clover has also been contraindicated with heparin, ticlopidine, and warfarin, based on its coumadin content. However, unless red clover herb is fermented, it is unexpected to have any anticoagulant effects.

It is unclear whether red clover is safe for consumption by women with a history of estrogen-receptor (ER) positive cancer. Although it may have competitive binding effects with stronger endogenous estrogens, and thus may actually reduce risks associated with elevated estrogen levels, an in vitro study demonstrated that red clover was equipotent to estradiol in its ability to stimulate cell proliferation in estrogen receptor-positive breast cancer cells. Regular consumption of soy has been associated with a decreased risk of breast cancer, but the results cannot necessarily be extrapolated, as soy contains additional compounds not found in red clover. Further, isoflavones can variably act as ER agonists or antagonists. Until more conclusive evidence is available, it is possible for women with a history of ER positive breast cancer to avoid using red clover.

Concerns have also arisen over the safety of consuming red clover due to the risk of uterine cancer associated with unopposed estrogen. Preliminary studies of less than 6 months have found no increases in endometrial thickness based on ultrasound examination. No changes in GnRH, SHBG, FSH, LH, vaginal cytology, or endometrial thickness have been seen in studies of women taking the red clover compared with placebo, even over 1 year. Nonetheless, as with those with breast cancer, women with a history of endometrial hyperplasia might be prudent to avoid regular consumption of red clover supplements.

USE IN PREGNANCY AND LACTATION

Because of its estrogenic properties, red clover is not recommended for regular or high-dose consumption during pregnancy and lactation. Infertility and abortion have been observed in cattle grazing extensively on red clover. The Botanical Safety Handbook Class 2b rating, not to be used in pregnancy

Herbs: Uses, Side effects

KAVA KAVA

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May 24, 2011 at 1:56 pm

Herbs: Uses, Side effects

SAFETY INFORMATION

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May 24, 2011 at 1:49 pm

SAFETY INFORMATION: HERB DRUG INTERACTIONS, TOXICITY, AND CONTRAINDICATIONS

A 1997 peer-reviewed appraisal of kava kava safety based on a comprehensive review of the scientific and historical ethnobotanical literature determined that

When used in normal therapeutic doses, kava appears to offer safe and effective anti-anxiety and muscle relaxant actions without depressing centers of higher thought. The safe use of kava as a dietary supplement in cultures that do not have historical experiences with its use depends on responsible manufacturing, marketing, individual consumption patterns, and education.

Since that time, 79 adverse event reports of hepatotoxic-ity reportedly associated with oral use of kava kava preparations have been reported worldwide, with most in Europe, but also in Canada and the United States, and have led to rigorous investigation of the safety of this herb. Although in most cases prescription pharmaceutical medications were being taken in conjunction with kava kava, there was regular alcohol intake, or prior hepatic disease existed. Several cases of severe hepatic damage, including fulminant hepatic failure, apparently occurred de novo. These cases subsequently led to the withdrawal or restriction of sales of kava kava products from many national commercial markets, particularly in Europe. In the Cochrane systematic review discussed previously, six of twelve trials reported adverse events experienced by patients receiving kava kava extract. Stomach complaints, restlessness, drowsiness, tremor, headache, and tiredness were reported most frequently. Four trials comprising 30% of patients in the reviewed trials report the absence of adverse events while taking kava kava extract. None of the trials reported any hepatotoxic events. Seven of the reviewed trials measured liver enzyme levels as safety parameters and report no clinically significant changes.

Warnings about kava kava and performance safety are common. It has been proposed that Piper methysticum may cause cytotoxic cell death by interfering with hepa-tocellular mitochondrial function. Performance safety and basic performance under the influence of kava kava were tested in a randomized double-blind crossover study (n = 18) in which healthy subjects were simultaneously given 400 mg kava kava extract (containing 240 mg kavalactones daily) and 4.5 mg bromazepam twice daily over a period of 14 days. This was compared with the effects of the substances administered individually. Stress tolerance, vigilance, and motor coordination were not changed from baseline when only kava kava was taken, whereas the performance of subjects taking bromazepam and the kava-bromazepan combination deteriorated equally. Nonetheless, several cases of individuals being cited for “driving under the influence” after having used kava kava have been reported, and it is generally recommended that individuals not drive or operate machinery or equipment while using this herb.

Kava kava is reported as being generally well tolerated in clinical trials with few reported herb-drug interactions. Potential interaction with benzodiazepines, serotinergic-and dopaminergic-acting medications, and medications that act on sodium ion channels have been proposed. Kava kava should not be used with selective serotonin reuptake inhibitors, tricyclic antidepressants, barbiturates, benzodiazepines, or antipsychotic medications. Kava kava may potentiate the effects of alcohol; thus they should not be taken simultaneously beyond the normal amount present in kava kava extracts.

Kava dermopathy, and ichthyosiform condition, is a well-known side effect of frequent, high-dose kava kava consumption. In fact, in Oceania, this yellowish, scaly skin condition is common among kava kava users, and is reversible upon discontinuation of kava kava intake. Allergic skin reactions also have been associated with kava kava use. Extrapyrimidal symptoms, including torticollis; involuntary neck, head, and trunk movements; oral and lingual dyskinesia; and impairments in movement and visual coordination have been reported occasionally by kava kava users in the absence of cognitive impairment.

Common side effects associated with kava kava use, including stomach complaints, restlessness, drowsiness, tremor, headache, and tiredness were reported most frequently. In the Cochrane review, four trials comprising 30% of patients in the reviewed trials reported the absence of adverse events with kava kava extract.

Kava kava use has been associated with rare but severe liver damage. Kava kava consumption should be discontinued immediately and a qualified health professional should be sought if any of the following signs of hepatotoxicity occur: unusual fatigue, weakness, loss of appetite, unintentional weight loss, yellow discoloration of the skin or ocular conjunctiva, dark urine, or discolored stools. Individuals with a history of liver disease and those taking medications that can cause liver damage should not take kava kava.

Herbs: Uses, Side effects | Tags: pal-sawmetto-and-pregnancy

GINGER

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May 24, 2011 at 1:47 pm

Botanical name: Zingiber officinalis

Family name: Zingiberacaea

Part used: Rhizome

MAJOR CHEMICAL CONSTITUENTS

The major chemical constituents are volatile oils, including P-bisabolene and zingiberene, sesquiterpenes, including zingiberol, zingiberenol, the oleoresin shaogol, numerous monoterpene hydrocarbons, alcohols, and aldehydes, oleoresins, free fatty acids including palmitic acid, oleic acid, linoleic acid, caprylic acid, capric acid, lauric acid, myristic acid, steric acid, and starch and amino acids.

PRINCIPAL USES

• Antiemetic for nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum

• Antiemetic and antianorectic for nausea and appetite loss associated with cancer and HIV chemotherapeutic treatments

• Anti-inflammatory and antispasmodic for dysmenor-rhea, uterine fibroids, and chronic pelvic pain

• Antiinflammatory for headache

• Digestive complaints associated with endometriosis and chronic pelvic pain

• Flavoring for herbal formulae

• Possible chemopreventative and cytotoxic activity in cancer treatment

TRADITIONAL AND HISTORICAL USES

Ginger has been used traditionally from Asia to the Caribbean for its antispasmodic, carminative, and diaphoretic properties. It has been used in traditional Chinese medicine (TCM), for example, since at least the ninth century for the treatment of nausea, diarrhea, and digestive complaints. Ginger was included in the United States Pharmacopoeia (USP) and the National Formulary as a carminative, stimulant, and aromatic herb. Because of geographic/climatic distribution of the herb, its use was not reported in northern European traditional herbalism, but its place in modern Western herbalism has become firmly established, as described in this profile.

CLINICAL INDICATIONS

Modern use of ginger has focused on its efficacy as an antiemetic for the treatment of nausea and vomiting in a variety of contexts, including during pregnancy and for patients undergoing chemotherapy. It has also been used for the treatment of appetite loss in cases of HIV, cancer, and the side effects of medications for their treatment. Herbal practitioners also widely use ginger for the treatment of gynecologic pain, including dysmenorrhea, pain associated with uterine fibroids, and chronic pelvic pain. It is also used for the treatment of premenstrual headaches and for the relief of diarrhea and cramping bowel pain that often accompanies dysmenorrhea, PMS, and endometriosis.

IN VITRO, ANIMAL, AND CLINICAL DATA

Ginger has been shown to have antiemetic effects in animal and human studies, possibly through an antiserotinergic effect. In seemingly contradictory animal studies, the herb has been shown to both increase stomach acid production, possibly interfering with the effects of antacid medications, and to significantly reduce gastric secretions and provide gastric mucosal protection with a reduction in gastric ulcers comparable to the effects provided by NSAIDs. At 62 mg/kg ginger extract has demonstrated protective effects against stress ulcer induction in rats, although to a lesser extent than cimetidine. The antiplatelet effects of ginger are also controversial. Although the herb does inhibit prostaglandin, thromboxane, and leukotriene synthesis, inhibition of platelet synthesis has been inconsistent among studies. Ginger has demonstrated anti-inflammatory activity in vitro, with COX-2 inhibition and resultant reductions of severe arthritis, paw and joint swelling in rats treated with ginger oil. Fresh ginger juice has a hypoglycemic effect in nondiabetic and diabetic rabbits and rats, with the effect more pronounced in diabetic animals.

MECHANISMS OF ACTION

The aromatic principles of ginger are considered responsible for its medicinal actions, including enzymatic inhibition of prostaglandin, thromboxane, and leukotriene synthesis. The mechanisms of action on nausea and vomiting remain uncertain, with studies demonstrating increased gastric motility contradictory to those showing no motility. Another theory is that the herb acts via a centrally mediated effect on 5-hydroxytryptamine-3 (5-HT3), an effect that has been demonstrated in vitro. There is some evidence that ginger increases stomach acid production, thus possibly interfering with antacid medications.

RATINGS

• Botanical Safety Handbook class 1: Herbs that can be safely consumed when used appropriately.

• No significant adverse events in clinical trials

• No case reports with significant adverse events and high probability of causality

• No identified concerns for use during pregnancy or lactation

• No innately toxic constituents

• History of safe traditional use

• Toxicity associated with excessive use is not a basis for exclusion from this class

• Idiosyncratic, minor, or self-limiting side effects are not bases for exclusion from this class.

• German Commission E Monographs: Approved for the treatment of dyspeptic complaints and prevention of the symptoms of motion sickness.

PREPARATIONS USED CLINICALLY

• Tea

• Powder

• Tincture

• Also taken as ginger candy, dried crystallized ginger, ginger syrup, and in foods (i.e., soup broth)

DOSAGE

• Tea: 1 tbs grated raw root per 1 cup of boiling water, 3 to 4 cups daily

• Powder: 1 to 2 g daily

• Tincture: 1.5 to 3 mL three times per day

SAFETY INFORMATION: HERB DRUG INTERACTIONS, TOXICITY, AND CONTRAINDICATIONS

Ginger has a long history of safe use both as a culinary and medicinal herb. It is considered safe when used as recommended, including when used within the prescribed pregnancy dose. Dose should not exceed 1 g daily in pregnancy, and 4 g per day for the general population. Theoretical herb drug interactions have been proposed (Herb-Drug Interactions with Ginger). Concerns have been expressed that ginger might increase the risk of bleeding, for example, with surgery, owing to platelet activating factor (PAF) inhibition; therefore, it is recommended that patients taking ginger should discontinue use 1 to 2 weeks prior to surgical procedures. Patients using oral hypoglycemic medications may require a dose adjustment as ginger may have hypoglycemic effects. Limited evidence suggests that ginger may interfere with antacids, sulcralfate, H2 antagonists, and proton pump inhibitors (PPIs) by increasing stomach acid production. Patients with gastric and duodenal ulcers are therefore sometimes advised to avoid using ginger other than for culinary purposes for this reason; however, animal experiments suggest a protective effect against gastric ulcers.

Patients with known allergy or hypersensitive to members of the Zingiberacae family, or those allergic to Balsam of Peru, may experience sensitivity or contact dermatitis with use of ginger. Ginger powder taken unencapsulated has been known to cause heartburn-like symptoms, and raw ginger taken in large boluses and poorly masticated has been reported in the literature to cause ileus in a limited number of case reports.

Herb-Drug Interactions with Ginger

DRUG	ACTUAL OR THEORETICAL	INTERACTION
Antacids, gastric acid inhibiting drugs	Theoretical	Ginger may increase stomach acid production, therefore interfering with the actions of antacids, sucralfate, H2 antagonists, and proton pump inhibitors (PPIs). Ginger also may have a gastroprotective effect.
Anticoagulants, antiplatelet drugs	Theoretical	Because ginger has been observed to inhibit both PAF and thromboxane synthetase, it has been proposed that ginger may increase bleeding time and increase the risk of bleeding with anticoagulant and thrombolytic medications. However, this is not supported by case reports, adverse events reports, or the clinical literature.
NSAIDs	Theoretical	Also caused by inhibition of thromboxane synthetase, theoretical interaction with NSAIDs has been proposed, also leading to increased bleeding risk and potentiation of effects.
CNS depressants	Theoretical	Large doses of ginger have been reported to lead to CNS depression; thus, there is a theoretical risk of interaction.
Cardiac drugs, including P-blockers, digoxin, and positive inotropes	Theoretical	Inotropic effects of ginger have been proposed; and thus a theoretical risk of interaction with cardiac drugs. However, this has not been observed clinically.
Oral hypoglycemic agents	Theoretical	Ginger has demonstrated hypoglycemic effects; thus, a dose-adjustment of oral hypoglycemic medications may be required for those taking this herb.

USE IN PREGNANCY AND LACTATION

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