Nettle-Pygeum Complex by Integrative Therapeutics

POSSIBLY EFFECTIVE

• Benign prostatic hyperplasia (BPH). Taking oral pumpkin seed or pumpkin seed oil may improve symptoms of BPH. Details: One study in patients with BPH shows that taking pumpkin seed 5 grams twice daily for 12 months may be more effective for controlling symptoms than pumpkin seed extract 1000 mg twice daily (92383). A specific pumpkin seed extract (Prosta Pink Forte) 1-2 capsules daily for 12 weeks has also been used (11231). Some preliminary clinical research also suggests that taking pumpkin seed oil (Prostafit, EuRho Vital) two tablets daily for 6 months may be as effective as the medication prazosin (92382). Pumpkin seed oil has also been compared with tamsulosin. A clinical study comparing pumpkin seed oil 360 mg twice daily to tamsulosin 0.4 mg once nightly for 3 months shows that both treatment groups report improvements in BPH symptoms and quality of life when compared with baseline, although improvement appears greater in the tamsulosin group, specifically when measured at 1 month and 3 months. In the pumpkin seed oil group, adverse effects were reported in 0% of patients, compared with 15% of patients taking tamsulosin (107842). The validity of this study is limited due to the short duration of treatment. Pumpkin seed oil or extracts have also been studied in combination with saw palmetto (6777), with saw palmetto, nettle root, and lemon extracts plus beta carotene (5093), and with saw palmetto, small flowered willow herb, lycopene, and pygeum (92379).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. Oral pumpkin seed oil might improve hair regrowth in males with mild to moderate hair loss. Details: Clinical research in males with mild to moderate hair loss shows that taking pumpkin seed oil (Octa Sabal Plus, Dreamplus Co. Ltd.) 400 mg daily in divided doses for 24 weeks increases hair count by 30% when compared with placebo. Self-rated improvement and satisfaction scores were 62% and 52% with pumpkin seed oil and placebo, respectively (92378). Clinical research in patients with female pattern hair loss shows that applying 1 mL of pumpkin seed oil to the scalp daily for 30 days improves hair regrowth similarly to minoxidil 5% foam, 1 mL daily (104974).
• Interstitial cystitis. Although there is interest in using oral pumpkin for interstitial cystitis, there is insufficient reliable information about the clinical effects of pumpkin for this condition.
• Intestinal parasite infection. Although there is interest in using oral pumpkin for intestinal parasite infection, there is insufficient reliable information about the clinical effects of pumpkin for this condition.
• Overactive bladder. Oral pumpkin seed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with overactive bladder shows that taking a specific combination product (Granu Fink femina, Omega Pharma) containing pumpkin seed oil 227 mg, sweet sumac bark extract 56 mg, and hops cone extract 18 mg three times daily for 12 weeks decreases the frequency of urination and leakage and improves quality of life when compared to baseline (103253). The validity of these findings is limited by the lack of a control group. Additionally, it is unclear if these findings are due to pumpkin seed oil, other ingredients, or the combination.
• Urinary tract infections (UTIs). Although there is interest in using oral pumpkin for UTIs, there is insufficient reliable information about the clinical effects of pumpkin for this condition. More evidence is needed to rate pumpkin for these uses.

(Read more about PUMPKIN)

LIKELY EFFECTIVE

• Benign prostatic hyperplasia (BPH). Most clinical research shows that taking oral pygeum reduces the frequency and severity of BPH symptoms in adults. However, it is unclear how pygeum compares with the standard prescription medications. Details: Meta-analyses of randomized clinical trials show that adults with BPH who take oral pygeum 75-200 mg daily for 60-90 days are about twice as likely to have improvement in BPH symptoms as those taking placebo. Taking pygeum also increases peak urine flow by 23% and reduces residual urine volume by 24% in patients with BPH (10425,10426). Preliminary clinical research also shows that once daily dosing is as effective as twice daily dosing (6368). Pygeum has also been evaluated in combination with other ingredients. One small study shows that taking a specific combination product (ProstateEZE Max, Caruso's Natural Health) containing pygeum, pumpkin seed oil, Epilobium parviflorum, lycopene, and saw palmetto as 1 capsule daily for 3 months decreases daytime urinary frequency by an additional 16% and nighttime urinary frequency by an additional 32% when compared with placebo (92164). In another clinical trial, taking a combination of pygeum and stinging nettle for 6 months did not improve BPH symptoms when compared with placebo; however, the study may have been inadequately powered to detect a difference between groups (70219).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. Although there has been interest in using oral pygeum for Alzheimer disease, there is insufficient reliable information about the clinical effects of pygeum for this purpose.

  
  Malaria. Although there has been interest in using oral pygeum for malaria, there is insufficient reliable information about the clinical effects of pygeum for this purpose.

  
  Psychosis. Although there has been interest in using oral pygeum for psychosis, there is insufficient reliable information about the clinical effects of pygeum for this purpose.

  
  Sexual desire. Although there has been interest in using oral pygeum for sexual desire, there is insufficient reliable information about the clinical effects of pygeum for this purpose.

  
  More evidence is needed to rate pygeum for these uses.

(Read more about PYGEUM)

POSSIBLY EFFECTIVE

• Diabetes. Oral stinging nettle seems to improve glycemic control in patients with diabetes. Details: A meta-analysis of 8 small heterogeneous clinical trials in adults with type 2 diabetes shows that taking stinging nettle 1.5-10 grams in divided doses daily for 8-12 weeks reduces fasting blood glucose (FBG) by 18 mg/dL when compared with placebo (102865). Glycated hemoglobin (HbA1c) was not improved, but the study durations were not adequate to detect an improvement in this measure. Despite positive results on FBG, taking stinging nettle does not seem to improve insulin secretion or measures of insulin sensitivity (91519,102865,108903). Another meta-analysis of 3 small clinical studies in adults with type 2 diabetes shows that taking stinging nettle reduces HbA1c by about 1.3% when compared with placebo. This analysis also suggests stinging nettle reduces post-prandial blood glucose by about 114 mg/dL; however, this is based on a single study. Stinging nettle did not improve fasting blood glucose or insulin resistance in this analysis (111503). The validity of these findings is limited by the low quality and heterogeneity of included studies, as well as unclear dosing. Furthermore, since most research has been conducted in Iran, it is unknown if these findings are generalizable to other geographic locations. Stinging nettle has also been used in combination with other natural medicines. One small clinical study in adults with type 2 diabetes shows that taking a product containing stinging nettle leaf extract 200 mg, milk thistle 200 mg, and Boswellia serrata gum 200 mg three times daily for 3 months reduces FBP by about 28 mg/dL and HbA1c by about 1.5%, compared with a smaller reduction in the placebo group (96742). It is unclear if this effect is due to stinging nettle, the other ingredients, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral stinging nettle is beneficial for hay fever. Details: Taking stinging nettle leaf extract 300 mg 3-7 times daily at the first sign of hay fever symptoms seems to provide subjective improvement (7035). However, adding stinging nettle to conventional allergy medication might not provide any additional benefit. One small clinical study shows that adding stinging nettle tablets (Urtidin, Barij Essence Pharmaceutical Co.) 150 mg four times daily for 1 month to treatment with loratadine and nasal saline rinses does not improve symptoms of allergic rhinitis when compared with placebo with loratadine and nasal saline rinses (96743).
• Anemia. Although there is interest in using oral stinging nettle for anemia, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Asthma. Although there is interest in using oral stinging nettle for asthma, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Benign prostatic hyperplasia (BPH). It is unclear if oral stinging nettle is beneficial for BPH. Details: A meta-analysis of clinical research, including 5 clinical studies and 1,128 patients with BPH, shows that taking stinging nettle root extract 360-600 mg in divided doses daily for 2-12 months improves peak urinary flow rate and symptom scores while modestly reducing prostate volume when compared with control. However, the validity of these results is limited by significant heterogeneity due to the variability in the products used and the specific endpoints investigated (96744). In the largest clinical trial in the analysis, patients took stinging nettle root extract 120 mg three times daily for 6 months (76406). Stinging nettle has also been evaluated in combination products. Clinical research in patients with BPH shows that taking a specific combination product (PRO 160/120, Dr. Willmar Schwabe Pharmaceuticals) containing a specific extract of stinging nettle root (WS 1031) 120 mg plus a specific extract of saw palmetto fruit (WS 1473) 160 mg twice daily for 24-48 weeks seems to improve urinary tract symptoms when compared with control; the effect may last at least 48 weeks after treatment (15195,15551,76409). However, taking a different combination product does not seem to be beneficial. A small clinical study in patients with BPH shows that taking a product containing stinging nettle root extract 240 mg, saw palmetto, pumpkin seed oil, lemon bioflavonoid, and beta-carotene, three times daily for 6 months, does not improve symptoms of BPH (5093).
• Bleeding. Topical stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that applying 4 mL of a specific product (Ankaferd blood stopper, Mefar Ilaç Sanayi A.S) containing alpinia, licorice, thyme, stinging nettle, and common grape vine to the affected area reduces bleeding, but does not improve the time for episiotomy repair, when compared with using saline (31010).
• Gingivitis. Stinging nettle in a mouthwash solution has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with moderate gingival inflammation suggests that using 10 mL of mouthwash solution containing a 1:1:1 mixture of stinging nettle, juniper, and yarrow twice daily for 3 months does not reduce plaque or bleeding when compared with control (76443). It is not clear if this effect is due to stinging nettle, the other ingredients, or the combination.
• Gout. Although there is interest in using oral stinging nettle for gout, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Gulf war syndrome. It is unclear if oral stinging nettle is beneficial for Gulf war syndrome. Details: A very small exploratory clinical trial in males with Gulf war syndrome shows that taking stinging nettle leaf (Nature's Way) 1305 mg in two divided doses daily for 30 days modestly improves symptom severity when compared with placebo (108311). The clinical relevance of this finding is limited by the use of an unvalidated scoring scale. Additionally, it appears that most patients had mild, unspecified symptoms at baseline; it is unclear if stinging nettle is beneficial for moderate to severe symptoms.
• Hyperandrogenism. It is unclear if oral stinging nettle is beneficial in patients with hyperandrogenism. Details: Preliminary clinical research in females with hyperandrogenism shows that taking dried extract of stinging nettle root 300-600 mg daily for approximately 4 months decreases total and free testosterone levels, but not menstrual cycle conditions, oily skin, or acne, when compared with taking spironolactone and cyproterone (91520).
• Insect bite. Oral stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a homeopathic after-bite gel, containing stinging nettle, Echinacea, and marsh Labrador tea, on affected areas does not reduce erythema or itching after a mosquito bite when compared with placebo (89235).
• Kidney stones (nephrolithiasis). Although there is interest in using oral stinging nettle for kidney stones, there is insufficient reliable information about the clinical effects of stinging nettle for this condition.
• Myalgia. Although there is interest in using topical stinging nettle for myalgia, there is insufficient reliable information about the clinical effects of stinging nettle for this purpose.
• Osteoarthritis. Small clinical studies suggest that topical stinging nettle may modestly improve pain in patients with osteoarthritis. It is unclear if oral stinging nettle is beneficial. Details: Topically, stinging nettle leaf may have a counterirritant effect which may improve osteoarthritis pain in some patients. A small clinical study in patients ages 45-82 with osteoarthritis of the thumb shows that applying raw stinging nettle leaf to the thumb for 30 seconds daily for 1 week reduces pain and disability when compared with white dead nettle leaf control (12490). However, in another small clinical study in patients with knee osteoarthritis, topical application of raw stinging nettle leaf to the knee for 1 minute daily for 7 days does not seem to be more effective for reducing pain than applying a leaf from a related stingless nettle (76412). Non-raw stinging nettle has also been tried. In a small open-label study, a formulation of stinging nettle extract (Liquid PhytoCaps Nettle Leaf, Gaia Herbs) 13.33% compounded with lipobase oil-in-water emulsion and applied to the affected area twice daily for 2 weeks, modestly improves pain and function in patients with radiologically confirmed osteoarthritis when compared with baseline (76414). The validity of this finding is limited by the lack of a comparator group. Stinging nettle has also been evaluated orally, in combination with other ingredients. A clinical study in adults with knee osteoarthritis shows that taking a specific combination solution (Rosaxan, medAgil Gesundheitsgesellschaft mbH) containing stinging nettle extract 160 mg, rose hip puree 20 grams, devil's claw 108 mg, and vitamin D 200 IU daily for 12 weeks improves symptoms by an additional 28% and pain scores by an additional 33% when compared with placebo (96741). It is unclear if this effect is due to stinging nettle, the other ingredients, or the combination.
• Tinnitus. Oral stinging nettle has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with tinnitus shows that taking a specific product containing stinging nettle, tansy, and rose hip (Neurotec, Rose Pharmed), 100 mg orally daily for 3 months does not improve auditory thresholds when compared with placebo. However, the product improved some subjective symptoms scores, such as perceived loudness and severity scores (110512).
• Urinary tract infections (UTIs). Although there is interest in using oral stinging nettle for UTIs, there is insufficient reliable information about the clinical effects of stinging nettle for this condition. More evidence is needed to rate stinging nettle for these uses.

(Read more about STINGING NETTLE)

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

POSSIBLY SAFE ...when the seed or seed oil is used orally and appropriately in medicinal amounts, short-term. Pumpkin seed has been used with apparent safety in a dose of up to 10 grams daily for up to 12 months (92383). Pumpkin seed oil has been used with apparent safety in a dose of up to 400 mg daily for up to 6 months (92378). There is insufficient reliable information available about the safety of pumpkin seed oil when used topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food.

(Read more about PUMPKIN)

LIKELY SAFE ...when used orally and appropriately. Pygeum 75-200 mg daily has been used safely in clinical trials for up to 12 months (3903,6368,10425,10426).

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

(Read more about PYGEUM)

POSSIBLY SAFE ...when used orally and appropriately. Stinging nettle root 360-600 mg has been used safely for up to 1 year (5093,11230,15195,76406,96744). ...when used topically and appropriately (12490).

PREGNANCY: LIKELY UNSAFE
when used orally due to possible abortifacient and uterine-stimulant effects (4,6,19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about STINGING NETTLE)

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Pumpkin might reduce excretion and increase levels of lithium.  Details Pumpkin is thought to have diuretic properties (92383). Theoretically, this might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, stinging nettle might have additive effects with antidiabetes drugs.  Details Clinical research shows that stinging nettle might decrease blood glucose levels in patients with diabetes (91519,102865).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining stinging nettle with diuretic drugs may have additive effects.  Details Animal research suggests that the above ground parts and roots of stinging nettle may have a diuretic effect (1,4,11,76402).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, stinging nettle might reduce excretion and increase levels of lithium.  Details Animal research suggests that stinging nettle has diuretic and natriuretic properties, which could alter the excretion of lithium (76402). The dose of lithium might need to be decreased.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D There is some concern that stinging nettle might decrease the effects of anticoagulant drugs such as warfarin.  Details Stinging nettle contains a significant amount of vitamin K (19). When taken in large quantities, this might interfere with the activity of warfarin.

(Read more about STINGING NETTLE)

General ...Orally, pumpkin products are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, diarrhea, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.

Dermatologic ...There are two case reports of adult females developing substantial transient hair loss 1-3 weeks after consumption of a meal containing either bitter-tasting pumpkin or undefined squash. This adverse effect was attributed to a high concentration of cucurbitacin, which is commonly found in wild pumpkins (104535).

Gastrointestinal ...Orally, pumpkin seed oil has been reported to cause mild abdominal discomfort in clinical trials (5093,92378). There are also two case reports of adults developing severe nausea, vomiting, and diarrhea following consumption of a meal containing either bitter-tasting pumpkin or undefined squash. These adverse effects were attributed to a high concentration of cucurbitacin, which is commonly found in wild pumpkins (104535).

Immunologic ...Orally, pumpkin seed oil and pumpkin pulp have been reported to cause anaphylactic reactions in children and adults. A case review highlights 4 cases of anaphylaxis in children (3 from pumpkin pulp, 1 from pumpkin seeds), and 7 cases in adults (1 from pumpkin flesh, 6 from pumpkin seeds). Symptoms of anaphylaxis include urticaria, angioedema of the lips or face, dyspnea, dysphagia, and oropharyngeal itching and swelling. A case report describes a 2-year-old male presenting with urticaria, swollen lips, and increased dyspnea 10 minutes after ingesting pumpkin seeds. The patient was found to have elevated allergen-specific immunoglobulin E (IgE) and a positive skin-prick test for pumpkin seeds. Symptoms resolved after treatment with epinephrine, systemic glucocorticoids, salbuterol, and antihistamines (107843).
There may also be concern for allergic reaction due to inhalation or topical exposure. One case report describes an 8-year-old child developing anaphylaxis while carving a pumpkin; another highlights that inhalation of pumpkin seed flour may have potentiated anaphylaxis in 3 individuals following the ingestion of pumpkin seeds (107843). Further research is necessary to assess the relationship between anaphylaxis and route of administration.

(Read more about PUMPKIN)

General ...Orally, pygeum is generally well tolerated.

Gastrointestinal ...Orally, pygeum has been associated with nausea and abdominal pain in some clinical research. However, the rate of these events were similar to placebo (10425,10426,70238).

(Read more about PYGEUM)

General ...Orally, stinging nettle seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea.
Topically: Contact with the raw plant causes itching, rash, and stinging.

Dermatologic ...Topically, fresh stinging nettle leaves and stalk can cause localized rash, itching, and stinging (12490,76399,76412,76414,76417,76428,76448,96746). Usually, short exposure to stinging nettle results in a transient urticarial reaction and a stinging sensation which may persist for more than 12 hours (76399,76414,76417,96746). In one report, a patient placed a fresh stinging nettle leaf on the tongue to suck out the sap of the leaf. Severe tongue edema, pain, and urticaria developed within 5 minutes. Symptoms continued for several hours after the leaf was removed (15197). In another case report, a young couple intoxicated with methamphetamine fell and laid in a stinging nettle bush for 20 minutes, after which urticaria and pain continued for 2-3 weeks, and a heightened sensitivity to cold persisted for several months (96746).

Endocrine ...A case of gynecomastia has been reported for a 33-year-old male who consumed stinging nettle tea 2 cups daily for one month prior to symptom onset. The condition subsided one month after discontinuing stinging nettle tea (76410).
There have been two cases of galactorrhea associated with the consumption of stinging nettle for one month (76410,108902). In one case, a 33-year-old female consuming stinging nettle tea showed high levels of estradiol and low levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). The levels of these hormones normalized 6 weeks after discontinuing stinging nettle tea (76410). In the other case report describing a 30-year-old female self-treating with stinging nettle 500 mg daily, hormone levels were not reported; however, a mammogram showed scattered areas of fibroglandular density and benign-appearing calcifications. This patient had complete resolution of symptoms 1 week after discontinuation of stinging nettle (108902).

Gastrointestinal ...Orally, stinging nettle root can cause gastrointestinal complaints, including diarrhea and constipation (1,7,11230). Stinging nettle above ground parts may cause mild gastrointestinal discomfort when taken on an empty stomach (7035). Stinging nettle juice may cause diarrhea (1). One patient taking a combination product containing stinging nettle root extract and pygeum bark extract (Prostatonin, Pharmaton) experienced continual gastrointestinal pain and hyperperistalsis. It is not clear if this effect was due to stinging nettle or pygeum (70230).

Genitourinary ...There is a case report of decreased ejaculatory volume associated with an herbal blend product containing stinging nettle root extract, saw palmetto extract, pumpkin seed oil extract, lemon bioflavonoid extract, and beta-carotene (5093). It is unclear if this was due to stinging nettle, other ingredients, or the combination.

Hepatic ...A case of idiosyncratic drug-induced liver disease (DILI) is reported in a 36-year-old female who presented with abdominal pain after 1 month of taking an herbal liver detox tea containing stinging nettle and other ingredients. Remarkable laboratory values included elevated liver enzymes, alkaline phosphatase, and total bilirubin. The patient received a loading dose of N-acetylcysteine and was hospitalized for 12 days (112178). However, it is unclear if the adverse effect was due to the stinging nettle, other ingredients, or the combination.

Other ...Orally, stinging nettle root can cause sweating (1,7).

(Read more about STINGING NETTLE)