Phytocidal by Ortho Molecular Products

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.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral hu zhang for allergic rhinitis, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Biliary disorders. Although there has been interest in using oral hu zhang for biliary disorders, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Constipation. Although there has been interest in using oral hu zhang for constipation, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Diabetes. Although there has been interest in using oral hu zhang for diabetes, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Gout. Although there has been interest in using oral hu zhang for gout, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Hepatitis. Although there has been interest in using oral hu zhang for hepatitis, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Menopausal symptoms. Although there has been interest in using oral hu zhang for menopausal symptoms, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Osteoarthritis. Although there has been interest in using oral hu zhang for osteoarthritis, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral hu zhang for RA, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Unstable angina. Oral hu zhang has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in patients hospitalized with unstable angina shows that taking hu zhang granules 7.5 grams and hawthorn granules 5 grams twice daily for 4 weeks, along with conventional therapy, improves quality of life and angina symptom scores, but does not reduce the frequency of angina attacks, when compared with conventional therapy alone (109610).
• Wound healing. Although there has been interest in using topical hu zhang for wound healing, there is insufficient reliable information about the clinical effects of hu zhang for this purpose. More evidence is needed to rate hu zhang for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Biliary disorders. Although there has been interest in using oral wormwood for biliary disorders, there is insufficient reliable information about the clinical effects of wormwood for this purpose.
• Crohn disease. Small clinical studies suggest that oral wormwood may modestly improve symptoms in patients with Crohn disease. Details: Preliminary clinical research in patients with Crohn disease shows that taking a specific product (SedaCrohn, Noor Herbals, LLC) containing powdered wormwood 750 mg 2-3 times daily for 6-10 weeks improves quality of life and mood, increases symptom remission, and reduces corticosteroid requirements when compared with placebo (86545,93468). Clinical remission occurred in 8 out of 10 patients taking wormwood, compared with only 2 out of 10 patients taking placebo (93468).
• Depression. Although there has been interest in using oral wormwood for depression, there is insufficient reliable information about the clinical effects of wormwood for this purpose.
• Dyspepsia. Although there has been interest in using oral wormwood for dyspepsia, there is insufficient reliable information about the clinical effects of wormwood for this purpose.
• Gastritis. Although there has been interest in using oral wormwood for gastritis, there is insufficient reliable information about the clinical effects of wormwood for this purpose.
• IgA nephropathy. It is unclear if oral wormwood is beneficial in patients with IgA nephropathy. Details: Preliminary clinical research in patients with IgA nephropathy shows that taking powdered wormwood (Seda-Leukin, Noor Herbals LLC) 600 mg three times daily for 6 months along with standard treatment reduces proteinuria when compared with baseline. The urinary protein:creatinine ratio decreased from 2340 mg/gram to 315 mg/gram over 6 months. Furthermore, systolic and diastolic blood pressures decreased by 10% and 14%, respectively (93469). The validity of these findings is limited by the lack of a comparator group.
• Insect bite. Although there has been interest in using topical wormwood for insect bites, there is insufficient reliable information about the clinical effects of wormwood for this purpose.
• Osteoarthritis. It is unclear if topical wormwood is beneficial in patients with knee osteoarthritis. Details: Preliminary clinical research in patients with knee osteoarthritis shows that applying an ointment or liniment containing wormwood extract 3% to the knee three times daily for 4 weeks might improve pain, although any pain improvement was not maintained 2 weeks after discontinuation. Topical wormwood appears to be less effective than topical piroxicam gel, which improves pain, stiffness, and physical function when compared with baseline, with benefits maintained 2 weeks after discontinuation (95925). More evidence is needed to rate wormwood for these uses.

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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.

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There is insufficient reliable information available about the safety of hu zhang.

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

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LIKELY SAFE ...when used orally in the amounts commonly found in foods. Wormwood extracts are included in bitters, vermouth, absinthe, and other food or drink products (12814,15007). Wormwood products that are thujone-free have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912); however, products containing thujone might not be safe. Wormwood is described in the pharmacopoeia of various European countries. After being banned for a period of time, it is now allowed in European Union countries; however, beverages must not contain thujone in concentrations greater than 35 mg/kg (12814,15007,86551).

POSSIBLY SAFE ...when wormwood products not containing thujone are used orally in medicinal amounts, short-term (93468,93469). A specific product

POSSIBLY UNSAFE ...when wormwood products containing thujone are used orally. Thujone is a neurotoxin that is present in wormwood oil (12617). Seizures, rhabdomyolysis, and acute kidney failure can occur when as little as 10 mL of wormwood oil is ingested (662,12817).

PREGNANCY:
LIKELY UNSAFE . .when used orally in amounts greater than those found in foods (662,12817). Some wormwood products contain thujone, a neurotoxin. Theoretically, thujone also has potential uterine and menstrual stimulant effects (12617). There is insufficient reliable information available about the safety of wormwood when used topically during pregnancy.

LACTATION:
Insufficient reliable information available; avoid using.

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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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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details Hu zhang contains the constituent resveratrol. Resveratrol seems to have antiplatelet effects (2949,2950,2951,2952,2961,70813,70828,70831,70892,70968,71106).

CARBAMAZEPINE (Tegretol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase the effects and adverse effects of carbamazepine.  Details In animals, blood and tissue levels of carbamazepine were increased when given in combination with hu zhang. It is thought that increased levels of carbamazepine are due to cytochrome P450 3A4 (CYP3A4) inhibition (101418). This interaction has not been reported in humans.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP1A1.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1A1 enzyme (70862,70811). This interaction has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP1A2.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1A2 enzyme (21733). This interaction has not been reported in humans.

CYTOCHROME P450 1B1 (CYP1B1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP1B1.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1B1 enzyme (70834). This interaction has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP2C19.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP2C19 enzyme (70896). This interaction has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP2E1.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP2E1 enzyme (7864,70896). Also, a pharmacokinetic study shows that taking resveratrol 500 mg daily for 10 days prior to taking a single dose of chlorzoxazone 250 mg increases the maximum concentration of chlorzoxazone by about 54%, the area under the curve of chlorzoxazone by about 72%, and the half-life of chlorzoxazone by about 35% (95824). Chlorzoxazone is used as a probe drug for CYP2E1.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP3A4.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP3A4 enzyme (7864,70896). However, a clinical study in adults with NAFLD found that adding resveratrol 3000 mg daily for 8 weeks did not necessitate dose adjustments to any established medications metabolized by CYP3A4 (91327).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might competitively inhibit the effects of estrogen replacement therapy.  Details In vitro research shows that hu zhang might have estrogenic activity (13124,16061).

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ANTICONVULSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking wormwood might interfere with the effects of anticonvulsant drugs.  Details Thujone, a constituent of wormwood, has convulsant effects (12816).

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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).

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General ...There is currently a limited amount of information on the adverse effects of hu zhang.

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General ...Wormwood contains thujone, a neurotoxin. When products containing thujone are used orally in medicinal amounts, wormwood may be unsafe.
Most Common Adverse Effects:
Orally: The oil from wormwood leaves can cause diffuse muscle aches, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: The oil from wormwood leaves can cause acute kidney toxicity, rhabdomyolysis, and seizures.

Dermatologic ...Topically, a single case report describes a sensitivity or first degree chemical burn reaction, with facial pain and erythema, after a 50-year-old adult applied a homemade poultice containing wormwood to the face for an unreported length of time (93466).

Gastrointestinal ...Orally, the oil from wormwood leaves can cause nausea and vomiting (662). Use of a home-prepared wormwood extract has been associated with vomiting and severe diarrhea in an infant (93467).

Hematologic ...Orally, use of a home-prepared wormwood extract has been associated with severe metabolic acidosis in an infant (93467).

Immunologic ...Theoretically, wormwood might cause an allergic reaction in people sensitive to the Asteraceae/Compositae family (12815). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Musculoskeletal ...Orally, the oil from wormwood leaves can cause diffuse muscle aches and rhabdomyolysis (662).

Neurologic/CNS ...Orally, the oil from wormwood leaves can cause seizures (662).

Renal ...Orally, the oil from wormwood leaves can cause acute kidney toxicity and acute kidney failure (662).

Other ...Chronic ingestion of absinthe, an alcoholic beverage that contains wormwood extract, has been linked to absinthism. Absinthism was first described in the 1800s when absinthe was at its peak levels of consumption. It has been characterized by addiction, gastrointestinal adverse effects, insomnia, auditory and visual hallucinations, tremors, paralysis, epilepsy, and brain damage. There is also increased risk of psychiatric disease and suicide (662,12814,15008). Increasing thujone concentrations of absinthe increases anxiety and decreases attention in healthy individuals (86541). A case of bradyarrhythmias associated with absinthe intoxication has also been reported (86543). However, there is speculation that some of the symptoms of absinthism originally described might be attributed to adulteration with metals or toxic plants such as calamus and tansy, rather than the ingredients usually used in absinthe drinks (15007). Some researchers also suggest that absinthism is not a unique condition and is indistinguishable from alcohol use disorder. In fact, some evidence suggests that the thujone concentrations in the absinthe formulations from the 1800s were too low to cause significant thujone-related toxicities (15008,15009).

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