Oxidation for Chronic Fatigue Syndrome and Fibromyalgia

A large proportion of my naturopathic patients present with some form of fatigue and fibromyalgia type pain. It is a common complaint even in cities such as Vancouver and Richmond, which have a relatively health conscious population. In many cases, the fatigue may be a symptom of a coexisting condition. For example, fatigue is one of the many symptoms of diseases such as rheumatoid arthritis, anemia, hypothyroidism, congestive heart failure, and so forth. In fact, fatigue can be a symptom of many disease processes. This is why a conventional workup, including history, examination, and when necessary, laboratory investigation, is necessary to rule out other disease processes that may attribute to fatigue. In these cases, the fatigue is secondary, and will likely improve when treatment for the primary condition has been successful.

But what about the patient, where fatigue persists and no conventional cause or diagnosis can be found? The numbers are actually quite staggering, as the CDC states that up to 4 million Americans suffer from the disease that has been labelled chronic fatigue syndrome. When specific types of pain and sensitivity are present, then the diagnosis is chronic fatigue syndrome and fibromyalgia. Diagnosis is a challenge for a conventional internal medicine approach because there are no consistent lab biomarkers that are specific for CFS, patient's do not “look sick,” as mentioned above, fatigue is common to many other illnesses, and finally, chronic fatigue syndrome and fibromyalgia can tend to relapse and remit. Can 4 million American's, (and many Vancouver and Richmond patients of course!) and many more world wide, all have chronic fatigue and fibromyalgia, and yet be correctly told that there is “nothing wrong with them?”

The CDC in the US has given the following two criteria for a diagnosis of chronic fatigue syndrome:

1. Unexplained, persistent fatigue that's not due to ongoing exertion, isn't substantially relieved by rest, is of new onset (not lifelong) and results in a significant reduction in previous levels of activity.

2. Four or more of the following symptoms are present for six months or more:

• Impaired memory or concentration

• Post-exertional malaise (extreme, prolonged exhaustion and sickness following physical or mental activity)

• Unrefreshing sleep

• Muscle pain

• Multi-joint pain without swelling or redness

• Headaches of a new type or severity

• Sore throat that's frequent or recurring

• Tender cervical or axillary lymph nodes

That is a reasonable list that covers most of my patients who have chronic fatigue and have had other, reasonably likely, diseases ruled out.

The Institute of Medicine has guidelines in 2015 that propose the following diagnostic criteria:

1.     A substantial reduction or impairment in the ability to engage in pre-illness levels of activity (occupational, educational, social or personal life) that:

1.          lasts for more than 6 months

2.     is accompanied by fatigue that is:

1.          often profound

2.          of new onset (not life-long)

3.     not the result of ongoing or unusual excessive exertion

4.     not substantially alleviated by rest

2. Post-exertional malaise (PEM)* – worsening of symptoms after physical, mental or emotional exertion that would not have caused a problem before the illness. PEM often puts the patient in relapse that may last days, weeks, or even longer.

3.     Unrefreshing sleep* – patients with ME/CFS may not feel better or less tired even after a full night of sleep despite the absence of specific objective sleep alterations.

At least one of the following two additional manifestations must be present:

1.     Cognitive impairment* – patients have problems with thinking, memory, executive function, and information processing, as well as attention deficit and impaired psychomotor functions. All can be exacerbated by exertion, effort, prolonged upright posture, stress, or time pressure, and may have serious consequences on a patient’s ability to maintain a job or attend school full time.

2.     Orthostatic intolerance – patients develop a worsening of symptoms upon assuming and maintaining upright posture as measured by objective heart rate and blood pressure abnormalities during standing, bedside orthostatic vital signs, or head-up tilt testing. Orthostatic symptoms including lightheadedness, fainting, increased fatigue, cognitive worsening, headaches, or nausea are worsened with quiet upright posture (either standing or sitting) during day-to-day life, and are improved (though not necessarily fully resolved) with lying down. Orthostatic intolerance is often the most bothersome manifestation of ME/CFS among adolescents.

*The frequency and severity of these symptoms need to be evaluated. The IOM committee specified that “The diagnosis of ME/CFS should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.”

Additional Naturopathic Work Up for chronic fatigue syndrome and fibromyalgia

Naturopathic medicine views a patient from a holistic perspective. It is not simply about using natural substitutes for drug products or surgery.

A naturopathic approach in depression might involve, depending on the detailed history, looking at subtle thyroid or adrenal hormone imbalances, toxicities that affect neurological function and communication, deficiencies or dependencies on nutrients that affect mood, or sometimes even infection or inflammatory disorders. It would not simply involve giving a natural substitute for the serotonin reuptake inhibitor drugs, although that could be a part of the whole plan.

In a naturopathic work up for chronic fatigue syndrome and fibromyalgia the following tests may be useful (case dependant):

– hsCRP

– ESR

– ANA/RF

– CBC

– ferritin

– blood chemistry panel

– thyroid panel with TSH, free T3, free T4, reverse T3, TPO

– 4 point salivary cortisol levels in 24 hours

– mold IgG and IgE panel, Mycotoxin panel

– Western Blot IgG for Lyme (Borrelia)

– blood mercury level and provoked urinary metals

Some of these tests, such as the western blot for Lyme, ferritin, and the thyroid panel, are still looking for conventional diseases, but may be overlooked by conventional medicine. The rest may be positive in chronic fatigue syndrome and fibromyalgia patients, but are not specific for that disease only. In other words, they can be positive in other conditions as well. However, may be able to help to guide the type, frequency and intensity of treatment, as well as provide objective markers for health improvement to correlate with subjective improvement in fatigue.

Many physicians and naturopathic doctors have firmly held the belief that chronic fatigue syndrome and fibromyalgia may be associated with multiple, silent, persistent infections.

Multiple because it would be considered rare for a single infection to cause such profound and long-lasting weakness. This is even the case in cases where Lyme disease is involved. The Borrelia organism that causes lyme disease creates a distinct subset of disease. However, in patients who have reacted with the full chronic disease syndrome manifestations, Borrelia may be primary but coinfections with other organisms likely are associated with the longstanding persistence and debilitating nature of the disease.

Silent because it is rare to have the typical manifestations of infections. Thus it is rare to see a patient with a fever, an elevated white blood cell count, or very high CRP or ESR levels. Silent also because the immune system is unable or unmotivated to mount an effective response to the infection.

Persistent for obvious reasons. Most of the patients who have had chronic fatigue syndrome and fibromyalgia have tried multiple approaches, and multiple natural alternatives to drugs.

The naturopathic treatment for chronic fatigue syndrome and fibromyalgia that I prefer is oxidation therapy and nutrient repletion. Nutrient repletion is treated with vitamin and mineral infusions, oxidation is achieved by ozone therapy.

The second step of my naturopathic treatment for chronic fatigue syndrome and fibromyalgia is either ozone or ultraviolet blood irradiation. This is an older therapy which was used in American hospitals before interest was lost with the advent of the “cure” of infections with penicillin. Ultraviolet blood irradiation, with the addition of ozone, stimulates the immune system to address both acute, and in the case of chronic fatigue syndrome, multiple silent chronic infections. The mechanism involves oxidation and stimulation of cytokines that regulate the immune system. In my experience, I often find that ozone therapy alone can give similar results as ozone combined with ultraviolet blood irradiation.

Robert Rowen, MD, author of Second Opinion Newsletter, has written a very comprehensive article about the use of ultraviolet blood irradiation in American hospitals for serious acute infections. The article is called the “Cure that time forgot,” and is available online. 

There are a few theorized mechanisms of how such a ozone / ultraviolet blood irradiation may help addressing multiple, silent, persistent chronic infections. What we do know is that although the small amount of blood treated (100-125 mls), the mechanism does not likely involve a simple direct killing of infections in the blood because it is only a small portion of the total blood supply that is treated.

One plausible and likely mechanism is that the ozone or ultraviolet blood irradiation acts as an ‘autologous stimulation’ that the infections or toxins produced by the infection are present in the blood stream already. The combination of UV exposure and ozone acts to break down the germ or toxin, exposing new areas to the immune system when the blood is reinfused. The immune system then becomes activated, and over a few stimulations, these infections are no longer “silent” and they stimulate an appropriate response from the white blood cells.

A more recent mechanism that has been elucidated involves the stimulation of cytokine release by the white blood cells. When UV energy or ozone reacts with the white blood cells in the blood, the chemical messengers that stimulate activation of the immune system are released. These cytokines are then reinfused into the body as the blood is returned to the patient. Cytokines are the messengers of the immune system, and with a proper coordinated release of cytokines, the immune system becomes much more adept at clearing chronic persistent infections.

A good summary of the mechanisms in ozone therapy is published at: Curr Med Chem. 2016;23(4):304-14. Ozone: A Multifaceted Molecule with Unexpected Therapeutic Activity.

There is also the mechanism of increasing circulation, oxygen delivery, and energy generation that I have described in an article on oxidative medicine in general. This involves the effect of peroxides that are created by ozone and UV when they react with the blood. The short chain fatty peroxides oxidize cofactors in the energy generating systems of the cell, called the Kreb's cycle and oxidative phosphorylation in the mitochondria. Chemicals like 2,3 diphosphoglycerate increase (helping red cells to deliver oxygen,) intracellular antioxidants such as catalase and glutathione increase, and blood viscosity decreases.

Is such therapy superior to antibiotic therapy for chronic fatigue syndrome and fibromyalgia?

In my experience, it depends. Unless lyme disease, or a similar intracellular pathogen (germ) is confirmed to be positive, it is difficult to find a drug that is active against the multiple infections present. In my opinion, it is generally better to actively involve and stimulate the immune system to clear the infection, so this ability to clear the infection lessens chances of recurrence. If only antibiotics are used, or antivirals, then on stopping the medicine, there is a chance of recurrence if exposure reoccurs, or if the latent infection becomes more active.

What does a course of therapy entail?

In most cases of chronic fatigue syndrome, the short course of IV nutrient and ozone treatments involves two to three treatments a week for 4-5 weeks. Follow up lab panel and treatment is given in 4 weeks.  Treatments may be then given as needed in the future.

 

Rationale for Myers’ / IV Nutrient Injections (in general):

  • IV administration of nutrients can result in serum levels much higher than possible with oral administration (Okayama et al, JAMA 1987; Sydow M et al, Intensive Care Med. 1993.) 

  • Magnesium may promote smooth muscle relaxation in blood vessels and bronchial muscle (Iseri LT et al. Am Heart J. 1984)(Brunner EH et al. J Asthma. 1985.), that may be beneficial for high blood pressure, bronchial asthma, migraine headache.

  • IV administration of 7.5 g of vitamin C over an hour has been demonstrated to reduce serum histamine levels by 31% (Hagel AF et al. Naunyn Schmiedebergs Arch Pharmacol. 2013.)  This may be beneficial for allergic conditions.

  • Some nutrients may exert effects that are concentration dependent, such as anti-viral effects of vitamin C at 10-15 mg/dl (Harakeh S et al. Proc Natl Acad Sci. 1990.), only achieved through IV administration

 

Conditions that may be improved by Myers’ (IV vitamin/mineral) injections (personal experience as per Alan Gaby, MD; Gaby, A, Nutritional Medicine 2nd Ed.)

  • Fatigue

  • Fibromyalgia / polymyalgia rheumatica

  • Depression

  • Asthma

  • Migraine

  • Cardiovascular disease

  • Upper respiratory tract infection

  • Sinusitis

  • Seasonal Allergic rhinitis

  • Chronic urticaria

  • Athletic performance

  • Hyperthyroidism

 

Modified Myers’ ingredients: Magnesium, sometimes calcium, Vitamin C, B-complex, B6, B5.  Formulation may be altered to better meet patient case specifics.  This may be diluted to ~35mL with sterile water and given as an IV push, or push into 100mL saline and given a slower an IV drip.

Myers’ injection safety: Generally well tolerated by most patients in our experience.  Dr Alan Gaby has had no adverse reactions in approximately 15,000 treatments when administered with caution and respect (Gaby, Alan. Nutritional Medicine, 2nd Ed.)  Extra caution should be taken in potassium depleting conditions and medications (e.g. taken potassium depleting medications; states of low potassium: potassium depleting diuretics, beta agonists, glucocorticoids, diarrhea, vomiting, malnourishment), as IV magnesium can potentially worsen low blood potassium levels (can increase risk of digoxin induced cardiac arrhythmias). Lower nutrient doses may be used in mild to moderate renal insufficiency. The Myers’ injection often causes a sensation of heat (from magnesium.)  Low blood pressure and excessive heat may be associated with rapid injection, and higher dose of magnesium.  Lower magnesium doses and slower injections (e.g. IV drip) may be indicated for those with lower blood pressure.  Anaphylactic reactions to thiamine (B1) have been reported in the medical literature on the rare occasion.  The Myers’ injection tends to be hypertonic (concentrated), thus tenderness, burning sensation at the injection site, vein irritation, phlebitis is possible.  Often repositioning the needle in the vein or further diluting nutrients can help reduce or eliminate pain or irritation.  Myers’ injection given as an IV drip (in 100cc of saline tends to be less hypertonic/concentrated).

 

Ozone therapy safety (major autohemotherapy): A survey done in Germany of close to 5 million ozone treatments showed an accident rate of 7 serious incidents, all associated with direct IV injection of the gas (not done in our clinic).  There is a slight possibility of allergy to heparin, though this is a commonly used blood thinner. Some patients do not like the site of their own blood, but they quickly become accustomed to this.

In our experience, the most frequently seen (but still rare) side effect is dizziness/vasovagal/fainting reaction due not at all to the volume of the blood, but rather the needle experience as well as seeing the blood. Possible but extremely rare complications may include soft tissue infection (as with any injection / blood draw), or vein inflammation and clots.

One recent case study has been published on ozone therapy where a single patient with kidney failure had high blood potassium and subsequent arrhythmia. The authors had concluded that the ozone therapy (which looked to be done 9 days in a row) was to blame, but this is not at all clear. The authors did not think that red cell breakdown was responsible for the high blood potassium, but that is the only mechanism that would make sense if the ozone was done daily. Theoretically low grade red cell breakdown would release potassium, and if the treatment is overdone and the kidneys can not excrete this could accumulate.

Photoluminescence therapy (ultraviolet blood irradiation) was used extensively in the 30's to 40's before the advent of antibiotics and the vaccine for polio.  It has an extensive safety and efficacy record. For a great summary of this treatment, buy the book "Into the Light" at www.drdouglass.com.  An online article also available is “The Cure that time forgot” which summarizes much of the published experience.  Potential side effects of ultraviolet blood irradiation are similar to those mentioned above for ozone therapy/major autohemotherapy.

 

 

References: Myers’, Intravenous vitamin/mineral injections

 

Gaby AR. 2002. Intravenous nutrient therapy: the "Myers' cocktail". Altern Med Rev. 2002 Oct;7(5):389-403.

 

Ali A, Njike VY, Northrup V, Sabina AB, Williams AL, Liberti LS, Perlman AI, Adelson H, Katz DL. 2009. Intravenous micronutrient therapy (Myers' Cocktail) for fibromyalgia: a placebo-controlled pilot study. J Altern Complement Med. 2009 Mar;15(3):247-57.

 

Okayama H, Aikawa T, Okayama M, Sasaki H, Mue S, Takishima T. 1987. Bronchodilating effect of intravenous magnesium sulfate in bronchial asthma. JAMA. 1987 Feb 27;257(8):1076-8.

 

Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Camargo CA Jr. 2000.  Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev. 2000;(2):CD001490.

 

Sydow M, Crozier TA, Zielmann S, Radke J, Burchardi H. 1993. High-dose intravenous magnesium sulfate in the management of life-threatening status asthmaticus. Intensive Care Med. 1993;19(8):467-71.

 

Harakeh S, Jariwalla RJ, Pauling L. 1990. Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7245-9.

 

Harakeh S1, Niedzwiecki A, Jariwalla RJ. 1994. Mechanistic aspects of ascorbate inhibition of human immunodeficiency virus. Chem Biol Interact. 1994 Jun;91(2-3):207-15.

 

Hagel AF, Layritz CM, Hagel WH, Hagel HJ, Hagel E, Dauth W, Kressel J, Regnet T, Rosenberg A, Neurath MF, Molderings GJ, Raithel M. 2013. Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases. Naunyn Schmiedebergs Arch Pharmacol. 2013 Sep;386(9):789-93.

 

Iseri LT, French JH. 1984. Magnesium: nature's physiologic calcium blocker. Am Heart J. 1984 Jul;108(1):188-93.

 

Brunner EH, Delabroise AM, Haddad ZH. 1985. Effect of parenteral magnesium on pulmonary function, plasma cAMP, and histamine in bronchial asthma. J Asthma. 1985;22(1):3-11.

 

Sharma SK, Bhargava A, Pande JN. 1994. Effect of parenteral magnesium sulfate on pulmonary functions in bronchial asthma. J Asthma. 1994;31(2):109-15.

 

 

 

References: Ozone and Diabetes

 

Bocci V, Zanardi I, Huijberts MS, Travagli V. 2011.  Diabetes and chronic oxidative stress. A perspective based on the possible usefulness of ozone therapy. Diabetes Metab Syndr. 2011 Jan-Mar;5(1):45-9.

 

Bocci V, Zanardi I1, Huijberts MS, Travagli V. 2014. It is time to integrate conventional therapy by ozone therapy in type-2 diabetes patients. Ann Transl Med. 2014 Dec;2(12):117.

 

Bocci V, Zanardi I, Huijberts MS, Travagli V4. 2014. Diabetes Metab Syndr. 2014 An integrated medical treatment for type-2 diabetes.  Jan-Mar;8(1):57-61.

 

de Monte A, van der Zee H, Bocci V. 2005. Major ozonated autohemotherapy in chronic limb ischemia with ulcerations. J Altern Complement Med. 2005 Apr;11(2):363-7.

 

Braidy N, Izadi M, Sureda A, Jonaidi-Jafari N, Banki A, Nabavi SF, Nabavi SM5. 2018. Therapeutic relevance of ozone therapy in degenerative diseases: Focus on diabetes and spinal pain. J Cell Physiol. 2018 Apr;233(4):2705-2714.

 

References: Ozone

 

Bocci V, Zanardia I, Valacchi G, Borrelli E, Travagli V. 2015. Validity of Oxygen-Ozone Therapy as Integrated Medication Form in Chronic Inflammatory Diseases. Cardiovasc Hematol Disord Drug Targets. 2015;15(2):127-38.

 

Giunta R, Coppola A, Luongo C, Sammartino A, Guastafierro S, Grassia A, Giunta L, Mascolo L, Tirelli A, Coppola L. 2001. Ozonized autohemotransfusion improves hemorheological parameters and oxygen delivery to tissues in patients with peripheral occlusive arterial disease. Ann Hematol. 2001 Dec;80(12):745-8.

 

Valacchi G, Bocci V. 2000. Studies on the biological effects of ozone: 11. Release of factors from human endothelial cells. Mediators Inflamm. 2000;9(6):271-6.

 

Inal M, Dokumacioglu A, Özcelik E, Ucar O. 2011. The effects of ozone therapy and coenzyme Q₁₀ combination on oxidative stress markers in healthy subjects. Ir J Med Sci. 2011 Sep;180(3):703-7.

 

Wu XN, Zhang T, Wang J, Liu XY, Li ZS, Xiang W, Du WQ, Yang HJ, Xiong TG, Deng WT, Peng KR, Pan SY. 2016. Magnetic resonance diffusion tensor imaging following major ozonated autohemotherapy for treatment of acute cerebral infarction. Neural Regen Res. 2016 Jul;11(7):1115-21.

 

Smith NL, Wilson AL, Gandhi J, Vatsia S, Khan SA. 2017. Ozone therapy: an overview of pharmacodynamics, current research, and clinical utility. Med Gas Res. 2017 Oct 17;7(3):212-219.

 

Molinari F, Simonetti V, Franzini M, Pandolfi S, Vaiano F, Valdenassi L, Liboni W. 2014. Ozone autohemotherapy induces long-term cerebral metabolic changes in multiple sclerosis patients. Int J Immunopathol Pharmacol. 2014 Jul-Sep;27(3):379-89.

 

 

 

References: Ultraviolet Blood Irradiation

 

Hamblin MR. 2017. Ultraviolet Irradiation of Blood: "The Cure That Time Forgot"? Adv Exp Med Biol. 2017;996:295-309.

 

Wu X, Hu X, Hamblin MR. 2016. Ultraviolet blood irradiation: Is it time to remember "the cure that time forgot"? J Photochem Photobiol B. 2016 Apr;157:89-96.

 

Kuenstner JT, Mukherjee S, Weg S, Landry T, Petrie T. 2015. The treatment of infectious disease with a medical device: results of a clinical trial of ultraviolet blood irradiation (UVBI) in patients with hepatitis C infection. Int J Infect Dis. 2015 Aug;37:58-63.

 

 

 

References: Acupuncture for Headaches, Pain

 

Mayrink WC1, Garcia JBS2, Dos Santos AM2, Nunes JKVRS3, Mendonça THN2.2018. 2018. Effectiveness of Acupuncture as Auxiliary Treatment for Chronic Headache. J Acupunct Meridian Stud. 2018 Oct;11(5):296-302.

 

Linde K, Allais G, Brinkhaus B, Fei Y, Mehring M, Shin BC, Vickers A, White AR. 2016. Acupuncture for the prevention of tension-type headache. Cochrane Database Syst Rev. 2016 Apr 19;4:CD007587.

 

Linde K, Allais G, Brinkhaus B, Fei Y, Mehring M, Vertosick EA, Vickers A, White AR. 2016. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev. 2016 Jun 28;(6):CD001218.

 

Nielsen A. 2017. Acupuncture for the Prevention of Tension-Type Headache (2016). Explore (NY). 2017 May - Jun;13(3):228-231.

 

Yin C, Buchheit TE, Park JJ. 2017. Acupuncture for chronic pain: an update and critical overview. Curr Opin Anaesthesiol. 2017 Oct;30(5):583-592.

 

Lin YC, Wan L, Jamison RN. 2017. Using Integrative Medicine in Pain Management: An Evaluation of Current Evidence. Anesth Analg. 2017 Dec;125(6):2081-2093.