Grapefruit Seed Extract as an Antimicrobial Agent

By Dónal P. O'Mathúna, BS (Pharm), MA, PhD. Dr. O'Mathúna is Senior Lecturer in Ethics, Decision-Making & Evidence, School of Nursing, Dublin City University, Ireland; he reports no financial relationship to this field of study.

Resistance to antibiotics continues to pose a serious problem in treating infections. While new pharmaceutical agents are being developed, interest in alternative treatments is also growing. Grapefruit seed extract is one commercially available antimicrobial that has attracted considerable attention.1 Manufacturers and other popular resources claim it is safe and effective for internal and external treatment of acne, allergies, athlete's foot, candida, the common cold, cold sores, various infections, sore throat, and thrush.2 It is advertised in particular for women to treat yeast infections like vaginal candidiasis or thrush.

Grapefruit seed extract is sometimes abbreviated as GSE, but so is grape seed extract. The two supplements should be clearly distinguished from one another as their source and uses are completely different.


Grapefruit seed extract is made from the seeds, pulp, and white membranes that remain after grapefruits are pressed to remove their juice. The leftover material was originally fed to cattle and pigs, and it was noticed that these animals seemed to get fewer infections. A number of methods have been used to extract the leftover plant material, but many of them are protected as proprietary information.3 These range from simply soaking the plant material in alcohol or another solvent, to complex processes that include high temperatures and the addition of ammonium chloride and acids.1 The extract was initially used as an environmentally friendly antimicrobial spray for fruit and vegetables.4 However, controlled trials have found it to vary widely in its effectiveness when sprayed on foods.3 After being found to be safe, the extract was marketed as a dietary supplement with a reputation for treating bacterial, viral, and fungal infections in humans.


The extract is known to contain numerous polyphenolic compounds (such as hesperidin and resveratrol) and quaternary ammonium compounds.1 An early study found that a commercial extract was active against 794 strains of bacteria and 93 strains of fungi.5 Another commercial extract was found to be active against 67 biotypes of gram-positive and gram-negative bacteria.1 An alcoholic extract made by the researchers themselves was tested against 20 bacterial strains and 10 yeast strains.6 The extract was active against all microbes in the broth dilution test, but on agar plates the extract was not active against gram-negative bacteria, yet was active against gram-positive bacteria and yeast. A Norwegian commercial extract has more recently been shown to be active against the bacteria causing Lyme disease.7

Mechanism of Action

Electron microscopy of bacteria treated with grapefruit seed extract revealed disrupted bacterial membranes, which is believed to be the extract's mechanism of action.8 This is also the accepted bactericidal mechanism of action for quaternary ammonium salts.2 Quaternary ammonium compounds are a class of compounds that include synthetic antimicrobials like benzethonium chloride and benzalkonium chloride. These are approved as disinfectants and antiseptics for use on hard surfaces and topically on humans.9 They are not approved as food additives in the United States or Europe, although they are in Japan.

Clinical Studies

The only clinical research readily located was published in 1990 and involved a commercial grapefruit seed extract.5 The publication reported two open-label trials involving patients with severe atopic eczema with accompanying gastrointestinal problems. Ten patients took 200 mL of a 0.5% solution twice daily for one month. The researchers reported that the patients had great difficulty taking the oral liquid because of its bitter taste. No significant changes occurred in fecal microflora testing with only two of 10 patients reporting intestinal improvements. The second trial gave 15 patients three 50 mg extract capsules three times daily for one month. The researchers reported significant antimicrobial activity against two pathogenic intestinal microorganisms, slight activity against three other microbes, and none against two others. No statistical analyses were reported. All 15 patients reported subjective improvements in their gastrointestinal symptoms, with no adverse effects.

Problematic Aspects

A serious problem with some commercial grapefruit seed extracts was revealed initially in 1999. Researchers at a German Institute of Pharmacy tested six commercially available grapefruit seed extracts.10 Five of the six products showed strong antimicrobial activity against a range of bacteria, yeast, and other microbes. However, further analysis of these five active samples found they contained between 1.25% and 10% benzethonium chloride. Three of the samples contained 0.012-0.025% triclosan and three contained methyl paraben (both are synthetic antimicrobials). The one sample which contained no benzethonium chloride also showed no antimicrobial activity. The researchers made their own grapefruit seed extract and it had no antimicrobial activity. A subsequent study was conducted to develop methods of easily separating the three synthetic compounds identified above. Of nine commercial grapefruit seed extract products purchased in the United States, seven contained benzethonium chloride (0.3-22%), three contained triclosan (0.01-1.13%), and none contained methyl paraben.11

One manufacturer claimed that what was identified as benzethonium chloride was a different quaternary ammonium compound formed during their extraction process.3 A subsequent analysis by a research laboratory in the U.S. Department of Agriculture found 8% benzethonium chloride in a commercial liquid grapefruit seed extract.3 The compound's identity was confirmed by several independent tests. Even higher concentrations of benzethonium chloride were found in powdered samples, leading the researchers to conclude that the chemical was unlikely to have been formed in such concentrations during extraction or processing of the grapefruit.

The same Department of Agriculture laboratory tested another commercial grapefruit seed extract and found it contained 22% benzalkonium chloride (BAC).2 BAC is a mixture of three closely related synthetic compounds widely used as a disinfectant and sanitizer, but not recommended for internal use. Poisonings have occurred when people have ingested products containing more than 10% BAC, and allergic reactions occur, especially in asthmatic patients.2 The researchers concluded that it was "unlikely" that 22% BAC could have formed during the processing of grapefruit seeds.

Another investigation was conducted into grapefruit seed extracts used in farming as organic antimicrobial sprays.4 Nine products were tested, of which seven contained various synthetic chemicals, most commonly benzethonium chloride. One of the "grapefruit seed extracts" that contained no synthetic antimicrobials also contained no grapefruit extract but was made from three other herbs.

In the most recent analysis published, 41 various products were purchased in Japan.12 These included food additives, cosmetics, dietary supplements, and disinfectant sprays. All but three contained one or more synthetic antimicrobials. One food additive contained 39% benzethonium chloride.

The effects of consuming grapefruit seed extract containing these preservatives are unknown. An investigation was triggered in Sweden when two patients, a married couple, had complications related to warfarin.13 Both patients had been stabilized on warfarin for years without problems. Three days after taking grapefruit seed extract, one patient developed a minor subcutaneous hematoma. Bleeding times were elevated in both patients and returned to normal when the grapefruit seed extract was stopped. The medical team had the grapefruit seed extract analyzed along with two other commercial products. The three samples contained no trace of grapefruit, but consisted of glycerin, water, and benzethonium chloride. An extract prepared from grapefruit seeds by the analytical laboratory contained no benzethonium chloride. Further testing revealed that benzethonium chloride and the commercial extracts were strong inhibitors of the cytochrome P450 enzyme that metabolizes warfarin, as well as many other drugs.


Grapefruit seed extracts have been found to be broad-spectrum antimicrobial agents. However, considerable questions have been raised by independent analyses as to whether this activity is natural or due to adulteration. A number of different synthetic antimicrobial agents have been found in commercial products, sometimes in very large concentrations. Inconsistent findings have also been reported where freshly prepared extracts have sometimes had antimicrobial activity but sometimes have not. Manufacturers consistently deny that their products are deliberately adulterated. However, even if the quaternary ammonium compounds are produced during processing, almost no clinical research has been conducted on these products for human use. The small number of studies using the extract as an agricultural antimicrobial spray have not produced consistent results.


Given the numerous findings of synthetic antimicrobials in grapefruit seed extracts, people should avoid consumption of these products. One of the remarkable features of this saga is that problems like those in Sweden have not been reported more often. This may be because grapefruit seed extract is usually taken after being diluted significantly because of its extremely bitter taste. It may also be possible that people do not suspect that complications with pharmaceuticals could be related to supplements they are taking. Given that some of these synthetic antimicrobials are approved for use in no-rinse hand washes, topical use of grapefruit seed extract on unbroken skin may not be problematic. Whether it prevents transmission of infections remains uncertain.


1. Reagor L, et al. The effectiveness of processed grapefruit-seed extract as an antibacterial agent: I. An in vitro agar assay. J Altern Complement Med 2002; 8:325-332.

2. Takeoka GR, et al. Identification of benzalkonium chloride in commercial grapefruit seed extracts. J Agric Food Chem 2005;53:7630-7636.

3. Takeoka G, et al. Identification of benzethonium chloride in commercial grapefruit seed extracts. J Agric Food Chem 2001;49:3316-3320.

4. Ganzera M, et al. Development and validation of an HPLC/UV/MS method for simultaneous determination of 18 preservatives in grapefruit seed extract. J Agric Food Chem 2006;54:3768-3772.

5. Ionescu G, et al. Oral citrus seed extract in atopic eczema: In vitro and in vivo studies on intestinal microflora. J Orthomol Med 1990;5:155-157.

6. Cvetnic Z, Vladimir-Knezevic S. Antimicrobial activity of grapefruit seed and pulp ethanolic extract. Acta Pharm 2004;54:243-250.

7. Brorson O, Brorson SH. Grapefruit seed extract is a powerful in vitro agent against motile and cystic forms of Borrelia burgdorferi sensu lato. Infection 2007;35: 206-208.

8. Heggers JP, et al. The effectiveness of processed grapefruit-seed extract as an antibacterial agent: II. Mechanism of action and in vitro toxicity. J Altern Complement Med 2002;8:333-340.

9. Mason Chemical Company; 2007. Available at: Accessed June 6, 2009.

10. von Woedtke T, et al. Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained. Pharmazie 1999;54: 452-456.

11. Avula B, et al. Simultaneous identification and quantification by liquid chromatography of benzethonium chloride, methyl paraben and triclosan in commercial products labeled as grapefruit seed extract. Pharmazie 2007;62:593-596.

12. Sugimoto N, et al. Survey of synthetic disinfectants in grapefruit seed extract and its compounded products. Shokuhin Eiseigaku Zasshi 2008;49:56-62.

13. Brandin H, et al. Adverse effects by artificial grapefruit seed extract products in patients on warfarin therapy. Eur J Clin Pharmacol 2007;63:565-570.