Unintended Consequences

I flew from London to Vienna last week and noticed that many of the young and trendy were carrying squeeze bottles of hand sanitiser, in their pockets or karabinered to their backpacks.

Why the outbreak of Sanex? 

The kids have been propagandised into thinking that the world is a dark and dirty place, where bacteria, viruses and worse are everywhere, ever ready to pounce on the unwary and unprotected. So these young e-adventurers pack their potions and amulets to ward off bio-hazards that, according to authorities as diverse as the Health Protection Agency and the Daily Mail, will otherwise strike them down. 

There are plenty of scare stories. The unfortunate person who scratched their hand and came down with a flesh-rotting infection that cost them an arm and a leg, is a tabloid staple. As if that weren’t bad enough, lately we’ve been regaled with reports of rare, potentially deadly flesh-eating genital infections – although these are generally a side effect of the refreshingly new SGL-2 anti-diabetic drugs. And of course there is always Ebola to worry about, and other assorted killer viruses such as Marburg, Congo-Crimea, Dengue, Lassa, and that perennial favourite, flu.

Companies that sell hand sanitizers love these scare stories and promote them whenever they can, so it’s hardly surprising that there are so many germophobes and hand sanitizer abusers.But hand sanitizers create problems of their own. A healthy skin and a healthy skin flora (pro-health microbes, also called symbionts) present two major barriers to pathogens. They are an important part of our innate immunity.

If you use too much alcohol-based hand sanitizer or wash your hands too frequently, you can damage the skin’s population of symbionts, creating niches for new and more dangerous microbes; and cause skin on the hands to dry out, crack and bleed. These two factors make it easier for pathogens to enter the body, and in unprecedentedly large numbers. This may increase the risk of new and potentially serious infections.

The sanitizer manufacturers are aware of this, and where nature has handed them a lemon, they make lemonade. Firstly, they can now co-sell you skin creams to stop the dryness and cracking. More profits! Then, they try to switch you to more expensive alcohol-free sanitisers, where the alcohol is replaced by antibiotic compounds such as Triclosan. This is not necessarily a good thing … As far back as 2006, Triclosan was known to encourage bacteria to develop resistance to antibiotics (1), and fears that this is a real-world problem continue to grow (2, 3). Now we learn that the over-use of Triclosan changes the entire microbiome in rodents (4), and in (human) mothers and children (5), making them less stable and more prone to developing antibiotic resistance.

This story illustrates one of the deepest problems of the pharmaceutical approach. Nature – or more precisely the evolutionary furnace in which every species is forged – has created in us an amazing complexity of feedback systems, a deeply interactive series of relationships between the individual and the environment where almost everything is connected; and where first order thinking (the typical pharma approach) inevitably causes as many problems as it solves. The English poet John Donne was profoundly correct when he told us that no man is an island; the Scottish naturalist John Muir equally so when he wrote, ‘”If we try to pick out anything by itself, we find it hitched to everything else in the Universe.”

First order thinking makes good comedy. In fact, almost all humour derives from the planed failure of first order thinking, from the sublime slapstick of Stan Laurel and Oliver Hardy to the word-play of P.G. Wodehouse and Ambrose Bierce, Eric Satie’s score for the ballet Relâche, the more metaphysical comedy of Joseph Heller and Kurt Vonnegut and when taken to an extreme, Uncyclopedia’s excellent and Wildely accurate article on self-referencing (6); which I cannot reference enough. But it makes for lousy medicine. 

19^th century pharma thinking has given us a bulging portfolio of drugs that are expensive, specific, and highly toxic. Every target we strike with our magic bullets causes perturbations elsewhere. No matter how precise the targeting, the effects of impact ripple out into the system and appear in other tissues, sickening and often killing our patients with adverse effects and interactions.

The medical profession’s latest booby trap is Diclofenac, an anti-inflammatory drug recently discovered to increase the risk of heart attack and stroke by a staggering 50% (7). The huge numbers of people dying of neo-opioid overdose, thanks in no small measure to the wisdom and generosity of the Sackler family, the Sassoons of our time, are another tragic example.

There are many other examples of this kind of problem. In fact, iatrogenic illness (illness caused by medical intervention), is a major cause of death (8-10), and will continue to be as we move into the increasingly specific realms of genomics, proteomics and metabolomics. The same gene may code for different proteins in different organs, due to differences in translation. This means, for example, that modifying a gene which codes for an enzyme in one tissue may result in changes to structural proteins in another – or vice versa.

Back to sanitizers. Attempting to sterilize skin is a simplistic and first order approach to the highly complex reality of host / flora / immune system interactions. We are throwing a chemical spanner into a very complicated machine, and this is guaranteed to cause problems.

There is an alternative approach. We could move on from Pasteurian first order thinking, and consider instead the more complex conceptual models of Claude Bernard, Pasteur’s colleague and friend, who showed us the ‘milieu interieur’ where everything connects. 

If we follow Claude’s thinking we can work with, not against, the stunning complexity of life. Instead of indiscriminately killing microbes, we can help the host (you and me) to improve the effectiveness of our innate immune systems. 

There is plenty of room for improvement, because various nutritional factors needed by the innate immune system have been removed from our diet. This has occurred for various reasons, including the development of the sterile food chain and the mass production of ultra-processed foods. So when we put those nutritional factors back, we restore nutritional and physiological normality.

There are two key compounds. One is (are?) the 1-3, 1-6 beta glucans, which prime innate immune cells and allow them to respond more aggressively to invaders (11). The most effective beta glucans are derived from bakers yeast, best taken in pure form because many people are intolerant of mannoproteins, which also occur in yeast.

The second key micronutrient is thiocyanate, the substrate used by the immune enzyme lactoperoxidase. Thiocyanate is formed in the body from glucosinolates, found in brassica vegetables, and from cyanogenic glycosides, which occur in certain cereals such as millet. You can eat millet and sauerkraut, or you can take thiocyanate in a supplement form.

This approach has side effects also, because everything still connects. But by enhancing a natural system, we create side effects that are uniformly positive. They include improved resistance to many different kinds of bacterial and viral infection (12, 13), reduced allergy (14) and reduced chronic inflammation! (15).

All adventurers, urban or otherwise, should eat 1-3, 1-6 beta glucans every day. By doing this, the world becomes a (slightly) safer place.

Gesundheit.

P.S. For the geeks. Reference 14, above, is a preliminary study. But I can vouch for the reduction in allergy, as I have witnessed it in several thousand patients.

REFERENCES:

1. Yazdankhah SP, Scheie AA, Høiby EA, Lunestad BT, Heir E, Fotland TØ, Naterstad K, Kruse H. Triclosan and antimicrobial resistance in bacteria: an overview. Microb Drug Resist. 2006 Summer;12(2):83-90.
2. Daniel E. Carey, Patrick J. McNamara. The impact of triclosan on the spread of antibiotic resistance in the environment. Front Microbiol. 2014; 5: 780.
3. Erica M. Hartmann, Roxana Hickey, Tiffany Hsu, Clarisse M. Betancourt Román, Jing Chen, Randall Schwager, Jeff Kline, G. Z. Brown, Rolf U. Halden, Curtis Huttenhower, Jessica L. Green. Antimicrobial Chemicals Are Associated with Elevated Antibiotic Resistance Genes in the Indoor Dust Microbiome. Environ Sci Technol. 2016 Sep 20; 50(18): 9807–9815.
4. Bei Gao, Pengcheng Tu, Xiaoming Bian, Liang Chi, Hongyu Ru, Kun Lu. Profound perturbation induced by triclosan exposure in mouse gut microbiome: a less resilient microbial community with elevated antibiotic and metal resistomes. BMC Pharmacol Toxicol. 2017; 18: 46. Published online 2017 Jun 12.
5. Jessica V Ribado, Catherine Ley, Thomas D Haggerty, Ekaterina Tkachenko, Ami S Bhatt, Julie Parsonnet. Household triclosan and triclocarban effects on the infant and maternal microbiome. EMBO Mol Med. 2017 Dec; 9(12): 1732–1741.
6. https://en.uncyclopedia.co/wiki/Self-reference
7. Dubreuil M, Louie-Gao Q, Peloquin CE, Choi HK, Zhang Y, Neogi T. Risk of myocardial infarction with use of selected non-steroidal anti-inflammatory drugs in patients with spondyloarthritis and osteoarthritis.

Ann Rheum Dis. 2018 Aug;77(8):1137-1142.

8. Madeira S, Melo M, Porto J, Monteiro S, Pereira de Moura JM, Alexandrino MB, Moura JJ. The diseases we cause: Iatrogenic illness in a department of internal medicine. Eur J Intern Med. 2007 Sep;18(5):391-9.

1. Pilgrim JL, Yafistham SP, Gaya S, Saar E, Drummer OH. An update on oxycodone: lessons for death investigators in Australia. Forensic Sci Med Pathol. 2015 Mar;11(1):3-12.
2. Starfield B. Is US health really the best in the world? JAMA. 2000 Jul 26;284(4):483-5.
3. Lee DY, Ji IH, Chang HI, Kim CW. High-level TNF-alpha secretion and macrophage activity with soluble beta-glucans from Saccharomyces cerevisiae. Biosci Biotechnol Biochem. 2002 Feb;66(2):233-8.
4. Yu X, Zhang D, Shi B, Ren G, Peng X, Fang Z, Kozlowski M, Zhou X, Zhang X, Wu M, Wang C, Yuan Z. Oral administered particulate yeast-derived glucan promotes hepatitis B virus clearance in a hydrodynamic injection mouse model. PLoS One. 2015 Apr 9;10(4):e0123559.
5. Kournikakis B, Mandeville R, Brousseau P, Ostroff G. Anthrax-protective effects of yeast beta 1,3 glucans. MedGenMed. 2003 Mar 21;5(1):1.
6. Sarinho E, Medeiros D, Schor D, Rego Silva A, Sales V, Motta ME, Costa A, Azoubel A, Rizzo JA. Production of interleukin-10 in asthmatic children after Beta-1-3-glucan. Allergol Immunopathol (Madr). 2009 Jul-Aug;37(4):188-92. doi: 10.1016/j.aller.2009.02.005. Epub 2009 Aug 4.
7. Cao Y, Sun Y, Zou S, Duan B, Sun M, Xu X. Yeast β-Glucan Suppresses the Chronic Inflammation and Improves the Microenvironment in Adipose Tissues of ob/ob Mice. J Agric Food Chem. 2018 Jan 24;66(3):621-629.