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Artikel von Nils Milman zu Marshall Protocol

Scandinavian Journal of Infectious Diseases, 2010; Early Online, 1–2 LETTER TO THE EDITOR What is the Marshall Protocol – and should we use it? NILS MILMAN, From the Department of Rheumatology, Rigshospitalet, University of Copenhagen, Denmark

To the Editor, Queries from the Danish Lung Foundation and from many patients with diffuse lung diseases have asked me what Dr Marshall ’ s treatment is all about. Furthermore,Dr Marshall has recently been touring in Scandinavia giving lectures and recruiting patients for his protocol. I therefore considered that it would be appropriate to provide information about Dr Marshall ’ s theories.

The Australian biologist Trevor G. Marshall has generated a theory or hypothesis on how chronic infl ammatory autoimmune disorders, e.g. connective tissue diseases, arise – this is termed Marshall’s Protocol [1 – 3]. These chronic inflammatory disorders comprise, among others, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma, sarcoidosis, Sjögren’s syndrome, autoimmune disorders of the thyroid gland, psoriasis, ankylosing spondylitis (Morbus Bechterew), Reiter’s syndrome, diabetes mellitus types I and II and chronic uveitis, i.e. inflammatory eye disorders [4].

According to Marshall, these diseases are caused by various bacteria including L-forms of bacteria (i.e., bacteria without a cell wall) and bacteria that grow in biofilms. Marshall suggests that these bacteria block the important vitamin D receptors in the cells in the body and thereby inhibit the body’s innate immune response. As a consequence, these bacteria are not eradicated by the body’s immune system, but survive and proliferate, thereby causing continuing damage. Well-functioning nuclear vitamin D receptors, present in the majority of the body’s cells, are necessary for a wide range of important body functions.

Marshall states that these diseases can be treated by activating the nuclear vitamin D receptors [4,5] and thereby the innate immune function by taking olmesartan medoxomil tablets at a dose of 4 tablets daily at 6-h intervals. Olmesartan medoxomil (Olmetec) belongs to the group of drugs termed angiotensin II receptor antagonists. These drugs have for some years been used to treat arterial hypertension with excellent effect. In addition to olmesartan medoxomil, patients should take small doses of 5 different antibiotics – minocycline, azithromycin, clindamycin, co-trimoxazole and demeclocycline – according to a planned schedule. These antibiotics are all bacteriostatic. Furthermore patients should avoid the intake of any sort of vitamin D and of nutrients containing vitamin D, including oily fish. Vitamin D is produced in the skin by exposure to direct sunlight, which means that the patients have to protect themselves against the sun and should not sunbathe. The serum 25-hydroxyvitamin D level should be targeted to 12 μg/l. All medical treatment that reduces the immune function should be stopped. This implies that patients should not take corticosteroids or cytostatics such as azathioprine or methotrexate. These are all drugs that are used in the treatment of severe sarcoidosis. Treatment should be continued for several years and Marshall states that the effect may vary considerably from one patient to another.

Marshall’s Protocol:

 “Take 4 doses of olmesartan medoxomil daily at regular intervals in order to activate the vitamin D receptors
  Take different combinations of low doses of 5 different bacteriostatic antibiotics
  Stop any medical treatment that weakens the immune function
  Do not take vitamin D or nutrients that weaken the immune function
  Patients whose skin does not tolerate sunlight exposure should protect themselves against direct sunlight and should not sunbathe ”

Marshall’s theories are controversial and provoke great discussion among scientists. They stand in contrast to our present knowledge about the multiple functions of vitamin D. The treatment implies that patients are brought to a state of vitamin D deficiency. There is an urgent need for more basic investigations and documentation of Marshall’s theories before this treatment can be recommended on a broad basis. For example, the postulated effect of the angiotensin II receptor antagonist olmesartan medoxomil is documented by biochemical simulation, i.e. laboratory studies have not been performed in order to confirm the theory [4,6].

Furthermore the treatment carries the risk of serious side effects, e.g. osteoporosis due to vitamin D deficiency, as well as low blood pressure and renal failure due to the antihypertensive effect of olmesartan medoxomil. The longstanding (for years) treatment with antibiotics implies the risk of development of resistant bacteria and the risk of allergy against these specific antibiotics.

Concerning sarcoidosis, the actual status is that no valid studies exist that we can use to evaluate the positive or negative effects of Marshall ’s treatment. Until such studies have been performed we cannot on the basis of our present knowledge advocate this treatment until better documentation has been produced. Declaration of interest: There is no conflict of interest with regard to this Letter.

References 1. Wikipedia. Trevor Marshall. Available at: http://en.wikipedia.org/wiki/Trevor_Marshall (accessed 22 November 2010). Autoimmunity Research Foundation. Marshall Protocol 2. Knowledge Base. Available at: http://mpkb.org (accessed 22 November 2010). 3. Milman N. Hvad er Marshall Protokol — og kan vi bruge den? Ugeskr Laeger 2010;172:1852 – 3. 4. Proal AD, Albert PJ, Marshall TG. Autoimmune disease in the era of the metagenome. Autoimmun Rev 2009;8:677 – 81. 5. Albert PJ, Proal AD, Marshall TG. Vitamin D: the alternative hypothesis. Autoimmun Rev 2009;8:639 – 44. 6. Marshall TG, Lee RL, Marshall FE. Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b. Theor Biol Med Model 2006;3:1