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Department of Research and Development, Wakunaga of America Company, Mission Viejo, CA 92691 and * Institute for OTC Research, Wakunaga Pharmaceutical Company, Hiroshima 739-11, Japan
2To whom correspondence should be addressed. E-mail: Haru-Amagase{at}wakunaga.com
ABSTRACT
The health benefits of garlic likely arise from a wide variety of
components, possibly working synergistically. The complex chemistry of
garlic makes it plausible that variations in processing can yield quite
different preparations. Highly unstable thiosulfinates, such as
allicin, disappear during processing and are quickly transformed into a
variety of organosulfur components. The efficacy and safety of these
preparations in preparing dietary supplements based on garlic are also
contingent on the processing methods employed. Although there are many
garlic supplements commercially available, they fall into one of four
categories, i.e., dehydrated garlic powder, garlic oil, garlic oil
macerate and aged garlic extract (AGE). Garlic and garlic supplements
are consumed in many cultures for their hypolipidemic, antiplatelet and
procirculatory effects. In addition to these proclaimed beneficial
effects, some garlic preparations also appear to possess
hepatoprotective, immune-enhancing, anticancer and chemopreventive
activities. Some preparations appear to be antioxidative, whereas
others may stimulate oxidation. These additional biological effects
attributed to AGE may be due to compounds, such as
S-allylcysteine, S-allylmercaptocysteine,
N
-fructosyl arginine and others, formed
during the extraction process. Although not all of the active
ingredients are known, ample research suggests that several
bioavailable components likely contribute to the observed beneficial
effects of garlic.
KEY WORDS: • garlic • extraction • process • S-allylcysteine • allicin
Preclinical and clinical studies reveal a close relationship between dietary habits and the occurrence of disease. Diets high in fat may increase the risk of heart disease and some forms of cancer. On the contrary, increased intake of fruits, vegetables, herbs and some of their constituents reduces risks and may even prevent some diseases. Alliums such as garlic have been studied extensively for their health benefits. More than a thousand publications over the past decade alone reveal the widespread interest in this class of foods. Several of the allium foods have been shown to reduce risks and/or modulate metabolism to favor the prevention of diseases. Garlic, in particular, is considered to be one of the best disease-preventive foods because of its potent and widespread effects. Although some studies have cast doubt on the benefits of garlic extract, careful examination of such data emphasizes the need to clarify the influence of processing on the benefits of garlic. An array of garlic preparations is available on the market. This article will clarify the effects of garlic supplements and the chemical and biological differences among commercial preparations.
Health benefits of garlic and current confusion
The potency of garlic (Allium sativum) has been
acknowledged for >5000 years. In ancient times, the Babylonians,
Egyptians, Phoenicians, Vikings, Chinese, Greeks, Romans and Hindus
used garlic frequently (Block 1985
). They took garlic as
a remedy for intestinal disorders, flatulence, worms, respiratory
infections, skin diseases, wounds, symptoms of aging and many other
ailments. The use of garlic to treat wounds surfaced repeatedly through
the middle ages into World War II, when garlic was used to treat the
wounds of soldiers (Essman 1984
). Garlic was ground or
sliced and was applied directly to wounds to inhibit the spread of
infections.
Garlic thus acquired a reputation in the folklore of many cultures over the centuries as a formidable prophylactic and therapeutic medicinal agent. To date, >3000 publications from all over the world have gradually confirmed the traditionally recognized health benefits of garlic. Many favorable experimental and clinical effects of the consumption of garlic preparations, including garlic extract, have been reported. These biological responses include reduction of risk factors for cardiovascular diseases and cancer, a stimulation of immune function, enhanced foreign compound detoxification, radioprotection, restoration of physical strength, resistance to various stresses and potential antiaging effects.
It has long been known that extraction of a food can increase its
potency and eliminate unpleasant characteristics. The irritating,
acidic and oxidizing compounds in raw garlic can be eliminated or
modified by extraction. In fact, in some cultures, garlic is soaked or
extracted with alcohol, wine, milk or vinegar before use. Many adverse
reactions to garlic can be attributed to an excess of oil-soluble
organosulfur constituents. For example, the lipid-lowering effects
of some oil-soluble sulfur compounds in hepatocytes coincide with
cytotoxicity, as revealed by increased lactate dehydrogenase release
from cells (Liu and Yeh 1999
). Water-soluble sulfur
compounds, on the other hand, although effective at reducing
cholesterol, were not cytotoxic (Fig. 1
). An array
of water-soluble constituents, including S-allylcysteine
(SAC),3
may account for the reduced toxicity of the hydroalcoholic extracts of
garlic compared with raw preparations. (Kanezawa et al. 1984
, Nakagawa et al. 1980, 1984a and 1984b
,
Sumiyoshi et al. 1984
, Yoshida et al. 1984
).
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). Thus, not all garlic preparations can be assumed
equivalent in their composition and, more importantly, in the
biological response they may precipitate.
Several clinical reports, including meta-analyses, have revealed a
cholesterol-lowering effect of garlic in humans (Lau et al. 1987
, Neil et al. 1996
, Silagy and Neil 1994
, Warshafsky et al. 1993
). These reports
have promoted public awareness about the cholesterol-lowering
effects of garlic. However, recent publications (Berthold et al. 1998
, Breithaupt-Grögler et al. 1997
,
Isaacsohn et al. 1998
, McCrindle et al. 1998
, Neil et al. 1996
, Simons et al. 1995
) suggested that not all preparations may be
hypocholesterolemic. These negative publications have caused confusion
within both the public and academic domains. Although the reason for
these inconsistencies remains unknown, it likely relates to components
occurring in the preparation, the quantity of the preparation provided
and/or the duration of the study.
Chemistry of garlic
The chemistry of garlic is quite complex and likely
developed as a self-protective mechanism against microorganisms and
other insults. The primary sulfur-containing constituents in whole,
intact garlic are the
-glutamyl-S-alk(en)yl-L-cysteines and
S-alk(en)yl-L-cysteine sulfoxides, including
alliin. The -glutamyl peptides are biosynthetic intermediates for
corresponding cysteine
sulfoxides(Lancaster and Shaw 1989
). Whole garlic typically
contains 
1% alliin, together with
(+)-S-methyl-L- cysteine sulfoxide (methiin) and
(+)-S-(trans-1-propenyl)-L-cysteine
sulfoxide. S-(2-Carboxypropyl)glutathione,
-glutamyl-S-allyl-L-cysteine,
-glutamyl-S-(trans-1-propenyl)-L-cysteine
and -glutamyl-S-allyl-mercapto-L-cysteine are
also present in garlic cloves (Fenwick and Hanley 1985
,
Sugii et al. 1964
). During storage of garlic bulbs at
cool temperatures, alliin accumulates naturally. On average, a garlic
bulb contains up to 0.9% -glutamylcysteines and up to 1.8% alliin.
In addition to these main sulfur compounds, intact garlic bulbs also
contain a small amount of SAC, but no allicin. SAC is formed from
-glutamyl cysteine catabolism (Fig. 2
) and has been reported to contribute to the health benefits of some
garlic preparations.
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) and
E,Z-ajoene (Block et al. 1984
).
Once garlic is processed by cutting or crushing, compounds in the
intact garlic are converted into hundreds of organosulfur compounds in
a short period of time. When garlic is "damaged," i.e., attacked by
a microbe, crushed, cut or chewed, or when it is dehydrated, pulverized
and then exposed to water, the vacuolar enzyme, alliinase, rapidly
lyses the cytosolic cysteine sulfoxides (alliin) to form the cytotoxic
and odiferous alkyl alkane-thiosulfinates (Fig. 2)
. The transiently
formed compound, allicin, an oily, colorless liquid, comprises 70–80%
of the thiosulfinates. Typically, alliin is converted to allicin by
alliinase.
Allicin is an odorous and extremely unstable compound that decomposes
to sulfides, including ajoene and dithiins. Allicin is sometimes
mislabeled as "garlic oil" because it is not present in intact
garlic or garlic products (Freeman and Kodera 1995
).
Although allicin has been shown to be an effective antimicrobial agent
in vitro, its effects in vivo are questionable. Recent studies reveal
that the bioavailability of allicin is poor (Lawson et al. 1992
,
Table 3
). Allicin was actually discovered to be a component of garlic
by Cavallito and Bailey (1944)
(Table 1
). At that time, the use of antibiotics to treat
infectious diseases was just being discovered. The discovery of allicin
in garlic was so sensational that garlic was patented in the United
States for its antibiotic and antifungal effects. However, the plan of
medicinal or antiseptic use of allicin soon faded because of its
instability. Within a few minutes after adding allicin to blood, it can
no longer be detected (Freeman and Kodera 1995
). Allicin
cannot be detected in the blood or urine after the ingestion of raw
garlic or pure allicin (Lawson et al. 1992
). Although
freshly crushed garlic may contain limited amounts of allicin, no
commercially available processed garlic preparations contain allicin.
The acidity of the stomach would be expected to prevent the conversion
of allium to allicin (Freeman and Kodera 1995
). As seen
in Table 3
, no allicin was detected in human blood after oral intake of
commercially available products standardized for allicin potential or
allicin yield. These findings clearly indicate that allicin does not
contribute to the in vivo effects of garlic. Freshly crushed garlic is
chemically unstable and has been shown to cause undesirable side
effects, such as stomach disorders (Desai et al. 1990
,
Nakagawa et al. 1980
) and allergic reactions
(Lybarger et al. 1982
).
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,
Lawson 1993
). Sulfur-containing compounds in
commercial garlic preparations vary, depending on their manufacturing
processes.
In addition to odoriferous oil-soluble compounds, less odorous
water-soluble organosulfur compounds have been shown to be
biologically active in various areas. SAC has an array of biological
effects including a reduction in carcinogen bioactivity and a
depression in oxidative damage (Amagase and Milner 1993
,
Imai et al. 1994
, Lee et al. 1994
,
Li et al. 1995
, Numagami et al. 1996
,
Sumiyoshi and Wargovich 1990
).
The nonvolatile sulfur-containing compounds, SAC and SAMC are
present in several garlic preparations, although the content varies
considerably (Imai et al. 1994
, Lawson 1993
).
Additional constituents of intact garlic include the following:
steroidal glycosides (Matsuura et al. 1988
), lectins
(Kaku et al. 1992
), prostaglandins, fructan, pectin,
essential oil, adenosine, vitamins B-1, B-2, B-6, C and E, biotin,
nicotinic acid, fatty acids, glycolipids, phospholipids, anthocyanins,
flavonoids, phenolics and essential amino acids (Fenwick and Hanley 1985
). The importance of the constituents in explaining
the health benefits of garlic remains to be resolved.
Garlic supplements and intake of garlic
According to the USDA National Agricultural Statistics Service,
the amount of garlic produced in the United States in 1998 was
252,000 metric tons. Over 60% of the garlic consumed worldwide is
produced in California. In 1997, the U.S. garlic market was valued at
$261 dollars. Australians consume 3000 metric tons of garlic
annually, two thirds of which is imported from the United States
(Woodward 1996
). Garlic products have experienced
increasing popularity in the last decade. The top supplements used by
U.S. households are presented in Figure 3
(Wyngate 1998
). This market research, conducted in 1997,
clearly showed that garlic products were the most popular of 91 dietary
supplements. The dozens of brands of garlic on store shelves can be
classified into four groups, i.e., essential oil, garlic oil macerate,
garlic powder and garlic extract (Table 2
). As indicated previously, the manufacturing process can markedly
influence the composition of the garlic product. Clearly, manufacturers
must ensure that garlic products are safe, stable and effective.
Documentation of the safety and effectiveness is crucial in the
evaluation of all products, including garlic, that are proposed for use
for health promotion.
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1–2
cloves garlic or 4 g of intact garlic may have health benefits.
Unfortunately, this recommendation is not substantiated with a
scientific reference. In many recent clinical studies, the daily dose
of dehydrated garlic powder has been 900 mg. Aged garlic extract
intakes ranging from 1 to 7.2 g/d have been used with success. Studies
showing immune enhancement in humans have shown as little as 1.8 g
to as much as 10 g/d of AGE to be effective (Abdullah et al. 1989
, Kandil et al. 1987 and 1988
).
Interestingly, no severe toxic side effects were reported in these
clinical studies, even at high dosages. Other garlic supplements do not
have studies of toxicity or safety, and few have any clinical studies
to confirm their efficacy.
Essential oil
Garlic essential oil is obtained by steam distillation of garlic.
The essential oil content of garlic cloves is 0.2–0.5% and consists
of a variety of sulfides, such as DADS and diallyl trisulfide
(Block 1985
, Yan et al. 1992
). Whole
garlic cloves, ground in water, are heat-distilled or extracted in
an organic solvent (e.g., hexane) to obtain the oil fraction.
Water-soluble compounds are totally eliminated by this process.
Allicin is also completely eliminated from the oil. Commercially
available garlic oil capsules generally contain vegetable oil and a
small amount of garlic essential oil because of pungent odors. More
attention to the ingredients in these products is warranted.
Dehydrated powder
Garlic powder is mass-produced as a flavoring agent for
condiments and processed foods. Garlic cloves are sliced or crushed,
dried and pulverized into powder. Garlic powder is thought to retain
the same ingredients as raw garlic; however, the proportions and
amounts of various constituents differ significantly (Iberl et al. 1990b
). For example, the main sulfur compound in both raw
garlic and garlic powder is alliin. On average, garlic cloves contain
0.8% alliin. A pure dehydration process, with no loss of
ingredients, would result in a 2–2.5 mg/g alliin content in the
powder. However, garlic powders contain only 1% alliin at most,
indicating that more than half of the alliin is lost during
dehydration. Crushed raw garlic is high in allicin, containing 3.7
mg/g (Lawson et al. 1992
). Although allicin is often
emphasized in dehydrated powder, many preparations contained no
allicin, possibly reflecting its instability (Freeman and Kodera 1995
, Yan et al. 1993
). Therefore, although
dehydrated garlic powders contain some constituents similar to those of
raw garlic, amounts may vary significantly.
Although no product on the market contains a detectable amount of
allicin (<1 ppm) (Freeman and Kodera 1995
), some garlic
powder products claim to be able to generate a certain amount of
allicin (so-called "allicin potential" or "allicin yield").
However, only a very small amount of allicin (<5%) has been produced
in simulated gastric fluid compared with water (Freeman and Kodera 1995
), demonstrating that is not generated in
appreciable amounts. This is likely due to the inactivation of
alliinase, the enzyme that catalyzes the conversion of alliin to
allicin at 
pH 3 (Lawson and Hughes 1992
). When
dehydrated garlic powder was exposed consecutively to simulated stomach
fluids and simulated intestinal fluids, which would occur when a garlic
powder is consumed orally, a 99% loss in allicin production was
observed (Freeman and Kodera 1995
). Therefore, allicin
cannot be the active compound in dehydrated garlic powders, nor is it
an appropriate marker compound for all garlic preparations. As stated
previously, some dehydrated powder products are reported to be
ineffective at reducing plasma cholesterol in humans (Berthold et al. 1998
, Breithaupt-Grögler et al. 1997
, Isaacsohn et al. 1998
, McCrindle et al. 1998
, Neil et al. 1996
, Simons et al. 1995
). Part of this inconsistency in the literature may relate
to poor standardization of products tested.
Oil macerate
Oil macerates were originally developed for use as condiments. Oil
macerate products are made of encapsulated mixtures of whole garlic
cloves ground into vegetable oil. During the manufacturing process,
some alliin is converted to allicin. Because allicin is unstable and
decomposes quickly, oil macerate preparations contain
allicin-decomposed compounds such as dithiins, ajoene and sulfides,
residual amounts of alliin and other constituents in garlic
(Block 1985
, Iberl et al. 1990a
).
Standardization for ingredients in macerates has not been explored
adequately.
Extract
For garlic extract, whole or sliced garlic cloves are soaked in an
extracting solution (e.g., purified water and diluted alcohol) for
varying amounts of time. After separation of the solution, the extract
is generally concentrated and used. Powdered forms of the extract are
also available. The extract, especially AGE, contains mainly the
water-soluble constituents in garlic and a small amount of
oil-soluble compounds (Weinberg et al. 1993
). The
extract is characterized by water-soluble sulfur-containing
compounds, including SAC and SAMC (Imai et al. 1994
).
Aged garlic extract is processed in a different way from the other
three types of garlic products. As the name indicates, this extract is
aged for up to 20 mo. During this aging process, the odorous, harsh and
irritating compounds in garlic are converted naturally into stable and
safe sulfur compounds. Aged garlic extract contains primarily
water-soluble sulfur compounds such as SAC and SAMC, as well as a
variety of oil-soluble sulfur compounds. SAC can be used for
standardization because it is bioavailable (Nagae 1994
).
Further, the safety of AGE has been confirmed by various toxicological
studies (Kanezawa et al. 1984
, Nakagawa et al. 1980, 1984a and 1984b
, Sumiyoshi et al. 1984
, Yoshida et al. 1984
).
Bioavailability of garlic compounds
Bioavailability of active ingredients in garlic is likely
essential. SAC is one of the water-soluble organosulfur compounds
in garlic. Its concentration increases during extraction/aging. The
pharmacokinetics of SAC are well established (Nagae et al. 1994
). SAC can be detected in the plasma, liver and kidney
after oral intake (Nagae et al. 1994
). The
bioavailability of SAC is 103.0% in mice, 98.2% in rats and 87.2% in
dogs (Nagae et al. 1994
). N-Acetyl-SAC has
been identified as a metabolite of SAC in the urine of dogs and humans.
This suggests that SAC could be transformed by
N-acetyltransferase. SAC and its metabolite(s) are possible
compliance-markers for clinical studies involving garlic
(Steiner and Li 2001
). Because SAC is found in many
preparations, it might be used for standardization and/or used to
compare various sources.
The oil-soluble organosulfur compounds in garlic, including
allicin, sulfides, ajoene and vinyldithiins, are not found in blood or
urine, even after consumption of a large amount of garlic (Fig. 4
; Lawson et al. 1992
). As shown in Table 3
, a preliminary study with garlic products, including enteric-coated
products, revealed that no allicin was found in blood after oral
ingestion. Allyl mercaptan and DAS were the first compounds identified
as the components that produce the strong odor detectable after
ingestion of garlic (Laakso et al. 1989
, Minami et al. 1989
). Allicin, perfused into isolated rat livers,
showed a remarkable first-pass effect and is metabolized to DADS
and allyl mercaptan, whereas ajoenes and vinyldithiins were recovered
in the effluent (Egen-Schwind et al. 1992b
). Allicin
disappeared very rapidly when incubated with liver homogenate
(Egen-Schwind et al. 1992a
). No allicin was detected in
either serum or urine from 1 to 24 h after ingestion of 25 g
of raw garlic (90 mg allicin) (Fig. 4
; Lawson et al. 1992
). Comparing the content of garlic products for their
ability to inhibit platelet aggregation on the basis of ajoene and
dithiin content (Lawson et al. 1992
) may be inadequate
because other compounds may act synergistically or independently to
bring about an effect. For example, AGE, which contains neither ajoene
nor dithiin, significantly reduced platelet aggregation and adhesion in
two double-blind, placebo-controlled clinical studies
(Rahman and Billington 2000
, Steiner and Lin 1998
). Thus, the concentration of various compounds and their
effects in vitro may not determine effectiveness. Preclinical or,
preferably, clinical studies are required to confirm or refute the
effectiveness of a product in question, whatever its chemical
composition.
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). The maximum concentration of radiolabeled DADS in the
liver of mice occurred 90 min after intraperitoneal administration
(Pushpendran et al. 1980
). Seventy percent of the
radioactivity, which was no longer DADS, was distributed in the liver
cytosol, of which 80% was metabolized to sulfate. DADS, like allicin,
was not detected in human blood or urine from 1 to 24 h after oral
ingestion of 25 g of crushed raw garlic (Lawson et al. 1992
).
Because allicin, ajoene, vinyldithiins and DADS are not found in the
blood or urine after garlic consumption, they are likely not the active
compounds per se. The instability and/or metabolism of such compounds
likely contribute to the inconsistent results found in the clinical
cholesterol studies using garlic oil (Berthold et al. 1998
) and garlic powder products (Berthold et al. 1998
, Breithaupt-Grögler et al. 1997
,
Isaacsohn et al. 1998
, McCrindle et al. 1998
, Neil et al. 1996
, Simons et al. 1995
).
SAC is a stable, odorless, water-soluble compound with the ability
to lower cholesterol (Yeh and Yeh 1994
), serve as an
antioxidant (Ide et al. 1997
, Imai et al. 1994
), inhibit the cancer process (Amagase and Milner 1993
, Li et al. 1995
) and protect the liver from
toxins (Nakagawa et al. 1988
). AGE, a product
standardized for SAC, has shown cholesterol-lowering effects in
several clinical studies (Lau et al. 1987
,
Steiner et al. 1996
, Yeh et al. 1995
).
Other metabolites of garlic constituents, such as
N-acetyl-S-(2-carboxypropyl)-cysteine,
N-acetylcysteine and hexahydrohippuric acid, have been
detected in human urine after ingestion of garlic (Jandke and Spiteller 1987
). After consumption of garlic,
N-acetyl-S-allyl-cysteine is found in human
urine. At present, SAC is the only reliable human compliance marker
used for studies involving garlic consumption because it is detectable
and increases quantitatively in the blood after oral intake of garlic
capsules (Steiner and Li 2001
).
Overall, the active principles in garlic have not been fully characterized. It is assumed that the bioavailability of these sulfur-containing compounds will play an important role in determining the biological response to various garlic preparations.
Safety and quality control of garlic preparations
The effectiveness of garlic may be in prevention rather than therapy. To obtain the preventative benefits of garlic, however, long-term supplementation may be necessary. Long-term use of supplements raises issues about toxicity. The general attitude of the public regarding safety is one of the important concerns associated with long-term use of any product. As mentioned previously, garlic preparations vary in constituents, necessitating toxicological tests of each product to ensure its safety. It is essential that safety be considered a major part of the quality control of all garlic preparations
Although garlic has been used safely in cooking as a popular condiment
or flavoring and used traditionally for medicinal purposes, it is
commonly known that excessive consumption of garlic can cause problems.
Garlic odor on breath and skin (Mader 1990
) and
occasional allergic reactions (Siegers 1992
) are
recognized. Reports since 1932 have revealed the following adverse
effects associated with raw garlic and garlic powder: 1)
stomach disorders and diarrhea (Caporaso et al. 1983
,
Desai et al. 1990
, Nakagawa et al. 1980
);
2) decrease of serum protein and calcium (Miyamoto 1938
, Shashikanth et al. 1986
); 3)
anemia (Katsunuma 1932
, Kuzutani 1934
,
Nakagawa et al. 1980
); 4) bronchial asthma
(Lybarger et al. 1982
, von Kirsten and Meister 1985
); 5) contact dermatitis (Burden et al. 1994
, Garty 1993
, Lembo et al. 1991
, McFadden et al. 1992
, Mitchell 1980
, Parish et al. 1987
); and 6)
inhibition of spermatogenesis (Dixit and Joshi 1982
,
Qian et al. 1986
).
Oil-soluble sulfur compounds are known irritants and allergens;
topically applied DAS is the most allergenic (Papageorgiou et al. 1983
). Imada (1990)
reported the following
toxicity effects of garlic: 1) allicin is one of the major
irritants in raw garlic; 2) oil-soluble sulfur compounds
are more toxic than water-soluble compounds; and 3) when
garlic is extracted in a certain period, its toxicity is greatly
reduced.
Crushed raw garlic is high in allicin (3.7 mg/g) (Lawson et al. 1982). Enteric-coated garlic products are designed to
deliver allicin (1–5 mg, depending on the product label claim)
directly into the intestinal tract. However, allicin can be an
oxidizing agent that not only impedes bacterial growth
(Shashikanth et al. 1985
) but also can damage the
intestinal lining and the stomach (Kodera 1997
). As
shown in Figure 5
, raw garlic juice (0.5 mL) caused significant damage to the epithelial
mucosal membrane after 2 h in rats. After 24 h of exposure,
ulcers, shrinkage and bleeding in the epithelial mucosa were detected.
When three kinds of commercially available enteric-coated garlic
preparations, i.e., Garlicin, Garlique and Garlinase 4000, were used at
dosages of 133, 108 and 60.5 mg/rat, respectively, each caused severe
damage to the duodenal mucosa after 2 h of exposure (Fig. 5)
.
Saline controls showed no damage to ligated duodenums. According to
this study, enteric-coated garlic powder products, which are
designed to generate allicin in the delicate intestine, may be
hazardous to the intestinal tract.
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); 2) chronic toxicity test (Sumiyoshi et al. 1984
); 3) mutagenicity tests (Yoshida et al. 1984
); 4) general toxicity tests (Kanezawa et al. 1984
, Nakagawa et al. 1980
); 5)
teratogenicity tests (Segments I, II, and III); 6) toxicity
test conducted by the U.S. Food and Drug Administration; and
7) clinical studies conducted on >1000 subjects
(Hasegawa et al. 1983
, Kawashima et al. 1989
, Steiner et al. 1996
).
One of the active ingredients of garlic preparations, including AGE, is
SAC. SAC is a very useful compound that has been well researched for
its pharmacologic effects. The United States National Cancer Institute
tested the toxicity of SAC vs. other typical garlic compounds and found
that it has 30-fold less toxicity than allicin and DADS (Imada 1990
). The 50% lethal oral dose for allicin in mice is as
follows (mg/kg body): male 309, female 363; for DADS: male 145, female
130; and for SAC: male 8890, female 9390.
Documentation of safety and effectiveness are crucial in the evaluation of products used for health purposes, such as drugs and food supplements. As mentioned above, different garlic preparations comprise different constituents, which necessitates detailed toxicological and biological tests of each product to ensure safety and efficacy.
U.S. Pharmacopoeia (USP) and other organizations are developing a
monograph dealing with garlic as part of a series on botanicals. USP
did not list allicin as a reference standard in its garlic and garlic
powder monograph (USP 1999
). Label statements on dietary
supplements must be based on science that can help consumers make
informed decisions.
Summary
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. 
3 Abbreviations used: AGE, aged garlic extract;
DADS, diallyl disulfide; DAS, diallyl sulfide; SAC,
S-allylcysteine; SAMC,
S-allylmercaptocysteine.
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