Garlic & Health

Consumption of garlic may contribute to the prevention of cancer and cardio-vascular diseases.  These diseases are by far the leading causes of death and morbidity in the EU. Increasing garlic consumption and improving the content of the active compounds, may therefore lower the annual costs of these diseases, which are estimated to be many millions of Euros. The European growers of garlic may also benefit from increased garlic consumption, especially through growing improved  garlic varieties with increased health promoting capacities.
Traditional medicine Garlic has been used for a long time as food with many therapeutic effects. In spite of this, few scientific studies have investigated the mechanisms of these effects. There is a crucial lack in studies in which well defined garlic preparations and compounds are used. The studies so far indicate that the sulphur containing flavour compounds of the garlic plant are the major component of the health promoting effects.
	New perspectives Modern pharmaceutical and genetic techniques may allow an effective study of the underlying mechanisms and the development of improved garlic types. Therefore, the European Union has financed a research project on the development of high quality garlic and on the influence of garlic consumption on biomarkers of atherosclerosis and cancer. The project is financed within the framework of the European research programme ‘Quality of Life and Management of Living Resources’, Key action 1: Food, Nutrition and Health. The project started in 2000 and has a running time of four years. The EU funding covers in total some four million Euros.

15 partners

The EU project (EU-contract: QLK1-CT-1999-0498) is carried out by a consortium of 15 independent research groups from six countries. The consortium consists of universities, research institutes, plant breeding and pharmaceutical companies, each bringing special knowledge and expertise, such as genetic resources, breeding, cultivation systems, sulphur biochemistry, or experience in studying pharmaceuticals and their effect on atherosclerosis and cancer.

Insights

The garlic and health project has two main scientific objectives. The first is to understand and improve the production of active compounds by garlic, through sophisticated breeding techniques. The second aim is to improve the understanding of the role of garlic in the diet and as a therapy in promoting and sustaining health and preventing cancer and cardiovascular-diseases like atherosclerosis.

Agro economy   The production of garlic (Allium sativum L.) in Europe is concentrated in Mediterranean countries such as Spain, France and Italy. The market price of European garlic is high, especially in comparison with the garlic grown in China. This price difference could severely threaten the European garlic growers if there was a free market in Europe for garlic. However, to protect the European garlic growers the European Commission issued a regulation in 1993 that only 12000 tons of Chinese garlic can be imported annually. The garlic and health project therefore aims to develop methods, through improved seed technology and genetics, which will enable European garlic growers to meet the internal demand for high quality products and to compete on an international level. Improved garlic varieties will be among the concrete products of the project. For this, genetic variation and the genetic background of the production of the active compounds will be studied and new breeding technologies will be developed and applied.

Targeting health benefits

The main objective of the health part of the project is to clarify the role of garlic for the prevention of chronic diseases like atherosclerosis and cancer. This will be achieved through modern cellular, molecular and clinical studies in cells, animals and humans. Specific biomarkers will be identified as indicators for modulation of these diseases on the cellular and tissue level and in humans. These will serve as a basis for new intervention studies.

Publications released from the project

Scientific publications

2001

• Kamenetsky R & HD Rabinowitch 2001. Floral development in bolting garlic. Sex Plant Reprod 13: 235-241
• Kik C, R Kahane & R Gebhardt, 2001. Garlic and Health. Nutrition, Metabolism and Cardiovascular Diseases 11(4): 57-65 (Suppl) .
• Kik C, R Kahane & R Gebhardt, 2001. Garlic & Health: a European initiative for the development of high quality garlic and its influence on biomarkers of atherosclerosis and cancer in humans for disease prevention. IPGRI Newsletter for Europe 22, 5.

2002

• Fereol L, V Chovelon, S Causse, N Michaux-Ferriere & R Kahane, 2002. Evidence of a somatic embryogenesis process and plant regeneration and acclimatisation in garlic (Allium sativum L.). Plant Cell Reports 21, 197-203.
• Germain E, J Auger, C Ginies, MH Siess & C Teyssier, 2002. In vivo metabolism of diallyl disulphide in rat: identification of two new metabolites. Xenobiotica 32 (12), 1127-1138.
• Kamenetsky R & HD Rabinowitch, 2002. Fertility restoration and production of true seeds in garlic. Bulletin of the EU (Israel Edition).
• Martin Urdiroz N, 2002. Advances in Garlic Tissue Culture and Transformation. PhD  Thesis, Cordoba, Spain.

2003

• Arnault I, JP Christidès, N Mandon, Th Haffner, R Kahane & J Auger, 2003. High-performance ion-pair chromatography method for simultaneous analysis of alliin, deoxyalliin, allicin and dipeptide precursors in garlic products using multiple mass spectrometry and UV detection. Journal of Chromatography A 991, 69-75.
• Gebhardt R, 2003. Variable influence of kaempferol and myricetin on hepatocellular cholesterol biosynthesis. Planta Med. 69:1071-1074.
• Germain E, J Chevalier, MH Siess & C Teyssier, 2003. Hepatic metabolism of diallyldisulphide in rat and man. Xenobiotica: 33(12) 1185-1199.
• Keiss HP, VM Dirsch, Th Hartung, Th Haffner, L Trueman, J Auger, R Kahane & AM Vollmar, 2003. Garlic (Allium sativum) modulates cytokine expression in LPS-activated human blood leading to an overall inhibitory effect on NF-kB activity. Journal of Nutrition 133, 2171 - 2175.
• Keiss HP, 2003. Interaction of Allium sativum L. and Leontopodium alpinum Cass. with mediators of inflammation involved in the molecular mechanisms of atherosclerosis. PhD thesis Ludwig-Maximilians Universität Munich, Germany.
• Le Bon AM, MF Vernevaut, L Guenot, R Kahane, I Arnault, J Auger, Th Haffner & MH Siess, 2003. Effects of garlic powders with varying alliin contents on hepatic drug-metabolizing enzymes in rats. Journal of Agricultural and Food Chemistry 51: 7617-7623.
• Zheng SJ, B Henken, FA Krens & C Kik, 2003. The development of an efficient cultivar independent plant regeneration system from callus derived from both apical and non-apical root segments of garlic (Allium sativum L.) In vitro Cell. Dev. Biol. Plant 39: 288-292.

2004

• Anonymous, 2004. Healthy Alliums help beat diseases. Prophyta Annual 2004, 24-25.
• Bergès R, MH Siess, J Auger, I Arnault, R Kahane, MF Pinnert, MF Vernevaut & AM le Bon, 2004. Comparison of the chemopreventive efficacies of garlic powders with different alliin contents against aflatoxin B1 carcinogenicity in rats. Carcinogenesis 25, 1-7.
• Collin HA, 2004. Garlic and cardiovascular disease. In: Functional foods, diet, cardiovascular disease and diabetes (A Arnoldi and F Dodds Eds), Woodhead Publishings, UK (accepted).
• Collin HA, J Hughes, A Tregova, G van der Werff, M Wilkinson, R Cosstick, L Trueman, T Crowther, L. Brown, MG Jones, B Thomas & AB Tomsett, 2004. Sulfur biochemistry of garlic: the biosynthesis of flavour precursors.  Accepted: Acta Hort.
• Dirsch VM, HP Keiss & AM Vollmar, 2004. Garlic constituents and metabolites fail to inhibit the activation of the transcription factor NF-kappaB and subsequent expression of the adhesion molecules E-selectin in human endothelial cells.  Eur J Nutr. 43, 55-59.
• Espirito Santo SMS, BJM van Vlijmen, R Buytenhek, W van Duyvenvoorde, LM Havekes, I Arnault, J Auger & JMG Princen, 2004. Well-characterised garlic-derived materials are not hypolipidemic in APOE*3-Leiden transgenic mice. J Nutr 134, 1500 - 1503.
• Espirito Santo SMS, BJM van Vlijmen, W van Duyvenvoorde, EH Offerman, LM Havekes, I Arnault, J Auger & JMG Princen, 2004. Absence of an atheroprotective effect of the garlic powder Printanor in APOE*3-Leiden transgenic mice. Accepted: Atherosclerosis, Thrombosis and Vascular Biology.
• Espirito Santo SMS, 2004. Modulation of lipoprotein metabolism and atherosclerosis in transgenic mouse models. PhD thesis, University of Leiden, the Netherlands.
• Huchette O, R Kahane & C Bellamy, 2004. Influence of environmental and genetic factors on the alliin content of garlic bulbs. Accepted: Acta Hort.
• Hughes J., Tregova A., Tomsett A.B., Jones M.G., Cosstick R. & Collin H.A. Synthesis of the flavour precursor, alliin, in garlic tissue cultures. Accepted: Phytochemistry.
• Jones MG, J Hughes, A Tregova, J Milne, AB Tomsett & H A Collin, 2004. Biosynthesis of the flavour precursors of onion and garlic. Journal of Experimental Botany 55,1903-1918.
• Kamenetsky R, I London Shafir, M Baizerman, F Khassanov, C Kik & HD Rabinowitch. Garlic (Allium sativum L.) and its wild relatives from Central Asia: evaluation for fertility potential. Acta Hort. 637, 83-91.
• Kamenetsky R, I London Shafir,  H Zemah, A Barzilay & HD Rabinowitch, 2004. Environmental Control of Garlic Growth and Florogenesis. Journal of the American Society for Horticultural Science, 129: 144-151.
• Kamenetsky, R, I London Shafir, F  Khassanov, C Kik, AW van Heusden, M Vrielink-van Ginkel, K Burger-Meijer, J Auger, I Arnault & HD Rabinowitch, 2004. Diversity in fertility potential and organo-sulphur compounds among garlics from Central Asia. Accepted: Biodiversity and Conservation.
• Martín-Urdíroz N, J Garrido, J Martín & X Barandiaran, 2004. Effect of light on the organogenic ability of garlic roots using a one step in vitro system. Plant Cell Reports 22: 721-724.
• Meyer K, E Ueberham & R Gebhardt, 2004. Influence of organosulphur compounds from garlic on the secretion of matrix metalloproteinases and their Inhibitor TIMP-1 by cultured HUVEC cells. Accepted: Cell Biol. Toxicol.
• Tregova A. A molecular analysis of the biosynthetic pathways for the formation of S allycysteine sulphoxide in Allium sativum L. PhD thesis University of Liverpool, UK.
• Zheng SJ, B Henken, YK Ahn, FA Krens & C Kik. The development of a reproducible Agrobacterium tumefaciens transformation system for garlic (Allium sativum L.) and the production of transgenic garlic resistant to beet armyworm (Spodoptera exigua Hübner). Accepted: Molecular Breeding.
• Zheng SJ, B Henken, FA Krens & C Kik. Gene transfer in Allium: recent developments and future prospects. Accepted: Acta Hort.
• Zheng SJ, B Henken, FA Krens, &C Kik. Genetic transformation of onion and shallot (Allium cepa L.). In: " Transgenic Crops of the World". Ian Curtis Ed. Kluwer Academic Publishers (accepted).
• Zheng SJ, B Henken, RA de Maagd, A Purwito, FA Krens & C Kik. Transgenic Bt-shallots (Allium cepa L.) resistant to beet armyworm (Spodoptera exigua Hübner). Accepted: Transgenic Research.

Submitted/ In preparation

Submitted:

• Belloir C, MH Siess, C Daurat &  AM le Bon. Protective effects of garlic sulfur compounds against DNA damage induced by direct- and indirect-acting genotoxic agents in HepG2 cells. Submitted: Mutation Research.
• Chevalier J, MH Siess, E Semon & C Teyssier. Metabolism of sulphur components of garlic after a single oral administration to rats. Submitted:  Xenobiotica
• Fereol L, V Chovelon, S Causse, D Triaire, N Michaux-Ferriere & R Kahane. Establishment of embryogenic cell suspensions cultures of garlic (Allium sativum L.), plant regeneration and biochemical analyses. Submitted: Plant Science.
• Fereol L, V Chovelon, S Causse &  R Kahane. Embryogenic cell suspension cultures of garlic (Allium sativum L.) as method for mass propagation and convenient material for genetic improvement. Submitted: In vitro Cell Dev. Biol.
• Garrido-Gala J, N Martín-Urdíroz, J Martín &  X Barandiaran. Improvement of Garlic (Allium sativum L.) micropropagation and biolistic transformation through basal plate culture. Submitted: Plant Cell Reports.
• Gebhardt R. Sensitive in vitro inhibition of cholesterol biosynthesis by diallyl disulfide and related garlic compounds. Submitted: J Pharmacol. Exp. Therap.
• Huchette O, R Kahane, C Bellamy, J Auger, I Arnault. Environment versus genotype as factors affecting the sulphur compounds content of garlic bulbs. Submitted: Environmental and Experimental Botany.
• Martín-Urdíroz N, J Garrido-Gala, J Martín &  X Barandiaran. Effects of Flurprimidol on the organogenic ability of garlic root-tips using a one step in vitro system.  Submitted: Plant Cell Reports.

Oral presentations

2001

• Kik C, R Kahane & R Gebhardt, 2001. Garlic & Health: a European initiative for the development of high quality garlic and its influence on biomarkers of atherosclerosis and cancer in humans for disease prevention. HEALFO Conference, Lanciano, Italy.
• Thomas B, 2001. Interview concerning the G&H project on BBC radio. http://news.bbc.co.uk/hi/english/health/newsid_784000/78361.stm

2002

• Barandiaran X, 2002. The Garlic & Health European Project. Garlic Technical and Marketing Seminars. Córdoba, Spain.
• Gebhardt R, 2002. Differential effects of garlic and garlic compounds on biosynthesis and serum levels of cholesterol and lipids. NIH workshop on 'Mechanistic studies of cardiovascular effects of botanicals', Bethesda, MD, USA.
• Kamenetsky R, I London Shafir, M Baizerman, F Khassanov, C Kik & HD Rabinowitch, 2002. Garlic (Allium sativum L.) and its wild relatives from Central Asia: evaluation for fertility potential. XXVIth International Horticultural Congress, Toronto, Canada.
• Kik C, 2002. Garlic & Health: an EU project on the interface between plant genetics and human health. Colloquium Facultad de Agronomia, Universidad de Republica, Montevideo, Uruguay.
• Meyer K, F Struck, J Salveter, D Reisig & R Gebhardt, 2002. Influence of garlic-derived organo-sulphur compounds on the secretion of matrix-metalloproteinases by vascular endothelial cells. Abstract GA-Meeting (Gesellschaft für Arzneipflanzenforschung). Erlangen, Germany.
• Meyer K, D Kellert, F Struck & R Gebhardt, 2002. Diallyl disulfide (DADS) reduces the secretion of matrix metalloproteinases by cultured HUVEC cells. Abstract annual meeting of the Gesellschaft für Molekularbiologie and Biochemie. Biological Chemistry 382 (supplement), S166. Bochum, Germany.

2003

• Kamenetsky R, 2003. Fertility restoration in garlic Allium sativum L. EU project “Garlic and Health”. Special seminar in ARO, The Volcani Center, Israel.
• Kamenetsky R, 2003. Flowering physiology and fertility restoration in garlic Allium sativum L. Special seminar at the University of Guelph, Canada.
• Le Bon AM. & MH Siess, 2003. Anticarcinogenic and antigenotoxic properties of Allium vegetables and their organosulfur constituents. 6th Winters Research Conferences on Free Radicals. Les Houches, France.
• Siess MH, 2003. Rôle de l’ail dans la prévention des cancers. Annual Meeting of French Dieticians, Menton France.

2004

• Collin HA, J Hughes, A Tregova, G van der Werff, M Wilkinson, R Cosstick, L Trueman, T Crowther, L. Brown, MG Jones, B Thomas & AB Tomsett, 2004. Sulfur biochemistry of garlic: the biosynthesis of flavour precursors. ISHS Allium symposium, Beijing, PR China.
• Fereol L, V Chovelon, S Causse & R Kahane, 2004. Embryogenic cell suspension cultures of garlic (Allium sativum L.) as a method for mass propagation and convenient material for genetic improvement. ISHS Allium symposium, Beijing, PR China.
• Gebhardt R, V Dirsch, S Espirito Santos, HP Keiß, K Meyer, S Zellmer, J Auger, Th Haffner, H Princen & AM Vollmar, 2004. Effects of high quality garlic on markers of arteriosclerosis and inflammation in vitro and in vivo. ISHS Allium symposium, Beijing, PR China.
• Huchette O, R Kahane, J. Auger, I Arnault & C Bellamy, 2004. Influence of environmental and genetic factors on the alliin content of garlic bulbs. ISHS Allium symposium, Beijing, PR China.
• Jones M, Hughes JM, Tregova A, Milne JGC, AB Tomsett and HA Collin, 2004. A molecular analysis of the biosynthesis of flavour precursors in garlic. Society for Experimental Biology, Annual main meeting, Edinburgh, UK.
• Kamenetsky R, I London Shafir, F Khassanov , C Kik, J Auger, B Thomas & HD Rabinowitch, 2004. Garlic from Central Asia: genetic resources and fertility potential. ISHS Allium symposium, Beijing, PR China.
• Kik C, 2004. Alliums and Health. ISHS Allium symposium, Beijing, PR China.
• Zheng SJ, 2004. Gene transfer in Allium: recent developments and future prospects. ISHS Allium symposium, Beijing, PR China.

Posters

2000

• The G&H consortium, 2000. Garlic & Health. ISHS Allium symposium, Athens, Georgia, USA.

2001

• Keiss HP, VM Dirsch, T Hartung & AM Vollmar, 2001. Extracts from garlic dry powders modulate LPS-induced liberation of cytokines. The "43. Frühjahrstagung der DGPT". German association of pharmacology and toxicology. Mainz, Germany.
• Kik C, R Kahane & R Gebhardt, 2001. Garlic & Health: a European initiative for the development of high quality garlic and its influence on biomarkers of atherosclerosis and cancer in humans for disease prevention. Symposium on Human Nutrigenomics, Wageningen, the Netherlands and HEALFO symposium, Lanciano, Italy
• Germain E, J Chevalier, M Steib, MH Siess & C Teyssier, 2001. In vitro and ex vivo metabolism of diallyl disulfide, a characteristic sulfur compound of garlic, in rat. VI international ISSX meeting; Muenchen, Germany.

2002

• Belloir C,  MH Siess, C Daurat & AM le Bon, 2002. Un constituant de l’ail , le disulfure de diallyle, et ses métabolites inhibent la génotoxicité de divers agents cancérogènes dans une lignée cellulaire humaine. 3th annual meeting of the french network NACRe (Nutrition and Cancer network), Dijon, France.
• Christidès JP, I Arnault, T Doussineau, N Mandon, Th Haffner, R Kahane & J Auger, 2002. Ion-pair HPLC method for simultaneous analysis of alliin, allicin and dipeptide precursors in garlic products using MSn and UV. Congress for Hypenated Technologies in Chromatography, HTC 7, Bruges, Belgium.
• Germain E, J Chevalier, M Steib, MH Siess & C Teyssier, 2002. Metabolism of diallyl disulfide, a naturally occurring component of garlic, in the rat. Third annual meeting of the French network NACRe (Nutrition and Cancer network), Dijon, France.
• Keiss HP, VM Dirsch, Th Hartung &  AM Vollmar, 2002. Extracts from garlic dry powders modulate LPS-induced liberation of cytokines. Frühjahrstagung der Deutschen Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, Mainz.

2003

• Bergès R, MF Pinnert, MF Vernevaut, C Vaudelin & MH Siess, 2003. Evaluation des potentialités anticancérogènes de l’ail déshydraté. 4th annual meeting of the French network NACRe (Nutrition and Cancer network). Paris, France.
• Belloir C, MH Siess, C Daurat & AM le Bon, 2003. Evaluation of the antigenotoxic potential of garlic sulfur compounds in HepG2 cells. Eighth international conference on mechanisms of antimutagenesis and anticarcinogenesis, Pisa, Italy.
• Tregova A, J. Hughes, HA Collin, MG Jones & AB Tomsett, 2003.Molecular analysis of cysteine synthase and allylcysteine synthase from garlic and their contribution to garlic flavour precursor biosynthesis. Seventh International Congress of Plant Molecular Biology, Barcelona, Spain.

2004

• Espirito Santo SMS, BJM Van Vlijmen, W van Duyvenvoorde, EH Offerman, LM Havekes, I Arnault, J Auger & HMG Princen. 2004. Absence of an atheroprotective and anti-inflammatory effect of garlic in APOE*3-Leiden transgenic mice. Dutch Atherosclerosis Society symposium, Ermelo, The Netherlands.
• Gebhardt R,  V Dirsch, SMS Espirito Santo, H-P Keiß, K Meyer, S Zellmer, J Auger, Th Haffner, H Princen &  AM Vollmar, 2004. Garlic & Health: Effects of high quality garlic on markers of arteriosclerosis and inflammation in vitro and in vivo. Fourth ISHS on Edible Alliaceae, Beijing, PR China.
• Kik C, R Kahane & R Gebhardt, 2004 Garlic & Health: the development of high quality garlic and its influence on biomarkers of atherosclerosis and cancer in humans for disease prevention. Fourth ISHS on Edible Alliaceae, Beijing, PR China.
• Le Bon AM, R Bergès, L Guénot, MF Pinnert, V Singh, MF Vernevaut & MH Siess, 2004. Garlic & Health: Mechanisms of action of garlic and its sulfur components on carcinogenesis. Fourth ISHS on Edible Alliaceae, Beijing, PR China.
• Princen HMG, SMS Espirito Santo, W van Duyvenvoorde, EH Offerman, LM Havekes, I Arnault, J Auger & BJM van Vlijmen, 2004. Absence of an atheroprotective and anti-inflammatory effect of garlic in APOE*3-Leiden transgenic mice. XV International Symposium on Drugs Affecting Lipid Metabolism, Venice, Italy.
• Le Bon AM, C Belloir, V Singh, R Bergès, L Guénot, MF Pinnert, MF Vernevaut & MH Siess, 2004. Anticarcinogenic properties of garlic and its sulfur components in the rat and in human cells. 7th Int. Symposium on Predictive Oncology and Intervention Strategies, Nice, France.
• Thomas B, L Trueman, L Brown, B Smith, A  Tregova, J  Hughes, J Milne, M Jones, B Tomsett, M Wilkinson, H Collin, O Huchette, R Kahane, J Auger, I Arnault, X Barandiaran, J Martin Sanchez & V Chovelon, 2004. Garlic and Health: Cultivation and sulfur biochemistry of garlic. Fourth ISHS on Edible Alliaceae, Beijing, PR China.
• Zheng SJ, R Kamenetsky, HD Rabinowitch, L Fereol, X Barandiaran & C  Kik. 2004. Garlic & Health: Fertility restoration, genetic transformation and mass propagation. Fourth ISHS on Edible Alliaceae, Beijing, PR China.

Web publications

1. Garlic & Health home page: http://www.plant.wur.nl/projects/garlicandhealth
2. http://rivierafitness.fitdv.com/new/articles/article.html?artid=390
3. via the FLAIR-FLOW initiative:
   1. Heart disease and cancer: is garlic the answer? (October 2002): http://www.flair-flow.com/health-docs/ffe55202.html
   2. Putting garlic through the press (October 2002): http://www.flair-flow.com/consumer-docs/ffe55502.html
4. via Chemistry Webmagazine 2004: http://www.reactivereports.com/39/39_1.html

Partners

Subcontractors

Project co-ordination

Dr. C. Kik
Overall co-ordination

Dr. R. Kahane
Research leader Plant

Prof. Dr. R. Gebhardt
Research leader Health

EU scientific officers

Dr. L. Breslin
e-mail: Liam.Breslin@cec.eu.int

Dr. R. D'Amario
e-mail: Rosanna.D'Amario@cec.eu.int 
European Commission
DG RTD, unit E-2
Square de Meeus 8
B-1050 Brussels
Belgium

More information

Dr. Chris Kik
Plant Research International
Wageningen University & Research Center
P.O. Box 16
6700 AA Wageningen
The Netherlands
tel.: +31 317 47 72 78/ 47 70 01
fax: +31 317 41 80 94
e-mail: chris.kik@wur.nl