PHYTOTHERAPY RESEARCH Phytother. Res. 16, 603615 (2002) Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ptr.

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REVIEW ARTICLE

OnionsA Global Benet to Health

Gareth Grifths,* Laurence Trueman, Timothy Crowther, Brian Thomas and Brian Smith
Department of Plant Genetics and Biotechnology, Horticulture Research International, Wellesbourne CV35 9EF, UK

Onion (Allium cepa L.) is botanically included in the Liliaceae and species are found across a wide range of latitudes and altitudes in Europe, Asia, N. America and Africa. World onion production has increased by at least 25% over the past 10 years with current production being around 44 million tonnes making it the second most important horticultural crop after tomatoes. Because of their storage characteristics and durability for shipping, onions have always been traded more widely than most vegetables. Onions are versatile and are often used as an ingredient in many dishes and are accepted by almost all traditions and cultures. Onion consumption is increasing signicantly, particularly in the USA and this is partly because of heavy promotion that links avour and health. Onions are rich in two chemical groups that have perceived benets to human health. These are the avonoids and the alk(en)yl cysteine sulphoxides (ACSOs). Two avonoid subgroups are found in onion, the anthocyanins, which impart a red/purple colour to some varieties and avanols such as quercetin and its derivatives responsible for the yellow and brown skins of many other varieties. The ACSOs are the avour precursors, which, when cleaved by the enzyme alliinase, generate the characteristic odour and taste of onion. The downstream products are a complex mixture of compounds which include thiosulphinates, thiosulphonates, mono-, di- and tri-sulphides. Compounds from onion have been reported to have a range of health benets which include anticarcinogenic properties, antiplatelet activity, antithrombotic activity, antiasthmatic and antibiotic effects. Here we review the agronomy of the onion crop, the biochemistry of the health compounds and report on recent clinical data obtained using extracts from this species. Where appropriate we have compared the data with that obtained from garlic (Allium sativum L.) for which more information is widely available. Copyright # 2002 John Wiley & Sons, Ltd.
Keywords: Allium cepa; Allium sativum; cysteine sulphoxides; avonoids; quercetin; health benets.

INTRODUCTION Genetic diversity and geographic distribution of onion The bulb onion (Allium cepa L.) is thought to have originated in central Asia (Hanelt, 1990) but is not known in the wild, so it may have become extinct or be a hybrid from ancient cultivation. Shallots and other so called multiplier onions, once classied as separate species, are now regarded as conspecic with bulb onions. Related cultivated species include garlic, leek, chives, bunching onion and some other species of signicant local importance (Table 1). Botanically, the Alliums are included in the Liliaceae and wild species are found across a wide range of latitudes and altitudes in Europe, Asia, N. America and Africa. They are generally adapted to temperate environments with low or erratic supplies of water, either in areas of sparse vegetation or accompanying grasses. However, they are widely adaptable and some species can occupy a wide range of ecological niches.
* Correspondence to: G. Grifths, Department of Plant Genetics and Biotechnology, Horticulture Research International, Wellesbourne CV35 9EF, UK. Tel (01789) 470382. Fax (01789) 470552. E-mail: gareth.grifths@hri.ac.uk Contract/grant sponsor: Department of the Environment, Food and Rural Affairs, UK. Contract/grant sponsor: European Union.

Allium cepa is a biennial plant that produces a large bulb in the rst year of growth. After vernalization by winter cold, rapid re-growth of foliage in spring is quickly followed by the production of several tubular ower stalks each producing a single, more or less spherical, umbel of around 200 owers. Each ower has the potential to produce up to six seeds. The hollow ower stalks are easily damaged whereas wild Alliums generally have strong wiry owering stems. A. cepa will not cross readily with other Allium species. For genetic analysis and in the search for improved pest and disease resistance traits, crosses with some degree of intervention have been made with several species including A. stulosum, A. royleii and A. galanthum but with little impact on present cultivation (Jones, 1990; de Vries et al., 1992).

Horticultural production of onion Onion production falls into three broad product segments; bulbs for fresh market (which, as a group has the greatest diversity), dehydrated onions for food processing and green salad onions for fresh consumption. Bulb onions are produced either from seed, sets (small bulbs produced at high density then grown on in the following year) or transplants. Although able to survive low moisture conditions, a good yield requires an adequate supply of water. A major advantage of onions as a crop is
Received 29 January 2002 Revised 17 June 2002 Accepted 17 July 2002

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Table 1. Cultivated Alliums

Species A. cepa Sub division cepa ascalonicum aggregatum proliferum Horticultural name Bulb onion Shallot Potato multiplier onion Tree onion Japanese bunching (Welsh onion) Garlic Leek Kurrat Chives Rakkyo Chinese chives

A. stulosum A. sativum A. ampeloprasum A. schoenoprasum A. chinense A. tuberosum

porrum aegyptiacum

have been selected with dry matter contents up to, and sometimes over 20% compared with a more average gure of around 12% (Wall et al., 1999) which makes the drying process less energy intensive. Even with the most suitable varieties it is only economic to produce onions for drying in areas with high total solar radiation during the growing season where the maximum dry matter levels are achieved. Because of their storage characteristics and durability for shipping, onions have always been traded more widely than most vegetables and this has become increasingly competitive in recent years with the European Community and Japan being notable importers, mainly from the Southern Hemisphere. Marketing and consumption trends The prominent role of onions sometimes seems surprising because their usage is often less visible compared with commodities like tomatoes or Brassicas. Onions, however, are highly versatile and are used as an ingredient in many dishes and are accepted by almost all traditions and cultures. In general the markets have traditionally supplied pungent onions intended for cooking. In the USA and Europe especially, these onions have white/yellow esh and yellow to brown skins although red/purple onions are preferred in many parts of the world. In the developed world where food supplies are plentiful and customers must be attracted to products, producers and marketeers are increasingly interested in broadening the range of choice they can offer. There is now a growing interest in the production of low pungency or so-called sweet onions that are more attractive for fresh uncooked use. Innovative marketing is promoting this type of onion and in the USA overall onion consumption is increasing signicantly (Lucier, 1998). This is at least partly because of heavy promotion that link avour and health benets of this type of onion. Onions are also very widely used in developed countries for food processing as powder and akes. Europe is the major importer of these products with 25 000 metric tonnes being imported annually primarily from USA, India and Egypt (Anon, 2001). Although sweet, less pungent onions are increasing in popularity, the more pungent varieties still dominate the onion market as they tend to impart more avour to cooked dishes, are easier to handle and have a longer storage and shelf life. Increasingly, processors specify onion purchases in partially prepared form with sliced, diced and chopped products being prepared directly by the onion producer or packer. The onion market is diversifying rapidly at all levels with more diverse onion genotypes becoming available to expand the range of products in an increasingly competitive marketing environment. This diversication is also mirrored in the wider use of prepared onion forms in food manufacturing ranging from very traditional products through to fast food chains and wider ethnic uses. In the USA the National Onion Association (NOA) has undertaken a drive to promote the health benets of onion consumption across the nation. The NOA was cosponsor for the Spring 2001 series of Taste of Home cooking schools. Over 130 cooking schools were held nationwide with a total of 120 000 attendees. The NOA has developed new onion health fact sheets entitled
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their storability. Plants, lifted at maturity and dried so that roots, shoots and skin are completely dry, keep well. The bulbs remain dormant at both low and high temperatures allowing high temperature storage in the tropics and refrigerated storage in temperate regions. Where modern refrigerated or controlled atmosphere storage is available, bulbs can be kept for up to 9 months (Anon, 1982; Smittle, 1988). Onions are grown in every part of the world where plants are farmed and exhibit a great diversity in form including colour, shape, dry matter content and pungency. This diversity is also reected in the success of the species in adapting to a very wide range of environments (Brewster, 1994). In the UK, bulb onions are produced from autumn and spring sowing from both direct seeding and sets. Immature salad onions can be harvested for around 89 months of the year. The formation of the bulb is largely genetically controlled by a day-length response but forms have been selected that allow production from tropical areas to near the Arctic Circle (Rubatsky and Yamaguchi, 1997). However, in the wet tropics and also very northern latitudes, various forms of vegetatively propagated shallot or multiplier onions are preferred. World onion production has increased by at least 25% over the past 10 years with current production being around 44 million tonnes making it the second most important horticultural crop after tomatoes. Among vegetables, onions account for around 10% of all the worlds vegetable production (Food and Agriculture Organization of the United Nations Production Yearbook, 1999). Asia accounts for well over half this production with China and India being the major producers. The UK has a very modern and progressive onion industry but grows less than 1% of world onion production. Green/spring/salad onions or scallions are immature onions grown at high density for a short season. The market often does not distinguish between A. cepa and A. stulosum for this use. These must be harvested and sold within a few days and are popular both for salad and cooked use. A similar product is semi-bulbed onions, again harvested before maturity and sold quickly it provides a larger amount of bulb tissue than scallions. Bulb onions are also produced specically for freezing, drying and dehydration. It is estimated in the USA that frozen onions account for around 10% of all onions consumed. For dehydration, specialist onion varieties
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Figure 1. Benecial health compounds in onion.

Onions for Your Health which have been widely distributed to over 700 national health and food syndicate writers, magazine writers and radio food shows to increase public awarness of health benets.

CHEMICAL COMPOSITION OF ONIONS AND THE KEY HEALTH COMPOUNDS Water makes up the majority (80%95%) of the fresh weight of onion. Of the rest, up to 65% or more of the dry weight may be in the form of non-structural carbohydrate. High dry matter onions store their non-structural carbohydrate in the form of fructan, a fructose based polymer (Darbyshire and Steer, 1990). By contrast, low dry matter onions often have little fructan but proportionally larger amounts of glucose, fructose and sucrose. Onions are rich in two chemical groups that have perceived health benets to man. These are the avonoids

and the alk(en)yl cysteine sulphoxides (ACSOs) (Fig. 1). Two avonoid subgroups are found in onion, the anthocyanins, which impart a red/purple colour to some varieties (such as the commercially grown variety, Red Baron) and avanols such as quercetin and its derivatives responsible for the yellow esh and brown skins of many other varieties (Leighton et al., 1992). The ACSOs are the avour precursors, which when cleaved by the enzyme alliinase, generate the characteristic odour and taste of onion.

The alkyl cysteine sulphoxides and associated breakdown products The avour of onion is mainly due to sulphur-containing compounds, formed by the cleavage of three S-alk(en)ylL-cysteine sulphoxides (ACSOs) by alliin alkyl-sulphenate-lyase (alliinase). These three ACSOs are ()-S-

Figure 2. Generation of the major avour groups in onion Copyright # 2002 John Wiley & Sons, Ltd. Phytother. Res. 16, 603615 (2002)

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methyl-L-cysteine sulphoxide (MCSO, methiin), ()-Spropyl-L-cysteine sulphoxide (PrCSO, propiin) and trans-()-S-(propen-1-yl)-L-cysteine sulphoxide (1-PeCSO, isoalliin). 1-PeCSO is by far the most abundant of the ACSOs often being more than 80% of the total and it is this compound that is responsible for the majority of the avour chemistry in onion. In intact tissue the ACSOs and alliinase are stored in separate cellular compartments (Lancaster and Collin, 1981). Disruption of these compartments due to tissue damage results in alliinase hydrolysing the ACSO to give a-iminopropionic acid and a S-alk(en)yl cysteine sulphenic acid (not illustrated). Both of these compounds are unstable and the aiminopropionic acid spontaneously hydrolyses to form ammonia and pyruvic acid (not illustrated). The mass per gram fresh weight of pyruvic acid generated is often used as a measure of onion avour. The major avour compounds are generated by the spontaneous reactions undergone by the S-alk(en)yl sulphenic acids amongst themselves and other compounds. The result is a mixture of over 50 sulphurcontaining compounds including thiosulphinates, thiosulphonates, mono-, di- and tri-sulphides as well as specic compounds such as the lachrymatory or tear factor, thiopropanal S-oxide. A simplied summary of the major reactions is shown in Fig. 2. The reader is referred to a more comprehensive treatise by Block (1992). The actual composition is dependent on the initial concentration and ratio of the three alk(en)yl sulphenic acids, the immediate molecular environment, pH and temperature. This latter consideration is important since most onion is eaten cooked. Kubec et al. (1998, 1999) have shown that MCSO and PCSO in the presence of water can also undergo thermal decomposition to give the disulphide, trisulphide, thiol and thiosulphonate. The lachrymatory factor dimerizes to form bi-sulphines and their derivative cyclic S-S compounds, the zwiebelanes. The large range of compounds formed, the instability of many of them, and the differences in chemistry that can occur, mean that advances in understanding avour generation have been slow. Recent advances include the identication of 3-mercapto-2-methylpentan-1-ol (Widder et al., 2000) as a new aroma compound of onions. Alliin alkyl-sulphenate-lyase (alliinase)

and Thomas, unpublished). The enzyme is synthesized as a pre-protein with the mature enzyme having a predicted size of 445 amino acids. The pyridoxal phosphate binding site has been identied as Lys 285 by Kitamura et al. (1997). Jin et al. (2001) have shown that Trp182 in garlic, equivalent to Trp 182 in onion, is essential for alliinase activity. Clark et al. (1998) reported that molecular analysis using an alliinase cDNA indicated the presence of two genes, although six different cDNAs have been isolated from the variety Ailsa Craig, at least four of which are expressed in the bulb (Trueman and Thomas, unpublished). The presence of several bulb isoforms raises the possibility of differences in substrate specicity. In garlic there is evidence for both alliin/isoalliin and methiin specic-enzymes (Lawson and Hughes, 1992). The pH optima of these enzymes are 5.0 and 6.57.0, respectively. The methiin specic enzyme appears to be less robust being more sensitive to heat and inhibitors such as amino-oxyacetate (Lawson and Hughes, 1992). The existence of ACSO specic enzymes would explain the apparent differences in the rate of cleavage of isoalliin (100% within 20 s) and methiin (50% after 2 h) on tissue damage (Lancaster et al., 1998; Grifths and Trueman, unpublished observations). Such differences in the rate of ACSO cleavage could dramatically alter the avour chemistry and thus the health properties of an onion bulb. In onion root a novel alliinase has been puried and the cDNA encoding this isoform has been cloned and shown to have only 50% homology with other alliinases. Unlike other Allium alliinases, the cloned onion root enzyme has activity towards cystine as well as cysteine sulphoxide (Lancaster et al., 2000a). There are several suggestions for the role of alliinase in the plant. The most obvious is a defensive function since the ACSO breakdown products deter and are often lethal to, a wide range of pests (see below). Alliinase may also have a role in remobilizing sulphur from ACSOs during conditions of sulphur deprivation, since the specic activity of the enzyme increases at lower sulphur levels in the soil (Lancaster et al., 2000b). Alliinase may also function as a storage peptide, since its quantity, vacuolar location, tendency to aggregate and high sulphur content are typical features of storage proteins. Alkyl cysteine sulphoxide biosynthesis

Alliin alkyl-sulphenate-lyase (alliinase- EC 4.4.1.4) catalyses the cleavage of ACSOs to give a sulphenic acid and a-iminopropionic acid. By analogy with garlic, the mechanism is likely to proceed via a pyridoxal-5'phosphate-schiff base derivative which undergoes belimination (Jansen et al., 1989). The pyridoxal-5'phosphate co-factor has been shown to be essential and tightly bound to the peptide in a 1:1 stoichiometry (Tobkin and Mazelis, 1979). Onion alliinase is a glycoprotein with a carbohydrate content of approximately 4.6% and comprising about 6% of total soluble protein of bulb tissue (Nock and Mazelis, 1987). In onion bulb, alliinase is located in the vacuole (Lancaster and Collin, 1981) in both monomeric and multimeric forms (Clark et al., 1998). This multimerization may, in part, be due to its likely association with mannose specic lectins as reported for garlic (Rabinkov et al., 1995). Several groups have cloned alliinase gene sequences (Van Damme et al., 1992; Gilpin et al., 1995; Trueman
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The pathway(s) by which ACSOs are synthesized in Alliums is still somewhat unclear. Much attention has been concentrated on the synthesis of the C3-ACSOs since 1-PeCSO and 2-PeCSO are the major ACSOs in onion and garlic, respectively, and these compounds have a major inuence on the avour of these Alliums and also their health benets. Granroth (1970) has proposed two pathways for the synthesis of the C3-ACSOs. The rst was based on observations using radiolabelled serine that suggested that PrCSO could be formed by the reaction of serine (more likely as the derivative Oacetylserine) with propanethiol to give S-propyl cysteine (Fig. 3). This is then oxidized to give the sulphoxide. Support for this pathway was provided by Prince et al., (1997) who showed that natural and novel cysteine sulphoxides could be formed by feeding the appropriate thiol to root cultures of onion. Signicantly, only the naturally occurring diastereomers were synthesized
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Figure 3. C3 alkyl cysteine sulphoxide (ACSO) synthesis in onion.

suggesting the involvement of a stereospecic oxidase. Reuter and Sendl (1994) have suggested that serine and 2-propenethiol may be involved in the synthesis of ()-Spropen-2-yl)-L-cysteine sulphoxide in garlic. The reaction of alkylthiols with both serine and Oacetyl serine may be catalysed by cysteine synthase. Ikegami et al. (1988) has shown that cysteine synthase isolated from Spinacea oleracea is able to catalyse the addition of alkylthiols to both serine and O-acetyl serine. There are many other reports of S-substituted cysteines along with b-substituted alanines being catalysed by this enzyme (reviewed by Ikegami and Murakoshi, 1994) suggesting that it has a broad substrate specicity. This could suggest a mechanism for the observations of Prince et al., (1997) that novel ACSOs can be synthesized by supplying the appropriate thiol to onion root cultures. The main problem with this pathway is the difculty in identifying an appropriate source of C3 thiols. Ironically the most likely source is from the breakdown products of the ACSOs themselves. Both propanethiol and 2propanethiol have been reported in onion juice extracts along with methanethiol and ethanethiol (Lancaster and Boland, 1990). This latter compound may explain the recent report of ethylcysteine sulphoxide (ethiin) in a number of Allium species (Kubec et al., 2000). This pathway, however, cannot be the route of 1-PeCSO synthesis since 1-propenethiol does not exist. A second pathway proposed by Granroth (1970) suggested that the C3 alkenyl moiety of 1-PeCSO is derived from valine via methacrylic acid (Fig. 3). He demonstrated that the formation of both S-2-carboxypropyl glutathione and S-2-carboxypropyl cysteine from methacrylic acid and glutathione or cysteine. Whether S2-carboxypropyl glutathione or S-2-carboxypropyl cysteine is the starting substrate, however, has not been established. Pulse-labelling studies in excised leaves by Lancaster and Shaw (1989) using 35SO4 found that the label was incorporated in the g-glutamyl peptides within 15 min but not in the ACSO pool until at least 6 h later. This has led to the suggestion that glutathione and the gCopyright # 2002 John Wiley & Sons, Ltd.

glutamyl peptides are intermediates in the biosynthetic pathway of the avour compounds. The common substrate for PrCSO and 1-PeCSO would be g-glutamyl S-2-carboxypropylcysteine formed by the reaction of methacrylate with either g-glutamylcysteine or with glutathione followed by the elimination of glycine. This pathway postulates that the nal step is the removal of the g-glutamyl moiety and Lancaster and Shaw (1991) have shown that the enzyme g-glutamyl transpeptidase is able to remove the g-glutamyl residue from g-glutamyl PeCSO to yield the free ACSO. Edwards et al. (1994) using intact plants, found that over 70% of the label was incorporated in to the ACSOs with no more than 20% appearing in the g-glutamyl peptides pool. They stated that little evidence was found to support g-glutamyl peptides as intermediates of ACSO synthesis, although admitted that their frequency of sampling would have missed a transient rise in gglutamyl peptide labelling as observed by Lancaster and Shaw (1989). g-Glutamyl peptides are not simply potential ACSO intermediates, however, since although ACSOs appear to have a role as storage peptides (as well as in defence), the g-glutamyl peptides are in fact the most important group of storage peptides in onion. Carson (1987) has reported g-glutamyl-trans-()-S-(1-propenyl)-cysteine sulphoxide as the major peptide in onions (13 mg/100 g fresh weight), representing approximately 50% of the potential avour and odour precursors. In this respect ACSOs may be viewed as breakdown products of the g-glutamyl peptides. Support for this comes from the observation that g-glutamyl transpeptidase is ve-fold more active in sprouting bulbs compared with dormant (Lancaster and Shaw, 1991) suggesting a role in the remobilization of glutamyl-N from this pool. How an onion effects a balance between the ACSO and the g-glutamyl peptides pools and whether this is done using one or multiple synthetic routes is unclear. However, it is clear that with the inability of alliinase to cleave the g-glutamyl peptides, this balance is
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important to the overall potential health benets, which may be derived from an individual bulb. The proposed pathways of MCSO (C1-ACSO) synthesis echo the pathways of C3-ACSO synthesis. Granroth (1970) has shown that MCSO can be synthesized by the addition of methylthiol to cysteine or O-acetyl serine in onion. Lancaster and Shaw (1989), however, have suggested that the precursor of MCSO is g-glutamyl Smethyl cysteine, formed from either the methylation of gglutamyl cysteine or of glutathione followed by the loss of the glycine moiety. However, MCSO is widespread in plants being found at high concentrations in members of the Cruciferae and Leguminosae. S-Methyl-L-cysteine can be synthesized in many plants by direct methylation of cysteine by S-adenosylmethionine to give MCSO, although this has yet to be demonstrated in onion.

has not been determined, it is likely that it follows the general scheme outlined by Harborne (1988).

THERAPEUTIC AND MEDICINAL VALUE OF ONION Background Government policy in the UK over the past 8 years has been to promote health awareness issues particularly with regard to the consumption of fresh fruit and vegetables and has led to the slogan Five-a-day in advertising campaigns, i.e. ve portions of fruit or vegetables per day is recommended to promote good health. Many of the health promoting compounds in fruit and vegetables have been identied and since many phytochemicals are colourful, they provide an easy way to communicate this chemical diversity to the public (Heber and Bowerman, 2001). Such compounds in red foods include, b-carotene in carrots, lycopene in tomatoes (Clinton and Giovannucci, 1998); red-purple foods contain anthocyanins (e.g. red apples, grapes, berries and wine); green foods, e.g. Brassicas (kale, Brussels sprouts) contain glucosinolates (Fahey et al., 1998); orange-yellow foods such as oranges and lemons contain citrus avonoids and white-green foods as in Alliums (onion and garlic) contain the organosulphur compounds, alk(en)yl cysteine sulphoxides. The use of Alliums by humans has a long history that can be traced back to the Egyptians. Olympic athletes were fed onions and garlic to improve performance in track and eld events and Europeans have treated blood clots in horses for centuries with onion. These folkloric traditions thus suggested an involvement in improved blood circulation. In the modern world, with technological advances and global communication networks, the Internet has become a major source of information for many people. Numerous Internet sites exist with information on suggested herbal uses of Alliums. Some of the claims include aphrodisiac properties, poultice for earaches, prevention of hair loss, treatment of warts and athletes foot. It was even reported on the British Broadcasting Corporation news programme Midlands Today that some farmers claimed that hanging bunches of onions in cow sheds kept away foot and mouth disease! Clearly there are many claims on health benets of Alliums, however, most, with the exception of garlic, have not received any rigorous (or even gentle) scientic investigation. Here we report some of the advances in dening the health benets of onion and where known the mechanisms behind these effects. However, it should be stated that we have often compared the action of onion with garlic in the text. It must be remembered that work on the health benets of onion is less advanced than that of garlic and although it is natural to assume that the underlying mechanisms may be the same for similar benets, this may well not be so. This is because the major chemistry of garlic is based on the breakdown product of 2-PeCSO, allicin and its derivatives (Lancaster and Boland, 1990). Onion does not synthesize 2-PeCSO and does not produce allicin when crushed. The major chemistry of onion is based on the 1-PeCSO and the resulting sulphenic acid cannot react with itself to form an allicin analogue (thiosulphinate) since the result is unstable and rearranges to form thiopropanal S-oxide (the
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Flavonoid content of onions It is widely believed that the antioxidant micronutrients obtained from fruit and vegetables afford signicant protection against cancer and heart disease as well as ageing (see below). Flavonoids are potential antioxidants found in a wide range of foods but can be particularly rich in onions. There are two major groups of avonoids in onion, the avonols and the anthocyanins which have attracted interest in recent years. The avonols are often found concentrated in the skin of most onions where they impart the yellow/brown colour, unless concealed by the red pigment, anthocyanin. Brown outer scales contain an antifungal component, 3,4-dihydroxybenzoic acid which is synthesized by the deglucosidation of quercetin glucosides to quercetin which is then oxidized by a peroxidase (Takahama and Hirota, 2000). In dried red onion, the avonol quercetin was found in concentrations up to 2.1% w/w. By comparison with other fruit and vegetables, onion has 300 mg/kg of quercetin, broccoli 100 mg/kg, apples 50 mg/kg blackcurrants 40 mg/kg and tea 30 mg/kg (Hollman and Arts, 2000). Indeed the quercetin content is only appreciably higher in kale where levels of around 450 mg/kg were reported. Flavonols are also found in the eshy scale tissue where they give a yellow colour in high concentrations or an ivory/cream hue at lower concentrations. This is in contrast to the esh of white skinned onions, garlic and leek, which contain only trace levels of avonols (Patil et al., 1995). The concentration of these compounds usually increases in the outer scales. Sixteen different avonols have been identied in onion consisting of the aglycones and glycosylated derivatives of quercetin, isorhamnetin and kaempferol (Breu and Dorsch, 1994; Fossen et al., 1998). Price and Rhodes (1997) showed that quercetin 3,4'-O-diglucoside is rapidly degraded in macerated tissues with a 50% decline after 5 h resulting in production of quercetin monoglycoside and free quercetin in the variety, Rijnsburger. A number of anthocyanins have been detected in onion, which are; cyanidin 3-glucoside, cyanidin 3laminaribioside, cyanidin 3-malonylglucoside and cyanidin 3-malonyllaminaribioside (Donner et al., 1997). In addition, four minor variants have been detected, two of which have been tentatively identied as peonidin 3glucoside and peonidin 3-malonylglucoside (Donner et al., 1997). Although the biosynthetic pathway in onion
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lachryamatory factor of onions). This compound can undergo several reactions forming a range of compounds including the cepaenes, a fairly new class of compounds thought to have antithromotic and antiasthmatic activity (see later). Garlic also contains small amounts of 1PeCSO and in theory can produce thiopropanal S-oxide, but this reaction is overwhelmed by the large amount of 2-PeCSO in the plant. Furthermore, onions are a rich source of avonoids and extensive research has focused on the health benets of these compounds (see below). However, these compounds are virtually absent in peeled garlic cloves (Koch and Lawson, 1996). Thus, while some commonality of responses between onion and garlic may exist, specic health benets may reside for each species. What are health benets based on? The assignment of a health benet label to a particular compound is always difcult to justify. Clues are sometimes found in epidemiological data in which studies of population diet are correlated with the incidence of a particular type of disease. Large-scale clinical trials involving volunteers who ingest a specied amount of product over a period of time are often very useful in assessing the efcacy of particular foods in the diet in disease prevention. Frequently though, the trials involve small numbers (a few hundred people) and the relevance is often challenged. In some respects, studies with animals often yield informative results since they can be maintained on specied diets and their intake carefully monitored. Rat, rabbit and dog have often been used in Allium studies. At the other end of the spectrum, in vitro cell cultures derived from animal (non-neoplastic) and human cell lines (neoplastic) are challenged with specic products and chemical markers or cytological changes are assessed such as oxidative DNA damage, apoptosis markers (such as DNA laddering) or increased production of free radical scavenging enzymes. Increased production of free radical scavenging enzymes is viewed as a positive effect, however, whether this translates to a health benet is unclear. Thus, ascribing compounds the attribute benecial to health, requires the collation of diverse data from many sources and different types of studies. Bioavailability One of the crucial questions in deciding whether a compound is likely to have a signicant effect in vivo is to determine how and in what form the component is taken up in the digestive tract. Recent studies on the uptake of avonoids and their in vivo antioxidant effects have been reported in a trial on six female volunteers in the age range of 2044 years. Flavonoid glucosides (quercetin-3-glucoside and isorhamnetin-4-glucoside) were signicantly elevated in plasma following ingestion of onions and these increases were associated with an increased resistance of lymphocyte DNA to DNA strand breakage 4 h post ingestion. A signicant decrease in the level of urinary 8-hydroxy-2'-deoxyguanosine (a marker of DNA oxidation) was evident after this time period. No signicant change, however, in the excretion of urinary malondialdehyde (a general marker of oxidative stress
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generally considered to be an end product of polyunsaturated fatty acid peroxidation) was observed. Thus, following ingestion, a transient decrease in some biomarkers of oxidative stress were observed although the particular markers affected differed (Boyle et al., 2000). Recent studies indicate that quercetin monoglucoside and quercetin diglucoside are efciently hydrolysed in the small intestine by b-glucosidases to quercetin most of which is then absorbed (Walle et al., 2000). The absorption of dietary quercetin glycosides in humans ranges from 20% to 50%. The sugar moiety is an important determinant of their bioavailability and absorption times vary from between less than 0.5 h to 9 h dependent on glycoside type. For quercetin 4'glucoside plasma levels peaked 11.5 h after ingestion with as little as 0.2% being excreted in the urine (Aziz et al., 1998). Excretion of quercetin glycosides is slow with elimination half-lives of around 24 h independent of glycoside type (Hollman and Arts, 2000). Quercetin can be absorbed in humans from dietary sources to sufcient levels to increase the overall antioxidant activity of the plasma. Quercetin, however, has a strong afnity for protein and provides no direct effect in preventing low density lipoprotein (LDL) oxidation (McAnlis et al., 1999). Recently, a study on the effects of high avonoid consumption (derived from dietary onion and black tea) revealed no signicant effect on the inhibition of lipid peroxidation in humans (OReilly et al., 2001). The greatest loss of avonoids takes place when onions are peeled. Cooking, frying or warm-holding for up to 2 h had little effect on avonoid content and it was concluded that onions in ready-made dishes and home cooked food may be good dietary sources of these compounds (Ewald et al., 1999). Antiarcinogenic properties Recent work indicates possible important roles for polyphenolic components (such as avonoids) as contributors to antioxidant activities and also as agents of other mechanisms contributing to anticarcinogenic actions. Thus it may be anticipated that quercetin and its glycosylated derivatives in onion may play a role in these chemoprotective actions. Alkyl sulphides and diallyl disulphides have also shown possible protective effects on the initiation of carcinogenesis through modulation of enzymes involved in the metabolism of carcinogenic substances (Siess et al., 1997; see below-Health benets relating to antioxidant properties). ()-S-Methyl-L-cysteine sulphoxide and related derivatives exerted signicant inhibitory effects on diethylnitrosamine-induced neoplasia of rat liver (Takada et al., 1997). Belman (1983) reported a great potency of onion oil over garlic oil in decreasing the number of tumours and the rate of their development in mice. By contrast, garlic and onion oil showed an almost equal ability to suppress growth of leukaemia HL60 cells and methyl allyltrisulphide was suggested to be the active component in garlic (Ariga et al., 2000). In human dietary studies, a protective effect against oesophageal and stomach cancer was found in a Chinese study conducted on Allium consumption which included onion, Welsh onion, Chinese chives and garlic (Gao et al., 1999). Onion as part of a diet was also indicated to be inversely related to the risk of developing brain cancer
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(Hu et al., 1999). In a French casecontrol study (345 patients with primary breast carcinoma), the risk of breast cancer was shown to decrease as consumption of onion, garlic and bre was increased (Challier et al., 1998). By contrast, the risk of female breast carcinoma in relation to onion and leek consumption and the use of garlic supplements evaluated in the Netherlands Cohort Study on diet and cancer (120 852 Dutch men and women aged 5569 years) showed no association between Allium consumption and the incidence of female breast carcinoma (Dorant et al., 1995). In the same study group there was also no evidence that consumption of these vegetables lowered the risk of lung carcinoma (Dorant et al., 1994). However, like the Chinese study, the Dutch study provided evidence for a strong inverse association between onion consumption and stomach cancer incidence (Dorant et al., 1996). Recently, Helicobacter pylori, the bacterium implicated in the aetiology of stomach cancer was shown to be susceptible to garlic at a fairly moderate concentration (Sivam, 2001). Effects on lipid metabolism The reader is referred to the recent review of Ali et al., (2000) on the effects of garlic and onions on eicosanoid metabolism and its clinical relevance. Diseases related to atherosclerosis such as ischaemic heart disease, stroke and peripheral arterial diseases are associated with elevated serum lipids. A cholesterol-lowering effect of garlic has been reported in a number of studies (Gebhardt et al., 1994; Ali et al., 2000). Exposure of human liver HepG2 cells to allicin and ajoene resulted in the concentration-dependent inhibition of cholesterol biosynthesis. At low concentration, both compounds inhibited the hydroxymethylglutaryl-(HMG)-CoA reductase, the enzyme at the start of the cholesterol biosynthetic pathway, while at higher concentration of both compounds, inhibition was observed at later steps in the pathway resulting in the accumulation of lanosterol, indicating inhibition of lanosterol 14 a-demethylase (Gebhardt, 1993; Gebhardt et al., 1994). Garlic powder (containing 1.3% alliin) has been shown to be benecial in reducing blood cholesterol, triglycerides levels and systolic blood pressure in hypercholesterolaemic rats (Ali et al., 2000). While work on onion is less advanced it has been demonstrated that ()-S-methyl-L-cysteine sulphoxide, (a constituent of onion) exhibits hypolipidaemic activity (Kumari et al., 1995). Recently, quercetin (again a constituent of onion) has also been shown to inhibit rat hepatic cholesterol biosynthesis in vitro (Glasser et al., 2002). However, whether such a benet translates to the human diet in vivo awaits further study. Certainly studies with cholesterol supplemented diets using rabbits revealed that garlic was effective in lowering serum cholesterol levels whereas onion extracts were ineffective (see Ali et al., 2000). Cardiovascular effects Recent work has focused largely on the antiplatelet activity of onion extracts and on atherosclerosis and alterations in serum lipid proles (see Ali et al., 2000). Studies on the antiplatelet actions of aqueous extracts of onions suggest that the release of arachidonic acid from
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phospholipids, which initiates eicosanoid metabolism in mammals leading to prostaglandins, thromboxanes and leukotrienes synthesis is inhibited as is throboxane A2 synthase activity (Moon et al., 2000). Extracts of Welsh onion (Allium stulosum L) can also modulate vascular responses in aortae (Chen et al., 1999). Raw extracts of this species lower systolic blood pressure and prolong bleed times in rats possibly through inhibition of platelet function and suppression of thromboxane production (Chen et al., 2000). Antiplatelet activity is signicantly affected by genotype, environment and duration of storage of onions (Debaene et al., 1999). Garlic is 13 times more potent than onion in inhibiting platelet aggregation and is more potent when consumed raw than in cooked or boiled form (Ali et al., 1999). Indeed raw garlic extract caused a signicant decrease in serum thromboxane (TXB2) in rabbits while onion extract at this dose was ineffective in lowering the TXB2 concentration. As garlic and onion are normally consumed in cooked food, their efcacy as preventative herbs in cardiovascular disease is questionable. Ali et al., (1999) were unable to demonstrate an anti-aggregatory effect of onion on human blood platelets while in an earlier study (Srivastava, 1984) a very strong effect was reported. Antiplatelet activity of mild versus pungent onion extracts revealed that the highest antiplatelet activity was observed in the pungent cultivars (Goldman et al., 1996). Recent studies on quantitative trait loci (QTLs) on soluble solids content, total dry matter, pungency and in vitro antiplatelet activity suggested that it would be difcult to develop onion populations with lower pungency and high in vitro antiplatelet activity (Galmarini et al., 2001). Similarly, no increase in antiplatelet activity was obtained from four onion cultivars grown hydroponically with supraoptimal sulphur in the media (Orvis et al., 2001). Intake of dietary avonols and avones has been reported to be inversely associated with risk of cardiovascular disease in several epidemiological studies (Yochum et al., 1999) although this has been challenged (Hollman and Katan, 1999). Indeed, this effect does not appear to be mediated by haemostatic variables since anti-aggregatory effects of avonoids seen in vitro cannot be attained in vivo (Janssen et al., 1998). Thus the antiplatelet activity of Alliums is considered to be a property of the organosuphur compounds. In particular, a class of a-sulphinyl-disulphides (cepaenes) has demonstrated antithrombotic activity (Block et al., 1997). These compounds have structural similarity to ajoene, considered the antiplatelet compound in garlic extracts. Effects on the respiratory system Compounds derived from onion are known to have antiasthmatic activity. Thiosulphinates and cepaenes (asulphinyl-disulphides) have been identied as the active components (Dorsch et al., 1989; Dorsch, 1996) and are suggested to mediate their effects through suppression of cyclooxygenase and lipoxygenase mediated reactions which initiate eicosanoid metabolism and lead to bronchial restriction (Wagner et al., 1990). There is a clear rank order of pharmacological activity with saturated thiosulphinates being less active than unsaturated ones. Conjugated, especially a,b-unsaturated or aromatic thiosulphinates were the most active (Breu and
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Table 2. Antioxidant status of some onion varieties

Variety Garlic Spanish 96002 Southport white Bessanovski Hysam Red Baron Purple intercross Outer scales Inner scales Pungency Mild Strong V. strong Strong Strong Mild Mild Anthocyanin (mg/g fwt) 3.5 0.5 4.5 0.5 0.1 0.05 Antioxidant content (mg/g dwt) 10 2 17 2 18 5 20 5 35 8 65 15 90 3 15 2

Antioxidant content was determined in 70% ethanol extracts of onion bulb tissues using the total antioxidant status colorimetric assay supplied as a kit by Randox (Antrim, UK) based on Miller et al. (1996). fwt, fresh weight; dwt, dry weight. (n = 3 SD).

Dorsch, 1994). Thiosulphinates are not broncholytic because neither histamine- nor acetylcholine-dependent asthmatic reactions were altered by these compounds. By contrast, the main thiosulphinate of garlic, allicin, was devoid of activity. Antibiotic activities Crude extracts of onion exert potent antifungal and antibacterial properties (Kim, 1997; Yin and Tsao, 1999). In addition to ACSOs, proteins, saponins and phenolic compounds may contribute to this activity. Onion oils and aqueous extracts were active against several grampositive bacteria but ineffective against gram-negative bacteria (Elnima et al., 1983; Zohri et al., 1995). By contrast, garlic extracts were effective against the latter class of bacteria (Yoshida et al., 1999a, 1999b). Onion juice is effective against many yeast species and the oil effective against dermatophytic fungi (Zohri et al., 1995). Onion extracts also inhibit oral bacteria which are associated with dental carie formation (Kim, 1997). A novel antifungal compound, stulosin (octadecyl 3hydroxyindole) was isolated from A. stulosum which showed high activity towards Fusarium oxysporum primarily inhibiting protein synthesis (Phay et al., 1999). An antimicrobial protein (Ace-AMP1) has been isolated from onion seeds and was highly effective against plant pathogenic fungi at low concentration (Cammue et al., 1995). To date, however, the relative instability of the organosulphur compounds and the strong odour seem to limit their use as practical food preservatives (Kyung and Lee, 2001). Health benets relating to antioxidant properties During aerobic metabolism cells are prone to oxidative damage initiated by reactive oxygen species (ROS) or free radicals. Plant cells contain a complex array of antioxidant components such as vitamin C, vitamin E, glutathione and phenolics (including avonoids) which offer protection against cellular damage. Pigments such as anthocyanins and carotenoids are also known to be free radical scavengers and limit ROS propagation within plant cells (Hodges et al., 1999; Miller et al., 1996). Ingestion of such compounds may also offer direct chemoprotective roles in animal cells and help reduce
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oxidative stress. In addition, many of these compounds may also initiate the animal cells to produce their own chemical oxidative defence mechanisms such as induction of phase II drug metabolizing enzymes like glutathione-S-transferase and UDP-glucuronosyl transferase (Williamson et al., 1998; Guyonnet et al., 1999; Teyssier et al., 2001). In vivo studies with rats challenged with a range of carcinogens revealed that diallyl disulphide, a downstream product of the allinase reaction (present in extracts of garlic but not in onions), was a particularly effective antimutagenic compound and phase II enzyme inducer (Guyonnet et al., 2001). Attempts to standardize what is meant by antioxidant levels in different tissues have been made in a study on a range of consumed fruit vegetables and beverages based on the ABTS(2,2-azino-di [3-ethylbenzthiazoline sulphonate]) assay ((Paganga et al., 1999). The antioxidant potential of a tissue extract is assessed relative to the ability of trolox (a vitamin E analogue) to prevent generation of the radical cation ABTS from ABTS incubated with peroxidase (metmyoglobin) and hydrogen peroxide. The assay is not specic for any group of compounds and as such can be viewed as a global assay for antioxidant constituents. Using this method 5.5 average servings of onion is equivalent to 2 cups of tea, 4 apples, 3.5 glasses of blackcurrant juice, 7 glasses of orange juice or 20 glasses of apple juice (Paganga et al., 1999). In this regard onion oil extracts derived from Allium cepa are as effective as vitamin E supplementation in nicotine induced lipid peroxidation in rats (Helen et al., 2000). We have surveyed several commercial varieties of onion and some breeding lines from our genetic resources and assessed their antioxidant status using the ABTS assay (Table 2). The results show that compared with all onion varieties, the antioxidant content was lower in garlic. Furthermore, there was little difference between the high pungency line Bessanovski and a milder Spanish onion (breeding line 96002Wellesbourne Genetic Resources collection). A high antioxidant content was detected in onions containing anthocyanin such as the commercially grown variety Red Baron and a purple breeding line from our stock collection. Indeed the outer pigmented scales of this line showed high levels of antioxidant compared with the non-pigmented inner scales. Higher antioxidant status was also found in the outer scales of the typical yellow/brown UK cooking onion variety, Hysam (data not shown). Thus the
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antioxidant content appears to be developmentally regulated and markedly correlated with the production of anthocyanin pigments in the tissues. Other effects Many foods can be enriched with fructan dietary bres without any negative impact on the taste of the product. With an additional uptake of 1015 g of fructans per day the recommended daily uptake of dietary bres (30 g) could be reached. Fructans stimulate the growth of specic microorganisms in the colon (e.g. bidobacteria, lactobacilli) with a general positive health effect (Gibson, 1998; Ernst and Feldheim, 2000). Inulin (a type of fructan) rich in chicory, artichoke, garlic, leek and onions also improved blood lipid proles and altered the colonic environment in a benecial manner and shows promise as a functional ingredient in many processed foods (Causey et al., 2000). A benecial ameliorating inuence of dietary onion on diabetic nephropathy may be mediated through onions ability to lower blood cholesterol levels and to reduce lipid peroxidation (Babu and Srinivasan, 1999). Anti-hyperglycaemic effects for ()-S-methyl-Lcysteine sulphoxide have been reported in alloxandiabetic rats (Kumari et al., 1995). Depression of cutaneous inammation and oedema formation by topical application of onion extracts have been reported and are likely to operate through suppression of prostanoid metabolism (Breu and Dorsch, 1994).

ONIONS FOR HEALTHTHE FUTURE There are, in some respects, two views on how best to use knowledge gained from scientic studies to benet human health. On the one hand there is the pill culture in which people are encouraged to take one-a-day encapsulated formulations of plant extracts in order to deliver potential health benets. However, there is the danger that this may lead to people substituting good eating practices with poor nutrition supplemented with pills. On the other hand, many believe that simply eating the vegetable in an unprocessed or cooked form is more natural and that life style and not pill formulations is the better, longer term strategy, to help alleviate some of our western diseases. Certainly garlic extracts encapsulated in gelatin are available and are widely used. For many, the halitosis associated with ingestion of Alliums is socially unacceptable and this may be particularly so in the UK where garlic, in culinary use, is relatively recent. Many people report problems associated with indigestion following Allium consumption and so encapsulated formulations may be benecial. At present there is still some considerable debate as to what component(s) of Alliums are essential for delivering health benets. Strategies based on the rening of specic chemical constituents of Allium (such as ajoene) may deliver certain benets at the expense of others. Such renement would result in loss of, for example, quercetin and potential benets associated with its intake. In St Johns Wort extracts attempts to purify the antidepressant hypericin and administer it in pure form have met with less success than the cruder extract (Linde et al., 1996). This may be due to a synergistic effect between many of
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the components in the extract that result in an overall health benet. Certainly a systematic approach to evaluating the effects of various renement practices on health benets of Alliums is required in order to draw rm conclusions before policies on health issues and advice to the public can be formulated. As well as being eaten by almost all consumer and ethnic groups, onion is found in a wide range of processed foods particularly in the so-called fast foods. In this context, it is a good candidate for a delivery system for benecial mineral nutrients such as selenium, making it a potential functional food. Selenium deciency, which results in Keshan disease or KaschinBeck disease (Morenoreyes et al., 1998), is rare in the western world, but even so, most UK citizens only consume approximately 60% of the recommended daily allowance (RDA, US). It is likely that raising the amounts of selenium consumed by the population to between 13 times the RDA could have major health benets for the population in the areas of mental health, fertility (both male and female), cancer and cardiovascular disorders (reviewed Rayman, 2000). In this regard, sulphur-rich vegetables, like onion, can potentially be manipulated to have a high selenium content, since biological systems are usually imperfect in discrimination between sulphur and selenium. It has been demonstrated that growing onions in a selenium-rich environment can elevate the endogenous amount to levels that can deliver 13 RDA equivalents in a standard 80 g serving (Kopsell and Randle, 1997; Trueman, Crowther and Smith, unpublished). In Allium tricoccum (ramps) it has been shown that selenium enriched plants were able to reduce chemically induced mammary tumour formation in rats by 43% (Whanger et al., 2000). In onion, selenium fertilization did not affect total avour precursor content but did affect several individual ACSOs and precursor intermediates decreasing g-L-glutamyl-1-PeCSO and increasing MCSO (Kopsell and Randle, 1999). In an age where the average consumer spends less than 30 min preparing their evening meal, foods like onion, ubiquitous in a wide range of processed food, may be particularly valuable in improving the national intake of mineral nutrients such as selenium particularly of highrisk sectors of the population. Given the genetic diversity within onions, a detailed chemical proling of their compositions is required in order to understand the range of variation which may exist and to identify further components which may offer enhanced health benets. It is now possible to transform onion using Agrobacteria (Eady et al., 2000; Zheng et al., 2001) and this opens up the possibility of introducing genes into the crop for such a purpose. Recently a model reaction system has been developed for generating pure thiosunates using isolated alliinase and isolated or synthetic cysteine sulphoxides (Shen and Parkin, 2000). The ability to produce dened sulphur metabolites in vitro has exciting potential to aid in the systematic evaluation of their potential benets to health.

Acknowledgements
We wish to thank the Department of the Environment, Food and Rural Affairs (DEFRA, UK) and the European Union for funding our Allium research programme. Phytother. Res. 16, 603615 (2002)

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