Chronic Fatigue Syndrome (CFS) is a complex and debilitating medical disorder characterized by severe fatigue that lasts at least six months and is not relieved by rest. To be diagnosed with CFS, patients must meet established criteria, which include chronic fatigue and four or more additional symptoms, such as impaired short-term memory or concentration; sore throat; tenderness in the lymph nodes; Muscle pain; joint pain without swelling or redness; headaches of a new type, pattern, or severity; non-restorative sleep; and post-exercise discomfort lasting more than 24 hours.

The exact cause of CFS can be difficult to find, although it has been suggested that it may be related to a previous viral infection, such as that caused by the Epstein-Barr virus. Furthermore, it has been proposed that CFS may be related to dysfunctions in the immune system and other biological processes as we will develop later.

Conventional drug treatment for CFS focuses on the management of individual symptoms, as no medication has been shown to influence the course of the disease. Additionally, non-pharmacological therapies, such as physical therapy and exercise, may be recommended to improve the patient’s ability to perform physical activities and reduce fatigue.

Importantly, many CFS patients may improve spontaneously over time, although they may also experience periods of remission and relapse. Additionally, it is essential to rule out other underlying medical conditions that may be causing the fatigue and other symptoms.

· Slight fever

· Recurrent sore throat

· Painful lymph nodes

· Muscular weakness

· Muscle pain

· Prolonged fatigue after exercise

· Recurrent headache

· Joint pain

· Depression

· Sleep disturbances (hypersomnia or insomnia)

· Extreme fatigue that is not relieved by rest

· Sleeping problems

· Difficulty concentrating or remembering things

· Sensitivity to light, noise and other stimuli

· Gastrointestinal disorders

· Palpitations or cardiac arrhythmias

Chronic Fatigue can be a complicated disorder to diagnose and treat, and may have various underlying causes that must be considered. I detail some of the possible causes that must be ruled out as the first line of diagnosis of Chronic Fatigue:

1. Cardio-respiratory: cardiovascular diseases, congestive heart failure and chronic obstructive pulmonary disease.

2. Neuroendocrine: hypothyroidism, hyperthyroidism, adrenal dysfunction and diabetes.

3. Gastrointestinal: malignant diseases, celiac disease, liver diseases and cirrhosis.

4. Hematological: anemia, autoimmune diseases, deficiencies (including iron), lymphoma and leukemia.

5. Infectious: Epstein Barr virus, HIV, Lyme disease and other viral infections.

6. Neuropsychiatric: sleep problems (such as apnea and disruptions of circadian cycles), depression, multiple sclerosis, myasthenia gravis, bipolar disorders, schizophrenia, dementia, anorexia nervosa and bulimia.

7. Other causes: use of certain medications and their side effects, abuse of substances such as alcohol and other drugs, accumulation of heavy metals in the body, fluctuations in body weight.

There are other possible causes that must be considered in the diagnosis of Chronic Fatigue.

1. Cell morphology in the red series: a variety of hematological disorders can contribute to Chronic Fatigue, including anemia and other alterations of the red series, macrocytosis, microcytosis.

2. Allergies: allergies, those that affect the lungs, as well as food allergies, can cause Chronic Fatigue.

When the immune system detects a foreign substance in the body, an inflammatory response occurs to eliminate it. This inflammatory response is mediated by various chemicals, such as cytokines and chemokines, that are produced by cells of the immune system.

During the inflammatory response, a cascade of biochemical events occurs that includes the activation of the NF-kB signaling pathway and the production of reactive oxygen species (ROS) and free radicals. These compounds can damage surrounding cells and tissues and contribute to chronic inflammation.

Chronic inflammation can affect brain function in several ways. First, inflammation can interfere with the blood-brain barrier, a structure that protects the brain from foreign substances in the blood. Inflammation can make the barrier more permeable, allowing inflammatory substances to enter the brain and affect brain function.

Additionally, chronic inflammation can affect the production of neurotransmitters in the brain. For example, the production of serotonin, a chemical that regulates mood and sleep, can be affected by inflammation. Inflammation can also affect the production of dopamine and norepinephrine, chemicals that are involved in regulating mood and attention.

Allergies can affect the brain through chronic inflammation, which can interfere with the blood-brain barrier and affect neurotransmitter production. These biochemical changes can contribute to chronic fatigue and other neurological disorders.

3. Environmental toxic exposure: Exposure to certain chemicals and heavy metals, such as mercury, can cause Chronic Fatigue.

4. Dysfunctions of the Autonomous System and Central Nervous System: these dysfunctions can contribute to Chronic Fatigue, including dysautonomia, postural orthostatic fatigue syndrome and other conditions.

5. Immune Dysfunctions: Chronic Fatigue can be the result of a dysfunctional immune system, as in the case of autoimmune disease.

6. Infections: Some chronic infections can contribute to Chronic Fatigue, including Lyme disease and herpes simplex and candida virus infection (detailed below)

7. Mental health-related dysfunctions: Chronic Fatigue can be caused or aggravated by mental health problems such as anxiety, depression and post-traumatic stress disorder.

8. Musculoskeletal dysfunctions: chronic diseases such as fibromyalgia and myofascial pain syndrome, mitochondrial dysfunction, can cause Chronic Fatigue.

9. Oxidative stress: Free radicals and oxidative stress can damage cells and tissues in the body, which can contribute to Chronic Fatigue.

10. Endocrine imbalances such as problems with glucose Hypoglycemia, Hyperglycemia, and that are causing oxidative stress, Adrenal Dysfunction, Hypothyroidism

11. Medications such as birth control pills, birth control, antihistamines, corticosteroids, depression medication, tranquilizers and sedatives

12. Candidiasis, Intestinal candidiasis, Candida feces Candida albicans infection can affect the function of T cells and natural killer cells, which has been linked to chronic fatigue. A significant number of patients with this syndrome have reported a positive response to oral antifungal agents and “anti-Candida” diets. Chronic candidiasis should be considered as a contributing factor to chronic fatigue in patients who have had recurrent vaginal infections or have been treated with antibiotics, oral contraceptives, or systemic glucocorticoids.

Female gender

• Age: 15 to 50 years General symptoms:
• Chronic fatigue
• Loss of energy
• General discomfort
• Decreased libido

Gastrointestinal symptoms:

• Oral candidiasis (thrush)
• Abdominal distension, gas
• intestinal cramps
• anal itching
• Alteration of intestinal function

Symptoms of the genitourinary system:

• Vaginal yeast infection
• Frequent urinary tract infections
• Mainly menstrual complaints

Symptoms of the nervous system:

• Depression
• Irritability
• Inability to concentrate

Immune system symptoms:

• Allergies
• Chemical sensitivity
• Low immune function

Background:

• Chronic vaginal yeast infections
• Chronic use of antibiotics for infections or acne
• Use of oral contraceptives
• Use of oral steroid hormones

Associated conditions:

• Premenstrual syndrome
• Sensitivity to foods, chemicals and other allergens
• Endocrine disorders
• Psoriasis
• Irritable bowel syndrome

This analysis could give us a general image of certain dysfunctions and would provide information to continue investigating in more depth the underlying causes of possible Chronic Fatigue.

• Complete Blood Count: This test allows us to identify if there is a possible anemia or infection in the body. It also allows us to evaluate cellular morphology, that is, the shape and size of blood cells, which could indicate the presence of a disease.

• Erythrocyte Sedimentation Velocity: The ESR measures the speed at which red blood cells settle in a test tube. An increase in ESR could indicate the presence of inflammation in the body.

• Ions or electrolytes: This test evaluates the levels of minerals such as sodium, potassium and chlorine in the blood. An imbalance in these levels can cause fatigue and other symptoms.

• Glucose and HbA1C: These tests measure blood sugar levels and can indicate the presence of diabetes, hypoglycemia, and the cause of oxidative stress.

• C-Reactive Protein: This protein is produced in the liver in response to inflammation in the body. An increase in CRP levels could indicate the presence of an inflammatory disease.

• CK (Creatine Kinase) The CK marker in patients with chronic fatigue can indicate muscle damage and mitochondrial dysfunction. Elevated CK levels may be related to the severity and duration of chronic fatigue symptoms.

• BUN and Creatinine: These tests evaluate kidney function. An increase in BUN and creatinine levels could indicate kidney dysfunction, loss of muscle mass, poor muscle metabolism, muscle atrophy.

• Liver Function (ALT, AST GGT): These tests evaluate liver function. An increase in the levels of these enzymes could indicate liver damage, also muscle damage (especially ALT), related to cardiovascular problems.

• Thyroid Function (TSH, T-3-T-4): These tests measure thyroid hormone levels and can indicate whether there is thyroid dysfunction.

• Cortisol: This hormone is related to stress and its level in the blood can indicate if there is dysfunction in the adrenal glands.

Below I detail substances that could be used in patients with Chronic Fatigue, which had optimal clinical results and were studied in clinical trials, but please consult with your doctor or therapist before taking any of these substances, it could be counterproductive depending on your clinical condition, not all substances are suitable for all patients nor do they have to be used all at the same time.

Magnesium: Magnesium is essential for the synthesis of adenosine triphosphate (ATP), the main form of energy storage in the body.

Several studies found that magnesium deficiency is associated with chronic fatigue in some patients.

Oral magnesium supplementation relieved symptoms in some patients, but others required parenteral therapy.

Moderate or severe magnesium deficiency has been successfully treated in patients with chronic fatigue by oral or intramuscular supplementation.

B12 vitamin. Studies suggest that patients with Chronic Fatigue (CFS) have a limited ability to transport vitamin B12 across the blood-brain barrier.

In an uncontrolled trial, frequent administration of large intramuscular doses of vitamin B12 was found to be beneficial for patients with CFS.

B vitamin complex, multivitamin-multimineral. Deficiency of B vitamins can cause fatigue and CFS patients have been found to have low levels of thiamine, riboflavin and vitamin B6.

In a double-blind crossover trial, administration of a high-potency multivitamin-multimineral formulation containing B vitamins improved CFS symptoms for 3 months, although the difference was not statistically significant.

Although there is no definitive evidence that B vitamins or a multivitamin-multimineral supplement can relieve symptoms in people with CFS, it is reasonable to include one or both supplements as part of a comprehensive treatment program.

Folinic acid. In an uncontrolled trial, treatment with folinic acid 3-4 times a day for 1-2 months decreased symptoms in a large proportion of patients with CFS or similar symptoms associated with another disease.

Nicotinamide Adenine Dinucleotide (NADH) in its reduced form, plays an important role in energy production through the electron transport chain. In a double-blind study, treatment with NADH was shown to have beneficial effects in some patients with Chronic Fatigue Syndrome (CFS).

Thirty-five CFS patients were randomly assigned to receive, double-blind, NADH or placebo as a single morning dose for 4 weeks. After a 4-week washout period, they received the alternative treatment for another 4 weeks. Nine patients who received psychotropic drugs during the study were excluded from the final analysis. Of the 26 evaluable patients, the proportion of those with a positive response (defined as an improvement of 10% or more in the cumulative symptom score) was significantly higher with NADH than with placebo (31% vs 8%; p < 0.05).

No serious side effects were seen, although a few patients reported mild side effects (such as being overstimulated, mild loss of appetite, or a strange taste and dryness) on the first day of taking NADH.

Of the patients evaluated, the proportion of those who had a positive response (defined as an improvement of 10% or more in a cumulative symptom score) was found to be significantly higher in the group receiving NADH than in the group receiving the placebo.

No serious side effects were observed, although some patients reported minor side effects on the first day of treatment with NADH.

Amino acids. 24-hour urinary amino acid excretion was subnormal in a high proportion of CFS patients in one study. In an uncontrolled trial, supplementation with a mixture of amino acids (individualized according to plasma amino acid concentrations) resulted in significant clinical improvement after 3 months in 15 of 25 patients with CFS.

Ribose: CFS is linked to poor mitochondrial energy production. Ribose plays a role in the synthesis of adenosine triphosphate (ATP) and may be useful in improving energy production. In an uncontrolled trial, ribose administration was associated with modest improvement in patients with CFS and/or fibromyalgia.

L-Carnitine: Carnitine is important for energy production. In patients with CFS, serum carnitine levels are significantly lower than reference values.

Fatty Acids: There are studies that have examined the effect of a preparation containing evening primrose oil and fish oil in patients with CFS. In one of the studies, the active treatment was significantly more effective than the placebo.

In another study, a greater proportion of patients improved in the placebo group than in the active treatment group.

It is suggested that patients with post-viral chronic fatigue syndrome may have different biochemical abnormalities than patients with other types of CFS.

More studies are needed to determine whether evening primrose oil and fish oil are beneficial for a subset of CFS patients.

These other substances were used in patients with chronic fatigue but should not be used under any circumstances without medical or therapeutic supervision.

Glycyrrhiza glabra (licorice root). A man with CFS who did not respond to numerous treatments experienced an almost complete recovery after a few days of treatment with Glycyrrhiza glabra (licorice root). It is believed that licorice worked by slowing the breakdown of cortisol and aldosterone, resulting in higher levels of these hormones in the body.

However, it is important to note that prolonged use of licorice can cause hypertension and hypokalemia.

Dehydroepiandrosterone (DHEA). Patients with CFS have abnormalities in the secretion or metabolism of DHEA. In an uncontrolled trial, women with CFS who had “suboptimal” serum concentrations of DHEA-S showed clinical improvement after treatment with DHEA for 6 months.

Adenosine monophosphate (AMP) has been used to treat herpes simplex and shingles infections, and the possibility has been raised that it may be beneficial for other viral infections, including chronic fatigue syndrome (CFS). In one study, 56% of CFS patients reported a decrease in fatigue, improved memory, and concentration after receiving intramuscular injections of AMP.

These injections may cause temporary chest pain, which can be prevented by dividing the dose and giving it twice.

It is important to ensure that it is not given with the needle directly into the vein as rapid administration of intravenous adenosine can cause cardiac arrhythmias and other side effects.

Hydrocortisone: It has been shown that patients with chronic fatigue have significantly lower levels of morning plasma cortisol compared to healthy controls.

In a double-blind trial, low-dose hydrocortisone administration improved fatigue in patients with chronic fatigue without causing adrenal suppression. In another study using a higher dose of hydrocortisone, clinical improvement was observed, but 34% of patients developed adrenal suppression, suggesting that it is dangerous to treat chronic fatigue with hydrocortisone at higher doses.

This substance in low doses may be an effective and safe treatment for some patients with chronic fatigue, especially those who have clinical or laboratory evidence of reduced adrenal function.

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