Fatigue is very common in all Th1 diseasesThe chronic inflammatory diseases caused by bacterial pathogens. and is unrelated to sleep or rest. The symptom is believe to be caused by inflammatory cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system., the release of which is a necessary part of immunopathology. Fatigue has been shown to resolve with the Marshall Protocol but can often take quite a while.

Inflammation causes fatigue

The hallmark of chronic diseases is inflammation, the body's response to infection. Inflammation plays an increasingly well-defined role in fatigue.1)

For example, most researchers believe that the fatigue so common in patients with multiple sclerosis, a typical Th1 diseaseAny of the chronic inflammatory diseases caused by bacterial pathogens., is caused by inflammatory cytokines such as TNF-alphaA cytokine critical for effective immune surveillance and is required for proper proliferation and function of immune cells. and interferon gamma that go along with elevated 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol.. One study found that TNF-alpha values significantly correlated with daytime sleepiness as measured by the Epworth Sleepiness Scale. Controlling for disease activity (as measured by the Cambridge Multiple Sclerosis Basic Score), disease duration, Expanded Disability Status Scale, and depression further increased the correlation of cytokineAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. production and fatigue.2)

Once on the MP, some patients report intense exacerbation of symptoms, severe lightheadedness, or profound fatigue, and are convinced that they are getting sicker. I have to assure them that what they are feeling is the natural result of their immune systems dealing with toxins, cellular debris and the remains of dead bacteria. Europeans are usually more open to the idea, but North Americans have really been brainwashed to equate symptoms with disease. In cases where people have trouble grasping this concept, the biggest hurdle is to get them through the first phase of the treatment when the immunopathology is often strongest.

Greg Blaney, MD

Virtues of fatigue

From an evolutionary perspectives, the fatigue caused by inflammation may benefit a person. Andrew Miller of Emory University School of Medicine states in New Scientist that “cytokines are trying to shut your body down so that you can devote your resources to healing.” In a 2009 paper, he goes on to conclude that fatigue is part of healing:

Taken together, these effects of cytokines on the brain and behavior appear to subserve competing evolutionary survival priorities that promote reduced activity to allow healing, and hypervigilance to protect against future attack.

Andrew Miller

Management of fatigue

Increased energy consumption by immune cells requires a metabolic adaptation of the whole organism. 3)

  • Develop an “energy conservation” program – Re-define “necessary” and sort out the really important activities from those that can wait. MP patients should pace themselves through the day, saving necessary activities for the time of day when they tend to have more energy. Forego jobs that need not be done every day, such as making beds.
  • Patients are advised not to overexert themselves.
  • If engaging in physical activity or exercise, increase activity level by no more than 5-10% per week.
  • Keep a journal to learn energy patterns.
  • Patients should ask their physician about an occupational therapy evaluation to teach energy-saving strategies.
  • Quercetin may help reduce intolerable fatigue – Bear in mind that quercetin does appear to interfere, somewhat, with the action of the antibiotics and should not be used at the beginning of the MP or routinely at any time.


In the management of fatigue, stimulants such as modafinil (Provigil) and caffeine are not recommended. There is limited data on how exactly stimulants modulate the immune response.

Caffeine ingestion can delay fatigue during exercise, but the mechanisms remain elusive. 4)

Patients experiences

I am amazed at what I can do in one day now. The really amazing days tend to happen at the end of the cycle but all my days are more active now. At times in the past, I really dreaded ‘time off’ at home because I couldn’t do the things I wanted to do anyway and I didn’t magically feel better either. Now I can enjoy a break from work and get out and about and have a social time.

~Vicki SA

I've been fatigued ever since starting mino. As long as I can get through the day and do the things I absolutely have to, it's good. If I can't, then it's gone over the line and something needs to be done. You'll have to set your own levels and expectations.

Sometimes my fatigue has been a general malaise, and other times it has been specific muscles or been more muscular in general. Feels like I have been lifting weights and the muscles are just wiped out. I still get that in the shoulders after more than a year on the MP. Not as bad as it was, but it's there. Sometimes it's my ribs - feels like I was picked up by a giant, given a squeeze and set back down in a slightly squashed condition. It moves around.

Pace yourself, and decide what things are “must do” and what are “nice to do” and get your herxing to a level where you can treat yourself once in a while. It will vary as you move through the doses anyway, so you'll have some good days. And some of them will be very good indeed, if my experience is any indication.

Do more sitting down when cooking. That seems to help with conserving energy. Get your minions to help (if you've got minions). As they say in the old song, “Every little bit added to what you've got, makes just a little bit more”.


When you feel fatigued are you able to lay down and sleep, or do you try to stay up and function? You might try laying down and just letting your body take a physical rest during that period and let the immunopathology run its course. That is what I find myself doing more and more. Then when I arise I'm able to accomplish more than I would have struggling through the fatigue.


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===== References =====

Miller AH. Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behav Immun. 2009 Feb;23(2):149-58. doi: 10.1016/j.bbi.2008.08.006. Epub 2008 Sep 3.
[PMID: 18793712] [PMCID: 2745948] [DOI: 10.1016/j.bbi.2008.08.006]
Heesen C, Nawrath L, Reich C, Bauer N, Schulz K, Gold SM. Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?. J Neurol Neurosurg Psychiatry. 2006 Jan;77(1):34-9. doi: 10.1136/jnnp.2005.065805.
[PMID: 16361589] [PMCID: 2117393] [DOI: 10.1136/jnnp.2005.065805]
Dolezal T. Adenosine: a selfish-immunity signal?. Oncotarget. 2015 Oct 20;6(32):32307-8. doi: 10.18632/oncotarget.4685.
[PMID: 26427038] [PMCID: 4741691] [DOI: 10.18632/oncotarget.4685]
Davis JM, Zhao Z, Stock HS, Mehl KA, Buggy J, Hand GA. Central nervous system effects of caffeine and adenosine on fatigue. Am J Physiol Regul Integr Comp Physiol. 2003 Feb;284(2):R399-404. doi: 10.1152/ajpregu.00386.2002. Epub 2002 Oct 24.
[PMID: 12399249] [DOI: 10.1152/ajpregu.00386.2002]
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