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  • Chronic fatigue syndrome appears to be rooted in mitochondrial dysfunction. Your mitochondria are responsible for energy production, and as the name implies, low energy and severe fatigue are hallmarks of this condition
  • Immune cells in the blood of patients diagnosed with chronic fatigue show clear signs of low energy production. The debilitating fatigue they experience is due to an inability to produce the cellular energy needed
  • A ketogenic diet, high in healthy fats and low in net carbohydrates, with moderate protein, is a key dietary strategy that helps optimize mitochondrial function
  • Patients with chronic fatigue also lack diversity in the gut microbiome, and the presence of certain inflammatory cytokines in their blood closely correlates with symptom severity
  • Strategies that reduce inflammation, heal your gut microbiome and support mitochondrial function and energy synthesis are all beneficial for chronic fatigue patients

Chronic fatigue syndrome (CFS), which is thought to affect up to 2.5 million Americans,1 is a debilitating condition in which sufferers experience unrelenting fatigue no matter how much rest they get. Pain and chronic inflammation are other hallmarks. A number of other names are also used for this condition, including:

  • Myalgic encephalopathy/myalgic encephalomyelitis (ME)
  • Post-viral fatigue syndrome (PVFS)
  • Chronic fatigue immune dysfunction syndrome (CFIDS)2
  • Systemic exertion intolerance disease (SEID)3

The most common designation is ME/CFS and, according to the CDC, about 90% of people with ME/CFS have not yet been diagnosed.4 In the past, ME/CFS was typically brushed off as being a psychological problem, but in more recent years, researchers have discovered physiological commonalities between groups of individuals that validate their symptoms.

For example, ME/CFS patients tend to have similar changes in gut bacteria, and certain inflammatory biomarkers in your blood appear to correlate with ME/CFS symptoms.5 Most recently, researchers have found additional support for the hypothesis that ME/CFS is rooted in mitochondrial dysfunction, which makes logical sense considering your mitochondria are responsible for energy production.

These tiny powerhouses are an interconnected network that rapidly and effectively distributes energy throughout your body’s cells.6 Your mitochondria are also responsible for programmed cell death, and serve as important signaling molecules that help regulate the expression of your genes.

When your mitochondria do not work properly, low energy is a natural side effect. Knowing this, the remedy becomes clearer as well. A ketogenic diet, high in healthy fats and low in net carbohydrates, with moderate protein, is a key dietary strategy that helps optimize mitochondrial function.

What Is Chronic Fatigue Syndrome?

Until recently, the diagnosis of ME/CFS has been one of exclusion. This meant all other illnesses mimicking the symptoms of ME/CFS had to first be ruled out before doctors could suggest you were suffering from ME/CFS. Symptoms of ME/CFS can vary widely from one individual to the next.

The most common symptom is one of overwhelming exhaustion that worsens with physical or mental energy expenditure and does not get better with rest.7 It may take up to 48 hours after activity to experience the full extent of the exhaustion. Other symptoms of the condition may mimic other medical conditions, and include:8,9,10

Muscle pain Memory problems Headaches
Sore throat Pain in multiple joints Difficulty sleeping
Tender lymph nodes Visible muscle twitching (fasciculations) Difficulty concentrating
Short attention span Word find problems Excessive sweating
Palpitations Fainting Clumsiness
Enlarged glands Intermittent flu-like symptoms Alcohol intolerance
Irritable bowl-like symptoms Mood swings Temperature control
Food intolerance Gastrointestinal problems Hypersensitivity to light and noise

ME/CFS Is a Side Effect of Cellular Exhaustion

As mentioned, researchers have now identified what appears to be a root problem: exhaustion at a cellular level. This study11 was published in PLOS One at the end of October 2017. Immune cells in the blood of patients diagnosed with ME/CFS “show clear signs of low energy production,” Science Alert reports.12 This strongly suggests mitochondrial dysfunction, as the mitochondria are responsible for energy production. As noted in the featured article:13

“Researchers looked specifically at the metabolic processes of oxidative phosphorylation and glycolysis — two ways cells break apart chemical fuel to transfer energy in respiration. White blood cells taken from 52 patients with CFS and 35 controls were put through their paces under optimal and stressful conditions, testing their capacity to deal with low oxygen levels.

There appeared to be a number of key differences in their metabolic processes. But none were as dramatic as the contrast in maximum levels of respiration. By forcing the cells to boost their energy production, the researchers found those with CFS could only squeeze about another 50 percent from their cells — unlike the controls, who nearly doubled their output.”

In short, ME/CFS patients lack the ability to compensate for increased stress on a cellular level, and the debilitating fatigue they experience is due to the inability to produce the cellular energy needed to keep the body fully functional. Their mitochondria are simply unable to produce enough ATP to maintain an energy gradient across their cell membranes. As noted by the authors:

“Lower reserve capacity observed in CFS patients are indicative of the cells of patients performing closer to their capacity in normal conditions without stress than healthy controls. Lowered maximal respiration suggests that the PBMCs [peripheral blood mononuclear cells] of CFS patients are not capable of the same levels of respiration as healthy controls.”

ME/CFS Also Linked to Lack of Microbial Diversity in Gut

Another study published in the journal Microbiome evaluated the blood and stool of 48 people diagnosed with ME/CFS and compared the results to those from 39 healthy people.14,15 Here, differences were found in both stool and blood samples. Using DNA sequencing, a process of determining the precise order of nucleotides in a DNA molecule, they found a distinct lack in diversity in the gut microbiome in affected individuals.

Although these changes could not be clearly identified as either the cause or consequence of ME/CFS, researchers were heartened by the presence of these markers in 83% of the sample, and the possibility of treatment options to reduce symptoms. Quoted in the Washington Journal, professor of molecular biology and genetics at Cornell University, Maureen Hanson said:16

“Our work demonstrates that the gut bacterial microbiome in chronic fatigue syndrome patients isn’t normal, perhaps leading to gastrointestinal and inflammatory symptoms in victims of the disease. Furthermore, our detection of a biological abnormality provides further evidence against the ridiculous concept that the disease is psychological in origin.”

Addressing Leaky Gut May Help ME/CSF Patients

The researchers theorize the inflammatory markers in the blood could be the result of a “leaky gut from intestinal problems that allow bacteria to enter the blood.”17 Indeed, other recent research18,19 has confirmed the presence of more than a dozen inflammatory cytokines in blood that closely correlate with reported symptom severity in patients suffering from ME/CFS.

This confirms a suspicion of some researchers that symptoms of fluctuating flu-like symptoms and body aches associated with ME/CFS is linked to an inflammatory response.20 It’s important to realize that there is a distinct link between leaky gut and the foods you eat. Probably the single most important factor here is the herbicide glyphosate, which is pervasive. Between 1974 and 2014, over 3.5 billion pounds of glyphosate were used in the U.S. alone.21

Worldwide in 2017, 4.4 billion pounds (2 billion kilograms) of glyphosate were being used annually.22 Glyphosate will decimate tight junctions and contribute to leaky gut. Fortunately, you can radically reduce your exposure by eating organic and avoiding processed foods, which are usually contaminated. You can also check your glyphosate level with a simple urine test, to see how badly you’ve been exposed.

Grains and lectins, even organic non-GMO, are particularly troublesome. Research shows that gluten stimulates a protein molecule in your gut called zonulin, which triggers the opening of junctures between the cells in your gut lining. In essence, it makes your gut more permeable, allowing food particles to escape into your bloodstream, causing inflammation, immune reactions and raising your risk of various autoimmune disorders.

Certain plant lectins may also contribute to leaky gut by binding to receptor sites on your intestinal mucosal cells, thereby interfering with the absorption of nutrients across your intestinal wall. As such, they act as “antinutrients” and can have a detrimental effect on your gut microbiome by shifting the balance of your bacterial flora.

Among the worst culprits are wheat germ agglutinin (WGA), found in wheat and other seeds in the grass family. In fact, according to Dr. Steven Gundry, author of “The Plant Paradox: The Hidden Dangers in ‘Healthy’ Foods That Cause Disease and Weight Gain,” gluten is a minor problem compared to WGA.

Evidence suggests lectins are strongly associated with autoimmune disorders in general, so anyone struggling with a dysfunctional immune system may want to seriously consider experimenting with a low-lectin diet. As for ME/CFS, leaky gut is not an automatic precursor. However, healing and sealing your gut and reducing the inflammatory response in your body may result in a significant reduction in chronic fatigue symptoms by supporting your immune system.

Ketogenic Diet May Speed Resolution of Chronic Fatigue

In 2015, Dr. Courtney Craig, a chiropractor and nutritionist, wrote about her personal experience with the ketogenic diet. Diagnosed with CFS in her teen years, she’s been able to control her condition using a number of integrative health strategies, including intermittent fasting and nutritional ketosis. Describing a particularly harrowing relapse, she goes on to discuss how switching to a ketogenic diet helped her rapidly recover. She writes, in part:23

I needed a serious immune and mitochondrial reset … So, I shifted my usual paleo-diet around, and astonishingly I bounced back very quickly … I started consuming about 80 percent of my calories from healthy fats … This is something I do periodically when the fatigue rears its ugly head … It’s also advocated by doctors like … Dr. Thomas Seyfried …

I flipped a switch on my metabolism. I stopped relying so much on glucose for metabolism, and instead encouraged my liver to break down those dietary fats into ketones — a much “cleaner” energy source … The downside of burning carbohydrate as fuel, is production of cellular stress and free radicals. Ketones provide a “cleaner” energy for cells and are less damaging to cell membranes … A ketogenic diet can be initiated with a 12 to 72 hour fast.

Then the diet is maintained by consuming 75-90% of calories as fat, with the remainder coming from moderate amounts of protein and very little carbohydrate. The ketogenic diet is one that should be considered when dealing with ME/CFS … A body of research in animals and humans have highlighted some of the mechanisms by which dietary ketones promote cellular health.

Indeed, when your body is able to burn fat for fuel, your liver creates water-soluble fats (ketones) that:

  1. Burn far more efficiently than carbs, thereby creating fewer reactive oxygen species and secondary free radicals that can damage your cellular and mitochondrial cell membranes, proteins and DNA
  2. Decrease inflammation, as they are histone deacetylase inhibitors
  3. Mimic the life span extending properties of calorie restriction, which includes improved glucose metabolism and reduced inflammation24
  4. Have a similar structure to branched-chain amino acids, thereby aiding the building muscle mass and promoting longevity

The Importance of Cyclical Ketosis

Nutritional ketosis is the metabolic state associated with an increased production of ketones in your liver; i.e., the biological reflection of being able to burn fat, and is defined as having blood ketones in the range of 0.5 to 3.0 millimoles per liter. As a general guideline, a dietary intake of 20 to 50 grams (or less) per day of net carbs (total carbohydrates minus fiber) while also keeping protein low-to-moderate is usually low enough to allow you to make the shift to nutritional ketosis.

However, once you achieve metabolic flexibility and are able to generate ketones with nutritional ketosis, it’s important to include higher carb intakes every now and then. For all its benefits, continuous ketosis actually has some downsides that are easily avoided by implementing a cyclical “feast and famine” regimen. I detail the reasons for this in my book, “Fat for Fuel.” In summary, long-term uninterrupted ketosis can trigger a rise in blood sugar by driving your insulin level too low.

This paradoxical situation can occur because the primary function of insulin is not actually to drive sugar into the cell but rather to suppress the production of glucose by your liver (hepatic gluconeogenesis).

Cycling in and out of nutritional ketosis will effectively prevent this rise in blood sugar in the absence of high glucose. So, once you are able to burn fat as fuel, having a day or two each week where you eat more net carbs and protein is important, especially when you’re doing strength training, to prevent sarcopenia.

After a day of “feasting,” you then cycle back into nutritional ketosis (the “fasting” stage) for the remainder of the week. By periodically pulsing higher carb intakes, consuming, say, 100 or 150 grams of carbs opposed to 20 to 50 grams per day, your ketone levels will dramatically increase and your blood sugar will drop.

Chronic Fatigue Patients Need Mitochondrial Support

In this 2016 interview, I discuss the importance of mitochondrial function and how it may impact your symptoms of chronic illnesses like ME/CFS. It stands to reason that a condition that triggers an inflammatory response and gut dysfunction, and that results in overwhelming fatigue, will respond favorably to treatment strategies that reduce inflammation, heal your gut microbiome and support mitochondrial function and energy synthesis.

Diet-wise, a cyclical ketogenic diet would be a foundational strategy. The following dietary recommendations will also help heal and seal your gut, lower inflammation and support healthy energy production. You can also read more about supporting your gut health in “Nourishing Your Gut Bacteria is Critical for Health and Mental Well-Being.”

Avoid gluten and wheat products — Gliadins, a component of gluten, are a class of protein found in wheat and cereals that increase the permeability of your gut. Keep in mind that gluten can also be found in other grains, not just wheat.
Avoid lectins — To learn more, including which foods are best avoided due to high lectin content, please see “How to Reduce Lectins in Your Diet.”
Reduce your net carbs — The carbohydrate sugar, like grains, will upset the balance of microbes in your gut. Sugar is the food source for bacteria that can prompt damage to your intestinal walls, while fiber is the food source for bacteria that build your intestinal membranes.

Your net carbs are the total grams of carbohydrates you’ve eaten in a day, minus the grams of fiber you’ve eaten. The difference is your net carbs. Seek to reduce your net carbs to 50 grams per 1,000 calories of food you eat each day.

Increase your fiber intake — The fiber you eat from whole foods is the nutrient source for bacteria in your gut that helps maintain and build the membrane cells in your intestinal walls. This helps to seal the “gaps” between the cells and reduces any leakage of waste products and bacteria into your blood stream. Focus on eating whole food vegetables, nuts and seeds (with the exception of lectin-rich varieties).
Eat fermented foods — Fermented foods are a great source of natural probiotics to feed healthy microbes in your gut. Olives, pickles, kimchi, cheese from grass fed cows, homemade yogurt and sauerkraut are just a few of the foods you may not have considered. Your best bet is to make your own. In this video, Julie and I demonstrate how to make your own fermented vegetables at home.

Supplement with nutrients important for cellular energy synthesis such as ubiquinol, the reduced form of CoQ10, and D-ribose, a core building block of adenosine triphosphate or ATP. Also eat foods rich in glutathione precursors, sulfur and selenium to encourage glutathione production. Glutathione is one of your body’s most important antioxidants and a natural detoxification agent.
Intermittently fast, making sure your last meal is taken at least three hours before bedtime. The rationale for avoiding late night eating is directly tied to the way your body produces energy.

Other Strategies to Help Reduce Chronic Fatigue Symptoms

There is no known cure for ME/CFS, but there are strategies that can help alleviate symptoms,25 over and beyond the dietary recommendations already mentioned. My full metabolic mitochondrial therapy program is described in my book, “Fat for Fuel.” Cold thermogenesisphotobiology, detoxification, exercise and avoiding electromagnetic fields are all strategies that will help improve mitochondrial health and function.

When it comes to exercise, work out according to your ability, with a focus on increasing the amount of exercise you can handle. Research shows that a combination of aerobic activity and strength training can improve pain and fatigue symptoms. Gentle exercise such as yoga can also be an excellent part of your program, and yoga benefits your mind as well as your body.

You may also want to address your mental outlook. In addition to talk therapy, I would recommend trying The Emotional Freedom Techniques (EFT) to help normalize your bioenergetic circuitry. Emotionally traumatic events can leave “energy blockages” for many years, which then interfere with your overall health, including immune function. There are many different techniques that can be used, but EFT is my favorite, and it’s easy to learn and apply.