Hold your nose

Garlic
Fall 2017
To food scientists and chemists who research the medicinal­ and health effects of garlic, the “stinking­ rose” has never smelled so sweet.

Garlic

Humanity’s use of essential oils goes back thousands of years, with natural agents such as frankincense playing a prominent role in making our world smell a little sweeter. That might not be true for garlic but this common plant and its biological cousins have had an unsurpassed impact throughout history and across cultures. And while references to this “stinking rose” can be found in the most ancient of texts, contemporary science continues to shed new light on its chemical behaviour.

In contrast to how long garlic has been a part of our foodstuffs, pharmacopeia and folklore, the formal scientific study of its properties only dates from the 1800s, when European chemists began to analyze the garlic oil they had extracted using the kind of equipment that is still being used today to distill cognac. Upon analyzing this oil, pioneering French and German investigators successfully identified the family of sulphur-containing compounds that include diallyl sulphides, which remain the focal point for present-day researchers like Xiaonan Lu of the University of British Columbia. 

Lu, an associate professor in UBC’s Faculty of Land and Food Systems, took a hard look at the antibacterial effects of garlic for a paper published in Applied and Environmental Microbiology in 2011. “We used biophysical techniques, namely infrared and Raman spectroscopy, to demonstrate that diallyl sulphide can freely penetrate bacterial membranes and combine with sulphur-containing proteins and enzymes. This is the major antimicrobial mechanism of these organosulphur compounds,” he says.

Food-borne pathogen Campylobacter jejuni­ is stymied when it comes into contact with even low concentrations of garlic.

Food-borne pathogen Campylobacter jejuni­ is stymied when it comes into contact with even low concentrations of garlic.

This research targeted Campylobacter jejuni, a pathogen regarded as one of the world’s foremost causes of food-borne illness. The results were significant, with even relatively modest levels of garlic concentrate being able to eliminate all of the pathogen cells at room temperature in just one day. This antimicrobial capability increased with the number of sulphur atoms, making diallyl trisulphide the most effective. That raises the prospect of being able to use garlic derivatives in a more systematic way to prevent food from being spoiled, such as impregnating storage wrap that would be used to keep fruit, vegetables or meat.

Wide-ranging health claims

This potential should come as little surprise, as the history of garlic is packed with health claims of wide-ranging validity, from fending off minor infections or stomach ailments to banishing vampires. With regard to its effect on C. jejuni, however, Lu notes that there had been no formal study, something he blames on the significant volatility of the agents in question. Anyone who has cut into a member of the Allium family of plants — which includes the common onions and garlic that we consume — will be all too familiar with how quickly their chemical structure changes and potent vapours emerge. “When you destroy the structure, an enzyme called allinase will have a chemical reaction with parent compounds of the sulphides and generate a group of very active intermediate sulphur compounds called thiosulphinates,” he says. This highly active material quickly degrades, which has made it challenging to investigate and is why Lu’s work deals with diallyl sulphide, one of the relatively stable sulphur compounds that survive the extraction process.

But thiosulphinates themselves may also have interesting or medically useful properties. Derek Pratt, winner of the Canadian Society for Chemistry’s Keith Fagnou Award in 2015, has been working with these agents in his laboratory in the University of Ottawa’s Department of Chemistry and Biomolecular Sciences and has specifically considered their role as antioxidants.

Antioxidants contained in foods — such as resveratrol in wine grapes or curcumin in the turmeric that goes into curry — have long been touted for their positive effects on health, based on their ability to trap the free radical molecules that are involved in various disease processes. Garlic’s reputation made thiosulphinates a likely addition to this list but when Pratt’s team pinned down their mechanism of action, the results did not point to antimicrobial action by neutralizing free radicals but simply the killing of microbial cells.  

In a 2015 paper that appeared in Chemical Science, these researchers described their work on the thiosulphinate compound allicin taken from garlic and an analogous compound called petivericin, taken from a South American plant. “The garlic-derived thiosulphinate allicin and the analogous secondary metabolite from the related species Petiveria alliacae do not trap peroxyl radicals in lipid bilayers,” they concluded. Pratt and his colleagues also worked with a synthesized thiosulphinate related to petivericin. It turned out to have true antioxidant properties, which they are still studying. 

Herbal medicine regimen 

Health Canada, for its part, continues to list garlic as a natural health product that can be employed as part of an herbal medicine regimen. An official monograph notes its use with symptoms such as upper respiratory tract infections, inflammation of mucous membranes in the nose or throat, elevated blood lipid levels and the general maintenance of cardiovascular health. 

However, such treatments barely begin to cover the vast collection of claims for garlic’s healing powers. In his comprehensive 2010 book Garlic and other Alliums, American chemist Eric Block reviews the spectrum of how these plants are used in traditional and complementary medicine. In addition to citing garlic’s well-established role as an antimicrobial, Block points to proprietary drugs based on diallyl trisulphide that are commonly prescribed in China to fight fungal and parasitic infections. 

Block takes an enthusiastic romp through garlic’s long medicinal career. Prior to the advent of modern antibiotics, for example, doctors employed a garlic oil-infused mask for tuberculosis patients. No less prominent an authority than French-German physician Albert Schweitzer turned to freshly crushed garlic as a remedy for Africans saddled with dysentery or intestinal worms. Block also points to a growing body of literature that explores the effect of thiosulphate on cancerous tumours, as well as dietary garlic’s effect on staving off the development of such tumours. Other bodies of research deal with garlic in relation to cardiovascular problems, diabetes and even bone loss. 

“Garlic teases us,” Block writes. “Testimony on the medicinal benefits of garlic, much of it anecdotal, coming not only from our grandparents but also from great sages of ancient civilizations, is reinforced by a well-ochestrated advertising campaign by purveyors of garlic supplements, taking advantage of the relaxed regulatory atmosphere toward dietary supplements.” 

American chemist Eric Block was inspired by the discovery that, when crushed, onion enzymes release a highly reactive three-carbon compound that reacts­ with another enzyme to reorganize­ its atoms into a tear-inducing compound of unique molecular structure.

American chemist Eric Block was inspired by the discovery that, when crushed, onion enzymes release a highly reactive three-carbon compound that reacts­ with another enzyme to reorganize­ its atoms into a tear-inducing compound of unique molecular structure.

Clinical findings scarce 

Nevertheless, Block and others are more than willing to admit that hard clinical findings are largely absent. Edzard Ernst, an emeritus professor at the University of Exeter’s Department of Complementary Medicine, suggests that garlic suffers from the same challenge as other promising natural remedies: a crying need for randomized clinical trials. Non-proprietary products such as garlic — which can’t be easily patented — provide far less incentive for a potential manufacturer to run the regulatory gauntlet necessary to mount such trials. But when that does happen, the outcome can be highly rewarding. 

This past spring, for example, Iranian researchers published the results of a trial to determine whether garlic tablets helped patients fend off hospital-based infections. Although only 94 subjects participated in the research, the results were encouraging enough to warrant a more ambitious effort. Similarly, a trial with 120 participants coordinated by the University of Florida in Gainesville indicated that aged garlic extract appears to increase the ability of the human immune system to repel the cold and flu infections that are often fatal to older members of the population.

Writing about this research on his blog early this past summer, Ernst cheered on these efforts while noting how very limited they are in scope. And he warns of the gap between what works on the laboratory bench and what benefits an ailing individual. “There is plenty of in vitro evidence to suggest that garlic and its compounds have anti-bacterial, anti-viral and anti-fungal effects,” Ernst says. “Yet, for a range of reasons, this may not translate into clinical effects. To find out, we need clinical trials. So far, such investigations were almost entirely missing.”

What has never gone missing, on the other hand, is the perennial human appetite for alliums, which shows no sign of waning. More remarkable, perhaps, is how this all-too-common staple has finally captured the imagination of chemists equipped with the wherewithal to extract not just essence of garlic and onions but their secrets as well. Block recounts his own pioneering work in the 1980s, which applied the power of nuclear magnetic resonance spectroscopy to sift through the product of a freshly crushed onion to reveal a previously unknown natural product ring system. Dubbed “zwiebelbane,” from the German for “onion,” his insight was just one of many that have been driven by his initial fascination with alliums as a young scientist in the 1960s. “I was amazed at how, from a stable, odorless white solid, an onion enzyme could instantly release a highly reactive three-carbon compound, which, through action of another enzyme, could rapidly reorganize its atoms forming a second, profoundly lachrymatory (tear-inducing) compound of unique molecular structure,” he writes. “The novelty of the chemical transformations that occur when garlic or onion are crushed seemed to me to be a story worth communicating to a broader audience than just my fellow chemists.”