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L-Serine: Treatment for Chronic Fatigue Syndrome (CFIDS)

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Recent research being done in Australia has led to the conclusion that people who suffer from CFIDS, especially those with more neurological symptoms, may actually have a treatable amino acid deficiency. At the February 1998 CFIDS conference in Sydney, doctors from Newcastle University in Callaghan, Australia, who have formed the Collaborative Pain Research Unit (CPRU), presented their intriguing discovery that a substantial number of CFIDS patients have a deficiency in the amino acid, serine.

The Benefits of Serine

Serine is one of 20 or so amino acids which form the building blocks of all the protein that make up the human body. Amino acids are also used in the formation of many enzymes needed for good health. Amino acids form living cells and the antibodies used by our immune systems, carry oxygen throughout the body and are involved in muscle activity. Since all the proteins crucial to our existence are composed of various combinations of amino acids, it is easy to understand their importance.

Serine’s known benefits to proper human functioning are numerous. Serine is an integral component of particular phospholipids (fatty compounds) which are important constituents of cellular membranes. Serine also makes up brain proteins and nerve coverings. Serine aids in the production of immunoglobulins and antibodies. Serine, in turn, is needed to produce the amino acid, tryptophan, which is imperative to the construction of other important neurotransmitters. Tryptophan is a natural relaxant, relieves stress, anxiety and depression, and most critically is used in the making of serotonin. This chain of events in our metabolism displays that when we have reduced levels of serine not only do we lose the direct benefit of serine alone, but we will also miss out on the many benefits of tryptophan and serotonin.

Serine and Fibromylagia

Interestingly, several studies in the past have revealed low plasma levels of amino acids in those with Fibromyalgia. Two studies reported in the Journal of Rheumatology, one done in Texas and another in Illinois, found decreased levels of various amino acids including serine and tryptophan among groups of FM patients. The Texas study results published in 1989 showed that “[p]atients with [FM] exhibited significantly lower levels of total serum tryptophan as well as six other amino acids” including serine. Likewise in 1992 it was reported that the Illinois study found that in addition to low plasma levels of tryptophan “plasma … serine levels were significantly decreased” in those with fibromyalgia. Hypotheses that these low levels of the precursors of serotonin indicate that serotonin itself also must be diminished in FM have since been proven correct. Similarly it has been reported that 5-HTP, a necessary intermediate in tryptophan’s conversion to serotonin, improves FM symptoms.

Serine Deficiency Found in CFIDS

Studies from the CPRU presented at the February 1998 Sydney conference indicate that serine deficiencies might be connected to CFIDS as well. The May/June 1998 issue of The CFIDS Chronicle reported that this group has been focusing on metabolites in urine as evidence of chemical processes within the body, particularly those involved in transforming food to energy.

Previously the findings of this group had also been presented in a handful of articles found in the journal, Biochemical and Molecular Medicine. That journal reported in 1996 that CPRU doctors had conducted a study to determine whether anomalies could be found in the urine excretion of CFIDS patients. Their study found three areas of significant difference in urinary content between 45 health controls and 25 CFIDS patients involved. One of these was abnormally low levels of serine. While all controls and patients had serine in their urine, in the CFIDS subjects “[serine] was significantly reduced.” This study then went even further by establishing that the severity of particular symptoms of each CFIDS patient correlated with the kind of anomaly found in their urine. Patients with low urinary serine were found to have predominant neurological symptoms and increased severity of pain.

Treatment with L-Serine

L-Serine is the form of serine used in protein synthesis and is readily assimilated by the digestive system. In October of 1998, Dr. Ian Buttfield commented that L-serine supplementation “should help about 60% of people with CFS significantly.” Dr. Buttfield starts patients on 500 mg in the morning, increasing to a daily total of 2 grams a day. Morning dosage is suggested because although this amino acid is remarkably free of side effects, some have complained of sleep disturbance while on serine.

Dr. Rosamund Vallings, a New Zealand general practitioner, spoke at the February Australian conference about her informal study of six CFIDS patients who were found to have low urinary serine levels. She prescribed 500 mg of L-serine twice daily. After one month, five of them saw improvement while one, the only child in the study, noted little change. The areas of greatest improvement with L-serine were 1) ear, nose, throat; 2) joints and muscles; 3) digestive tract; and 4) energy. Dr. Vallings concluded that “[a]ttempting to supplement this possible deficit has so far proved worthwhile.”

When interviewed, Dr. Vallings revealed that she had now been using L-Serine for about four months on two dozen or so patients. She has continued to have them take 500 mg twice daily but is considering increasing this to 2 grams a day, as Dr. Buttfield has been doing. Dr. Vallings acknowledges that while some patients have benefited with sleep, emotional, and cognitive function, other of her patients have not been helped by the serine supplements. Dr. Vallings cautions that amino acids should not be given if the patients’ serine levels are not known to be low, as this could effect the proper balance of these within the body. Supplementation should be under medical/health supervision.


To summarize the findings of the CPRU at Newcastle University, Dr. Hugh Dunstan states, “Evidence is now emerging that there are several distinct types of CFS which can be differentiated on the basis of symptom presentation and biochemical anomalies.” In particular, Dunstan believes that “[s]erine deficiency may be an important factor for certain types of CFS patients.” The findings and diligent scientific endeavors of this Australian team are most encouraging to the CFIDS community. Further studies will shed more light as to whether this group’s research will translate into viable treatment options for the many who suffer with this ailment.

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