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Beta-Carotene Stimulation of Natural Killer Cell Activity in Adult Patients with Chronic Fatigue Syndrome

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By Author: Burke A. Cunha, M.D. • • December 1, 1994

In my opinion, the cause of chronic fatigue syndrome (CFS) is clearly viral. From a therapeutic point of view, it makes little difference which virus or viruses are responsible, since there are so few antiviral agents. Antiviral chemotherapy, e.g., acyclovir, has been tried in patients with CFS with little success. The data on immunoglobulin therapy is conflicting at best. Similarly, the efficacy of Ampligen has not been convincingly demonstrated, even though it has benefited some individuals. Therefore, the treating physician has little to offer the patient in terms of antiviral chemotherapy or immune modulation therapy. Some clinicians prescribe mood elevators or sleep aids to provide symptomatic relief to some patients. Aside from counseling to help the patient cope with CFS, the doctor can only offer strategies to minimize fatigue and maximize mental function.

Since effective antiviral chemotherapy is not available, research efforts have been focused on indirect antiviral measures that will eliminate or decrease the virus or viral effects responsible for CFS. It has been demonstrated that although there are many immunological perturbations in patients with CFS, the most consistent abnormality is a decrease in natural killer (NK) cell numbers and/or activity. NK cells can be increased in a dose-dependent phase by beta-carotene, a vitamin A precursor. For the past two years, we have been administering beta-carotene to outpatients who show decreased NK cell numbers (below six percent; normal range is 6 to 22 percent). Patients who are candidates to receive beta-carotene therapy often state that they are already taking beta carotene as part of their multivitamin supplements. In our experience, conventional therapeutic and natural vitamins all contain inadequate concentrations of beta-carotene for NK cell augmentation. Therefore we have spent the past two years trying to determine the optimal dose of beta-carotene to augment NK cell numbers in our CFS population.

We routinely assess our patients' signs and symptoms before and after treatment by questionnaire/physical examination. Our patients meet the CDC definition of the syndrome as well as our own clinical diagnostic criteria for CFS, as outlined in our Internal Medicine article (Walsh RD, Cunha BA: The diagnostic approach to chronic fatigue syndrome. Intern Med 1993; 14:48-52). Since beta-carotene is a vitamin A precursor, we also obtain serum vitamin A concentrations prior to initiating beta-carotene therapy. If pre-treatment vitamin A levels are low, i.e, they fall within or below the therapeutic range (30 to 95), beta-carotene therapy is continued for three weeks. The patients then return for repeat vitamin A levels and NK cell counts. Patients are warned not to continue beyond three weeks of therapy to avoid carotenemia due to excessive vitamin A. We have found that beta-carotene increases the number of NK cells in the majority of patients who have low pretreatment NK cell numbers and also results in a decrease in fatigue. We have not been able to consistently demonstrate that beta-carotene therapy improves cognitive function in patients with CFS, although it clearly seems to be of benefit to some individuals.

We are happy to be able to offer CFS patients a rational, indirect therapeutic approach to combating the presumed CFS virus or its effects on the immune system. Theoretically, beta carotene may work by increasing NK cell function, which seems to result in enhanced antiviral activity in vivo. We postulate that anti-viral activity induced by beta-carotene therapy may translate into clinical improvement in many patients. In our experience, beta carotene therapy is less efficacious in improving symptoms in patients with normal NK cell numbers pre-treatment. Interestingly, other researchers have reported that beta-carotene therapy is helpful in stimulating the immune system in patients with HIV. This information suggests that the beta-carotene stimulation of the NK cell population may not only be useful in CFS, but may also be useful as indirect antiviral treatment in selected viral illnesses with NK cell abnormalities.

Editor's Note: Dr. Cunha uses 25,000-50,000 IU daily, depending on the patient's needs. Reprinted with permission from The CFIDS Chronicle, Winter 1993.

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