Fibromyalgia syndrome (FMS) is characterized by diffuse muscle pain, poor sleep, and unrelenting fatigue. Individuals with fibromyalgia may also experience headaches, anxiety, depression, poor memory, numbness and tingling in the extremities, cold hands and feet, irritable bowel syndrome, lowered immune function, and chemical sensitivities. Over 10 million Americans suffer with fibromyalgia; 90% of them are women between 25 and 45 years old. (1)
Diagnostic tests are currently unavailable to confirm fibromyalgia. The diagnosis is usually reached after ruling out other conditions, including neurological, autoimmune, endocrine, musculoskeletal, immunological, and mental disorders. Patients have typically had the illness at least 7 years and been seen by a dozen different doctors before being diagnosed with fibromyalgia.
In 1990 the American College of Rheumatology (ACR) first proposed the current criteria for defining fibromyalgia syndrome. The criteria include a history of widespread pain lasting more than 3 months and the presence of at least 11, out of a possible 18, tender points. Pain is considered to be widespread when it affects all four quadrants of the body; that is, you must have pain in both your right and left sides as well as above and below the waist to be diagnosed with fibromyalgia. (2)
Fibromyalgia shares several of the symptoms associated with chronic fatigue syndrome (CFS). One study that compared 50 CFS patients with 50 FMS patients found that their symptoms of low-grade fever (28%), swollen lymph nodes (33%), rash (47%), cough (40%), and recurrent sore throats (54%) were the same for both groups. (3)
Another study comparing CFS patients with FMS patients showed that the brain-wave patterns, tender points, pain, and fatigue were virtually identical in both groups. (4)
While there are common characteristics shared by FMS and CFS patients, I’ve found some distinct differences between the two syndromes
Those with what I call “true fibromyalgia” suffer from fatigue but always list poor sleep and diffuse muscle pain as their primary complaints. They consistently demonstrate symptoms associated with low serotonin levels: poor sleep, increased pain, irritable bowel, brain fog, anxiety, and depression. (5)
Patients with “true CFS” have a compromised immune system, which is the root of their illness: elevated blood antibodies, intermittent sore throats, and tender lymph nodes. They tend to have chronic sinus, upper respiratory, or other infections, which linger for extended periods of time. Unlike those with fibromyalgia, individuals with CFS may have normal serotonin levels. And, unlike those with fibromyalgia, chronic fatigue patients may not have any trouble sleeping. They usually report that they sleep all the time, yet never feel rested.
What Causes Fibromyalgia?
Research suggests that fibromyalgia may be the result of:
- trauma, especially whiplash injuries (6), (7)
- hypothalamus-pituitary-adrenal (HPA) axis dysfunction (8)
- emotional/physical/mental stress (9)
- low thyroid function (10)
- low serotonin states (11)
- adrenal dysfunction (12), (13), (14)
- chronic viral, mycoplasmal, and/or bacterial infections (15)
- endocrine disorders (16)
- sleep disorders (17), (18)
The truth is, we really don’t know for sure what causes fibromyalgia.
What We Do Know
Fibromyalgia is now thought to arise from a miscommunication between the impulses of the central nervous system. The neurons, which supply the brain, become more excitable, exaggerating the pain sensation. This overamplication of pain is referred to as central sensitization. (19)
Fibromyalgia patients have a reduction in their pain threshold (allodynia), an increased response to painful stimuli (hyperalgesia), and an increase in the duration of pain after nociceptor stimulation (persistent pain).
Individuals with FMS have low levels of serotonin, a 4-fold increase in nerve growth factor (NGF), and elevated levels of substance P. (20) NGF is a member of a family of peptides known as the neurotrophins. The exposure of nociceptive sensory neurons to NGF leads to upregulation of substance P in sensory neurons. (21)
Substance P, the neuropeptide in spinal fluid, is a neurotransmitter released when axons are stimulated. Increased levels of substance P raise the sensitivity of nerves to pain or heighten awareness of pain. Although it is not fully understood, fibromyalgia patients have an imbalance of the HPA axis. This imbalance creates hormonal inconsistencies, which disrupt the body’s ability to maintain homeostasis.
Many of the most common FMS symptoms, including widespread muscle pain, fatigue, poor sleep, gastrointestinal problems, and depression, regularly occur in people with various neuroendocrine disorders, including those manifested by HPA dysfunction. (22)
Researchers believe that suppression of the HPA (quite likely from chronic stress), which results in lowering human growth hormone (HGH), dehydroepiandrosterone (DHEA), cortisol, and other hormones, is aggravated by the chronic pain and poor sleep associated with fibromyalgia. (23), (24)
Hypothalamus-Pituitary-Adrenal Axis (HPA) Dysfunction
The main function of the hypothalamus is homeostasis, or maintaining the body’s status quo. The hypothalamus receives and transmits messages from the nervous system and hormonally through the circulatory system. Because of its broad sphere of influence, the hypothalamus could be considered the body’s master computer. The hypothalamus receives continuous input about the state of the body, and must be able to initiate compensatory changes if anything drifts out of line.
The hypothalamus regulates such bodily functions as:
- blood pressure: often low in those with fibromyalgia;
- digestion: bloating, gas, indigestion, and reflux are common in FMS patients;
- circadian rhythms (sleep/wake cycle): consistently disrupted in FMS;
- sex drive: loss of libido is a common complaint for FMS patients;
- body temperature: often low in FMS patients;
- balance and coordination: FMS patients have balance and coordination problems;
- heart rate: mitral valve prolapse (MVP) and heart arrhythmias are a common finding in FMS patients;
- sweating; it is not unusual for FMS patients to experience excessive sweating;
- adrenal hormones: consistently low in FMS patients;
- thyroid hormones and metabolism: hypothyroid is a common finding in FMS patients.
Recent studies show that over 43% of FMS patients have low thyroid function. It’s estimated that those with FMS are 10 to 250,000 times more likely to suffer from thyroid dysfunction. (25)
A Vicious Cycle
1. Chronic stress disrupts HPA homeostasis, leading to allodynia.
2. Chronic pain disrupts the circadian rhythm.
3. Dysfunction in the circadian rhythm results in poor sleep.
4. Poor sleep reduces growth hormone production, leading to poor repair of damaged muscle fibers, poor memory, fatigue, suppressed immune function, and more pain. (26)
5. Increased pain further disrupts sleep and leads to depletion of stress-coping chemicals, including serotonin. (27), (28)
6. A reduction in serotonin causes an increase in the neurotransmitter, substance P. Substance P enhances pain receptors, creating even more pain.
7. Poor sleep and ongoing stress lead to fatigue, mood disorders, and irritable bowel syndrome (IBS) and may cause thyroid dysfunction. (29)
8. Chronic stress contributes to adrenal fatigue, decreased DHEA, and lowered resistance to stress. Decreased stress-coping abilities then lead to lowered immune function. (30)
9. Lowered blood volume from adrenal dysfunction (and resultant hypotension) leads to further fatigue. (31)
Stress and Fibromyalgia
A survey by the Fibromyalgia Network reports that 62% of respondents list physical or emotional stress as the initiating factor in their acquiring fibromyalgia. (32)
I believe that chronic stress is the underlying catalyst for the onset of HPA dysfunction and fibromyalgia. Several studies have demonstrated how chronic stress undermines the normal HPA function. (33)
The following analogy may help put the role of stress in fibromyalgia into perspective: We are all born with a stress-coping “savings account.” This account is filled with numerous chemicals–serotonin, norepinephrine, cortisol, magnesium, and other important hormones and nutrients–to help us deal with daily stress. The more stress we encounter, the more of these chemicals we use. We replenish our account with adequate rest. Consistent deep restorative sleep ensures that we are making more deposits than withdrawals from our stress-coping account. Since fibromyalgia patients struggle with getting a consistent good night’s sleep, they eventually bankrupt their stress-coping account.
No doubt, treating fibromyalgia patients and their plethora of symptoms can be intimidating. There are several hormonal, nutritional, and biochemical deficiencies that must be corrected before a patient can truly beat fibromyalgia. However, l’ve consistently found that many of the most troubling symptoms–poor sleep, fatigue, chronic pain, IBS, mood disorders, and “brain fog”–are diminished (sometimes dramatically) when serotonin levels are boosted and normal circadian rhythms restored.
The Importance of a Good Night’s Sleep
Studies have shown that individuals who were prevented from going into deep sleep for a period of a week develop the symptoms associated with FMS and CFS: diffuse pain, fatigue, depression, anxiety, irritability, stomach disturbances, and headaches. (34), (35)
Sleep deprivation markedly increases inflammatory cytokines (pain-causing chemicals)–by a whopping 40%. (36)
Serotonin regulates sleep, digestion, pain, mood, and mental clarity. (37) It helps:
- raise the pain threshold, by blocking substance P;
- you fall asleep and stay asleep through the night;
- regulate moods. “The happy hormone” reduces anxiety and depression;
- reduce sugar cravings and overeating;
- increase a person’s mental abilities;
- regulate normal gut motility (transportation of foodstuff) and reverse IBS.
Surveys have shown that as many as 73% of FMS patients have IBS. There are more serotonin receptors in the intestinal tract than in the brain. Emotionally stressful situations cause the body to release adrenaline, Cortisol, and insulin. These stress hormones stimulate the brain to secrete serotonin. Long-term stress and poor dietary habits can deplete the body’s serotonin stores. (38)
Tryptophan, 5 Hydroxytryptophan (5-HTP), and Serotonin
Individuals with fibromyalgia have low levels of tryptophan, serotonin, and 5-HTP. (38-40) Studies show that fibromyalgia patients have higher levels of metabolites in the kynurenine pathway, which diverts tryptophan from serotonin production. (41)
Tryptophan is one of eight essential amino acids. It is absorbed from the gut into the bloodstream and then dispersed throughout the body. Ninety percent of tryptophan is used for protein synthesis, 1% is converted to serotonin, and the balance is used to make niacin. In the formation of serotonin, tryptophan is hydroxylated to 5-HTP by tryptophan hydroxylase.
5-HTP is converted to serotonin by the decarboxylase enzyme, which is vitamin-B6 dependent. Tryptophan is transported across the blood–brain barrier via a transport molecule, which also carries leucine, isoleucine, and valine, and prefers leucine.
However, 5-HTP easily crosses the blood–brain barrier and does not utilize this transport mechanism; thus it does not compete for passage through the blood–brain barrier with these amino acids. (39)
And unlike tryptophan, which is made from bacterial fermentation (and hence subject to contamination), 5-HTP is derived from the West African plant Grifonia simplicifolia.
In the body, 5-HTP is converted directly into serotonin. It is not broken down by tryptophan pyrrolase, and does not have to compete for transport across the blood–brain barrier.
Selective Serotonin Reuptake Inhibitor (SSRI) Medications
Prescription antidepressants can be helpful; however, they have potential side effects, including anxiety, depression, fatigue, decreased sex drive, and disruption of normal circadian rhythms. (42)
SSRIs are supposed to help a patient hang onto and use her naturally occurring stores of serotonin. It’s like using a gasoline additive to help increase a car’s fuel efficiency. But most of the patients I see with fibromyalgia are running on fumes, and an additive won’t help.
Please keep in mind that several studies show that between 19% and 70% of those taking antidepressant medications do just as well by taking a placebo or sugar pill. (43)
I recommend that my patients boost their serotonin levels by taking 5-HTP. Studies (including double-blind) comparing SSRIs and tricyclic antidepressants with 5-HTP have consistently shown that 5-HTP is as good if not better than prescription medications in treating mood disorders. Furthermore, 5-HTP doesn’t have some of the more troubling side effects associated with prescription medications. (44), (45)
5-HTP and Sleep
5-HTP has been shown to be beneficial in treating insomnia, especially in improving sleep quality by increasing REM sleep, and increases the body’s production of melatonin by 200%. (46), (47)
5-HTP and Fibromyalgia
Double-blind placebo-controlled trials have shown that patients with FMS could see the following benefits from taking 5-HTP (48):
- decreased pain
- improved sleep
- fewer tender points
- less morning stiffness
- less anxiety
- improved moods in general, including in those with clinical depression (49)
- increased energy
Irritable Bowel Syndrome, 5-HTP, and Serotonin
There are more serotonin receptors in the intestinal tract than in the brain. This is one reason that people get butterflies in the stomach when they are nervous. (50) The brain and gut are connected through the neuroreceptors 5-hydroxytriptamine-3 (5-HT3) and 5-hydroxytriptamine-4 (5-HT4). These serotonin receptors regulate the perception of visceral pain and the gastrointestinal (GI) motility. Serotonin controls how fast or how slowly food moves through the intestinal tract. (51), (52)
It’s common for the symptoms associated with IBS, diarrhea and constipation, to disappear within 1 to 2 weeks once serotonin levels are normalized with 5-HTP replacement therapy.
My 5-HTP and Sleep Restoration Protocol
I instruct my patients to take 50 mg of 5-HTP 30 minutes before bed on an empty stomach (90 minutes after or 30 minutes before eating), with 4 ounces of grape juice. I know that 5-HTP doesn’t have to compete with other amino acids to cross the blood–brain barrier, but this routine seems to heighten the effect of 5-HTP.
One of three things will happen when taking 5-HTP:
1. The patient falls asleep within 30 minutes and sleeps through the night. If so, he stays on this dose until his next scheduled visit with me (typically 2 weeks).
2. Nothing. This is typical response to such a low dose. The patient should add an additional 50 mg each night (up to a max of 300 mg) until she falls asleep within 30 minutes and sleeps through the night.
3. Instead of making the patient sleepy, the first dose makes him more alert. This occurs more often in CFS and chemical sensitivity patients who have a sluggish liver. If this happens, he is to discontinue taking 5-HTP at bedtime and instead take 50 mg with food for 1 to 2 days. Taking 5-HTP with food seems to help slow down its absorption, allowing the liver to process it more effectively. Taking 5-HTP with food will not (usually) make a person sleepy. After 1 to 2 days on 5-HTP with no further problems, he should increase to 100 mg with each meal (300 mg a day).
Melatonin is the primary hormone of the pineal gland and acts to regulate the body’s circadian rhythm, especially the sleep/wake cycle. One percent of serotonin turns into melatonin, which then promotes deep restorative sleep. Melatonin is an extremely important hormone, playing a vital role in the circadian rhythm.
Normally, melatonin levels begin to rise in the mid to late evening, remain high for most of the night, and then decline in the early-morning hours. Natural melatonin production is partly affected by light. During the shorter days of winter, melatonin production may start earlier or, more often, later. This change can lead to symptoms of seasonal affective disorder (SAD), or winter depression. (53)
Natural melatonin levels decline gradually with age. Some older adults produce very small amounts of melatonin or none at all.
Melatonin Replacement Therapy
When administered in pharmacological doses (1-6 mg before bed), melatonin acts as a powerful sleep-regulating agent that controls the circadian rhythm. In a recent study, volunteers were given either a 0.3 mg or a 1 mg dose of melatonin, or a placebo. Both levels of melatonin were effective at decreasing the time needed to fall asleep. (54)
Studies have shown that 5 mg of melatonin given at 11 p.m. helps advance and reset circadian rhythms. (55)
What Can Affect Melatonin Levels?
Elements that decrease melatonin levels (56):
- exposure to bright lights at night
- exposure to electromagnetic fields
- NSAIDs (Celebrex, Vioxx, Mobic, Aleve, Bextra, etc.)
- SSRIs–yes, the very same antidepressants that many take for FMS, including Prozac, Zoloft, Celexa, Paxil, and Lexapro
- anxiety meds (benzodiazepines) like Klonopin, Ativan, Xanax, and Restoril
- antihypertensive meds (beta blockers, adrenergics, and calcium channel blockers) including Inderal, Toprol, Tenormin, and Lorpressor
- over 3 mg of vitamin B12 in a day
- evening exercise (for up to three hours afterward)
Foods high in melatonin (57):
- sweet corn
- Japanese radish
Drugs that raise melatonin levels (58):
- fluvoxamine (Luvox)
- desipramine (Norpramin)
- most MAOIs
- St. John’s wort (acts as an MAOI and may help raise melatonin levels)
Although adequate levels of melatonin are essential for a good night’s sleep, fibromyalgia patients should initially try boosting their serotonin with 5-HTP. (59)
Can my patients take 5-HTP along with antidepressant medications?
Yes, I’ve treated thousands of patients with amino acid replacement therapy, 95% of whom were already taking antidepressants when they come to see me. I’ve never had a patient report a problem with combing 5-HTP with prescription drugs. It can happen, but I believe it to be rare.
Can my patients take 5-HTP with sleep medications?
Yes. I don’t recommend that patients discontinue taking their sleep medications. Instead, I suggest they start using 5-HTP and increase the bedtime dose until they sleep through the night. At some point they should be able to work with their doctor and slowly wean off the prescription sleep medication. Remember, all prescription sleep medications have side effects. No one has an Ambien deficiency; however, fibromyalgia patients certainly have 5-HTP and serotonin deficiencies, which need to be corrected.
What if my patient is taking a prescription sleep medication and sleeping through the night?
Prescription drugs that promote deep restorative sleep include Ambien, Elavil, Trazadone, Flexeril, and Lunesta. These medications can be helpful. However, they have potential side effects that may cause the very symptoms associated with fibromyalgia. Ambien may cause short-term memory loss, fatigue, depression, and flu-like aches and pains.
Other common sleep-inducing drugs, including benzodiazepines, muscle relaxants (Zanaflex), Neurontin, and Lyrica don’t promote deep delta wave sleep and therefore are not recommended. Remember, the reason that they’re taking these prescription drugs is because they have a serotonin (and perhaps melatonin) deficiency, not a drug deficiency. You want them to build up their serotonin levels so that eventually they may not need prescription sleep medications. You should have them add 5-HTP (50 mg) three times daily with food. If no problems arise after 2 to 3 days, they should then increase to 100 mg with each meal.
What if someone has a serotonin syndrome reaction?
A serotonin syndrome may occur if a person gets too much serotonin. This can cause rapid heartbeat, increased pulse rate, elevated blood pressure, agitation, and, in its worst-case scenario, life-threatening irregular heartbeats (arrhythmia).
I’ve recommended 5-HTP to thousands of individuals over the last 7 years; rarely have I encountered a problem. I always start with a low dose (50 mg) and warn the patient to stop taking it at bedtime if she has a funny reaction.
What are some of the other potential side effects of 5-HTP?
Other than some patients’ becoming more alert when taking 5-HTP at bedtime, I have had very few complaints. The literature reports that individuals may have transient headaches and nausea from taking 5-HTP. I have had fewer than half a dozen patients have one of these side effects. The headaches and any nausea usually go away after a couple of days.
When should I increase my patient’s 5-HTP dose?
If your patient is taking 100 mg of 5-HTP, sleeping through the night, and dreaming, then I would leave him at that dose. However, if he continues to have IBS symptoms, sugar cravings, low moods, or a lot of pain, I would have him continue to take the night dose that is putting him to sleep, along with taking additional 5-HTP with food during the day (up to a total of 300 mg daily).
What do you do when your patient still can’t fall asleep and sleep through the night even when taking 300 mg of 5-HTP?
If after two weeks, someone is not falling asleep and staying asleep through the night, I add melatonin. First, I make sure she is taking 5-HTP as she should be and at the maximum dose of 300 mg.
Melatonin Replacement Therapy
If patients can’t fall asleep within 30 minutes (while taking 300 mg of 5-HTP), I have them take 3 to 9 mg of sublingual (dissolves under tongue for rapid absorption) melatonin 30 minutes before bed, along with the 300 mg of 5-HTP.
What if your patient falls asleep within 30 minutes but can’t stay asleep?
If a patient is falling asleep but has trouble staying asleep, I’ll add 3 mg of timed-release melatonin to his normal bedtime dose of 5-HTP and regular melatonin.
Can patients take 5-HTP, melatonin, and prescription sleep medications at the same time?
If they don’t consistently fall asleep and stay asleep while combining their prescription sleep medication (preferably one that puts them into deep sleep, see list above) with 300 mg of 5-HTP, then you need to add melatonin as well.
What if none of the above works?
OK, nobody said that this was going to be easy. Consistent deep restorative sleep the crucial first step in restoring HPA function and helping fibromyalgia patients get their lives back. If 5-HTP and melatonin have failed, they should try one of the recommended sleep drugs above. If these don’t help, you should consider referring them for a sleep study to rule out sleep apnea. Females should have their progesterone and estrogen levels checked. Cortisol and DHEA levels should also be investigated.
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Dr. Rodger Murphree is a board-certified nutritional specialist and chiropractic physician who has been in private practice since 1990. He is the founder and past clinic director for a large integrated medical practice on the campus of Brookwood Hospital in Birmingham, Alabama. The clinic was staffed with medical doctors, chiropractors, acupuncturists, nutritionists, and massage therapists, and combined prescription and natural medicines for acute and chronic illnesses. Dr. Murphree is the author of five books for patients and doctors, including Treating and Beating Fibromyalgia and Chronic Fatigue Syndrome, Heart Disease: What Your Doctor Won’t Tell You, and Treating and Beating Anxiety and Depression with Orthomolecular Medicine. In 2002 he sold his medical practice and now maintains a busy solo practice specializing in fibromyalgia, heart disease, and mood disorders. Dr. Murphree is a frequent guest on local and national radio and television programs, appearing on networks NBC, Fox, and ABC. He writes for several professional and public health-related publications. His articles have appeared in the Washington Post as well as peer-reviewed professional journals, including Chiropractic Economics, Alternative Fibromyalgia News Magazine, the American Chiropractor, and Nutri-News. Dr. Murphree conducts continuing-education seminars throughout North America, helping doctors become proficient in nutritional medicine. He can be reached at 205-879-2383. His public website is at www.treatingandbeating.com.