CoQ10
Antioxid Redox Signal. 2015. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Chronic fatigue syndrome (CFS) is a chronic and extremely debilitating illness characterized by prolonged fatigue and multiple symptoms with unknown cause, diagnostic test, or universally effective treatment. Inflammation, oxidative stress, mitochondrial dysfunction, and CoQ10 deficiency have been well documented in CFS. We conducted an 8-week, randomized, double-blind placebo-controlled trial to evaluate the benefits of oral CoQ10 (200 mg/day) plus NADH (20 mg/day) supplementation on fatigue and biochemical parameters in 73 Spanish CFS patients. A significant improvement of fatigue showing a reduction in fatigue impact scale total score was reported in treated group versus placebo. In addition, a recovery of the biochemical parameters was also reported. NAD+/NADH, CoQ10, ATP and citrate synthase were significantly higher, and lipoperoxides were significantly lower in blood mononuclear cells of the treated group. These observations lead to the hypothesis that the oral CoQ10 plus NADH supplementation could confer potential therapeutic benefits on fatigue and biochemical parameters in CFS. Larger sample trials are warranted to confirm these findings.

Ribose - one small study indicates that perhaps ribose may be helpful. At least 2 or 3 more studies showing the same results from different researchers would solidify this finding.

Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome.
Psychosom Med. 2004.
We compared the effects of acetylcarnitine, propionylcarnitine and both compounds on the symptoms of chronic fatigue syndrome. In an open, randomized fashion we compared 2 g/d acetyl-L-carnitine, 2 g/d propionyl-L-carnitine, and its combination in 3 groups of 30 chronic fatigue syndrome patients during 24 weeks. Effects were rated by clinical global impression of change. Secondary endpoints were the Multidimensional Fatigue Inventory, McGill Pain Questionnaire, and the Stroop attention concentration test. Scores were assessed 8 weeks before treatment; at randomization; after 8, 16, and 24 weeks of treatment; and 2 weeks later. Clinical global impression of change after treatment showed considerable improvement in 59% of the patients in the acetylcarnitine group and 63% in the propionylcarnitine group, but less in the acetylcarnitine plus propionylcarnitine group (37%). Acetylcarnitine significantly improved mental fatigue and propionylcarnitine improved general fatigue (p =.004). Attention concentration improved in all groups, whereas pain complaints did not decrease in any group. Two weeks after treatment, worsening of fatigue was experienced by 52%, 50%, and 37% in the acetylcarnitine, propionylcarnitine, and combined group, respectively. In the acetylcarnitine group, but not in the other groups, the changes in plasma carnitine levels correlated with clinical improvement. Acetylcarnitine and propionylcarnitine showed beneficial effect on chronic fatigue syndrome and attention concentration. Less improvement was found by the combined treatment. Acetylcarnitine had main effect on mental fatigue and propionylcarnitine on general fatigue.

The use of eicosapentaenoic acid in the treatment of chronic fatigue syndrome.
Prostaglandins Leukot Essent Fatty Acids. 2004.
There is evidence that there is an association between chronic fatigue syndrome, a condition of unknown etiology, and essential fatty acids. This evidence is based on the actions of essential fatty acids, the results of proton neurospectroscopy studies, and essential fatty acid trial data. A series of patients with chronic fatigue syndrome were treated solely with a high-eicosapentaenoic acid-containing essential fatty acid supplement. All showed improvement in their symptomatology within eight to 12 weeks. These results, which are consistent with a recent detailed report of cerebral and clinical changes associated with a high intake of eicosapentaenoic acid, suggest that this n-3 highly unsaturated fatty acid may offer the hope of effective treatment for at least some patients with chronic fatigue syndrome.

Eicosapentaenoic acid-rich essential fatty acid supplementation in chronic fatigue syndrome associated with symptom remission and structural brain changes.
Hammersmith Hospital, London, UK. Int J Clin Pract. 2004.
Lateral ventricular enlargement has been reported in chronic fatigue syndrome, while cerebral neurospectroscopy has recently indicated that essential fatty acid treatment may be of value in this condition. An essential fatty acid supplement rich in eicosapentaenoic acid (EPA) was therefore given daily to a female patient with a 6-year history of unremitting symptoms of chronic fatigue syndrome. Cerebral magnetic resonance scanning was carried out at baseline and 16 weeks later. The EPA-rich essential fatty acid supplementation led to a marked clinical improvement in her symptoms of chronic fatigue syndrome, starting within 6-8 weeks. Accurate quantification of the lateral ventricular volumes in the baseline and 16-week follow-up registered images of high-resolution magnetic resonance imaging structural scans showed that the treatment was accompanied by a marked reduction in the lateral ventricular volume during this period.

Green tea extract and catechin ameliorate chronic fatigue-induced oxidative stress in mice.
J Med Food. 2005.
Chronic fatigue syndrome is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of chronic fatigue syndrome remains unclear, but a number of studies have shown that oxidative stress may be involved in its pathogenesis. The present study was designed to investigate the protective effect of green tea extract and catechin in the mouse model of chronic fatigue syndrome. Animals were subjected to a forced swimming test session of 6 minutes every day for 7 days; a significant increase in immobility time on successive days represented the chronic fatigue syndrome in mice. Biochemical analysis revealed that the chronic swim test significantly increased lipid peroxidation levels and decreased glutathione levels in mouse whole-brain homogenate. Treatment with green tea extract (25 or 50 mg/kg, i.p.) and catechin (50 or 100 mg/kg, i.p.) for 7 days reversed the increase in immobility time. Protection was correlated with the lowered levels of lipid peroxidation and restoration of reduced glutathione levels in the brains of fatigued mice. These findings strongly suggest the pivotal role of oxidative stress in the pathophysiology of chronic fatigue syndrome and that green tea extract and catechin could be used as potential agents in the management of chronic fatigue syndrome and warrant the inclusion of green tea extract and catechin in the treatment regimen of chronic fatigue syndrome patients.

Multivitamins may be helpful
Med Sci Monit. 2014. Multivitamin mineral supplementation in patients with chronic fatigue syndrome. 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.

Diagnosis of chronic fatigue syndrome
Diagnosis is primarily by exclusion with no definitive laboratory test or physical findings. The primary feature of chronic fatigue syndrome is severe, incapacitating fatigue. A diagnosis can be made if a patient has had severe fatigue for six months or longer, and other medical conditions have been excluded. The patient must also have four or more of the following symptoms: impairment in short-term memory or concentration; sore throat; tender lymph nodes; muscle pain; multiple joint pain without swelling or redness; headaches; sleep does not not improve the fatigue; and malaise after physical exertion.

Causes
Medical research continues to examine the many possible causes for chronic fatigue syndrome. These include infectious agents, along with immunologic, neurologic, and psychiatric conditions. But the answer remains elusive. It is known that this condition is a heterogeneous disorder possibly involving an interaction of biologic systems. Similarities with fibromyalgia exist and concomitant illnesses include irritable bowel syndrome, depression, and headaches.
   Some patients with chronic fatigue syndrome appear to have a chronic enteroviral infection that can be detected by a stomach biopsy. Enteroviruses are acid and bile resistant and are believed to be common causes of acute gastritis. Some patients have persistent or intermittent, upper and/or lower gastrointestinal symptoms.
   Emotional and sexual abuse in childhood are important risk factors for CFS.
   Researchers are disputing a 2009 study that found a virus in the blood of people with chronic fatigue syndrome. No evidence was found of XMRV infection in some of the same patients who were involved in the original study. Additionally, some of the authors of the original trial announced that they were retracting some of their results after finding evidence of contamination in some of their study samples.
   Endometriosis is caused when tissue that normally lines the uterus grows at other sites. It may produce more than pelvic pain. It seems to increase the risk of migraine headache. Previous reports have linked endometriosis with a variety of disabling conditions, such as autoimmune diseases, chronic fatigue syndrome, and fibromyalgia.
   Perhaps in rare cases mercury amalgam dental fillings can be a contributing factor.

A study, published in the Oct. 28 2014 issue of Radiology, found patients with chronic fatigue syndrome had less overall white matter (nerve tracts that carry information from one part of the brain to another) than the people who didn't have the condition. CFS may involve chronic inflammation, which may be due to an unidentified viral infection. Such an infection can take a toll on white matter.

Is it genetic?
Results from a large study of chronic fatigue syndrome to date suggests that there are specific genes and gene activity patterns that make some people more prone to develop the disorder. Pharmacogenomics, 2006.

Suggestions by CDC
Chronic fatigue syndrome is a real disease that affects more than a million Americans, the U.S. Centers for Disease Control and Prevention said in November 2006. Up to 80 percent of people with chronic fatigue do not know they have it, the CDC said. Its causes are unknown but it can cause profound exhaustion, sleep difficulties, and problems concentrating and remembering. Flu-like symptoms, including pain in the joints and muscles, tender lymph nodes, sore throat and headaches are also common. A distinctive characteristic of the illness is a worsening of symptoms following physical or mental exertion. "Diagnosis is primarily made by taking a patient's medical history, completing a physical exam and lab tests to rule out other conditions," says the CDC. "The CDC considers chronic fatigue syndrome to be a significant public health concern, and we are committed to research that will lead to earlier diagnosis and better treatment of the illness," CDC Director Dr. Julie Gerberding said. Several other illnesses have symptoms that mimic chronic fatigue syndrome, including fibromyalgia syndrome, myalgic encephalomyelitis, neurasthenia, multiple chemical sensitivities, and chronic mononucleosis. There are tens of millions of people with similar fatiguing illnesses who do not fully meet the strict research definition of chronic fatigue syndrome. No one therapy works but reducing stress, dietary restrictions, gentle stretching and nutritional supplementation have all been shown to help. "Patients should be advised to avoid herbal remedies like comfrey, ephedra, kava, germander, chaparral, bitter orange, licorice root, yohimbe and any other supplements that are potentially dangerous in high doses," says the CDC.

Research
Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome.
BMC Neurol. 2004
Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue. Using magnetic resonance imaging, we conducted voxel-based morphometry of sixteen patients and 49 age-matched healthy control subjects. We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects. CONCLUSION: These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue.

Randomised controlled trial of graded exercise in chronic fatigue syndrome.
Med J Aust. 2004.
Graded exercise was associated with improvements in physical work capacity, as well as in specific psychological and cognitive variables in chronic fatigue syndrome. Improvements may be associated with the abandonment of avoidance behaviors.

Randomized controlled trial of Siberian ginseng for chronic fatigue.
Psychol Med. 20041.
This randomized controlled trial evaluated the effectiveness of Siberian ginseng. Overall efficacy was not demonstrated.

Emails
Q. I have Chronic fatigue syndrome and FMS and am taking Elavil. The studies I have read suggested the ingredients I should try to boost my energy. I stumbled across panax ginseng and take Advanced Ginza-Plus. I then noticed Triple-boost, and have noticed a definite difference. My question is System-six and Advance ginko smart have helpful ingredients also. I want to try them, but am wary of mixing them, or how to try them to see which is more beneficial for me.
     A. We generally recommend taking a supplement for a few days to see how it does and then taking a break for at least 2 days before trying another one. There may be several different supplements that could be helpful.

Q. I have chronic fatigue syndrome and bipolar. I am taking 500 mg acetyl carnitine with R- alpha lipoic acid  once a day and I am loving the effect, I am able to do a lot more which is REALLY saying something, considering I have a serious illness.

Q. Physician Formula R-Alpha Lipoic acid. Why would my wife and I be taking this supplement? What kind of benefit have we noticed and now appreciate? How can it help others with similar health problems to ourselves? Good questions, but the results are real and exciting for the two of us who were suffering from just making it through each day as it descended upon us...... and I'll bet there are many others out there who just exist each day also. As a long-time sufferer of Chronic Fatigue Syndrome, with it's diabetic-like symptoms of fluctuating blood sugar problems, fuzzy brain and VERY low energy through inefficient cellular metabolism and consequent low ATP production, I personally have more than doubled my energy output since regularly taking R-ALA supplementation over the last few months. Life is getting exciting again, I have a clearer mind and I am able to output work more constantly in my business plus look forward to waking up each day instead of dreading it. My lovely wife also has just quietly "existed" each day. She has suffered from problems with "....." (can't legally use that word) with subsequent draining of her bodily energy as her immune system fights to keep her condition in check. She has only been taking R- Alpha Lipoic for a few weeks and I have noticed her with much more energy and spending a lot more time outside in the garden, feeling like life has arrived for her again. She actually stayed up late to watch the world's number one in tennis play a critical final in his career, and did not suffer for the late night next day. We both feel more relaxed and enjoy each day as it comes to us and I know that the only dietary or lifestyle change we have both made recently to bring this about is our becoming "ALA poppers" - two each per day. If it helps us so dramatically, how many others with energy-related problems will it also give a feeling of really living again.  From "The Land Down Under".

Q. On your chronic fatigue syndrome information page you state "Some patients with chronic fatigue syndrome appear to have a chronic enteroviral infection that can be detected by a stomach biopsy. Enteroviruses are acid and bile resistant and are believed to be common causes of acute gastritis. Some patients with chronic fatigue syndrome have persistent or intermittent, upper and/or lower gastrointestinal symptoms." I definitely have "persistent or intermittent, upper and/or lower gastrointestinal symptoms" -- the primary and most distressing being nausea -- and I have often wondered if I have a chronic enteroviral infection. I have had several endoscopies that are always negative for H. pylori. I do not know if the biopsies are checked for any other kind of infectious agent. My question is, what can be done about this? Are there any effective anti-viral medications that can eradicate the problem? I'm desperate for a solution.
   A. Sorry but we have not studied this area of medicine enough to have clear answers. Perhaps a gastroenterologist may be more up to date.

Thanks for all of your great work in natural medicine, the world needs this, as you know. I am writing to you about this because I have not been able to find any answer on the Internet. I have had severe, long term CFS for years, and that maybe be caused by the reactivation of viruses like HHV 6, for which I test positive. The thing is, I get ill from taking antivirals, and even antiviral herbs. The ONE THING that does really help with my extreme low energy ( need to lie down most of the day), is high dose vitamin C. I am now up to 8 Grams a day. I have been taking bioidential hormones for several years, estrogen and progesterone, and this has eradicated my hot flashes. But ever since I began the high dose C a few weeks ago, I am getting hot flashes all again! They go away when I stop the C. But this C maybe well be my way out of my situation. So, do you know what the relationship of high dose C and hormones is, and how I might adapt them so I can take both? I have been testing it on myself, and it seems like at 6 grams of C a day, I have to lower my estrogen to 50 or even 25 percent of what I normally take. I have seen studies where estrogen levels were raised by taking high C. Maybe the C makes the estrogen more bioavailable. But for me, when I raised my C levels, I had really bad symptom of estrogen excess. I am sort of a my own guinea pig. I noticed this over and over. Now I know how to work it. Best wishes, thanks for all your great research, and for answering my query,
   I have not come across long term clinical trials that have tested high levels of this vitamin with changes in levels of estrogen, progesterone, or other hormones.

My wife has had Chronic Fatigue Immune Dysfunction Syndrome for 25 years .Insomnia has always been a problem for her. She began taking 5-htp several years ago wit h great success. She was taking 25mg before bedtime and sleeping well with no effects. Eventually she had to discontinue the product because she experienced nightmares, etc. It has been 2 years since then and she restarted taking the 5-htp ( just a sprinkle of several grains in water before bedtime). It is helping her sleep but in the morning she is a slug for hours as if she is drugged, She has always been told that she has an excess of serotonin in the brain.
   Some individuals are very sensitive to 5HTP and may need even less.