Doctor:” What seems to be going on today?”   doctor-patient-relationship

Patient: “Well Doc, I have been tired for a while”

Doctor: ”Really? How long have you been fatigued?”

Patient: “I would guess a little over 6 months.”

Doctor: “So would you consider yourself to have chronic fatigue?”

Patient: “Yes I would say it is def. chronic”

Doctor:” Well, through my education I would say you have chronic fatigue syndrome”

 

Really?!   Is that what we have sunken too? Creating disease syndrome with the patient’s own subjective complaints? I think sometimes we get so caught up in labeling things that it clouds the true underlying issue. Let us start with a little history of chronic fatigue syndrome.

In the 19th century, a doctor by the name of George Beard, M.D. coined the term neurasthenia, also known as nervous system exhaustion. The symptoms that accompanied neurasthenia were anxiety, exhaustion, depression and sexual dysfunction to name a few. Eventually the disorder caught on in the medical community and quickly droves of patients were being diagnosed with chronic fatigue syndrome, CFS or myalgic encephalomyelitis, ME . With push from the health profession to figure out the cause, active viral infections were first in mind due to the symptoms of these patients. Epstein Barr (EBV, cytomegalovirus (CMV)), and herpes simplex virus (HSV) were studied. Research reported that high titers of EBV, CMV and HSV were found in those patients that were symptomatic CFS. So finally we had a solid connection between the mysterious symptoms of CFS and a causative agent; until 2 studies by Buchwald et al. and Koelle et al. were published. They looked at 13 different viruses in symptomatic CFS patients and found that there was no relationship between the titers of antibodies to the viruses and the symptoms of patients. This means the association between the aforementioned viruses and CFS could not be definitively confirmed by viral infections alone.

Xenotropic murine leukemia virus or XMRV, has long be touted as a cause for CFS; but current research has dismissed this virus as a single causative agent much like the ones above.

Although no single one of these viruses are pathognomonic (disease causing) of CFS, it is still important to rule them out as these symptoms mimic those of CFS. Your physician, through public labs such as LabCorp and Quest, can order viral load tests. There are other labs geared toward infectious disease analysis if you want more in-depth studies ran.

The data continues to be mixed on this particular syndrome, but most agree that it is heavily rooted in some sort of immunological dysfunction. Through the article I will mention fibromyalgia and CFS as if they were interchangeable conditions. Although they are separate and distinct, they share many commonalities in their etiology. In this article we will concentrate on general nutritional deficiencies and digestive function as it pertains to immunology, but we must appreciate that there are numerous other factors such as viral load, environmental toxins, endotoxins, and mitochondrial dysfunction. These will all be broken down into sub-topics at a later date.

The Gut and Nutrition

UntitledWe’ll start with nutrition, as it can be the most influential factor in our lives. The average American adult consumes over 2000 pounds of food per year – most of which is now processed, poorly farmed or full of harmful additives. Some argue that foods can be broken down into just 2 categories: harmful or helpful. This is true, but can be highly dependent on the persons biochemistry.

When we treat patients that have fibromyalgia or CFS with antibiotics or natural anti-microbials, we see reduction in pain, increased energy, and restoration of proper neural firing mechanisms. This leads us to believe that there is a gastro-intestinal bacteria component to these disease processes, which will be discussed later, but its mention here was important as this is a common theme in most autoimmune or multi-system disorders.

We find B vitamin, L-carnitine and CoQ10 deficiencies in most patients. These subsets of nutrients are extremely valuable in the production of energy and the health of mitochondria. Mitochondria make cellular energy or ATP. Adequate intake of B vitamins can be consumed from the diet/supplements, but these also must be taken in proper forms. For instance, folic acid (vitamin B9) must be methylated to be absorbed. Nearly 55% of the population has some form of genetic defect in their methylation cycle meaning that folic acid will never properly be metabolized and absorbed completely. In fact, folic acid can be toxic at high amounts in the body, so it is important for your physician to do a proper work up including lab testing for the “MTHFR” defects. Methylated folate or calcium folinate are the preferred forms of vitamin B9. Taking a good complex B vitamin or multi-vitamin high in the B’s is good wellness practice. L-carnitine is to fat, like insulin is to glucose. L-carnitine drags fat into the mitochondria to burn for energy in the form of ATP. Most folks with CFS have a dysfunction in their mitochondria, thus L-carnitine can be extremely powerful for them. Acetyl-L-carnitine is the preferred form due to its bioavailability and its ability to aid in cognition.

 

Low serum CoQ10 is seen in nearly 40% of patients with CFS. CoQ10 is an essential nutrient for the mitochondria, ATP production and an antioxidant. Furthermore, CoQ10 helps with cognition and heart function. Animal models have shown beneficial results in gut function and decreased overall inflammation when supplemented with CoQ10. This is most likely due to its antioxidant properties as well as its ability to promote proper mitochondrial function and ATP production. Signs of low serum CoQ10 are memory disturbances, muscle pain, fatigue, and depression.

 

A basic characteristic of patients with CFS is inadequate diet in amino acids or poor absorption from a dysfunctional digestive tract. Amino acids are broken down into two main categories: essential and non-essential. Essential amino acids must be obtained from the diet as our bodies cannot manufacture them, but they are integral to our health. The non-essential amino acids our bodies can produce when necessary. Important note: the term essential does not mean they are “more important” than non-essential amino acids.   To confuse things a bit more, L-carnitine is conditionally essential; meaning that the body can manufacture it, but it must also be consumed from an external source in certain instances when the individual does not synthesize it in adequate amounts. L-carnitine is made in the liver and kidneys (important to check the function of these organs as well) from lysine and methionine and is necessary to shuttle fats to the mitochondria for energy. Mitochondria dysfunction is one of the hallmark causes seen in CFS. The Journal of Applied Nutrition published a study, Treatment of Chronic Fatigue Syndrome with Specific Amino Acid Supplementation, which concluded that 75% of those tested and treated with a specific amino acid regimen saw complete resolution of symptoms; 15% had moderate, and 10% little or no relief. This was a small study of only 25 patients but produced good clinical data stating that proper amino acid administration positively effects the TCA cycle (aka citric acid cycle), thus creating more ATP, which is lacking in CFS patients. A good broad spectrum of amino acid supplements or a high quality complete protein, such as cold processed whey protein, can supply most with adequate amounts of amino acids. Some chronic fatigue patients must have a custom formula made to meet their unique demands. In order to assess these unique demands, a blood and urine combination test much be performed.

Screen Shot 2014-04-20 at 4.28.19 PM

Picture taken from MedScape.com

 Neurotransmitters

Neurotransmitters are communication proteins and almost 70% of them are made in our gut! The most well known neurotransmitters are serotonin, Chronic Fatiguedopamine, and GABA. Many patients I see have an altered balance of these nervous system hormones and can present with depression, fatigue, mental fogginess and lapses in memory. Testing for neurotransmitters is still up for debate. I prefer to look at the breakdown compounds from neurotransmitter metabolism rather than the formed hormone. Organic acid testing can be performed at home (urine test) and is unique in its ability to present different metabolic processes such as neurotransmitter metabolism, detoxification, etc.

Chronic fatigue syndrome is often associated with fibromyalgia due to the commonality of their etiology (close relationship of causes). One phenomenon known as “central sensitization” is commonly present in these patients. Central sensitization is a non-painful stimulus causing pain, i.e. the sheets on your bed touch your legs would cause you discomfort or full on pain- hyperalgesia. One theory behind central sensitization is receptors in your brain, NDMA receptors, become bombarded with stimulus due to the break down of the blood-brain barrier, BBB, from inflammation. The blood brain barrier is supposed to protect the brain from harmful chemicals. Nutrients, such as magnesium, can block or regulate the NDMA receptor, as well as help produce serotonin and melatonin both of which are seen to be deficient in CFS. Magnesium can also be found modulating the release of acetylcholine. Acetylcholine is a neurotransmitter that helps muscle motor firing. Like most chemicals in the body it is all about balance- too much acetylcholine and we get muscle splinting/spasm that causes pain and fatigue. Magnesium is an antagonist to acetylcholine, which means it helps to regulate the amount a muscle is exposed to. Without enough magnesium we can get a lot of muscular tension. Stay away from less expensive forms of magnesium, such as lactate or oxides, as humans poorly absorb these. Supplementing with 5-HTP and pre-formed melatonin also produce good results. Nutrition for the blood brain barrier is equally as important- omega 3 fatty acids, alpha lipoic acid and phosphatidylserine are some of my favorite.

All of these metabolic pathways can become disturbed by inflammation. So where does this inflammation come from?…mostly from the gut.

 

Digestion, the gut and probiotics

Most chronic fatigue patients complain, at some point in their life, of having irritable bowel syndrome (IBS). There is a strong correlation in the research between IBS and both fibromyalgia and chronic fatigue syndrome. Both of these conditions are often looked at simultaneously because of their similar etiologies. In one study published in the Annals of the Rhuematic Diseases, it stated that the degree of abnormal gut bacteria was greater in those patients who were experiencing higher pain. Another way to say that is, the more bad gut bacteria, the more pain they would experience.

A 2011 study published in Gut, looked at the effects of patients who were infected with Giardis lamblia. Giardia lamblia is a commonly known cause of gastritis and what was unique about this article was they looked at these patients 3 years after their acute infection: “Infection with Giardia lamblia in a non-endemic area was associated with a high prevalence of IBS and chronic fatigue 3 years after acute illness, and the risk was significantly higher than in the control group. This shows that the potential consequences of giardiasis are more serious than previously known.” These residual symptoms can be evidence of the long-term effects of these infections even after they have been removed from the body.

The overgrowth of these bacterial colonies is referred to as SIBO or small intestinal bacterial overgrowth. One paper looked at the prevalence of SIBO and its relationship to certain health conditions and concluded: 40% of Rheumatoid Arthritis patients, 84% of patients with IBS, and 90-100% of those with fibromyalgia all had the presence of SIBO. In fact the degree or severity of SIBO was directly proportional to the patients subjective symptoms.

Studies examine the microbiota or environment in our digestive track to identify specific microorganisms that are present in patients with CFS. The pathogenic microorganisms begin to breakdown the protective layers in our intestines and increase the immune response, which brings inflammation. Eventually, this becomes so severe to the point we have what is known as “leaky gut”. These bacteria (can also be viruses, parasites, toxins etc.) begin to cause immunological dysfunction not only in the gut, but also have the ability to translocate or produce endotoxins that trigger whole body inflammation and neuro-excitation. Altered GI microecology, break down of the mucosal barrier and immune dysregulation/dysfunction all play a role in CFS. It should be part of every patients medical work-up to be evaluated for pathogenic bacteria as well as interventions with antimicrobials, if the need presents itself.

“Those that suffer from CFS are nearly six times more likely to be depressed or anxious than those without.”

Vitamin D has been shown to improve intestinal layer migration and tighten gap junctions in the gut lining according to “Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier”, published in the American Journal of Gastrointestinal Liver Physiology.  Curcumin and Acetyl-L-carnitine can also be beneficial in these patients to help reduce bowel wall inflammation.

Probiotics have become essential in the course of treatment; they make beneficial changes in the micro flora of the gut which can improve gastric motility, restore mucosal barrier integrity and reduce overall inflammatory load on the body due to the reduction in cytokine production from antigenic bacteria. Probiotics can be found in some foods (particularly dairy products). I do not recommend getting your probiotics from dairy products. As humans we are very sensitive to cows milk and it can be hard to digest. Some studies report that cows milk can trigger Type I Diabetes. Also, cow milk based products, such as yogurt, are high in sugar which can further lead to free radical production and bowel inflammation. I highly recommend a good quality source of probiotics with an adequate amount of fiber in your diet.  Pharmaceutical grade probiotic blends with multiple strains of gut bacteria are best.

Royalty-Free Stock Photography by Rubberball In conclusion

Chronic fatigue syndrome is not only about energy levels; it can affect your life in many different ways. Those that suffer from CFS are nearly six times more likely to be depressed or anxious than those without. It is important that you are evaluated thoroughly as there are many causes and no one finding can be assumed to be the only contributor. We have only scratched the surface in this article — proper digestion, balanced gut bacteria, a quality diet high in nutritional valued foods and proper recovery can go far in treating patients with chronic fatigue syndrome.  Although some of the research presented in the beginning of the article may lead you to believe that viruses are not a major component of CFS — they can be.  It is important to rule these out whenever presented with chronic fatigue.

Medicine is currently satisfied with the clinical diagnoses of CFS as an idiopathic process (or a process of unknown origin), which allows them to now search for a drug to cover up the symptoms.   Most patients wind up on anti-depressant meds that further cause mitochondrial dysfunction, hepatic-toxicity, inflammation and, in some instances, suicide. This is no way to be treated. Ask your doctor to run the right tests and, if they refuse, find another that will!

happypeople

Suggested testing

  • Blood chemistries to include a comprehensive thyroid and metabolic profile
  • Organic acid testing
  • Adrenal and sex hormone profile (saliva or urine)
  • Viruses such as EBV, CMV, etc.

 

 

References:

Kong J et. al.: Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 294: G208–G216, 2008.
Pimentel M. et. al: A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing. Ann Rheum Dis. 2004 Apr;63(4):450-2
Alexander Bralley J, Lord Richard: Treatment of chronic fatigue syndrome with specific amino acid supplementation. Jour of Applied Nutrition 1994, 46-3.
Louden K: Controversy Continues on Whether XMRV Retrovirus Contributes to Chronic Fatigue Syndrome. Medscape; Jun 2010
Komaroff AL, Buchwald D: Symptoms and signs of chronic fatigue syndrome. Rev Infect Dis 1991, 13:S8–11.
Komaroff AL, Fagioli LR, Geiger AM, Doolittle TH, Lee J, Kornish RJ, Gleit MA, Guerriero RT, et al.: An examination of the working case definition of chronic fatigue syndrome. Am J Med 1996, 100:56–64.
Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC: Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Intern Med 2003, 163:1530–1536.
Engel MA, Neurath MF: New pathophysiological insights and modern treatment of IBD. J Gastroenterol 2010.
Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S: A community-based study of chronic fatigue syndrome. Arch Intern Med 1999, 159:2129–2137.
Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatiguesyndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk fact explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett 2009,30:470-476.
Buchwald D et al.:A Chronic Illness Characterized by Fatigue, Neurologic and Immunologic Disorders, and Active Human Herpesvirus Type 6 Infection; Annals of Internal Medicine 1992.
Koelle D et al: Markers of Viral Infection in Monozygotic Twins Discordant for Chronic Fatigue Syndrome; Clinical Infectious Disease. 2002
Knut-Arne Wensaas et al: Irritable bowel syndrome and chronic fatigue 3 years after acute giardiasis: historic cohort study. Gut doi:10.1136/gutjnl-2011-300220 1991 Mar;44(3):293-9.
The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states.