Case Study by Niki Gratrix
Director of Nutrition
The Optimum Health Clinic

17th December 2008
University of Bedfordshire

Aims and Objectives

The aim of this case sudy is to analyse the effectiveness of natural dietary and supplement therapy prescribed by a licenced nutritional therapist for the treatment of a patient diagnosed with with Chronic Fatigue Syndrome (CFS). An introduction to the history, key aspects of the illness will be discussed, followed by analysis of some the current scientific literature on dietary interventions to determine the likely implications of treatment on the patient. The results of the treatment will be reported, followed by a discussion on how well these findings bear out expectations based on the analysis.

Introduction
CFS, also known as myalgic encephalomyalitis (ME), and post viral syndrome (PVS) is currently most commonly defined by the 1994 Fukuda et al. case defintion which used by researchers throughout the world (1). This definition requires a person to experience six or more months of chronic fatigue of new or definite onset. In addition there must be at least 4 of the below 8 symptoms:
• Sore throat
• Lymph node pain
• Muscle pain,
• Joint pain
• Post exertional malaise
• Headaches of a new or different type
• Memory or concentration difficulties
• Unrefreshing sleep

Currently CFS is a diagnosis of exclusion – meaning there is no specific biomarker that can be used to dignose the condition. The first outbreaks of CFS were reported back in medical literature in the 1930s. For many years the illness was purely seen as psychosomatic and “deviant” psychiatric behaviour, however, this changed when studies of CFS patients in 1996 and 1997 confirmed patients have disability rates similar to muliple sclerosis, rheumatoid arthritis, lupus, heart disease, diabetes and other serious illnesses (2-4).

The Report from the CFS/ME Working Group in 2002 summarised that approximately 0.2-0.4% of the population suffer from CFS (122,000 – 244,000 people based on population estimates of UK as 61 million) and the illness is about twice as common in women as it is in men (5). Children as young as five can also have CFS.

Per the 2002 CFS/ME Working Goup Report, there is a wide variation in the prognosis of the illness. However, there is a general consensus that full recovery after being ill for 5 years is rare, patients seem most like to recover if they have been ill for less then 2 years, and the probability of recovery reduces after 2 years.

There are currently no curative treatment recommendations for CFS. Many studies have shown subgroups of CFS/ME patients with sometimes serious abnormalities in the hypothalamic-pitutitary-adrenal (HPA) axis, heart function, gut function, mitochondrial function, immunity, coagulation abnormnalities and evidence of chronic low grade infections. Extensive overviews of these phsycial imbalances can be found in two papers by two leading CFS experts Kent Holtort and Leonard Jason (6-7).

There is now a concensus among leading researchers that people diagnosed with CFS are a hetergeneous group of patients with different underlying aetiologies and illness precedents as well as differences in symptoms. Like the disease cancer, subgroups of the disease need to be defined and only once clearer subgroups are identified will research be able to make headway (7).

Current Treatment Guidelines
Due to the nature of the illness, only large trials based on a psychosocial model of the illness have rendered consistent, if only weak positive results (8-9). The National Institute for Health and Clinical Excellence (NICE) issued treatment guidelines in 2007 which recommend cognitive behavioural therapy (CBT) and graded graded exercise therapy (GET) as treatments, as well as goal orientated activity management (10).

The only pharmacological recommendations are the use of low-dose tricyclic antidepressants (Amitrityline) for managing poor sleep or pain. Use of tricyclic antidepressants have been found to be unsatisfying due to the risk of adverse reactions and poor patient prognosis (11-12).

NICE guidelines for diet for CFS patients are to follow a well balanced diet as per the guidelines on the Food Standards Agency (13). The guidelines specifically prohibit GPs recommending any nutritional supplements above levels recommended by the Food Standards Agency, and prohibits recommending any form of complementary therapy because there is “not enough evidence they are effective” (14).

A study published in 1996 in the Journal of the American Dietetic Association concluded that diet did not play an important role in CFS and that the diets of CFS patients were generally not lacking in specific nutrients (15). Regarding supplementation, a randomized placebo-controlled double-blind trial of 53 patients in 2002 given a ploynutrient supplement (multi vitamin and mineral) found no difference between the placebo group and the treated group (16). In addition numerous tests for IgE food intolerances were done on CFS patients, no significant allergies were found, leading authors to conclude that the self-reported intolerances to foods must be part of the psychiatric model of CFS as a somatization disorder (17).

Based on official NICE guidleines and these studies, nutritonal therapy should make little or no difference for CFS patients.

Method
The subject is a 36 year old male, with a medical diagnosis of ME/CFS. The patient has been ill for 14 years. The medical history includes a healthy childhood except for developing asthma between the age of 5-10, and chest infections twice per year between the ages of 5 and 15. Severe CFS/ME began at age 21. The patient reports his mother also also has CFS/ME, his father has asthma and Parkinson’s disease, and a sibling has high blood pressure. The patient had a BMI of 23.53 at the beginning of treatment which is normal.

At the beginning of treatment the patient rated themselves with severe fatigue, which included being unable to do any exercise and frequent rest periods required daily. The patient had 5 of the other 8 criteria from the Fukuda 1994 diagnostic criteria including moderate muscle pain, moderate headaches, mild to moderate memory or concentration difficulties, mild sore throat or sore glands and mild sleep problems. The patient also reported moderate levels of depression and digestive problems including bloating, indigestion and constipation. The patient had completed full blood tests in October 2007, and apart from “borderline high” blood pressure, all results were normal.

At the start of treatment the patient was taking antidepressants Sertraline and Amitriptyline as well as Salbutamol and Beclomethasone inhalers for asthma. The patient was also receiving 1000mcg weekly of hydroxocabalamin (vitamin B12) by injection and regular treatment from a Perrin Practitioner – a form of deep lympahtic massage designed for CFS patients.

Before starting treatment the patient had been taking a multivitamin and mineral, a magnesium calcium and zinc supplement, milk thistle, vitamin C and an Omega 3 and 6 supplement daily.

Dietary Recommendations

The patient was not eating any dairy, eggs, additives, preservatives or fish and did not drink caffeine, fizzy drinks or alcohol at the start of treatment.

Key dietary recommendations were to:
• Cut out wheat
• Cut down on sugar and confectionary
• Avoid avoid hydrogenated and trans fats
• Eat a good portion of protein at each meal from a mixture of meat, fish and vegetable sources
• Have a portion of fruit or vegetables at each meal daily
• Have a portion of starchy carbohyrate with lunch and dinner from non-wheat sources
• Option to drink ½ pint of vegetable juice daily

A detailed list of foods allowed or to be avoided, a five day example plan of recommendations, with recipe ideas and quality and preparation recommendations given to the patient is found in the booklet enlcosed called the “Recipes for the Balanced Diet plan” and the “Juicing Handout.”

Test Results and supplement recommendations
At the initial consultation in May 2008 the following supplements were recommended:
• Ultramuscleze – contains high dosagage magnesium and malic acid
• Vianesse – contains protein powder
• Wholly immune – muti vitamin and mineral with emphasis on immune support, antioxidants and natural anti-inflammatory support
• ProEFAs – omega 3 and 6 supplement
• Progreens – probiotics for gut health and a range of living green foods high in antioxidants
• Liquid Zinc
• Vitamin D approximately 2000ius from all supplement sources
• Ionic Cal – a calcium and magnesium supplement
• Nutrigest – containing betaine HCL and pancreatic enzyme support
• Oxpowder – containing magnesium oxide to promote daily bowel movement and cleansing the colon.

Details on all supplements recommended are included.

Adrenal Testing and Treatment
A salivery adrenal stress index test was carried out in June 2008 with Diagnostechs Ltd, a registered lab in the United States (the lab complies with all regulatory agencies in the United States and World Health Organisation parameters for medical lab testing) showing that while DHEA was normal, and cortisol was sub-optimal. Total daily cortisol levels were 6.1nmol/L and the reference range is 21-41nmol/L

As a result the patient was moved onto two supplements, one called Dynamite Adrenal by Allergy Research – a multi vitamin and mineral with focus on specific adrenal support, containing tyrosine, licorice, porcine glandulars, ashwaganda as well as a range of vitamins and minerals and Adrenal Rebuilder by Dr Wilson, a multi-glandular product containing additional extracts of porcine adrenal, gonad, pituitary, thyroid, hypothalamus. Both supplements are processed so the glandulars contain no hormones.

Gut Testing and Treatment
A stool test carried was carried out by Diagnotech Ltd in June 2008 which showed the following abnormalities:
• Moderate to rare overgrowth of pathogenic bacteria
• A small amount of yeast overgrowth
• Very low stool levels of intestinal SigA
• Borderline elevated levels of alpa anti-chymotrypsin (inflammation)
• Low levels of chymotrysin (pancreatic enzyme output)
• No worms, parasites or secretory IgA food intolerances were found.

As a result it was concluded the patient had some degree of “leaky gut” and was recommended to continue avoiding wheat, to add in Nutrigest which contains betaine HCL and glandular pancreatic enzymes to help absorption of nutrients, to continue Progreens as it contains 5 billion bacteria per serving and Saccharmyces boulardii, a probiotic which is a non-colonizing yeast to increase secretory IgA and help healthy gut bacteria colonize in the gut. The patient was also told to continue zinc to support gut healing.

Results
Changes in Symptoms
Changes in the patients reported symptoms per the follow up questionnaire filled out in November 2008 are shown in the table below.

*Ratings 0-10:

0 = no symptoms

1= very mild

5 = moderate

10 = severe

Other reported changes in symptoms included that the asmtha was “much improved” and the patient is now no longer using the Beclomethasone and has reduced usage of the Salbutamol inhaler. The patient also stopped taking Sertraline and reported trying this twice before but was unsuccessful due to the reduction in energy. The patient reported no longer needing to take frequent rest periods during the day and was able to excerise again after treatment. Final comments from the patient were:

“I generally feel more energized, stamina has at least tripled, crashes are less severe and I’m recovering much quicker from them (less than a day compared to 2-3 days before). I feel more able to cope with stress. My blood pressure is no longer high. I rarely have asthma symptoms now – I’m clear as long as I stay away from dairy, additives and perfumes. My face is less pale and my skin is less dry. The dry flaky skin on my elbows which I have had for life has cleared up. People are commenting on how well I look!”

Adrenal Salivary hormone Results
A second adrenal stress index test completed in December 2008 showed an improvement from the original test – total daily cortisol increased from 6.1nmol/L to 10.3nmol/L, with the largest increase found in the morning cortisol sample which rose from 2.8nmol/L to 6.4nmol/L. Overall cortisol was still low showing fruther treatment with supplemental adrenal support maybe beneficial.

Dietary Changes Achieved per Dietary Analysis
Electronic analysis using Dietplan 6 software showed that the patient followed most of the dietary recommendations made.
There was a significant increase in antioxidants – retinol increased from 10 to 25ius, carotene from 12261 to 14215 ug, vitamin E from 11.7 to 12.28mg. Re minerals: selenium from 23.8 to 72.8ug, manganese 4.86 to 5.84mg and copper 1.86 to 2.76. Zinc and vitamin C were slightly down.

Generally all the minerals levels increased (potassium, calcium, magnesium, iron) although sodium levels fell.

The patient cut down significantly on confectionary resulting in total sugars reducing from 145g to 70.3g daily. Currently the patients carbohydrate intake by weight is well below the recommended daily amount for a man of his age and activity levels.

Total fats were down 89.1g to 48.4g and trans fats reduced to almost reduced to zero. As the patient eats no dairy, eggs or read meat, the total saturated fat intake is below the recommended daily amount.

Currently total daily protein is above the daily recommended amount.

Most likely due to the low carbohydrate and saturated fat levels, the patient is eating some 1000 calories below the recommended daily amount. The patient lost weight during the treatment down to 78kg from 81kg, although the BMI is still in the normal range at 22.8.

Discussion
While large randomised controlled trials in nutritional treatments are lacking in CFS, there are scientifc studies which suggest treatment with nutritional therapy and natural supplementation could make a difference for CFS patients.

Sub-Optimal Adrenal Function
Abnormalities in the HPA axis are now known to occur in CFS patients, specifically subtly low levels of cortisol have been found which when treated with low dosage cortisol, produce significant improvement in CFS patients (6). Although adrenal glandulars have not been specifically tested on CFS patients, injected procine liver extract has been found to help CFS patients in a study in 1994 by Steinback (18) and injections of thymus extract from calves have seen a 59% remission rate of immuno supressive diseases in children, showing that glandulars (also known as live cell therapy) is an effective treatment for humans (19).

Some improvement in the patients symptoms could be due to the improvement in cortisol output, however, whether this increased output is due to the glandular treatment, or improving the gut and general absorption of antioxidants, is unclear.

Food intolerances and leaky gut
Logan, Nismebaum and Emms et al confirmed that food intolerances are implicated in CFS patients symptoms (20-22). Intolerances are not the same as secretory IgE intolerances, and were not recognised by the medical community until recently. In 2000 a study in the Lancet by Jacobsen at al showed that non-allergic food intolerances created immune activation accompanied by increases in systemic symptoms (23). As studies have shown CFS patients have type 2 helper cell dominate cytokine profiles and frequently self report intolerances to foods, taking out foods which cause reactions should be helpful treatment for CFS patients (20,24). The Lancet study also explains why IgE tests for allergies are not found in CFS patients, and self reported symptoms of intolerances to foods may not be due to somatization traits.

In 2004 Logan et al in Medical Hypothesis suggested that lactic acid bacteria given to CFS patients could be benefitical after two studies showed CFS patients had marked alterations in intestinal microflora (24). Since then in 2006 Maes et al in Belgium confirmed again that they found significant microflora imbalances in CFS patients (25). In 2007 Maes et al made the link between gut flora imbalances and leaky gut, and presented a case study in which treating a CFS patient for leaky gut (including giving gut healing support including glutamine, zinc and putting the patient on a low-allergenic diet) caused complete remission in the CFS patient (26).

The patient in this case study showed signs of leaky gut and a microflora imbalance. Although no follow up stool analysis test was completed due to the costs involved, the patient did comply with the recommendation of cuting out wheat and taking gut supportive supplementation therefore some of the symptoms improvement maybe atrributed to treatment for the gut and food intolerances. Gut symptoms were an area in which the patient reported one of the highest reductions in symptoms.

Antioxidants
Many studies of CFS patients now confirm there is an increased level of oxidative stress in CFS patients (27-31). Pall suggested in Medical Hypothesis in 2000 that antioxidant supplementation might be useful therapy for CFS patients (32).

The dietary changes made by the patient showed an increase in antioxidants, and plenty were added through supplementation. It is possible that some of the improvement felt by the patient was due to the increase in antioxidants.

This patient also showed they had pancretic enzyme deficiency. Although no studies have yet been completed on CFS and pancreatic enzyme output, deficiency could be common in CFS patients. This alongside malabsorption that is often associated with microflora imbalances, means that just taking a relatively low dosage multi vitamin and mineral with no gut support, may result in supplements not being absorbed, and could explain the non-response in the 2002 trial with a polynutrient high in antioxidants.

One final note on the likihood of the placebo effect occurring with this patient is that it is unlikely the improvement found was down to the placebo response because the patient was taking supplements previous to treatment, and they had also been to see numerous practitioners before coming into treatment with this practitioner. Cho et al have shown that such cases have a low placebo response (33).

Recommendations to patient to improve diet
The patient should decrease protein intake and increase total carbohydrate from wheat-free slow release starchy carb sources, such as adding in more lentils, potatoes, brown rice and grains like quinoa to ensure they are obtaining enough daily calories for energy amd to prevent unnecessary weight loss.
As the patient eats no eggs, dairy or red meat, saturated fat is low – the patient could increase saturated fat intake using coconut oils and milks, and certain nuts including brazils and macademia nuts. The patient could also add in some organic red meat for variety as there is a lot of emphasis on soya and processed forms of mushrooms for protein in his diet at present.

Conclusion
Dietary intervention and/or natural supplementation could produce sigificant improvement for patients with CFS. Whether the improvement for this particular patient was due to the elimination of wheat, the increase in antioxidant intake or treatment for adrenal imbalance or gut health is unclear. Further research is warranted.

References
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5. The CFS/ME Working Group Report is available at government website http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4064840
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