Metabolism Elimination

De Rooij et al. (82) conducted a study to evaluate the urinary excretion of N-acetyl-S-allyl-L-cysteine (allylmercapturic acid, ALMA). The importance of this study lies in the use of ALMA as a biomarker for occupational exposure to alkyl halides; if garlic produces detectable urine concentrations of ALMA, garlic consumption could interfere with toxicological studies. Six human volunteers were administered 200 mg of garlic extract in tablet form (Kwai). The volunteers ranged from 20 to 27 years of age, with body weights ranging from 60 to 90 kg. Urine samples were collected prior to administration of the garlic and up to 24 hours postadministration. Gas chromatography-mass spectrom-etry (GC-MS) was used to evaluate the excretion of ALMA. y-Glutamyl-S-allyl-L-cysteine (GAC) is ALMA's most likely precursor. y-Glutamine is hydrolyzed from GAC by glutamine-transpeptidase, resulting in S-allyl-L-cys-teine. This compound then undergoes acetylation via N-acetyl transferase to form ALMA. It is difficult to calculate to what extent GAC is excreted as ALMA in the urine because GAC content of garlic varies depending on the product. By assuming that GAC represents 1% of the dry weight of garlic bulbs, and that the tablets represented 100% dry garlic, the researchers approximated that 10% of GAC is excreted as ALMA within the first 24 hours of garlic ingestion. The average elimination half-life of ALMA was 6.0 ± 1.3 hours (82).

N-acetyl-S-(2-carboxypropyl) cysteine, N-acetyl-S-allyl-L-cysteine (ALMA), and hexahydrohippuric acid were identified in the urine of humans ingesting garlic or onions (83). It is important to note that the study participants' urine contained N-acetyl-S-(2-carboxypropyl)-cysteine at baseline in minute amounts, even before garlic ingestion, but increased after ingestion of garlic or onions. As with the study by De Rooij, the importance of these findings lies in the use of urinary excretion of mercapturic acids as a marker for industrial exposure to halogenated alkanes, such as vinyl chloride. Elimination of other garlic components has also been studied. Allicin is metabolized in rat liver homogenate more rapidly than the vinyl dithiins, the main constituents of oily preparations of garlic.

As discussed in Subheading 6.2. Distribution, 1,2-vinyldithiin is lipophilic and tends to accumulate in fat, whereas 1,3-vinyldithiin is less lipophilic and more quickly eliminated from the serum, fat, and kidney. Both vinyldithiins can be detected in the serum, fat, and kidney using GC-MS for at least 24 hours after oral administration (78).

SAC is thought to undergo first-pass metabolism in rats based on nonlinear increases in AUC (area under the plasma concentration vs time curve) after oral administration. SAC is likely metabolized to ALMA by acetyltransferase in the liver and kidney. The high concentration of SAC in rat kidney has been attributed to conversion of ALMA back into SAC by kidney acylase. Of the full SAC dose, 30-50% is excreted in the urine of rats as ALMA, and less than 1% of the dose is excreted as unchanged SAC in the urine and bile. In mice, both SAC (16.5%) and the N-acetylated metabolite (7.2%) are excreted in the urine, whereas in dogs, less than 1% of the dose was found in the urine as either SAC or ALMA. The half-life of SAC in rats ranges from 1.49 hours with an intravenous dose of 12.5 mg/kg, to 2.33 hours with an oral dose of 50 mg/kg. In mice, the half-life of SAC is 0.77 hour when given orally, and 0.43 hour for intravenous administration, and in dogs approx 10 hours after either oral or intravenous administration (77).

ALMA is also detectable in human urine and concentrations in blood increase in response to ingesting garlic (20). Therefore, because SAC is found in many garlic preparations, it may be the best standardization compound and compliance marker for garlic preparations.

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