Master Enzyme Switch Deactivated In Chronic Fatigue Syndrome and Fibromyalgia

Monday, April 20, 2015
By: Linda J. Dobberstein, Chiropractor, Board Certified in Clinical Nutrition

Brand new research published in the last few weeks reveals important information for people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and Fibromyalgia (FM). The research helps explain why individuals dealing with these complex disorders have poor response to physical activity and poor energy production. The cutting-edge studies offer new insight and tools for supporting these devastating illnesses. 

AMPK and Chronic Fatigue Syndrome

The Institute of Medicine recently made national headline news by recommending the renaming of CFS/ME to Systemic Exertion Intolerance Disorder (SEID). Many within this community may be dissatisfied at yet another attempt at a dismal name change and limited parameters with the diagnostic criteria, but research published April 2, 2015 helps explain some of the mechanics of exertion intolerance with CFS/ME.

The ground breaking study is entitled “Abnormalities of AMPK Activation and Glucose Uptake in Cultured Skeletal Muscle Cells from Individuals with Chronic Fatigue Syndrome”. Scientists studied skeletal muscle tissue obtained from muscle biopsies of 10 patients with CFS/ME. The muscle cell samples were placed in cultures and stimulated by small electrical pulses for up to 24 hours to cause the muscle cells to contract. They were then compared to healthy control samples.

The results showed that CFS muscle cell cultures had no increase in AMPK phosphorylation or glucose uptake after several hours of electrical stimulation. The test also showed increased myogenin expression at rest and diminished release of IL6. This lack of AMPK activity equates to poor exercise tolerance. While this is a very small sample, this is the first study ever published on this topic of CFS and AMPK activation. It is also important to note that each culture from CFS patients was identified to have this problem.

AMPK and Fibromyalgia

Researchers tested connective tissue samples taken from Fibromyalgia patients. In testing the fibroblasts found in the connective tissue samples, they found that the AMPK enzyme was also not activated in FM patients. Like the CFS study, the FM patients had a newly identified problem with AMPK function. This loss of AMPK activation causes new mitochondria to not be made and compromises mitochondria function. It also caused reduced oxygen consumption or increased anaerobic activity, and decreased activity of antioxidant enzymes. Both patient groups had impaired AMPK function from oxidative stress.

What Is AMPK?

AMPK (5’-adenosine monophosphate-activated protein kinase) is an enzyme switch found in cells throughout the body, especially in the hypothalamus, liver, muscle, adipose tissue and pancreas. It is a master regulator or master switch of energy levels within the cells. It keeps cellular energy in a state of homeostasis or balance. When AMPK is turned on, it helps cells burn fat and glucose resulting in ATP production.

Healthy AMPK Function

Healthy AMPK function helps with fat and blood sugar burning to make energy. By doing this it helps prevent belly fat. It improves insulin sensitivity, reduces cholesterol and triglyceride production, and suppresses chronic inflammation. It helps remove cellular debris and damaged proteins. It is directly influenced by the hormone leptin. This enzyme switch is intimately critical for helping the body make new mitochondria and keeping mitochondria healthy. It also controls exercise endurance.

AMPK and Sleep

Interestingly, sleep is influenced by AMPK activity. AMPK plays a role in the regulation of sleep homeostasis. When the brain is engaged in a healthy sleep pattern and circadian rhythm, AMPK and the energy molecules ATP talk to each other, repairing from the previous day’s activity and getting ready for the next day. When this balance is off, it causes disrupted circadian rhythms, sleep-wake cycles and non-restorative sleep. These are often difficult, massive problem for patients with CFS/ME and FM. Clearly there is involvement.

AMPK Deficits and Consequences

The body uses trillions of mitochondria to burn fat and glucose to make energy. If the AMPK switch is turned off, poor energy production occurs, interfering with mitochondria regeneration and function. Results lead to problems like obesity, metabolic syndrome, diabetes, elevated triglycerides, cholesterol, LDL, and more. Exercise intolerance, leptin resistance and stress-energy imbalances also occur. Scientists have largely focused on these types of metabolic concerns, but we now see that CFS/ME and FM disorders are affected by this broken switch as well. 

Failed Trash Clean Up

In addition to the making and use of energy, the body’s clean-up process is also affected. Scientists found that failure of the AMPK activation leads to a build-up in cellular trash. The clean-up process, known as autophagy, is on strike. This is problematic because mitochondria require 24/7 clean up in order to maintain efficiency. This means that older, less efficient mitochondria are left with the brunt of the work and new mitochondria are not being made; less efficiency and more trash. This is a major problem for high energy, high mitochondria dependent organs like the brain, muscles, and heart. This trash makes tissues stiff and damages these proteins. Without AMPK activation, nerves cells are not protected as AMPK protects neurons under pathological conditions. This slippery slope leads to brain fatigue and breakdown in repair, eventually tumbling into neurodegeneration including Alzheimer’s disease. Impaired trash removal in the cells is like trying to make a gourmet meal in a kitchen that has a month’s worth of unwashed dishes piled up. It doesn’t work. This is often the state of health found in people struggling with significant problems with CFS and FM.

Healthy AMPK function is like a vibrant, active, and athletic youngster with energy to burn. Poor AMPK function is like the individual who needs naps, sleeps poorly, has lots of chronic pain, forgets where they put the car keys, has extra fat around the mid-section, and has trouble reaching down to pick up something off the floor. Nothing works well.

AMPK, Inflammation, and Chronic Pain

AMPK deactivation, damaged proteins, poor trash removal, and defunct mitochondria lead to disrupted pain pathways, and compromised brain plasticity. For CFS/ME patients, the disabling neurological fatigue symptoms and inflammation and severe headaches may reflect this phenomenon. For FM patients, major problems with central sensitization and wind-up often lock in severe chronic neuropathy and chronic pain problems. These disorders often occur after a motor vehicle collision, acute illness or trauma, or severe stress reflecting the overwhelmed system. Identification of AMPK deficits that locks in the chronic pain and inflammation provides major possibilities of intervention other than narcotics or medications.


This exciting breakthrough news leaves a lot of work to be done in terms of how, what, when, why, etc., It has not been determined why the AMPK enzyme activity is derailed in these CFS/ME and FM patients. No one knows if it is from toxins, germs, stress, lack of nutrients, or what the culprits may be. One study does show a link with Epstein Barr Virus and AMPK inactivation but it is in the context of throat cancer. Many CFS/ME and FM patients as well other neurodegenerative disease patients suffer with Chronic Active Epstein Barr Virus. Is this a cause breakdown of AMPK? It is too early to tell.

Tools and Support for AMPK

In the context of CFS/ME and FM associated with AMPK activation, specific studies on this inter-relationship and specific tools of support are scarce. There are however, many studies performed on several other disorders linked with AMPK deficits and how to improve AMPK function. There are many tools available. Here are some of them.

We do know that high calorie (high fat, high sugar) intake cause AMPK problems in general. We also know that physical activity, good sleep patterns, and healthy leptin function support proper AMPK activation. Thus, reducing fat and sugar intake and not overeating helps AMPK function. This means that following The Leptin Diet and eating organic, nutrient-dense foods should be fundamental for anyone.

Several nutrients have been shown to be essential in restoring AMPK activation. Coenzyme Q10 ubiquinol was studied specifically in the context of FM and AMPK. Researchers showed that a small group of FM patients taking a dose of 300 mg/day of coenzyme Q10 ubiquinol had very positive benefits. It showed very strong improvements in pain reduction, general fatigue, morning fatigue, mitochondrial regeneration, and activity of the AMPK enzyme. Several studies done over the years clearly show coenzyme Q10 deficits in CFS/ME and FM patients, so this study may not come as a surprise.

Resveratrol is shown to be a potent activator of AMPK for all kinds of metabolic problems. In addition, researchers studied the use of resveratrol in acute and chronic neuropathic pain problems in animals. They found that resveratrol stopped the nerve tissue from inflammation and pain becoming locked in. These results indicated that activation of AMPK at high levels was able to treat inflammation-associated pain and provided fewer unwanted side effects than current drug approaches. This is incredibly valuable for all, but especially CFS and FM patients who are often extremely sensitive to medications and have unrelenting pain problems.

Grape seed extract and the omega-3 oil DHA also help AMPK function. Both nutrients were shown to help the body use more fat as fuel, improve muscle mitochondria function, and reduce insulin resistance, protecting the body from complications related to obesity and poor AMPK function.

Researchers found that quercetin protected mitochondria from damage and reduced plaque build-up in the brain in an animal study. Quercetin activated AMPK function which led to a marked improvement in learning and memory, fatigue problems, and less oxidative stress in the hippocampus. Quercetin stopped the development and progression of neurodegeneration or Alzheimer’s disease in the mice. While patients with CFS and FM don’t have Alzheimer’s disease, cognitive, memory, and fatigue problems and neurological deterioration certainly exist. The dose used in this animal study that provided the best results was 40 mg/kg per day for 16 weeks. For a 150 pound or 68 kilogram person, this equates to about 2000 mg of quercetin per day. There is clearly tremendous potential and support with quercetin for multiple serious concerns.

Green tea extract and caffeine improved AMPK function in animal studies. Curcumin is a profound anti-inflammatory nutrient that helps to activate AMPK. Lycopene, ginger, and indole-3-carbinole (I3C) from cruciferous veggies also activate AMPK.

Acetyl-l-carnitine, which has been shown to be lacking in CFS/ME patients, also benefits AMPK activation, insulin function, and muscle cells. Research published in the last month also confirms that FM patients would be benefit by acetyl-l-carnitine for pain and neurological health. Dosage used in this study was 1500 mg/day.

Consider adding in two minutes of vigorous exercise periodically throughout the day which helps turn on AMPK with any of these nutrients to optimize its effect. Even for those who are severely ill with CFS and FM and struggling with exertion intolerance, doing some type of physical activity as vigorously as they can for 30 seconds up to 2 minutes helps to prime and activate AMPK. Vigorous activity may mean 30 seconds of jumping jacks, standing push-ups against the wall, or partial knee bends. It just means doing something as vigorously as you can for very brief period of time to engage the body within your energy envelope. 

CFS/ME and FM disorders place an enormous burden on the individual, their family and society because of the pervasive loss health and inability to work. The recognition of AMPK deactivation helps provide validation in these illnesses that elude easy fixes. The recognition also helps individual take charge of their health by using calculated healthy diet choices, physical activity to tolerance, and other nutritional measures. Tremendous resources have been identified and allow intervention into this activation and restoration of this broken, depleted enzyme. Nutrients work synergistically with each other. They support and help recycle each other. Use a consistent combination of these nutrients at therapeutic amounts to offer the possibility of strong support and change. These disorders are challenging, but use this knowledge to open the doors to a healing journey.

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