January 2014
Daniela Maric, Snezana Brkic, Aleksandra Novakov Mikic, Slavica Tomic, Tatjana Cebovic, and Vesna Turkulov

 

Abstract

Background: Chronic fatigue syndrome (CFS) is characterized by medically unexplained persistent or reoccurring fatigue lasting at least 6 months. CFS has a multifactorial pathogenesis in which oxidative stress (OS) plays a prominent role. Treatment is with a vitamin and mineral supplement, but this therapeutic option so far has not been properly researched.

Material/Methods: This prospective study included 38 women of reproductive age consecutively diagnosed by CDC definition of CFS and treated with a multivitamin mineral supplement. Before and after the 2-month supplementation, SOD activity was determined and patients self-assessed their improvement in 2 questionnaires: the Fibro Fatigue Scale (FFS) and the Quality of Life Scale (SF36).

Results: There was a significant improvement in SOD activity levels; and significant decreases in fatigue (p=0.0009), sleep disorders (p=0.008), autonomic nervous system symptoms (p=0.018), frequency and intensity of headaches (p=0.0001), and subjective feeling of infection (p=0.0002). No positive effect on quality of life was found.

Conclusions: Treatment with a vitamin and mineral supplement could be a safe and easy way to improve symptoms and quality of life in patients with CFS.

Keywords: chronic fatigue syndrome, oxidative stress, quality of life, vitamins

 

Background

Fatigue is one of the most common complaints. It is defined as a lack of energy and its causes are numerous. About 10% of people experience fatigue that lasts for more than 6 months. Chronic fatigue syndrome (CFS) is characterized by medically unexplained persistent or reoccurring fatigue lasting at least 6 months [1]. This disease is often accompanied by numerous symptoms involving various body systems, including headache, joint pain, gastrointestinal (GI) disturbance, sore throat, painful lymphoadenomegaly, cognitive disturbances, and paresthesia [1–3]. The debilitating fatigue and the accompanying symptoms significantly influence everyday activities, thus patients with CFS generally experience a lower quality of life [4–7].

There have been reports that only approximately 20% of people living with CFS have been diagnosed [8]. The disease is more frequent in females in all epidemiological studies but the prevalence varies depending greatly on CFS definition, method of assessment and country (region) observed, and range from 0.03% to over 3% [8–10].

CFS most likely has a multifactorial pathogenesis in which oxidative stress (OS) plays a prominent role. Evidence supporting the pivotal role of OS in CFS is strong and extensive. Symptoms such as fatigue, pain, gastrointestinal problems, and cognitive impairment can all be connected to either direct toxic effects or indirect effects of reactive oxygen species [12–15]. Although most of the exact mechanisms by which OS causes some of the symptoms are yet to be defined, increased lipid and protein oxidation has been established in patients with CFS compared to controls. In these studies the degree of lipid and protein oxidation correlated with symptom severity. There is also some evidence of DNA damage due to OS in patients with CFS. Currently, there is general consensus that CFS is characterized by low-level inflammation and oxidative and nitrosative stress pathways [12–18].

Oxidative stress in CFS is due to diminished antioxidant capacity and/or decreased activity of antioxidant enzymes. Treatment with a vitamin and mineral supplement could be a safe and easy way to improve symptoms and quality of life in patients with CFS. However, this therapeutic option thus far has not been properly researched. In this study, we aimed to determine objective parameters of antioxidant capacity in patients with CFS before and after multivitamin mineral supplementation, as well as subjective parameters of treatment success.

Although CFS is a well-recognized condition world-wide, this is the first study of this condition in our region.

 

Material and Methods

Study population and clinical examinations
The research was conducted at the Infectious Diseases Clinic at the Clinical Center of Vojvodina during 2011. This was a prospective study of 38 women of reproductive age (18–50 years old) who were consecutively diagnosed and treated for CFS at the clinic. CFS diagnosis was established according to the CDC definition [19]. Before starting treatment, all the patients signed a written consent to participate in the study.

All patients were treated for 2 months with the multivitamin mineral supplement Supradyn® (Bayer Schering Pharma). Its contents are shown in Table 1. Patients purchased the supplement themselves and kept the boxes for inspection. We selected Supradyn® by Bayer Schering Pharma because at the time of the investigation, this supplement was one of the most affordable and its composition suited the purposes of the study. The study was a part of a regional project approved of and funded by the provincial Ministry of Science and was not in any way sponsored by a pharmaceutical company.

Ingredients of the multivitamin mineral supplement Supradyn® (Bayer Schering Pharma).

  • Vitamin B6    6 mg
  • Vitamin A    800 μg
  • Beta-carotene    0.72 mg
  • Vitamin D    5 μg
  • Vitamin E    10 mg
  • Vitamin C    180 mg
  • Vitamin B1    4.2 mg
  • Vitamin B2    4.8 mg
  • Vitamin B3    54 mg
  • Folic acid    600 μg
  • Vitamin B12    3 μg
  • Biotin    450 mg
  • Vitamin B5    18 mg
  • Vitamin K    0.03 mg
  • Calcium    120 mg
  • Phosphorus    120 mg
  • Iron    5.6 mg
  • Magnesium    45 mg
  • Zink    6 mg
  • Iodine    60 μg
  • Copper    1 mg
  • Chrome    0.05 mg
  • Manganese    1.4 mg
  • Potassium    20 mg
  • Selenium    28 μg
  • Silica    2 mg
  • Molybdenum    60 μg
  • Chloride    18.5 mg

 

We did not include patients who had known allergies to any of the components of the supplement, who were pregnant or lactating, who had current chronic or acute diseases, or who were taking antidepressants, antipsychotics, and/or anxiolytics.

Before and after the treatment, laboratory and clinical tests were performed to exclude active inflammatory syndrome.

To assess antioxidant status, superoxide dismutase (SOD) activity was measured in all patient plasma samples before and after treatment. SOD activity was determined using a commercial ELISA test based on the spectrophotometric principle. The signal strength correlated to activity of the enzyme. The SOD activity was expressed as both a percentage (%) and in equivalents (mEq).

Two self-rating scales were used to determine treatment outcome. Patients were questioned before and after treatment with multivitamin mineral supplement.

The Fibro Fatigue Scale (FFS) was used as an instrument to assess symptom severity and change after treatment in patients with CFS. The 12-item questionnaire included questions on aches and pain, muscular tension, fatigue, concentration difficulties, failing memory, irritability, sadness, sleep disturbances, autonomic disturbances, irritable bowel, headache, and subjective experience of infection. Based on the information obtained from a clinical interview, each item was scored 0 (absence of symptom) to 6 (maximum degree of symptom). To assist in scoring, a short description (anchoring point) was given for scores 0, 2, 4, and 6. If the patient’s condition fell somewhere in between the anchoring points, a score of 1, 3, or 5 (which were not defined) was given.

The short-form Quality of Life Questionnaire (QOL SF-36), which is widely used to measure disability in CSF research, was used to assess the impact of illness on everyday physical, psychological, and social functioning. The 36 items on the questionnaire are aggregated in 8 scales: physical functioning (PF), physical role (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), emotional role (RE), and mental health (MH). These are then aggregated into 2 summary measures (physical and mental health). Three scales (PF, RP, and BP) are strongly correlated with the physical component and contribute most to the scoring of the Physical Component Summary (PCS). The psychological component is most strongly correlated with MH, RE, and SF scales, which also contribute most to the scoring of the Mental Component Summary (MCS) measure. Three of the scales (VT, GH, and SF) have noteworthy correlations with both components.

 

Conclusions

This study is only the second study done on multivitamin mineral supplementation in CFS that used both biochemical and subjective markers of treatment success. Similar to other experimental studies on CFS, this one was also done on a relatively small number of patients. In our case this was due to the small number of patients diagnosed with the condition in our region, where CFS is rarely diagnosed and the incidence is unknown. We believe the power of this study lies in promising results in normalization of antioxidant enzyme activity and improvement of symptoms. Since immune activation and oxidative stress are now well documented in CFS, we believe this type of supplementation could be a safe addition to other therapeutic options for CFS patients.