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Bastyr University, Research Institute, Kenmore, WA 98028
ABSTRACT
Louis Pasteur was the first to describe the antibacterial effect of onion and garlic juices. Historically, garlic has been used worldwide to fight bacterial infections. Allium vegetables, particularly garlic (Allium sativum L.) exhibit a broad antibiotic spectrum against both gram-positive and gram-negative bacteria. Noteworthy results published include the following: 1) raw juice of garlic was found to be effective against many common pathogenic bacteria-intestinal bacteria, which are responsible for diarrhea in humans and animals; 2) garlic is effective even against those strains that have become resistant to antibiotics; 3) the combination of garlic with antibiotics leads to partial or total synergism; 4) complete lack of resistance has been observed repeatedly; 5) even toxin production by microorganisms is prevented by garlic. Helicobacter pylori (H. pylori) is a bacterium implicated in the etiology of stomach cancer and ulcers. The incidence of stomach cancer is lower in populations with a high intake of allium vegetables. We have demonstrated in vitro that H. pylori is susceptible to garlic extract at a fairly moderate concentration. Even some antibiotic-resistant H. pylori strains are susceptible to garlic. Clinical trials are necessary to explore the possibility of using garlic as a low-cost remedy for eradicating H. pylori.
KEY WORDS: • garlic • Allium • antibacterial activity • Helicobacter pylori
Garlic has had an important dietary and medicinal role for centuries.
Most of its prophylactic and therapeutic effects are ascribed to
specific oil- and water-soluble organosulfur compounds, which are
responsible for the typical odor and flavor of garlic (Block
1985
). During crushing or cutting of the clove, the odorless
amino acid alliin, present in the garlic clove, is metabolized by the
enzyme allinase (a cysteine sulfoxide lyase) to yield allicin and other
thiosulfinates that are the source of the characteristic odor of
garlic. Thiosulfinates and other secondary metabolites of garlic,
including 
-glutamyl peptides, scordinins, steroids, terpenoids,
flavonoids and other phenols, may be responsible for the range of
therapeutic effects reported for garlic. Reuter et al. (1996)
recently reviewed the therapeutic effects of garlic,
namely, effects on the cardiovascular system, antibiotic, anticancer,
antioxidant, immunomodulatory, anti-inflammatory, hypoglycemic and
hormone-like effects. This review will focus on recent research on
protective effects of garlic against Helicobacter pylori and
other bacterial infections.
Standardization of garlic preparations.
Before reviewing the literature on the antibacterial effects of garlic,
a fundamental problem in garlic research must be addressed. There are
>2000 publications on the chemistry and biological effects of garlic.
This may give the impression that garlic is a thoroughly investigated
medicinal plant; the problem, however, is that the biological studies
have not gone hand in hand with the chemical studies, with the frequent
use of garlic products of undefined composition. Very few studies have
used a chemically characterized product. The composition of garlic
depends on the source, age, storage conditions, type of processing and
method of consumption. Unfortunately, the different forms of garlic are
frequently referred to as "garlic" in both the lay and scientific
literature. To add to this complexity, Lawson (1996)
showed that the amount and composition of organosulfur compounds vary
within the different strains of garlic, and the problem is compounded
by the volatile and reactive nature of these compounds. Hence, there is
a clear necessity for standardization of garlic preparations,
especially for use in biological studies. More recent biological
studies have attempted to rectify this problem.
Antibacterial activity of garlic.
There is extensive literature on the antibacterial effects of fresh
garlic juice, aqueous and alcoholic extracts, lyophilized powders,
steam distilled oil and other commercial preparations of garlic.
Fenwick and Hanley (1985)
undertook a thorough review of
the antibacterial effects of garlic and other allium vegetables up to
mid-1984; more recently, the antibacterial effects of garlic have been
reviewed by Reuter et al. (1996)
. Garlic has been
reported to inhibit Aerobacter, Aeromonas,
Bacillus, Citrella, Citrobacter,
Clostridium, enterobacter,
Escherichia, Klebsiella,
Lactobacillus, Leuconostoc,
Micrococcus, Mycobacterium, Proteus,
Providencia, Pseudomonas, Salmonella,
Serratia, Shigella, Staphylococcus,
Streptococcus and Vibrio. Noteworthy among the
reported findings are the following: 1) Garlic exhibits a
broad antibiotic spectrum against gram-positive and
gram-negative bacteria (Kabelik and Hejtmankova-Uhrova 1968
). 2) Enterotoxic coli strains and other
pathogenic intestinal bacteria, which are responsible for diarrhea in
humans and animals, are more easily inhibited by garlic than the normal
intestinal flora (Caldwell and Danzer 1988
, Kumar and Sharma 1982
, Rees 1993
). 3)
Garlic is active even against organisms that have become resistant to
antibiotics (Jezowa et al. 1966
). 4) The
combination of garlic extracts with antibiotics leads to partial or
total synergism (Didry et al. 1992
). 5) A
garlic oil preparation showed good antituberculosis activity in guinea
pigs with a intraperitoneal dose of 0.5 mg/kg (Jain 1993
). 6) Complete lack of resistance of bacteria to
garlic has been found (Dankert et al. 1979
, Singh and Shukla 1984
). 7) As a result of the bactericidal
activity of garlic, toxin production by the bacteria is also prevented
(Dewitt et al. 1979
, Sanick 1975
).
Garlic and Helicobacter pylori.
Gastric cancer is the major cancer in the developing world and one of
the top two worldwide. Helicobacter pylori is a bacterium
implicated in the etiology of stomach cancer (Fuchs and Mayer 1995
). The incidence of stomach cancer is lower in individuals
with a high intake of allium vegetables in developed and developing
(high risk) countries (Steinmetz and Potter 1991a
and 1991b
). Because allium vegetables, particularly garlic, have antibiotic activity, we investigated the antimicrobial activity of garlic against H. pylori (Sivam et al. 1997
). An aqueous extract of a known variety of garlic (Oswego white) was used. The extract was standardized for thiosulfinate concentration. The
minimum inhibitory concentration was found to be 40 µg/mL.
At this concentration, the control organism Staphylococcus
aureus was not inhibited by the garlic extract. Thus H.
pylori is more susceptible to garlic extract. Cellini et al. (1996)
reported a similar study. They tested 16 clinical
isolates of H. pylori and showed 90% inhibition of the
isolates with aqueous garlic extract at 5 mg/mL. The concentration used
in that study is the total weight of garlic per milliliter. However,
calculations show that the minimum inhibitory concentrations reported
in the two studies are comparable. It is plausible that the sensitivity
of H. pylori to garlic extract at such a low concentration
may be related to the reported lower risk of stomach cancer in those
with a high allium vegetable intake. The inhibitory concentration of
garlic reported in the two studies above is achievable in the stomach
by consuming a medium size clove of garlic or equivalent amount of
garlic supplements. Thus, this finding may identify a strategy for
low-cost intervention for stomach cancer, with few side effects, in
populations at high risk, particularly in the case of high resistance
to antibiotics.
Mechanism of action.
Thiosulfinates play an important role in the antibiotic activity of
garlic. Hughes and Lawson (1991)
showed that the
antimicrobial activity of garlic is completely abolished when the
thiosulfinates (e.g., allicin) are removed from the extract. Also, upon
reduction of allicin to diallyl disulfide, the antibacterial activity
is greatly reduced (Reuter et al. 1996
). Feldberg et al. (1988)
showed that allicin exhibits its antimicrobial
activity mainly by immediate and total inhibition of RNA synthesis,
although DNA and protein syntheses are also partially inhibited,
suggesting that RNA is the primary target of allicin action. The
structural differences of the bacterial strains may also play a role in
the bacterial susceptibility to garlic constituents (Tynecka and Gos 1975
). The cell membrane of Escherichia coli
contains 20% lipid, whereas that of Staphylococcus aureus
contains only 2% lipid (Salton 1964
). The lipid content
of the membranes will have an effect on the permeability of allicin and
other garlic constituents. On the basis of this hypothesis, it is
interesting to recall the difference in susceptibility we observed
between gram-negative H. pylori (40 µg/mL)
and gram-positive Staphylococcus aureus (>160
µg/mL) to garlic extract (Sivam et al. 1997
).
Summary
The antibacterial activity of garlic is well documented. This knowledge could be utilized in two different areas.
Antibiotics.
Microbial drug resistance is a difficult problem. As medicinal chemists
advance in their search for new bacterial targets to attack, bacteria
relentlessly evolve; as a result, a large number of bacterial species
have become resistant to antibacterial drugs (Garau 1994
, Gould 1994
, Sanders and Sanders 1992
). Thus there is a need to develop alternate strategies.
Because garlic is known to act synergistically with antibiotics, and
resistance has not been reported for garlic, more dose-response
preclinical studies and eventually clinical studies should be done to
assess the use of an antibiotic/garlic combination for bacteria that
are difficult to eradicate. Antibiotic resistance is a problem in the
case of H. pylori as well (Graham 1998
).
Because H. pylori is a worldwide problem and the cost of
eradicating it using standard antibiotic regimen is also high, this
bacterium is another candidate for clinical trial, using garlic either
alone or in combination with a less expensive antibiotic regimen.
Food preservation.
Garlic inhibits the growth of microorganisms as well as toxin production. More research must be done to assess the value of garlic as an alternative to chemical food preservatives, especially in foods in which the garlic flavor would be an added bonus. There is also potential use for garlic by itself or in combination with other herbs and spices to extend the shelf life of raw meat products.
FOOTNOTES
1 Presented at the conference "Recent Advances
on the Nutritional Benefits Accompanying the Use of Garlic as a
Supplement" held November 15–17, 1998 in Newport Beach, CA. The
conference was supported by educational grants from Pennsylvania State
University, Wakunaga of America, Ltd. and the National Cancer
Institute. The proceedings of this conference are published as a
supplement to The Journal of Nutrition. Guest editors:
John Milner, The Pennsylvania State University, University Park, PA and
Richard Rivlin, Weill Medical College of Cornell University and
Memorial Sloan-Kettering Cancer Center, New York, NY. 
REFERENCES
1. Block E. The chemistry of garlic and onions. Sci. Am. 1985;252:114-119[Medline]
2. Caldwell D. R., Danzer C. J. Effects of allyl sulfides on the growth of predominant gut anaerobes. Curr. Microbiol. 1988;16:237-241
3. Cellini L., Di Campli E., Masuli M., Di Bartolomeo S., Allocati N. Inhibition of Helicobacter pylori by garlic extract (Allium sativum). FEMS Immunol. Med. Microbiol. 1996;13:273-277[Medline]
4. Dankert, J., Tromp, T.F.J., De Vries, H. & Klasen, H. J. (1979) Antimicrobial activity of crude juices of Allium ascalonicum, Allium cepa, and Allium sativum. Zentrabl. Bakteriol. Parasitenkd. Infektkrankh. Hyg. Abt. 1 Org. 245: 229–239.
5. Dewitt J. C., Notermans S., Gorin N., Kampelmacher E. H. Effect of garlic oil or onion oil on toxin production by Clostridium botulinum in meat slurry. J. Food Prot. 1979;42:222-224
6. Didry N., Dubreuil L., Pinkas M. Antimicrobial activity of naphthaquinones and Allium extracts combined with antibiotics. Pharm. Acta Helv. 1992;67:148-151[Medline]
7.
Feldberg R. S., Chang S. C., Kotik A. N., Nadler M., Neuwirth Z., Sundstrom D. C., Thompson N. H. In vitro mechanism of inhibition of bacterial growth by allicin. Antimicrob. Agents Chemother. 1988;32:1763-1768
8. Fenwick G. R., Hanley A. B. The genus Allium—part 3. Medicinal effects. CRC Crit. Rev. Food Sci. Nutr. 1985;1:1-74
9.
Fuchs C. S., Mayer R. J. Gastric carcinoma. N. Engl. J. Med. 1995;333:32-41
10. Garau, J. (1994) ß-Lactamases: current situation and clinical importance. Intensive Care Med. 20 (suppl.): 3: S5–S9.
11. Gould I. M. Risk factors for acquisition of multi-drug-resistant gram-negative bacteria. Eur. J. Clin. Micrbiol. Infect. Dis. 1994;13(suppl.):S30-S38
12. Graham D. Y. Antibiotic resistance in Helicobacter pylori: implications for therapy. Gastroenterology 1998;115:1272-1277[Medline]
13. Hughes B. G., Lawson L. D. Antimicrobial effects of Allium sativum L. (garlic), Allium ampeloprasum (elephant garlic), and Allium cepa (onion), garlic compounds and commercial garlic supplement products. Phytother. Res. 1991;5:154-158
14. Jain R. C. Antitubercular activity of garlic oil. Indian Drugs 1993;30:73-75
15. Jezowa L., Rafinski T., Wrocinski T. Investigations on the antibiotic activity of Allium sativum L. Herba Pol 1966;12:3-13
16. Kabelik J., Hejtmankova-Uhrova N. The antifungal and antibacterial effects of certain drugs and other substances. Vet. Med. (Pragu) 1968;13:295-303
17. Kumar A., Sharma V. D. Inhibitory effect of garlic (Allium sativum Linn.) on enterotoxigenic Escherichia coli. Indian J. Med. Res. 1982;76:66-70
18. Lawson, D. L. (1996) The composition and chemistry of garlic cloves and processed garlic. In: Garlic: The Science and Therapeutic Applications of Allium sativum L. and Related Species, 2nd ed. (Koch, H. P. & Lawson, D. L., eds.), pp. 37–107. William & Wilkins, Baltimore, MD.
19. Rees L. P., Minney S. F., Plummer N. T., Slater J. H., Skyrme D. A. A quantitative assessment of the antimicrobial activity of garlic (Allium sativum). World J. Micrbiol. Biotechnol. 1993;9:303-307
20. Reuter, H. D., Koch, H. P. & Lawson D. L. (1996) Therapeutic effects and applications of garlic and its preparations. In: Garlic: The Science and Therapeutic Applications of Allium sativum L. and Related Species, 2nd ed. (Koch, H. P. & Lawson, D. L., eds.), pp. 135–212. William & Wilkins, Baltimore, MD.
21. Salton M. R. J. The Bacterial Cell Wall 1964 Elsevier Amsterdam, The Netherlands.
22. Sanders C. C., Sanders W. E., Jr ß-Lactam resistance in gram-negative bacteria: global trends and clinical impact. Clin. Infect. Dis. 1992;15:824-839[Medline]
23. Sanick, I. H. (1975) Preserving foods. Australian Patent no. 499 390.
24. Singh K.V., Shukla N. P. Activity on multiple resistant bacteria of garlic (Allium sativum) extract. Fitoterapia 1984;55:313-315
25. Sivam G. P., Lampe J. W., Ulness B., Swanzy S. R., Potter J. D. Helicobacter pylori—in vitro susceptibility to garlic (Allium sativum) extract. Nutr. Cancer 1997;27:118-121[Medline]
26. Steinmetz K., A & Potter J. D. Vegetables, fruit, and cancer. I. Epidemiology. Cancer Causes Control 1991a;2:325-357[Medline]
27. Steinmetz K.A., Potter J. D. Vegetables, fruit, and cancer. II. Mechanisms. Cancer Causes Control 1991b;2:4527-4542
28. Tynecka Z., Gos Z. The fungistatic activity of garlic (Allium sativum) in vitro. Ann. Univ. Mariae Curie-Sklodowska Sect. D Med. 1975;30:5-13
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