The age of antibiotics may be coming to an end- what can we turn to?

By Paul Clayton, Ph.D.

 

Scientists speculate that the age of antibiotics may be coming to an end. This is because there has been a relentless increase in antibiotic resistance across all classes of drug. Furthermore, recent articles on antibiotic resistance in China paint an alarming picture of a near-future where antibiotics will have little therapeutic value (Heddini et al 2009).

Sadly, the use of antibiotics inevitably leads to the selection of resistance traits; the overuse and misuse of antibiotics in medical and other situations makes it increasingly unlikely that we will be able to stay ahead in the war against infection. Important work in such areas as quorum-sensing blockade may produce important new drugs, but these will not be available soon.

Various alternatives have been proposed from the natural world, and this article reviews one of the most prominent candidates that being the lactoperoxidase system, specifically thiocynate ions as contained in 1^st Line™.

 

Lactoperoxidase/ Thiocynates

The enzyme LPO is one of the body’s major first-line defences against infection (Pruit ’87, Ratner & Prince 2000, Gerson 2000, Wijkstrom-Frei et al ‘03). LPO produces ions such as HOSCN, which have a broad spectrum of activity against gram-positive and gram-negative bacteria, HIV-1 and other viruses, moulds, yeasts, mycoplasma and protozoa (Pruitt & Reiter ’85, de Wit & van Hooijdonk ’96, Wang et al 2000, van Hooijdonk et al 2000, Seifu et al ’05, Fweja et al ’08). LPO is critical for the control of pathogens in milk from lactating animals (Reiter et al ’86) including humans (Shin et al 2000). It also plays a key role in defending the respiratory and gastro-intestinal tracts (Wijkstrom-Frei et al ‘03).

LPO utilises dietary thiocyanate as one substrate, producing hypothiocyanite (HOSCN) ions. These ions kill pathogenic bacteria (Table 1) via three separate mechanisms. They inhibit bacterial glycolysis; they inhibit bacterial nicotinamide adenine dinucleotide (NADH)/nicotinamide adenine dinucleotide phosphate (NADPH)–dependent reactions (Reiter & Perraudin ‘91); and they oxidise bacterial sulphydril groups (Slungaard & Mahoney ’91, Thomas & Aune ‘78). LPO also utilises iodine, forming hypohalide ions. These have an additional spectrum of anti-bacterial activity.

 

Table 1: LPO activity in vitro: (number of strains tested) 

Bacteria •    Escherichia coli (10) •    Yersinia enterocolitica (4) •    Klebsiella pneumoniae (13) •    Klebsiella oxytoca (10) •    Streptococcus agalactiae •    Streptococcus mutans •    Staphylococcus aureus •    Salmonella species (12) •    Shigella sonnei (15) •    Listeria monocytogenes •    Acinetobacter species (40) •    Neisseria species (20) •    Haemophilus influenzae (20) •    Campylobacter jejuni (14)

•    Aeromonas hydrophila (8) •    Pseudomonas aeruginosa (6) •    Capnocytophaga ochracea •    Selenomonas sputigena •    Wolinella recta •    Enterobacter cloacae (12)Viruses •    Herpes simplex virus •    Immunodeficiency virus •    Respiratory syncytial virus Yeasts•    Candida albicans

Uniquely, HOSCN ions also have potent anti-viral activity. Many viruses have sulfhydryl groups on their coat (ie Mangold & Streeck ‘93); when these are oxidised (ie by thiocyanate) the viral coat structure is damaged or destroyed (Almeida et al ‘79).

HOSCN ions are not toxic to human cells at the levels produced by LPO, and have little if any effect on probiotic species, making them a near-perfect antibiotic system. Furthermore, it is very difficult for microorganisms to acquire resistance to LPO; if it was easy for pathogens to become LPO-resistant, a key element in our immune system would have been disabled and we would not have survived as a species.

Today, however, the LPO system is frequently compromised. Lactoperoxidase is a ferroprotein, and iron depletion / deficiency is one of the most common forms of dysnutrition. There are also growing problems with two of LPO’s substrates, thiocyanate and iodine. Thiocyanates are derived from dietary glucosinolates (in brassica), or from cyanogenic glycosides (in beans, sweet potato and millet). Since 1950, UK consumption of fresh vegetables has fallen by 24% (Hinton ‘08). Iodine depletion is becoming more prevalent, due inter alia to reductions in salt intake and the use of (non-iodinated) sea salt (Li et al ‘06, Nawoor et al ‘06). The net effect of depletion in iron, iodine and cyanogens on LPO activity is likely to be very significant in reducing our ability to ward off infections.

Due to its chemistry, LPO is not a suitable therapeutic tool; if the milk-derived enzyme were to be consumed it would, like other milk proteins, be digested and rapidly rendered ineffective. However, the bactericidal effects of LPO can be mimicked and amplified by delivering HOSCN ions directly. This technology was initially developed in France for food plant sterilisation, and subsequently to sterilise salad leaves. It is used as an antiseptic in Belgium, and has been adapted by the WHO for bulk milk sterilisation in China and Korea (FAO/WHO ‘05).

We have reviewed the possibility that the extensive use of HOSCN might encourage the development of microbial resistance strategies, and believe that this is unlikely. Only a small number of intrinsically LPO-resistant microorganisms are known (ie Oram & Reiter ’66). While resistance may be acquired in certain specific circumstances (ie Leyer & Johnson ’93), the evolutionary historical evidence indicates that this is clinically insignificant. Moreover, most mammals utilize LPO / HOSCN on a daily basis and it remains an effective element in the innate immune system.

With regard to safety, it should be pointed out that the level of hypothiocyanous ions in 1^st Line is well below the safe and tolerable levels of thiocyanate ions produced within the body (Borgers & Junge ’79, Medizinische ’82, WHO ‘95).

 

1^st Line™, the world’s first thiocynate ion producing kit

1st Line’s patented formula makes up into a drink containing hypothiocyanite and hypothiocyannous ions, identical to those in tears, saliva and milk. These ions are a critical defence against a wide range of pathogens including bacteria, yeasts, fungi and viruses; many of which they destroy on contact.

Until recently, the unstable hypothiocyanite ions could not be stored. In a technical breakthrough, the 1st Line kit enables the ions to be produced immediately prior to use so they can be consumed ‘fresh’, whenever required. For the first time, hypothiocyanite ions can be used as a supplement.

These bio-identical immune molecules differ from antibiotics in two ways:

1. The ions are very small molecules, with a molecular weight of around 90. They therefore diffuse further and faster though tissues than the much larger synthetic antibiotics.
2. They kill a surprisingly wide range of disease-causing micro-organisms, but unlike synthetic antibiotics do not damage probiotic species such as lactobacilli and bifidobacteria. Our immune systems and these beneficial bacterial species have co-evolved, and have ‘learned’ to co-exist.

1st Line should be used at the first symptom of an infection. Only one kit should be used per day and often only one is required. If symptoms persist another kit can be consumed the following day. Persons with more serious symptoms can use 1^st Line up to twice a week, dependent upon need. For those who want to prevent the symptoms of infection 1st Line can be used once every few months.

And let us rememeber that hypothiocyanite ions are not toxic to human cells, they appear to have excellent tissue penetration and have little if any effect on probiotic species, making them a near perfect antibiotic system.

 

Summary

In the war against infectious micro-organisms, where we are currently losing ground, 1st Line is a break-through. For the first time, it enables the clinician or indeed any user to utilise one of the most powerful elements in our array of immune defences, namely the innate immune enzyme lactoperoxidase (LPO).

In the body, LPO utilises dietary thiocyanates from such sources as brassica vegetables to produce HOSCN ions, which kill a wide range of bacterial and viral pathogens (see Table 1, below). Uniquely, and as would be expected from an innate immune defence, this wide spectrum of anti-microbial activity does not include the essential probiotic species which are immune to LPO activity.

Lactoperoxidase therefore has all the attributes of an ideal antibiotic, and this has lead many scientists to explore its therapeutic uses. All previous attempts, however, have failed because the commercial enzyme is a dietary protein derived from milk. When eaten, LPO is rapidly broken down in the stomach and small intestine and its enzymatic activity is lost.

1st Line™ is a far more intelligent approach. It uses phase-bound lactoperoxidase remotely, supplying it with the substrates it would normally use to produce HOSCN ions outside the body. These ions are then ingested, mimicing the endogenous effects of the enzyme exactly.

Given the known efficacy and safety of the LPO / HOSCN system, and access to preliminary clinical trial data, I regard the development of this system as a medical break-through. I believe that the development of the LPO / HOSCN system is as important as the discovery of penicillin, and will make as great an impact on infection control.

To the bureaucratic mind, however, it presents a substantial problem. First direct devolves infection control to the end-user, who now has direct access to a safe, food-derived anti-infection strategy. This is the internal equivalent to anti-septics, which everyone can use, and thus runs counter to the interests of the pharmaceutical industry, their profit margins and regulatory bodies.

There is no question about the value of the enzyme system. The only question is how long this anomaly will be allowed to continue before big Pharma and its regulatory muscle either forcibly re-classify 1st Line™ as a drug, or suppress it altogether.

 

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