Blood Pressure Support by Herb Pharm

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Angina. Although there has been interest in using oral coleus for angina, there is insufficient reliable information about the clinical effects of coleus for this purpose.
• Asthma. It is unclear if inhaled forskolin, a constituent of coleus, is beneficial in patients with asthma. Details: A preliminary clinical trial in patients with asthma shows that a single-dose inhalation of the powdered coleus constituent, forskolin, 10 mg, from a Spinhaler inhaler increases forced expiratory volume in one second (FEV1) when compared to baseline (7281,44432). Another, low-quality, trial in patients with asthma found that using a specific forskolin product (Pro-longevity Forskolin, Life Extension Foundation Buyers Club, Fort Lauderdale, Florida, USA) providing forskolin 10 mg per day orally for 6 months did not improve lung function, but resulted in fewer asthma attacks when compared to two inhalations of sodium cromoglycate three times daily for 6 months (91889). However, another preliminary trial in adults and children with mild asthma shows that taking oral forskolin 10 mg taken daily for 2 months, neither reduced asthma attacks nor improved lung function when compared with beclomethasone inhalations or when compared to baseline (91883).
• Atopic dermatitis (eczema). Although there has been interest in using oral coleus for atopic dermatitis, there is insufficient reliable information about the clinical effects of coleus for this purpose.
• Cancer. Although there has been interest in using oral coleus for cancer, there is insufficient reliable information about the clinical effects of coleus for this purpose.
• Congestive heart failure (CHF). Although there has been interest in using intravenous forskolin, a constituent of coleus, for CHF, there is insufficient reliable information about the clinical effects of forskolin or coleus for this purpose.
• Dilated cardiomyopathy. It is unclear if intravenous forskolin, a constituent of coleus, is beneficial in patients with dilated cardiomyopathy. Details: Preliminary clinical research in patients with dilated cardiomyopathy shows that using intravenous coleus 0.5 mcg/kg/minute, titrated at 15 minute intervals to 3 mg/kg/minute, increases cardiac output and pulmonary vascular pressure when compared to baseline (7278). The validity of this study is limited by the lack of a comparator group.
• Dry eye. Oral coleus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with dry eyes shows that taking a specific combination supplement (Kronek, SOOFT Italia, Montegiorgio, Italy) containing an extract of Coleus forskolii 150 mg (10% forskolin), rutin 200 mg, thiamine 0.7 mg, and riboflavin 0.8 mg, 2 capsules by mouth daily for 30 days moderately decreases dry eye symptoms when compared with placebo (91888). It is unclear if this benefit is due to coleus, other ingredients, or the combination.
• Dysmenorrhea. Although there has been interest in using oral coleus for dysmenorrhea, there is insufficient reliable information about the clinical effects of coleus for this purpose.
• Erectile dysfunction (ED). It is unclear if intracavernosal forskolin, a constituent of coleus, is beneficial in patients with ED. Details: Preliminary clinical evidence in males with ED treated with intracavernosal injections of phentolamine, papaverine, and prostaglandin E shows that intracavernosal forskolin, a constituent of coleus, 1 mg once daily improves penile rigidity scores and average erection duration when compared to no additional intervention (44441).
• Glaucoma. Oral coleus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking two tablets of a specific combination supplement (Kronek Sooft Italia SpA, Montegiorgio, Italy) containing forskolin 15 mg, rutin 200 mg, vitamin B1 1.5 mg, and vitamin B2 1.5 mg for 7 or 30 days prevents increases in intraocular pressure and decreases intraocular pressure by 10% when compared with placebo in glaucoma patients (91887,91890). Preliminary clinical research on another specific combination supplement (Gangliolife, SOOFT Italia), two tablets taken twice daily for 1 year in addition to standard topical therapy results in a decrease in intraocular pressure compared to standard therapy alone in patients with primary open angle glaucoma. One tablet of the supplement contains coleus extract 150 mg (standardized to 10% forskolin), homotaurine 100 mg, L- carnosine 50 mg, vitamin B1 1.1 mg, vitamin B2 1.4 mg, vitamin B6 1.4 mg, folic acid 0.2 mg, and magnesium 150 mg (91886).
• Hypertension. It is unclear if oral coleus is beneficial in patients with hypertension. Details: Preliminary clinical research shows that taking coleus root tuber 1 gram or coleus whole root 1.4 grams orally three times daily after food for 2 months modestly decreases blood pressure compared to baseline in elderly patients with hypertension (91884). The validity of this study is limited by the lack of a comparator group.
• Insomnia. Although there has been interest in using oral coleus for insomnia, there is insufficient reliable information about the clinical effects of coleus for this purpose.
• Irritable bowel syndrome (IBS). Although there has been interest in using oral coleus for irritable bowel syndrome, there is insufficient reliable information about the clinical effects of coleus for this purpose.
• Obesity. It is unclear if oral coleus is beneficial in patients with obesity. Details: Preliminary clinical research in overweight and obese males shows that taking a specific coleus supplement (Forslean, Sabina Corp., Piscataway, NJ) containing a 10% forskolin extract 250 mg twice daily for 12 weeks does not decrease body weight when compared with placebo. However, taking the supplement lowered body fat by 4% compared with 1% in placebo (91882). Another small clinical trial in overweight and obese patients following a calorie-restricted diet shows that taking a coleus extract capsule 250 mg twice daily before meals for 12 weeks does not reduce body weight when compared with placebo (91885).
• Psoriasis. Although there has been interest in using oral coleus for psoriasis, there is insufficient reliable information about the clinical effects of coleus for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral coleus for UTIs, there is insufficient reliable information about the clinical effects of coleus for this purpose. More evidence is needed to rate coleus for these uses.

(Read more about COLEUS)

POSSIBLY INEFFECTIVE

• Head and neck cancer. Subcutaneous European mistletoe extract does not seem to improve survival in patients with head and neck cancer. Oral European mistletoe has not been evaluated for this use. Details: A large clinical trial in patients with head and neck squamous cell carcinoma shows that subcutaneous administration of European mistletoe extract before or after surgery or radiation does not improve overall survival or disease-free survival when compared with surgery or radiation alone (8842).
• Melanoma. Subcutaneous European mistletoe extract does not seem to improve long-term survival rates in patients undergoing surgery for stage II or III melanoma. Oral European mistletoe has not been evaluated for this use. Details: A phase III clinical trial in patients with stage II or III melanoma undergoing surgical removal of lesions and positive lymph nodes shows that subcutaneous administration of a specific European mistletoe extract (Iscador M) does not improve disease-free interval or overall survival over a period of 8 years when compared with observation alone (24780).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bladder cancer. It is unclear if subcutaneous or intravesical European mistletoe extract is beneficial in patients with bladder cancer. Oral European mistletoe has not been evaluated for this use. Details: One small clinical study in patients who have had transurethral resection for superficial urothelial bladder carcinoma shows that intravesical administration of a specific European mistletoe extract 50 mL, containing mistletoe lectin 10 ng/mL to 5000 ng/mL, weekly for 6 weeks might reduce bladder cancer recurrence rates at 12 months, with similar rates to those observed with bacillus Calmette-Guerin (BCG) therapy (15258). Also, a small retrospective chart review of patients with recurrent bladder cancer has found that subcutaneous administration of a specific European mistletoe extract (Iscucin Salicis, Wala Heilmittel GmbH) for several months might be associated with reduced tumor recurrence and an increased duration of tumor-free periods (93268).
• Breast cancer. It is unclear if subcutaneous European mistletoe extract is beneficial in patients with breast cancer. Oral European mistletoe has not been evaluated for this use. Details: Observational research in patients with solid tumors of the breast has found that subcutaneous administration of certain specific European mistletoe extracts (Iscador, Weleda; Helixor, Helixor Heilmittel GmbH & Co. KG) is associated with reduced tumor progression and improved survival when compared with a control (7045,15351,24798). However, these findings were not replicated in a randomized, controlled study. A small clinical trial in patients with breast cancer receiving chemotherapy shows that subcutaneous injection of European mistletoe extracts (Helixor A, Iscador M Spez) three times weekly for 18 weeks does not reduce the rate of relapse or metastasis or improve quality of life when compared with chemotherapy alone (99497).
• Cancer. A meta-analysis of several small, low-quality clinical studies suggests that subcutaneous European mistletoe extract might improve quality of life in some patients with cancer. Oral European mistletoe has not been evaluated for this use. Details: Several small clinical studies have assessed the impact of various European mistletoe extracts (PS76A2, Helixor, Isorel, Eurixor, and AbnobaViscum Quercus), given subcutaneously either alone or with chemotherapy, on quality of life in patients with various types of cancer (24777,24782,24786,24788,24803,24804,93259,93260,93262,93269). A meta-analysis of these and many other small clinical studies shows that subcutaneous administration of European mistletoe extract has a moderate effect on overall quality of life when compared with a control group, with significant improvements on various subdomains. A larger effect size is observed with more recent trials; however, this may be due to the inclusion of patients with less severe disease in more recent studies when compared with earlier studies (105839). The validity of these findings is limited by the high risk of bias of most of the included studies and the heterogeneity of the studies and patient populations.
• Cancer-related fatigue. A meta-analysis of several low-quality studies suggests that subcutaneous European mistletoe extract might improve fatigue in some patients with cancer. Oral European mistletoe has not been evaluated for this use. Details: A meta-analysis of 12 mostly small, unblinded randomized studies in 1525 patients with a variety of cancers shows that various European mistletoe extracts (e.g., Abnobaviscum, Eurixor, Helixor, Iscador, Lektinol) given subcutaneously at undefined doses modestly improves patient-reported fatigue scores when compared with placebo or usual care (110441). This report also describes a meta-analysis of 7 mostly large nonrandomized, retrospective studies in the same patient population. This analysis suggests that various European mistletoe extracts given subcutaneously may modestly improve clinician-reported fatigue when compared with usual care (110441). The validity of these findings is limited by the low quality and heterogeneity of the included studies.
• Chemotherapy-induced diarrhea. It is unclear if subcutaneous European mistletoe extract can reduce the rate of chemotherapy-induced diarrhea. Oral European mistletoe has not been evaluated for this use. Details: A small clinical study in patients with gastric cancer recovering from surgery and receiving chemotherapy with doxifluridine shows that subcutaneous administration of a specific European mistletoe extract (Abnobaviscum Quercus, Abnoba GmbH) three times weekly for 24 weeks reduces the risk of chemotherapy-induced diarrhea by 86% when compared with doxifluridine alone (93262).
• Colorectal cancer. Several small, low-quality clinical and observational studies suggest that subcutaneous administration of specific European mistletoe extracts may improve survival or tumor response in patients with colorectal cancer when used as adjunct therapy. Oral European mistletoe has not been evaluated for this use. Details: One small clinical study in patients with solid tumors of the colon shows that subcutaneous administration of a specific European mistletoe extract (Iscador, Weleda) increases survival time when compared with matched controls not receiving European mistletoe (7045). Another small clinical study in patients with advanced colorectal cancer shows that infusions of another specific European mistletoe extract (Isorel, Novipharm GmbH), in combination with chemotherapy and surgery, improves survival by at least 38% when compared with chemotherapy plus surgery or surgery alone (24783). Other small clinical studies in patients with colorectal cancer show that subcutaneous administration of another specific European mistletoe extract (Helixor, Helixor Heilmittel GmbH & Co. KG) 100-200 mg three times weekly, in addition to chemotherapy, nearly doubles survival over 2 years when compared with chemotherapy alone; however, between-group differences in tumor progression were not observed (24785,24789). Additionally, a small observational study in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy shows that subcutaneous administration of a specific European mistletoe extract (Abnobaviscum Quercus, Abnoba GmbH) 0.02 mg three times weekly for three weeks, and then slowly titrated up to 20 mg three times weekly for a total of 24 weeks, improves tumor response rates when compared with chemoradiotherapy alone (107285). Despite these promising results, much research in this field suffers from poor study design (10672).
• Common cold. It is unclear if subcutaneous European mistletoe extract can prevent the common cold. Oral European mistletoe has not been evaluated for this use. Details: One small clinical study in healthy individuals shows that subcutaneous administration of a specific European mistletoe extract (Iscador P or Iscador Qu, Weleda) twice weekly for 12 weeks does not reduce the frequency or duration of the common cold when compared with placebo (24806).
• Epilepsy. Although there has been interest in using oral European mistletoe for epilepsy, there is insufficient reliable information about the clinical effects of European mistletoe for this purpose.
• Gastric cancer. It is unclear if subcutaneous European mistletoe extract is beneficial in patients with gastric cancer. Oral European mistletoe has not been evaluated for this use. Details: One small clinical study in patients with solid tumors of the stomach shows that subcutaneous administration of a specific European mistletoe extract (Iscador, Weleda) improves survival when compared with matched controls not receiving European mistletoe (7045). Another small clinical study in patients with gastric cancer recovering from surgery shows that subcutaneous administration of a different European mistletoe extract (Abnobaviscum Quercus, Abnoba GmbH) three times weekly for 24 weeks plus chemotherapy improves quality of life, increases total white blood cell and eosinophil counts, and reduces the risk of chemotherapy-induced diarrhea by 86% when compared with chemotherapy alone. However, there is no effect on lymphocyte responses (93262). Much research in this field suffers from poor study design (10672).
• Hepatitis C. It is unclear if subcutaneous European mistletoe extract is beneficial in patients with chronic hepatitis C. Oral European mistletoe has not been evaluated for this use. Details: While a small case series of patients with chronic hepatitis C has found that subcutaneous injection of a specific aqueous extract of European mistletoe (Iscador Qu, Weleda) may decrease viral load and improve quality of life (9770), a small observational study in patients with chronic hepatitis C has found that subcutaneous administration of a different European mistletoe product (Abnobaviscum Quercus, Abnoba GmbH) three times weekly for 6 months does not normalize viral load or liver enzymes, but is associated with improved disease-related symptoms, when compared to baseline (24805). The validity of the findings from these studies is limited by their retrospective nature and lack of a control group.
• Hypertension. Although there has been interest in using oral European mistletoe for hypertension, there is insufficient reliable information about the clinical effects of European mistletoe for this purpose.
• Kidney Transplant. It is unclear if retroperitoneal instillation of European mistletoe extract is beneficial in kidney transplant patients with significant postoperative lymphatic drainage. Oral European mistletoe has not been evaluated for this use. Details: A large retrospective chart review in hospitalized kidney transplant patients with a large amount of postoperative lymphatic drainage suggests that retroperitoneal instillation of European mistletoe extract (Helixor M) 100 mg via the drainage tube may reduce drainage by about 83 mL from postoperative days 7 to 14 and decrease the length of hospitalization when compared with usual care (110442) The validity of these findings is limited by the retrospective study design.
• Leukemia. It is unclear if subcutaneous European mistletoe extract is beneficial in patients with leukemia. Oral European mistletoe has not been evaluated for this use. Details: A small clinical study in patients with chronic myeloid leukemia shows that subcutaneous administration of a specific European mistletoe extract (Helixor) at doses up to 350 mg increases survival by up to 25.7 months when compared with survival times previously published in the scientific literature (24781). The validity of this finding is limited by the lack of a randomized comparator group.
• Lung cancer. It is unclear if subcutaneous European mistletoe extract is beneficial in patients with lung cancer. Oral European mistletoe has not been evaluated for this use. Details: Observational research in patients with non-small cell lung cancer (NSCLC) has found that subcutaneous administration of European mistletoe extracts (Abnobaviscum, Helixor, and Iscador) along with chemotherapy is associated with increased survival in patients with stage IV NSCLC, but not stage I-IIIA NSCLC, when compared with chemotherapy alone (99498,105840). Additionally, a small, randomized clinical study in patients with NSCLC shows that treatment with a specific European mistletoe extract (Iscador) does not significantly increase median survival time or tumor response when compared with placebo (24784,24790).
• Malignant pleural effusions. It is unclear if intrapleural European mistletoe extract is beneficial in patients with malignant pleural effusions. Oral European mistletoe has not been evaluated for this use. Details: A small clinical study in patients with malignant pleural effusions shows that intrapleural administration of a specific European mistletoe extract (Helixor M; Helixor Heilmittel GmbH & Co. KG) 100 mg, repeated every other day up to 5 times with doses increased by 100 mg with each successive procedure, increases response rate when compared with doxycycline. The response rate, defined as the percentage of patients who achieved complete or partial response, was 91% with European mistletoe extract and 67% with doxycycline (24774). Another small clinical study in patients with lung cancer and malignant pleural effusions shows that intrapleural administration of this same European mistletoe extract and dosing regimen leads to a one-month pleural effusion recurrence rate of 48% (102547). The validity of this findings if limited by a lack of control group.
• Osteosarcoma. It is unclear if subcutaneous European mistletoe extract is beneficial in patients with osteosarcoma. Oral European mistletoe has not been evaluated for this use. Details: A small, open-label clinical study in patients with complete surgical remission following a second osteosarcoma relapse shows that subcutaneous administration of a specific European mistletoe extract (Iscador P), 3 times weekly for 12 months, improves post-relapse disease-free survival when compared with oral etoposide 50 mg/m2 daily for 21 days of each 28-day cycle for 6 cycles. After one year, 5 of 9 patients who completed treatment with European mistletoe extract had not relapsed, compared with 3 of 10 patients who completed etoposide therapy (105854). In a follow-up report, after a median of 83 months, disease-free survival remained the same in those receiving European mistletoe extract, whereas 0 of 10 patients remained disease-free after completion of etoposide treatment (105837).
• Ovarian cancer. It is unclear if subcutaneous European mistletoe extract is beneficial in patients with ovarian cancer. Oral European mistletoe has not been evaluated for this use. Details: A small observational study in patients with ovarian cancer has found that subcutaneous administration of a specific European mistletoe extract (Iscador) along with conventional therapy is associated with improved survival by more than one year when compared with conventional therapy alone (93260).
• Pancreatic cancer. It is unclear if subcutaneous or intratumoral European mistletoe extract is beneficial in patients with pancreatic cancer. Oral European mistletoe has not been evaluated for this use. Details: Some observational research in patients with stage IV pancreatic cancer has found that subcutaneous administration of European mistletoe extract is not associated with improved rates of partial or complete remission (3707,8848). However, another observational study in patients with inoperable pancreatic cancer being treated with chemotherapy and palliative surgical interventions has found that intratumoral administration of European mistletoe (Helixor, AbnobaViscum, and/or Iscucin) is associated with improved survival when compared with historical survival rates in patients receiving chemotherapy alone (93264). Additionally, a small, open-label clinical study in patients with stage III or IV pancreatic cancer who are no longer eligible for chemotherapy shows that subcutaneous administration of a specific European mistletoe extract (Iscador Qu spezial) at doses starting at 0.01 mg and titrated up to 10 mg three times weekly for up to 12 months increases survival by about 2 months when compared with supportive care alone (93267).
• Radiation exposure. It is unclear if subcutaneous European mistletoe extract is beneficial in children with radiation exposure. Oral European mistletoe has not been evaluated for this use. Details: A small clinical study in children with recurrent respiratory infections due to exposure to ionizing radiation from the Chernobyl nuclear accident shows that subcutaneous administration of a specific European mistletoe extract (Iscador) at doses ranging from 0.001 mg twice weekly to 1 ng/kg twice weekly for 5 weeks reduces the frequency of recurrent respiratory infections by 73% to 78% and improves symptoms such as fatigue, sweating, headache, joint pain, emotional instability, and muscle pain when compared to baseline (24779). The validity of these findings is limited by the lack of a comparator group.
• Uterine cancer. It is unclear if subcutaneous European mistletoe extract is beneficial in patients with uterine cancer. Oral European mistletoe has not been evaluated for this use. Details: A small observational study in patients with uterine cancer has found that subcutaneous administration of a specific European mistletoe extract (Iscador) is associated with improved survival when compared with matched controls (24794). More evidence is needed to rate European mistletoe for these uses.

(Read more about EUROPEAN MISTLETOE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Angina. It is unclear if oral hawthorn is beneficial in patients with angina. Details: Preliminary clinical research in patients with angina taking chronic beta-adrenergic receptor blockers or ACE inhibitor therapy shows that taking a hawthorn (Crataegus pinnatifada) extract 100 mg orally three times daily for four weeks improves angina and electrocardiogram (ECG) findings and reduces nitroglycerin intake when compared with placebo (19242). Other preliminary clinical research in patients with unstable angina shows that taking hawthorn 10 grams and hu zang 15 grams orally daily for 4 weeks does not reduce the frequency of angina pectoris attacks when compared with control. However, taking hawthorn and hu zang improved some subjective symptom scores and quality of life scores (109610).
• Anxiety. Oral hawthorn has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in adults with mild to moderate generalized anxiety shows that taking a specific product (Sympathyl, not available in the US) containing hawthorn, magnesium, and California poppy for 90 days modestly improves anxiety scores when compared with placebo (12583). Also, a clinical study in adults with adjustment disorder and anxious mood shows that hawthorn, in combination with black horehound, passion flower, valerian, kola nut, and guarana, modestly improves anxiety scores when compared with placebo (6250). It is unclear if these effects are due to hawthorn, other ingredients, or the combination. Another small clinical study in healthy adults shows that taking a combination of herbal extracts containing hawthorn, passionflower, ballota, and valerian root daily for 14 days reduces subjective anxiety and objective sympathetic and autonomic nervous system activation in response to a psychosocial stressor when compared with placebo (111222). It is unclear if these effects are due to hawthorn, other ingredients, or the combination.
• Arrhythmia. Although there has been interest in using oral hawthorn for arrhythmia, there is insufficient reliable information about the clinical effects of arrhythmia for this condition.
• Atherosclerosis. Although there has been interest in using oral hawthorn for atherosclerosis, there is insufficient reliable information about the clinical effects of arrhythmia for this condition.
• Cardiovascular disease (CVD). Although there has been interest in using oral hawthorn for CVD, there is insufficient reliable information about the clinical effects of arrhythmia for this condition.
• Cognitive function. Oral hawthorn has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In a preliminary clinical trial, a single dose of 25 drops of a combination product of D-camphor and hawthorn berry extract (Korodin) was superior to placebo for increasing cognitive performance in elderly female patients as measured by visuomotor speed and information processing capacity. The active treatment group showed an improvement in attentional and mental performance (19240,91504).
• Congestive heart failure (CHF). The evidence on the effects of oral hawthorn in patients with CHF is conflicting. Although some older research suggests it may be beneficial, more recent, larger studies suggest it may actually increase the risk for complications. Details: There is contradictory evidence about the effects of hawthorn extract in heart failure patients. Several clinical studies show that taking specific hawthorn leaf and flower extracts (LI 132, Faros 300, Lichtwer Pharma; WS 1442, Crataegutt forte, Dr. Willmar Schwabe Pharmaceuticals; or HeartCare, Nature's Way) 240-600 mg daily improves ejection fraction and exercise tolerance, reduces subjective symptoms, and decreases the risk of death in patients with New York Heart Association (NYHA) stage II heart failure. In these studies, the maximum effect was usually seen after 6-12 weeks of treatment (8279,8280,11449,19221,19223,19225,19226,19227,19228). Another clinical trial shows that hawthorn extract (WS 1442, Crataegutt forte, Dr. Willmar Schwabe Pharmaceuticals or HeartCare, Nature's Way) 1800 mg daily, combined with diuretic therapy, improves exercise tolerance and reduces subjective symptoms in NYHA stage III heart failure. In this study, maximum effect was usually seen after 16 weeks of treatment (8281). In another trial, patients with NYHA II heart failure taking either hawthorn (LI 132, Faros) 300 mg three times daily or captopril 12.5 mg three times daily experienced similar improvements in cardiac performance and symptoms (19230). However, other clinical research suggests no benefit and possible harm with hawthorn. A large-scale clinical trial (SPICE) in patients with NYHA stage II or III heart failure shows that taking specific hawthorn extracts (WS 1442, Crataegutt forte, Dr. Willmar Schwabe Pharmaceuticals; HeartCare, Nature's Way) 900 mg daily for 24 months, in combination with conventional treatment, does not decrease hospitalization due to progressive heart failure, non-fatal myocardial infarction, or cardiac death (17203). Another clinical trial in patients with NYHA stage II or III heart failure shows that taking these same specific hawthorn extracts at the same dose for up to 6 months does not slow the progression of heart failure when compared with placebo (19222). In a retrospective analysis of this study, it was shown that heart failure progression was significantly increased in patients taking hawthorn when compared with placebo. The rate of death was also increased by 1.7% over placebo, and heart failure-related hospitalizations increased by 8% over placebo in patients treated with hawthorn (16824).
• Hyperlipidemia. Although there has been interest in using oral hawthorn for hyperlipidemia, there is insufficient reliable information about the clinical effects of arrhythmia for this condition.
• Hypertension. It is unclear if oral hawthorn is beneficial for lowering blood pressure. Details: One preliminary clinical trial showed that taking hawthorn standardized extract 1,000-2,500 mg daily for three days does not significantly reduce blood pressure in hypertensive or prehypertensive patients when compared with placebo (19244). However, another study in patients with diabetes and hypertension shows that taking a specific hawthorn extract (LI 132) 1,200mg daily for 16 weeks significantly decreased diastolic, but not systolic, blood pressure when compared with placebo (19245).
• Obesity. Although there has been interest in using oral hawthorn for obesity, there is insufficient reliable information about the clinical effects of hawthorn for this condition.
• Orthostatic hypotension. Oral hawthorn has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in older adults with orthostatic hypotension shows that taking a specific combination product containing hawthorn and camphor (Korodin Herz-Kreislauf-Tropfen) 25 drops orally three times daily for 7 days attenuates the blood pressure reduction upon standing when compared with placebo. Signs and symptoms of orthostatic hypotension such as dizziness, blurry vision, and falls also seem to be reduced when compared with baseline (39614,39617). A meta-analysis of 4 studies shows that giving single doses of 20-25 drops of the same combination product increases systolic and diastolic blood pressure when compared with placebo (103620). However, the studies have methodologic problems and, while 2 were conducted in females with orthostatic hypotension, the others involved health young adults or normotensive elderly subjects. The effect of hawthorn alone for treatment of orthostatic hypotension has not been determined. The combination product used in these studies is not available in the US. More evidence is needed to rate hawthorn for these uses.

(Read more about HAWTHORN)

There is insufficient reliable information available about the effectiveness of linden.

(Read more about LINDEN)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dyspepsia. Oral olive leaf extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in healthy adults shows that taking a specific combination product containing olive leaf extract 24% and prickly pear cactus 33% (Mucosave, Bionap S.R.L.) 400 mg daily for 8 weeks seems to improve dyspepsia and other gastrointestinal symptoms when compared with placebo (105904). It is unclear if this benefit would occur in patients with clinically diagnosed dyspepsia.
• Exercise-induced respiratory infections. It is unclear if oral olive leaf extract is beneficial for reducing respiratory infections from exercise. Details: A small clinical study in high school athletes shows that taking one tablet of olive leaf extract providing eleuropein 100 mg daily for 2 months during training season does not reduce the incidence of the common cold when compared with placebo. While it may reduce the number of sick days by 28%, a sub-group analysis suggests that this reduction is only evident in female athletes (101860).
• Gastroesophageal reflux disease (GERD). Although there is interest in using oral olive leaf for GERD, there is insufficient reliable information about the clinical effects of olive for this condition.
• Herpes zoster (shingles). Although there is interest in using oral olive leaf for shingles, there is insufficient reliable information about the clinical effects of olive for this condition.
• Influenza. Although there is interest in using oral olive leaf for influenza, there is insufficient reliable information about the clinical effects of olive for this condition.
• Metabolic syndrome. It is unclear if oral olive leaf extract is beneficial for improving body composition and cardiovascular risk factors in patients with metabolic syndrome. Details: A small clinical trial in overweight, middle-aged males at risk for metabolic syndrome shows that taking four capsules of olive leaf extract providing oleuropein 51.1 mg and hydroxytyrosol 9.7 mg daily for 12 weeks improves insulin sensitivity by 15% when compared with placebo. However, body composition, blood pressure, cholesterol levels, and other cardiovascular risk factors were not improved (92245).
• Osteoarthritis. It is unclear if oral olive fruit or leaf extract is beneficial for improving osteoarthritis. Details: Preliminary clinical research shows that taking a freeze-dried aqueous extract of olive fruit 400 mg daily for 8 weeks decreases pain and increases mobility in people with osteoarthritis (14844). Other preliminary clinical research in adults with knee osteoarthritis shows that taking olive leaf extract 50.1 mg daily for 4 weeks improves overall pain measurements by 14%, compared to only 4% in the placebo group. However, many individual measurements of pain are not improved (92252).
• Osteoporosis. It is unclear if oral olive leaf extract is beneficial for osteoporosis. Details: Clinical research shows that taking olive leaf extract (Bonolive, BioActor BV) 250 mg daily for 12 months, along with elemental calcium 400 mg daily, increases osteocalcin levels by about 32% when compared to baseline; this increase was significant when compared to those taking calcium 400 mg plus placebo, who showed a 6% decrease in osteocalcin levels. However, taking olive leaf extract does not significantly increase bone mineral density of the lumbar spine or femur neck when compared with placebo (92247).
• Rheumatoid arthritis (RA). It is unclear if oral olive fruit extract is beneficial for improving RA symptoms. Details: Preliminary clinical research in adults with RA shows that taking an aqueous freeze-dried extract of olive fruit 400 mg daily for 8 weeks does not improve symptoms when compared with control (14844). More evidence is needed to rate the effectiveness of olive for these uses.

(Read more about OLIVE)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Coleus extract 500 mg daily has been used for up to 3 months without significant adverse effects (91885,100851). ...when used intravenously and appropriately, short-term. Intravenous forskolin, a constituent of coleus, seems to be safe when given at an appropriate rate of 0.5 mcg/kg/minute and increased at 15 minute intervals to 1.0, 2.0, and 3.0 mcg/kg/minute up to 1 hour (7278,7279). ...when used by inhalation and appropriately. Single-dose inhalation of forskolin powder 10 mg from a Spinhaler inhalator seems to be safe and well-tolerated (7281). ...when used ophthalmologically and appropriately. Coleus suspension eye drops (1%) have been safely used in clinical studies (7282,7283,7284,7402,7403,7405).

POSSIBLY UNSAFE ...when used orally in higher doses. Although coleus extracts have been used with apparent safety in doses up to 1.4 grams daily for 2 months (91884), taking coleus extract in doses exceeding 500 mg daily has been associated with an increased incidence of adverse effects, which are primarily gastrointestinal (100851).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Evidence from animal research suggests that high doses of coleus can inhibit embryo implantation and/or delay fetal development (25174); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about COLEUS)

POSSIBLY SAFE ...when used orally, subcutaneously, or intravenously and appropriately. There is some evidence that European mistletoe extracts can be used safely (7039,9769,15351,24773,24778,93261,93266,93267,96487,107285). However, they have a narrow therapeutic range; high doses are not safe. Tell patients not to consume more than three mistletoe berries or two leaves (12). Advise patients not to use European mistletoe for self-medication.

LIKELY UNSAFE ...when used orally in high doses. Ingestion of high doses of mistletoe berry or leaf can cause serious adverse reactions. More than three berries or two leaves can cause seizures, bradycardia, hypotension, and death (7039).

PREGNANCY: LIKELY UNSAFE
when used orally or subcutaneously. European mistletoe might have uterine stimulant and abortifacient activity (19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about EUROPEAN MISTLETOE)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Hawthorn preparations in doses of up to 1800 mg daily seem to be safe when used for up to 16 weeks. Although hawthorn might be safe for long-term use, current studies have not evaluated safety past 16 weeks (8279,8280,8281,10144,17203,104689). There is insufficient reliable information available about the safety of hawthorn when used topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about HAWTHORN)

LIKELY SAFE ...when linden leaf is used orally and appropriately in amounts normally found in foods (12). Linden leaf has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of linden when used orally or topically in medicinal amounts.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about LINDEN)

LIKELY SAFE ...when olive fruit is used orally and appropriately in amounts commonly found in foods.

POSSIBLY SAFE ...when olive leaf extract is used orally and appropriately. Olive leaf extract providing 51-100 mg oleuropein daily has been used with apparent safety for 6-8 weeks (92245,92247,101860). There is insufficient reliable information available about the safety of olive fruit extract when used in amounts greater than those found in foods.

PREGNANCY AND LACTATION:
Insufficient reliable information available; stick with amounts commonly found in foods.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of coleus and anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.  Details In vitro and animal research shows that forskolin, a constituent of coleus, can inhibit platelet aggregation and adhesion (7410,7411,7412).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining coleus with antihypertensive drugs might cause additive blood pressure lowering effects and increase the risk of hypotension.  Details Animal research shows that forskolin, a constituent of coleus, may lower blood pressure (7278,7279,44424,44431).

CALCIUM CHANNEL BLOCKERS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Theoretically, combining coleus with calcium channel blockers might increase the coronary vasodilatory effects.  Details Forskolin, a constituent of coleus, and calcium channel blockers both cause coronary vasodilatory effects (7278,7279).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking coleus may affect drugs metabolized by CYP2C9 and increase the risk of adverse effects or reduce the effectiveness.  Details Research on the effect of coleus on CYP2C9 is conflicting. Some animal research shows that coleus extract can induce CYP2C9, while in vitro research shows that coleus can inhibit CYP2C9 (91891). Until more is known, advise patients that taking coleus might increase or decrease levels of drugs metabolized by CYP2C9.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking coleus might decrease serum levels of drugs metabolized by CYP3A4.  Details In vitro research shows that coleus can activate the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4 (44399,44412). Although the clinical significance of this is not known, use caution when considering concomitant use of coleus and other drugs affected by these enzymes.

NITRATES Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Theoretically, combining coleus with nitrates might increase the coronary vasodilatory effects.  Details Forskolin, a constituent of coleus, and nitrates both cause coronary vasodilatory effects (7278,7279,44424).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking coleus may affect the metabolism of warfarin and increase the risk of adverse effects or reduce the effectiveness.  Details Some animal research shows that coleus extract can induce cytochrome P450 2C9 (CYP2C9), an enzyme that metabolizes warfarin. However, other in vitro research shows that coleus can inhibit CYP2C9 (91891). Theoretically, taking coleus with drugs metabolized by CYP2C9 might affect drug levels and the risk of adverse effects. Until more is known, advise patients that taking coleus might increase or decrease levels of warfarin.

(Read more about COLEUS)

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, European mistletoe might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research suggests that European mistletoe extracts have hypotensive effects (93270,96492).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, European mistletoe might decrease the effectiveness of immunosuppressants.  Details Clinical and in vitro studies suggest that European mistletoe might have immunostimulant effects (7039,8843,8844,24775,24779).

(Read more about EUROPEAN MISTLETOE)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, hawthorn may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal research shows that hawthorn can inhibit platelet aggregation (95528,95529,95530,95531). However, its effect in humans is unclear. One observational study shows that patients taking hawthorn shortly before undergoing coronary artery bypass graft (CABG) surgery or valve replacement surgery have a 10% incidence of postoperative bleeding, compared with 1% in those who never consumed hawthorn extract (95527). However, clinical research shows that taking a specific preparation of dried hawthorn leaves and flowers (Crataesor, Soria Natural Lab) 800 mg three times daily for 15 days does not affect platelet aggregation or levels of thromboxane B2, the metabolite of thromboxane A2, in healthy humans (54664).

BETA-BLOCKERS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might cause additive effects on blood pressure and heart rate.  Details Some evidence shows that hawthorn might lower blood pressure and heart rate (12595,19245,113112,113113).

CALCIUM CHANNEL BLOCKERS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might cause additive coronary vasodilation and hypotensive effects.  Details Some evidence shows that hawthorn might lower blood pressure due to vasodilatory effects (12595,19245).

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hawthorn might potentiate the effects and adverse effects of digoxin.  Details Hawthorn appears to improve cardiac output (12595); however, hawthorn does not appear to affect digoxin pharmacokinetics (19249). Case reports suggest that at least one species of hawthorn root extract (Crataegus mexicana) may produce adverse effects similar to digoxin and can cross-react with digoxin assays, leading to falsely elevated plasma digoxin levels (113112,113113).

NITRATES Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use might cause additive coronary vasodilatory effects.  Details Some evidence shows that hawthorn might lower blood pressure due to vasodilatory effects (12595,19245).

PHOSPHODIESTERASE-5 INHIBITORS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use might result in additive vasodilation and hypotension.  Details Hawthorn might inhibit PDE-5 and cause vasodilation (12595).

(Read more about HAWTHORN)

(Read more about LINDEN)

(Read more about OLIVE)

General ...Orally, intravenously, ophthalmologically, and by inhalation, coleus seems to be well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, nausea, vomiting.
Intravenously: Flushing, hypotension, tachycardia.
Ophthalmologically: Conjunctival hyperemia, stinging eyes.
Inhalation: Irritation of the respiratory tract, restlessness, tremor.

Cardiovascular ...Intravenously, the coleus constituent, forskolin, can cause tachycardia, flushing and hypotension (7279,44424,44431).

Dermatologic ...Two cases of contact dermatitis have been reported following airborne exposure to coleus (44426,44418).

Gastrointestinal ...Orally, coleus can cause dose-related diarrhea and other gastrointestinal symptoms. Increased bowel movements and loose stools have been reported in 1 of 15 patients taking coleus extract in a clinical trial (91885). Some retrospective evidence reports about a 10% rate of gastrointestinal adverse effects from oral coleus use; 81% of these adverse effects were related to diarrhea. Other reported adverse effects which occurred at a much lower rate, include nausea, vomiting, and/or constipation. Gastrointestinal effects appear to be dose-related; those taking less than 250 mg of coleus extract did not report any diarrhea, while all patients taking 1000 mg of coleus extract reported diarrhea (100851).

Neurologic/CNS ...Inhalation of forskolin, a constituent of coleus, can cause tremor and restlessness (7281).

Ocular/Otic ...Ophthalmologically, forskolin, a constituent of coleus, can cause stinging of the eyes and conjunctival hyperemia (7283).

Pulmonary/Respiratory ...Inhalation of forskolin, a constituent of coleus, can cause throat and upper respiratory tract irritation, and mild to moderate cough (7281).

(Read more about COLEUS)

General ...Orally, European mistletoe seems to be well tolerated when used in small amounts. However, a thorough evaluation of safety outcomes has not been conducted. Parenterally, European mistletoe may be safe when administered by a healthcare provider. High oral or parenteral doses may be unsafe.
Most Common Adverse Effects:
Orally: Diarrhea, intestinal cramps, and vomiting at high doses.
Parenterally: Chills, diarrhea, eosinophilia, fever, flatulence, headache, malaise, nausea, pruritus, vomiting, and pain and inflammation at the injection site.
Serious Adverse Effects (Rare):
Orally: Hepatitis, seizures, coma, and death at high doses.
Parenterally: Necrosis at injection site. Allergic reactions, including anaphylaxis, in sensitive individuals.

Cardiovascular ...Subcutaneously, European mistletoe may cause angina and orthostatic circulatory disturbances (7044,7045,9769).

Dermatologic ...Subcutaneously and intravenously, European mistletoe may cause pruritus, skin rash, and angioedema (93261,93265,93266,96476,107285,107286). When administered subcutaneously, the use of an extended dose-escalation regimen may limit the development of localized reactions in comparison to rapid dose escalation (96476).

Endocrine ...Intravenously, aviscumine, a pure form of mistletoe lectin I produced by recombinant DNA techniques, may cause hypokalemia (16385).

Gastrointestinal ...Orally, European mistletoe may cause vomiting, diarrhea, and intestinal cramps (18). Intraperitoneal and intratumoral injection may cause nausea, vomiting, and abdominal pain (7106,93264,96495). Subcutaneously, European mistletoe may cause flatulence, loose stools, diarrhea, nausea, and vomiting (93261,93265). Intravenously, aviscumine, a pure form of mistletoe lectin I produced by recombinant DNA techniques, may cause nausea and vomiting (16385,93261).

Genitourinary ...Intravenously, aviscumine, a pure form of mistletoe lectin I produced by recombinant DNA techniques, may change urinary frequency (16385,93261).

Hematologic ...Subcutaneously, intraperitoneally, or intratumorally, European mistletoe may cause eosinophilia (7044,7045,7106,9769).

Hepatic ...Orally, European mistletoe has been associated with two cases of hepatotoxicity when used in combination with other herbal ingredients. In one case, in which a patient took a combination herbal product, it was deemed unlikely that European mistletoe was the causative agent. It was determined to be most likely due to another ingredient or product contamination (3932). In another case, a previously healthy male presented to the hospital with mild fever, brownish urine, and elevated liver function enzymes after frequent use of European mistletoe extract for 1 month and kudzu root extract for 10 days. Upon discontinuation of the two extracts, liver function slowly returned to normal with no other symptoms (88777). It is unclear if European mistletoe, kudzu, or the combination was responsible for this adverse effect.
Intravenously, aviscumine, a pure form of mistletoe lectin I produced by recombinant DNA techniques, may cause elevated liver enzymes (16385,93261).

Immunologic ...Subcutaneously, European mistletoe may cause allergic reactions (7044,7045,9769) or flu-like symptoms or mild infections (93261). Early research shows that European mistletoe is not associated with an increase in side effects when it is administered in conjunction with targeted cancer treatments such as monoclonal antibodies and immunotherapy regimens, including PD-1/PD-L1 or CTLA-4 inhibitors (96490,96489). There are two case reports of apparent immunologic response to the application of European mistletoe for pleurodesis, resulting in acute respiratory distress and pneumonitis (96488,96494).
There are at least 5 reports of anaphylactic reactions associated with subcutaneous European mistletoe extract (15352,107286). In one case, anaphylaxis did not occur until after 2 years of treatment with European mistletoe (15352). Aviscumine has also been associated with anaphylactic reactions in people who have previously used European mistletoe products (16385).

Musculoskeletal ...Subcutaneous, intratumoral, intraperitoneal, and intravenous administration of European mistletoe can cause pain at the injection site (7044,7045,9769,93264,93266,7106,93261,96495). There is one report of a benign abdominal wall mass developing at the European mistletoe injection site, which was likely the result of a local inflammatory response (15350). Necrosis can also occur at the site of injection (8).

Neurologic/CNS ...Orally, European mistletoe may cause seizures, coma, and death (18). Subcutaneously, European mistletoe can cause headaches (7044,7045,9769,93261,93265) or fatigue or malaise (93261,93265). When injected into the tumor, European mistletoe can cause headaches (93264,96495). Intravenous infusion of aviscumine, a pure form of mistletoe lectin I produced by recombinant DNA techniques, can cause fatigue (16385,93261).

Ocular/Otic ...Orally, European mistletoe may cause contraction of the pupil and uncontrollable eye movement (18). Subcutaneously, European mistletoe may cause dry eyes (93261).

Pulmonary/Respiratory ...There are multiple reports of acute respiratory effects after application of European mistletoe for pleurodesis. In one case, a 52-year-old male presenting with pneumothorax received European mistletoe extract 40 mg (ABNOBAviscum F, ABNOBA Helmittel GmbH) with 50 mL of normal saline into the pleural space. After 3 days, the patient experienced worsening dyspnea with right pleural effusion and bilateral lung infiltration requiring intubation and mechanical ventilation (96488). In another case, a 58-year-old male presenting with postoperative pleural effusion received pleurodesis with European mistletoe extract 500 mg (ABNOBAviscum F) on days 6, 8, 12, and 16 after surgery. Imaging revealed apparent acute respiratory distress and pneumonitis, but without corresponding clinical symptoms, which improved after 5 days of supportive care (96494). In a small retrospective study, 28% of elderly patients with secondary spontaneous pneumothorax who underwent chemical pleurodesis with European mistletoe extract 60 mg (Abnova Viscum-F) in 50 mL of normal saline experienced dyspnea with associated desaturation. These adverse effects were attributed to pain caused by the induced pleural inflammation, and may have also been related to the patients' underlying impaired pulmonary function. Treatment with oxygen via nasal cannula resulted in improvement of symptoms in most patients within 24 hours (105838).

Other ...Subcutaneously, intravenously, and intratumorally, European mistletoe can cause malaise, chills, and high fever (7044,7045,9769,93261,93264,93265,93266,93268,96495,99499). Intravenous infusion of aviscumine, a pure form of mistletoe lectin I produced by recombinant DNA techniques, can cause fever (16385,93261).

(Read more about EUROPEAN MISTLETOE)

General ...Orally, hawthorn seems to be well tolerated when used appropriately. Topically, no adverse effects have been reported, although a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Multiorgan hypersensitivity reactions resulting in acute renal failure have been reported rarely.

Cardiovascular ...Orally, tachycardia (with facial pains) of uncertain relationship to hawthorn was reported in a multicenter clinical trial (54640). Palpitations (19244) were reported in three patients in a large surveillance trial of 3,664 patients with cardiac failure (54692) and in 11 patients with congestive heart failure (CHF) in a literature review of 5,577 patients (19247). Circulation failure has been reported in two patients with CHF in a literature review of 5,577 patients (19247). Incidences of hospitalization, hospitalization due to CHF, worsening of CHF, angina, and atrial fibrillation have also been reported with the use of hawthorn extract WS 1442 (Crataegutt forte), although it is unclear if these events are related to hawthorn supplementation or existing CHF (19222). In clinical trials, chest pain (8281), short-term increases in blood pressure (19240), and other non-specific heart problems (17203) have also been reported following the use of various hawthorn preparations (e.g. WS 1442, Korodin).
Orally, severe bradycardia, bradypnea, and Mobitz type 1 second degree heart block have been reported in a 16-year-old female who consumed Hawthorn root extract. Blood tests indicated plasma digoxin levels in the therapeutic range, despite no history of digoxin use. Medical treatment for digoxin cardiotoxicity did not improve symptoms. Symptoms gradually normalized over 3 days after discontinuation of the product (113112). Similarly, a 40-year-old female presented with bradycardia and elevated plasma digoxin levels after taking hawthorn root extract 196 mg daily for 2 days with no history of digoxin use. Symptoms resolved within 24 hours (113113).

Dermatologic ...Orally, erythematous rash has been reported in patients with CHF in a literature review of 5,577 patients (19247). Non-specific rashes and itching (19222,19243) as well as toxiderma from the fruits of hawthorn (54670) have also been reported.

Gastrointestinal ...Orally, rare abdominal discomfort of uncertain relationship to hawthorn has been reported in a large clinical trial, surveillance study, case reports, and a literature review (19247,54640,54692,113112). Digestive intolerance (19241), diarrhea (19243,113112), flatulence (8281), gastroenteritis (8281), increased bowel movements (19243), obstipation (8281), mild and rare nausea (10144,19247,19244), vomiting (113112), nutritional and metabolic problems (17203), and other non-specific gastrointestinal effects (19222), have also been reported. Furthermore, gastrointestinal hemorrhage has been reported in two patients with CHF in a literature review of 5,577 patients (19247).

Musculoskeletal ...In clinical trials, arthritis (8281), back pain (8281), weakness (19243), and other non-specific musculoskeletal effects (19222) have been reported following the use of various hawthorn preparations g. WS 1442, CKBM-A01). Additionally, in a case report, myalgia has been reported following use of hawthorn root extract (113113).

Neurologic/CNS ...Orally, headache and dizziness/vertigo were reported in 2 patients in a large surveillance trial of 3,664 patients with cardiac failure (54692), in 15 patients with CHF as reported in a literature review of 5,577 patients (19247), in a varying number of clinical trial participants (8281,19222,19244), and in case reports (113112,113113). Incidences of fainting (19222), fever (17203), and infrequent, mild and transient sleepiness have also been reported (19221,54692).

Psychiatric ...Orally, agitation was reported in a large surveillance trial of 3,664 patients with cardiac failure (54692).

Pulmonary/Respiratory ...Orally, bronchitis has been reported following the use of hawthorn extract WS 1442 (8281), and bradypnea has been reported following the use of hawthorn root extract (113112).

Renal ...A case of multiorgan hypersensitivity reaction and acute renal failure following the consumption of C. orientalis has been reported (54654).

Other ...Flu-like syndrome (8281) and other non-specific infections have been reported following the use of the hawthorn extract WS 1442 (17203,19222). Hawthorn has also been reported to cause nosebleeds (8281,10144).

(Read more about HAWTHORN)

General ...There is limited information about the adverse effects of linden. Orally, there is one case report of allergic reaction to linden pollen in a linden flower tea (12). Frequent consumption of linden tea is thought to be associated with cardiac damage, but this seems to be rare (6).
Topically, linden extract can cause contact urticaria (12).

Cardiovascular ...Frequent consumption of linden tea is thought to be associated with cardiac damage, but this seems to be rare (6).

Immunologic ...Orally, there is one case report of allergic reaction to linden pollen in a linden flower tea (12). Topically, there is one case report of contact urticaria following the use of a linden extract-containing shampoo (12).

(Read more about LINDEN)

General ...Orally, olive fruit is well tolerated when used in typical food amounts. Olive leaf extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Headache and stomach discomfort.

Dermatologic ...Orally, one patient in one clinical trial reported bad skin and acne after using olive leaf extract (101860).

Gastrointestinal ...Orally, three patients in one clinical trial reported stomach ache after using olive leaf extract (101860).

Neurologic/CNS ...Orally, three patients in one clinical trial reported headache after using olive leaf extract (101860).

Psychiatric ...In one case report, a 67-year-old female experienced irritability, anger, a lack of control, and feelings of sadness and negativity after consuming a multi-ingredient product containing olive leaf extract 5 grams, horseradish root, and eyebright daily for 38 days. All psychiatric symptoms disappeared within days of stopping the combined product. It is hypothesized that the hydroxytyrosol component of olive leaf extract contributed to these symptoms due to its chemical similarity to dopamine; however, it is not clear if these symptoms were due to the olive leaf extract or to the other ingredients (96245).

Pulmonary/Respiratory ...Olive tree pollen can cause seasonal respiratory allergy (1543).

(Read more about OLIVE)