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{{Short description|Extract derived from grapefruit seeds}}
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'''Grapefruit seed extract''' (GSE), also known as '''citrus seed extract''', is a liquid [[extract]] derived from the [[seed]]s, [[citrus#Uses|pulp]], and [[juice vesicles|white membranes]] of [[grapefruit]].<ref name=Pharmazie/> Self-made natural GSE processed in the laboratory without synthetic agents is prepared by grinding the grapefruit seed and juiceless pulp, then mixing with glycerin.<ref name=Pharmazie/> Commercially available GSE sold to consumers are made from the seed, pulp, glycerin (and in some cases synthetic preservatives) all blended together.<ref name=Pharmazie/> Grapefruit seed extract is sold as a [[dietary supplement|food supplement]] and used in [[cosmetics]] because it is a claimed natural [[antimicrobial]].<ref name=Preservatives/>
{{distinguish|grape seed extract}}
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'''Grapefruit seed extract''' (GSE), also known as '''citrus seed extract''', is a liquid [[extract]] derived from the [[seed]]s, [[citrus#Uses|pulp]], and [[juice vesicles|white membranes]] of [[grapefruit]].<ref name=Pharmazie/> GSE is prepared by grinding the grapefruit seed and juiceless pulp, then mixing with [[glycerin]].<ref name=Pharmazie/> Commercially available GSEs sold to consumers are made from the seed, pulp, and glycerin blended together.<ref name=Pharmazie/> GSE is sold as a [[dietary supplement]] and is used in [[cosmetics]].<ref name=Preservatives/>


== Grapefruit history ==
An early proponent was Dr. Jacob Harich (1919&ndash;1996).<ref name="E-Book"/> A long time promoter of GSE was [[Aubrey Hampton]], the founder of Aubrey Organics.<ref name="Happi"/> Some marketers of GSE affirm this extract to be a safe, natural, and effective preservative.<ref name=Contamination/> This [[herbal extract|extract]] has been stated by some practitioners of [[alternative medicine]] to possess [[antiseptic|antibacterial]], [[antiviral drug|antiviral]], and [[antifungal drug|antifungal]] properties.<ref name="E-Book"/> It has been recommended by some [[nutritionist]]s for the treatment of [[candidiasis]], [[otalgia|earache]], throat infections, and [[diarrhea]].<ref name="E-Book"/> GSE is promoted at [[health food store|health food shops]] and on the [[internet]].<ref name=Adulteration/><ref name="preservative_compounds"/>


⚫
The grapefruit is a subtropical [[citrus]] [[tree]] grown for its [[fruit]] which was originally named the "[[forbidden fruit]]" of [[Barbados]].<ref name="Forbidden_Fruit">{{cite book |author1=Dowling, Curtis F. |author2=Morton, Julia Frances |title=Fruits of warm climates |publisher=J.F. Morton |location=Miami, Fla |year=1987 |pages=152–8 |isbn=978-0-9610184-1-2|url=http://www.hort.purdue.edu/newcrop/morton/grapefruit.html}}</ref> The fruit was first documented in 1750 by Rev. [[Griffith Hughes]] when describing specimens from Barbados.<ref name="Q_A:Grapefruit">Michael Quinion. [http://www.worldwidewords.org/qa/qa-gra3.htm World Wide Words: Questions & Answers; Grapefruit]. 2009.</ref> All parts of the fruit can be used. The fruit is mainly consumed for its tangy [[juice]].<ref name="Citrus_Juice">{{cite journal |vauthors=Fellers PJ, Nikdel S, Lee HS |title=Nutrient content and nutrition labeling of several processed Florida citrus juice products |journal=J Am Diet Assoc |volume=90 |issue=8 |pages=1079–84 |date=August 1990 |doi=10.1016/S0002-8223(21)01704-1 |pmid=2380455 |s2cid=25833812 }}</ref> The peel can be processed into [[aromatherapy]] [[oil]]s<ref name=Valerie>{{cite book |author=Worwood, Valerie Ann |title=The complete book of essential oils and aromatherapy |publisher=New World Library |location=Novato, Calif |year=1991 |isbn=978-0-931432-82-8 |url-access=registration |url=https://archive.org/details/completebookofes00worw }}</ref> and is also a source of [[dietary fiber]].<ref name="Pectin_Benefits">{{cite journal |vauthors=Cerda JJ, Robbins FL, Burgin CW, Baumgartner TG, Rice RW |title=The effects of grapefruit pectin on patients at risk for coronary heart disease without altering diet or lifestyle |journal=Clin Cardiol |volume=11 |issue=9 |pages=589–94 |date=September 1988 |pmid=3229016 |doi=10.1002/clc.4960110902 |s2cid=45520617 |doi-access=free }}</ref> The seed and pulp, as [[byproduct]]s of the juice industry, are retrieved for GSE processing<ref name="gravura">{{cite web|author1=Scott Gravura|date=10 March 2016|title=Not natural, not safe: Grapefruit seed extract|url=https://sciencebasedmedicine.org/not-natural-not-safe-grapefruit-seed-extract/|accessdate=17 November 2018|publisher=Science-based Medicine}}</ref> or sold as [[Cattle feeding|cattle feed]].<ref name="Cattle_Feed">{{cite journal |vauthors=Arthington JD, Kunkle WE, Martin AM |title=Citrus pulp for cattle |journal=Vet. Clin. North Am. Food Anim. Pract. |volume=18 |issue=2 |pages=317–26, vii |date=July 2002 |pmid=12235663 |doi=10.1016/S0749-0720(02)00023-3 }}</ref>
There are conflicting scientific demonstrations of the efficacy of GSE.<ref name=Pharmazie/> Suspicions about the true nature of the active compounds in GSEs arose when synthetic additives were found in commercial products.<ref name=Preservatives/> Suspected counterfeit grapefruit seed extracts were adulterated with [[chemical synthesis|synthetic]] [[preservative]]s.<ref name="Pharmazie_2007"/><ref name="synthetic_disinfectants"/><ref name="counterfeit_products"/> When preservatives were not present in some of the extracts, laboratory tests found the natural extracts had no natural antimicrobial attributes of their own.<ref name=Contamination/> Some manufacturers of GSE have stated that their extract has compounds nearly identical to benzethonium chloride, but a 2001 study supervised by [[chemist]] G. Takeoka has documented that commercial GSE preparations contain the synthetic compound [[benzethonium chloride]] that could not have been made from GSE.<ref name=Contamination/>

== History ==

⚫
The grapefruit is a subtropical [[citrus]] [[tree]] grown for its [[fruit]] which was originally named the "[[forbidden fruit]]" of [[Barbados]].<ref name="Forbidden_Fruit">{{cite book |author1=Dowling, Curtis F. |author2=Morton, Julia Frances |title=Fruits of warm climates |publisher=J.F. Morton |location=Miami, Fla |year=1987 |pages=152–8 |isbn=0-9610184-1-0|url=http://www.hort.purdue.edu/newcrop/morton/grapefruit.html}}</ref> The fruit was first documented in 1750 by Rev. [[Griffith Hughes]] when describing specimens from Barbados.<ref name="Q_A:Grapefruit">Michael Quinion. [http://www.worldwidewords.org/qa/qa-gra3.htm World Wide Words: Questions & Answers; Grapefruit]. 2009.</ref> All parts of the fruit can be used. The fruit is mainly consumed for its tangy [[juice]].<ref name="Citrus_Juice">{{cite journal |vauthors=Fellers PJ, Nikdel S, Lee HS |title=Nutrient content and nutrition labeling of several processed Florida citrus juice products |journal=J Am Diet Assoc |volume=90 |issue=8 |pages=1079–84 |date=August 1990 |pmid=2380455 }}</ref> The peel can be processed into [[aromatherapy]] [[Oil|oils]]<ref name=Valerie>{{cite book |author=Worwood, Valerie Ann |title=The complete book of essential oils and aromatherapy |publisher=New World Library |location=Novato, Calif |year=1991 |isbn=0-931432-82-0 }}</ref> and is also a source of [[dietary fiber]].<ref name="Pectin_Benefits">{{cite journal |vauthors=Cerda JJ, Robbins FL, Burgin CW, Baumgartner TG, Rice RW |title=The effects of grapefruit pectin on patients at risk for coronary heart disease without altering diet or lifestyle |journal=Clin Cardiol |volume=11 |issue=9 |pages=589–94 |date=September 1988 |pmid=3229016 |doi=10.1002/clc.4960110902 }}</ref> The seed and pulp, as by-products of the juice industry, are sold as cattle feed.<ref name="Cattle_Feed">{{cite journal |vauthors=Arthington JD, Kunkle WE, Martin AM |title=Citrus pulp for cattle |journal=Vet. Clin. North Am. Food Anim. Pract. |volume=18 |issue=2 |pages=317–26, vii |date=July 2002 |pmid=12235663 |doi=10.1016/S0749-0720(02)00023-3 }}</ref> Another application of the seed is in the production of grapefruit seed extract <ref name=Pharmazie/> Aubrey Hampton, founder of Aubrey Organics, has promoted citrus seed extract as a component of "Aubrey’s Preservative" for more than 25 years.<ref name="Happi">Melissa Meisel. [http://www.happi.com/contents/view_features/2007-05-29/cosmetics-go-green/ Cosmetics Go Green]. Happi, Rodman Publishing, June 2007.</ref> Today, GSE is mostly promoted at [[health food store|health food shops]] and on the [[internet]].<ref name=Adulteration/><ref name="preservative_compounds"/>


== Efficacy ==
== Efficacy ==


Anecdotal claims for an antimicrobial effect are based on abstract scientific experiments which show some antimicrobial activity in commercial grapefruit seed extracts and ethanol grapefruit seed extract but not natural GSE.<ref name=BrandStudy>{{cite journal |vauthors=Reagor L, Gusman J, McCoy L, Carino E, Heggers JP |title=The effectiveness of processed grapefruit-seed extract as an antibacterial agent: I. An in vitro agar assay |journal=J Altern Complement Med |volume=8 |issue=3 |pages=325–32 |date=June 2002 |pmid=12165190 |doi=10.1089/10755530260128014 }}</ref><ref name=BrandTest>{{cite journal |vauthors=Heggers JP, Cottingham J, Gusman J, etal |title=The effectiveness of processed grapefruit-seed extract as an antibacterial agent: II. Mechanism of action and in vitro toxicity |journal=J Altern Complement Med |volume=8 |issue=3 |pages=333–40 |date=June 2002 |pmid=12165191 |doi=10.1089/10755530260128023 }}</ref><ref name=EthanolGSE>{{cite journal |author=Cvetni&#x107; Z, Vladimir-Knezevi&#x107; S |title=Antimicrobial activity of grapefruit seed and pulp ethanolic extract |journal=Acta Pharm |volume=54 |issue=3 |pages=243–50 |date=September 2004 |pmid=15610620 }}</ref> The preliminary studies for the antimicrobial effect state that the Citricidal commercial brand of GSE was used for testing.<ref name=BrandStudy/><ref name=BrandTest/> There is considerable scientific evidence that the anti-microbial activity associated with grapefruit seed extract can be attributed to the contamination or adulteration of commercial GSE preparations with synthetic antimicrobials or preservatives.<ref name=Preservatives>{{cite journal |vauthors=Ganzera M, Aberham A, Stuppner H |title=Development and validation of an HPLC/UV/MS method for simultaneous determination of 18 preservatives in grapefruit seed extract |journal=J. Agric. Food Chem. |volume=54 |issue=11 |pages=3768–72 |date=May 2006 |pmid=16719494 |doi=10.1021/jf060543d }}</ref> According to a 2001 study, branded commercial GSE preparations were contaminated with synthetic [[benzethonium chloride]] that was unlikely to have been made from grapefruit seeds.<ref name=Contamination>{{cite journal |vauthors=Takeoka G, Dao L, Wong RY, Lundin R, Mahoney N |title=Identification of benzethonium chloride in commercial grapefruit seed extracts |journal=J. Agric. Food Chem. |volume=49 |issue=7 |pages=3316–20 |date=July 2001 |pmid=11453769 |doi=10.1021/jf010222w }}</ref> Some of the marketers claimed that their product did not contain benzethonium chloride and the error was due to the similarity in [[molecular mass|molecular weight]] of the [[quaternary ammonium cation|quaternary ammonium compound]] which was formed through a proprietary manufacturing process.<ref name=Contamination/> It is highly improbable that the preservative benzethonium chloride is formed during any extraction and/or processing of grapefruit seeds and pulp.<ref name=Contamination/> Researchers conclusively demonstrated the presence of benzethonium chloride in commercial GSE using various [[analytical chemistry|analytical methods]] including [[High-performance liquid chromatography|HPLC]], one- and two-dimensional [[Nuclear magnetic resonance|NMR]], [[Particle-induced X-ray emission|PIXE]] analysis, and electrospray ionization [[mass spectrometry|MS]].<ref name=Contamination/> Another in vitro study claimed GSE had antibacterial properties.<ref name=EthanolGSE/> As with the branded in vitro test<ref name=BrandStudy/><ref name=BrandTest/> this extract was contaminated.<ref name=Contamination/> The ethanolic grapefruit seed and pulp extract tested was prepared or contaminated with ethanol, a chemical solvent used in the extraction process.<ref name=EthanolGSE/> [[Ethanol]], also known as ethyl alcohol, is effective in inhibiting bacteria.<ref name="Ethanol_Alcohol_Effectiveness">{{cite journal |vauthors=Kampf G, Kramer A |title=Epidemiologic Background of Hand Hygiene and Evaluation of the Most Important Agents for Scrubs and Rubs |journal=Clin. Microbiol. Rev. |volume=17 |issue=4 |pages=863–93, table of contents |date=October 2004 |pmid=15489352 |pmc=523567 |doi=10.1128/CMR.17.4.863-893.2004 }}</ref>
Despite [[health claim|claims]] that GSE has [[antimicrobial]] effects,<ref name=EthanolGSE>{{cite journal |author=Cvetnić Z, Vladimir-Knezević S |title=Antimicrobial activity of grapefruit seed and pulp ethanolic extract |journal=Acta Pharm |volume=54 |issue=3 |pages=243–50 |date=September 2004 |pmid=15610620 }}</ref> there is no scientific evidence that GSE has such properties.<ref name="drugs">{{cite web|date=15 January 2018|title=Grapefruit|url=https://www.drugs.com/npp/grapefruit.html|accessdate=17 November 2018|publisher=Drugs.com}}</ref><ref name=gravura/> Some evidence indicates that the suspected antimicrobial activity of GSE was due to the contamination or adulteration of commercial GSE preparations with synthetic antimicrobials or [[Preservative|preservatives]].<ref name=Pharmazie>{{cite journal |vauthors=von Woedtke T, Schlüter B, Pflegel P, Lindequist U, Jülich WD |title=Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained |journal=Pharmazie |volume=54 |issue=6 |pages=452–6 |date=June 1999 |pmid=10399191 }}</ref><ref name=Preservatives>{{cite journal |vauthors=Ganzera M, Aberham A, Stuppner H |title=Development and validation of an HPLC/UV/MS method for simultaneous determination of 18 preservatives in grapefruit seed extract |journal=J. Agric. Food Chem. |volume=54 |issue=11 |pages=3768–72 |date=May 2006 |pmid=16719494 |doi=10.1021/jf060543d }}</ref><ref name=Adulteration>{{cite journal |vauthors=Takeoka GR, Dao LT, Wong RY, Harden LA |title=Identification of benzalkonium chloride in commercial grapefruit seed extracts |journal=J. Agric. Food Chem. |volume=53 |issue=19 |pages=7630–6 |date=September 2005 |pmid=16159196 |doi=10.1021/jf0514064 }}</ref> These chemicals were not present in grapefruit seed extracts prepared in the [[laboratory]], and GSE preparations without the contaminants were found to possess no detectable antimicrobial effect.<ref name=Pharmazie/> Although citrus seed extract is sold in [[Health food store|health food markets]],<ref name=Adulteration/> there is no good evidence for any antimicrobial activity.<ref name=Pharmazie/>


== Phytochemicals ==
Independent studies have shown some commercial preparations to contain the compound [[benzalkonium chloride]], which is a synthetic antimicrobial commonly used in disinfectants and cleaning products, the related compound benzethonium chloride, the antibiotic [[triclosan]], or the preservative [[paraben|methylparaben]].<ref name=Pharmazie>{{cite journal |vauthors=von Woedtke T, Schlüter B, Pflegel P, Lindequist U, Jülich WD |title=Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained |journal=Pharmazie |volume=54 |issue=6 |pages=452–6 |date=June 1999 |pmid=10399191 }}</ref><ref name=Adulteration>{{cite journal |vauthors=Takeoka GR, Dao LT, Wong RY, Harden LA |title=Identification of benzalkonium chloride in commercial grapefruit seed extracts |journal=J. Agric. Food Chem. |volume=53 |issue=19 |pages=7630–6 |date=September 2005 |pmid=16159196 |doi=10.1021/jf0514064 }}</ref><ref name=Study>{{cite journal |vauthors=Sakamoto S, Sato K, Maitani T, Yamada T |title=[Analysis of components in natural food additive "grapefruit seed extract" by HPLC and LC/MS] |language=Japanese |journal=Eisei Shikenjo Hokoku |volume= |issue=114 |pages=38–42 |year=1996 |pmid=9037863 }}</ref> Some samples were shown to contain up to 22% benzalkonium chloride by weight, despite the known [[allergy|allergenicity]]<ref name=Alergenicity>{{cite journal |vauthors=Chiambaretta F, Pouliquen P, Rigal D |title=[Allergy and preservatives. Apropos of 3 cases of allergy to benzalkonium chloride] |language=French |journal=J Fr Ophtalmol |volume=20 |issue=1 |pages=8–16 |year=1997 |pmid=9099278 }}</ref> and [[toxicity]]<ref name=Toxicity>{{cite journal |vauthors=Liu H, Routley I, Teichmann KD |title=Toxic endothelial cell destruction from intraocular benzalkonium chloride |journal=J Cataract Refract Surg |volume=27 |issue=11 |pages=1746–50 |date=November 2001 |pmid=11709246 |doi=10.1016/S0886-3350(01)01067-7 }}
</ref> of the compound at higher doses.<ref name=Adulteration/> These chemicals were not present in grapefruit seed extracts prepared in the [[laboratory]], and GSE preparations without the contaminants were found to possess no detectable antimicrobial effect.<ref name=Pharmazie/> Although citrus seed extract is sold in health food markets,<ref name=Adulteration/> there is no good evidence for any natural antimicrobial activity.<ref name=Pharmazie/><ref name="preservative_compounds"/>


Analysis shows the [[phytochemical]]s of the seed extract and pulp are [[flavonoids]],<ref name=Drewnowski>{{cite journal |vauthors=Drewnowski A, Gomez-Carneors C |title=Bitter taste, phytonutrients, and consumer: a review |journal=Am. J. Clin. Nutr. |volume=72 |pages=1424–35 |year=2000 |pmid=11101467 |issue=6 |doi=10.1093/ajcn/72.6.1424 |doi-access=free }}</ref><ref name=Tirillini>{{cite journal |author=Tirillini B |title= Grapefruit: the last decade acquisitions |journal=Fitoterapia |volume=71 |pages=29–37 |year=2000 |doi=10.1016/S0367-326X(00)00176-3 |pmid=10930710}}</ref> [[ascorbic acid]] ([[vitamin C]]), [[tocopherol]]s, [[citric acid]], [[limonoid]]s,<ref name="Glucosides_Of_Acidic_Limonoids">{{cite journal |vauthors=Bennett RD, Hasegava S, Herman Z |title=Glucosides of acidic limonoids in citrus |journal=Phytochemistry |volume=28 |pages=2777–81 |year=1989 |doi=10.1016/S0031-9422(00)98087-7 |issue=10 |bibcode=1989PChem..28.2777B |url=https://zenodo.org/record/1259689 }}</ref><ref name="Limonoide_Glucosides">{{cite journal |author=Ohta H, Fong CH, Berhow M, Hesegawa |title=Thin-layer and high-performance liquid chromatographic analyses of limonoids and limonoid glucosides in citrus seeds |journal=J. Chromatogr. |volume=639 |pages=295–302 |year=1993 |doi=10.1016/0021-9673(93)80266-B |issue=2 |url=https://zenodo.org/record/1253912 }}</ref> [[sterols]], and [[Mineral (nutrient)|minerals]].<ref name=Tushiswilli>{{cite journal |vauthors=Tushiswili LS, Durmishidze SV, Sulaberidze KV |title=Sterols of grapefruit, orange, mandarin pulps (''Citrus paradisi, Citrus sinensis, Citrus unshiu'') |journal=Chemistry of Natural Compounds |volume=18 |pages=445–7 |year=1983 |doi=10.1007/BF00579640 |s2cid=4814220 }}</ref>
A study that examined the antiviral properties of GSE found that GSE had no efficacy as a disinfectant for [[feline calicivirus]] and [[feline panleukopenia|feline parvovirus]].<ref name="Virucidal_Efficacy">{{cite journal |vauthors=Eleraky NZ, Potgieter LN, Kennedy MA |title=Virucidal efficacy of four new disinfectants |journal=J Am Anim Hosp Assoc |volume=38 |issue=3 |pages=231–4 |year=2002 |pmid=12022408 }}</ref>
Grapefruit seed extract has been advocated to be a powerful [[antimicrobial]] with proven activity against [[bacteria]] and [[fungus|fungi]]. However, independent studies have shown the efficacy of grapefruit seed extract as an antimicrobial is not demonstrated. Although citrus seed extract is claimed to be a highly effective plant-based preservative by some [[natural skin care|natural personal care]] manufacturers, studies asserted that the universal antimicrobial benefits associated with GSE are merely from the presence of synthetic [[preservative]]s. [[Nature|Natural]] GSE has no antimicrobial properties.<ref name=Pharmazie/><ref name=Preservatives/> Newer studies found many commercial grapefruit seed extracts contaminated with synthetic preservatives.<ref name="Pharmazie_2007">{{cite journal |vauthors=Avula B, Dentali S, Khan IA |title=Simultaneous identification and quantification by liquid chromatography of benzethonium chloride, methyl paraben and triclosan in commercial products labeled as grapefruit seed extract |journal=Pharmazie |volume=62 |issue=8 |pages=593–6 |date=August 2007 |pmid=17867553 }}</ref><ref name="synthetic_disinfectants">{{cite journal |vauthors=Sugimoto N, Tada A, Kuroyanagi M, etal |title=[Survey of synthetic disinfectants in grapefruit seed extract and its compounded products] |language=Japanese |journal=Shokuhin Eiseigaku Zasshi |volume=49 |issue=1 |pages=56–62 |date=February 2008 |pmid=18344660 |doi=10.3358/shokueishi.49.56 }}</ref><ref name="counterfeit_products">{{cite journal |vauthors=Bekiroglu S, Myrberg O, Ostman K, etal |title=Validation of a quantitative NMR method for suspected counterfeit products exemplified on determination of benzethonium chloride in grapefruit seed extracts |journal=J Pharm Biomed Anal |volume=47 |issue=4–5 |pages=958–61 |date=August 2008 |pmid=18456447 |doi=10.1016/j.jpba.2008.03.021 }}</ref> In a 2007 study the main synthetic antimicrobial agent identified in commercial GSE samples was benzethonium chloride.<ref name="Pharmazie_2007"/> In a 2008 study synthetic disinfectants such as benzethonium or benzalkonium chloride were identified in most of the commercial GSE products.<ref name="synthetic_disinfectants"/> In a 2008 study suspected counterfeit products were determined to contain benzethonium chloride in grapefruit seed extract samples.<ref name="counterfeit_products"/>

== Methodology ==

Grapefruit seed extracts are added to [[cosmetics]], [[dietary supplement|food supplements]], and [[pesticide#Alternatives|pesticides]] for their antimicrobial effect, but suspicions about the true nature of the active compounds in GSEs arose when synthetic additives were found in commercial products.<ref name=Preservatives/> Various [[analytical chemistry|analytical methods]] were developed to determine the constituents or compounds in GSE samples which include [[particle-Induced X-ray Emission|particle-induced x-ray emission]] (PIXE),<ref name=Contamination/> [[electrospray ionization|electrospray ionization mass spectrometry]] (ESI-MS),<ref name=Contamination/> [[high performance liquid chromatography]] (HPLC),<ref name=Preservatives/> [[liquid chromatography-mass spectrometry]] (LC-MS),<ref name="synthetic_disinfectants"/> and [[nuclear magnetic resonance]] (NMR) analysis.<ref name="counterfeit_products"/>

== Properties ==

There is evidence that the extract of citrus grapefruit seed has [[antioxidant]] properties.<ref name=Extract>{{cite journal |vauthors=Armando C, Maythe S, Beatriz NP |title=Antioxidant activity of grapefruit seed extract on vegetable oils |journal=Journal of the Science of Food and Agriculture |volume=77 |issue=4 |pages=463–7 |date=December 1997 |url=http://www3.interscience.wiley.com/cgi-bin/abstract/10007270/ABSTRACT |doi=10.1002/(SICI)1097-0010(199808)77:4<463::AID-JSFA62>3.0.CO;2-1}}</ref><ref name="Antioxidant_Activity">{{cite journal |vauthors=Giamperi L, Fraternale D, Bucchini A, Ricci D |title=Antioxidant activity of Citrus paradisi seeds glyceric extract |journal=Fitoterapia |volume=75 |issue=2 |pages=221–4 |date=March 2004 |pmid=15030930 |doi=10.1016/j.fitote.2003.12.010 }}</ref> Analysis shows the constituents of the seed extract and pulp are [[flavonoids]],<ref name=Drewnowski>{{cite journal |vauthors=Drewnowski A, Gomez-Carneors C |title=Bitter taste, phytonutrients, and consumer: a review |journal=Am. J. Clin. Nutr. |volume=72 |pages=1424–35 |year=2000 |pmid=11101467 |issue=6 }}</ref><ref name=Tirillini>{{cite journal |author=Tirillini B |title= Grapefruit: the last decade acquisitions |journal=Fitoterapia |volume=71 |pages=29–37 |year=2000 |doi=10.1016/S0367-326X(00)00176-3 |pmid=10930710}}</ref> [[ascorbic acid]] (commonly known as [[vitamin C]]),<ref name="Vitamin_C">Andrew W. Saul, Ph.D. [http://www.orthomolecular.org/resources/omns/v02n02.shtml Vitamin C Has Been Known To Fight 30 Major Diseases... For Over 50 Years]. ''Orthomolecular Medicine News Service.'' March 15, 2006.</ref><ref name="ACS_C">[http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Vitamin_C.asp?sitearea=ETO Vitamin C]. ''American Cancer Society.'' 2009.</ref><ref name=WHF>[http://www.whfoods.com/genpage.php?tname=foodspice&dbid=25 The World's Healthiest Foods; Grapefruit]. ''The George Mateljan Foundation.'' 2009.</ref> [[tocopherol]]s, [[citric acid]],<ref name=Extract/> [[limonoid]]s,<ref name="Glucosides_Of_Acidic_Limonoids">{{cite journal |vauthors=Bennett RD, Hasegava S, Herman Z |title=Glucosides of acidic limonoids in citrus |journal=Phytochemistry |volume=28 |pages=2777–81 |year=1989 |doi=10.1016/S0031-9422(00)98087-7 |issue=10 }}</ref><ref name="Limonoide_Glucosides">{{cite journal |author=Ohta H, Fong CH, Berhow M, Hesegawa |title=Thin-layer and high-performance liquid chromatographic analyses of limonoids and limonoid glucosides in citrus seeds |journal=J. Chromatogr. |volume=639 |pages=295–302 |year=1993 |doi=10.1016/0021-9673(93)80266-B |issue=2 }}</ref><ref name=Braddock>{{cite journal |vauthors=Braddock RJ, Bryan CR |title=Extraction parameters and capillary electrophorisis analysis of limonin glucoside and phlorin in citrus products |journal=J. Agric. Food Chem. |volume=49 |pages=5982–8 |year=2001 |doi=10.1021/jf010737n |pmid=11743796 |issue=12 }}</ref> [[sterols]], and [[minerals]].<ref name=Tushiswilli>{{cite journal |vauthors=Tushiswili LS, Durmishidze SV, Sulaberidze KV |title=Sterols of grapefruit, orange, mandarin pulps (''Citrus paradisi, Citrus sinensis, Citrus unshiu'') |journal=Chem. Nat. Comp. |volume=18 |pages=445–7 |year=1983 }}</ref> A study suggests the consumption of the bioactive compounds found in grapefruit seed and pulp may help suppress the development of colon cancer.<ref name=Vanamala>{{cite journal |vauthors=Vanamala J, Leonardi T, Patil BS, etal |title=Suppression of colon carcinogenesis by bioactive compounds in grapefruit |journal=Carcinogenesis |volume=27 |issue=6 |pages=1257–65 |date=June 2006 |pmid=16387741 |doi=10.1093/carcin/bgi318 }}</ref> Another study showed the [[flavonoid]] naringin is an excellent plasma lipid lowering and plasma antioxidant active elevating flavonone.<ref name=Naringin>{{cite journal |vauthors=Gorinstein S, Leontowicz H, Leontowicz M, etal |title=Changes in plasma lipid and antioxidant activity in rats as a result of naringin and red grapefruit supplementation |journal=J. Agric. Food Chem. |volume=53 |issue=8 |pages=3223–8 |date=April 2005 |pmid=15826081 |doi=10.1021/jf058014h }}</ref>


== Preparations ==
== Preparations ==


Self-made pure GSE processed without solvents is prepared by grinding the grapefruit seed and juiceless pulp, then mixing with glycerin.<ref name=Pharmazie/>
GSE is prepared by grinding the grapefruit seed and juiceless pulp, then mixing with glycerin.<ref name=Pharmazie/> Commercially available GSE is made from the seed, pulp, glycerin, and synthetic preservatives all blended together.<ref name=Pharmazie/>


==Health claims and safety concerns==
Commercially available GSE sold to consumers are made from the seed, pulp, glycerin, and synthetic preservatives all blended together.<ref name=Pharmazie/>


Although various health claims for using GSE are marketed in the [[dietary supplement]] industry, there is no [[evidence-based medicine|scientific evidence]] from high-quality [[clinical research]] that it has any health effects, as of 2018.<ref name=gravura/><ref name=drugs/> Phytochemicals in grapefruit seeds, particularly [[ furanocoumarin]]s and flavonoids, may cause [[adverse effect|adverse effects on health]] resulting from [[grapefruit–drug interactions]] that influence the intended therapeutic effects of some 85 [[prescription drug]]s.<ref name=drugs/><ref name="bailey">{{cite journal |last1=Bailey |first1=D. G. |last2=Dresser |first2=G. |last3=Arnold |first3=J. M. O. |title=Grapefruit-medication interactions: Forbidden fruit or avoidable consequences? |journal=Canadian Medical Association Journal |volume=185 |issue=4 |year=2012 |pages=309–316 |doi=10.1503/cmaj.120951 |pmid=23184849 |pmc=3589309}}</ref> The main safety concern about GSE is inhibition of the [[liver]] [[enzyme]], [[cytochrome P450]], which controls liver [[Drug metabolism|metabolism of drugs]]; consequently, its inhibition by GSE unpredictably increases the blood concentrations of prescribed drugs.<ref name=bailey/>
== Precautions ==

Grapefruit can have a [[List of drugs affected by grapefruit|number of interactions]] with certain [[drug]]s, increasing the potency of many compounds,<ref name=NYTimes/> including [[warfarin]] (coumadin).<ref name="artificial_grapefruit_seed_extract"/> Grapefruit has components that inhibit the [[CYP3A4]] enzyme in the intestine.<ref name=NYTimes>Bakalar, Nicholas. [http://www.nytimes.com/2006/03/21/health/21grap.html?ex=1300597200&en=61e834f36b9afac9&ei=5090&partner=rssuserland&emc=rss Experts Reveal the Secret Powers of Grapefruit Juice]. ''The New York Times.'' March 21, 2006.</ref> Thus, it is this effect that increases the rate of absorption of several drugs.<ref name="GSE_Drug_Effect">{{cite journal |vauthors=He K, Iyer KR, Hayes RN, Sinz MW, Woolf TF, Hollenberg PF |title=Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice |journal=Chem. Res. Toxicol. |volume=11 |issue=4 |pages=252–9 |date=April 1998 |pmid=9548795 |doi=10.1021/tx970192k }}</ref> There are concerns about the [[safety]] of ingesting synthetic preservatives found in grapefruit seed extract.<ref name="preservative_compounds"/>

== Controversy ==

GSE usage has been popularized by many companies within the scope of the health food industry.<ref name=Contamination/> There are books exclusively dedicated to GSE.<ref name="E-Book">Sims, Judith. Gale Encyclopedia of Alternative Medicine. Available in e-book format. ''Thomson Gale.'' 2001.</ref><ref name="Healing_Powers">Sharamon, S., Baginski, B.J. The Healing Power of Grapefruit Seed. ''Lotus Press, Wisconsin.'' 1996. ISBN 0-914955-27-6</ref><ref name="GSE_Guide">{{cite book |author=Allan Sachs |title=The authoritative guide to grapefruit seed extract |publisher=LifeRhythm |location=Mendocino, CA |year=1997 |isbn=0-940795-17-5 }}</ref> This extract is promoted by marketers on the internet, there are health food stores that recommend its use, and proponents maintain that it is safe.<ref name=Contamination/><ref name="preservative_compounds">Todd Caldecott. [http://medherb.com/eletter/GSE-Caldecott.pdf Grapefruit Seed Extract]. Medical Herbalism 2005:14(3);1.</ref> Some consumers believe this extract is an effective natural preservative even though multiple scientific studies have concluded that the universal antimicrobial activity is merely from contamination with synthetic antimicrobials.<ref name=Pharmazie/><ref name=Preservatives/><ref name=Contamination/><ref name=Adulteration/><ref name=Study/><ref name="artificial_grapefruit_seed_extract">{{cite journal |vauthors=Brandin H, Myrberg O, Rundlöf T, Arvidsson AK, Brenning G |title=Adverse effects by artificial grapefruit seed extract products in patients on warfarin therapy |journal=Eur. J. Clin. Pharmacol. |volume=63 |issue=6 |pages=565–70 |date=June 2007 |pmid=17468864 |doi=10.1007/s00228-007-0289-1 }}</ref>


== References ==
== References ==
{{reflist|2}}
{{reflist|30em}}

== External links ==
*[http://www.denvernaturopathic.com/news/GSE.html Grapefruit seed extract may owe its antimicrobial action to toxic chemical additives.]
*[http://www.wellvet.com/grapefruitseedextracts.html WellVet Company — Grapefruit Seed Extract: Articles, Conclusions, and References.]
*[http://www.spectroscopynow.com/coi/cda/detail.cda?chId=4&id=13654&type=Feature&page=1 Ecofriendly Pesticides Are Not What They Seem — Article by Steve Down; June 1, 2006.]


[[Category:Antioxidants]]
[[Category:Dietary supplements]]
[[Category:Dietary supplements]]
[[Category:Grapefruit]]
[[Category:Grapefruit]]

Latest revision as of 18:53, 12 July 2024

Not to be confused with grape seed extract.

Grapefruit seed extract (GSE), also known as citrus seed extract, is a liquid extract derived from the seeds, pulp, and white membranes of grapefruit.[1] GSE is prepared by grinding the grapefruit seed and juiceless pulp, then mixing with glycerin.[1] Commercially available GSEs sold to consumers are made from the seed, pulp, and glycerin blended together.[1] GSE is sold as a dietary supplement and is used in cosmetics.[2]

Grapefruit history

[edit]

The grapefruit is a subtropical citrus tree grown for its fruit which was originally named the "forbidden fruit" of Barbados.[3] The fruit was first documented in 1750 by Rev. Griffith Hughes when describing specimens from Barbados.[4] All parts of the fruit can be used. The fruit is mainly consumed for its tangy juice.[5] The peel can be processed into aromatherapy oils[6] and is also a source of dietary fiber.[7] The seed and pulp, as byproducts of the juice industry, are retrieved for GSE processing[8] or sold as cattle feed.[9]

Efficacy

[edit]

Despite claims that GSE has antimicrobial effects,[10] there is no scientific evidence that GSE has such properties.[11][8] Some evidence indicates that the suspected antimicrobial activity of GSE was due to the contamination or adulteration of commercial GSE preparations with synthetic antimicrobials or preservatives.[1][2][12] These chemicals were not present in grapefruit seed extracts prepared in the laboratory, and GSE preparations without the contaminants were found to possess no detectable antimicrobial effect.[1] Although citrus seed extract is sold in health food markets,[12] there is no good evidence for any antimicrobial activity.[1]

Phytochemicals

[edit]

Analysis shows the phytochemicals of the seed extract and pulp are flavonoids,[13][14] ascorbic acid (vitamin C), tocopherols, citric acid, limonoids,[15][16] sterols, and minerals.[17]

Preparations

[edit]

GSE is prepared by grinding the grapefruit seed and juiceless pulp, then mixing with glycerin.[1] Commercially available GSE is made from the seed, pulp, glycerin, and synthetic preservatives all blended together.[1]

Health claims and safety concerns

[edit]

Although various health claims for using GSE are marketed in the dietary supplement industry, there is no scientific evidence from high-quality clinical research that it has any health effects, as of 2018.[8][11] Phytochemicals in grapefruit seeds, particularly furanocoumarins and flavonoids, may cause adverse effects on health resulting from grapefruit–drug interactions that influence the intended therapeutic effects of some 85 prescription drugs.[11][18] The main safety concern about GSE is inhibition of the liver enzyme, cytochrome P450, which controls liver metabolism of drugs; consequently, its inhibition by GSE unpredictably increases the blood concentrations of prescribed drugs.[18]

References

[edit]
  1. ^ a b c d e f g h von Woedtke T, Schlüter B, Pflegel P, Lindequist U, Jülich WD (June 1999). "Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained". Pharmazie. 54 (6): 452–6. PMID 10399191.
  2. ^ a b Ganzera M, Aberham A, Stuppner H (May 2006). "Development and validation of an HPLC/UV/MS method for simultaneous determination of 18 preservatives in grapefruit seed extract". J. Agric. Food Chem. 54 (11): 3768–72. doi:10.1021/jf060543d. PMID 16719494.
  3. ^ Dowling, Curtis F.; Morton, Julia Frances (1987). Fruits of warm climates. Miami, Fla: J.F. Morton. pp. 152–8. ISBN 978-0-9610184-1-2.
  4. ^ Michael Quinion. World Wide Words: Questions & Answers; Grapefruit. 2009.
  5. ^ Fellers PJ, Nikdel S, Lee HS (August 1990). "Nutrient content and nutrition labeling of several processed Florida citrus juice products". J Am Diet Assoc. 90 (8): 1079–84. doi:10.1016/S0002-8223(21)01704-1. PMID 2380455. S2CID 25833812.
  6. ^ Worwood, Valerie Ann (1991). The complete book of essential oils and aromatherapy. Novato, Calif: New World Library. ISBN 978-0-931432-82-8.
  7. ^ Cerda JJ, Robbins FL, Burgin CW, Baumgartner TG, Rice RW (September 1988). "The effects of grapefruit pectin on patients at risk for coronary heart disease without altering diet or lifestyle". Clin Cardiol. 11 (9): 589–94. doi:10.1002/clc.4960110902. PMID 3229016. S2CID 45520617.
  8. ^ a b c Scott Gravura (10 March 2016). "Not natural, not safe: Grapefruit seed extract". Science-based Medicine. Retrieved 17 November 2018.
  9. ^ Arthington JD, Kunkle WE, Martin AM (July 2002). "Citrus pulp for cattle". Vet. Clin. North Am. Food Anim. Pract. 18 (2): 317–26, vii. doi:10.1016/S0749-0720(02)00023-3. PMID 12235663.
  10. ^ Cvetnić Z, Vladimir-Knezević S (September 2004). "Antimicrobial activity of grapefruit seed and pulp ethanolic extract". Acta Pharm. 54 (3): 243–50. PMID 15610620.
  11. ^ a b c "Grapefruit". Drugs.com. 15 January 2018. Retrieved 17 November 2018.
  12. ^ a b Takeoka GR, Dao LT, Wong RY, Harden LA (September 2005). "Identification of benzalkonium chloride in commercial grapefruit seed extracts". J. Agric. Food Chem. 53 (19): 7630–6. doi:10.1021/jf0514064. PMID 16159196.
  13. ^ Drewnowski A, Gomez-Carneors C (2000). "Bitter taste, phytonutrients, and consumer: a review". Am. J. Clin. Nutr. 72 (6): 1424–35. doi:10.1093/ajcn/72.6.1424. PMID 11101467.
  14. ^ Tirillini B (2000). "Grapefruit: the last decade acquisitions". Fitoterapia. 71: 29–37. doi:10.1016/S0367-326X(00)00176-3. PMID 10930710.
  15. ^ Bennett RD, Hasegava S, Herman Z (1989). "Glucosides of acidic limonoids in citrus". Phytochemistry. 28 (10): 2777–81. Bibcode:1989PChem..28.2777B. doi:10.1016/S0031-9422(00)98087-7.
  16. ^ Ohta H, Fong CH, Berhow M, Hesegawa (1993). "Thin-layer and high-performance liquid chromatographic analyses of limonoids and limonoid glucosides in citrus seeds". J. Chromatogr. 639 (2): 295–302. doi:10.1016/0021-9673(93)80266-B.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ Tushiswili LS, Durmishidze SV, Sulaberidze KV (1983). "Sterols of grapefruit, orange, mandarin pulps (Citrus paradisi, Citrus sinensis, Citrus unshiu)". Chemistry of Natural Compounds. 18: 445–7. doi:10.1007/BF00579640. S2CID 4814220.
  18. ^ a b Bailey, D. G.; Dresser, G.; Arnold, J. M. O. (2012). "Grapefruit-medication interactions: Forbidden fruit or avoidable consequences?". Canadian Medical Association Journal. 185 (4): 309–316. doi:10.1503/cmaj.120951. PMC 3589309. PMID 23184849.
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