Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a clinical condition characterised by unexplained disabling fatigue combined with a variety of accompanying symptoms, which may include headaches, muscle and joint pain, post-exertion malaise, cognitive difficulties, non-refreshing sleep and depression.
The cause of CFS/ME is unknown. Defects in mitochondrial function leading to decreased energy, impaired immune response and activation of stress pathways resulting in the production of numerous inflammatory by-products – these all appear to play a direct role in CFS/ME. The onset of symptoms appears to be induced by a number of trigger factors, including psychological stress, strenuous exercise and persistent viral infection.
Treatment for CFS/ME aims to manage symptoms but the diversity and different level of severity of symptoms from person to person means there is no single treatment that works for everyone. The increase in the success of nutritional interventions as adjuvants to (or in place of) pharmaceutical treatments is leading inevitably to an increase in demand for and understanding of quality effective supplements. Current evidence supports a number of nutrients for therapeutic benefit. This article outlines some of those considered most effective (see table 1).
|Commonly used supplements||Actions||Main benefits in CFS/ME|
|Coenzyme Q10||Involved in the production of “energy molecules” such as ATP, NADH, and FADH||Improves energy, reduces fatigue, improves ‘brain fog’|
|EPA (eicosapentaenoic acid)||Important component of cell membranes and precursor to immune and inflammatory regulating eicosanoids||Improves immune function, potent anti-inflammatory, aids against viral infections, improves energy, reduces fatigue, improves ‘brain fog’, concentration and mood|
|GLA (gamma-linolenic acid)||Important component of cell membranes and precursor to immune and inflammatory regulating eicosanoids||Improves sleep, improves immune function and acts as an anti-inflammatory|
|D-ribose||Involved in the production of “energy molecules” such as ATP, NADH, and FADH||Improves energy, reduces fatigue, reduces muscle discomfort|
|Acetyl L-carnitine||Transports fatty acids across and into the mitochondria and helps the body produce energy||Improves energy|
|Magnesium||Maintains normal muscle and nerve function, involved in energy production||Improves energy, concentration and mood, decreases pain|
|Malic acid||Produced by metabolic pathways and provides the cells with energy and carbon skeletons for the formation of amino acids||Improves energy|
|Vitamin B12||Improves energy production, decreases fatigue, aids in the regulation of the nervous system, reduces depression and stress||Improves energy, reduces fatigue, improves ‘brain fog’|
Table 1 – supplements commonly used for CFS/ME
Several lines of evidence suggest that low levels of Coenzyme Q10 (CoQ10) play a direct role in the pathophysiology of ME/CFS and that symptoms such as fatigue, and autonomic and neurocognitive symptoms including concentration and memory disturbances may be caused, in part, by CoQ10 depletion1. CoQ10 plays a fundamental role in the production of cellular energy by acting as a cofactor in the mitochondrial electron transport chain (respiratory chain) and hence in the production of ATP – the body’s energy ‘currency’.
Coenzyme Q10, also called ubiquinone (a derivative of the Latin word ubique, meaning “everywhere”), is required by every human cell. Once absorbed, more than 90% of ingested ubiquinone is converted into the potent antioxidant form – ubiquinol. The reduction of ubiquinone to ubiquinol is dependent on several factors and any impairment in the conversion process will impact on ubiquinol levels which, if they become low or depleted, can result in muscle cramp, fatigue and an increase in oxidative stress leading to cell and tissue damage (see table 2).
|Factors influencing ubiquinol production||Conditions associated with low ubiquinol production|
|Use of statins||Mitochondrial disorders|
|Increased metabolic demands||Neurodegenerative diseases|
|Increasing age||Cardiovascular disease|
|Insufficient dietary CoQ10 intake||Myopathy/neuropathy|
Table 2 – the importance of CoQ10
Ubiquinone is the more common form of commercially available CoQ10. In the past several years, extensive efforts have been made to improve oral bioavailability and formulation strategies aimed at improving the absorption of CoQ10 include oil-based formulations, solubilised formulations and molecular complexes (such as colloidal delivery) designed to mimic the natural absorption process. The latter two come with a hefty price tag, however, and so the key to sourcing a good quality but affordable supplement is to source one that contains the reduced form – ubiquinol, which is clinically proven to offer superior bioavailability over supplements containing ubiquinone.
CoQ10 key points
- Consuming CoQ10 with food is known to improve CoQ10 absorption (via presence of dietary fat)
- Oil suspensions are superior to powder-based products
- Ubiquinol supplements are more cost effective than ubiquinone supplements by offering superiorhealth benefits
- Absorption and bioavailability of ubiquinone and ubiquinol products can be enhanced by both colloidal and solubilised delivery but are generally high in price
- Split dosing (i.e., 100-200 mg twice daily) is superior to single dosing as the efficiency of absorption decreases as the dose increases.
Polyunsaturated fatty acids
There is increasing evidence that ME/CFS is associated withpersistent viral infection and that such infections are likelyto impair the ability of the body to make omega-3 and omega-6long-chain polyunsaturated fatty acids by inhibiting the action of delta-6desaturase, the key enzyme involved in fatty acid metabolism. This appears to impairthe proper functioning of cell membranes, with adverse effects on the biosynthesis of eicosanoids involved in the regulation of immune function and inflammation. A potential therapeutic avenuecould be offered by bypassing the inhibition of the enzyme delta 6-desaturaseby direct supplementation with long-chain fatty acids.
Vegepa E-EPA 70 is a unique synergistic formulation which combines ultra-pure EPA and GLA from organic virgin evening primrose oil, providing a highly concentrated source of omega-3 and omega-6 fatty acids and botanical triterpenes. Two grams of EPA daily taken as a split dose appears to be an effective dose for CFS/ME2:
- Supplementary EPA and GLA help to restore a healthy omega-6/omega-3 ratio known to be dysregulated in ME/CFS
- EPA and GLA enhance the integrity and fluidity of cell membranes and mitochondrial membranes and are the precursors to anti-inflammatory and immune regulating substances and can help reduce symptoms of fatigue, pain and ‘brain-fog’
- EPA and GLA can help restore affected sleep patterns seen in individuals with long-chain fatty acid deficiencies
- EPA has antidepressant actions similar to conventional pharmaceuticals
EPA and triterpenes are potent virucidal agents, capable of destroying or inactivating viral infections commonly observed in ME/CFS.
Other supplements to consider
D-ribose – D-ribose is a naturally occurring carbohydrate, the sugar moiety of ATP and a key structural component of substances such as coenzymes needed by mitochondria to maintain cellular energy homeostasis. Supplemental D-ribose not only enhances the production of ATP but also offers additional benefits by reducing free radical formation arising from oxidative stress. D-ribose at a daily dose of 3 x 5 grams for a total of 280 grams (i.e. 19 days) has been shown to significantly reduce clinical symptoms in patients suffering from fibromyalgia and CFS in the areas of energy, sleep, mental clarity, pain intensity and general well-being3.
Acetyl L-carnitine – Carnitine (L-carnitine or acetyl-L-carnitine) is an amino acid involved in the transport of fat into cells so that it can be converted into energy. Patients with CFS/ME often show low levels of serum acetyl-L-carnitine, correlating directly with score ratings of fatigue . Taking acetyl-L-carnitine at a daily dose of 500 to 1,000mg could improve symptoms of fatigue, but higher doses of up to 3-4 grams daily also appear to be well tolerated.
Magnesium malate – Magnesium malate supplies magnesium chelated to the Kreb’s cycle intermediate. Both substances help produce ATP and the product is well documented for increasing energy levels and helping combat fatigue and pain. The chelated magnesium increases both absorption and bioavailability, making it a superior product to the commonly available magnesium oxide. Magnesium malate should be taken three times daily and Source Naturals Magnesium Malate delivers an impressive 2500mg malic acid and 425mg magnesium in just three capsules.
Vitamin B12 – Studies suggest a direct relationship between vitamin B12 deficiency and increased levels of both fatigue and depression. Methylcobalamin, the active coenzyme form of vitamin B12 is essential for proper cell growth and neurological function and is absorbed either bound to intrinsic factor or through a receptor mediated mechanism in the ileum. Given the issues with saturation with the latter, absorption of vitamin B12 can decrease as the oral dose is increased. 1000mcg appears to be a generally accepted dose and it may be advisable to split the dose throughout the day or seek advice on vitamin B12 injections, which offer an effective, safe and inexpensive alternative to oral treatment in the management of CFS/ME.
There is no known cure for CFS/ME and options usually focus on treatments that can help relieve symptoms. The effectiveness of these treatments appears to be dependent in part on each individual’s symptoms with no one size fits all’ therapeutic offering. Addressing common deficiencies in key nutrients involved in vital metabolic pathways and known to play a role in the onset and progress of symptoms can, however, help to manage many of the symptoms of CFS/ME, allowing sufferers to lead as normal a life as possible.
- Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro endocrinology letters 2009, 30:470-476.
- Puri BK: Long-chain polyunsaturated fatty acids and the pathophysiology of myalgic encephalomyelitis (chronic fatigue syndrome). Journal of clinical pathology 2007, 60:122-124.
- Teitelbaum JE, Johnson C, St Cyr J: The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. Journal of alternative and complementary medicine 2006, 12:857-862.
- Kuratsune H, Yamaguti K, Lindh G, Evengard B, Hagberg G, Matsumura K, Iwase M, Onoe H, Takahashi M, Machii T, et al: Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. NeuroImage 2002, 17:1256-1265.