Metagenics
Gastro Aid
Alleviates Heartburn
Clinically effective in alleviating symptoms of heartburn, indigestion, upper abdominal fullness / pain, belching, bloating and nausea.
- For treatment of heartburn and indigestion
- Soothes mucus membranes
- Aids digestion and improves gastric motility
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BENEFITS
CLINICALLY PROVEN;
Clinically effective in reducing symptoms such as reflux and heartburn
Potent anti-inflammatory agent for the relief of upper gastrointestinal tract complaints
High efficacy in the treatment of gastric and duodenal ulcers
Alleviates symptoms of upper abdominal fullness, upper abdominal pain, belching, bloating, early satiety, nausea, vomiting, regurgitation, heartburn, and loss of appetite
Improves gastric motor function
Possesses anti-Helicobacter pylori activity
Increases concentration of beneficial prostaglandins that promote protective mucus secretion and cell proliferation / renewal in the stomach lining.
Increases mucosal blood flow, which may enhance healing.
Glycyrrhiza glabra (liquorice):
Has been used medicinally for several centuries throughout the world. Liquorice root is indicated for the use for gastric and duodenal ulcers in Western herbal medicine,[15] and for gastrointestinal hyperacidity and ulcers in Ayurvedic medicine.[16] Liquorice is reported to have expectorant, diuretic, laxative, sedative, antipyretic, antimicrobial, hepatoprotective and antioxidant properties.[17]
GutGard® :
A flavonoid rich, deglycyrrhizinated,[*] standardised extract of liquorice root which contains ≥10% w/w of total flavonoids, including significant levels of glabridin (≥3.5% w/w).[18] Glabridin (Figure 3) is a key active ingredient in liquorice, and is a proven, potent anti-inflammatory agent.[19] GutGard® has also been found to possess potent antioxidant activity; research has shown it has a high hydrophilic and lipophilic oxygen radical absorbance capacity (ORAC),[**] yielding 1290 and 5279 trolox equivalents (TE)/g, respectively.[20]
Curcumalonga (turmeric) dried rhizome:
Has long traditional use for gastrointestinal conditions. In Ayurvedic medicine, it has been used for “all intestinal infections and mucus conditions,” for reducing pathogenic bacteria and for treating dyspepsia.[22] The digestive stimulant properties are also reflected in Western herbal medicine usage, where turmeric is also used for poor liver function, and is recognised to have antimicrobial and carminative properties.[23]
BCM-95™ :
A patent-pending proprietary 100% natural turmeric extract containing curcuminoids and various volatile compounds of turmeric. It is a reconstituted, purified and standardised turmeric extract which enhances the bioavailability of curcumin. Human studies have shown that as well as up to 700% enhanced bioavailability, BCM-95™ gives enhanced retention of curcumin in the blood when compared with a standard turmeric extract.
Cynara scolymus (globe artichoke):
Has been used traditionally for constipation, dyspepsia and associated symptoms, due to its choleretic, prokinetic and antispasmodic effects.[26] Extracts of globe artichoke leaves are rich in flavonoids and bitter compounds, such as cynaropicrin, which are responsible for its therapeutic actions.[27],[28]
Matricaria chamomilla (German chamomile):
Has been used externally in traditional support of gastrointestinal spasm, inflammatory diseases of the gastrointestinal tract, flatulence, bloating and nervous dyspepsia. German chamomile flowers contain a number of key active ingredients such as essential oils, including α-bisabolol; flavonoids including apigenin, rutin, luteolin and quercetin; and the proazulenes matricin and matricarin.[29] Laboratory research has identified several key actions of chamomile flowers that may be important for the management of digestive conditions.
These effects appear to be due to several anti-inflammatory constituents, with the flavonoid apigenin proving most potent. Apigenin has been found in vivo to reduce interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) which may explain part of its anti-inflammatory effect.[30]
Foeniculum vulgare (fennel):
Commonly used to support upper gastrointestinal complaints such as pain, nausea, belching and heartburn.[31] Fennel seeds contain volatile oils, flavonoids (rutin, quercetin, and kaempferol glycosides), coumarins and sterols, which are believed to contribute to fennel’s anti-ulcer and antioxidant activity. Animal studies have shown that fennel seeds promote gastrointestinal motility, reduce spasm, reduce food transit time and protect against ethanol-induced gastric lesions.[32],[33]
FUNCTIONAL DYSPESIA
A randomised, controlled trial was conducted to evaluate the effect of the liquorice extract, GutGard®, for the treatment of patients with functional dyspepsia.
Fifty patients received either 4.2 g/day of GutGard® or a placebo for 30 days and rated their severity of 10 gastrointestinal symptoms (upper abdominal fullness, upper abdominal pain, belching, bloating, early satiety, nausea, vomiting, regurgitation, heartburn, and loss of appetite).
Those receiving GutGard® showed a significant decrease in total symptom score on day 15 and day 30 (p<0.05). As a secondary outcome measure, the Nepean Dyspepsia Index (NDI) was used to measure the quality of life in these patients.
The results found that patients receiving GutGard® had a significant decrease (p<0.05) in the NDI on day 15 and day 30 compared to the placebo group (Figure 5), demonstrating an improvement in quality of life in those taking GutGard®.[34]
Additional analysis was performed on the global efficacy of the treatment; it was found one patient was completely free of symptoms using GutGard®, with a further 23 patients reporting significant improvements.
Overall 24/25 subjects reported benefit from the use of GutGard® with 56% patients considered to markedly improve from the treatment. In comparison, only 11/25 patients receiving the placebo reported (moderate) benefit with 56% finding no change after 30 days. Figure 6 details the global efficacy of GutGard® versus the placebo.[36]
A randomised controlled trial demonstrated that globe artichoke is also effective for the management of functional dyspepsia. The study included 247 patients with functional dyspepsia who received either 9 g/day of globe artichoke (divided across three doses), or a placebo for 6 weeks.
Those administered the globe artichoke reported a significantly greater improvement in symptoms of dyspepsia compared to the placebo (p=0.006). Patients receiving the globe artichoke also reported significant improvement in symptoms of fullness (p=0.005), early satiety (p=0.0032), and flatulence (p=0.0112) compared to placebo.
The authors suggest that globe artichoke’s ability to improve these symptoms is due to its choleretic effects; that is, by increasing bile secretion gastrointestinal transit time is increased, thus alleviating bloating and fullness.[38]
Results from an open label pilot trial also provide evidence that globe artichoke is effective for the management of dyspepsia. Four hundred and fifty four subjects with dyspepsia received either 1.6 g or 3.2 g/day of globe artichoke for two months and recorded their dyspepsia symptoms daily.
After the two months of therapy, both groups recorded a significant improvement in their symptoms from baseline (p<0.01). Moreover, there was a significant improvement in all symptoms in both groups from baseline (Table 1).[39]
It is suggested that globe artichoke assists functional dyspepsia by its prokinetic action (promoting gastric motor function).
A randomised placebo-controlled double-blind cross-over study found that after a single dose of 2 g of globe artichoke subjects recorded a large increase in bile secretion at 120 and 150 minutes after ingestion. An increase in bile secretion 2-3 hours after a meal is considered clinically important as this will help promote enzymatic digestion and stimulate intestinal motor function.[41]
A randomised controlled trial on turmeric showed it was superior to a placebo for the management of dyspepsia. In this seven day trial, 38 patients received 500 mg of turmeric four times a day (2 g/day total) and were compared to 38 patients receiving a placebo.
Symptoms of abdominal pain associated with empty stomach or spicy food (acid dyspepsia) and epigastric discomfort associated with frequent belching (flatulent dyspepsia) were recorded before and after the trial. It was found that those receiving turmeric reported significant improvement in symptoms compared to those receiving the placebo (p=0.003).[42]
GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
In a clinical trial investigating GutGard® the efficacy of the treatment was assessed in 50 GORD patients using the 7-point Likert scale, which included the symptom of heartburn. The results found that those administered GutGard® demonstrated a significant decrease in total symptoms score on both day 15 and day 30 (p<0.05). The changes in symptom score for heartburn are illustrated in Figure 7.[43]
Results from a pilot study indicate that curcumin improves symptoms of GORD. Fourteen GORD patients, who were dependant on PPIs or H2-blockers on a daily basis for complete symptomatic relief, were administered 2 g/day of curcumin alongside their usual medications for two weeks.
After the two weeks, volunteers were asked to discontinue their PPI or H2-blocker therapy and continue taking the curcumin alone for eight weeks. After eight weeks of curcumin therapy alone, 11 out of 14 patients (79%) were asymptomatic. Of the three non-responders, one patient was able to achieve symptomatic relief on a lower dose of their PPI therapy.[45]
PEPTIC ULCER
Deglycyrrhizinised liquorice (DGL) has shown high efficacy in the treatment of gastric and duodenal ulcers. In a trial, 33 gastric ulcer patients were treated with either DGL at a dose of 760 mg three times daily, or placebo for one month. The DGL group experienced a 78% reduction in ulcer size compared to 34% in placebo. Complete healing occurred in 44% of the treatment group, but only in 6% of the placebo group.[46]
Another study of DGL was conducted in 40 patients with severe chronic duodenal ulcers of four to twelve years duration, experiencing more than six relapses yearly. All patients had been referred for surgery due to relentless pain, sometimes with frequent vomiting, despite treatment.
Twenty patients received 3 g/day of DGL for eight weeks, and the remaining twenty received 4.5 g/day DGL for six weeks. The higher dose was found to be more effective, but all 40 patients showed significant improvement within seven days. None required surgery within the one year follow up. Treatment with DGL was well tolerated and safe.[47]
Animal models and in vitro studies have identified several mechanism of liquorice’s anti-ulcer action. GutGard® extracts have demonstrated in several animal studies to significantly inhibit gastric mucosal lesions caused by pylorus ligation, cold-restraint stress and NSAID treatment.
The authors suggest that the flavonoids in GutGard® possess potent antioxidant activity (as demonstrated by its high ORAC value) which prevents reactive oxygen species from mediating damaging effects and promoting the development of ulcers.
Other studies suggest liquorice have shown this herb exerts other effects that may help in the management of peptic ulcers, such as:
Glabridin and glabrene, the flavonoids found in high quantities in GutGard®, have been shown to possess anti-Helicobacter pylori activity in vitro.[48]
Liquorice inhibits the conversion of prostaglandin E2 and F2α to their inactive forms, thereby increasing the local concentration of these beneficial prostaglandins that promote mucus secretion and cell proliferation in the stomach lining.[49]
Liquorice increases mucosal blood flow, which may enhance healing.[50]
In vitro studies indicate that curcumin, from turmeric, can inhibit H. pylori-induced NF-kB activation and the subsequent release of interleukin 8 (IL-8), a cytokine that plays a key role in the virulence of H. pylori infections.[51]
Additionally, the H. pylori-induced motogenic response was found to be blocked by curcumin.[52] Additional benefits may be provided via antibacterial effects. Turmeric and curcumin have both been found to have bactericidal effects on H. pylori.[53],[54]
INGREDIENTS
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DIRECTIONS
Adults:
Acute - Take 1 capsule three times daily.
Maintenance - Take 1 capsule twice daily.
EVIDENCE
References
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[16] Pole S. Ayurvedic Medicine: The Principles of Traditional Practice. Philadelphia; Elsevier, Churchill Livingstone, 2006: 220-221.
[17] Raveendra KR, et al. An extract of Glycyrrhiza glabra (GutGard®) alleviates symptoms of functional dyspepsia: a randomized, double- blind, placebo-controlled study. Evid Based Complement Alternat Med. 2012;2012:216970.
[18] Raveendra KR, et al. An extract of Glycyrrhiza glabra (GutGard®) alleviates symptoms of functional dyspepsia: a randomized, double- blind, placebo-controlled study. Evid Based Complement Alternat Med. 2012;2012:216970.
[19] Chandrasekaran CV, Deepak HB, Thiyagarajan P, Kathiresan S, Sangli GK, Deepak M, Agarwal A. Dual inhibitory effect of Glycyrrhiza glabra (GutGard®) on COX and LOX products. Phytomedicine. 2011 Feb 15;18(4):278-84.
[20] Mukherjee M, Bhaskaran N, Srinath R, Shivaprasad HN, Allan JJ, Shekhar D, Agarwal A. Anti-ulcer and antioxidant activity of GutGard®. Indian J Exp Biol. 2010 Mar;48(3):269-74.
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WARNINGS
Contraindications
Allergy or Hypersensitivity: Turmeric,[55],[56] globe artichoke,[57],[58],[59] and chamomile,[60][61] may cause allergies or hypersensitivity in sensitive individuals. Avoid use in individuals with known sensitivities.
Turmeric: Contact dermatitis has been reported, as has a single case of anaphylaxis.[62] Avoid if allergic or hypersensitive to turmeric and/or curcuminoid, and in known sensitivity to salicylates.[63]
Globe artichoke: Avoid in individuals with known allergy or hypersensitivity to artichoke and/or members of the Asteraceae/Compositae family.[64],[65],[66]
Chamomile: Avoid in individuals with known allergy or hypersensitivity to chamomile and/or members of the Asteraceae/Compositae family.[67],[68]
Moderate level Cautions
Anticoagulant/Antiplatelet drugs: The curcuminoids in turmeric have antiplatelet effects.[69],[70] Concomitant use alongside anticoagulant or antiplatelet agents such as aspirin and warfarin might increase the risk of bleeding.[71] Use with caution, and for patients taking warfarin, monitor International normalised ratio (INR).
Bleeding disorders: Due to the antiplatelet properties of turmeric, there have been safety concerns with regards to the risk of increased bleeding tendency in patients with bleeding disorders.[72],[73] Studies are limited, however it still warrants caution in situations that carry a high risk of bleeding, such as haemorrhagic stroke and postoperative events. To minimise the risk of exacerbation of these serious bleeding events, it is recommended to discontinue use of turmeric during acute bleeding episodes.
Chemotherapy/Radiotherapy: It has generally been thought that antioxidants may interfere with chemotherapy and/or radiotherapy by decreasing the efficacy of the treatment. However, review studies have found that antioxidants are safe to use in conjunction with these treatments.[74],[75] Given the serious nature of the condition, it is still advisable to check with a patient’s oncologist before recommending a formula containing antioxidants.
Whilst curcumin has been shown to enhance chemotherapy in ovarian cancer,[76] it may suppress chemotherapy-induced apoptosis in breast cancer: curcumin was found to inhibit chemotherapeutic effects by reducing camptothecin-, mechlorethamine- or doxorubicin-induced apoptosis in breast cancer cells, and reduce the effectiveness of cyclophosphamide in an in vivo mouse model.[77] In contrast, curcumin has also been shown to augment the cytotoxic effects of other chemotherapeutic drugs, including doxorubicin, tamoxifen, cisplatin and camptothecin, 5-fluorouracil, paclitaxel, daunorubicin, vincristine, and melphalan, with no effect on the toxicity of etoposide, daunorubicin, and idarubicin.[78] Use with caution and only under the supervision of a patient’s oncologist.
Gallstones, gallbladder disease and/or bile duct obstruction: Globe artichoke,[79],[80],[81] and turmeric,[82],[83] may stimulate bile flow. Use with caution and only under medical supervision in patients with any history of gallbladder or bile duct complaints.[84],[85],[86]Globe artichoke: Globe artichoke may worsen bile duct obstruction and/or increase the risk of gall bladder issues by increasing bile flow.[87],[88],[89]
Turmeric: Turmeric can benefit gallbladder health through promoting the flow of bile via stimulation of gallbladder contraction.[90],[91]
Surgery: Due to the anticoagulant properties of turmeric, there have been safety concerns with regards to the risk of increased postoperative bleeding.[92],[93] Studies are limited, however it would still warrant caution in postoperative events. To minimise the risk of exacerbation of these bleeding events, it is recommended to discontinue use of turmeric four to seven days before elective procedures which have a high risk for bleeding complications.
Warfarin: Turmeric,[94],[95] liquorice,[96],[97],[98],[99] and chamomile,[100],[101],[102],[103],[104],[105],[106] may affect the activity of warfarin through either increased risk of bleeding, or through changes of the drug’s P450 metabolism. Use cautiously in patients on this medication and monitor International normalised ratio (INR) levels, and signs of excess bleeding.P450 enzymes: This anticoagulant medication is metabolised by cytochrome P450 enzymes 1A1,1A2,[107],[108] and 3A4,[109],[110] and has a narrow therapeutic range.[111],[112],[113] Turmeric may inhibit the activity of CYP1A1 and CYP1A2,[114],[115] and chamomile,[116],[117],[118],[119],[120] may inhibit CYP3A4[121],[122] and CYP1A2.[123],[124],[125] Whilst liquorice may induce the activity of CYP3A4.[126],[127] These interactions with P450 enzymes may theoretically alter the drug’s therapeutic effect.[128],[129],[130]
Low level Cautions
Amiodarone: This class III anti-arrhythmic drug is metabolised by the cytochrome P450 enzymes 3A4[131],[132] and 1A2,[133],[134] and has a narrow therapeutic range.[135],[136]Turmeric,[137],[138] and chamomile,[139],[140],[141] may inhibit the activity of CYP1A2, and chamomile may also inhibit the activity CYP3A4.[142],[143] Liquorice may induce the activity of CYP3A4.[144],[145] These interactions with P450 enzymes may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Antihypertensive medication: The mineralocorticoid effects of liquorice can increase blood pressure,[146],[147] and therefore may alter the efficacy of the antihypertensive medication. This effect is attributed to the glycyrrhizin in liquorice.[148] This supplement contains deglycyrrhized liquorice and is therefore unlikely to have the same effect, however it is recommended to still monitor patients for any changes.
Atazanavir: This HIV antiretroviral protease inhibitor is metabolised by the cytochrome P450 enzyme 3A4 and has a narrow therapeutic range.[149],[150] Chamomile may inhibit,[151],[152] whilst liquorice may induce the activity of this enzyme.[153],[154] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Benzodiazepines, barbiturates and/or CNS depressants: Chamomile may enhance drowsiness by acting synergistically when taken alongside these medications due to mild sedative effects. Use with caution and monitor if combining.[155],[156]
Carbamazepine: This anti-epileptic, neurotropic and psychotropic drug is metabolised by cytochrome P450 3A4,[157],[158] and has a narrow therapeutic range.[159],[160] Chamomile may inhibit,[161],[162] whilst liquorice may induce the activity of this enzyme.[163],[164] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Ciprofloxacin: It has been proposed that fennel may alter the effectiveness of the antibiotic ciprofloxacin by altering absorption, tissue distribution and elimination of the drug,[165] however MIMS does not list this caution. Separate intake by 2 hours and inform medication prescriber.
Corticosteroids: Concurrent use of liquorice with oral corticosteroids may potentiate the effects of the corticosteroids. When used in combination, liquorice may increase potassium loss and increase the risk of potassium depletion.[166] This effect is attributed to the glycyrrhizin in liquorice.[167] This supplement contains deglycyrrhized liquorice and is therefore unlikely to have the same effect, however it is recommended to still monitor patients for any changes to potassium levels
Cyclosporine (ciclosporin): This potent immunosuppressant anti-rejection drug is metabolised by cytochrome P450 3A4,[168],[169]and has a narrow therapeutic range.[170],[171] Chamomile may inhibit,[172],[173] whilst liquorice may induce the activity of this enzyme.[174],[175] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and consult the patient’s specialist if prescribed to manage organ transplant.
Darunavir: This HIV antiretroviral protease inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[176],[177]Chamomile may inhibit,[178],[179] whilst liquorice may induce the activity of this enzyme.[180],[181] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Delavirdine: This HIV antiretroviral non-nucleoside reverse transcriptase inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[182],[183] Chamomile may inhibit,[184],[185] whilst liquorice may induce the activity of this enzyme.[186],[187] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Digoxin: Liquorice,[188],[189],[190],[191],[192],[193] and chamomile,[194],[195] may affect the activity of digoxin. Use cautiously in patients on this medication, and only under medical supervision.Cardiac/digitalis toxicity: Due to the potassium-decreasing activity of liquorice, the combination of liquorice with digoxin may increase the risk of cardiac/digitalis toxicity due to potassium loss.[196],[197] This effect is attributed to the glycyrrhizin in liquorice.[198] This supplement contains deglycyrrhized liquorice and is therefore unlikely to have the same effect.
P450 enzymes: This cardiac glycoside drug is metabolised by cytochrome P450 3A4,[199],[200] and has a narrow therapeutic range.[201],[202] Human evidence shows constituents of liquorice induce the activity of this enzyme,[203] with animal evidence showing the whole herb to exert a similar effect.[204] Chamomile may on the other hand inhibit the activity of this enzyme.[205],[206] Both these actions may theoretically change the drug’s therapeutic effect.[207],[208]
Disopyramide: This class IA anti-arrhythmic drug is metabolised by cytochrome P450 3A4,[209],[210] and has a narrow therapeutic range.[211],[212],[213] Chamomile may inhibit,[214],[215]whilst liquorice may induce the activity of this enzyme.[216],[217] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Diuretics: Due to the potassium-decreasing activity of liquorice, the combination of liquorice with diuretics (including loop, thiazide and potassium-depleting) may compound diuretic-induced potassium loss, thus increasing the risk of hypokalaemia.[218] This effect is attributed to the glycyrrhizin in liquorice.[219] This supplement contains deglycyrrhized liquorice and is therefore unlikely to have the same effect, however it is recommended to still monitor patients for any changes to potassium levels.
Efavirenz: This HIV antiretroviral non-nucleoside reverse transcriptase inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[220],[221]Chamomile may inhibit,[222],[223] whilst liquorice may induce the activity of this enzyme.[224],[225] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Ethosuximide: This anticonvulsant drug is metabolised by cytochrome P450 3A4,[226],[227] and has a narrow therapeutic range.[228],[229] Chamomile may inhibit,[230],[231] whilst liquorice may induce the activity of this enzyme.[232],[233] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Etravirine: This HIV antiretroviral non-nucleoside reverse transcriptase inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[234],[235]Chamomile may inhibit,[236],[237] whilst liquorice may induce the activity of this enzyme.[238],[239] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Fosamprenavir: This HIV antiretroviral protease inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[240],[241] Chamomile may inhibit,[242],[243] whilst liquorice may induce the activity of this enzyme.[244],[245] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Gastrointestinal Irritation: Turmeric benefits gastrointestinal health,[246] however in some people large doses of turmeric may cause gastrointestinal irritation (e.g. in people with history of peptic ulcers, reflux etc.[247],[248])Due to the potential benefits in these conditions, recommend use after food in these patients and monitor progress/adjust dosing down if required.
Heart disease: The mineralocorticoid effects of liquorice can worsen congestive heart failure and fluid retention, as well as increase the risk of arrhythmias.[249],[250] This effect is attributed to the glycyrrhizin in liquorice.[251] This supplement contains deglycyrrhized liquorice and is therefore unlikely to have the same effect, however it is recommended to still monitor patients for any changes.
Hypertension: The mineralocorticoid effects of liquorice can increase blood pressure.[252],[253] This effect is attributed to the glycyrrhizin in liquorice.[254] This supplement contains deglycyrrhized liquorice and is therefore unlikely to have the same effect, however it is recommended to still monitor patients for any changes.
Hypokalaemia: The mineralocorticoid effects of liquorice can decrease serum potassium levels and exacerbate hypokalaemia.[255],[256] This effect is attributed to the glycyrrhizin in liquorice.[257] This supplement contains deglycyrrhized liquorice and is therefore unlikely to have the same effect, however it is recommended to still monitor patients for any changes.
Indinavir: This HIV antiretroviral protease inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[258],[259] Chamomile may inhibit,[260],[261] whilst liquorice may induce the activity of this enzyme.[262],[263] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Levothyroxine: This thyroid hormone is a substrate for cytochrome P450 3A4,[264],[265] and has a narrow therapeutic range.[266],[267] Chamomile may inhibit,[268],[269] whilst liquorice may induce the activity of this enzyme.[270],[271] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Lopinavir: This HIV antiretroviral protease inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[272],[273] Chamomile may inhibit,[274],[275] whilst liquorice may induce the activity of this enzyme.[276],[277] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Nelfinavir: This HIV antiretroviral protease inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[278],[279] Chamomile may inhibit,[280],[281] whilst liquorice may induce the activity of this enzyme.[282],[283] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Nevirapine: This HIV antiretroviral non-nucleoside reverse transcriptase inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[284],[285]Chamomile may inhibit,[286],[287] whilst liquorice may induce the activity of this enzyme.[288],[289] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Oestrogen therapy and/or oestrogen-sensitive conditions: Liquorice may have phytoestrogenic properties, thus exerting a balancing effect on oestrogen levels.[290] Use with caution alongside oestrogen therapy or in patients with a history of oestrogen-sensitive cancers (e.g. breast, overian, uterine) or conditions such as endometriosis or fibroids.[291]
Olanzapine: This antipsychotic medication is used for the treatment of schizophrenia and bipolar disorder. It is metabolised by cytochrome P450 1A2,[292],[293] and has a narrow therapeutic range.[294],[295] Turmeric,[296],[297] and chamomile,[298],[299],[300] may inhibit the activity of this enzyme which theoretically may change the drug’s therapeutic effect. Use cautiously in patients on this medication and only under medical supervision.
Oral contraceptive pill (OCP): Use cautiously in patients on this medication, monitor blood pressure and consider alternative contraceptive options whilst combining liquorice with OCP’s.Most OCP’s (e.g. those containing levonorgestrel, ethinyloestradiol, drospirenone) are metabolised by cytochrome P450 3A4.[301] Human evidence shows glycyrrhizin from liquorice can induce the activity of this enzyme,[302] with animal evidence showing the whole herb to exert a similar effect,[303] which theoretically may reduce the drug’s therapeutic effect.[304],[305]
The mineralocorticoid effects of liquorice can increase the risk of side effects from the OCP including hypokalaemia, fluid retention and elevated blood pressure.[306] This effect is attributed to the glycyrrhizin in liquorice.[307] This supplement contains deglycyrrhized liquorice and is therefore unlikely to have the same effect, however it is recommended to still monitor patients for any changes.
Liquorice may have phytoestrogenic properties,[308] and therefore may theoretically affect estraogen therapies.
Phenobarbital (phenobarbitone): This barbiturate is a widely used anti-seizure medication that is metabolised by cytochromes P450 enzymes 1A1, 1A2,[309],[310] and 3A4 [311],[312] and has a narrow therapeutic range.[313],[314] Turmeric may inhibit CYP1A1 and CYP1A2,[315],[316]and chamomile may inhibit the activity of CYP3A4[317],[318] and CYP1A2.[319],[320],[321]Liquorice may induce the activity of CYP3A4.[322],[323] These interactions with the P450 enzymes may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Phenytoin: This anti-epileptic, anticonvulsant and anti-seizure drug is metabolised by cytochrome P450 1A2,[324],[325] and 3A4,[326],[327] and has a narrow therapeutic range.[328],[329],[330] Turmeric,[331],[332] and chamomile,[333],[334],[335] may inhibit the activity of CYP1A2, and chamomile may inhibit the activity of CYP3A4.[336],[337] Liquorice may induce the activity of CYP3A4.[338],[339] These interactions with the P450 enzymes may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Propafenone: This class IC anti-arrhythmic drug is metabolised by cytochromes P450 3A4[340],[341] and 1A2,[342],[343]and has a narrow therapeutic range.[344],[345] Turmeric,[346],[347] and chamomile,[348],[349],[350] may inhibit the activity of CYP1A2, and chamomile may inhibit the activity of CYP3A4.[351],[352] Liquorice may induce the activity of CYP3A4.[353],[354] These interactions with the P450 enzymes may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Quinidine: This anti-malarial and class IA anti-arrhythmic drug is metabolised by cytochrome P450 3A4,[355],[356] and has a narrow therapeutic range.[357],[358] Chamomile may inhibit,[359],[360] whilst liquorice may induce the activity of this enzyme.[361],[362] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Renal (kidney) disease/insufficiency: The mineralocorticoid effects of liquorice may worsen renal function.[363],[364] This effect is attributed to the glycyrrhizin in liquorice.[365] This supplement contains deglycyrrhized liquorice and is therefore unlikely to have the same effect, however it is recommended to still monitor patients for any changes.
Rifampicin (rifampin): This antibiotic drug is metabolised by cytochromes P450 3A4[366],[367] and 1A2,[368],[369] and has a narrow therapeutic range.[370],[371] Turmeric,[372],[373] and chamomile,[374],[375],[376] may inhibit the activity of CYP1A2, and chamomile may inhibit the activity of CYP3A4.[377],[378] Liquorice may induce the activity of CYP3A4.[379],[380] These interactions with the P450 enzymes may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Ritonavir: This HIV antiretroviral protease inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[381],[382] Chamomile may inhibit,[383],[384] whilst liquorice may induce the activity of this enzyme.[385],[386] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Saquinavir: This HIV antiretroviral protease inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[387],[388] Chamomile may inhibit,[389],[390] whilst liquorice may induce the activity of this enzyme.[391],[392] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Sirolimus (rapamycin): This immunosuppressant anti-rejection drug is metabolised by cytochrome P450 3A4,[393],[394]and has a narrow therapeutic range.[395],[396]Chamomile may inhibit,[397],[398] whilst liquorice may induce the activity of this enzyme.[399],[400] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and consult the patient’s specialist if prescribed to manage organ transplantation.
Tacrolimus: This potent immunosuppressant anti-rejection drug is metabolised by cytochrome P450 3A4,[401],[402] and has a narrow therapeutic range.[403],[404]Chamomile may inhibit,[405],[406] whilst liquorice may induce the activity of this enzyme.[407],[408] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and consult the patient’s specialist if prescribed to manage organ transplant.
Testosterone: Liquorice may decrease testosterone levels,[409] however conflicting results exist in clinical trials.[410] Monitor patients for reduction in testosterone levels.
Theophylline: This methylxanthine drug is used for acute relief in respiratory diseases such as COPD and asthma. This drug is metabolised by P450 enzymes 1A1, 1A2, [411],[412] and 3A4[413],[414] and has a narrow therapeutic range.[415],[416] Turmeric may inhibit CYP1A1 and CYP1A2,[417],[418] and chamomile may inhibit the activity of CYP3A4[419],[420] and CYP1A2.[421],[422],[423] Liquorice may induce the activity of CYP3A4.[424],[425]These interactions with the P450 enzymes may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for adverse effects.
Tipranavir: This HIV antiretroviral protease inhibitor is metabolised by cytochrome P450 3A4 and has a narrow therapeutic range.[426],[427] Chamomile may inhibit,[428],[429] whilst liquorice may induce the activity of this enzyme.[430],[431] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for symptom changes.
Valproate (sodium valproate): This anti-epileptic, anticonvulsant and anti-seizure drug is metabolised by cytochrome P450 3A4,[432],[433] and has a narrow therapeutic range.[434] Chamomile may inhibit,[435],[436] whilst liquorice may induce the activity of this enzyme.[437],[438] These interactions with the CYP3A4 enzyme may theoretically alter the drug’s therapeutic effect. Use cautiously in patients on this medication and monitor for any adverse effects.
Pregnancy and Lactation
Pregnancy
Fennel is contraindicated during pregnancy[439]
Breastfeeding
Fennel is contraindicated during breastfeeding[440]
Children
Not recommended in children under 12 years old.[441]
MGXGASA
