What Do Historical Evidence and Modern Clinical Trials Tell Ethnopharmacologists About The Usefulness Of Hop Alpha and Beta Acids As A Tool In The Fight Against Antibiotic Immunity?
Hops have been cultivated and used from around the 10th century (Delyser,1994) and have been viewed as ‘a wicked weed that would spoil the taste of the drink (beer) and endanger the people’ in Henry VIII’s time (Hornsey, 2003) to being carefully ‘cultivated for the sole interest of the brewing industry’ (Alfa- Laval, 1983). They have also had a long association with having a medicinal effect, most interestingly their antibacterial and sedative properties have been noted as far back as 4000 years (Simpson et al, 1992). Antibiotic resistance is one of the biggest problems facing the medical world with a massive increase in the past two decades of drug resistant strains bacteria such as MRSA. I will argue in this essay that, while not a hugely potent antibacterial agent, hop acids have a place in the fight against antibiotic resistance. I will do this by detailing the history of hop use focusing on brewing, evidence from other species, clinical research in humans and examining the causes of antibiotic immunity. I will focus other two main compounds active in hops that have an antibacterial effect, and a common isomer of one of them.
The hop is a genus of flowering bines, native to the temperate European and
American areas. Female flowers of the hop bine are called cones; it is in these cones that the hop oils containing the active ingredients are held. The hop is part of the family Cannabaceae, which also includes the genusCannabis (Greive, 1972). There is evidence of hops being used as a preservative in beer since the 1500’s (Hornsey, 2003) although it’s use was not universally approved of. Henry VIII famously claimed they were little more than a ‘weed’, which ‘spoiled the taste (of beer)’ (Hornsey, 2003) this statement is true to a certain extent. Due to their climbing nature and rhizomic spreading it is possible for hop bines to overrun a cultivated area, suffocating other plants
Traditionally many different herbs and plants were added as a flavouring to beer however, it was noticed that when hops were added to a beer it lasted longer (Behre, 1998). This was due to the fact that the α and β acids allowed the growth of yeast, but killed other bacteria by disintegrating phospholipid bilayer cell membranes (Teuber et al, 1972 and Teuber, 1970). Around the same period the rise of Britain as a seafaring nation required the storage of drinkable water for long periods at sea, which at the time was unfeasable. Beer kept for a much longer period of time and so was used as the main source of drinking water for sailors of the time. This weak, low gravity beer became known as ‘small beer’ (Behre, 1998). As the length of time at sea increased, so did the alcohol and hop content of beer. During the colonisation of India by the British India Pale Ale was born, this contained the highest levels of hops ever seen in a beer so it survived the long sea journey. It became so popular it was eventually only brewed for internal consumption (Spring et al, 1977).
As with all medicinal plants there are many chemicals that potentially have an effect on the body, including methylbutenol which induces a mild sedative effect, and a chemical; 8-Prenylnaringenin which mimics the action of oestrogen (Pratt et al, 2004, Takamura-Enya et al, 2003 and Beuchat et al 1989).
The active compounds I wish to closer examine however, are the α acid humulone which has the chemical formula C12H30O5 and the β acid lupulone which has the chemical formula C26H35O4. Due to extensive research carried out by brewers we now know humulone is not a single chemical compound but rather a mixture of 3 closely related compounds called humulone, adhumulone and cohumulone (Alpha-Laval, 1983). When hops are boiled during the beermaking process the components of the humulone and lupulone are isomerised to create the complexes: isohumulone, isoadhumulone, isocohumulone, isolupulone, isoadlupulone and isocolupulone (Alfa-Laval, 1983) . It is these compunds that give beer it’s bitter flavour and the isohumulone that has an antibacterial effect (Delyser et al, 1994).
Many antibiotic compounds are used by doctors to aid the fight against unwanted bacteria in our bodies, due to abuse of these substances however bacteria are able to evolve immunity from them, rendering them useless. It is often described as a ‘medical arms race’ between bacteria and the developers of antibiotics (Burke, 1998). As successive generations of bacteria are generated, mutations within their DNA that favour resistance to certain antibiotics are selected for, ultimately rendering the antibiotic useless. This has a massive impact on the way in which doctors now prescribe antibiotics and the instructions given to patients on how they must finish the course (Cirz et al, 2005). The problem with people not finishing a course of antibiotics is that it causes a bottleneck in the population of the bacteria, allowing the more resistant genes to be passed on to future generations. If this happens several times it is possible within the scale of a few years to develop a resistance (Burke, 1998).
Penicillin resistance was first found in 1947 a mere four years after the drug was commercially introduced. Methicillin, a similar antibiotic to penicillin has developed a resistant form of Staphylococcus Aureus known as MRSA. The first note of this resistant strain in the U.K. was in 1961 (Maple et al, 1989) and is now ‘quite common’ in hospitals (Levy, 2000). According to Levy’s analysis ‘MRSA was responsible for 37% of fatal cases of blood poisoning in
the UK in 1999, up from 4% in 1991. Half of all S. aureus infections in the US are resistant to penicillin, methicillin, tetracycline and erythromycin’ (Levy, 2000).
A key problem within human antibiotic resistance is that due to the feeding of antibiotics to farm animals a constant low level of antibiotic is ingested . This base level aids the development of resistant strains of certain bacteria (Sapkota et al, 2007). The need to feed antibiotics to animals from birth is caused by the intensive farming methods used in many countries, examples of which include battery hens and caged pigs. In these cramped quarters it is easy for infection to spread quickly, potentially killing a large proportion of a farmer’s livestock (Castanon, 2007). For many hundreds of years livestock, especially pigs due to their omnivorous nature have been fed the spent hops and yeast from the brewing process (Brorson et al, 2002). It was noted these animals were generally in better health than those not fed brewing waste products (Delyser et al, 1994).
Due to this, there have been clinical trials run mainly on battery hens in which by adding spent hops to their diet show similar effects to antibiotic administration (Cornelison et al, 2006 and Pizarski, 2005). Further to this, more research on human subjects has been undertaken to discover how hop acids may help fight infection. Natarajan et al discuss a positive antibacterial co-action between hops and selected antibiotics when used to fight several different bacteria (Natrajan et al, 2007). Ohsugi et al also discuss that they were able to significantly reduce the levels of Helicobacter pylori, a stomach bacterium linked with chronic inflammation, ulceration and cancer (Ohsugi et al, 2007).
Despite this the there are no pharmaceutical companies working on hops as an antibacterial product, which in my opinion is an oversight based on the evidence that is present both clinically and historically. People may choose to self medicate with hops to fight minor infections but this is problematic in that there are other active chemicals as mentioned previously. Men may develop swelling of the breast tissue, reduced sperm count and emotional instability (Thuille et al, 2003).
This further adds weight to the argument that the acids themselves need to be isolated and used so as to reduce side effects. It is well noted that the old, ill and the young are particularly susceptible to infection form bacteria such as MRSA. Would it be possible to dose these
individuals with a base level of these acids to avoid infection as demonstrated in livestock? I feel more research is needed. In conclusion, both clinical trials and historical evidence show a strong case for the commercial development of α and β acids extracted from hops. History and clinical trials prove their ability as an antibacterial agent There are potentially many practical applications for their antibacterial effects including in animal feeds as a less aggressive form of disease control. There are also applications In humans to provide a baseline protection against antibiotic resistant strains of bacteria. I however feel that much research is needed into these compounds before any sort of pharmaceutical product becomes available.
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