Guggul [Discontinued] by Himalaya

POSSIBLY INEFFECTIVE

• Obesity. Oral guggul does not seem to reduce body weight in patients who are overweight or obese. Details: Several small clinical studies in overweight or obese individuals shows that taking guggul 1.5-4 grams daily for 4-12 weeks or standardized tablets containing guggul (Medohar) 1.5-3 grams daily for 4 weeks does not reduce body weight when compared with no treatment or placebo (54447,54502,54511). Another clinical study in patients with hypercholesterolemia shows that taking a standardized guggul extract 1-2 grams three times daily for 8 weeks does not improve body weight when compared with placebo (10371). Guggul has also been evaluated in combination with other ingredients. One small clinical study in overweight individuals shows that taking guggul 250 mg in combination with phosphate 550 mg, garcinia 250 mg, and L-tyrosine 250 mg three times daily for 6 weeks, along with exercise and calorie restriction, reduces body weight and body fat percentage when compared to baseline, but not when compared with placebo (8152). It is unclear if these findings are due to guggul, other ingredients, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if oral guggul is beneficial in patients with acne. Details: A very small clinical study in patients with nodulocystic acne shows that taking guggul, providing guggulsterone 25 mg, twice daily for 3 months leads to similar reductions in inflammatory lesions and the risk for relapse when compared with tetracycline (3268).
• Hemorrhoids. Topical guggul has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in adults with symptomatic mild to moderate (first- and second-degree) internal hemorrhoids shows that application of a cream containing sesame oil and aqueous extracts of guggul and Allium ampeloprasum as a thin layer to the anus twice daily for 3 weeks improves anal irritation and itching, bleeding, pain, defecation discomfort, and swelling sense when compared to baseline. In contrast, patients using a placebo cream experienced an improvement only in anal itching (105751). The poor study methodology and lack of statistical comparison to the placebo group limit the validity of these findings.
• Hypercholesterolemia. Several small, low-quality clinical studies in Indian populations suggest that oral guggul may reduce cholesterol levels in patients with hypercholesterolemia; however, more recent evidence in patients on Western diets contradicts these findings. Details: A small clinical study in patients with hypercholesterolemia following a Western diet shows that taking guggul 1-2 grams three times daily for 8 weeks increases low-density lipoprotein (LDL) cholesterol by 9% to 10% with no improvements in total cholesterol, triglycerides, or high-density lipoprotein (HDL) cholesterol when compared with placebo (10371). Another small clinical study in adults with hyperlipidemia and low to moderate cardiovascular risk shows that taking a methanolic extract of guggul 200 mg along with an aqueous extract of Terminalia and Indian gooseberry 450 mg three times daily for 3 months does not improve total, LDL, or HDL cholesterol levels or triglyceride levels when compared with placebo (105741). This is in contrast to several low-quality studies of guggul in Indian populations, which show that taking guggul extract (guggulipid) 1-2.25 grams two to three times daily for up to 16 weeks seems to lower total cholesterol, LDL cholesterol, and triglyceride levels when compared with baseline measures, placebo, or other controls (366,3267,8158,51219,54485,54497,54508). Also, some clinical research shows that taking a specific guggul extract fraction called "Fraction A" 500 mg three times daily for up to 75 weeks can reduce cholesterol and triglycerides in Indian patients with hypercholesterolemia (54492,54501). Most of the studies with positive findings were published in the 1970s and 1980s and may not be generalizable to patients on Western diets or taking conventional antihyperlipidemic agents, most of which were approved after the publication of these findings.
• Osteoarthritis. It is unclear if oral guggul is beneficial in patients with osteoarthritis. Details: Two small clinical studies in patients with osteoarthritis show that taking guggul may improve pain and other symptoms of osteoarthritis, measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) assessment, when compared to baseline (54453,111720). One study used guggul (containing 3.5% guggulsterones) 500 mg three times daily for 2 months (54453) and the other used a polyherbal ayurvedic formulation, abha guggulu, 1500 mg two times daily for 1 month (111720). The validity of these findings is limited by the lack of a comparator group.
• Rheumatoid arthritis (RA). It is unclear if oral guggul is beneficial in patients with RA. Details: A small, uncontrolled clinical study in patients with RA shows that taking guggul 1 gram three times daily for 4 months improves symptoms of RA when compared to baseline (54512). The validity of these findings is limited by a lack of placebo group. More evidence is needed to rate guggul for these uses.

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POSSIBLY SAFE ...when the prepared gum resin is used orally and appropriately. It has been used with apparent safety in clinical trials for up to 24 weeks (3267,3268,10371). There is insufficient reliable information available about the safety of guggul when used topically.

PREGNANCY: LIKELY UNSAFE
when used orally; avoid using. Guggul gum resin appears to stimulate menstrual flow and the uterus (12).

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 = B Theoretically, guggul might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.  Details In vitro research and preliminary clinical studies suggest that guggul might have antiplatelet and anticoagulant effects (3267,9557,54503,54505).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, guggul might increase the risk of adverse effects when taken with contraceptive drugs.  Details In vitro research shows that guggul has estrogen-alpha receptor agonist activity (12444).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, guggul might reduce the effects of CYP3A4 substrates.  Details In vitro research shows that guggul constituents known as guggulsterones can induce CYP3A4 (12444).

DILTIAZEM (Cardizem, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Guggul might reduce the effects of diltiazem.  Details A small pharmacokinetic study shows that concomitant use of guggul with diltiazem reduces the bioavailability of diltiazem (383).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, guggul might increase the risk of adverse effects when taken with estrogens.  Details In vitro research shows that guggul constituents known as guggulsterones have estrogen-alpha receptor agonist activity (12444).

PROPRANOLOL (Inderal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Guggul might reduce the effects of propranolol.  Details A small pharmacokinetic study shows that concomitant use of guggul with propranolol reduces the bioavailability of propranolol (383).

ROSUVASTATIN (Crestor) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, guggul might increase the effects and adverse effects of rosuvastatin.  Details Animal research shows that guggul increases the bioavailability and hypolipidemic effects of rosuvastatin (109584). The mechanism of this interaction is unclear.

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, guggul might interfere with tamoxifen therapy.  Details In vitro research shows that guggul has estrogen-alpha receptor agonist activity (12444).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, guggul might increase the risk for adverse effects when taken with thyroid hormone therapy.  Details Animal research suggests that guggul has thyroid-stimulating effects (8153).

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General ...Orally, guggul seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, bloating, diarrhea, headache, nausea, unpleasant taste, and vomiting. Allergic and non-allergic skin reactions.
Topically: Allergic contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Rhabdomyolysis.

Dermatologic ...Orally, guggul can cause hypersensitivity reactions including rash and pruritus (10371,54457). Guggul can also cause nonallergic adverse skin reactions. The risk of skin reactions appears to be dose-dependent. In one study, the incidence of skin reactions was 3% with a dosage of 1000 mg three times daily, compared with 15% with a dosage of 2000 mg three times daily. The severity of the reactions ranged from pruritus to swelling and erythema of the face to bullous lesion on the lower legs associated with headaches, myalgias, and pruritus (13662).
Topically, guggul can cause allergic contact dermatitis (54464,54467). Also, in a small clinical study, one patient using a cream containing aqueous extracts of guggul and Allium ampeloprasum as well as sesame oil complained of rash at the application site (105751). It is unclear if this reaction was due to guggul, other ingredients, or other factors.

Gastrointestinal ...Orally, guggul can cause nausea, vomiting, loose stools, diarrhea, belching, bloating, hiccups, and mild gastrointestinal discomfort (3267,8155,8158,10371,52033,54492).

Hepatic ...A case of severe hypertransaminasemia has been reported for a 63-year-old female who took a specific product (Equisterol) containing guggulsterone and red yeast rice extract daily for 6 months. Liver function normalized after discontinuing the supplement. It is unclear if the adverse effect was due to guggulsterone, red yeast, or the combination. However, the patient had previously developed hepatotoxicity while taking lovastatin, and red yeast contains monacolin K, which is identical to lovastatin (54477). Also, a case of acute liver failure requiring liver transplantation has been reported for a previously healthy young female who used a mixed-ingredient dietary supplement containing extracts of green tea, guggul, and usnic acid. It is unclear if the hepatotoxicity was due to guggul or other ingredients; green tea has been associated with hepatotoxicity (54027).

Immunologic ...Orally, guggul can cause hypersensitivity reactions including rash and pruritus (10371,54457). In a small clinical study, two adults with hyperlipidemia developed a hypersensitivity rash, one with facial edema, within minutes of oral administration of a methanolic extract of guggul, together with Terminalia extract (105741). It is unclear if this reaction was due to guggul, Terminalia, or other factors.
Topically, guggul can cause allergic contact dermatitis (54464,54467).

Musculoskeletal ...There is one case of rhabdomyolysis reported in a patient who took guggul 300 mg three times daily. The patient developed hemoglobinuria within 2 weeks of starting guggul in addition to increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase, creatine kinase, and myoglobinemia. The patient did not have any muscular symptoms. The patient's condition improved when guggul was discontinued. The patient had a history of developing elevated creatine kinase levels after taking simvastatin; however, the patient was not taking a statin at the time of this episode of rhabdomyolysis (13029).

Neurologic/CNS ...Orally, guggul can cause headaches (3267,8155,8158,10371,42692,49583). Less commonly, guggul may cause restlessness and apprehension (49583,54492).

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