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Megan Malek NUTR 5304 5.3.14 1 Garlic and Onion Introduction The cultivation of garlic (Allium sativum L.) and onion (Allium cepa L.) for both food and medicinal usage have been documented since ancient times. The referencing of these plants was first cited in 1550 BC within the Codex Ebers, an Egyptian medical papyrus. The Codex Ebers, also called the Ebers Papyrus, documented their historical usage for tumors, headaches, cardiac issues, worms, and bites. 1 Garlic and onion are both derived from the Allium genus, which translates to “to avoid” in Greek due to their offensive odor. 2 The Allium genus is the largest genus in the Alliaceae family that includes approximately 450 different species that are widely disbursed across the Northern Hemisphere. 3 In addition to garlic and onion, other species from allium including chives, shallots, leeks, kurrat, and scallions, are often used for culinary purposes. Sativum, from the scientific name for garlic, is translated to “cultivated”, which is consistent with the fact that wild garlic is unknown. The word garlic itself is derived from the word “gar-leac”; “gar” meaning spear due to the spear-like cloves and “leac” meaning herb or plant. The word onion is derived from the Latin word “unio”, meaning one or unity, because onions grow as a single bulb. In Latin, onion was called “cepa”, hence the scientific name. 2 In addition to the above mentioned Egyptian medicinal usage of garlic and onion, cloves of garlic were found in King Tut’s tomb and other sacred underground temples to prevent insect and parasite infestation and aid in the embalming process. Additionally, onion bulbs were placed within the body cavities of mummies in hopes to bring the dead back to life. Egyptians also consumed large amount of garlic and onion to aid in endurance and relieve bronchial/pulmonary ailments. 2 Later, the Greek and Romans used garlic and onion for healing, as do current day Mediterraneans. 4 The Greeks also consumed garlic to aid in endurance and strength building during the first Olympic Games. In India, garlic has long been used as an antiseptic lotion for washing ulcers and wounds. In China, garlic and onion tea has been used for centuries to treat headaches, fever, dysentery, and cholera. Lastly, garlic was used in both World Wars as an antiseptic to prevent gangrene. 1 The origin of the allium species is speculative, however evidence suggests that garlic and onion were domesticated in the central Asian mountainous regions of Uzbekistan, Turkmenia, Tajikstan, and northern Iran, Pakistan, and Afghanistan. 5 According to Block, Marco Polo and other Silk Road/spice route travelers most likely brought these plants to the Middle East. More specifically, recent research speculates the Tien Shan Mountains of Kyrgyzstan and Kazakhstan to be garlics’ center of origin. It is purposed that onion’s center of origin lies within the Iran and Pakistan region. 6 Botanists describe alliums as low-growing perennials plants in which rhizomes (underground stems), roots, and bulbs are the major storage organs. The leaves are tubular in onions and flat in garlic and arise from the rhizome. The leaves often have long bases, which give the appearance of a stem, as seen in leeks. 5 The bulb grows underground and is surrounded by a white papery sheath, and in garlic is composed of numerous cloves, which are clumped together. The bulb is structurally attached to the stem and several fleshy leaves, held together by

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Page 1: Garlic and Onion Research Paper

Megan Malek NUTR 5304 5.3.14

1

Garlic and Onion

Introduction

The cultivation of garlic (Allium sativum L.) and onion (Allium cepa L.) for both food

and medicinal usage have been documented since ancient times. The referencing of these plants

was first cited in 1550 BC within the Codex Ebers, an Egyptian medical papyrus. The Codex

Ebers, also called the Ebers Papyrus, documented their historical usage for tumors, headaches,

cardiac issues, worms, and bites.1 Garlic and onion are both derived from the Allium genus,

which translates to “to avoid” in Greek due to their offensive odor.2 The Allium genus is the

largest genus in the Alliaceae family that includes approximately 450 different species that are

widely disbursed across the Northern Hemisphere.3 In addition to garlic and onion, other species

from allium including chives, shallots, leeks, kurrat, and scallions, are often used for culinary

purposes. Sativum, from the scientific name for garlic, is translated to “cultivated”, which is

consistent with the fact that wild garlic is unknown. The word garlic itself is derived from the

word “gar-leac”; “gar” meaning spear due to the spear-like cloves and “leac” meaning herb or

plant. The word onion is derived from the Latin word “unio”, meaning one or unity, because

onions grow as a single bulb. In Latin, onion was called “cepa”, hence the scientific name.2

In addition to the above mentioned Egyptian medicinal usage of garlic and onion, cloves

of garlic were found in King Tut’s tomb and other sacred underground temples to prevent insect

and parasite infestation and aid in the embalming process. Additionally, onion bulbs were placed

within the body cavities of mummies in hopes to bring the dead back to life. Egyptians also

consumed large amount of garlic and onion to aid in endurance and relieve bronchial/pulmonary

ailments.2 Later, the Greek and Romans used garlic and onion for healing, as do current day

Mediterraneans.4 The Greeks also consumed garlic to aid in endurance and strength building

during the first Olympic Games. In India, garlic has long been used as an antiseptic lotion for

washing ulcers and wounds. In China, garlic and onion tea has been used for centuries to treat

headaches, fever, dysentery, and cholera. Lastly, garlic was used in both World Wars as an

antiseptic to prevent gangrene.1

The origin of the allium species is speculative, however evidence suggests that garlic and

onion were domesticated in the central Asian mountainous regions of Uzbekistan, Turkmenia,

Tajikstan, and northern Iran, Pakistan, and Afghanistan.5 According to Block, Marco Polo and

other Silk Road/spice route travelers most likely brought these plants to the Middle East. More

specifically, recent research speculates the Tien Shan Mountains of Kyrgyzstan and Kazakhstan

to be garlics’ center of origin. It is purposed that onion’s center of origin lies within the Iran and

Pakistan region.6

Botanists describe alliums as low-growing perennials plants in which rhizomes

(underground stems), roots, and bulbs are the major storage organs. The leaves are tubular in

onions and flat in garlic and arise from the rhizome. The leaves often have long bases, which

give the appearance of a stem, as seen in leeks.5 The bulb grows underground and is surrounded

by a white papery sheath, and in garlic is composed of numerous cloves, which are clumped

together. The bulb is structurally attached to the stem and several fleshy leaves, held together by

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a centrally-located disk.2 The bulb(s) of onion and garlic are the part of the plant which is

commonly consumed.

Onions can be separated into two main categories, storage and sweet. Storage onions are

available year-round and are more pungent than sweet onions. They come in a variety of colors

including: yellow, the most common; white, the stronger favored; and red or purple, the milder

flavored. Sweet onions are short-lived and are sweeter in taste, hence the name. Onions are able

to grow in most climates, with a preference for cool to tropical climates. Post-harvest, onions

require a curing time of about two weeks in well-ventilated, warm environment.2

The two main sub-species of garlic are hardneck (stiffneck), also called ophio or top-set,

and softneck. Hardneck garlic yields flower stalks and favors northerly climates with cold

winters. Upon slicing through the bulb’s mid-section, the hardneck-type exposes six to eleven

cloves in a single circle surrounding a central woody stalk. Before flowering, the scape, or top-

set, curls upward as it grows, looping into one to three coils. The scape can also be consumed,

and removal of the scape will enhance the growth of the bulb. Softneck garlic is named as such

because it produces a short scape which lacks a flower-top. It less tolerable than hardneck to

colder climates and has a longer shelf-life. Upon slicing through the bulb’s mid-section, the

softneck-type exposes up to 24 cloves in several layers surrounding a soft central stalk.7 The two

major types of softneck garlic are silverskin and artichoke. The silverskin is the type that is most

commonly found in grocery stores due to its long shelf life. All types of garlic are sterile and

propagate asexually from cloves. Post-harvest, garlic is bundled, or braided, and dried, or cured,

away from sunlight in a well-ventilated, low-humid environment.2

All alliums are odorless until the plants cell, or parenchyma, is damaged or bruised.

Consequently, they produce characteristic highly reactive, sulfur-containing compounds. These

and other compounds are classified as secondary metabolites because they do not aid in the

growth and development of the plant. The two important functions of these aromatic compounds

include a defensive mechanism against disease, insects, and other predators; and to attract

pollinators.2 The damaging of the bulb by cutting or mastication also releases the characteristic

flavor of both onion and garlic. The key enzyme responsible for the pungent flavor of garlic is

allicin and lachrymatory factory in onion. The synthesis of allicin is dependent on the conversion

of alliin via the enzyme alliinase. Garlic and onion can be heated to lessen the strong flavor and

aroma by deactivating heat-sensitive alliinase; however this will also reduce the beneficial

sulfur-containing compounds.

The common methods of consumption of onion are raw, onion powder, dehydrated onion

pieces, onion flavoring encapsulated flavors (oleoresins and essential oils), onion salt, pickled

onion, and canned or packaged onions.6

The common methods of consumption of garlic are raw, dehydrated garlic, garlic oil

macerate (softened by steeping in a liquid), and aged garlic extract (AGE).8

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Bioactive Compounds

Many biological effects of garlic and onion are related to the volatile sulphur-compounds,

called thiosulfinates, which are also responsible for their pungent smell and flavor. The major

sulphur-containing constituents in garlic and onion are s-alk(en)yl-L-cysteine sulphoxides

(ACSOs), such as alliin and isoaliin; and γ-glutamylcysteines, which function as important

storage peptides and biogenic intermediates for the corresponding ACSOs. These volatile

compounds are present in the bulb of both garlic and onion and released upon damage to the

parenchyma cells. The major non-volatile compounds consist of phenolic compounds including

flavonoids, flavanols, and anthocyanins; saponins and saponegins; and fructans, which all

function as biological health promoters.3

The bioactive composition of onion and garlic varies depending on cultivation,

maturation, environmental factors, storage time, agronomic conditions, and bulb selection. In

addition, garlic can be chemically manipulated to produce various compounds which can alter

the bioavailability of the compound. Common forms of processing include heating, aging, and

dehydrating; however there is limited research of the exact concentrations of these compounds

post-processing.8

Onion In onion, the γ-glutamylcysteines undergo hydrolysis and oxidation to the ACSOs

including isoaliin, the most abundant; alliin; and propiin. Upon damage to the cell, alliinase

rapidly cleaves the cytosolic cysteine sulphoxides on alliin to sulphenic acid. The sulphenic acid

undergoes self-condensation to produce thiosulphinates, which are allicin analogues. The

thiosulphinates can have multiple fates to bis-sulphines; thiosulphonates; mono- and di-

sulphides, which further rearrange to thiophenes and di- and tri-sulphides; cyclic zwiebelanes;

and/or cepaenes. In addition, isoaliin, which is the source of lachrymatory factor, undergoes an

enzymatic reaction via lachrymatory factor synthase to 1-propenesulfenic acid. This intermediate

is highly unstable and rearranges to 1-propanethial-S-oxide, or lachrymatory factor (LF). The LF

can rearrange to also form cepaenes or hydrolyze to propionaldehyde.8 (See Figure 1).

The dry weight of onions (65%) is composed of non-structural carbohydrates (CHOs)

including glucose, fructose, sucrose, and fructooligosaccharides (fructans). Non-structural CHOs

and fructans are present in the highest concentration within the inner scales of the bulb and to a

lesser extent in the outer two scales. Total fructan concentrations within the bulb yielded

16.1g/100g dry weight (dw), which is approximately 39% of dw, compared to the leaves which

contained 16% of dw.9

Quercetin, the most abundantly found flavonol in onion, accumulates in the highest

concentrations in the outer skin and decreases towards the center.2 Analysis of four onion

varieties revealed the outer skin contained quercetin concentrations ranging from 25-35 mg Q/g

dw compared to 4-7mg Q/mg dw in the edible fleshy portion. 10 (See Figure 3). The aglycone

form of quercetin is found in the outer-most dried protective layers, and its derivatives, quercetin

monoglucoside and quercetin diglucoside, are found in the underlying edible portion after

peeling.10 These drastic concentration differences are due to the presence of glycosidic linkages

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which affect their transport into the cell. In another study to test to variability of phenolic

compounds between onion varieties, white and red onion were blanched, boiled, and fried to

imitate normal cooking methods. Quercetin was present at 48.8mg/100g dw in white onion

compared to 110.6mg/100g dw in red onion. In addition, p-hydroxybenzoic acid was present at

4.4mg/110g dw in white onions and protocatechuic acid was present at 5.08mg/100g dw in red

onions.11

As expected, red onion had higher phenolic activity than yellow and white onions,

especially in the skin extracts, due to the anthocyanins. Red onion contained 3.5 µg/g fresh

weight (fw) of anthocyanins compared to purple onion which contained 4.5 µg/g fw in the outer

scales and 0.1 µg/g fw in the inner scales (other varieties contained none to negligible amounts.4

In the edible portion of red onion, quercetin monoglucoside accounted for 79% of onion’s total

flavonoid concentrations and anthocynanins accounted for 27%. Cyanidin derivatives accounted

for more than 50% of total anthocyanins.12 Storage time of six weeks and longer can result in 64-

74% decrease in total anthocyanins concentrations, which further decreases antioxidant activity

by 29-36%. Storage of red onion less than six weeks at low temperatures may better preserve

anthocyanins and therefore antioxidant activity.3

In 2001, the highest flavonoid concentrations were found in the onion leaves (2720.5

mg/kg) when compared to 62 other vegetables. The flavonoids which appeared in high

concentrations in onion leaves are quercetin (1497.5 mg/kg of dry weight), kaempferol (832

mg/kg), and luteolin (391 mg/kg).13

Saponins are a unique group of glycosides that dissolve in an aqueous solution to form

colloidal dispersions which foam upon shaking.14 Alliums contain steroidal saponins which are

present in the plant tissue.15 In 1978, Russian scientists were the first to identify saponins and

sapogenins (aglycones) including sitosterol, gitogenin, oleanolic acid, and amyrin in onions,

garlic, and leeks.3 More recently, Lanzotti discovered three new furostanol saponins, named

ceposides A-C, in white onions.15

Garlic

In garlic, the ACSOs present are alliin, the most abundant; and methiin. Similar to onion,

upon damage to the cell, alliin undergoes an enzymatic reaction via vacuolar alliin lyase,

alliinase. This enzyme rapidly cleaves the cytosolic cysteine sulphoxides and synthesizes the

short-lived intermediate 2-propenesulfenic acid. The end products of garlic are synthesized via

dehydration reaction to yield thiosulphinates, primarily allicin.8 Allicin is extremely volatile and

unstable; therefore it easily undergoes decomposition to other organosulphur compounds

including thiosulfonates, ajoene, 2-vinyl-2,4-dihydro-1,3-dithiin, 3-vinyl-3,4-dihydro-1,2-dithiin,

and diaallyl sulfides (DAS), diallyl disulfides (DADS), and diallyl trisulfides (DATS), which

display bioactive activity.3,8 These volatile compounds give garlic it’s distinctive, pungent aroma

and flavor. (See figure 2).

The bioactivity of garlic cannot be contributed to allicin and other thiosulfinates due to

their instability. These compounds rapidly degrade to DAS (14%), DADS (66%), DATS (9%),

and sulfur dioxide when kept at 20°C for 20 hours in vitro. In fresh garlic oil, DATS are the most

abundant and in commercially garlic oil, DADS are more abundant. Vinyldithiins are also

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present in garlic oil and oil-marcerates, which can be detected in the fat tissue, serum, and kidney

of animal models 24 hours after ingestion.17 In addition, non-volatile sulphur-containing

compounds, S-allyl cysteine (SAC) and S-allyl mercaptocysteine (SAMC), are synthesized via

the enzymatic transformation of γ-glutamylcysteines when garlic is extracted from an aqueous

solution or aged garlic extract (AGE).8 (See figure 4). SAC can be detected in the blood and

urine, which verifies it’s bioactivity in animal studies. The bioavailability of SAC is 103% in

mice, 98.2% in rats, and 87.2% in dogs (Amagase, 2006). Ajoene is also formed during AGE

processing and is not normally found in steam distillates of garlic.16 In human consumption of

25g grated garlic, no allicin or DADS was detected from 1-24 hours after ingestion. However,

SAMC and DADS were detected in human breath analysis but this is not considered to be a

reliable test due to the uncertainty of absorption. More recently, SAC was found in human blood

after ingestion of AGE, which may provide a more reliable marker for bioavailability in

human.17

The flavonols that appeared the high concentrations in the garlic bulb are myricetin (639

mg/kg), apigenin (217 mg/kg), and quercetin (47 mg/kg).12 The flavonoid allixin was the first

compound isolated from garlic as a phytoalexin. Allixin is released from garlic after continuous

stress or damage and appears to have 31% bioavailability when paired with an inclusion

compound in animal models.18 Additionally, six phenolic compounds were found in garlic skin

including ferulic acid and courmaric acid. These garlic skin compounds were found to be most

effective at .01% concentration.19

As mentioned previously, the Allium genus is known for the production of steroidal

saponins. In 1982, the presence of spirostanol (benzene ring) steroidal saponins was first

identified in raw garlic.17 In1988, furostanol (pentacyclic) steroidal saponins were isolated from

frozen garlic by inhibiting β-glucosidase and therefore inhibiting the transformation to

spirostanol saponins. Within the same study, new steroidal glycosides named sativoside R1 and

sativoside R2 were discovered in garlic root. Seven spirostanol and ten furostanol saponins were

identified within AGE (Matsuura, 2001). These results show that processing of AGE can lead to

bioactive saponins and sulphur-compounds.

Health Benefits

Onion

Antioxidant Properties

It has been noted that an increase in fruits and vegetables can result in increased plasma

antioxidant levels in human. This positive correlation is strongly related to the high

concentrations of phenolic flavonoids present within these fruits and vegetables.20 As previously

mentioned, onion leaves were found to have the highest flavonoid concentrations out of 62 other

edible plants.13 In addition, the dry outer scales of the onion are a rich source of flavonoids,

including nine phenolic compounds-quercetin, quercetin glycosides, and their oxidative products.

According to Ly et al, quercetin has a higher antioxidant capacity compared to α-tocopherol in

vitro. These findings could be due to structural differences between the compounds. The authors

hypothesized the compounds with the highest activity are located near the surface of the

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membrane to better scavenge peroxyl radicals, and because α-tocopherol is located within the

inner lipid phase of the membrane, it had a lower antioxidant capacity.21

A clinical trial was conducted to investigate the antioxidant power of quercetin from fried

onions on five healthy volunteers. Following the consumption of 225g of fried onions, quercetin

plasma levels increased from baseline of 28.4 ± 1.9 ng/ml to peaking at 248.4 ± 103.9 ng/ml

after two hours. The total plasma antioxidant activity started at the baseline of 1.7 ± .4 mmol/l

trolox equivalents (TE) and increased to 1.75 ± .1 mmol/l TE after 2 hours with similar findings

after 4 hours. Quercetin has no effect on low-density lipoproteins (LDLs) or very-low-density

lipoproteins (VLDLs). However, high-density lipoproteins (HDLs) significantly increased at the

baseline, two hours, and four hours (69.3 ± 0, 79.7± 62.5, 117.4 ± 78 ng/ml, respectively). It

should be noted that there was also an increase in albumin along with HDL and after removal of

albumin no significant HDLs were present. These findings indicate that quercetin has no direct

effect on LDL oxidation and has a strong affinity for proteins in vivo. However, quercetin is

bioavailable and can increase total antioxidant activity in the plasma.22

In a follow-up study on 805 elderly men age 65-84, five major flavonoids were measured

including the flavonols-quercetin, kaempferol, and myricetin and the flavones-apigenin and

luteolin in accordance with their dietary intake. The total flavonoid intake was 25.9 mg daily,

with quercetin making up 63% of that total (16.3 mg), followed by kaempferol at 32% (8.2 mg).

The primary sources of flavonoids included black tea (61%), onions (13%), and apples (10%).

Mean daily consumption of onions was estimated to be 9.4g per day. Relative risk of coronary

heart disease (CHD) mortality and incidence of myocardial infarction was 50% lower in the

highest fertile of flavonoid intake compared to the lowest. Therefore, flavonoid intake showed an

inverse relationship with CHD (P=0.015) and fatal and non-fatal myocardial infarction

(P=.08).23

Antimicrobial Properties: Infectious Disease

The antimicrobial properties of onion have been associated with its sulfur-containing

chemical structure and the presence of phenolic compounds.4 To investigate the effect of

essential oil extract of various types of onion, a study was conducted on antimicrobial activity

against two bacterial strains and three fungal species that usually cause rotting in the Allium

genus. The bacteria strains included Staphylococcus aureus, Salmonella Enteritidis, and the fungi

strains included Aspergillus niger, Penicillum cyclopium, and Fusarium oxysporum. Three types

of onion include green, yellow, and red which were extracted by steam distillation to produce an

essential oil. The results showed clearance of each strain in a dose-dependent manner. After 48

hours, red onion extract (500ml/L) showed the highest bacterial clearance against S. aureus (8.8

± .2 mm) compared to yellow (7.5 ± .4) and green (8.6 ± .5). Similar results were found against

Salmonella Enteritidis in red onion (11.1 ± .2) compared to yellow (9.8 ± .4) and green (8.9 ± .9).

The antifungal activity against A. niger, P. cyclopium, and F. oxysporum was less inhibited at

low concentrations; however at higher concentrations red onion showed the highest inhibitory

effect compared to yellow and green onion. It should also be noted that all types had an

inhibitory effect against bacteria and fungi; however greater clearance was found in red onion.24

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Prior to this study, there has been lacking evidence linking fructans and antimicrobial

activity in the Allium genus. Recently, the potential benefit of fructans from the green leafy

portion Welsh onions was analyzed against the influenza-A (flu) virus. The fructan was extracted

from the green leaf portion and yielded a molecular weight of 1.5 x 103. Both in vitro and in vivo

tests were conducted to analyze its antiviral activity. The in vitro tests revealed no inhibitory

effect by fructans against the flu virus. The in vivo tests used ten mice per treatment and control

group. The treatment group was further divided into low (.5mg/d) and high (1.5mg/d) orally

administered fructans groups and the control group was further divided into oseltamivir

(Tamiflu) and no Tamiflu treatment groups. The fructans were orally administered twice a day

for three days prior to inoculation of the flu virus. The efficacy of the fructan administration was

measured on the basis of weight loss and virus titers in the bronchoalveolar fluid (BALF) and

lung. The no Tamiflu group showed at body weight loss of 74.7% at eight days and the control

with Tamiflu had no body weight loss during the 14 day experiment. The treatment group

showed continuous weight loss for 3-7 days post-virus and recovered after nine days. No

differences where shown between the high and low fructan group in weight loss. However,

fructans significantly decreased virus titers in the BALF and lung when compared to the control

group. The two treatment groups showed a dose-dependent reduction in virus titers, however the

Tamiflu control group showed significantly reduced the virus compared to all treatment groups.

Results also revealed a significant increase in antibody production against the virus in the fructan

group compared to the Tamiflu control group. In addition, the antiviral mechanism of fructan

was analyzed by measuring nitric oxide (NO) production, which is an antiviral mediator, in

macrophages. Murine macrophage cells were incubated with fructan for 24 hours. The results

showed a stimulatory effect on the production of NO in a dose-dependent manner. Overall, these

results indicate that fructans from Welsh onions may contribute to the inhibitory effect against

the flu virus in vivo.25

Cancer

To analyze the protective effects of the Allium genus against esophageal cancer (EC) and

gastric cancer (GC), an observational study was conducted in a high-risk cancer area of Southern

China. The motivation behind this study was due to the drastic difference of low EC and GC

incidence in the Northern region of China and their high consumption of raw Allium vegetables.

Food frequency question was obtained from approximately 180 men (60.3 control, 59.5 EC, 60.4

GC) and approximately 175 women (58.2 control, 59.1 EC, 57.9 GC) in Southern China. The

study reported that frequent intake of allium vegetables (garlic, onion, Welsh onion, and Chinese

chives), tomatoes, and snap peas greatly lowered the odds ratio (OR) for EC and GC. More

specifically, to measure EC incidence in persons with pre-existing EC, frequent onion

consumption of >1 time/week resulted in 0.25 OR and 1-3 times/wk resulted in 0.45 OR

compared to <1 time/wk resulting in 1.00 OR. Similar finding were found in GC incidence,

where consumption of onion >1 time/week resulted in 0.17 OR and 1-3 times/wk resulted in 0.51

OR compared to <1 time/wk resulting in 1.00 OR. The author’s purposed mechanism of action is

the antimicrobial function of the Allium genus inhibits gastric bacteria, thus reducing the

production of N-nitroso compounds.26

A Finnish study was conducted to analyze the association between flavonoids intake and

the risk of cancer and chronic diseases. Dietary intake was recorded from 10,054 men and

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women using a dietary history method. Total flavonoid intake in the total population was 24.2 ±

26.7 mg/d (3.3 ± 2.4 quercetin, 0.6 ± 0.7 kaempferol, 0.1± 0.2 myricetin, 15.1 ± 18.8 hesperetin,

and 5.1 ± 8.8 naringenin) Majority of quercetin came from apples and onions. The total

incidence of cancer was significantly lower with higher intake of quercetin (.77 RR), and more

specifically, lower in lung cancer in men (.42 RR) and breast cancer in women (.62 RR). There

was also a lower incidence of ischemic heart with increased consumption of onions (.77 RR).27

Cardiovascular Disease

In a double-blind clinical study, quercetin-rich supplement (250 mg quercetin, 50 mg

rutin, and 250 mg other bioflavonoids) was administered to healthy individuals to measure

plasma quercetin levels and its effect on LDLs, HDLs, total cholesterol and triglycerides. The

subjects that consumed the quercetin supplement had 23-fold higher plasma levels compared to

the control group. However, there was no effect on the cholesterol or lipid profile in the

treatment group, therefore quercetin had no direct effect CVD in healthy individuals.28

To investigate if onion and garlic pose as an effective antithrombotic agent, an in vivo

study was conducted on rat models. Aqueous solution extracts of onion and garlic were

administered at low (50mg/kg) and high (500mg/kg) doses daily for four weeks. Results showed

onion produced a significant lowering effect on thromboxane B2 (TXB2) only at high doses. It is

purposed that orally administered onion may be beneficial is consumed at low doses over a

longer period of time. Garlic at high doses showed an inhibitory effect on platelet aggregation

and TXB2, which was comparable to NSAIDs. However, high doses of garlic posed a toxic

effect on rat organs. Boiled onion and garlic had little effect on TXB2 inhibition, which leads the

authors to conclude that cooking may destroy the active antithrombotic agent.29

Hypertension

Previous studies have noted the anti-hypersensitive effects that quercetin has on rat

models. If administered daily, quercetin relaxes vascular smooth muscle and reduces blood

pressure and endothelial dysfunction in hypertensive rats. Therefore, this in vitro study analyzed

the effects of quercetin and isorhamnetin (1 and 10 µmol/L of each) on rat aortic endothelial

dysfunction induced by angiotension II (angII) for six hours. AngII induced superoxide

production at six hours, which was prevented by quercetin and isorhamnetin. In addition, angII

also induced the expression of p47 (regulatory moiety of NADPH oxidase membrane), which

was also prevented by quercetin and isorhamnetin. These results show that quercetin and

isorhamnetin when taken together can prevent angII-induced endothelial dysfunction by

inhibiting p47 and subsequent superoxide production in vitro.30

Diabetes

The effect of 3% freeze fried onion powder was analyzed in albino diabetes-induced rats.

The onion diet was maintained for eight weeks and was shown to significantly reduce

hyperglycemia and lowered relative liver weight compared to the diabetic control group. The

onion diet also significantly lowered plasma cholesterol, including LDLs and VLDLs, plasma

phospholipids, and triglycerides. Overall, the diabetic rats consuming the onion diet had

improved metabolic status.31

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The effects of two freeze-dried onion powders on diabetes-induced rates in combination

with a high-fat diet were analyzed in rat models. The rats were all fed a high-fat (HF) diet for

two weeks and then divided into four groups: HF control, diabetic control, low onion powder

(.5%), and high onion powder (2%). Diabetes was induced in all treatment groups except the HF

control group. After four weeks, the results suggest that the HF onion diets may increase insulin

secretion and therefore insulin resistance in dose-dependent manner when compared to the

diabetic control group. The authors concluded that the effect of dietary onion with a high fat diet

may impair the anti-diabetic effect of onion in rat models.32

Inflammation

To assess the anti-inflammatory effects of aqueous extract from Welsh onion green

leaves (WOE), a study was conducted on mice models. The mice were administered .25-1g/kg of

WOE and results showed a reduction in paw edema (9-46%). The anti-inflammatory effects were

associated with decreased levels of nitric oxide and tumor necrosis factor-α (24-51%). In

addition, WOE was associated with reduced lipid oxidation (20-49%), increased anti-oxidant

enzyme activity including catalase (122-145%), superoxide dismutase (168-319%), and

glutathione peroxidase (121-176%) when compared to the control group in vivo.33

Obesity

The anti-obesity effects of 3% and 5% onion extract were assessed on obese and diabetic

rats. The rats consuming the onion diet had significantly lower body and adipose tissue weights

compared to the control group with no onion diet after 18 days. The fasting blood glucose, serum

triglyceride, and free fatty acid levels levels were all improved in a dose-dependent manner. The

mechanism of action was measured by the effectiveness of sulphur-containing (alliin, methiin,

propiin, and DATS) compounds to inhibit oil drop formation in cells. The sulphur compounds,

especially methiin, were effective oil drop inhibitors within the cell, which suggests these

compounds may play a vital role in reducing obesity.34

Asthma

The effects of onion extracts on bronchial asthma in animal models as well as humans

have previously reported. However, the compounds responsible for this effect were unknown.

Previous research by Wager et al, reported the anti-asthmatic effects are associated with

thiosulfinates present within the onion extract. The thiosulfinates showed an inhibitory effect on

histamine release, leukotriene and thromboxane biosynthesis, chemotaxis, and

chemoluminescence of granular leukocytes in vitro. In addition, the inhibition of allergen and

PAF-induced bronchial obstruction and hyperreactivity was noted in vivo. This study compared

the inhibitory effect of thiosulfinates and cepaenes on arachidonic acid (AA) in vitro. The results

showed thiosulfinates to only be effective at inhibiting cyclooxygenase (COX) and 5-

lipoxygenase (5-LOX) if at least one unsaturated or aromatic substituent was present. However,

thiosulfinates are quickly degraded upon damage to the cell. Additionally, cepaenes were shown

to be the most active inhibitors of COX and 5-LOX due to presence of two double bonds in

vitro.35

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Garlic

Antioxidant Properties

As previously mentioned, garlic can be processed in a multitude of ways, which produce

varying biologically active compounds. Some of the products include garlic homogenate, heat

treated garlic, garlic powder, aged garlic extract (AGE), oil-macerated, etc. (See figure 4).

According to various studies, AGE may be a more effective and safer product than raw and

dehydrated garlic, due its extraction method. Unlike allicin, SAC which is a product of AGE, has

shown to be bioavailable, therefore is can be used as a reliable biomarker for standardization of

garlic preparations.8 In addition, AGE has shown high antioxidant activity due to presence of

sulphur-containing compounds including SAC and SAMC. The mechanism by AGE is purposed

to exert antioxidant activity is by scavenging ROS and inhibiting the formation of lipid

peroxides.36 These effects were reported in a clinical study on 35 normotensive subjects given

AGE which contained 305g/L of extracted solids, with 1.47g/L SAC concentrations. Platelet

aggregation was first induced via ADP in order to test the effects of AGE. The subject’s platelet

aggregation was significantly reduced after dietary supplementation of 5 mL of AGE per day for

13 weeks. However, no effect was seen on serum lipid levels in the normotensive control group

with AGE.37

Antimicrobial Properties: Infectious Disease

According to Block, garlic has long been used for its antibacterial, antiviral, and

antifungal properties.1 However, the effects of garlic on oral hygiene are not well studied. Garlic

extract (51.1% w/v) which contains 220 mg/ml of allicin, was shown to inhibit Porphyromonas

gingivalis almost immediately and the inhibition of Streptococcus mutans was delayed but still

effective. The garlic extract was also successful in inhibiting trypsin-like and total protease

activity of P. gingivalis (92.7-94.88%, respectively). The findings are indicative of garlic’s

inhibitory effect on oral pathogens.38

Previous research has linked the antimicrobial effects of garlic to the sulfur containing

chemical structure of thiosulfinates. It has been reported that allicin, when administered in low

doses, reacts with the free sulfhydryl-group present on active site of cysteine proteases.39

Therefore, the antimalarial activity of allicin was tested by its inhibitory effect on cysteine

protease activity on Plasmodium in various life cycles of erythrocytes. When allicin was

administered in a dilute aqueous solution in a low dose of 1.8 mg/ml, it inhibited proteolytic

cleavage of circumsporozoite protein, the major surface protein present on Plasmodium, as well

as inhibited host cell invasion in vitro. In vivo, the mice that were injected with allicin showed

inhibition against Plasmodium compared to the control group. In addition, a four day regimen of

allicin administered orally or intravenously significantly reduced parasitemias and increased the

lifespan of the mice by 10 days.40

Cancer

Alliums are a sulfur-rich plant, and therefore contain high concentrations of selenium,

especially garlic.2 Due to sulfur and selenium’s chemical similarities, plants and yeast can

substitute selenium for sulphur in the biogenesis of methionine to synthesize selenomethionine;

which can produce the selenium analogues of cysteine including selenocysteine and its

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derivatives. While animals can integrate selenomethionine into protein, we cannot integrate

selenocysteine. Therefore, the selenocysteine enters the secretory pathways or incorporates into

25 other selenoproteins. Additionally, selenocysteine is essential for ribosome-directed protein

synthesis and protein turnover.41 In a 1996 clinical trial, Clark et al found 200 µg of selenium per

day administered as selenium yeast, reduced the onset of colon, lung, and prostate cancer by as

much as 50%. However, in 2009 the SELECT clinical trial found a significant increase in

prostate cancer with 200 µg of selenium and/or vitamin E.42 In addition, 200 µg per day may

increase the risk for type 2 diabetes in humans.43

In a clinical study to observe the biological effects of garlic extract on advanced cancer

patients, AGE proved to be beneficial. A placebo or AGE was administered to 55 cancer patients

(87% liver cancer, 14% pancreatic cancer, 2% colon cancer), and the effects were measured by a

quality of life (QOL) survey and by the activity and number of natural killer (NK) cells. Results

showed no difference in the QOL survey in the treatment group, however, there was increased

number and activity of NK cells. The authors did not purpose a mechanism of action but did

conclude that AGE is safe and could provide an effective cancer-prevention modality.44

Cardiovasular Disease

The cholesterol-lowering effects of raw garlic and its derivatives are variable about

studies. Therefore, a clinical study was conducted on moderate hypercholesterolemic subjects

(LDL levels of 130-190 mg/dL), who were divided into four groups: raw garlic, powdered garlic,

AGE, and placebo. The three treatment groups were administered garlic in the equivalence of 4

cloves per day for six months. The results showed garlic had no significance effect in all

treatment groups when administered at that particular concentration on total cholesterol, LDLs,

HDLs, and triglycerides.45

In another clinical study, garlic was analyzed by observing the short-term and long-term

effects on cardiovascular disease. Garlic was extracted in ethyl acetate and administered via

capsule in the equivalence of 1g of raw garlic. In the short-term group, five normotensive males

were administered the garlic supplement at different dosages (14, 10, 8, 6 capsules) with a five

day wash-out period in between and blood samples were collected after four hours. The long-

term effects of garlic were analyzed on five healthy males and ten males with CHD. Blood was

drawn and three aggregators were tested including ADP, epinephrine, and collagen. Results

showed an inhibitory effect of garlic in dose-dependent manner. Inhibition of platelet

aggregation only occurred when garlic was administered at six capsules for one month in the

CHD group. The authors conclude that the body may build up garlic, which provides a protective

effect against platelet aggregation in subjects with CHD.29

Plant saponins have been reported to have a cholesterol lowering effect in animal models

Due to the amphiphilic character of saponins, they are said to interact with the cell membrane of

cholesterol and cause perforations, similar to hemolysis.46 However, the direct link of garlic

saponins and cardiovascular has yet to be defined. Two garlic extract, one frozen and one raw,

were administered to rat models with hyperlipidemia for 16 weeks. Total plasma cholesterol

decreased in all rat groups, and significantly decreased in the raw garlic extract, which is rich in

spirostanol saponins. Interestingly, the raw garlic extract at the lowest dose was the most active

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in lowering total cholesterol. There was also a significant decrease in LDLs (40-57%) in the raw

garlic extract and increase in HDLs (30-50%) in the frozen garlic extract (Matsuura, 2001).

Hypertension

To measure the anti-hypertensive effects of garlic a clinical study was conducted on 20

hypertensive and 20 normotensive subjects. Both groups were administered garlic pearls in a

dose of 250mg per day for two months. The hypertensive group showed a significant decrease in

to systolic and diastolic blood pressure, as well as, a significant decrease in oxidized LDLs and

8-iso-prostglandin F2α. Additionally, a moderate increase was observed in total antioxidant status

in the hypertensive group compared to the normotensive group. These findings conclude that

garlic supplementation may be beneficial in reducing blood pressure and reduce oxidative stress

in hypertensive subjects.47

Inflammation

The anti-wrinkle and anti-inflammatory effects of garlic components including caffeic

acid, SAC, and uracil were analyzed in mice. Each garlic component was administered at 5µm

and 20µm with 150 mJ/cm2 of UV-B irradiation. Matrix-metalloproteinase (MMP) was used as a

marker for UV-B-induced wrinkles and an inflammation marker in skin cells, due to its

activation by pro-inflammatory mediators upon UV irradiation. The results showed that all garlic

components significantly inhibited the degradation on type I procollagen and expression on

MMPs in vivo. Moreover, caffeic acid and SAC were found to reduce oxidative stress and

inflammation by regulating the activities of NF-κB and AP-1 and uracil indirectly exhibited an

antioxidant effect by reducing COX-2 and inducible nitric oxide synthase expression levels.48

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Figure 1. Formation of sulphur-containing compounds during the metabolic pathway of onion.8

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Figure 2. Formation of sulphur-containing compounds during the metabolic pathway of garlic.8

Figure 3. Total quercetin concentration expressed in the onion flesh and dried onion skin (mg Q/g dm)10

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Figure 4. Different garlic preparation and their associated organosulfur compound.8

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http://www.refworks.com/refworks2/default.aspx?r=file::get_file&file_name=mm2219%40txstate.edu-

RefList.txt&content_type=text%2Fplain&file_token=OspcVgAkXOSsJwisJEAVWW6VXhYmUBTbYAntLE03Nb

SkNbvtLb5kLbPsLoSlWOG-UtxkXwjgYtvjXu1oLe44