Blood Sugar Balance [Discontinued] by Eclectic Institute

POSSIBLY INEFFECTIVE

• Night vision. Most research suggests that oral bilberry does not improve night vision in healthy individuals. Details: There is contradictory evidence about the effectiveness of bilberry for improving night vision; however, much of the research is of poor quality. In general, the most rigorous research shows that bilberry is not effective for improving night vision in healthy individuals (8139,9739,14280,35446). Whether bilberry can improve night vision in patients with night blindness is unclear.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. Oral bilberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study of elderly Norwegian males with subjective cognitive impairment shows that drinking 330 mL of bilberry and red grape juice twice daily for 9 weeks does not improve measures of memory or motor skills when compared with placebo (110641).
• Age-related macular degeneration (AMD). Although there has been interest in using oral bilberry for AMD, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Asthenopia (eye strain). Small clinical studies suggest that oral bilberry fruit extract may improve objective measures of asthenopia, but it is unclear if oral bilberry improves subjective symptoms of asthenopia. Details: Two small clinical studies in adults who report general eye strain or those who look at computer or other display screens at work for long periods of time show that taking bilberry-derived anthocyanins 43.2 mg daily for 6 weeks or bilberry extract 240 mg daily for 12 weeks improves objective measures of eye strain after staring at computer screens when compared with placebo (103190,104195). However, bilberry extract did not improve subjective measures of eye strain in the study that evaluated these outcomes (104195). This study may have been underpowered to detect significant differences between groups. Bilberry has also been evaluated in combination with other ingredients for improving eye strain. A small clinical trial in patients with eye strain shows that a combination of fish oil, lutein, and bilberry extract containing bilberry anthocyanidins 59 mg, taken daily for 4 weeks, reduces dry eye, lower back pain, shoulder stiffness, and stuffy head when compared with placebo (35470). It is unclear if these effects are due to bilberry, other ingredients, or the combination.
• Atherosclerosis. Although there has been interest in using oral bilberry for atherosclerosis, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Cataracts. Although there has been interest in using oral bilberry for cataracts, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Chronic venous insufficiency (CVI). It is unclear if oral bilberry is beneficial in patients with CVI. Details: One small clinical study in patients with CVI shows that taking bilberry extract containing anthocyanins 173 mg daily for 30 days reduces symptoms of CVI when compared with placebo (35510).
• Diabetes. It is unclear if oral bilberry is beneficial in patients with diabetes. Details: One small clinical trial in patients with type 2 diabetes shows that taking a specific extract of bilberry fruit (Mirtoselect, Indena S.p.A) 470 mg once, prior to taking an oral glucose tolerance test, lowers plasma glucose levels when compared with placebo (91507). However, a small crossover trial in Chinese patients with type 2 diabetes shows that taking bilberry fruit extract 700 mg twice daily for 4 weeks does not improve glycated hemoglobin (HbA1c), body weight, blood pressure, or lipid levels when compared with placebo (104194). The validity of the HbA1c-related findings is limited due to the short study duration.
• Diabetic retinopathy. It is unclear if oral bilberry is beneficial in patients with diabetic retinopathy. Details: One small clinical trial in adults with diabetic and hypertensive retinopathy shows that taking bilberry fruit extract 160 mg daily for 6 months, in addition to standard management, improves edema and measures of retinal circulatory health when compared with standard management alone. Bilberry in the form of a generic, commercially available product appears to produce less dramatic improvements than a branded formulation (Mirtoselect, Indena S.p.A.) containing matching anthocyanin content. This specific product also reduced flow velocity in those with high-flow, diabetic retinopathy when compared with either the generic bilberry extract or standard management alone (97032).
• Dry eye. Oral bilberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with severe dry eye symptoms suggests that taking bilberry extract 600 mg and docosahexaenoic fish oil 240 mg once daily for 3 months may modestly improve measures of tear quality and patient-reported scores for dry eye symptoms when compared with control (112415). However, the validity of these results is limited by the lack of a statistical comparison between groups. Additionally, it is unclear if these effects are due to bilberry, fish oil, or the combination.
• Dysmenorrhea. It is unclear if oral bilberry is beneficial in patients with dysmenorrhea. Details: One small clinical study in patients with dysmenorrhea shows that a specific bilberry product (Tegens) containing bilberry anthocyanoside 160 mg, taken twice daily beginning 3 days prior to menses and continuing for 8 days, reduces pelvic pain, lumbosacral pain, breast pain, nausea, vomiting, and headache when compared with placebo (35512).
• Exercise-induced muscle soreness. It is unclear if oral bilberry is beneficial for reducing exercise-induced muscle soreness. Details: A small clinical study in trained athletes shows that drinking 200 mL of bilberry juice, containing about 744 mg phenols and 80 mg anthocyanins, twice daily for 5 days prior to running a half-marathon modestly worsens muscle soreness immediately after the run when compared with placebo. There was no longer a difference in muscle soreness between groups within 1-2 days after the run (99540).
• Glaucoma. Small clinical studies suggest that oral bilberry fruit extract, when taken with maritime pine extract, may lower intraocular pressure in patients with glaucoma. It is unclear if oral bilberry alone is beneficial in patients with glaucoma. Details: One small, uncontrolled clinical trial in Japanese patients with open-angle glaucoma shows that taking a specific product (Sante Glagenox, Saten Pharmaceutical Co. Ltd.) containing bilberry fruit extract 90 mg and maritime pine extract 40 mg daily for 4 weeks reduces intraocular pressure by 8.7% when compared to baseline (104192). Another small clinical study in patients with high intraocular pressure shows that taking a specific product (Mirtogenol) containing bilberry fruit extract (Mirtoselect, Indena S.p.A.) 80 mg and maritime pine extract (Pycnogenol, Horphag Research) 40 mg twice daily for 6 months lowers intraocular pressure and improves intraocular blood flow when compared with no treatment (35456). It is unclear if these findings are due to bilberry, maritime pine, or the combination. A retrospective chart review of patients with normal tension glaucoma has found that taking bilberry anthocyanin 60 mg twice daily for at least 12 months is associated with improvements in visual function when compared to pretreatment (35472).
• Hemorrhoids. Although there has been interest in using oral bilberry for hemorrhoids, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Hyperlipidemia. It is unclear if oral bilberry is beneficial in patients with hyperlipidemia. Details: A small clinical study in adults with hyperlipidemia shows that taking bilberry-derived anthocyanins 320 mg daily for 4 weeks does not improve total cholesterol, low-density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, or triglyceride levels. Further, no improvements in other biomarkers of cardiovascular disease were reported (110640). The validity of this study is limited by its short duration.
• Hypertension. Oral bilberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in adults with hypertension shows that consuming 500 mL of a juice containing bilberry, red grape, and chokeberry, with or without black currant (MANA Blue, TINE SA), daily for 12 weeks does not improve blood pressure when compared with placebo (92371).
• Hypertensive retinopathy. It is unclear if oral bilberry is beneficial in patients with hypertensive retinopathy. Details: One small clinical trial in adults with diabetic and hypertensive retinopathy shows that taking bilberry fruit extract 160 mg daily for 6 months, in addition to standard management, improves edema and measures of retinal circulatory health when compared with standard management alone. Bilberry in the form of a generic, commercially available product appears to produce less dramatic improvements than a branded formulation (Mirtoselect, Indena S.p.A.) containing matching anthocyanin content. This specific product also increased flow velocity for those with ischemic, hypertensive retinopathy when compared with either the generic bilberry extract or standard management alone (97032).
• Impaired glucose tolerance (prediabetes). Oral bilberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with impaired glucose tolerance and two markers of metabolic syndrome shows that consuming a diet high in whole grain products, fatty fish, and bilberries three times daily for 12 weeks reduces levels of plasma glucose when compared to baseline (35468). However, it is unclear if these findings are due to bilberry, another component of the diet, or the combination.
• Irritable bowel syndrome (IBS). Oral bilberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in adults with IBS shows that consuming a formula containing powdered bilberry fruit, aerial agrimony parts, cinnamon quills, and slippery elm bark modestly improves bowel movement frequency and reduces symptoms such as abdominal pain, bloating, flatulence, and straining when compared to baseline (35462). It is unclear if these findings are due to bilberry, other ingredients, or the combination.
• Metabolic syndrome. It is unclear if oral bilberry is beneficial in patients with metabolic syndrome. Details: One small clinical study in patients with metabolic syndrome shows that consuming a diet containing 400 grams of fresh bilberries daily does not affect body weight, glucose metabolism, or lipid metabolism when compared with a control diet (35473).
• Myopia. It is unclear if oral bilberry is beneficial in patients with myopia. Details: One small clinical trial in adults with myopia shows that a specific fermented bilberry fruit extract (Fermented Blueberry, Ajinomoto, Co., Inc.) 200 mg, taken twice daily for 4 weeks, improves night vision as well as the eye's ability to adjust focus when compared with placebo. The amplitude of accommodation was also significantly increased from 4.62 to 5.33 (91505).
• Obesity. It is unclear if oral bilberry is beneficial in patients with obesity. Details: One small clinical study in obese and overweight females shows that consuming 100 grams of frozen, whole bilberries daily for 33-35 days decreases weight and waist circumference when compared to baseline (35463). The validity of these findings is limited by the lack of a comparator group.
• Osteoarthritis. Although there has been interest in using oral bilberry for osteoarthritis, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Ulcerative colitis. It is unclear if oral bilberry is beneficial in patients with ulcerative colitis. Details: One small, open-label clinical study in adults with mild-to-moderate ulcerative colitis shows that consuming sieved bilberries and concentrated bilberry juice (Symrise GmbH & Co) 160 grams daily for 6 weeks induces remission in 46% of patients. Furthermore, 91% of patients achieved remission at the end of treatment, and 72% of patients achieved remission at the end of the study (91506). The validity of these findings is limited by the lack of a comparator group.
• Urinary tract infections (UTIs). Although there has been interest in using oral bilberry for UTIs, there is insufficient reliable information about the clinical effects of bilberry for this purpose.
• Varicose veins. Although there has been interest in using oral bilberry for varicose veins, there is insufficient reliable information about the clinical effects of bilberry for this purpose. More evidence is needed to rate bilberry for these uses.

(Read more about BILBERRY)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Amenorrhea. Although there is interest in using oral bitter melon for amenorrhea, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• Athletic performance. It is unclear if oral bitter melon is beneficial for improving athletic performance. Details: Preliminary clinical research in ten male tennis players taking part in high-intensity training at high temperatures shows that taking bitter melon extract orally, 100 mL six times daily for 4 weeks, improves some biomarkers of fatigue and physical fitness parameters including balance, flexibility, and cardiorespiratory fitness when compared with baseline. Levels of adrenocorticotrophic hormone and cortisol are decreased, suggesting a reduction in oxidative stress (103295,106407). The validity of these results is limited by the lack of a comparator group.
• Constipation. Although there is interest in using oral bitter melon for constipation, there is insufficient reliable information about the clinical effects of bitter melon for this purpose.
• Diabetes. Although some research suggests that bitter melon may improve glycemic control in adults with type 2 diabetes, evidence is conflicting and of limited quality. Details: A meta-analysis of 10 low-quality studies in patients with type 2 diabetes shows that taking bitter melon powdered whole fruits or juice in doses of 0.5 to 12 grams daily for 4-16 weeks reduces fasting blood glucose (FBG) by 13 mg/dL, postprandial glucose by 26 mg/dL, and glycated hemoglobin (HbA1c) by 0.26% when compared with placebo (100632). Another meta-analysis, pooling the results of 7 trials in patients with type 2 diabetes, shows that bitter melon modestly reduces HbA1c by 0.3% and FBG by 14 mg/dL when compared with no treatment, but a separate analysis of 2 other trials shows that bitter melon does not improve either outcome when compared with oral antidiabetic drugs (111503). Additionally, a meta-analysis of 3 clinical trials shows that taking bitter melon 1-6 grams daily for 4-12 weeks does not significantly improve fasting plasma glucose or HbA1c when compared with placebo in patients with type 2 diabetes (92124). Some other clinical research in patients with type 2 diabetes shows that bitter melon fruit, fruit pulp, fruit juice, and extract improve glucose tolerance and insulin secretion, reduce blood glucose levels, and lower HbA1c (34,35,36,38,12530). One clinical study shows that taking powdered bitter melon fruit 2-4 grams daily for 10 weeks lowers HbA1c similarly to glyburide 2.5 mg daily (92126). Reasons for the discrepancies among the evidence are not clear but may relate to the small study sizes, shorter durations of treatment, and varying dosages and formulations of bitter melon.
• Dyspepsia. Although there is interest in using oral bitter melon for dyspepsia, there is insufficient reliable information about the clinical effects of bitter melon for this purpose.
• Genital herpes. Although there is interest in using topical bitter melon for genital herpes, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• HIV/AIDS. Although there is interest in using oral bitter melon for HIV/AIDS, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• Impaired glucose tolerance (prediabetes). It is unclear if oral bitter melon is beneficial in patients with prediabetes. Details: A small clinical study in patients with impaired glucose tolerance shows that drinking a beverage containing bitter melon extract 1.25-3 grams as a single dose does not affect blood glucose or insulin response when compared with baseline (97508). A moderate-sized clinical study in adults with prediabetes shows that taking bitter melon (SugarKatcherS52, Kolmar BNH) 800 mg three times daily for 12 weeks reduces blood glucose by 22 mg/dL two hours after oral glucose tolerance test when compared with placebo, but does not improve insulin, C-peptide, or glucagon levels, nor markers of insulin resistance (112372). The validity of these results is limited by the lack of statistical adjustment for multiple comparisons which can lead studies to erroneously show differences between treatment groups (i.e., false positive findings).
• Intestinal parasite infection. Although there is interest in using oral bitter melon for intestinal parasite infection, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• Kidney stones (nephrolithiasis). Although there is interest in using oral bitter melon for kidney stones, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• Liver disease. Although there is interest in using oral bitter melon for liver disease, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• Metabolic syndrome. Although there is interest in using oral bitter melon for metabolic syndrome, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• Obesity. It is unclear if oral bitter melon is beneficial for weight loss. Details: A very small clinical study in patients with obesity shows that taking bitter melon 1 gram twice daily for 12 weeks does not reduce body weight, body mass index (BMI), waist circumference, or body fat percentage when compared to baseline. However, when compared with placebo, body weight and BMI were reduced by around 4 kg and 1.6 kg/m², respectively. Patients in the placebo group experienced an increase in these measures (109583).
• Osteoarthritis. It is unclear if oral bitter melon is beneficial in patients with osteoarthritis. Details: A small preliminary clinical study in patients with osteoarthritis shows that taking bitter melon 1500 mg three times daily for 3 months reduces the need for rescue analgesic medications when compared with placebo. However, subjective scores of osteoarthritis symptoms improved similarly in both groups (100631).
• Peptic ulcers. Although there is interest in using oral bitter melon for peptic ulcers, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• Polycystic ovary syndrome (PCOS). Although there is interest in using oral bitter melon for PCOS, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• Psoriasis. Although there is interest in using oral bitter melon for psoriasis, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• Ulcerative colitis. Although there is interest in using oral bitter melon for ulcerative colitis, there is insufficient reliable information about the clinical effects of bitter melon for this condition.
• Wound healing. Although there is interest in using topical bitter melon for wound healing, there is insufficient reliable information about the clinical effects of bitter melon for this purpose. More evidence is needed to rate bitter melon for these uses.

(Read more about BITTER MELON)

There is insufficient reliable information available about the effectiveness of devil's club.

(Read more about DEVIL'S CLUB)

POSSIBLY EFFECTIVE

• Obesity. Oral Phaseolus vulgaris extract may reduce body weight and waist circumference in overweight and obese adults. Details: A meta-analysis of 6 small clinical studies shows that taking Phaseolus vulgaris extract daily for 4-12 weeks reduces body weight by around 1.6% when compared with placebo (107439). While some small studies show conflicting findings (12186,26158), most research in overweight and obese adults suggests that taking white kidney bean extract 800-1000 mg or cranberry bean extract 100 mg three times daily for 5-12 weeks reduces body weight by 1.5-4 kg, body mass index by about 0.7 kg/m2, and waist circumference by about 1.5-5 cm when compared with placebo or other control (26156,29926,93075,93077,104875). Specific products evaluated include Phase 2 (Pharmachem Labs; also marketed as Starchlite and Phaselite) (26156,29926); Carb Intercept with Phase 2 (Natrol LLC) (93075); and Beanblock (Indena S.p.A) (93077). Phaseolus vulgaris extract has also been evaluated in combination with other ingredients, with modestly positive results. These combination products include Blokcal (Pharmachem Labs) containing white kidney bean extract (Phase 2, Pharmachem Labs) 445 mg daily and elemental chromium 50-60 mcg daily for 30 days (15518); Suco-Bloc (Med-Eq), containing white kidney bean extract (Phaseolamin, Leuven Bioproducts) 200 mg, inulin from chicory root (Raftiline, Orafti SA) 200 mg, and garcinia extract 50 mg per tablet, 2 tablets three times daily with meals for 12 weeks (26157); Phaseolamin 1600 diet (Metabolic Inc.), containing the Phaseolus vulgaris constituent phaseolamin 750 mg with clove 200 mg, lysine 20 mg, arginine 20 mg, and alanine 20 mg, taken in two divided doses daily for 8 weeks (93076); and Bonvit (Indena), containing Phaseolus vulgaris extract 100 mg and artichoke 200 mg three times daily for 8 weeks (93080).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Colorectal cancer. It is unclear if oral Phaseolus vulgaris is beneficial for the prevention of colorectal cancer recurrence. Details: Observational research has found that dietary intake of several varieties of Phaseolus vulgaris, including baked beans, kidney beans, pinto beans, lima beans, and navy beans, is inversely associated with the risk of advanced colorectal adenoma recurrence. Results from the study show that the odds for advanced adenoma recurrence is 65% lower for patients who consume higher amounts of Phaseolus vulgaris when compared with those who consume lower amounts (29922).
• Diabetes. Small clinical studies suggest that oral Phaseolus vulgaris may not improve postprandial glucose levels in patients with type 2 diabetes. Details: While results from some small clinical studies in patients with type 2 diabetes suggest that taking Phaseolus vulgaris extract or consuming Phaseolus vulgaris beans can reduce postprandial glucose levels, most studies, including a meta-analysis of 6 small clinical trials, show that Phaseolus vulgaris does not significantly reduce postprandial glucose when compared with placebo or other control (93078,107439). Another small clinical study in patients with type 2 diabetes shows that taking 15 grams of a combination of Phaseolus vulgaris pod, white mulberry, and bilberry three times daily for 2 months decreases blood glucose by up to 24% when compared with baseline (33943). It is unclear if these findings are due to Phaseolus vulgaris, other ingredients, or the combination. Additionally, the validity of these findings is limited by the lack of a control group.
• Hypercholesterolemia. Oral Phaseolus vulgaris has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small, open-label clinical study in overweight and obese patients shows that taking Phaseolus vulgaris (white kidney bean) extract 300-600 mg plus carob gum extract 50-100 mg three times daily for 3-9 months modestly reduces total cholesterol levels and increases excretion of fat in the feces when compared to baseline (10633). The validity of these findings is limited by the lack of a comparator group.
• Kidney stones (nephrolithiasis). It is unclear if oral Phaseolus vulgaris extract is beneficial in patients with kidney stones. Details: A small clinical study in adults with small kidney stones shows that taking a Phaseolus vulgaris extract made from 250 grams of green beans three times a week for 6 weeks modestly reduces the size of kidney stones and lowers urinary calcium and oxalate levels when compared with a control group (104874).
• Lung cancer. It is unclear if oral Phaseolus vulgaris is beneficial for the prevention of lung cancer. Details: Observational research has found that consuming higher amounts of dietary phytoestrogens, such as isoflavones from Phaseolus vulgaris beans and soy, is associated with a 44% to 72% lower risk of developing lung cancer when compared with consuming lower amounts. The beneficial effect appears to be more pronounced in males than females (13190).
• Myocardial infarction (MI). Although there has been interest in using oral Phaseolus vulgaris for the prevention of MI, there is insufficient reliable information about the clinical effects of Phaseolus vulgaris for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral Phaseolus vulgaris for UTIs, there is insufficient reliable information about the clinical effects of Phaseolus vulgaris for this purpose. More evidence is needed to rate Phaseolus vulgaris for these uses.

(Read more about PHASEOLUS VULGARIS)

POSSIBLY EFFECTIVE

• Diabetes. Oral prickly pear cactus might help reduce postprandial blood glucose in patients with diabetes. Details: Some preliminary clinical research shows that prickly pear cactus decreases blood glucose levels in patients with type 2 diabetes. Single doses can decrease blood glucose levels by 17% to 48% in some patients (14807,65322,65326). For example, one small clinical study in adults with diabetes shows that adding prickly pear cactus to breakfast meals decreases postprandial glucose when compared with the equicaloric breakfast meals without prickly pear cactus (14807). However, it is not known if long-term use consistently lowers blood glucose levels and decreases glycated hemoglobin (HbA1c) levels.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral prickly pear cactus prevents age-related cognitive decline in older adults. Details: A small clinical study in healthy adults 55 years and older living in Korea shows that taking ethanolic prickly pear pad extract 960 mg (containing about 0.5 mg dihydrokaempferol) daily for 12 weeks does not affect performance on cognitive tests when compared with placebo. However, in a subgroup of patients 70 years or younger, there was a small improvement on certain cognitive tests when compared with placebo (105903).
• Benign prostatic hyperplasia (BPH). It is unclear if oral prickly pear cactus is beneficial in patients with BPH. Details: Preliminary clinical research shows that some patients with BPH who take powdered prickly pear cactus flowers 500 mg three times daily for 2-8 months have subjective improvements in symptoms such as urgency and feelings of fullness in the bladder (12175).
• Familial hypercholesterolemia. It is unclear if oral prickly pear cactus is beneficial in patients with BPH. Details: One very small clinical study in patients with familial hypercholesterolemia shows that consuming prickly pear cactus pulp 250 grams daily for 4 weeks, in combination with dietary intervention, reduces total cholesterol by 30 mg/dL and low-density lipoprotein (LDL) cholesterol by 34 mg/dL when compared to baseline. However, taking prickly pear cactus does not improve high-density lipoprotein (HDL) cholesterol or triglyceride levels in these patients (65274). The validity of this finding is limited by the lack of a comparator group.
• Dyspepsia. Oral prickly pear cactus 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 prickly pear cactus and olive extract (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 the benefit is from prickly pear cactus, olive, or the combination. It is also unclear if this benefit would occur in patients with clinically diagnosed dyspepsia.
• Hangover. It is unclear if oral prickly pear cactus is beneficial in patients with hangover. Details: A small clinical study in healthy adults shows that taking 1600 IU of a specific prickly pear cactus fruit extract (Tex-OE, Extracts Plus Inc.) as a single dose 5 hours prior to binge alcohol consumption does not reduce overall hangover symptoms when compared with placebo. However, it may help to reduce specific symptoms such as nausea, anorexia, and dry mouth when compared with placebo. Furthermore, there was a 62% lower odds of severe hangover in the prickly pear cactus group when compared with placebo (12085).
• Hypercholesterolemia. It is unclear if oral prickly pear cactus lowers cholesterol levels. Details: A small clinical study in patients with primary isolated hypercholesterolemia or combined hyperlipidemia shows that, when used in combination with a Step 1 diet, taking prickly pear cactus pulp 250 grams daily can reduce total cholesterol by 12%, low-density lipoprotein (LDL) cholesterol by 15%, and triglycerides by 12%; however, levels of high-density lipoprotein (HDL) cholesterol do not seem to be affected (65263). It is unclear how these results compare to the control group.
• Metabolic syndrome. It is unclear if oral prickly pear cactus is beneficial in patients with metabolic syndrome. Details: One small clinical study in females with metabolic syndrome shows that taking a specific dehydrated prickly pear cactus pad product (NeOpuntia, Bio Serae) 4.8 grams in 3 divided doses daily for 6 weeks does not affect blood lipid levels when compared with placebo (65293). Another small study in adults with 1-2 risk factors for metabolic syndrome shows that consuming durum wheat pasta 500 mg, containing prickly pear cactus pad extract 3%, weekly for 1 month modestly reduces waist circumference, blood glucose, and triglycerides, but not other lipid parameters or weight, when compared with baseline (105902). The validity of these findings is limited by the lack of a comparator group.
• Obesity. It is unclear if oral prickly pear cactus is beneficial for weight loss. Details: A meta-analysis of 4 clinical trials shows that taking prickly pear cactus orally for 8 weeks to 2 years does not improve weight loss when compared with placebo. However, the results of this analysis are limited by the low methodological quality and small sample sizes of many of the included studies (92146). Studies in the meta-analysis used prickly pear cactus pads 3-15 grams daily for up to 2 years or prickly pear cactus fruit skin extract 400 mg daily for 16 weeks. Specific prickly pear cactus pad products included NeOpuntia (Bio Serae) 4.8 grams daily and Litramine (InQpharm North America LLC) 3 grams daily (92146). More evidence is needed to rate prickly pear cactus for these uses.

(Read more about PRICKLY PEAR CACTUS)

LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods. Bilberry has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately for medicinal purposes. Bilberry fruit extracts have been used with apparent safety in clinical trials at a dose of up to 160 mg daily for up to 6 months (39,40,8139,9739,14280,35472,35510,35512,103190,104192,104195). A higher bilberry extract dose of 1.4 grams daily has been used with apparent safety for up to 4 weeks (104194). Whole bilberries or bilberry juice have also been consumed with apparent safety in quantities of 100-160 grams daily for up to 35 days (35463,91506).

POSSIBLY UNSAFE ...when the leaves are used orally in high doses or for a prolonged period. Death can occur with chronic use of 1.5 gram/kg daily (2).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in the amounts commonly found in foods. However, there is insufficient reliable information available about the safety of bilberry when used in medicinal amounts during pregnancy and lactation; avoid using.

(Read more about BILBERRY)

POSSIBLY SAFE ...when the fruit is used orally and appropriately, short-term. Powdered bitter melon fruit 0.5-12 grams daily for up to 4 months has been used (92126,100631,100632,109583). Extracts of bitter melon fruit have also been used safely for up to 3 months (36,15566,106408). There is insufficient reliable information available about long-term use of bitter melon or the safety of bitter melon when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used orally. Animal research shows that two proteins isolated from the raw fruit of bitter melon possess abortifacient properties (3724,35719,35722,35728). Also, one animal study shows that bitter melon juice significantly reduces the fertility rate of mice (35728). However, these effects of bitter melon have not been assessed in humans.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about BITTER MELON)

There is insufficient reliable information available about the safety of devil's club.

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

(Read more about DEVIL'S CLUB)

POSSIBLY SAFE ...when used orally and appropriately. Most research has evaluated a specific Phaseolus vulgaris (white kidney bean) extract (Phase 2, Pharmachem Labs), which appears to be safe in doses of up to 3 grams daily for 2-3 months (12186,15518,26157,29926). Other Phaseolus vulgaris (white kidney bean) extracts also seem to be safe in doses of 0.9-2.4 grams daily when used for up to 3 months (10633,104875).

POSSIBLY UNSAFE ...when large amounts of fresh Phaseolus vulgaris husks are ingested. Raw Phaseolus vulgaris husks contain lectins that can cause gastrointestinal upset. Cooking destroys the lectins (18).

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

(Read more about PHASEOLUS VULGARIS)

LIKELY SAFE ...when prickly pear cactus fruit and pads are used orally as a food (5969).

POSSIBLY SAFE ...when prickly pear cactus fruit and pads are used orally and appropriately in supplemental amounts, short-term. Prickly pear cactus fruit pulp 250 grams twice daily has been used with apparent safety for up to 2 weeks (12086) and prickly pear cactus pads 3-15 grams daily have been used with apparent safety for up to 2 years (92146). Extracts of prickly pear fruit skin 400 mg daily or prickly pear pads 960 mg daily have been used with apparent safety for 12-16 weeks (92146,105903).

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

(Read more about PRICKLY PEAR CACTUS)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bilberry fruit extract might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro, animal, and clinical research suggest that anthocyanidin extracts from bilberry can inhibit platelet aggregation (16631,35455,35503,35504,35505).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bilberry leaf or fruit extract may increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal research suggests that bilberry leaf extract might have blood glucose-lowering activity (1264). Also, one small clinical trial in patients with type 2 diabetes shows that taking bilberry fruit extract 470 mg as a single dose prior to an oral glucose tolerance test lowers plasma glucose levels when compared with placebo (91507).

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bilberry fruit extract might decrease levels of drugs metabolized by CYP2E1.  Details Animal research shows that exposure to small concentrations of bilberry extract in drinking water for around one month increased CYP2E1 activity by 31%. However, exposure over a 2-month period did not increase CYP2E1 activity (103191). This effect has not been reported in humans.

ERLOTINIB (Tarceva) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bilberry fruit extract might reduce the efficacy of erlotinib.  Details In vitro research suggests that bilberry fruit extract and its constituents, delphinidin and delphinidin-3-O-glucoside, inhibit the activity of erlotinib (97031). This interaction has not been reported in humans.

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Taking bitter melon with antidiabetes drugs might increase the risk of hypoglycemia.  Details Bitter melon can lower blood glucose levels and might have additive effects when used with antidiabetes drugs (34,35,36,38,8181,12530,92124,92126,92129,100632,111503). This might increase the risk of hypoglycemia in some patients. Monitor blood glucose levels closely.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bitter melon might increase levels of P-glycoprotein substrates.  Details Bitter melon might inhibit the p-glycoprotein (P-gp) intestinal pump and increase intracellular levels of P-gp substrates. In vitro research in intestinal cells shows that 1-monopalmitin, a constituent of bitter melon, increases levels of daunomycin, a P-gp substrate (97509). Additionally, drinking bitter melon juice has been associated with a case of acute pancreatitis in a patient who had been taking pazopanib, a P-gp substrate, for 8 years. Researchers theorize that inhibition of P-gp led to increased levels of pazopanib, resulting in pazopanib-induced pancreatitis (109581).

PAZOPANIB (Votrient) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bitter melon might increase levels of pazopanib, potentially increasing the risk of adverse effects.  Details In one case, a 65-year-old patient taking pazopanib for 8 years for renal cell carcinoma experienced signs and symptoms consistent with acute pancreatitis 4 days after drinking bitter melon juice at a dose of 100-150 mL daily. The patient's symptoms, amylase levels, and lipase levels improved upon discontinuation of bitter melon and pazopanib. Pazopanib treatment was re-initiated with no further evidence of pancreatitis. Researchers theorize that inhibition of P-glycoprotein by bitter melon led to increased levels of pazopanib, a P-glycoprotein substrate, resulting in pazopanib-induced pancreatitis (109581).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Phaseolus vulgaris might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Small clinical studies suggest that Phaseolus vulgaris beans or bean pods, ingested alone or along with white mulberry leaf and bilberry, reduce blood glucose levels in some patients with diabetes (29921,29925,33943).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Combining prickly pear cactus with antidiabetes drugs might increase the risk of hypoglycemia.  Details Case reports show that combining prickly pear cactus with antidiabetes drugs such as chlorpropamide, glyburide, glipizide, and metformin can increase the risk of hypoglycemia in patients with type 2 diabetes (5968,14806,17226,65319,92146). Advise patients to monitor glucose levels closely. Dose adjustments may be necessary.

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General ...Orally, bilberry fruit, juice, and extracts seem to be well tolerated.
Most Common Adverse Effects:
Orally: Dark-colored stools, flatulence, and gastrointestinal discomfort.

Gastrointestinal ...In one small clinical trial, mild-to-moderate flatulence was reported in 33% of patients taking sieved bilberries and concentrated bilberry juice (91506). However, the patients in this study had ulcerative colitis, and the study lacked a control group, limiting the validity of this finding. In another small clinical study of males with age-related cognitive impairment, temporary adverse gastrointestinal (GI) effects were reported in 13% of patients drinking a combination of bilberry and grape juice. However, the adverse GI effect rate was identical in patients drinking a placebo juice (110641). A post-marketing surveillance report of 2295 patients using bilberry extract (Tegens) found that 1% of patients complained of GI discomfort and less than 1% experienced nausea or heartburn (35500).
Theoretically, fresh bilberry fruit may have laxative effects. One clinical trial noted an increased frequency of bowel movements following the administration of a combination formulation containing aerial agrimony parts, cinnamon quills, powdered bilberry fruit, and slippery elm bark (35462). It is unclear if these effects were due to bilberry, other ingredients, or the combination.

Other ...Orally, bilberry may cause discoloration of feces and the tongue. In one study, a dark-bluish to black discoloration of both the feces and the tongue was observed following consumption of sieved bilberries and concentrated bilberry juice. In one patient, a slight discoloration of the teeth has also been observed (91506). In another study, 50% of patients reported dark green stools after taking bilberry extract 700 mg twice daily for 4 weeks (104194).

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General ...Orally, bitter melon is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, constipation, diarrhea, dizziness, fatigue, flatulence, headache, heartburn, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Hypoglycemic coma and seizures (in children).

Dermatologic ...In one clinical study, two out of 31 patients taking bitter melon 4 grams daily experienced skin rash. Reports of skin rashes did not occur for patients taking bitter melon 2 grams daily (92126).

Endocrine ...Two cases of hypoglycemic coma have occurred in children after administration of a bitter melon tea (15568).

Gastrointestinal ...The most common adverse effects associated with bitter melon in clinical studies are gastrointestinal, such as heartburn, anorexia, nausea, vomiting, diarrhea, constipation, flatulence, and abdominal discomfort (92126,100632,100633,106408). In one study, these events occurred in about 3% to 16% of patients taking bitter melon (92126).

Neurologic/CNS ...Headaches, dizziness, and fatigue have been reported after the ingestion of bitter melon (15568,92126,100633,112372). In one clinical study, about 5% of patients taking bitter melon 2-4 grams daily reported dizziness (92126). Two cases of seizures have occurred in children after administration of a bitter melon tea (15568).

Renal ...In one case report, a 60-year-old female was diagnosed with acute interstitial nephritis after a gradual decline in renal function over 9 months. The patient later admitted to taking bitter melon extract 600 mg daily for 3 months followed by 1200 mg daily for 4 months for diabetes. Upon discontinuation of bitter melon and treatment with prednisolone, serum creatinine levels returned to baseline within 3 months (109582).

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General ...Orally, devil's club might cause diarrhea, nausea, vomiting, and lightheadedness (95732). Topically, devil's club might cause allergic reactions (47178).

Dermatologic ...The spines on the stems and leaves are known to cause a topical allergic reaction (47178).

Gastrointestinal ...Orally, nausea and vomiting has been reported for an otherwise healthy patient who drank two 80-mL servings of devil's club 5 hours apart. The tea was prepared by boiling devil's club root, bark, and berries for 4-6 hours (95732). Diarrhea and nausea have been reported in some individuals after chewing and swallowing the inner bark of 40 sticks of devil's club (95732).

Neurologic/CNS ...Orally, lightheadedness has been reported for two healthy individuals who drank two to five 80-mL servings of devil's club tea. The tea was prepared by boiling devil's club root and bark, with or without the berries, for 4-6 hours (95732).

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General ...Orally, Phaseolus vulgaris extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, flatulence, nausea, stomach pain, and vomiting.
Serious Adverse Effects (Rare):
Orally: Hypersensitivity reactions, including anaphylaxis, in sensitive individuals.

Dermatologic ...Topically, Phaseolus vulgaris may cause contact dermatitis in sensitive individuals. A case of occupational contact dermatitis characterized by pruritus, erythema, eczema, and dyspnea has been reported for a 41-year-old farmer who handled the green parts of Phaseolus vulgaris (29920).

Gastrointestinal ...Orally, an extract of the Phaseolus vulgaris variety white kidney bean, as well as alpha-amylase inhibitors isolated from Phaseolus vulgaris, might cause nausea, vomiting, diarrhea, flatulence, constipation, satiety, and stomach pains (11265,18223,29925,104874). Also, white kidney bean extract, taken orally along with carob gum, may cause constipation, flatulence, soft stools, and reduced levels of vitamin B12 and folic acid (10633). Consuming large amounts of raw or undercooked Phaseolus vulgaris beans or extract can cause nausea, vomiting, diarrhea, and gastroenteritis due to the content of phytohaemagglutinin, a plant protein lectin (18223,29916,93082). Cooking usually destroys lectins (18).

Immunologic ...Orally, Phaseolus vulgaris may cause hypersensitivity reactions, including anaphylaxis, in sensitive individuals. A case of severe anaphylactic shock requiring epinephrine and steroid treatment has been reported for a 23-year-old following ingestion of cooked kidney beans, a variety of Phaseolus vulgaris. The causative agents were reported to be phaseolin (vicilin) and phytohaemagglutinin (29918). Also, a case of angioedema resulting from type I hypersensitivity has been reported for a one-year-old child following inhalation of vapors from or ingestion of cooked white beans, another variety of Phaseolus vulgaris (29919).

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General ...Orally, prickly pear cactus is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal fullness, dyspepsia, mild diarrhea, nausea.

Dermatologic ...Orally, prickly pear cactus has been linked to rare cases of urticaria and pruritus. In a clinical study of 41 patients taking prickly pear cactus pad ethanolic extract, three patients experienced pruritus and one patient experienced urticaria (105903).

Gastrointestinal ...Orally, prickly pear cactus may cause mild diarrhea, dyspepsia, nausea, increased stool volume and frequency, and abdominal fullness (7028,65266,105903). Cases of low colonic obstruction and rectal phytobezoars resulting in rectal perforation have been reported for patients who ingested prickly pear cactus fruit seeds (65260,65266). However, these events are extremely rare and attributed to the ingestion of a large number of fruits. Because dried prickly pear cactus swells into a mass much larger than its original size, it may potentially cause dangerous blockages of the esophagus or intestines. Similar products have been associated with serious or even fatal blockages, but cases of such blockages from prickly pear cactus are lacking in the scientific literature.

Neurologic/CNS ...Orally, prickly pear cactus has been linked to rare cases of headache, insomnia, and dizziness (65266,105903). In a clinical study of 41 patients taking prickly pear cactus pad ethanolic extract, two patients experienced headache, one patient experienced dizziness, and one patient experienced insomnia (105903).

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