Editor’s Note: Arnold Mervyn Levin, M.B., B.Ch., D.O.H., is in private general practice in South Africa. The following is Levin’s hypothesis paper regarding his theory about the relationship of bowel yeast to the onset of Chronic Fatigue Syndrome (CFS). He concludes this paper with recommendations for reducing the levels of yeast in the bowel and bloodstream, reducing the effects of nitric oxide, and supplementing low levels of thyroid hormone.

Chronic Fatigue Syndrome (CFS), sometimes referred to as myalgic encephalomyelitis, or Yuppie Flu, is a chronic illness whose origin has not yet been clearly defined. It consists of disabling fatigue, where this fatigue has been experienced for at least six months with a total reduction of daily activities by at least 50%. Among the many symptoms required for the diagnosis are fever, painful nodes, sore throat, muscle weakness and muscle pain, prolonged fatigue after exercise, headaches, loss of concentration, painful joints, and difficulty in sleeping.

Many theories abound as to the cause of CFS, but none have been proven conclusively. Because of the prevalence of the condition in many different countries throughout the world, it is becoming increasingly necessary to find a common link in the causative mechanism. The cause must be present at an international level.

The overgrowth of bowel yeast and its infiltration through the bowel wall into the bloodstream would appear to be the starting point in the development of CFS. This invasion of yeast can occur for different reasons. Injudicious use of antibiotic therapy and diabetes have been claimed to be responsible for this overgrowth of bowel yeast. But what appears to be more common, and one that occurs very widely, is that of an “incorrect diet” as a result of bad eating habits due to a significant change in the individual’s lifestyle. Junk food, e.g., hamburgers and fast foods, fit into this category.

Stage One

It has been clearly established that under normal circumstances, vasodilatation and the concomitant blood flow through the blood vessel, is a result of the chemical nitric oxide, which is produced in the vessel endothelium.

Nitric oxide (NO) is derived from the amino acid L-arginine, and the reaction is controlled by the enzyme NO synthase. Glutamic acid (glutamate) would appear to play an important role in the formation of nitric oxide by stimulating glutamic acid receptors, as seen in the central nervous system. It probably plays a similar role in the cells of different tissues, which include blood vessel endothelium, the brain, and the immune system.

Many factors are responsible for the stimulation, or reduction of the endothelial nitric oxide. Among these is the presence of hypertriglyceridemia.

Ingestion of food with a high fat content, e.g., hamburgers, raises the blood triglyceride levels and reduces the flow dependent vasodilatation seen in the brachial artery. This vascular impairment with resulting reduction in blood flow, occurs as early as two hours after the ingestion of high fat content food. Endothelial dysfunction in resistance blood vessels, may limit or reduce organ perfusion.

The transient hypertriglyceridemia induced by hamburger ingestion contributed to decreased vascular reactivity, by either preventing the diffusion of endothelial nitric oxide to the vessel smooth muscle, or by inactivating nitric oxide via the oxidative mechanism.

It seems reasonable to postulate that long-term ingestion of hamburgers and fast foods, which in themselves represent a significant change in people’s eating habits, results in damage to the endothelium of the blood vessels of the intestinal mucosa. The latter blood vessels would probably be the first to be exposed to the hypertriglyceridemia. Over a lengthy period, this vascular dysfunction will result in reduced tissue perfusion, and subsequent cellular derangement of the intestinal epithelium. The latter will alter the protective function of the intestinal epithelium with influx of uninvited products from the bowel lumen into the body’s blood stream. One of these unwanted “invaders” would be the bowel yeast, with its ultimate overgrowth in the blood circulation and its resultant effects.

Stage Two

Yeast contains the enzyme glutumate dehydrogenase, and is therefore able to metabolize alpha ketoglutarate to glutamic acid (glutumate). Glutamic acid is a nutritionally non-essential amino acid found in all forms of life. Glutamic acid is of fundamental importance for amino acid synthesis.

Glutamic acid plays an important role in the central nervous system. It appears to be the only amino acid metabolized by the brain tissue. Glutamic acid stimulates the appropriate glutamate receptors in the brain, which then triggers the formation of nitric oxide. This nitric oxide is synthesized in the same manner as occurs in the vascular endothelium using the substrate L-arginine and the same enzyme NO synthase. Nitric oxide is a central nervous system neuronal mediator. Nitric oxide in small doses is an important neurotransmitter, but in large doses, becomes toxic and destructive. Nitric oxide is also an important brain neurotransmitter involved in learning and memory.

Glutamic acid serves as a precursor for the production of GABA, i.e., gamma amino butyric acid. Decarboxylation of glutamic acid produces GABA, and requires the presence of an enzyme found in the brain tissue, especially in the gray matter. This enzyme requires pyridoxal phosphate as a co-enzyme. GABA is a normal regulator of neuronal activity, being active as in inhibitor of brain function.

Thus, yeast in the bloodstream, through its production of glutamic acid, may be responsible for the excessive production by the brain of the neurotransmitters nitric oxide and GABA. This excess nitric oxide and GABA have toxic and inhibiting effects on the central nervous system, probably including suppression of the hypothalamus. These effects may subsequently be responsible for the central nervous system signs and symptoms found in CFS sufferers.

Stage Three

The hypothalamus has an overall influence on the body’s blood levels of hormones. This is achieved via the hypothalamus’ regulation of the pituitary gland, the latter’s activity influencing the end target glands’ production of their respective hormones.

The hormonal gland that is primarily concerned with total body metabolic and energy processes, is the thyroid. The hypothalamic suppression of the pituitary will result in a deficiency in hormone production, including that of the thyroid.

Hypothyroidism is manifest with many different signs and symptoms indicative of a low metabolic rate. Common ones are lethargy, irritability, overweight, anemia, hair loss, poor skin texture, and loss of libido. Many of these complaints are found in CFS.

Stage Four

The cells of the immune system, which contain NO synthase, are capable of producing nitric oxide. I propose that one of the stimulators of this nitric oxide production may well be glutamic acid, much as occurs in the central nervous system. Increase in the levels of glutamic acid will result in high concentrations of nitric oxide. I also propose that the immune cell population may well have to increase in numbers in order to cope with this increased biochemical activity. This hyperplasia will present clinically with painful enlarged lymph nodes and lymphoid tissue.

Summary

In summary, chronic fatigue syndrome may develop over a lengthy period of time, during which there is a disturbance in the usual bowel yeast relationship. The latter may be due particularly to the eating of incorrect foods, especially those with a high fat content. The increase in the yeast content in the circulating blood will stimulate the production of large amounts of glutamic acid, which in turn will stimulate the appropriate receptors in the brain tissue. The latter action will result in excess amounts of nitric oxide and GABA being synthesized, and subsequently, having an inhibitory effect on brain activity. This suppression of brain activity, particularly at the hypothalamic level, will produce a reduction in the activity of the hormonal glands. This is particularly applicable to the thyroid gland. The resulting hypothyroidism (whether clinical or subclinical) will produce the signs and symptoms commonly seen in CFS.

Likewise, the effects of this excessive glutamic acid on the immune system will result in an increase in nitric oxide production, with concomitant enlarged lymph nodes and lymphatic tissue.

Based on the above concept, treatment of CFS would hypothetically entail the following principles:

1) Reduce the levels of yeast both in the bloodstream and the bowel · Dietary: Avoid foods with yeast and “yeast-like” products, e.g., bread · Avoid foods with high carbohydrate and high fat content, e.g., fast foods, hamburgers · Medical: Use of anti-fungal medicines with the imidazole structure, which will help reduce the blood levels of yeast. The course of medication may have to extend over a varying period of time.

2) Reduce the effects of nitric oxide · It has been speculated that suppressing the activity of the enzyme NO synthase will reduce the production nitric oxide. It has been found that the imidazole group of medicines will inhibit the NO synthase. As yet, no clinical trials appear to have been carried out to evaluate the effects of this medication on the improvement of the signs and symptoms of CFS. If indeed the imidazole does suppress NO synthase activity, then it will serve a dual purpose in the therapy of CFS, namely, to reduce the levels of circulating yeast, as well as limit nitric oxide activity. The exact dose of the medication at this stage is empirical, and will vary from individual to individual.

3) Supplement the low levels of thyroid hormone · Supplementation of thyroid hormone will help to alleviate the symptoms of hypothyroidism. The duration of the treatment will once again vary according to individual needs. In this respect, one study suggests a positive effect on fatigue and depression of low dose thyroxine supplementation in essentially euthyroid individuals.