Japanese Research on CFS Treatments

Since 1992 various ministries of the Japanese government, including the Ministry of Health and Welfare of Japan and the Japanese Ministry of Education, Culture, Sports, Science and Technology, have sponsored comprehensive research to uncover the molecular mechanisms of fatigue. Recently a study group of Japanese investigators from various fields have been investigating CFS specifically. The following information is from studies into various treatments for CFS (adapted from the book Fatigue Science for Human Health by Yasuyoshi Watanabe, MD, PhD). A report on their research into the cause of CFS was published in the summer 2008 issue of the CFIDS Chronicle.

There is currently no “magic bullet” treatment for chronic fatigue syndrome (CFS). However, our research in Japan (and that of other investigators) is shedding light on the mechanisms of the illness, and some treatments have been reported to be effective for the symptoms that CFS patients experience.

Here’s a brief overview of some of the treatments we’ve examined.

Herbal medicine

Some classic Chinese herbal medicines are reported to be effective for certain symptoms of CFS. This led us to study the effects of the herbal medicine TJ-41 (Tsumura Hoch-ekki-to) on 29 patients with CFS for 8 to 12 weeks, using a dosage of 7.5 g per day.

Results showed a noticeable improvement in 10 of the patients (34.5%). Two patients showed a slight improvement, 15 showed no change and 2 showed a slight increase in symptoms. Unfortunately, none of the patients was totally cured of their fatigue symptoms after treatment. Still, TJ-41 seemed to be an effective substance for treating fatigue in many of the cases.

TJ-41 also appeared to improve the quality of life for some patients. The number of patients who indicated that they were frequently unable to concentrate was dramatically reduced from 12 (41.4%) to 2 (6.9%) following treatment.

In addition, 10 of 17 patients in the study had low natural killer (NK) cell activity—a dysfunction of the immune system—before treatment, but all but one of these 10 patients showed an increase in NK activity after treatment.

High-dose administration of vitamin C

Research shows that vitamin C provides protection against oxidation. In fatigue experiments with mice, our research showed that a high dose of vitamin C reduced evidence of fatigue.

In human beings, a daily dose of 50-100 mg is adequate to protect against vitamin C deficiency, but the dose needed for protection against oxidation is many times higher. When we administered 3,000-4,000 mg of vitamin C per day to the CFS patients we studied, one-third of them reported an improvement in several symptoms of the illness, such as low-grade fever, fatigue and myalgia (muscle pain).

Vitamin B complex

It’s been reported that vitamin B1 plays an important role in glucose metabolism. Vitamin B1 and vitamin B12 are also reported to play an important role in neural function.

When we studied the effect of vitamin B1 on our fatigue-model mice, we noticed improvement in fatigue and performance. When we administered a high dose of vitamin B12 to patients with CFS, some of them showed an objective improvement in their sleep quality.

Since there are few adverse effects of vitamins B1 and B12, we routinely prescribe both for patients with CFS (30 to 100 mg/day of B1 and 3,000 mcg/day of B12).

Selective serotonin reuptake inhibitor (SSRI) and serotonin noradrenaline reuptake inhibitor (SNRI)

Our research suggests that serotonergic dysfunction is one of the aspects of the pathogenesis of CFS.

When we used the SSRI fluvoxamine maleate to treat 39 patients with CFS, 11 of them

withdrew from the treatment within two weeks because of side effects from the medication. The remaining 28 patients were given the SSRI for more than two months. Two of these patients were cured of CFS after the treatment, and eight of them recovered enough to return to work.

Paroxetine is also classified as an SSRI, and we found that it was equally as effective for the treatment of CFS. Although an SSRI, this drug formula is quite different from that of fluvoxamine maleate, and patients who have an adverse reaction to one can generally tolerate the other. Recently milnacipran hydrochloride (an SNRI) was also found to have a similar benefit for CFS patients.

It’s important to stress, however, that these SSRI and SNRI drugs are not only used for treating patients in a depressive state. We found that some CFS patients without depression still had serotonergic hypofunction, and that an SSRI or SNRI was frequently effective against their fatigue and pain.


Research indicates that acetylcarnitine dysmetabolism may be part of the pathogenesis of CFS. When we administered acetylcarnitine to several CFS patients who had acetylcarnitine deficiency, some of them showed a marked improvement in daily activities and reduction in their symptoms. Since few side effects are caused by this type of supplementation, it might become a useful treatment for CFS patients, or at least those patients with acetylcarnitine deficiency.


Recent research by others has shown that amantadine successfully inhibits Borna disease virus (BDV) in both cultured cells and in an infected human. Among the CFS patients we studied, some had antibodies against BDV in their plasma and BDV RNA in their blood. One group of these patients, from a single family, began using amantadine and found improvement in their CFS symptoms.

To further investigate this dymanic, we administered amantadine to 22 patients with CFS. Three patients withdrew from the study because of side-effects from the treatment. The other 19 took 200 mg per day of amantadine for eight weeks. When we evaluated the effects of the substance on patients with and without antibodies against BDV in their plasma, 6 of 11 patients with BDV antibodies showed a good response, whereas only 2 of 6 patients without the antibodies showed improvement.

There have been many conflicting reports about the effectiveness of amantadine on BDV. So the mechanism of the effect of this substance is unclear, but we consider it one of a range of therapies for some CFS patients.

Supportive Care

Patients with CFS are frequently plagued by a broad range of symptoms such as myalgia, arthralgia, sleep disturbance and digestive problems. We frequently use various kinds of supportive therapies such as acupuncture, massage, aroma therapy and laughter therapy depending on the symptoms.

September 1, 2008