Garlic

This consists of bulbs of the plant known as Allium sativum Linn.

Family: Liliaceae.

Pharmacopoeias

Garlic (USP 32); Garlic Delayed Release Tablets (USP 32); Garlic Fluid Extract (USP 32); Garlic for Homeopathic Preparations (BP 2009, Ph Eur 6.4); Garlic Powder (Ph Eur 6.4, BP 2009); Powdered Garlic (USP 32); Powdered Garlic Extract (USP 32).

Constituents

• Garlic products are produced from the bulbs of garlic and are usually standardised according to the content of the sulphur-containing compounds,

  • • • • Alliin, Allicin (produced by the action of the enzyme alliinase on alliin) and/or γ-glutamyl-(S)-allyl-L-cysteine.

        • Other sulphur compounds such as

          • • • • Allylmethyltrisulfide, allylpropyldisulfide,

                • Diallyldisulfide, diallyltrisulfide, ajoene and vinyldithiines, and mercaptan are also present.

• Garlic also contains various glycosides, monoterpenoids, enzymes, vitamins, minerals and flavonoids based on kaempferol and quercetin.

Use and indications

• Garlic has been used to treat respiratory infections (such as colds, flu, chronic bronchitis, and nasal and throat catarrh) and cardiovascular disorders.

• It is believed to possess antihypertensive, antithrombotic, fibrinolytic, antimicrobial, anticancer, expectorant, antidiabetic and lipid-lowering properties.

• It is also used extensively as an ingredient in foods.

Garlic + Antiplatelet drugs

Garlic may have antiplatelet properties. It might therefore be expected to increase the risk of bleeding with conventional antiplatelet drugs and other drugs that have antiplatelet adverse effects.

Mechanism

An experimental study suggest that ajoene inhibits the binding of fibrinogen to the fibrinogen receptor, which occurs in the final step of the platelet aggregation pathway. Ajoene would therefore be expected to interact synergistically with antiplatelet drugs that act at an earlier step in the pathway

Garlic + Chlorzoxazone

The metabolism of chlorzoxazone is modestly inhibited by garlic

Mechanism

Garlic appears to inhibit the activity of the cytochrome P450 isoenzyme CYP2E1, which metabolises chlorzoxazone to 6-hydroxychlorzoxazone.

Garlic + Herbal medicines; Fish oil

Garlic supplements and fish oils may have beneficial effects on blood lipids.

Mechanism

Unclear. In the experimental study, garlic oil synergistically increased the induction of the antioxidant superoxide dismutase by fish oils, and the combination additive increased the protein levels of CYP1A1, CYP2E1 and CYP3A1.

Garlic + Isoniazid

The interaction between garlic and isoniazid is based on experimental evidence only.

Mechanism

• Unclear. It was anticipated that garlic might increase isoniazid levels by inhibiting the cytochrome P450 isoenzyme CYP2E1, but decreased levels were seen.

• While the authors speculate that garlic extract may induce enzymes in the intestinal mucosa, which interferes with the absorption of isoniazid, they suggest that the findings cannot be explained solely on this basis.

Garlic + Protease inhibitors

A garlic supplement reduced the plasma levels of saquinavir in one study, but had little effect in another. Another garlic supplement did not significantly affect the pharmacokinetics of a single dose of ritonavir.

Mechanism

• The mechanism of this interaction is uncertain, but it is thought that garlic reduced the bioavailability of saquinavir by increasing its metabolism in the intestine.

• Why there was a disparity in the effect of garlic on saquinavir between patients is unclear.

• Allicin is thought to have inhibited the activity of P-glycoprotein in vitro, which caused the build-up of ritonavir within the cell.

Garlic + Warfarin and related drugs

An isolated report described increases in the anticoagulant effects of warfarin in two patients taking garlic supplements.

Another report described a decrease in anticoagulant effects of fluindione in a patient taking garlic tablets. Garlic supplements alone have also rarely been associated with bleeding.

However, in one study, aged garlic extract did not increase the INR or risk of bleeding in patients taking warfarin.

Mechanism

• Garlic has been associated with decreased platelet aggregation.

• This effect on platelet aggregation has, on at least two documented occasions, led to spontaneous bleeding in the absence of an anticoagulant.

• These effects might therefore increase the risk of bleeding with anticoagulants. However, this would not cause an increase in INR, and the mechanism for this effect in the cases seen is unknown.

References

1. Rahman K, Billington D. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr (2000) 130, 2662–5.

2. Steiner M, Li W. Aged garlic extract, a modulator of cardiovascular risk factors: a dosefinding study on the effects of AGE on platelet functions. J Nutr (2001) 131, 980S–4S.

3. Apitz-Castro R, Escalante J, Vargas R, Jain MK. Ajoene, the antiplatelet principle of garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole [sic] on human platelets. Thromb Res (1986) 42, 303–11.

4. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CYW. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther (2002) 72, 276–87.

5. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CYW. Clinical assessment of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John’s wort, garlic oil, Panax ginseng, and Ginkgo biloba. Drugs Aging (2005) 22, 525–39.

6. Loizou GD, Cocker J. The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone. Hum Exp Toxicol (2001) 20, 321–7.

7. Chen L, Yang CS. Effects of cytochrome P450 2E1 modulators on the pharmacokinetics 132 of chlorzoxazone and 6-hydroxychlorzoxazone in rats. Life Sci (1996) 58, 1575–85.

8. Adler AJ, Holub BJ. Effect of garlic and fish-oil supplementation on serum lipid and lipoprotein concentrations in hypercholesterolemic men. Am J Clin Nutr (1997) 65, 445–50.

9. Chen H-W, Tsai C-W, Yang J-J, Liu C-T, Kuo W-W, Lii C-K. The combined effects of garlic oil and fish oil on the hepatic antioxidant and drug-metabolizing enzymes of rats. Br J Nutr (2003) 89, 189–200.

10. Dhamija P, Malhotra S, Pandhi P. Effect of oral administration of crude aqueous extract of garlic on pharmacokinetic parameters of isoniazid and rifampicin in rabbits. Pharmacology (2006) 77, 100–4.

11. Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis (2002) 34, 234–8.

12. Jacek H, Rentsch KM, Steinert HC, Pauli-Magnus C, Meier PJ, Fattinger K. No effect of garlic extract on saquinavir kinetics and hepatic CYP3A4 function measured by the erythromycin breath test. Clin Pharmacol Ther (2004) 75, P80.

13. Gallicano K, Foster B, Choudhri S. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol (2003) 55, 199–202.

14. Laroche M, Choudhri S, Gallicano K, Foster B. Severe gastrointestinal toxicity with concomitant ingestion of ritonavir and garlic. Can J Infect Dis (1998) 9 (Suppl A), 76A.

15. Patel J, Buddha B, Dey S, Pal D, Mitra AK. In vitro interaction of the HIV protease inhibitor ritonavir with herbal constituents: changes in P-gp and CYP3A4 activity. Am J Ther (2004) 11, 262–77.

16. Pathak A, Leger P, Bagheri H, Senard J-M, Boccalon H, Montastruc J-L. Garlic interaction with fluindione: a case report. Therapie (2003) 58, 380–1.

17. Sunter W. Warfarin and garlic. Pharm J (1991) 246, 722.

18. Sunter W. Personal communication. July 1991.

19. Macan H, Uykimpang R, Alconcel M, Takasu J, Razon R, Amagase H, Niihara Y. Aged garlic extract may be safe for patients on warfarin therapy. J Nutr (2006) 136 (Suppl 3), 793–5.

20. Shalansky S, Neall E, Lo M, Abd-Elmessih E, Vickars L, Lynd L. The impact of complementary and alternative medicine use on warfarin-related adverse outcomes. Pharmacotherapy (2002) 22, 1345.

21. German K, Kumar U, Blackford HN. Garlic and the risk of TURP bleeding. Br J Urol (1995) 76, 518.

22. Rose KD, Croissant PD, Parliament CF, Levin MP. Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. Neurosurgery (1990) 26, 880–2.