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"As a trained biochemist I was particularly impressed by the synthesis of science with the naturopathic model of healing in The Natural Recovery Plan, which you don't often find in the same book."
Patricia Worby MSc. ACMT, Dip PSGD, Naturopathic massage therapist

L-Form Bacteria

L-form bacteria, which are also known as L-phase variants, or cell wall-deficient (CWD) bacteria, are strains of bacteria that have lost their cell walls. They were given their name by the researcher who first identified them in 1935 and who named them after the Lister Institute in London where she was working.

There are two types of L-form bacteria. One form is unstable but is capable of dividing and of reverting back to its original morphology, and the other form is stable and unable to revert back to its original bacteria.

Although mycoplasma lack a cell wall, they are not considered to be L-forms because the bacteria from which they are derived do not normally have cell walls.

The shapes of bacteria are determined by their cell walls, and with no cell wall, the L-forms have different shapes from their parent cells. For example, the L-forms of rod-shaped bacteria are typically spherical. L-forms also lack the internal cytoskeleton and cell organelles of their parent cells, creating novel morphological units including filaments, vesicles and granules.

The cell wall also plays an important role in cell division as one bacterium grows and then splits into two. However, the lack of a cell wall in L-forms means that cell division is disorganised and produces a variety of cell sizes, from very small to very large. The L-forms appear to reproduce by producing protrusions which become 'pinched off' to form new cells and this may represent a very ancient form of reproduction.

Precisely because they lack a cell wall, many antibiotics are unable to kill L-form bacteria directly and they also cannot be detected by many standard laboratory tests that rely upon staining the cell wall. The lack of a cell wall also means that they are able to enter and proliferate inside body cells and also to go undetected by the immune system.

In particular, they enter the macrophages - the very immune cells deployed to kill invading pathogens. And, once inside the body's cells, they cause the production of inflammatory cytokines which can cause chronic pain and fatigue. 

In the laboratory, L-forms can be produced either by treating cultures with antibiotics, by using an enzyme to digest the cell walls or by restricting the space available for growth. And in the body, the use of antibiotics may be one of the main factors causing the mutation of pathogens to an L-form and this may also be one of the mechanisms involved in the acquisition of antibiotic resistance.

Many of these bacterial forms do not lend themselves to standard culturing methods which employ a medium in a petri dish and their presence has only been revealed by new molecular analysis techniques. It is now thought that the traditional methods may only have identified about 1% of the pathogens present - namely those that grow fairly rapidly in any given medium, and that are not strict anaerobes.  

Another great advantage of molecular analysis is that it is much faster being completed in a matter of hours rather than days and it also holds out the hope of being able to use treatment specific to the patient.

One of the chief suspects for creating L-form bacteria in vivo is the use of antibiotics including the penicillins and the cephalosporins - and this is the method used to create L-forms in the laboratory. There appear to be two or possibly three responses of a bacterium when exposed to antibiotics.

One, is that the bacteria dies although this may happen a lot less than was imagined. The second possibility is that the bacterium sheds its identifying cell wall and goes incognito as an L-form, and the third possibility is that the bacteria form a cooperative colony on a surface and erect a protective adhesive protein matrix and this is known as a biofilm. In this way there is strength in numbers and the biofilm bacteria receive protection from the antibiotic. 

The bacteria that cause many diseases including tooth decay and gum disease are thought to be biofilm in origin and are able to spread within the body colonising other surfaces. In the particular instance of oral bacteria, they are known to grow on any prostheses or the heart valves and antibiotics need to be prescribed prophylactically in at-risk patients. 


Is chronic illness infective in nature?

The Human Microbiome project which is cataloguing all the microorganisms associated mankind has revealed that bacteria are far more pervasive than was previously thought. And with over 90% of the cells in the human body not being human in origin and the millions of genes carried in the human microbiota greatly outnumbering the 23,000 genes in the human genome, the chances of chronic illness being infective in origin is looking ever more likely. 

In particular, some researchers suggest that these L-forms may be the hitherto unrecognised cause of many of the 'mysterious' illnesses - whilst others maintain that they are only produced under extreme laboratory conditions.

The allopathic world is coming to appreciate that the harmful effects of acute infections may take decades to manifest. And, because any pathogens that remain may reproduce slowly, the effects may only become apparent decades later. In particular, some researchers now believe that chronic and recurrent illness - and particularly the 'mysterious' and autoimmune illnesses - may be the result of an ongoing challenge to the immune system by L-form bacteria. 

In addition to challenging the immune response, initial infections can alter the expression of human genes and also affect human host-cell pathways. So that when the number of pathogens reaches a critical mass, childhood viral infections can reactivate, or the individual can acquire Candida (pathogenic yeast) and Mycoplasma infections as well. 

Evidence to support this hypothesis of chronic illness aetiology includes the fact that: 

  • One in ten people who suffered from E. coli food poisoning later developed kidney and/or other organ failure.
  • Respiratory tract and gastrointestinal infections particularly with Campylobacter are often antecedents to developing the autoimmune disease, Guillian–Barré syndrome (GBS). 
  • Prenatal infections such as rubella, influenza, and toxoplasmosis are all associated with a higher incidence of developing schizophrenia later in life.
  • Infections with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2 increase the risk of having a stroke.
  • Both prenatal exposure to influenza and infant diarrhoea have been linked with the later development of cardiovascular disease. 
  • Over 40% of those who survived the 2003 SARS pandemic went on to develop persistent mental health problems and chronic fatigue syndrome (CFS).
  • Exposure to airborne infectious diseases in infancy is associated with a much higher risk of dying of an airborne infectious disease later in life.
  • There is a link suggested between childhood streptococcal infections and later Obsessive Compulsive Disorder (OCD). 
  • Infants who harbour Staphylococcus aureus are more likely to become overweight and obese later in life. 
  • A perinatal herpes virus infection dramatically increases the risk of developing chronic liver disease. 


In addition, none of the definitions used by doctors for diseases are clear cut, with many individuals suffering with several chronic illnesses and doctors differing as to the diagnosis. This suggests that these disease states are not discrete as imagined by allopathic medicine, but are all connected as maintained by natural medicine. 

Every individual accumulates a unique microflora over the course of their life from their mothers, from foods, and from others with whom they have contact. This unique microbiota is often referred to as our 'pathogen burden'. 

And this process is like a snowball rolling downhill in that each pathogen acquired further disables the immune response so that subsequent pathogens can proliferate and the effect is additive. This is known as 'successive infection' and means that infections early in life can predispose an individual to later chronic disease. 

And whilst approximately half the global population carry Chlamydia pneumoniae and Helicobacter pylori, the individual mix of bacteria is as unique to us as our fingerprints. One study of the bacteria present on student's hands found that they carried an average of 150 species on each hand and that the flora on their two hands had little in common! Also, that this flora changes dynamically - even over the course of a few days.

Although the processes of cell division in bacteria are simple, they are also able to exchange packets of genetic material known as plasmids with other pathogens. Some bacteria have more than 20 plasmids and so given time it is easy to understand that the number of combinations of pathogenic DNA in our cells becomes virtually infinite.

There is also evidence to suggest that L-forms can survive within the ovum and sperm and also that they can pass through the placental barrier, meaning that illnesses that run in families may be infective rather than genetic in nature. The infant can also acquire infections at or after birth, before their adaptive immune system is up and running.


The role of vitamin D in infections

The ability of these pathogens to proliferate in the body is directly related to the vitamin D receptor which controls the innate immune system which serves as the first line of defense against infection. In addition, this receptor is also responsible for controlling a wide range of genes and chemical pathways including the production of antimicrobial peptides and calcium metabolism.

The precursor form of vitamin D is actually a steroid and elevated amounts of this hormone can bind to and inactivate the vitamin D receptor - shutting down the innate immune system. L-form bacteria are also able to produce substances that block the vitamin D receptor thus causing the immune system to become increasingly compromised and allowing the bacteria to proliferate and spread.

When vitamin D levels are high, they displace various hormones and metabolites from their target nuclear receptors, disrupting the body’s hormonal pathways. This, may in part, account for why most people with chronic disease find they have difficulty tolerating stress, changes in temperature, and a variety of other hormone-related issues. 

Some chronic disease sufferers may have found that they have felt better for supplementing vitamin D and steroids. However, both these compounds have further inactivated the vitamin D receptors thus preventing the immune system from effectively killing the pathogens. This means that fewer bacteria are killed leading to short term relief of die-off symptoms, but long-term allows the bacteria to spread more easily.


The Marshall Protocol

The Marshall protocol has been developed by the biomedical researcher, Professor Trevor Marshall Ph.D who has a special interest in autoimmune diseases. It is used by doctors worldwide to treat a variety of chronic inflammatory and autoimmune diseases.

Practitioners following the Marshall Protocol seek to eliminate the L-form and other bacteria that they regard as being the cause of chronic ill health using various drugs. These include a medication called Olmesartan medoxomil (or Benicar in the US), which binds to and activates the vitamin D receptor by displacing other forms of vitamin D and bacterial proteins from the receptor. This, in theory, enables the body to 'turn on' the innate immune system thus killing the pathogens and other co-infections.

Patients following the Marshall protocol take intermittent, low-doses of antibiotics (monocycline) which are more effective against the bacteria in biofilms and are able to weaken these pathogens to the point that the patient’s own immune system is able to get the upper hand and destroy them.

Each dose of antibiotics produces a die-off or Herxheimer reaction which can be unpleasant. Second tier antibiotics including clindamycin, Bactrim and azithromycin may also be deployed. Patients are required to avoid sunlight and vitamin D rich foods and to follow the protocol for several years. 

Diagnostic blood tests of vitamin D metabolites are done to determine whether the treatment would be of value or a trial of the drug(s) is tried to assess the response.


My thoughts on the Marshall protocol

I am very much of the "If it works - good!" school of thought but I have several concerns about this approach.

On the one hand some chronically sick people have obviously experienced improvements following the Marshall protocol. However, the website acknowledges a number of quite serious side-effects including an increased risk of Addison's disease, cancer, heart attack, diabetes, depression and osteoarthritis when following the programme. 

It is also obviously not an easy option since there are potent detox reactions, the whole process takes several years and individuals need to avoid the sun and vitamin D containing foods for the duration.

First, this way of looking at things sees the microbes as being the primary problem and having infected the person from without. The protocol deploys a protracted arsenal of antibiotics in order to try and control the unwanted pathogens over a period of years. This is the military 'killing the enemy' model which many allopathic medical practitioners subscribe to.

In contrast, the natural health world tends to regard pathogens as either having arisen from within under toxic conditions, or having found fertile soil in the toxic terrain of the body. This is a totally different way of looking at the problem and requires fundamentally rectifying the conditions which allowed the problem to establish in the first place.

An analogy might be mosquitoes being attracted to - and flourishing in - a stagnant swamp. The Marshall protocol tackles the pathogens using antibiotics, but fails to address the underlying milieu. This is a bit like throwing some bleach into the stagnant swamp in order to kill the mosquitoes that dwell there.

Does it work? Possibly in the short term. 

However, another approach could be to perhaps create some means of circulating fresh water at which point the mosquitoes will either find another habitat or fail to breed and the problem will be solved permanently.   

Chronic illness is regarded by the naturopathic world as being due to an accumulation of toxins layed down in layers along with various pathogens, and when the immune system is sufficiently burdened, parasites too may establish as shown below.  

Comparison of Marshall protocol and Natural Recovery Plan

A Comparison of the Marshall Protocol and Natural Recovery Plan Approaches


The method advocated in the Marshall Protocol seeks to decrease the pathogen burden by using antibiotics to the point where the body can re-establish control. Whereas, the Natural Recovery Plan seeks to restore balance by using natural means to gently draw out toxins while simultaneously killing the pathogens. So that it is addressing the toxicity of the milieu that helped to establish the pathogen problem in the first place.

There are also concerns about deliberately avoiding sunlight and vitamin D containing foods so that the blood levels of vitamin D fall abnormally low. Many now think that vitamin D has profound effects on all body systems as outlined in the article Sun Exposure and Vitamin D and that this could be potentially very damaging. 

Also, in using antibiotics over a period of years you are doing more of what probably created the problem in the first place. And this may have repercussions (as yet unseen) for both the individual involved and for society at large as further antibiotic resistant bacterial strains may develop.

The drugs used are all synthetic, laboratory creations and have to be detoxified - along with the dead bacterial cells generated - by the liver which is invariably struggling. 

I also imagine that, by the time you have factored in doctor's fees, blood tests and several years worth of pharmaceuticals it is quite expensive. 

Finally, the idea that we will ever get the 'upper hand' on nature is absurd, but we are constantly offered that carrot by allopathic medicine. The only way to reestablish health is to reestablish balance - which means doing it nature's way and harnessing the natural systems already in place. 


Further resources

For more information see Amy Proal's website at or the Marshall Protocol website. 

You might also be interested in the following: 

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Lyme Disease: Under Our Skin

Sun Exposure and Vitamin D

Antibiotics: Use and Abuse

Stealth Viruses

Mycoplasma and Fatigue Syndromes


Candida Albicans: The Enemy Within

The Epstein-Barr Virus

The Amazing Properties of Samento

Book Review: Doctors are More Harmful Than Germs

For an explanation of the aetiology of fatigue syndromes and a plan for recovery using natural means, please refer to The Natural Recovery Plan book

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L-Form Bacteria listed under Fatigue Syndromes and Toxicity in the Audio hub

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L-form bacteria: Article summary

This article looks at the possible role of L-form bacteria in causing chronic and recurrent illness. L-form bacteria are bacteria the do not have a cell wall and can be created by exposure to antibiotics. The possibility of chronic disease having an infective origin is discussed along with the Marshall protocol a way of using low dose antibiotics to control the overgrowth of pathogenic species to the point where the individual's immune system can start to re-exert control. 


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The Natural Recovery Plan Ezine March 2012 Issue 27. Copyright Alison Adams 2012. All rights reserved
Dr Alison Adams Dentist, Naturopath, Author and Online Health Coach

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