Ageing Research Reviews

2 (2003) 3956
Garlic and aging: new insights into an old remedy
Khalid Rahman

School of Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK
Received 10 July 2002; accepted 12 July 2002
Abstract
There has been an impressive gain in individual life expectancy with parallel increases in
age-related chronic diseases of the cardiovascular, brain and immune systems. These can cause
loss of autonomy, dependence and high social costs for individuals and society. It is now accepted
that aging and age-related diseases are in part caused by free radical reactions. The arrest of aging
and stimulation of rejuvenation of the human body is also being sought. Over the last 20 years
the use of herbs and natural products has gained popularity and these are being consumed backed
by epidemiological evidence. One such herb is garlic, which has been used throughout the history
of civilization for treating a wide variety of ailments associated with aging. The role of garlic in
preventing age-related diseases has been investigated extensively over the last 1015 years. Garlic
has strong antioxidant properties and it has been suggested that garlic can prevent cardiovascular
disease, inhibit platelet aggregation, thrombus formation, prevent cancer, diseases associated with
cerebral aging, arthritis, cataract formation, and rejuvenate skin, improve blood circulation and
energy levels. This review provides an insight in to garlics antioxidant properties and presents
evidence that it may either prevent or delay chronic diseases associated with aging.
2003 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Garlic; Aging; Chronic diseases; Antioxidants
1. Introduction
Medicinal herbs have been used in primary health care over many centuries before the
advent of modern medicine. Over the last 20 years there has been an international resurgence
of medicinal herbs in Western culture, especially in the USA which has coincided with the
greening issues and an enhanced interest in natural systems and the questioning of an
over-dependence on synthetic drugs to maintain health. Similar trends have been observed
in Europe and the growth rate of phytotherapeutics in Europe has been reported to be

Tel: +44-151-231-2087; fax: +44-151-298-2821.

E-mail address: k.rahman@livjm.ac.uk (K. Rahman).
1568-1637/03/$ see front matter 2003 Elsevier Science Ireland Ltd. All rights reserved.
PII: S1568- 1637( 02) 00049- 1
40 K. Rahman / Ageing Research Reviews 2 (2003) 3956
greater than that for pharmaceuticals (Wills et al., 2000). Several epidemiological studies
have shown that a diet rich in plant foods may reduce the development of certain chronic
diseases such as cancer and atherosclerosis (Keys, 1995); one such plant food is garlic.
2. Garlic
2.1. Historical perspective
Garlic (Allium sativum) is believed to have originated in Central Asia and to date the
genus Alliumcomprises over 600 known species, which include Alliumcepa (onion), Allium
porrum(leek) and Alliumschoenoprasum(chives). The genus Alliumbelongs to the Alliacae
family. Garlic is used universally as a avoring agent, traditional medicine and a functional
food to enhance physical and mental health. The benecial effects of garlic consumption
in treating a wide variety of human diseases and disorders have been recorded and passed
down by many civilizations.
2.2. Composition of garlic
The general composition of garlic is shown in Table 1. The majority of garlic (65%) is
water and the bulk of the dry weight is composed of fructose-containing carbohydrates,
followed by sulfur compounds, protein, bre and free amino acids (Lawson, 1996). Garlic
also contains high levels of saponins, phosphorus, potassium, sulfur, zinc, moderate levels
Table 1
General composition of garlic
Component Amount (fresh weight; %)
Water 6268
Carbohydrates (mainly fructans) 2630
Protein 1.52.1
Amino acids: common 11.5
Amino acids: cysteine sulphoxides 0.61.9
-Glutamylcysteines 0.51.6
Lipids 0.10.2
Fibre 1.5
Total sulphur compounds
a
1.13.5
Sulphur 0.230.37
Nitrogen 0.61.3
Minerals 0.7
Vitamins 0.015
Saponins 0.040.11
Total oil-soluble compounds 0.15 (whole)0.7 (cut)
Total water-soluble compounds 97
Taken from Lawson, 1996.
a
Excluding protein and inorganic sulphate (0.5%).
K. Rahman / Ageing Research Reviews 2 (2003) 3956 41
of selenium and Vitamins A and C, and low levels of calcium, magnesium, sodium, iron,
manganese and B-complex vitamins. It also has a high phenolic content (Vinson et al.,
1998). Nearly all of these compounds present in garlic are water-soluble (97%) with a
small amount of oil-soluble compounds (0.150.7).
Garlic contains unique organosulfur compounds, which provide its characteristic avor
and odor and most of its potent biological activity (Block, 1985). In fact, over 90% of
investigations on garlics active principles have focussed on the sulfur compounds of which
about 85% comprise of alliin and two main -glutamylcysteines. Alliin is considered the
parent substance of the therapeutically active sulfur components of garlic. When garlic is
crushed, cut or chewed alliin is exposed to the enzyme alliinase and the thiosulnate allicin
is formed. Allicin is a reactive intermediate species that can be transformed into a variety
of compounds depending on environmental conditions and extraction methods and is also
thought to be responsible for the usual odor of fresh cut or crushed garlic. Besides the
organosulfur compounds, garlic also contains carbohydrates (e.g. fructans), enzymes (e.g.
alliinase, catalase), proteins and free amino acids (e.g. arginine), lipids, polyphenols and
phytosterols.
Because of the intense interest in garlic, commercial garlic preparations have over the
years become available. These include aged garlic extract (GEX), which is formulated by
soaking sliced raw garlic in 1520% aqueous ethanol for up to 20 months at room tempera-
ture. The extract is then ltered and concentrated under reduced pressure at lowtemperatures
and is marketed in both dry (tablets and powder capsules) and liquid form which contains
10% (w/v) ethanol. The major sulfur compound in GEX is S-allylcysteine (SAC) and this is
used to standardize the commercial GEX. Other commercial garlic preparations are garlic
powder tablets (containing known amounts of allicin), oil of steam-distilled garlic, oil of
oil-macerated garlic and ether extracted oil of garlic. Some garlic preparations also contain
known amounts of vitamins and other phytochemicals.
Throughout the history of civilization the medicinal properties of garlic have been greatly
valued and have been used to treat a wide variety of human ailments. Garlic is most com-
monly used to prevent or delay many of the chronic diseases associated with old age such as
atherosclerosis, stroke, cancer, immune disorders, cerebral aging, arthritis, cataract forma-
tion and promoting general health including increasing energy levels and general circulation
(Rahman, 2001).
2.3. Biochemistry of aging
Aging can generally be dened as a progressive decline in the efciency of biochemical
and physiological processes after the reproduction phase of life. This contribution of the
aging process to changes occurring with age are small early in life but rapidly increase with
age because of the exponential nature of the process. Many theories have been put forward
to explain the phenomenon of aging (Finkel and Holbrook, 2000; Biesalski, 2002) its likely
that all these theories contribute to its mechanisms. Among the theories proposed, the free
radical theory of aging originally proposed by Harman (1956) is widely accepted. This
theory postulates that aging is caused by free radical reactions which may be involved in
production of the aging changes associated with the environment, disease and intrinsic aging
process. It is based on the chemical nature of free radical reactions and their ubiquitous and
42 K. Rahman / Ageing Research Reviews 2 (2003) 3956
prominent presence in living beings. This free radical theory of aging is in good agreement
with another theory, the rate of living hypothesis, which inversely correlates metabolic
rate with life span (Ku et al., 1993). It is generally accepted that reactive oxygen species
(ROS) are generated in vivo and can cause cellular damage. The most important sources of
ROS generation are mitochondrial electron transport, peroxisomal fatty acid metabolism,
cytochrome P450 reactions and phagocytic cells (respiratory burst). However, in addition to
these four originators, numerous enzymes exist, capable of generating ROS under normal
and pathological conditions. Based on Harmans (1956) assumptions, aging is a conse-
quence of accumulation of ROS-induced damage to proteins and DNA in the mitochondria
and it has been frequently proposed that the major targets for free radical attack are the
membranes of cells and the nuclear genome. The nuclear genome and mitochondrial DNA
are especially vulnerable to the accumulation of free radical damage (Barga and Herrero,
2000) and aging results fromthe accumulated non-repaired damage caused by free radicals.
Over the last 1015 years the results of many studies have indicated that oxidative dam-
age to human cells accumulates with age and is a major contributor to degenerative diseases
associated with aging such as cancer, Alzheimers disease, cardiovascular disease and ner-
vous system dysfunction (Ames et al., 1993; Ambrosone et al., 1999; Christen, 2000).
On the transactional level, many studies suggest that the process of aging and the onset
of age-related diseases can be slowed, either through genetics or through dietary restric-
tion (Prolla and Mattson, 2001). Unfortunately, genetic changes are unethical and dietary
restriction is difcult and is unlikely to be followed by majority of elderly individuals.
Since it is well accepted that oxidative free-radical stress is an important contributor
to the aging process and to many age-related diseases, the focus must be on reducing
oxidative stress in vivo. This can be achieved by limiting exposure to outside oxidative
agents such as cigarette smoke and other environmental exposures such as UV sunlight
etc. This is important because oxidative damage apparently increases with age and thus
may overwhelm the natural repair systems in the elderly (Kowald and Kirkwood, 2000).
The best way to neutralize free-radical mediated oxidative stress in the elderly is to ingest
diet rich in phytochemicals with antioxidant properties or to take dietary supplements of
antioxidants. These are widely found in nature, especially in plant products and are an
extremely diversied group of chemicals. One such naturally occurring antioxidant is garlic
and its role in preventing diseases associated with old age is presented in this review. It must
be remembered that any dietary supplement which can counteract oxidative stress has the
potential to extend life expectancy or improve the quality of life, whether or not it alters the
aging process per se.
2.4. Garlic and cardiovascular disease
Epidemiological studies have identied a number of risk factors for the development
of atherosclerosis which include elevated serum lipids (cholesterol and triglycerides), in-
creased plasma brinogen and coagulation factors, increased platelet activation, alterations
in glucose metabolism and smoking (Wood, 2001). However, the oxidative modication
of low-density lipoprotein (LDL) is now considered an important mechanism in the devel-
opment of atherosclerosis (Keaney, 2000). There is strong epidemiological evidence that
atherosclerosis-related conditions (coronary artery disease, ischemic stroke and peripheral
K. Rahman / Ageing Research Reviews 2 (2003) 3956 43
artery disease) all increase with age (Gallotta et al., 1997) and its effects are mainly ev-
ident in the muscular arteries e.g. coronary, carotid, femoral and iliac arteries as well as
the aorta. Aging causes the changes in the structure and function of the vessels that leads
to an increase in the incidence of certain cardiovascular diseases causing enhancement of
both morbidity and mortality. When aging is associated with hypertension, these changes
are increased. Aging also alters endothelial cells and hence the vascular tone regulation,
reducing the endothelium-dependent relaxations, probably by a decrease in endothelial
synthesis or release of nitric oxide (Marin and Rodriguez-Martinez, 1999). With increas-
ing age, there is also an increase in vascular wall stiffening which is characterized by
an increase of the collagen-elastin ratio and deposition of calcium and lipids within the
blood vessels (Robert, 1999). Enhanced oxidative stress with aging may also play an im-
portant role in the increased prevalence of atherosclerosis in older individuals. Evidence
from both in vitro and in vivo studies suggests that oxidation of LDL may contribute to
early atherosclerotic lesion formation (Reaven and Witztum, 1996) and there is also a
continuous increase in LDL hydroxy fatty acids content with age in healthy, elderly indi-
viduals (Jira et al., 1996). A different type of lipoprotein aging can occur in conditions
where lipoprotein removal from the plasma is delayed. This can then lead to a progres-
sively more senescent form of circulating lipoprotein that is more susceptible to oxygen
radical-induced modications (Walzem et al., 1995). Oxidized LDL elicits pro-atherogenic
properties, these include increased smooth muscle proliferation (Koba et al., 1999), cyto-
toxicity to vascular endothelial cells, smooth muscle cells and broblasts (Sevanian et al.,
1995) together with the induction of apoptotic cell death in vascular endothelial cells (Napoli
et al., 2000).
Garlic has been used to treat a variety of cardiovascular problems over the years. Various
garlic extracts have been shown to reduce diet-induced hypercholesterolemia in rats and
rabbits (Bordia and Verma, 1980; Slowing et al., 2001). Aged garlic extract (GEX) supple-
mentation has been shown to be effective in lowering plasma cholesterol and triglyceride
and LDL-cholesterol in hyperlipidemic subjects (Steiner et al., 1996) whilst it had no effect
in normolipidemic subjects (Rahman and Billington, 2000). In support of this, supplemen-
tation with garlic powder preparations has also been reported to reduce plasma cholesterol
in hypercholesterolemic subjects (Kannar et al., 2001), however, some conicting data has
also been reported (Gardner et al., 2001). It is likely that garlic and its constituents lower
plasma cholesterol and triglycerides by inhibiting the key enzymes involved in cholesterol
and fatty acid synthesis (Liu and Yeh, 2001).
Platelet aggregation and subsequent thrombus formation is signicantly and efciently
decreased by garlic and its constituents and rbrinolysis is also enhanced resulting in dis-
solution of clots and thrombi (Bordia et al., 1998). At low intake (2.4 g per day), sup-
plementation with GEX has been shown to increase the threshold levels of collagen and
epinephrine-induced platelet aggregation and platelet adhesion to brinogen in healthy
individuals (Steiner and Li, 2001). This study also demonstrated that high intake (7.2 g
per day) of GEX increased the threshold level of ADP-induced platelet aggregation and
platelet adhesion to collagen and von Willebrand factor. More importantly, this inhibition
of ADP-induced platelet aggregation after dietary intervention with GEX (5 ml per day
(equivalent to 1.5 g per day)) has also been observed in normolipidemic subjects in our
laboratory (Rahman and Billington, 2000).
44 K. Rahman / Ageing Research Reviews 2 (2003) 3956
Fig. 1. ADP-induced platelet aggregation in humans before and after ingestion of aged garlic extract (GEX). Platelet
aggregation was initiated by the addition of various concentrations of ADP to platelet-rich plasma. Aggregation
curves were analyzed for : (A) the total percentage aggregation, and, (B) the initial rate of aggregation (%/min).
Values are means SEM, n = 23.

Signicantly different (P < 0.05) before and after ingestion of GEX.
(reproduced from Rahman and Billington, 2000).
Aged garlic extract signicantly inhibited both the total percentage and the initial rate
of platelet aggregation at concentrations of ADP up to 10 mol/l (Fig. 1A and B). The
K
M
for ADP-induced platelet aggregation was approximately doubled after dietary supple-
mentation with GEX, where as the maximum rate of aggregation was unaffected. In other
studies, dietary garlic oil has been shown to inhibit platelet aggregation induced by arachi-
donic acid, adrenaline, collagen and calcium and has been shown to decrease the formation
of the pro-aggregatory prostaglandin thromboxane-A
2
(TXA
2
) in platelets (measured as
thromboxane-B
2
) in coronary artery disease patients (Bordia et al., 1998). In comparison,
fresh garlic extracts have also been shown to inhibit cyclooxygenase activity in cell free
systems and in animal studies (Thomson et al., 2000).
In vitro studies have identied that GEX improves microcirculation and blood properties
by preventing lipid peroxidation and hemolysis in oxidized erythrocytes (Moriguchi et al.,
K. Rahman / Ageing Research Reviews 2 (2003) 3956 45
2001). This is supported by a study in which chronic garlic powder consumption was shown
to attenuate age-related increases in aortic stiffness, thus protecting the elastic properties of
the aorta which are related to aging in humans (Grogler-Breithaupt et al., 1997).
A garlic extract has also been shown to modulate the production and function of both
endothelium-derived relaxing factor (NO) and constricting factors (endothelin-I) in rat-
isolated pulmonary arteries (Kim-Park and Ku, 2000) and reduce blood pressure in hyper-
cholesterolemic subjects (Steiner et al., 1996).
One of the most important biochemical properties of garlic is its antioxidant potential.
The antioxidant actions of garlic and its constituents have been determined by their abil-
ity to scavenge reactive oxygen species (ROS), inhibit lipid peroxide formation and LDL
oxidation, and enhance endogenous antioxidant systems.
Aged garlic extract and its main constituents have been reported to scavenge the t-butyl
hydroperoxide radical and hence prevent lipid peroxidation of liver microsomes (Imai et al.,
1994). This study also reported that water extracts of raw and heat-treated garlic enhanced
peroxidation of liver microsomes induced by t-butyl hydroperoxide whilst garlic powder
extracts have demonstrated the ability to scavenge reactive species such as OH

and pe-
roxyl radicals (Aruoma et al., 1997).
Dietary supplementation with GEX for 7 days signicantly reduced the susceptibil-
ity of subsequently isolated LDL to Cu
2+
-mediated lipid peroxidation (Munday et al.,
1999; Steiner and Lin, 1998). Interestingly, in this study ingestion of raw garlic had no
signicant effect on the same parameters. Similar studies have also been performed using
garlic powder extracts but the results are inconsistent.
Previous studies have reported that GEX increases intracellular glutathione (GSH) levels
in vascular endothelial cells by modulation of the GSH redox cycle specically increasing
glutathione disulde (GSSG) reductase activity and superoxide dismutase (SOD) activity
(Geng and Lau, 1997). This is supported by a study in which garlic supplementation pre-
vented the increase in oxidative stress associated with gentamicin-induced nephrotoxicity in
rats. Oxidative stress was ameliorated by preserving superoxide dismutase and glutathione
peroxidase activities (Pedraza-Chaverri et al., 2000). In vivo animal studies have been used
to investigate the effect of garlic oil supplementation on nicotine-induced lipid peroxida-
tion in rats. Garlic oil supplementation reduced lipid peroxidation as assessed by numerous
methods in all major organs of the rat (heart, lung, liver and kidney). This decrease in lipid
peroxidation was associated with an increase in activity of antioxidant enzymes (catalase,
SOD and glutathione peroxidase) and increased levels of GSH (Helen et al., 1999). If gar-
lic is to be recommended as an antioxidant then its important that it is efcacy be proven
in human clinical trials. There are no reported studies in the aging population in which
garlics efcacy has been tested. However, the data to date support the notion that garlic
consumption by the elderly may prevent or reduce diseases associated with oxidative stress
and aging. We in our laboratory have investigated the effects of dietary supplementation
with GEXon the plasma and urine concentrations of 8-iso-Prostaglandin F
2
(8-iso-PGF
2
)
in smoking and non-smoking men and women. Its quantication in plasma and urine is a
sensitive and specic indicator of lipid peroxidation and, hence of oxidative stress in vivo.
Dietary supplementation with GEXfor 14 days reduced plasma and urine concentrations of
8-iso-Prostaglandin F
2
by 29% and 37% in non-smokers and by 35 and 48% in smokers.
Fourteen days after cessation of dietary supplementation, plasma and urine concentrations
46 K. Rahman / Ageing Research Reviews 2 (2003) 3956
of 8-iso-Prostaglandin F
2
returned to values not different from those before ingestion
of GEX in both groups (Fig. 2A and B) (Dillon et al., 2002). No other changes in other
biochemical parameters were observed. In this study it was observed that the antioxidant
capacity of non-smokers was approximately twice that of smokers. More importantly the
plasma antioxidant capacity of smokers had signicantly increased by 53% following sup-
plementation with GEX for 14 days. Interestingly, the signicant difference observed in the
plasma antioxidant capacity between non-smokers and smokers prior to ingestion of GEX
was reduced after 2 weeks of dietary supplementation. The plasma antioxidant capacity
of non-smokers remained unaffected by the 2-week washout period. However, after the
2-week washout period plasma antioxidant capacity decreased by 49% in smokers and was
now similar to that prior to ingestion of GEX. (Fig. 3). The results indicate that dietary
supplementation with garlic may reduce oxidative stress especially in the elderly as they
tend to have a higher levels of this.
Garlic is a complex mixture of phytochemicals and its likely that they all interact
synergistically to provide it benecial effects, especially its antioxidant capacity. Dietary
avonoids are potent antioxidants and their consumption has resulted in signicantly re-
duced susceptibility of isolated LDL to lipid peroxidation (Avriam et al., 2000). Intake of
avonoids has also been inversely correlated with risk of mortality from coronary artery
disease (Geleijnse et al., 1999) and it is likely that some of the benecial effects of garlic
are due to its contents of avonids such as apigenin, myricetin and quercetin (Miean and
Mohamed, 2001).
2.5. Garlic and cancer
Carcinogenesis is a complicated, multi-stage process; a small population of abnormal
cells is generated and then increases in abnormality as a result of a series of mutations and
changes in the patterns of gene expression. Factors predisposing to malignancy include,
inherited traits, environmental agents, diet, and the risk of cancer increases with age (Ames
and Shigenaga, 1992). It is well established that oxidative insults to DNA can lead to
mutations in crucial genes, which ultimately may lead to cancer (Ames and Shigenaga,
1992) and that potent antioxidants and nutrients from fruits and vegetables may be able to
quell the effects of oxidative DNA damage in the aged, in addition to lowering the overall
risk of cancer (Block, 1991).
Epidemiological studies have shown that enhanced garlic consumption is closely related
with reduced cancer incidence (Bianchini and Vainio, 2001). Many studies have reported
the anti-cancer effects of garlic. For example, diallyl disulde (DADS) is an oil-soluble
organosulfur compound found in garlic and is reported to have anticancer properties against
both hormone-dependent and -independent breast cancers and may hormonize with polyun-
saturated fatty acids which are known as modulators of breast cancer cell growth. (Nakagawa
et al., 2001). In support of this, other recent studies have also indicated that derivatives of
garlic can inhibit proliferation of a human prostate cancer cell line and a human breast
cancer cell line (Pinto and Rivlin, 2001). Garlic also inhibits the proliferation of human
colon, lung and skin cancer cells and induces apoptosis of human colon tumor cells by
increasing intracellular calcium concentrations (Sundaram and Milner, 1996a, Sundaram
and Milner, 1996b). In another study a recently identied Se compound in natural garlic
K. Rahman / Ageing Research Reviews 2 (2003) 3956 47
Fig. 2. Plasma and urine concentrations of 8-iso-PGF
2
in smoking and non-smoking subjects before and after
GEX consumption. (A) Plasma total concentration of 8-iso-PGF
2
. Signicant difference (P < 0.05) is indicated
by

from control (non-smokers) and

from day 0. (B) Urine concentration of 8-iso-PGF

2
. Signicant difference
(P < 0.05) is indicated by

from control (non-smokers),

from day 0 and

from day 14. Values for both are
means SEM, n = 10.
Fig. 3. Antioxidant capacityof plasma innon-smokers andsmokers before andafter GEXconsumption. Antioxidant
capacity is expressed as ascorbate equivalent antioxidant units (mol/l). Values are means SEM, n = 10.
Signicant difference (P < 0.05) is indicated by

from control (non-smokers),

from day 0 and

from day 14.

48 K. Rahman / Ageing Research Reviews 2 (2003) 3956
and selenised garlic, gamma-glutamyl- Se-methylselenocysteine has been shown to be a
cancer chemopreventative agent (Dong et al., 2001). Garlic can also detoxify carcinogens
by stimulation of cytochrome P450 enzymes, antioxidant activity or sulfur compound bind-
ing. Other studies have demonstrated a direct toxic effect of garlic on sarcoma and gastric,
colon, bladder and prostate cancer cells in tissue culture. It is likely that this effect of garlic
is obtained by the ability of garlic to prevent the suppression of the immune response which
is associated with increase risk of malignancy (Lamm and Riggs, 2001). In support of this
GEX has been shown to inhibit both early and late stages of carcinogenesis, resulting in in-
hibition of tumor growth in many tissues, including colon, mammary glands, skin, stomach
and oesophagus (Milner, 2001). Aged garlic extract exerts its cancer-inhibitory action in
different and complementary ways, due to the variety of compounds present in the extract
such as water and lipid-soluble organosulfur compounds, phenolic compounds, notably al-
lixin, saponins and selenium. Thus, the anticarcinogenic action of GEX, which contains all
of these compounds is broad in scope (Borek, 2001) and GEX is effective in blocking a
myriad of chemically induced tumors. Garlic can also inhibit carcinogenesis by modulating
carcinogen metabolism and decreasing carcinogen binding to DNA and it may also prevent
ROS-induced DNA damage since garlic has strong antioxidant properties. Thus, GEX has
also shown to inhibit DNA adduct formation in mammary cells (Milner, 1996).
The elderly population is exposed to a life time of UV-radiation which can cause DNA
damage and it is well established that inhibition of UV-and ionizing radiation carcino-
genesis can be reduced by the intake of antioxidants (Borek, 1997). Garlic being a strong
antioxidant provides radioprotective effects by its ability to scavenge free radicals, and en-
hance scavenging systems in the cell, including glutathione, SOD, catalase and glutathione
peroxidase (Wei and Lau, 1998). This is supported by a study in which GEX was shown
to protect bald mice from UV-light induced skin carcinogenesis (Reeve et al., 1993) and
allixin, a avonoid present in garlic inhibited tumor promotion in a multistep in vivo car-
cinogenesis skin tumor model and in vitro (Nishino et al., 1990). Aged garlic extract is
also reported to inhibit nuclear factor-B which is a transcription factor that is regulated by
the redox state of the cell and implicated in the inducible expression of a variety of genes
involved in oxidative stress and cellular responses to stress. It can be activated by mitogens,
bacteria and viruses and by ROS producing agents such as UV, ionizing radiation, hydrogen
peroxide and tumor necrosis factor (Borek, 2001). The collective evidence presented here
supports the notion that consumption of garlic by the elderly population may either prevent
or reduce the incidence of cancer. This is supported by a study by Smith et al. (1999) in
which they showed that supplementation with fruit and vegetable extracts, which are rich
in antioxidants, may decrease DNA damage in the peripheral lymphocytes in the elderly
population.
2.6. Garlic and cerebral function
The impressive gain in individual life expectancy is overshadowed by the loss of mental
function in old age. Decrements in motor function and decrements in memory are two main
behavioral parameters that are altered in senescence in both humans and animals. These
changes occur even in the absence of specic age-related neurodegenerative diseases, but
these could contribute to the changes. Primary degenerative brain disease and diseases
K. Rahman / Ageing Research Reviews 2 (2003) 3956 49
related to cerebral vascular disturbances are the leading cause of disability in old age and
can cause loss of autonomy, dependence and high social costs for individuals and the society.
Cognitive impairment reduces an individuals ability to function independently and the most
devastating consequence of cognitive impairment occurs when it progresses to clinical
dementia. Hence, prevention and treatment of disorders leading to mental impairment have
emerged as major challenge of the modern health care system.
Numerically the most important sub-type of dementia is Alzheimers disease (AD), fol-
lowedbyvascular dementia (VD) (Launer, 2000). There is increasingevidence that oxidative
stress is involved in cerebral aging and dementia and that free-radical reactions generated by
oxidation may contribute to both vascular and AD pathology. The brain is a good substrate
for oxidation: it is a large consumer of oxygen and a major component of cell membranes,
polyunsaturated fatty acids, are highly susceptible to lipid peroxidation and the brain also
has areas rich in pro-oxidant iron. Furthermore, the brain is low in anti-oxidant substances,
which could stop the free-radical chain reactions, which can also interact with other proteins
resulting in glycation and other Maillard reactions. Together, these processes disturb cell
structure and function, inactivate proteins, damage mitochondria and DNA, cause collagen
cross linking and damage the arterial system (Kristal and Yu, 1992). Evidence for oxidative
processes in AD comes from experimental and neuropathologic studies (Markesbery and
Carney, 1999; Yves, 2000). Briey, activated reactions may result from-amyloid toxicity,
activated microglial cells, defects in energy metabolism and altered capacity to inactivate
free radicals.
Oxidative stress may also mediate the damage in vascular dementia. There is a large
body of research describing mechanisms that generate free radicals in vessels and how
these free radicals contribute to atherosclerosis which in turn leads to cerebral ischemia
and reperfusion (Hall and Braughler, 1989), which in turn generate new free radicals. In
addition, elevated blood pressure leads to endothelial damage, dysregulation of nitric oxide
production and generation of free radicals which can then lead to tissue damage and neuronal
death. Cognitive impairment results if the damage is localized in regions or the interface
between regions important for cognition.
Since antioxidants are thought to play a role in stopping free-radical chain reactions,
interventions with antioxidants may help to reduce or prevent the incidence or progression
of dementing diseases. Thus, garlic, a strong antioxidant may have a role to play in reducing
cerebrovascular disease in the elderly.
Several epidemiological studies in elderly people have revealed a correlation between
antioxidants and cognitive performance (Stahelin, 1999). This epidemiological evidence
is supported by a number of laboratory investigations including experiments with garlic.
Allixin, a component of garlic was found to promote the survival of neurons derived from
various regions of the brain and also increased the number of branching points per axon in
hippocampal neurons (Moriguchi et al., 1997a). In another study by the same authors, using
a senile dementia model in mice it has been shown that GEX prevented atrophic changes in
the frontal brain, improved learning abilities and memory retention and increased longevity
in the senescence-accelerated mouse (Moriguchi et al., 1997b). This senescence-accelerated
mouse (SAM) model is particularly useful, as it has been shown to exhibit both morpho-
logical and neurological impairments observed in normal aging (Potier et al., 1993). Other
studies have found that SAM supplemented with GEX displayed both increased lifespan
50 K. Rahman / Ageing Research Reviews 2 (2003) 3956
and improved learning as assessed by active and passive avoidance tests (Moriguchi et al.,
1994). This protection by GEXwas found to be most predominant in the frontal brain areas,
thus likely contributing to the observed improvements in cognitive and behavioral tasks.
While a direct protective effect cannot be dismissed, the benecial effects promoted by
garlic could also be attributed to improved antioxidant activity within brain regions, which
potentially could result in reduction in membrane lipid peroxidation. Thus, protection of
neuronal cells from free-radical damage by garlic may improve certain brain functions.
In addition to antioxidant activity, changes in the immune response may contribute to a
number of age-related impairments in cognitive performance. In support of this, in thymec-
tomised mice supplemented with GEX, it has been shown that GEX displays a marked
improvement in a number of markers of immune function, thus GEX may be exerting some
protective effects in SAM through immunomodulatory mechanisms (Youdim and Joseph,
2001).
Free-radical damage andinammatoryprocesses linkedtoenhancedlevels of eicosanoids,
play an important role in cerebral ischemia-reperfusion injury. Using a rat model, GEX and
its components showed a dose-related attenuation of ROS production and inhibition of brain
damage caused by ischemia-reperfusion, reducing post-ischemia edema (Numagami et al.,
1996). Garlic being a strong antioxidant may also protect against age-related maculopathy
and cataract formation in the elderly as a reduced prevalence of nuclear cataract and antiox-
idant potential has been reported (Cumming et al., 2000). The role of garlic in preventing
cerebral aging and dementia is well supported by other studies which have indicated that
phytochemicals displaying antioxidant properties can improve neurological dysfunctions
(Youdim and Joseph, 2001; Deschamps et al., 2001).
2.7. Garlic and other anti-aging properties
The arrest of aging and stimulation of rejuvenation of the human body is being investi-
gated intensively and garlic has also been investigated for this purpose. The Hayick system
of cellular aging in culture has been used to test the anti-aging effects of garlic on long-term
growth characteristics, morphology and macromolecular synthesis of human skin brob-
lasts. This study has shown that garlic has some youth-preserving, anti-aging and benecial
effects on human broblasts in terms of maximumproliferative capacity and morphological
characteristics (Svendsen et al., 1994). Garlic may also have a protective role to play in re-
versing certain clinical features of cutaneous aging (i.e. ne lines and wrinkles) as has been
shown for other nutraceuticals and antioxidants (Murad and Tabibian, 2001). It has been
shown to increase perfusion in healthy volunteers as judged by an increase in erythrocyte
ow velocity which was mainly due to vaso dilation in both arterial and venous vessels
(Wohlrab et al., 2000). In addition, the administration of alliin and volatile S-containing
compounds in garlic have shown to enhance thermogenesis by increasing norepinephrine
secretion via -adrenergic action in an animal model (Oi et al., 1998). Aged garlic extract
has also been shown to modify the function of mast cells, basophils and activated T lym-
phocytes which play a leading role in allergic cascade reactions including inammation
(Kyo et al., 1997) and it has been also suggested that garlic may prevent bacteria-caused
food poisoning (Sasaki et al., 1999). Aging is associated with a decline in immune function,
which is believed to be responsible for the high prevalence of rheumatic, malignant, and
K. Rahman / Ageing Research Reviews 2 (2003) 3956 51
infectious diseases in the elderly. It is well known that older adults are at risk of malnutrition
which may contribute to an increased risk of infection and this may be increased in immune
senescence (Castle, 2000). Thus, garlic consumption may be benecial by the elderly as
it has strong antioxidant properties since it is known that antioxidants can modulate the
immune system (Fuente and Victor, 2000).
The glutathione redox system is a major component of overall antioxidant defenses in
the cells. It is irreversibly consumed in the detoxication of electrophilic metabolites and
xenobiotics and is a very efcient free-radical scavenger and protects cells from the toxic
effects of reactive oxygen compounds. The elderly have lower concentrations of glutathione
in plasma, whole blood and gastric mucosa indicative of impaired antioxidant defenses.
It has also been shown that there is a higher incidence of age-related chronic illnesses in
elderly individuals with lower than normal blood glutathione concentrations compared with
elderly individuals with normal concentrations (Lang et al., 2000). Cataracts and retinopathy
have been linked directly to impaired glutathione status and aged garlic extract has been
shown to increase cellular glutathione in a variety of cells including those in normal liver
and mammary tissue and thus consumption of garlic may enhance glutathione levels and
provide protection from chronic diseases associated with old age.
2.8. Summary and future directions
The summary of the possible role of garlic in preventing age-related diseases is shown
in Table 2. The accumulated knowledge over the last few years suggests that intake of
garlic by humans may either prevent or decrease the incidence of major chronic diseases
associated with old age such as atherosclerosis, stroke, cancer, immune disorders, cerebral
aging, arthritis and cataract formation. The majority of the diseases associated with old age
are initiated by free radicals. Garlic has strong antioxidant properties and epidemiological
studies support the fact that diets rich in antioxidants may prevent some of the above
mentioned chronic diseases. Thus, garlic is reported to decrease serum cholesterol and
triglyceride levels, inhibit platelet aggregation and increase blood circulation. Garlic may
also prevent cancer, boost the immune system and prevent cerebral aging, arthritis and
cataract formation. It may also promote general health by preventing pre-mature aging of
the skin and increases glutathione and energy levels. Thus, garlic can be benecial if taken
by the elderly, in either preventing or reducing chronic diseases associated with old age.
The principal sources of dietary recommendations have historically failed to address the
unique needs of the aging population. The use of herbal medicines in the Western world
is now a signicant factor in modern health care and conrmation of their efcacy will
stimulate rapid and continued growth in the herbal market. However, mechanisms of action
of herbs and phytochemicals need to be established in vitro; and in vivo. The rapid growth
in the use of garlic requires that standardized preparations are available with the backing
of safety and efcacy data and that studies are conducted in which the active constituents
of garlic are known. At the moment the studies have been conducted using fresh garlic
and a host of different garlic preparations. Further controlled human clinical trials are
required with garlic especially in the elderly. These studies need to take in to account the
bioavailability, metabolismof the bioactive components of garlic and their interactions with
drugs commonly taken by older people. This will help the modern and elderly consumer and
52 K. Rahman / Ageing Research Reviews 2 (2003) 3956
Table 2
Summary of the role of garlic in preventing age-related diseases
meet their expectations of product safety, efcacy and reliability. This can only be achieved
by a more collaborative approach by all the different health professionals with an interest
in the prevention by garlic of chronic diseases associated with old age.
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