The image is "natural", but is grapefruit seed extract a case of misleading advertising?

The image is “natural”, but is grapefruit seed extract a case of misleading advertising?

Where do you draw the line between “supplement” and “drug”? And how much processing of a “natural” substance can occur before it’s no longer “natural”? These seemingly-philosophical questions are very real when it comes to the supplement industry. In many countries, regulators have implemented weaker safety, effectiveness and quality standards for anything branded a supplement or natural health product. The result has been a boon and boom for manufacturers, with thousands of products flooding the market. This same boom has challenged consumers and health professionals who are seeking products that are safe, effective, and manufactured to high quality standards (and in the bottle you are buying). Nowhere is this challenge better illustrated than a supplement that I’ve seen for sale for some time. Grapefruit seed extract (GSE), according to promoters, is a panacea that destroy bacteria, viruses and fungi anywhere in the body, without any risk of harm. But the actual science is quite telling. Grapefruit seed is a supplement that’s of such poor quality that even herbal medicine boosters recommend against its use.

Grapefruit seed extract is claimed to treat virtually every infection

GSE is claimed to be produced from the seeds of the grapefruit (Citrus x paradisi). The production method isn’t clearly described but different manufacturers say they grind the seeds and pulp in water, and then process this chemically to yield an extract. The methodology of production doesn’t appear standardized, nor is it disclosed in sufficient details to given consumers any assurance that the product is consistent (in content) or safe to consume.

GSE is primarily promoted to treat or prevent infections. It is believed to be simultaneously antibacterial, antiviral, and antifungal. As a liquid, it can be applied topically to surfaces as a disinfectant, or to skin as an antiseptic. It is also consumed orally based on claims that it can treat infections of the gastrointestinal tract (or elsewhere in the body). It is particularly popular for the alternative medicine treatment of what’s called “chronic candida” infection. Chronic candida is not a real condition, but is a fake disease created out of thin air as an explanation for often non-specific gastrointestinal symptoms. In the “treatment” of chronic candida, it’s claimed that GSE selectively kills fungi but leaves normal gastrointestinal species intact. In addition to being consumed in the belief that it can treat candida infections, it’s also claimed that GSE can treat toenail fungus, restore normal blood lipids, heal wounds, “alkalize” the body, is an effective douche, cures warts, treat “dysbiosis”, and more.

There’s no evidence grapefruit seed extract has any meaningful effectiveness

Does grapefruit seed extract actually work? Before looking at the evidence, it is important to distinguish between in vitro use (i.e. in glass dishes on lab benches) and in vivo use (i.e. in an actual human or animal). What kills bacteria, viruses and fungi in a test tube or on an agar plate isn’t necessarily going to be effective when you swallow the same ingredient. Consider the following scenario: Tequila, based on its alcohol content, is going to be an effective disinfectant on surfaces. You can probably disinfect your hands with it, just like you would with an alcohol gel. But no matter how many margaritas you may drink, tequila will not cure your cold or any other infection in body. To be effective after it’s consumed, an ingredient must be absorbed into the body, distributed via the bloodstream to the appropriate location at a minimum concentration, and be present long enough at that location to have an antiviral, antibacterial, or antifungal effect. At the same time it has to do so without causing you or your body more harm than good. Tequila fails spectacularly on all counts. It’s not effective because it’s not possible to have enough in your body to have an effect without killing you. The bottom line is that the only way GSE can truly be evaluated is through actual clinical trials. Test tube or any other in vitro studies are irrelevant when looking at any internal use. GSE, or any supplement or drug for that matter, isn’t exempted from basic efficacy requirements; the only true measure of efficacy is rigorous testing against a specific infection.

Perhaps not surprisingly, there is a lack of evidence showing that GSE has any effectiveness for any condition. A search for clinical trials with grapefruit seed extract reveals no results.

Commercial grapefruit seed extract products may be adulterated with synthetic disinfectants and antibacterials

There is a serious problem with commercially available GSE products sold on the market. There’s an over 20-year history of adulteration of GSE products with synthetic antibacterial disinfectants and cleansers. The first report appeared in the 1990s when testing of a commercially-available GSE product found benzalkonium chloride and triclosan, which were not found in an extract of the seeds themselves. A 1999 study tested six products. Five were effective inhibitors of bacteria and fungus in test tubes. In all five products, the synthetic preservative benzethonium chloride was detected. Three extracts also contained triclosan and methylparaben. The one GSE product with no additives also had no efficacy. The investigators also tested their own seed extract, as well as pulp. No antibacterial or antifungal properties were noted. In their own words:

Thus, it is concluded that the potent as well as nearly universal antimicrobial activity being attributed to grapefruit seed extract is merely due to the synthetic preservative agents contained within. Natural products with antimicrobial activity do not appear to be present.

A 2001 paper drew similar conclusions:

This work has conclusively demonstrated that benzethonium chloride is present in commercial GSE samples. Higher amounts of benzethonium chloride were present in powder GSE samples than in liquid GSE samples, although though we did not determine the exact concentration. This research confirms an earlier study that found benzethonium chloride in commercial GSE samples. It seems unlikely that benzethonium chloride is formed during any extraction and/or processing of grapefruit seeds and pulp.

There have been several other studies conducted. All point to the same conclusion. GSE products that are commercially available are regularly adulterated with synthetic antibacterial and antifungal disinfectants. GSE products that are not adulterated have no efficacy, because GSE has no intrinsic efficacy at all.

The American Botanical council summed this up nicely in a 2012 paper:

A significant amount, and possibly a majority, of ingredients, dietary supplements and/or cosmetics labeled as or containing grapefruit seed extract (GFSE) is adulterated, and any observed antimicrobial activity is due to synthetic additives, not the grapefruit seed extract itself. Tests conducted in multiple laboratories over almost 20 years indicated that all commercial GFSE preparations that exhibited antimicrobial activity contained one or more synthetic microbicides/disinfectants, while freshly-prepared extracts of grapefruit seeds made with a variety of extraction solvents neither exhibited antimicrobial activity nor contained the antimicrobial synthetic compounds found in the commercial ingredient materials. Furthermore, over the course of the 18 years covered by the various analyses, the actual antimicrobial compounds found in the putative grapefruit seed extracts changed from triclosan and methyl p-hydroxybenzoate in early samples to benzethonium chloride in the middle years to mixtures of benzalkonium and/or alkonium chlorides in more recent years. The suggestion on a commercial website that these antimicrobial compounds are formed from the phenolic compounds naturally occurring in grapefruit seed and pulp by heating them with water, ammonium chloride, and hydrochloric acid is not supported by chemical evidence, or any known organic chemistry pathway. None of these compounds could be formed from flavonoids like naringenin, the most abundant flavonoid in grapefruit seeds, pulp, and peel, or other grapefruit seed constituents (e.g., limonoids) and ammonium chloride; the alkyl chains and substituent arrays found in the antimicrobial adulterants are not naturally present in grapefruit seed and cannot be prepared from those materials. The fact that the antimicrobial components found in GFSE changed from 1991 to 2008 not only argues against such in situ synthesis (i.e., occurring naturally or synthesized in the processing of grapefruit seed material itself), but is suggestive of efforts by manufacturers of these commercial materials to stay one step ahead of analytical methods to detect adulteration.

Grapefruit seed extract products may cause unpredictable effects with prescription drugs

GSE products have the potential to cause significant drug interactions. One case report notes that a GSE product significantly increased the levels of warfarin (Coumadin), which means a significantly increased risk of bleeding for patients taking the drug. Upon further examination of the product it was determined that the active ingredient was actually benzethonium chloride. Benzethonium is an antiseptic that is for surface disinfection and is also in consumer products like mouthwash.

The Natural Medicines Database says that GSE is possibly safe based on this paper. The paper describes the open-label use of an extract and provides no data or statistical analysis, yet concludes the product is effective and safe. I am not convinced that these conclusions are appropriate given the methodological quality of this paper and the widespread adulteration issues documented above. Given the risk of potentially harmful drug interactions, and the unknown ingredients that may be used to adulterate commercially available supplies, GSE products have the potential to cause significant harm when combined with medications like anticoagulants.

What’s the bottom line with GSE?

There is no evidence suggesting that actual grapefruit seed extract has any meaningful antibacterial, antifungal, or antiviral effects. Repeated testing over the past 20 years has demonstrated that any GSE efficacy is due to product adulteration with one or more synthetic chemical disinfectants. Adulterated or not, there is no reason to take GSE at all. The fact that it continues to be widely sold is testament to the ineffectiveness of regulations that should put consumer safety ahead of a manufacturer’s right to sell a dodgy product.

Photo via flickr user Dan Zen used under a CC licence.

Posted by Scott Gavura