Amazon C F by Raintree Nutrition, Inc.

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.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there is interest in using oral cat's claw for allergic rhinitis, there is insufficient reliable information about the clinical effects of cat's claw for this condition.
• Alzheimer disease. Although there is interest in using oral cat's claw for Alzheimer disease, there is insufficient reliable information about the clinical effects of cat's claw for this condition.
• Asthma. Although there is interest in using oral cat's claw for asthma, there is insufficient reliable information about the clinical effects of cat's claw for this condition.
• Atopic dermatitis (eczema). Oral cat's claw has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that using a specific spray combination of cat's claw (Uncaria tomentosa) 1% and Rhealba oat plantlet extract 0.25% (Pierre Fabre Dermo Cosmetique) up to 6 times daily for 22 days subjectively reduces skin symptoms of atopic dermatitis when compared with baseline (103170). The validity of this finding is limited by the lack of a comparator group. Additionally, it is not clear whether the results are due to cat's claw, oat extract, spray excipients, or the combination.
• Cancer. It is unclear if oral cat's claw is beneficial for improving quality of life in patients with cancer. Details: Preliminary clinical research in patients with terminal advanced solid tumors shows that taking a specific cat's claw (Uncaria tomentosa) extract, standardized to 5% mitraphylline, 100 mg three times daily for at least 8 weeks improves quality of life, social functioning, and fatigue when compared with baseline (92502). The validity of this finding is limited by the lack of a comparator group.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral cat's claw for CFS, there is insufficient reliable information about the clinical effects of cat's claw for this condition.
• Denture Stomatitis. It is unclear if oral cat's claw is beneficial for the treatment of denture stomatitis. Details: In patients with denture stomatitis, a small clinical trial shows that topical application of 2.5 mL of a gel containing cat's claw (Uncaria tomentosa) 2% to the base of dentures three times daily after meals for one week is as effective as miconazole 2% for improvement of symptoms. However, these treatments were also similarly effective to placebo (105186).
• Diarrhea. Although there is interest in using oral cat's claw for diarrhea, there is insufficient reliable information about the clinical effects of cat's claw for this purpose.
• Hemorrhoids. Although there is interest in using oral cat's claw for hemorrhoids, there is insufficient reliable information about the clinical effects of cat's claw for this purpose.
• Human papillomavirus (HPV). Oral cat's claw has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking three tablets of a specific combination supplement containing cat's claw, echinacea, andrographis, grapefruit, papaya, and pau d'arco daily for one month reduces the recurrence of anal condylomata in patients following surgical removal of anal condylomata. After one month, recurrence was 4% in the supplement group compared with 18% in the control group; after six months the recurrence rates were 7% and 27%, respectively (20073). However, the validity of these findings is limited due to poor study methodology. Additionally, it is unclear if this effect is due to cat's claw, other ingredients, or the combination.
• Inflammatory bowel disease (IBD). Although there is interest in using oral cat's claw for ulcerative colitis and Crohn disease, there is insufficient reliable information about the clinical effects of cat's claw for these conditions.
• Osteoarthritis. It is unclear if oral cat's claw is beneficial for osteoarthritis. Details: A small clinical trial shows that taking a specific freeze-dried cat's claw (Uncaria guianensis) extract 100 mg daily orally relieves knee pain related to physical activity within one week of treatment, but does not decrease pain at rest or knee swelling (7317). Other clinical research shows that taking a specific combination supplement (Reparagen) 1800 mg twice daily for 8 weeks can reduce pain and stiffness, improve function, and reduce the need to use rescue medication similarly to glucosamine sulfate. This specific combination supplement contains cat's claw (Vincaria) 300 mg and maca (RNI 249) 1500 mg per dose (33614). It is unclear if this effect is due to cat's claw, maca, or the combination. Additionally, it is unclear how these outcomes compare to the use of placebo.
• Osteoporosis. Although there is interest in using oral cat's claw for osteoporosis, there is insufficient reliable information about the clinical effects of cat's claw for this condition.
• Psoriasis. Oral cat's claw has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that using a specific spray combination of cat's claw (Uncaria tomentosa) 1% and Rhealba oat plantlet extract 0.25% (Pierre Fabre Dermo Cosmetique) up to 6 times daily for 22 days subjectively reduces skin symptoms of psoriasis when compared with baseline (103170). The validity of this finding is limited by the lack of a comparator group. Additionally, it is not clear whether the results are due to cat's claw, oat extract, spray excipients, or the combination.
• Rheumatoid arthritis (RA). It is unclear if oral cat's claw is beneficial for RA. Details: A small clinical trial shows that taking a specific cat's claw (Uncaria tomentosa) extract 20 mg three times daily orally, containing 14.7 mg/gram pentacyclic oxindole alkaloids and no tetracyclic oxindole alkaloids, appears to modestly improve symptoms of RA. When taken orally in combination with sulfasalazine or hydroxychloroquine for 24 weeks, cat's claw seems to reduce the number of painful joints when compared with placebo. However, there is no effect on the number of swollen joints, pain, or the patient assessment of disease (8661). More evidence is needed to rate cat's claw for these uses.

(Read more about CAT'S CLAW)

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

(Read more about SIMARUBA)

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)

POSSIBLY SAFE ...when used orally, short-term. A specific freeze-dried aqueous extract seems to be safe when used in doses of 100 mg daily for up to four weeks (7317). Another extract of cat's claw, free of tetracyclic oxindole alkaloids, seems to be safe when used in doses of 60 mg daily for up to 24 weeks (8661). There is insufficient reliable information available about the safety of cat's claw when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used orally. There is concern that cat's claw might be unsafe based on its traditional use as a contraceptive (12); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about CAT'S CLAW)

There is insufficient reliable information available about the safety of simaruba.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally during pregnancy due to apparent abortifacient effects (18,4500); avoid using. There is insufficient reliable information available about the safety of simaruba during lactation.

(Read more about SIMARUBA)

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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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, cat's claw may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Cat's claw contains rhynchophylline and isorhynchophylline. Animal research suggests that these alkaloids can inhibit platelet aggregation (40220,40276). This interaction has not been reported in humans.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking cat's claw with antihypertensive drugs might increase the risk of hypotension.  Details Cat's claw contains rhynchophylline. In vitro and animal research suggests that rhynchophylline can lower blood pressure (40255,40268,40276). This interaction has not been reported in humans.

CALCIUM CHANNEL BLOCKERS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking cat's claw with calcium channel blockers might increase the risk of hypotension.  Details Cat's claw contains various alkaloids, including rhynchophylline, isorhynchophylline, corynoxeine, and isocorynoxiene. Animal research suggests that these alkaloids can lower blood pressure by acting as calcium channel blockers (40255,40268). This interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cat's claw might increase the levels and adverse effects of drugs metabolized by CYP3A4.  Details In vitro research shows that cat's claw can inhibit CYP3A4 enzymes (6450,25522). In one case report, a patient taking cat's claw (at an unspecified dose) experienced increased serum levels of atazanavir, ritonavir, and saquinavir, all of which are CYP3A4 substrates. Levels returned to normal 15 days after discontinuation of the cat's claw supplement, suggesting inhibition of CYP3A4 by cat's claw (25522).

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(Read more about SIMARUBA)

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).

(Read more about BITTER MELON)

General ...Orally, cat's claw seems to be well tolerated. Topically, no adverse effects have been reported; however, a thorough safety evaluation has not been conducted.
Serious Adverse Effects (Rare):
Orally: Kidney injury.

Dermatologic ...Orally, itchy skin lesions occurred rarely in one clinical study. As the patients in this study had solid tumors with no further therapeutic options, it cannot be determined if any adverse effects were due to the course of disease or to cat's claw. No placebo was used in the study (92502).

Gastrointestinal ...Orally, cat's claw has been reported to cause nausea, vomiting, abdominal pain, abdominal distention, constipation, epigastric pain, and diarrhea in 2% to 10% of individuals in one clinical study. As the patients in this study had solid tumors with no further therapeutic options, it cannot be determined if any adverse effects were due to the course of disease or to cat's claw. No placebo was used in the study (92502).

Hematologic ...In one clinical study of oral cat's claw, anemia occurred in 12% of patients and leukopenia and thrombocytopenia each occurred in 2% of patients. As the patients in this study had solid tumors with no further therapeutic options, it cannot be determined if any adverse effects were due to the course of disease or to cat's claw. No placebo was used in the study (92502).

Neurologic/CNS ...In one clinical study of oral cat's claw, headache occurred in 2% of patients, fatigue and insomnia each occurred in 4% of patients, and neuropathy occurred in 8% of patients. As the patients in this study had solid tumors with no further therapeutic options, it cannot be determined if any adverse effects were due to the course of disease or to cat's claw. No placebo was used in the study (92502).

Renal ...Several case reports link cat's claw to kidney injury. A patient with systemic lupus erythematosus developed acute kidney failure after taking cat's claw, which improved upon its discontinuation (40279). Another patient with a history of cancer who consumed keto-diet shakes containing cat's claw developed biopsy-confirmed acute interstitial nephritis requiring treatment with prednisone. The patient's serum creatinine normalized three months later after stopping the shake (111737). A separate case cited nephrolithiasis linked to a product containing cat's claw (Digestive Advantage and FlexProtex), likely due to its excipient silica dioxide. The patient's symptoms were reduced after discontinuation (40244).
A clinical study also reported a mild serum creatinine increase in 6% of patients taking oral cat's claw, but causality remains unclear due to the advanced disease states of the participants. No placebo was used in the study (92502).

(Read more about CAT'S CLAW)

General ...Orally, ingesting large amounts of simaruba can cause vomiting (18).

Gastrointestinal ...Orally, ingesting large amounts of simaruba can cause vomiting (18).

(Read more about SIMARUBA)