| Ingredients | Amount per Serving |
|---|---|
|
Proprietary Blend
|
750 mg |
|
(Chlorella )
(cracked cell)
|
|
|
(leaf)
|
|
|
(Laminaria Kelp)
|
|
|
(Spirulina )
|
|
|
(bulb)
|
|
|
Kelp
|
|
| 50 mg | |
|
(N-Acetyl-Cysteine)
|
50 mg |
| 20 mg |
Vegetable Capsule (Form: Vegetable Fiber, and Water)
Below is general information about the effectiveness of the known ingredients contained in the product Heavy Metal Cleanse 2 Evening Formula. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
There is insufficient reliable information available about the effectiveness of algin.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
There is insufficient reliable information available about the effectiveness of cilantro.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Heavy Metal Cleanse 2 Evening Formula. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally in amounts typically found in foods (11). There is insufficient reliable information available about the safety of algin when used orally in medicinal amounts.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Alpha-lipoic acid has been used with apparent safety in doses of up to 2 grams daily for 3 months to 2 years. Lower doses of 600 mg daily have been used with apparent safety for up to 4 years (3540,3541,3542,20479,96449,97630,101867,101869,103327,103333)(103335,104651,104660,113892,113897). ...when used topically and appropriately. A cream containing alpha-lipoic acid 5% has been used with apparent safety in clinical trials lasting up to 12 weeks (12021). ...when given intravenously and appropriately. Intravenous alpha-lipoic acid has been used safely in doses of up to 6000 mg weekly in clinical trials lasting up to 3 weeks (3540,3557,10148,12106).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Alpha-lipoic acid has been used with apparent safety in doses of up to 600 mg daily for 3 months in children aged 10-17 years (103330).
CHILDREN: POSSIBLY UNSAFE
when used orally in amounts over 600 mg daily.
At least five cases of alpha-lipoic acid intoxication have been reported for children aged 14 months to 16 years who consumed alpha-lipoic acid at doses up to 226 mg/kg (approximately 2400 mg). Symptoms of alpha-lipoic acid-induced intoxication included seizures, acidosis, vomiting, and unconsciousness (90444,96227,96234,104653).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term.
Alpha-lipoic acid has been used safely during pregnancy at doses up to 600 mg daily for up to 4 weeks (96222).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when non-contaminated species of spirulina blue-green algae are used orally and appropriately (91713). The blue-green algae species Arthrospira platensis has been used with apparent safety in doses up to 19 grams daily for 2 months, or 10 grams daily for 6 months (18296,18300,18306,75944,91705,99703,104567,109965). The blue-green algae species Arthrospira fusiformis has been used with apparent safety in doses up to 4 grams daily for 3 months, or 1 gram daily for 12 months (15782,91717). Another blue-green algae species, Arthrospira maxima, has been used with apparent safety in a dose of 4.5 grams daily for up to 12 weeks (18297,99654,99655,102688). ...when non-contaminated, non-toxin producing strains of blue-green algae from the Aphanizomenon flos-aquae species are used orally and appropriately. Doses up to 1.6 grams daily have been used with apparent safety for up to 6 months (14842,18310). Some blue-green algae species can produce toxins called microcystins. According to the World Health Organization (WHO), the tolerable daily intake of microcystins in adults is 0.04 mcg/kg (96549).
POSSIBLY UNSAFE ...when contaminated blue-green algae are used orally. Blue-green algae can be contaminated with heavy metals (including mercury, cadmium, lead, or arsenic), neurotoxins, and toxic microcystin-producing cyanobacteria such as Microcystis aeruginosa (9171,75966,91704,91711,96550). Microcystins are most commonly reported in the blue-green algae species Aphanizomenon flos-aquae harvested from Upper Klamath Lake in Oregon. The Oregon Department of Health has set a limit of 1 mcg of microcystin-LR equivalents per gram dry weight of blue-green algae, assuming consumption of about 2 grams/day by adults (91704,91713). However, many samples of Aphanizomenon flos-aquae have been reported to contain higher levels than this (9171,91704). According to the World Health Organization (WHO), the tolerable daily intake of microcystins in adults is 0.04 mcg/kg (96549). When consumed orally, microcystins accumulate in the liver, binding to and inhibiting protein phosphatases, causing hepatocyte damage and possible tumor promotion (9171). Aphanizomenon flos-aquae can also produce neurotoxic compounds that may be present in supplements containing this organism (91704).
CHILDREN: POSSIBLY UNSAFE
when blue-green algae products are used orally.
Blue-green algae can accumulate heavy metals such as lead and mercury (91704,91711). They can also contain toxic microcystins produced by contaminating species of cyanobacteria such a Microcystis aeruginosa (91704). Children are more sensitive to poisoning by microcystins (3536). The Oregon Department of Health has set a limit for microcystins of 1 mcg per gram dry weight of blue-green algae, but some countries have set very low exposure limits of 0.2 mcg per day and 0.8 mcg per day for infants and children, respectively (91704).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Some blue-green algae products, specifically those of the species Aphanizomenon flos-aquae, have been found to contain low amounts of beta-methylamino-L-alanine (BMAA). BMAA is associated with neurodegenerative diseases, and breast milk has been shown to be a potential source of BMAA exposure in infants (96550).
LIKELY SAFE ...when used orally and appropriately. BCAAs 12 grams daily have not been associated with significant adverse effects in studies lasting for up to 2 years (68,72,73,74,10117,10146,10147,37120,92643,97531,103351,103352). ...when used intravenously and appropriately. BCAAs are an FDA-approved injectable product (13309).
CHILDREN: LIKELY SAFE
when used orally in dietary amounts of 71-134 mg/kg daily (11120,13308).
CHILDREN: POSSIBLY SAFE
when larger, supplemental doses are used orally and appropriately for up to 6 months (13307,13308,37127).
PREGNANCY:
Insufficient reliable information available; avoid using amounts greater than those found in food.
Although adverse effects have not been reported in humans, some animal research suggests that consumption of supplemental isoleucine, a BCAA, during the first half of pregnancy may have variable effects on birth weight, possibly due to abnormal placental development (103350).
LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food.
Although the safety of increased BCAA consumption during lactation is unclear, some clinical research suggests that a higher concentration of isoleucine and leucine in breastmilk during the first 6 months postpartum is not associated with infant growth or body composition at 2 weeks, 2 months, or 6 months (108466).
LIKELY SAFE ...when used orally and appropriately, short-term. Tablets and liquids containing chlorella 3-10 grams or 60-100 mL daily have been safely used in clinical studies lasting 2-3 months (5890,92130,92131). Also, chlorella extract 200-1800 mg daily has been safely used in clinical research for 4-6 weeks (10388,92132). There is insufficient reliable information available about the safety of chlorella when used topically.
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately in medicinal amounts for up to approximately 28 weeks.
A commercially available chlorella supplement (Sun Chlorella A, Sun Chlorella Corp.) has been safely used in doses of 6 grams daily, starting during the 12-18th week of gestation and continuing until delivery (95013).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when applied topically to the skin. A gel containing 1% Fucus vesiculosus extract, applied to the skin twice daily, has been used in clinical research with apparent safety for up to 5 weeks (12799).
POSSIBLY UNSAFE ...when used orally due to its iodine content and possible heavy metal content. Fucus vesiculosus contains up to 0.05% iodine or 226 mcg/gram dry weight (12789,74217). Ingesting more than 150 mcg of iodine daily can cause hyperthyroidism or exacerbate existing hyperthyroidism (12788). Fucus vesiculosus can also contain heavy metals, including cadmium, arsenic, and lead, and can cause heavy metal nephropathy (12789,12800,74213).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally because it may contain iodine and heavy metals (12789,74213,74217); avoid using.
LIKELY SAFE ...when used orally and appropriately. Garlic has been used safely in clinical studies lasting up to 7 years without reports of significant toxicity (1873,4782,4783,4784,4785,4786,4787,4789,4790,4797)(4798,6457,6897,14447,96008,96009,96014,102016,102670,103479)(107238,107239,107352,108607,110722,111763,114892).
POSSIBLY SAFE ...when used topically. Garlic-containing gels, lipid-soluble garlic extracts, garlic pastes, and garlic mouthwashes have been safely used in clinical research for up to 3 months (4766,4767,8019,15030,51330,51386). ...when used intravaginally. A vaginal cream containing garlic and thyme has been safely used nightly for 7 nights (88387).
POSSIBLY UNSAFE ...when raw garlic is used topically (585). Raw garlic might cause severe skin irritation when applied topically.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (3319).
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Garlic is reported to have abortifacient activity (11020). One study also suggests that garlic constituents are distributed to the amniotic fluid after a single dose of garlic (4828). However, there are no published reports of garlic adversely affecting pregnancy. In clinical research, garlic 800 mg daily was used during the third trimester of pregnancy with no reported adverse outcomes (9201,51626). There is insufficient reliable information available about the safety of topical garlic during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (3319).
LACTATION: POSSIBLY UNSAFE
when used orally in amounts greater than those found in foods.
Several small studies suggest that garlic constituents are secreted in breast milk, and that nursing infants of mothers consuming garlic are prone to extended nursing (3319,4829,4830). There is insufficient reliable information available about the safety of topical garlic during lactation.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately for up to 8 weeks.
Garlic extract 300 mg three times daily has been used with apparent safety for up 8 weeks in children ages 8-18 years (4796). There is insufficient reliable information available about the safety of garlic when used over longer durations or in higher doses.
CHILDREN: POSSIBLY UNSAFE
when raw garlic is used topically.
Raw garlic might cause severe skin irritation when applied topically (585,51210).
LIKELY SAFE ...when used orally, intravenously, intratracheally, or by inhalation and appropriately. N-acetyl cysteine is an FDA-approved prescription drug (832,1539,1705,1710,2245,2246,2252,2253,2254,2256)(2258,2259,2260,5808,6176,6611,7868,10270,10271,16840)(91243,91247,102027,102660,102666,99531).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
N-acetyl cysteine has been safely used at doses of 900-2700 mg daily for 8-12 weeks (91235,91239,91241,102666). ...when used intravenously and appropriately. Intravenous N-acetyl cysteine 140 mg/kg/day plus oral N-acetyl cysteine 70 mg/kg four times daily for up to 10 months has been safely used (64547).
PREGNANCY: POSSIBLY SAFE
when used orally, intratracheally, intravenously, or by inhalation.
N-acetyl cysteine crosses the placenta, but has not been associated with adverse effects to the fetus (1711,64615,64493,97041). However, N-acetyl cysteine should only be used in pregnancy when clearly indicated, such as in cases of acetaminophen toxicity.
LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Heavy Metal Cleanse 2 Evening Formula. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, algin can alter the absorption of oral drugs. Laboratory research shows that algin, when consumed as part of the diet or used as a thickening agent in infant formula, reduces the absorption of certain minerals. Also, algin has been used as a tablet binder and disintegrant to enhance drug bioavailability (103721,40007,104058). To avoid changes in absorption, take algin 30-60 minutes after oral medications.
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Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of alkylating agents.
 Details
The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy. Advise patients to consult their oncologist before using alpha-lipoic acid.
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Theoretically, alpha-lipoic acid may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
In vitro, alpha-lipoic acid inhibits platelet aggregation (98682).
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Theoretically, taking alpha-lipoic acid with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Although some small clinical studies have suggested that alpha-lipoic acid can lower blood glucose levels (3545,3874,3875,3876,20490,20493,104650), larger clinical studies in patients with diabetes have shown no clinically meaningful effect (20494,20495,20496,90443,90445,110118). Additionally, co-administration of single doses of alpha-lipoic acid and glyburide or acarbose did not cause detectable drug interactions in healthy volunteers (3870).
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Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of antitumor antibiotics.
Details
The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of antitumor antibiotic drugs, which work by generating free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using alpha-lipoic acid.
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Theoretically, alpha-lipoic acid might decrease the effects of thyroid hormone drugs.
Details
Animal research suggests that co-administration of thyroxine with alpha-lipoic acid reduces conversion into the active T3 form (8946).
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Theoretically, spirulina blue-green algae might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs. However, this is unlikely.
Details
Spirulina blue-green algae have shown antiplatelet and anticoagulant effects in vitro (18311,18312,75892,92162,92163). However, one preliminary study in 24 patients receiving spirulina blue-green algae 2.3 grams daily for 2 weeks showed no effect on platelet activation or measures of clotting time (97202).
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Theoretically, taking blue-green algae with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Human research shows that spirulina blue-green algae can have hypoglycemic effects in patients with diabetes, at least some of whom were using antidiabetes drugs (18299). However, blue-green algae does not seem to improve glycated hemoglobin (HbA1c) levels in patients with diabetes (102689,109970). A meta-analysis of animal studies also suggests that spirulina blue-green algae have hypoglycemic effects (109970).
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Theoretically, concurrent use of blue-green algae might interfere with immunosuppressive therapy.
Details
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Theoretically, BCAAs might alter the effects of antidiabetes medications.
Details
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BCAAs in large doses can reduce the effects of levodopa.
Details
BCAAs may compete with levodopa for transport systems in the intestine and brain and decrease the effectiveness of levodopa (66,2719). Small clinical studies how that concomitant ingestion of protein or high doses of leucine or isoleucine (100 mg/kg) and levodopa can exacerbate tremor, rigidity, and the "on-off" syndrome in patients with Parkinson disease (3291,3292,3293,3294).
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Theoretically, chlorella might have additive effects with photosensitizing drugs.
Details
Chlorella has been reported to cause photosensitization (3900,5852). In five case reports, patients who had ingested chlorella exhibited swelling followed by erythematopurpuric lesions on sun-exposed areas of the body (5852). Theoretically, concomitant use with photosensitizing drugs may exacerbate effects.
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Theoretically, chlorella might reduce the clinical effects of warfarin.
Details
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In vitro research suggests that extracts of cilantro can inhibit platelet aggregation (26583). Theoretically, cilantro might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs. Some of these drugs include aspirin, clopidogrel (Plavix), nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
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Evidence from in vitro research suggests that coriandrin, a constituent of cilantro, has photosensitizing effects (46228). Theoretically, concomitant use with photosensitizing drugs might increase photosensitivity. Some drugs that cause photosensitivity include amitriptyline (Elavil), quinolones (Ciprofloxacin, others), sulfa drugs (Septra, Bactrim, others), and tetracycline.
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Theoretically, combining Fucus vesiculosus with amiodarone might cause excessively high iodine levels.
Details
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Theoretically, taking Fucus vesiculosus with antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.
Details
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Due to its iodine content, Fucus vesiculosus might alter the effects of antithyroid drugs.
Details
Fucus vesiculosus contains high concentrations of iodine (7135). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking Fucus vesiculosus while using antithyroid drugs could alter the effects of the antithyroid drugs (2138,17574).
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Theoretically, concomitant use of Fucus vesiculosus with CYP2C8 substrates might increase the risk for adverse effects.
Details
In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP2C8 (97791). This interaction has not been reported in humans.
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Theoretically, concomitant use of Fucus vesiculosus with CYP2C9 substrates might increase the risk for adverse effects.
Details
In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP2C9 (97791). This interaction has not been reported in humans.
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Theoretically, concomitant use of Fucus vesiculosus with CYP2D6 substrates might alter the effects of these substrates.
Details
In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, both inhibits and induces CYP2D6 (97791). This interaction has not been reported in humans.
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Theoretically, concomitant use of Fucus vesiculosus with CYP3A4 substrates might increase the risk for adverse effects.
Details
In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP3A4 (97791). This interaction has not been reported in humans.
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Concomitant use of Fucus vesiculosus and lithium has resulted in hyperthyroidism.
Details
There is a case of hyperthyroidism occurring in a patient taking Fucus vesiculosus and lithium (74217). Monitor thyroid hormones closely in patients taking lithium and Fucus vesiculosus concomitantly.
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Due to its iodine content, Fucus vesiculosus might alter the effects of thyroid hormone.
Details
Fucus vesiculosus contains high concentrations of iodine (7135). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking Fucus vesiculosus while using thyroid hormone could alter the effects of thyroid hormone.
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Garlic may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
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Theoretically, taking garlic with antidiabetes drugs might increase the risk of hypoglycemia.
Details
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Theoretically, taking garlic with antihypertensive drugs might increase the risk of hypotension.
Details
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Theoretically, garlic might decrease levels and effects of atazanavir.
Details
In a case report, a patient consuming six stir-fried garlic cloves three times weekly developed suboptimal atazanavir levels and increases in HIV viral load. While the exact cause of this interaction is unclear, there is speculation that garlic might decrease the intestinal absorption of atazanavir or increase its metabolism by inducing cytochrome P450 3A4 (CYP3A4) (88388). Until more is known, advise patients not to consume large amounts of garlic while taking atazanavir.
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Garlic might increase levels of drugs metabolized by CYP2E1.
Details
Clinical research suggests garlic oil can inhibit the activity of CYP2E1 by 39% (10847). Use garlic oil cautiously in patients taking drugs metabolized by these enzymes.
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Theoretically, garlic products containing allicin might induce intestinal CYP3A4 and inhibit hepatic CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
Details
Some human research suggests that garlic may induce INTESTINAL CYP3A4, reducing levels of drugs metabolized by this enzyme. This is primarily based on a study showing that taking a specific allicin-containing garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induced CYP3A4 in the gut mucosa (7027,93578). Another study shows that giving docetaxel intravenously, bypassing the CYP3A4 enzymes in the gut mucosa, along with the same specific garlic product for 12 consecutive days, does not affect docetaxel levels (17221). Conversely, there is concern that garlic may inhibit HEPATIC CYP3A4. In a single case report, increased tacrolimus levels and liver injury occurred in a liver transplant patient after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days (96010). Several other studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506).
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Theoretically, garlic might decrease levels of isoniazid.
Details
Animal research suggests that an aqueous extract of garlic reduces isoniazid levels by about 65%. Garlic reduced the maximum concentration (Cmax) and area under the curve (AUC), but not the half-life, of isoniazid. This suggests that garlic extract might inhibit isoniazid absorption across the intestinal mucosa (15031); however, the exact mechanism of this potential interaction is not known.
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Theoretically, garlic products containing allicin might decrease levels of PIs.
Details
Protease inhibitors are metabolized by cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4, reducing plasma levels of protease inhibitors. This is primarily based on a study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces levels of saquinavir, a PI, by approximately 50%. It is speculated that the allicin constituent induce CYP3A4 in the gut mucosa (7027,93578). Several studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506).
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Theoretically, garlic containing allicin might decrease levels of saquinavir.
Details
Saquinavir is a substrate of cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4 and cause subtherapeutic levels of saquinavir. This is primarily based on a pharmacokinetic study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induces CYP3A4 in the gut mucosa (7027,93578). Several pharmacokinetic studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506). Until more is known about this potential interaction, use garlic containing allicin cautiously in patients taking saquinavir.
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Theoretically, taking garlic with sofosbuvir might decrease its effectiveness.
Details
Animal research in rats shows that giving aged garlic extract 120 mg/kg orally daily for 14 days decreases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 36%, increases the clearance by 63%, and decreases the plasma concentrations at 1 and 8 hours by 35% and 58%, respectively. This interaction is hypothesized to be due to induction of intestinal P-glycoprotein expression by garlic (109524).
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Theoretically, garlic might increase levels of tacrolimus.
Details
In one case report, a liver transplant patient taking tacrolimus experienced increased tacrolimus levels and liver injury after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. It is speculated that garlic inhibited hepatic cytochrome P450 3A4 (CYP3A4), which increased plasma levels of tacrolimus (96010).
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Theoretically, garlic might increase the risk of bleeding with warfarin.
Details
Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time (586,616,1874,3234,4366,4802,4803,51397). In addition, there is a report of two patients who experienced an increase in a previously stabilized international normalized ratio (INR) with concomitant garlic and warfarin use (51228,51631). However, this report has been subsequently debated due to limited clinical information. Other clinical studies have not identified an effect of garlic on INR, warfarin pharmacokinetics, or bleeding risk (15032,16416). More evidence is needed to determine the safety of using garlic with warfarin.
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N-acetyl cysteine might reduce the effects of activated charcoal, while activated charcoal might reduce the absorption of N-acetyl cysteine.
Details
N-acetyl cysteine appears to reduce the capacity of activated charcoal to adsorb acetaminophen and salicylic acid (7869). Conversely, although clinical research suggests that although activated charcoal can reduce the absorption of N-acetyl cysteine by up to 40%, it does not seem to reduce its clinical effects (1755,22774,22775,64501,64647). Other clinical evidence suggests that activated charcoal does not affect the absorption of N-acetyl cysteine (22776,22777).
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Theoretically, N-acetyl cysteine might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Details
Clinical research suggests that intravenous N-acetyl cysteine decreases prothrombin time, prolongs coagulation time, decreases platelet aggregation, and increases blood loss in surgical patients (64511,64644). Furthermore, in vitro research suggests that N-acetyl cysteine increases the anticoagulant activity of nitroglycerin (22780,64780).
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Theoretically, N-acetyl cysteine might increase the risk of hypotension when taken with antihypertensive drugs.
Details
Animal research suggests that N-acetyl cysteine potentiates the hypotensive effects of the angiotensin-converting enzyme inhibitors (ACEIs) captopril and enalaprilat (22785). Theoretically, combining N-acetyl cysteine with other antihypertensive drugs might increase the risk of hypotension.
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Theoretically, N-acetyl cysteine might interfere with the antimalarial effects of chloroquine.
Details
Animal research suggests that N-acetyl cysteine might reduce the antimalarial effects of chloroquine by increasing cellular levels of glutathione (22786).
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N-acetyl cysteine can increase the risk for hypotension and headaches when taken with intravenous or transdermal nitroglycerin.
Details
Clinical research shows that concomitant administration of N-acetyl cysteine and intravenous or transdermal nitroglycerin can cause severe hypotension (2246) and intolerable headaches (2245,2280). Furthermore, in vitro research suggests that N-acetyl cysteine increases the anticoagulant activity of nitroglycerin (22780,64780).
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Below is general information about the adverse effects of the known ingredients contained in the product Heavy Metal Cleanse 2 Evening Formula. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General ...Orally, algin is well tolerated in amounts typically found in foods (11). No adverse effects related to medicinal amounts of algin have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
General
...Alpha-lipoic acid appears to be generally well tolerated when used orally, intravenously, or topically.
Most Common Adverse Effects:
Orally: Headache, heartburn, nausea, and vomiting.
Topically: Irritation and rash.
Intravenously: Nausea and vomiting.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about insulin autoimmune syndrome (IAS).
Cardiovascular ...Orally, hypotension has been reported rarely in a clinical trial (104650).
Dermatologic ...Orally, skin rash and itching have been reported after use of alpha-lipoic acid (16391,20490,21674,96233,104650). Topically, alpha-lipoic acid can cause local irritation, including burning, stinging, mild rash, or contact dermatitis (12021,30836,111701). In one case, an 86-year-old female developed allergic contact dermatitis with severe itching and oozing after applying alpha-lipoic acid 5% cream to her lower extremities. The patient had a positive skin patch test for alpha-lipoic acid, confirming the causative agent (111701). In another case, a 47-year-old female developed contact dermatitis characterized by a pruritic rash and labial adhesions hours after applying a 5% vulvar serum containing lipoic acid 0.9 grams, vitamin E, vitamin C, hyaluronic acid, and retinol palmitate to the vulva to treat vulvar lichen sclerosis. Testing confirmed that the causative agent was alpha-lipoic acid (111704). Intravenously, local allergic reactions have occurred at the injection site (1547).
Endocrine ...Orally, at least 50 published cases of insulin autoimmune syndrome (IAS) thought to be associated with use of alpha-lipoic acid have been reported (16392,104656,104657,104658,104659,107893,112941). Most reported cases have been associated with alpha-lipoic acid supplements or enriched foods; IAS has not been reported with intake of alpha-lipoic acid in food. IAS has been linked to compounds, such as alpha-lipoic acid, that contain sulfhydryl groups, but it is unclear if taking alpha-lipoic acid with other drugs known to trigger IAS increases the risk (107893,112941). IAS is characterized by very high serum insulin levels and high titers of autoantibodies against endogenous insulin. Sulfhydryl groups interact with disulfide bonds of insulin, increasing its immunogenicity (112941). Symptoms include severe spontaneous hypoglycemic episodes, as well as hunger and neuroglycopenic symptoms such as blurred vision, weakness, confusion, dizziness, sweating, and palpitations (104656,104657,107893,112941). Time to onset of IAS ranges from 1 week to 4 months (107893). Most cases of IAS have been reported in Japan and have occurred in individuals with the human leucocyte antigen (HLA)-DRB1*04:06 allele (16392,104656,107893). For patients of European decent, cases of IAS have mainly occurred in individuals with the HLA-DRB1*04:03 allele (104656,104658,104659,107893). This suggests that either of these alleles might produce a genetic predisposition to alpha-lipoic acid-associated IAS. Reported doses of alpha-lipoic acid have ranged from 200-800 mg daily, most commonly 600 mg daily (104656,104658,104659,107893). IAS-related hypoglycemic episodes have been treated with oral or intravenous glucose or sucrose, as well as prednisone. Episodes decline following discontinuation of alpha-lipoic acid, and insulin values normalize within 3-9 months (104656,104658,104659,107893).
Gastrointestinal ...Orally, heartburn, nausea, and vomiting have been reported after use of alpha-lipoic acid (3557,12106,16391,20475,30844,96225,101868,103327,103328,103333)(103335,104650,104654,104655). Higher doses (1200-1800 mg daily) seem to cause more severe effects than lower doses (600 mg daily) (3557,20475,30844,96225). Alpha-lipoic acid may also cause a burning sensation from the throat to the stomach, abdominal discomfort, or bitter taste when used orally (20478,20490,21664,96225). Intravenously, alpha-lipoic acid can cause gastrointestinal upset, including nausea and vomiting. Adverse effects are more common in patients receiving higher intravenous doses (3557) and may be more common in the elderly (96225).
Genitourinary ...Orally, alpha-lipoic acid may cause urinary disorders (20479). Oral alpha-lipoic acid has also been associated with a change in urine odor (96225,103327).
Neurologic/CNS
...Orally, alpha-lipoic acid may cause headache (21664,103328,104655) or dizziness (104650).
Intravenously, paresthesias have been reported to worsen temporarily at the beginning of therapy. Also, intravenous alpha-lipoic acid can cause headache. Adverse effects are more common in patients receiving higher intravenous doses (3557).
General
...Orally, spirulina blue-green algae seem to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, bloating, diarrhea, dizziness, fatigue, flatulence, headache, nausea, and vomiting.
Dermatologic ...Orally, a severe rash has been reported in a 49-year-old woman after taking a spirulina blue-green algae supplement (species and dose unknown). After stopping the supplement, inflammatory myopathy with muscle weakness and elevated creatine kinase occurred. The condition resolved with corticosteroid and cyclophosphamide treatment (75936). In another case report, an 82 year-old woman developed a blistering skin condition over a 2-year period while taking spirulina blue-green algae (A. platensis, dose unknown). She had partly hemorrhagic bullae, secreting erosions and macerations. These symptoms resolved when the supplement was stopped and the patient was treated with oral prednisone, topical silver sulfadiazine, and topical triamcinolone / neomycin (75921).
Gastrointestinal ...Orally, gastrointestinal complaints are amongst the most common adverse effects associated with spirulina blue-green algae, including nausea, vomiting, diarrhea, and abdominal cramps (19272,75924,91713,109969). Similarly, common adverse effects associated with the blue-green algae species Aphanizomenon flos-aquae are stomach upset, flatulence, diarrhea, and bloating (14842).
Hematologic ...Orally, three cases of mild gum bleeding and one case of mild bruising have been reported in patients taking spirulina blue-green algae (Cyactiv, Cerule LLC) 2. 3 grams daily (containing approximately 1 gram of phycocanin) for 2 weeks (97202).
Hepatic ...Orally, significant elevations of liver function tests within 2 weeks of starting a spirulina blue-green algae supplement (species and dose unknown) have been reported in a 52-year-old man stabilized on amlodipine, simvastatin, and acarbose. A biopsy showed feathery degeneration and ballooning of hepatic cells. Cholestasis was present, and an ex-vivo lymphocyte stimulation test for spirulina blue-green algae was positive. All drugs and the spirulina blue-green algae supplement were stopped, with return of the LFTs to normal (9172).
Immunologic
...Orally, urticarial rashes and pruritus have occurred as part of generalized allergic reactions to blue-green algae (91706,91711,91712).
In one case report, a 14-year-old male experienced anaphylaxis with urticaria, lip edema, and asthma 6 hours after taking five tablets of spirulina blue-green algae (A. platensis, strength unknown). He had a positive skin prick test. Oral challenge to an extract of the tablets, and IgE from his serum, reacted with the beta chain of C-phycocyanin from A. platensis (91712).
In another case report, a 17-year-old male with a history of multiple allergies developed rash, pruritus, angioedema, wheezing, and dyspnea within 10 minutes of taking spirulina blue-green algae (A. platensis) 300 mg. He had a positive skin test to A. platensis but no other ingredients of the tablets (91706).
Musculoskeletal ...Orally, after a 49-year-old woman stopped taking a spirulina blue-green algae supplement (species and dose unknown), the patient experienced inflammatory myopathy with muscle weakness and elevated creatine kinase. The condition resolved with corticosteroid and cyclophosphamide treatment (75936). Another case report describes acute rhabdomyolysis that occurred after consumption of spirulina (Arthrospira platensis, Hawaiian spirulina, Solgar Inc., Leonia, NJ) 3 grams daily for 1 month. The 24-year old man presented with weakness, myalgias, elevated creatine kinase and liver function tests, and myoglobinuria (75922).
General
...Orally or intravenously, BCAAs are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal distension, diarrhea, nausea, vomiting.
All routes of administration: High doses can lead to fatigue and loss of motor coordination.
Cardiovascular ...Orally, a single case of hypertension following the use of BCAAs has been reported (37143).
Dermatologic ...Orally, a single case of skin blanching following the use of BCAAs has been reported (681). It is not known if this effect was due to use of BCAAs or other factors.
Gastrointestinal ...Orally, BCAAs can cause nausea, vomiting, diarrhea, and abdominal distension. Nausea and diarrhea has been reported to occur in about 10% of people taking BCAAs (10117,37143,92643,97531).
Neurologic/CNS ...Orally and intravenously, BCAAs can cause fatigue and loss of motor coordination due to increased plasma ammonia levels (693,694,10117). Short-term use of 60 grams of BCAAs containing leucine, isoleucine, and valine for 7 days in patients with normal metabolic function seems to increase levels of ammonia, but not to toxic plasma levels (10117). However, liver function should be monitored with high doses or long-term use (10117). Due to the potential of increased plasma levels of ammonia and subsequent fatigue and loss of motor coordination, BCAAs should be used cautiously before or during activities where performance depends on motor coordination (75). Orally, BCAAs may also cause headache, but this has only been reported in one clinical trial (681).
General
...Orally, chlorella is generally well-tolerated.
Most Common Adverse Effects:
Orally: Allergic reactions, abdominal cramping, constipation, diarrhea, fatigue, flatus, nausea, photosensitivity, and stool discoloration.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.
Dermatologic ...Orally, photosensitivity reactions have occurred following ingestion of chlorella (3900,5852). According to case reports, five patients who had ingested chlorella exhibited swelling followed by erythematopurpuric lesions on sun-exposed areas of the body (5852). The photosensitizing agent in the chlorella tablets was identified as pheophorbide-a and its ester.
Gastrointestinal
...Orally, chlorella can cause diarrhea, abdominal cramping, flatus, and nausea, especially during the first two weeks of treatment (5890,6804,92130,92132).
In one clinical trial, one out of 42 patients reported nausea and one reported diarrhea (92132). In another trial, taking chlorella tablets (Sun Chlorella A, Sun Chlorella Corp) and a chlorella extract (Wakasa Gold, Sun Chlorella Corp) resulted in transient worsening of constipation in 4 of 13 patients and transient mild diarrhea in 2 of 13 patients (92130).
Green discoloration of the feces has also been reported, due to the chlorophyll content of chlorella (6804,95013).
Hematologic ...Orally, chlorella has been linked to one case of thrombocytopenia; however, causality has not been determined. A 49-year-old female living in Turkey presented with thrombocytopenia (a platelet count of 27,000/mm3) after taking chlorella 1080 mg daily for 20 days. Platelet counts had been normal one month earlier, and returned to normal two weeks after discontinuing the chlorella supplement (99879).
Immunologic ...Allergic reactions, including asthma and anaphylaxis, have been reported in people taking chlorella and in those preparing chlorella tablets (3900,5847,41827,105645).
Neurologic/CNS
...Orally, manganese (Mn)-induced parkinsonism has been reported after long-term consumption of chlorella extract.
In this case, a patient on maintenance hemodialysis reported gait disturbance, dysarthria, elevated serum and cerebrospinal fluid manganese levels, and abnormal magnetic resonance imaging (MRI) findings of the brain. The authors identified the condition as a rare case of Mn-induced parkinsonism, which may have been due to long-term ingestion of a chlorella extract containing 1.7 mg of Mn in the usual daily dose. The patient underwent edetic acid infusion therapy, which improved the MRI abnormalities and the other symptoms improved four months later (41817).
In one study, fatigue was reported in 18 of 41 patients receiving chlorella 200 mg (10388).
General ...Topically, cilantro has been reported to cause contact dermatitis (46230). In sensitive individuals, it has also been reported to cause anaphylaxis (92663).
Dermatologic ...Topically, cilantro may cause contact dermatitis, with symptoms including hives or itching (46230).
Endocrine ...Orally, cilantro extract has been associated with a case of endocrine toxicity. A case report describes severe diarrhea, stomach pain, skin darkness, depressed mood, amenorrhea, and dehydration following consumption of 200 mL of a 10% cilantro extract for 7 days (10635).
Immunologic ...Cilantro can cause anaphylaxis in some patients. One case report describes a 52 year-old man who experienced diffuse urticaria following a single ingestion of cilantro, followed by severe angioedema of the face, urticaria, and laryngeal edema following a second ingestion of cilantro. Treatment consisted of treatment with intravenous methylprednisolone, diphenhydramine, and famotidine (92663).
General
...When used orally, Fucus vesiculosus may be unsafe due to its iodine content.
Topically, Fucus vesiculosus appears to be well tolerated.
Most Common Adverse Effects:
Orally: Goiter, hyperthyroidism, hypothyroidism.
Serious Adverse Effects (Rare):
Orally: Thyroid cancer.
Cardiovascular ...In one report, a young adult with obesity developed palpitations and syncope after taking an oral weight loss supplement containing a combination of Fucus vesiculosus, dandelion, and boldo for 3 weeks. The patient was found to have a prolonged QT interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether Fucus vesiculosus, another ingredient, or the combination of ingredients is responsible for this adverse effect. The product was not analyzed to determine the presence of any potential toxic contaminants.
Endocrine
...Orally, Fucus vesiculosus can cause or exacerbate hyperthyroidism due to its high iodine content (12789,13061,74217).
One case of hyperthyroidism has been reported for a 60-year-old patient taking lithium for bipolar disorder and a combination product containing Fucus vesiculosus 0.125 grams, cascara 0.170 grams, and Frangula 0.222 grams per tablet for laxative purposes. The patient had been taking one tablet of the combination laxative product daily for several years. Following discontinuation of the supplement, thyroid levels normalized (74217). Similar cases of hyperthyroidism have been reported for patients taking other seaweed-containing herbal supplements (Dream Shape; Ever Youth). Analyses of these supplements shows that these products contain triiodothyronine 1 mcg and thyroxine 3-4 mcg. In addition to seaweed, Dream Shape also contains hydrangea vine, maltose, chrysanthemum, Chinese matrimony vine, and sucrose, while Ever Youth contains radish, lotus leaf, chrysanthemum, hawthorn, senna tea, and Chinese matrimony vine (13061).
Orally, prolonged use of Fucus vesiculosus has been associated with hypothyroidism (13664). The iodine in Fucus vesiculosus can cause idiosyncratic reactions.
According to the Institute of Medicine Food and Nutrition Board, prolonged, high dietary intake of iodine is associated with goiter and an increased risk of thyroid cancer (7135).
Genitourinary ...A case of hemorrhagic cystitis characterized by dysuria and polyuria has been reported in a young adult who took a specific product (Slim-Kombu, Balestra and Mech) containing Fucus vesiculosus and 19 other herbal extracts orally for weight loss. Upon discontinuation, symptoms improved (46959). It is unclear if this effect was due to Fucus vesiculosus or other ingredients in the supplement.
Renal ...A case of hemorrhagic cystitis characterized by dysuria and polyuria has been reported in a young adult who took a specific product (Slim-Kombu, Balestra and Mech) containing Fucus vesiculosus and 19 other herbal extracts orally for weight loss. Upon discontinuation, symptoms improved (46959). It is unclear if this effect was due to Fucus vesiculosus or other ingredients in the supplement. Nephrotoxicity has been associated with oral intake of Fucus vesiculosus that was contaminated with arsenic (12800).
General
...Orally, garlic is generally well tolerated.
Topically, garlic seems to be well tolerated. Intravenously, there is insufficient reliable information available about adverse effects.
Most Common Adverse Effects:
Orally: Abdominal pain, body odor, flatulence, malodorous breath, and nausea. Allergic reactions in sensitive individuals.
Topically: Burns and dermatitis with fresh garlic.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about increased risk of bleeding with garlic.
Dermatologic
...Orally, garlic may cause pruritus (51316,51474,107239), flushing, and acne (107239).
Oral intake of a specific garlic product containing allicin (Allimax) has been associated with a case of pruritic rash (51474). Enteric-coated garlic tablets standardized to 1.5% allicin have also been associated with a case of pruritus (51316). Garlic has also been associated with a case of superficial pemphigus in a 49-year-old male with type 2 diabetes (51564). Garlic-induced oral ulcers have also been reported (51467).
Topically, garlic may cause contact dermatitis and urticaria (4833,5004,12635,51258,51265,51375,51403,51412,51459,51483)(51511,51512,51530,51616,51617,51618,111769), as well as contact cheilitis (51384). Fresh garlic may be more likely to elicit a reaction than garlic extract. Most reactions have resolved following withdrawal of garlic therapy. In one case report, applying crushed garlic on the neck to help ease a sore throat resulted in an itchy, burning, erythematous lesion in a young female patient. The lesion healed after one week of treatment with topical antibiotics, steroids, and antihistamine ointments (88390). Cases of occupational eczema or dermatitis have been reported in cooks (51303,51210), food handlers (51292), and caterers (51304). According to one case report, dermatitis appeared in chefs exposed to garlic (15033). Treatment with acitretin 25 mg daily or topical psoralen-ultraviolet A (PUVA) for 12 weeks proved effective in mitigating the symptoms. A 34-year-old female with a history of hand dermatitis and paronychia had a worsening of these conditions after peeling raw garlic. She had a positive skin patch test to fresh, raw garlic but not to any other tested allergens, and the conditions resolved when she avoided contact with garlic (105528). Topically, garlic may also cause chemical burns, usually within 12 hours of application. Second- and third-degree chemical burns have been reported in adults, children, and infants exposed to topical garlic, often as an unintended consequence of using garlic medicinally on the skin (585,4832,51226,51230,51252,51281,51377,51418,51468,51495,51536)(51558,51576,51577,88409,96006). A case of painful blisters on the soles of the feet of a 23-year-old Chinese female has been attributed to chemical burns caused by applying crushed raw garlic for 3 hours (51440). Topically, garlic may also cause hyperpigmentation, ulcers, necrotic lesions, facial flushing, and local irritation (4832,15030,51268,51269,108606). In one case report, applying crushed raw garlic to the palatal mucosa for several minutes to relieve mouth pain resulted in a chemical burn that produced a 3 cm necrotic ulcer in an adult female with trigeminal neuralgia (108606).
Gastrointestinal
...Orally, dehydrated garlic preparations or raw garlic may cause malodorous breath (51438,51444), body odor (732,1873,4784,4793,4795,4798,9201,10787,42692,49769)(51269,51316,51467,51602), abdominal pain or fullness, anorexia, diarrhea, constipation, flatulence, belching, heartburn, nausea, unpleasant taste, reflux, and bowel obstruction (1884,6457,6897,9201,49769,51269,51343,51380,51438,51442)(51450,51457,51466,51471,51474,51520,51593,51602,51623,88398)(88405,111766,114892).
Large quantities of garlic may damage the gastrointestinal tract. In one case report, a patient taking garlic for hypertension reported odynophagia and retrosternal pain after taking garlic without any water the previous day. An esophageal lesion 3 cm in length was detected upon endoscopy. The symptoms resolved 3 days after starting a liquid diet and taking lansoprazole 30 mg twice daily and sucralfate four times daily (88389). One case of bowel obstruction was reported in a 66-year-old male who ingested an entire garlic bulb (51525). Esophageal perforation has been reported in at least 17 individuals who consumed entire garlic cloves. In one case the perforation led to mediastinitis and death (102672).
Garlic has also been associated with eosinophilic infiltration of the gastrointestinal tract. In one case report a 42-year-old female presented with symptoms of eosinophilic gastroenteritis, which included pollinosis, asthma, diarrhea, heart burn, peripheral eosinophilia, and urticaria. After stopping use of garlic and sesame, the patient improved (51441). In a case report of eosinophilic esophagitis, garlic was determined to be the causative agent in a patient with long-standing gastrointestinal symptoms. The patient had attempted to treat upper gastrointestinal symptoms as gastrointestinal reflux disease without success for many years. Skin prick testing showed a positive reaction to garlic, of which the patient noted frequent consumption. Marked symptom improvement was noted within 3 weeks of garlic avoidance (88393).
Intravenously, garlic 1 mg/kg of body weight daily diluted into 500 mL saline and administered over 4 hours has been reported to cause abdominal discomfort, vomiting, diarrhea, nausea, anorexia, flatulence, weight loss, and garlicky body odor (51462).
Clinical research suggests that patients with metabolic syndrome taking 1600 mg of powdered garlic by mouth daily for 3 months may experience improved intestinal transit time when compared with placebo, suggesting that garlic powder may reduce symptoms of constipation (110722).
Genitourinary ...Orally, garlic might cause dysuria, hematuria, or polyuria (51438,51450,51467,113618). In one case, an older male with high dietary and supplemental garlic intake at doses of 300-5400 mg daily for 3-4 years developed severe hematuria with clots after undergoing a minimally invasive prostate procedure (113618).
Hematologic
...Oral use of dietary garlic or supplements containing garlic has caused platelet dysfunction, increased fibrinolytic activity, prolonged bleeding time, retrobulbar hemorrhage (bleeding behind the eye) postoperative bleeding, and spinal epidural hematoma (586,587,4801,4802,11325,51397,51473,51491,51532,51534)(51570,51584,51593,51594,113618).
Also, a case of kidney hematoma following extracorporeal shock-wave lithotripsy (SWL) has been reported in a patient with nephrolithiasis who took aged garlic (51630). A case of increased bleeding time that complicated epistaxis management has been reported in a patient taking garlic, aspirin, and milk thistle (51426).
Intravenously, garlic has been associated with the development of thrombophlebitis at the injection site (51462).
Immunologic
...There is a case report of an immediate sensitivity reaction to oral raw garlic, resulting in wheals, in a 31-year-old female.
The patient did not react to cooked garlic, and skin prick tests showed allergy only to raw garlic (96015). Researchers note that at least some allergens in raw garlic are heat labile (88392,96012,96015). This suggests that consuming cooked rather than raw garlic may help avoid this reaction in patients allergic to raw garlic. However, different people react to different allergens in garlic. At least some of these allergens are heat stable (96012). While rare, garlic-induced anaphylaxis has been reported (88392,96012).
Topically, allergic contact dermatitis has been reported in case reports (51406,51498,51510,51519,51560).
Musculoskeletal ...Orally, garlic has been associated with individual cases of gout and low back pain (51474,51467), but it is not clear if these adverse events can be attributed to garlic.
Neurologic/CNS ...Orally, dizziness, insomnia, headaches, diaphoresis, fever, chills, somnolence, increased appetite, euphoria, and weight loss have been reported with garlic (15032,42692,51316,51467,51471,51520). In one case, the smell of garlic was identified as a trigger for migraines in a 32-year-old female. The subject reported fortification spectra along with visual spots for a few seconds followed by instantaneous biparietal, crushing level (10/10) headaches upon exposure to the scent of garlic or onion (88404).
Pulmonary/Respiratory ...Garlic exposure, most notably in occupational settings, may cause asthma and other symptoms such as sneezing, nasal obstruction, rhinorrhea, and sinusitis (40661,51218). A case of minor hemoptysis has been reported for one patient with cystic fibrosis following intake of garlic capsules orally once daily for 8 weeks (51438). A 77-year-old female developed pneumonia related to the intake of one whole black garlic clove daily. The cloves were prepared by heating a whole garlic bulb in a pot for one month. Symptoms included dyspnea and coughing, and test results were positive for lymphocyte-induced stimulation by black garlic and raw garlic. The patient required treatment with oral steroids and was told to avoid garlic (96011).
General
...Orally, intravenously, and as an inhalation, N-acetyl cysteine is generally well-tolerated when used in typical doses.
Most adverse effects to N-acetyl cysteine occur when single doses of greater than 9 grams are used or when a regimen of greater than 30 grams daily is followed.
Most Common Adverse Effects:
Orally: Diarrhea, dry mouth, dyspepsia, heartburn, loss of appetite, nausea, and vomiting.
Intravenously: Skin rash and hypersensitivity reactions.
Inhaled: Bronchospasm, cough, epigastric pain, throat irritation, and wheezing.
Serious Adverse Effects (Rare):
Orally: Chest tightness, hemoptysis, and palpitations have been reported.
Intravenously: Anaphylaxis, angina, dystonic reactions, tachycardia, and transient sinus bradycardia have been reported.
Cardiovascular
...Intravenously, N-acetyl cysteine has been reported to significantly increase systolic and diastolic blood pressure after exposure to nitroglycerin when compared with placebo (2280).
Tachycardia, chest pain, angina, and transient sinus bradycardia have been rarely reported after administration of intravenous N-acetyl cysteine (2280,7872,64658).
Intratracheally, infants receiving 5% N-acetyl cysteine every four hours for chronic lung disease have developed bradycardia (64490).
Orally, palpitations and chest tightness have been reported rarely in clinical research evaluating oral N-acetyl cysteine at doses up to 600 mg twice daily (64675,64717,64762).
Dermatologic
...Orally, N-acetyl cysteine may cause hives (64713,64739,64813), flushing (2260,64715), and edema (64714).
Rash has also been reported (64510,64715,64717,102656). In one study, flushing was reported in 2% of patients receiving 600 mg of N-acetyl cysteine orally twice daily for six months (2260).
Intravenously, N-acetyl cysteine may cause rash, and the occurrence seems to be more common than with oral use (2254,64492,64562,64658,64759,64794). Hives (2280,64794), facial edema (2280), flushing (64412), and pruritus (64658,64763) have also been reported. In a small case series of 10 healthy male patients receiving 150 mg/kg of intravenous N-acetyl cysteine for muscle fatigue, erythema was experienced 30 minutes after infusion. Other side effects reported by these patients include facial erythema, palmar erythema, and sweating (64763). In other clinical research, three patients developed an erythematous flare at the sites of previous venipunctures after receiving 5.5 gm/m2 of N-acetyl cysteine with doxorubicin therapy (64712). Pain, inflammation, and excoriation of the skin have been reported after a 20% N-acetyl cysteine solution leaked from the catheter in one patient (64726).
Gastrointestinal
...Orally, gastrointestinal complaints are the most common adverse effects reported with N-acetyl cysteine.
These include heartburn (64608,64715,64717,64738,64739,102666), dyspepsia (1710,64715,64717,64724,64738), and epigastric pain (2260,10429,64715,64717). In one case report, esophagitis related to ulcerations occurred following intake of N-acetyl cysteine while in the supine position with inadequate water (102655). Other common side effects include loss of appetite (64715,64812), flatulence (2256,64510), diarrhea (64713,64715,97049), constipation (64715), dry mouth (64715,64724), nausea (7868,11430,64715,64724,64738,64812,97049), vomiting (64717,64724,64715,97049), gastric upset (64510,64545,97045,97049), acid reflux (108450), changes in bowel habits (108450), and intolerance to taste and odor (64510,64545). N-acetyl cysteine's unpleasant odor makes it difficult for some patients to take orally. Using a straw to drink N-acetyl cysteine solutions can improve tolerability. Additionally, placement of a nasogastric or duodenal tube and administration of metoclopramide or ondansetron can be helpful for patients unable to tolerate oral N-acetyl cysteine (17).
Intravenously, N-acetyl cysteine may cause diarrhea (64712), dyspepsia, nausea, vomiting (64763), mild gastrointestinal upset (102657), and metallic taste (64763).
When inhaled, N-acetyl cysteine may cause epigastric pain and throat irritation (64703,64707,64674).
Genitourinary ...Orally, dysuria was reported in 2% of patients receiving 600 mg of N-acetyl cysteine twice daily for 6 months in one clinical trial (2260).
Hematologic
...In general, hematologic adverse reactions are reported more frequently with intravenous N-acetyl cysteine compared with oral use.
In surgical patients, decreased prothrombin time (1341,64511), prolonged coagulation time (64511), increased blood loss (64511,64644), and decreased platelet aggregation (64511) have been reported after administration of IV N-acetyl cysteine. In one clinical trial, six healthy patients were administered a loading dose of IV N-acetyl cysteine 10 mg/kg followed by 10 mg/kg per hour for 32 hours. All patients experienced a decrease in prothrombin time by 30% to 40%. The decrease prothrombin time (25.4 sec to 20.6 sec) reached a steady state after 16 hours (1341). In a clinical trial evaluating patients with acute myocardial infarction, hemorrhage occurred in three patients taking intravenous N-acetyl cysteine 10 mg/min, heparin (per study protocol), and aspirin (7872). Two pediatric patients receiving intravenous N-acetyl cysteine (loading dose: 140 mg/kg followed by 70 mg/kg) experienced episodes of coagulopathy; however, patients were being treated for acetaminophen overdose (64794).
Hemoptysis was reported in six patients receiving 200 mg of N-acetyl cysteine orally twice daily for 6 months for treatment of chronic bronchitis (64739).
Immunologic
...Orally, anaphylaxis to N-acetyl cysteine has been rarely reported (64794).
However, anaphylactic reactions to intravenous N-acetyl cysteine appear to be more common (1716,64412,64449,64628,64710,64711,64721,64786,64789).
Anaphylactic reactions to N-acetyl cysteine have involved rash, angioedema, hypotension, and bronchospasm (64449,64711,64720). The mechanism of this reaction is unclear, but some data suggest it is not an immunologic hypersensitivity reaction but rather an acute toxic effect of N-acetyl cysteine (64786,64641,64720). Management guidelines for the treatment of anaphylactoid reactions to intravenous N-acetyl cysteine have been published. In most cases, treatment is not required or treatment with diphenhydramine or salbutamol is sufficient to continue or restart N-acetyl cysteine infusion. Antihistamines are useful in controlling and preventing recurrence of anaphylactoid symptoms (1716).
Musculoskeletal ...In one clinical trial, joint pain was reported in more than 15% of patients receiving oral N-acetyl cysteine (64608). In other research, one patient experienced pain in the legs while taking 600 mg of N-acetyl cysteine twice daily for the treatment of chronic bronchitis (64762).
Neurologic/CNS
...Orally, headache has been frequently reported with N-acetyl cysteine in clinical research (7873,11430,64510,64608,64672,64713,64715,64724,64762).
Other less common adverse effects reported in patients taking oral N-acetyl cysteine at a total daily dose of 600-1200 mg include dizziness (64715,64717,64724,64762), tiredness (64675,64717), vivid dreams (102666), disorientation, and inability to concentrate (64673). One pediatric patient receiving oral N-acetyl cysteine (loading dose: 140 mg/kg followed by 70 mg/kg) experienced encephalopathy (64794).
Intravenously, N-acetyl cysteine has been associated with rare neurologic adverse reactions , including headache (7872), lightheadedness (64763), and dystonic reactions (64794). In a previously healthy 2-year-old female, status epilepticus occurred during intravenous N-acetyl cysteine therapy for paracetamol ingestion (64781). Increased deterioration in bulbar function in patients with amyotrophic lateral sclerosis has also been reported with IV N-acetyl cysteine (2254).
Ocular/Otic ...While rare, blurred vision has been reported in research on oral N-acetyl cysteine (64715). Additionally, in a previously healthy 2-year-old female, status epilepticus followed by cortical blindness occurred during intravenous N-acetyl cysteine therapy for paracetamol ingestion. In this case, vision was almost completely recovered 18-months later (64781).
Psychiatric ...Intravenously, dysphoria was experienced 30 minutes after infusion of N-acetyl cysteine in 8 of 10 healthy males assessed in one clinical study (64763).
Pulmonary/Respiratory
...Respiratory adverse reactions to N-acetyl cysteine are most commonly reported with inhalable dosage forms.
These include wheezing (64455,64707), bronchospasm (64455,64699), and cough (64455,64456,64703,64811). While less frequent, wheezing (64675), bronchospasm (64675), increased sputum production (7868), cough (7868,64510), decreased peak flow (64510), dyspnea (64714), and cold symptoms (64510) have been reported with oral N-acetyl cysteine in clinical research. A few cases of wheezing (64718,64719), cough (64763), and bronchospasm (64658) have also been reported with intravenous N-acetyl cysteine. Additionally, respiratory arrest has been reported in one case where a 16 year-old female was being treated for acetaminophen toxicity with intravenous N-acetyl cysteine (64450).
Two premature infants receiving 5% N-acetyl cysteine via intratracheal instillation for the treatment of chronic lung disease had an increased frequency of cyanotic spells (64490).
Other ...Injection site reactions, including burning and phlebitis, have been reported in patients receiving IV N-acetyl cysteine (1341,64763). Fever associated with IV N-acetyl cysteine was reported in one patient during clinical research (64759).
