L-carnitine is required for energy production in the powerhouses of cells (the mitochondria). There may be a problem in the mitochondria in people with CFS. Deficiency of carnitine has been seen in some CFS sufferers.² One gram of carnitine taken three times daily for eight weeks led to improvement in CFS symptoms in one preliminary trial.³ Supplementation with 6 grams of L-carnitine per day for four weeks also improved fatigue in a preliminary study of patients with advanced cancer.⁴ Similar improvements were seen in another study of patients with advanced cancer given up to 3 grams of L-carnitine per day for one week.⁵

NADH (nicotinamide adenine dinucleotide) helps make ATP, the energy source the body runs on. In a double-blind trial, people with CFS received 10 mg of NADH or a placebo each day for four weeks.⁶ Of those receiving NADH, 31% reported improvements in fatigue, decreases in other symptoms, and improved overall quality of life, compared with only 8% of those in the placebo group. Further double-blind research is needed to confirm these findings.

Magnesium levels have been reported to be low in CFS sufferers. In a double-blind trial, injections with magnesium improved symptoms for most people.⁷ Oral magnesium supplementation has improved symptoms in those people with CFS who previously had low magnesium levels, according to a preliminary report, although magnesium injections were sometimes necessary.⁸ These researchers report that magnesium deficiency appears to be very common in people with CFS. Nonetheless, several other researchers report no evidence of magnesium deficiency in people with CFS.^9,10,11 The reason for this discrepancy remains unclear. If people with CFS do consider magnesium supplementation, they should have their magnesium status checked by a doctor before undertaking supplementation. It appears that only people with magnesium deficiency benefit from this therapy.

NADH (nicotinamide adenine dinucleotide) helps make ATP, the energy source the body runs on. In a double-blind trial, people with CFS received 10 mg of NADH or a placebo each day for four weeks.¹² Of those receiving NADH, 31% reported improvements in fatigue, decreases in other symptoms, and improved overall quality of life, compared with only 8% of those in the placebo group. Further double-blind research is needed to confirm these findings.

The combination of potassium aspartate and magnesium aspartate has shown benefits for chronically fatigued people in double-blind trials.^13,14,15,16 However, these trials were performed before the criteria for diagnosing CFS was established, so whether these people were suffering from CFS is unclear. Usually 1 gram of aspartates is taken twice per day, and results have been reported within one to two weeks.

Vitamin B12 deficiency may cause fatigue. However, some reports,¹⁷ even double-blind ones,¹⁸ have shown that people who are not deficient in B12 have increased energy following a series of vitamin B12 injections. Some sources in conventional medicine have discouraged such people from taking B12 shots despite this evidence.¹⁹ Nonetheless, some doctors have continued to take the limited scientific support for B12 seriously.²⁰ In one preliminary trial, 2,500 to 5,000 mcg of vitamin B12 given by injection every two to three days led to improvement in 50 to 80% of a group of people with CFS; most improvement appeared after several weeks of B12 shots.²¹ While the research in this area remains preliminary, people with CFS considering a trial of vitamin B12 injections should consult a doctor. Oral or sublingual B12 supplements are unlikely to obtain the same results as injectable B12, because the body’s ability to absorb large amounts is relatively poor.

Adaptogenic herbs such as Asian ginseng and eleuthero may also be useful for CFS patients—the herbs not only have an immunomodulating effect but also help support the normal function of the hypothalamic-pituitary-adrenal axis, the hormonal stress system of the body.²² These herbs are useful follow-ups to the six to eight weeks of taking licorice root and may be used for long-term support of adrenal function in people with CFS. However, no controlled research has investigated the effect of adaptogenic herbs on CFS.

DHEA (dehydroepiandrosterone) is a hormone now available as a supplement. In one report, DHEA levels were found to be low in people with CFS.²³ Another research group reported that, while DHEA levels were normal in a group of CFS patients, the ability of these people to increase their DHEA level in response to hormonal stimulation was impaired.²⁴ Whether supplementation with DHEA might help CFS patients remains unknown due to the lack of controlled research. DHEA should not be used without the supervision of a healthcare professional.

Adaptogenic herbs such as Asian ginseng and eleuthero may also be useful for CFS patients—the herbs not only have an immunomodulating effect but also help support the normal function of the hypothalamic-pituitary-adrenal axis, the hormonal stress system of the body.²⁵ These herbs are useful follow-ups to the six to eight weeks of taking licorice root and may be used for long-term support of adrenal function in people with CFS. However, no controlled research has investigated the effect of adaptogenic herbs on CFS.

One study found that an eleuthero extract improved symptoms in patients suffering from mild-to-moderate chronic fatigue. However, after one month of treatment, the benefit began to wane, and eleuthero was not more effective than a placebo after two months of treatment.These findings support the observation of herbalists that eleuthero is more effective when used in a pulsed manner (a few weeks at a time) than when used continuously.

In a preliminary study, four patients with chronic fatigue syndrome reported an improvement in their symptoms after taking an essential fatty acid supplement daily for at least 12 weeks.²⁶ The amount used was 10 to 18 capsules per day, and each capsule contained 93 mg of eicosapentaenoic acid (EPA), 29 mg of docosahexaenoic acid (DHA), and 10 mg of gamma-linolenic acid. Because there was no placebo group in this study and, because fatigue often improves after treatment with a placebo, additional research is needed to confirm this report.

One case report described a man with CFS whose symptoms improved after taking 2.5 grams of licorice root daily.²⁷ While there have been no controlled trials to test licorice in patients with CFS, it may be worth a trial of six to eight weeks using 2 to 3 grams of licorice root daily.