The Encyclopedia of Natural Medicine, 3rd Ed.

Chronic Fatigue Syndrome

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• Some combination of the following symptoms:

  images Recurrent fatigue

  images Mild fever

  images Recurrent sore throat

  images Painful lymph nodes

  images Muscle weakness

  images Muscle pain

  images Recurrent headache

  images Migratory joint pain

  images Depression

  images Sleep disturbance (hypersomnia or insomnia)

Chronic fatigue syndrome (CFS) includes varying combinations of the symptoms listed above. Although relatively newly defined, CFS is not a new disease. References to a similar condition in the medical literature go back as far as the 1860s. In addition, symptoms of CFS mirror symptoms of neurasthenia, a condition first described in 1869. In the past, CFS has also been known by various other names, including chronic mononucleosis-like syndrome, chronic Epstein-Barr virus (EBV) syndrome, yuppie flu, postviral fatigue syndrome, postinfectious neuromyasthenia, chronic fatigue and immune dysfunction syndrome (CFIDS), Iceland disease, and Royal Free Hospital disease.

In 1988 the Centers for Disease Control and Prevention (CDC) established a formal (and controversial) set of diagnostic criteria for CFS (see the first list below).1 One of the major complaints from physicians about the CDC definition is that it appears better suited for research than for clinical purposes. Another problem with the CDC criteria is that they ignore many of the common symptoms reported by patients with CFS (described in the second list).

The British and Australian criteria for the diagnosis of CFS are less strict than those of the CDC.2 In particular, the minor diagnostic criteria are not required and the major diagnostic criteria are not as strict. For example, in the Australian definition the major criterion is simply fatigue at a level that causes disruption of everyday activities in the absence of other medical conditions associated with fatigue.

On the basis of the CDC criteria, the prevalence of CFS in individuals suffering from chronic fatigue in the United States is thought to be about 11.5%. On that of the British criteria, it is about 15%; and on that of the Australian criteria, it is about 38%.2

Centers for Disease Control and Prevention Diagnostic Criteria for Chronic Fatigue Syndrome

Major criteria (both required)

• New onset of fatigue causing 50% reduction in activity for at least six months

• Exclusion of other illnesses that can cause fatigue

• Minor criteria (8 of the 11 symptoms listed below, or 6 of 11 symptoms and 2 of 3 signs)

• Symptoms

  images Mild fever

  images Recurrent sore throat

  images Painful lymph nodes

  images Muscle weakness

  images Muscle pain

  images Prolonged fatigue after exercise

  images Recurrent headache

  images Migratory joint pain

  images Neurological or psychological complaints:

Sensitivity to bright light

Forgetfulness

Confusion

Inability to concentrate

Excessive irritability

Depression

  images Sleep disturbance (hypersomnia or insomnia)

  images Sudden onset of symptom complex

• Signs:

  images Low-grade fever

  images Nonexudative pharyngitis

  images Palpable or tender lymph nodes

Causes

Owing in part to its similarity to acute or chronic infection, chronic fatigue syndrome was initially thought to be caused by a virus (such as EBV). It now seems clear that CFS is not caused by any single recognized infectious agent. A CDC study found no association between CFS and infection by a wide variety of organisms, including EBV, human retroviruses, herpes virus, rubella, Candida albicans, and others. However, the possibility remains that CFS may have multiple causes leading to a common end point, in which case some viruses or other infectious agents may be contributing factors.

Frequency of Chronic Fatigue Syndrome Symptoms Reported by Patients

SYMPTOM/SIGN

FREQUENCY (%)

Fatigue

100

Low-grade fever

60–95

Muscle pain

20–95

Sleep disorder

15–90

Impaired mental function

50–85

Depression

70–85

Headache

35–85

Allergies

55–80

Sore throat

50–75

Anxiety

50–70

Muscle weakness

40–70

Postexercise fatigue

50–60

Premenstrual syndrome (women)

50–60

Stiffness

50–60

Visual blurring

50–60

Nausea

50–60

Dizziness

30–50

Joint pain

40–50

Dry eyes and mouth

30–40

Diarrhea

30–40

Cough

30–40

Decreased appetite

30–40

Night sweats

30–40

Painful lymph nodes

30–40

There is little doubt that a disturbed immune system plays a central role in CFS. A variety of immune system abnormalities have been reported in CFS patients, with the most common one being decreased number or activity of natural killer (NK) cells.36 NK cells received their name because of their ability to destroy cells that have become cancerous or infected by viruses. In fact, for a time, CFS was also referred to as low natural killer cell syndrome (LNKS).

Other consistent findings include a reduced ability of lymphocytes, a type of white blood cell that is key in the battle against viruses, to respond to stimuli.7 One reason for this lack of response may be reduced activity or decreased production of interferon—a natural antiviral compound. Although both low and high levels of interferon have been reported in CFS, levels are low in most cases. When interferon levels are low, reactivation of latent viral infection is likely. On the other hand, when interferon levels are high, the condition can produce many of the symptoms observed in CFS.

Immunological Abnormalities Reported for Chronic Fatigue Syndrome

Elevated levels of antibodies to viral proteins

Decreased natural killer cell activity

Low or elevated antibody levels

Increased or decreased levels of circulating immune complexes

Increased cytokine (e.g., interleukin-2) levels

Increased or decreased interferon levels

Altered ratio of T helper cells to T suppressor cells

Two conditions similar to CFS are fibromyalgia (FM) and multiple chemical sensitivities (MCS).3,4,7,8 In fact, the only difference in the diagnostic criteria for FM and CFS is the requirement of musculoskeletal pain in fibromyalgia and fatigue in CFS. The likelihood of being diagnosed as having fibromyalgia or CFS depends on the type of physician consulted. Specifically, if a rheumatologist or orthopedic specialist is consulted, the patient is much more likely to be diagnosed with fibromyalgia. (The box below presents the diagnostic criteria for fibromyalgia.)

images

DIAGNOSTIC CRITERIA FOR FIBROMYALGIA

MAJOR CRITERIA (ALL THREE REQUIRED)

• Generalized aches or stiffness of at least three anatomical sites for at least three months

• Six or more typical reproducible tender points

• Exclusion of other disorders that can cause similar symptoms

MINOR CRITERIA (FOUR OR MORE REQUIRED)

• Generalized fatigue

• Chronic headache

• Sleep disturbance

• Neurological and psychological complaints

• Joint swelling

• Numbness or tingling sensations

• Irritable bowel syndrome

• Variation of symptoms in relation to activity, stress, and weather changes

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One group of researchers carefully compared the symptom picture of 90 patients who had been diagnosed as having CFS, MCS, or FM (30 in each category).8 They used the same questionnaire for all 90 patients and found that 70% of the patients diagnosed with FM and 30% of those diagnosed with MCS met the CDC criteria for CFS. Particularly significant was the observation that 80% of both the FM and the MCS patients met the CFS criteria of fatigue lasting more than six months with a 50% reduction in activity. More than 50% of the CFS and FM patients reported adverse reactions to various chemicals.

In addition to CFS, chronic fatigue can be caused by various physical and psychological factors. The following list shows the major causes of chronic fatigue; the order represents how common the cause is among sufferers of chronic fatigue. The list is based on the findings of several large studies as well as the authors’ clinical experience.

Causes of Chronic Fatigue

Preexisting physical condition

Diabetes

Heart disease

Lung disease

Rheumatoid arthritis

Chronic inflammation

Chronic pain

Cancer

Liver disease

Multiple sclerosis

Prescription drugs

Antihypertensives

Anti-inflammatory agents

Birth control pills

Antihistamines

Corticosteroids

Tranquilizers and sedatives

Depression

Stress and/or low adrenal function

Impaired liver function, environmental illness, or both

Impaired immune function

Chronic candida infection

Other chronic infections

Food allergies

Hypothyroidism

Hypoglycemia

Anemia and nutritional deficiencies

Sleep disturbances

Mitochondrial dysfunction

Diagnostic Considerations

The importance of a thorough medical exam cannot be overstated. The goal is to identify and eliminate or deal with as many factors as possible that may be contributing to the feeling of fatigue. Undiagnosed disease is surprisingly common. For example, 50% of diabetics in the United States have not yet been diagnosed.

A detailed medical history and a review of body systems go a long way toward identifying important factors, but in many cases of chronic fatigue, further evaluation is necessary. The next steps can include a complete physical examination and laboratory studies. In particular, low thyroid function (hypothyroidism) is a common cause of chronic fatigue and is often overlooked. In the physical examination, it is important to look for clues that may point to the cause of chronic fatigue. For example, swollen lymph nodes may indicate a chronic infection, and the presence of a diagonal crease on both earlobes usually indicates impaired blood flow to the brain, a significant cause of fatigue in the elderly.

Therapeutic Considerations

Because chronic fatigue is generally a multifactorial condition, the therapeutic approach typically involves multiple therapies that address different facets of the disease. A person’s energy level, as well as his or her emotional state, is determined by an interplay between two primary factors—internal focus and physiology. Many people with chronic fatigue focus on how tired they are. They repeatedly reaffirm their fatigue to themselves and to anyone who will listen. Their physiology includes not only the chemicals and hormones circulating in the body but also the way they hold their bodies (usually slouched) and the way they breathe (shallowly). In most patients with chronic fatigue, both the mind and the body must be addressed. The most effective treatment is a comprehensive program designed to help people use their mind, attitudes, and physiology to fuel higher energy levels.

Lifestyle Practices Associated with Higher Natural Killer Cell Activity

Not smoking

Increased intake of green vegetables

Regular meals

Proper body weight

More than seven hours of sleep a night

Regular exercise

A vegetarian diet

Depression

The mind and attitude play a critical role in determining the status of the immune system and energy levels. Many patients with chronic fatigue (including CFS) either are depressed or just seem to have lost enthusiasm for life. Of course, it is not easy to have much enthusiasm when you do not have much energy, but the two usually go hand in hand. Depression is one of the major causes of chronic fatigue, and it is a common feature of CFS. In the absence of a preexisting physical condition, depression is generally regarded as the most common cause of chronic fatigue. However, it is often difficult to determine whether the depression preceded the fatigue or vice versa. (Depression is fully discussed in the chapter “Depression”).

One interesting finding is that CFS patients tend to lack social support.9 An open question is whether the lack of energy affects the CFS patient’s ability to maintain a relationship or vice versa, or possibly both.

Cognitive behavioral therapy has shown some effective results in clinical use.10,11 The first step is for CFS patients to understand that they can get better. Many patients with CFS are told that this is “something they will have to live with” and that “there is no cure.” A positive mental attitude is critical to good health and high energy levels, especially in patients with CFS. In order to achieve a positive mind-set, a person must exercise or condition the attitude, much as one would condition the body. Mental exercises such as visualizations, goal setting, affirmations, and empowering questions, as detailed in the chapter “A Positive Mental Attitude,” should be performed every day.

Stress and Low Adrenal Function

Stress and low adrenal function are other factors to consider in CFS. Stress can be an underlying factor in patients with depression, low immune function, or another cause of chronic fatigue. The adrenal glands are very much involved in the body’s energy level and ability to deal with stress. Low adrenal function and adrenal exhaustion were first proposed as causes of chronic fatigue more than 50 years ago.12Laboratory tests of adrenal function now confirm that low function is common in CFS.13,14 However, whether the low adrenal function is the cause of the illness or an effect is not yet known.15 Either way, one of the major symptoms of adrenal hormone deficiency is debilitating fatigue. In particular, suspect insufficient cortisol when a stressful event is followed by feverishness, joint and muscle pain, swollen lymph glands, post-exertional fatigue, worsening of allergic responses, and disturbances of mood and sleep (i.e., the typical presentation of CFS). There is also significant evidence that a drop in adrenal hormone secretion is a factor in the development of many of the biological and behavioral features of CFS.16 For complete information on supporting the adrenal glands, see the chapter “Stress Management.”

Impaired Liver Function, Environmental Toxin Overload, or Both

Enhancing detoxification processes is another important goal in CFS. Exposure to food additives, solvents (cleaners, formaldehyde, toluene, benzene), pesticides, herbicides, heavy metals (lead, mercury, cadmium, arsenic, nickel, aluminum), and other toxins can greatly stress the liver and detoxification processes and produce CFS-like symptoms.1719 Specifically, people who have impaired detoxification processes or who have been exposed to toxic chemicals often complain of fatigue along with the following:

• Depression

• General malaise

• Headaches

• Digestive disturbances

• Allergies and chemical sensitivities

• Premenstrual syndrome

• Constipation

For a complete discussion of detoxification processes, see the chapter “Detoxification and Internal Cleansing.” A couple of studies using a comprehensive detoxification program featuring a hypoallergenic diet along with a dietary food supplement rich in nutrients that assist liver detoxification has shown good results in CFS. In one of these studies, 52% of patients reported a reduction in symptoms after 10 weeks.19 In the other, the clinical improvement in CFS was paralleled by improved liver detoxification function.20

The hypoallergenic diet appears to be quite useful, because excessive gastrointestinal permeability and food allergies are important considerations in CFS. In fact, as far back as 1930, chronic fatigue was recognized as a key feature of food allergies.21 Originally, the term allergic toxemia was used to describe a syndrome that included the symptoms of fatigue, muscle and joint aches, drowsiness, difficulty in concentration, nervousness, and depression. Around the 1950s, this syndrome began to be referred to as the “allergic tension-fatigue syndrome.”22 With the popularity of CFS as a diagnosis, many physicians and others are forgetting that food allergies can lead to chronic fatigue. Furthermore, between 55% and 85% of individuals with CFS have allergies. For more information on food allergies, see the chapter “Food Allergy.” Another important consideration is gastrointestinal overgrowth of Candida albicans (see the chapter “Candidiasis, Chronic”).

Diet

Energy levels appear to be directly related to the quality of foods routinely ingested. We recommend the dietary guidelines in the chapter “A Health-Promoting Diet.” It is especially important to eliminate or restrict caffeine and refined sugar. Hypoglycemia can produce significant fatigue and other symptoms associated with CFS.

Although occasional use of caffeine can give you a boost, regular caffeine intake may actually lead to chronic fatigue. Mice fed one dose of caffeine demonstrated significant increases in their swimming capacity, but when the dose of caffeine was given repeatedly for six weeks, a significant decrease in the mice’s swimming capacity was observed.23

Several studies have found caffeine intake to be extremely high in individuals with psychiatric disorders. Another interesting finding is that the degree of fatigue experienced is often related to the quantity of caffeine ingested. In one survey of hospitalized psychiatric patients, 61% of those ingesting at least 750 mg per day of caffeine (the amount found in about five cups of coffee) complained of fatigue, compared with 54% of those ingesting 250 to 749 mg per day and only 24% of those ingesting less than 250 mg per day.24 Of course, this is not necessarily causative, as those who are fatigued may try to cope by consuming large amounts of caffeine.

In patients who routinely drink coffee, abrupt cessation of coffee drinking will probably result in symptoms of caffeine withdrawal, including fatigue, headache, and an intense desire for coffee.25,26Fortunately, this withdrawal period does not last more than a few days.

Nutritional Supplements

Nutritional supplementation is essential in the treatment of CFS. A deficiency of virtually any nutrient can produce the symptoms of fatigue as well as render the body more susceptible to infection. Individuals with chronic fatigue require, at the bare minimum, a high-potency multiple vitamin and mineral formula along with extra vitamin C (1,000–3,000 mg per day in divided doses) and magnesium (500 to 1,200 mg per day in divided doses). Fish oil supplements have also been shown to be quite beneficial.27,28

Magnesium

An underlying magnesium deficiency, even if very mild, can result in chronic fatigue and symptoms similar to those of CFS. In addition, low red blood cell magnesium levels, a more accurate measure of magnesium status than routine blood analysis, have been found in many patients with chronic fatigue and CFS. The literature demonstrates that magnesium deficiency is not necessarily due to low dietary intake,29 and several studies have shown good results with supplementation with improvements in magnesium stores.

For example, in one double-blind, placebo-controlled trial, 32 CFS patients received an intramuscular injection of either magnesium sulfate (1 g) or a placebo for six weeks. At the end of the study, 12 of the 15 patients receiving magnesium reported, on the basis of strict criteria, significantly improved energy levels, improved emotional state, and less pain. In contrast, only 3 of the 17 placebo patients reported that they felt better and only 1 reported improved energy levels.30

This study seems to confirm some impressive results obtained in clinical trials during the 1960s on patients suffering from chronic fatigue.3134 These studies used oral magnesium and potassium aspartate (1 g each) rather than injectable magnesium. Between 75 and 91% of the nearly 3,000 patients studied experienced relief of fatigue during treatment with the magnesium and potassium aspartate. In contrast, the proportion of patients responding to a placebo was between 9 and 26%. The beneficial effect was usually noted after only 4 to 5 days, but sometimes it took as long as 10 days to achieve results. Patients usually continued treatment for four to six weeks; afterward, fatigue frequently did not return.

Injectable magnesium is not necessary to restore magnesium status.35 Studies indicate that magnesium is easily absorbed orally when it is bound to aspartate or citrate. In addition, both of these compounds may also help to fight fatigue. Aspartate feeds into the Krebs cycle, the final common pathway for the conversion of glucose, fatty acids, and amino acids to chemical energy, while citrate is itself a component of the Krebs cycle. Krebs cycle components (including aspartate, citrate, fumarate, malate, and succinate) usually provide a better mineral chelate: evidence suggests that these chelates are better absorbed, used, and tolerated compared with inorganic or relatively insoluble mineral salts (such as magnesium chloride, oxide, or carbonate).35,36

Carnitine

Carnitine is an essential nutrient for the transport of long-chain fatty acids into the mitochondria, the energy-producing compartments in cells of the body. In 30 CFS patients, carnitine or the drug amantadine was given. Amantadine was poorly tolerated and produced no statistically significant difference in any of the clinical indicators. With carnitine, there was a statistically significant clinical improvement in 12 of the 18 studied indicators after eight weeks of treatment, with none of the clinical indicators showing any deterioration.37 Carnitine is extremely safe, with no significant side effects having been reported in any of the human clinical studies.

Coenzyme Q10 (CoQ10)

CoQ10 also plays a role in mitochondrial function and acts as an essential cofactor for the cellular production of energy. Low blood levels of CoQ10 have been found in CFS patients compared with normal subjects, suggesting that supplementation may be useful.38

Other Therapies

Breathing, Posture, and Bodywork

Proper care of the body is critical to the achievement of high levels of energy. Breathing with the diaphragm, good posture, and bodywork (e.g., massage, spinal manipulation) are all important in helping to relieve the stress that is a common contributor to fatigue.

Exercise

Exercise alone has been demonstrated to have a tremendous impact on mood and the ability to handle stressful life situations.39,40 Regular exercise has also been shown to lead to improved immune status. For CFS patients, regular exercise has been shown to lead to a significant increase (up to 100%) in natural killer cell activity.41,42 Although relatively strenuous exercise is required to benefit the cardiovascular system, light to moderate exercise may be best for the immune system. One study found that immune function was significantly increased by the practice of tai chi exercises.43 Tai chi is a martial art technique that features movement from one posture to the next in a flowing motion that resembles dance. Gradual increases in exercise intensity (for example, begin with gradual walking and weight exercises and increase duration and intensity over time as is comfortable) may be the best approach.44,45

Botanical Medicines

Several botanical medicines support adrenal function and may offer significant benefits in CFS. Most notable are adaptogens such as Chinese ginseng (Panax ginseng), Siberian ginseng (Eleutherococcus senticosus), rhodiola (Rhodiola rosea), and ashwaganda (Withania somnifera). The adaptogenic effects of these herbs were discussed in the chapter “Stress Management.” Of these herbal adaptogens, both Siberian ginseng and rhodiola have shown effects specific to CFS.

Siberian Ginseng

In addition to supporting adrenal function and acting as a nonspecific adaptogen, Siberian ginseng (E. senticosus) has been shown to exert a number of beneficial effects on immune function that may be useful in the treatment of CFS. In one double-blind study, 36 healthy subjects received either 10 ml of a fluid extract of Siberian ginseng or a placebo per day for four weeks.46 The group receiving the ginseng demonstrated significant improvements in various immune system indicators. Most notable were a significant increase in T-helper cells and an increase in NK cell activity, both of which are of value in the treatment of CFS.

Rhodiola rosea

Rhodiola rosea (Arctic root) is a popular plant in traditional medical systems in Eastern Europe and Asia, where it has traditionally been recommended to help combat fatigue and restore energy. In one randomized, placebo-controlled trial of 60 patients with stress-related fatigue, rhodiola was found to have an antifatigue effect that increased mental performance, particularly the ability to concentrate, as well as decreased the cortisol response to stress.47

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QUICK REVIEW

• A disturbed immune system plays a central role in chronic fatigue syndrome (CFS).

• Fibromyalgia and multiple chemical sensitivity disorder have symptoms similar to those of CFS.

• Chronic fatigue can be caused by a variety of physical and psychological factors other than CFS.

• The importance of a thorough medical exam cannot be understated. The goal is to identify and eliminate or deal with as many factors as possible that may be contributing to the feeling of fatigue.

• A person’s energy level and emotional state are determined by the interplay between internal focus and physiology.

• Enhancing detoxification processes is another important goal in CFS.

• As far back as 1930, chronic fatigue was recognized as a key feature of food allergies.

• The mind and attitude play a critical role in determining the status of the immune system and energy levels.

• Energy levels appear to be directly related to the quality of foods routinely ingested.

• A deficiency of virtually any nutrient can produce the symptoms of fatigue and render the body more susceptible to infection.

• An underlying magnesium deficiency, even if very mild, can result in chronic fatigue and symptoms similar to those of CFS.

• Carnitine and coenzyme Q10 are essential cofactors in the manufacture of energy within the mitochondria.

• Breathing with the diaphragm, good posture, and bodywork are all important in helping to relieve the stress that is a common contributor to fatigue.

• In CFS patients regular exercise has been shown to lead to a significant increase (up to 100%) in natural killer cell activity.

• Siberian ginseng has been shown to exert a number of beneficial effects that may be useful in the treatment of CFS.

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TREATMENT SUMMARY

Successful treatment of CFS requires a comprehensive diagnostic and therapeutic approach. Especially important is identifying underlying factors that may be affecting the patient’s energy levels or immune system. The strong correlation between CFS, FM, and MCS suggests that all three conditions may respond to liver detoxification, food allergy control, and a gut-restoration diet. Special attention should be paid to the advice in the chapter “Immune System Support.”

Diet

Identify and control food allergies. Increase water consumption, and stop consuming caffeine-containing drinks and alcohol. The diet should be rich in whole, organically grown foods. Hypoglycemia should be controlled through the elimination of sugar and other refined foods and the regular consumption of small meals and snacks.

Lifestyle

Key practices include diaphragmatic breathing exercises, proper posture, and a regular exercise program focusing on low-intensity activities. For other recommendations see the chapter “A Health-Promoting Lifestyle.”

Nutritional Supplements

• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures”

• Key individual nutrients:

  images Vitamin B6: 25 to 50 mg per day

  images Folic acid: 800 to 2,000 mcg per day

  images Vitamin B12: 800 mcg per day

  images Vitamin C: 500 to 1,000 mg per day

  images Vitamin E (mixed tocopherols): 100 to 200 IU per day

  images Magnesium (bound to aspartate, citrate, fumarate, malate, or succinate): 200 to 300 mg three times per day

  images Selenium: 100 to 200 mcg per day

  images Zinc: 30 to 45 mg per day

  images Vitamin D3: 2,000 to 4,000 IU per day (ideally, measure blood levels and adjust dosage accordingly)

• Fish oils: 1,000 mg EPA + DHA per day

• One of the following:

  images Grape seed extract (>95% procyanidolic oligomers): 100 to 300 mg per day

  images Pine bark extract (>95% procyanidolic oligomers): 100 to 300 mg per day

  images Or some other flavonoid-rich extract with a similar flavonoid content, super greens formula, or another plant-based antioxidant that can provide an oxygen radical absorption capacity (ORAC) of 3,000 to 6,000 units or more per day

• Specialty supplements:

  images Carnitine: 900 to 1,500 mg per day

  images Coenzyme Q10: 100 to 200 mg per day

  images SAM-e: 200 mg twice per day

Botanical Medicines

• Siberian ginseng (E. senticosus):

  images Dried root: 2 to 4 g three times per day

  images Fluid extract (1:1): 2 to 4 ml three times per day

  images Solid (dry powdered) extract (20:1 or standardized to contain more than 1% eleutheroside E): 100 to 200 mg three times per day

• Rhodiola rosea: The therapeutic dose varies according to the rosavin content. The typical daily dosage is 200–300 mg per day of an extract standardized to contain 3% rosavins and 0.8 to 1% salidroside.