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Restless legs syndrome and related disorders

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of RLS.

Alternative Names

Ekbom's syndrome; Nocturnal leg cramps; Periodic limb movement disorder

Treatment

The initial approach to a patient who complains of sleeplessness and restless legs syndrome is to try non-drug treatments to improve sleep and eliminate possible causes of RLS. A non-drug approach is a particularly important first step for elderly patients.

• The doctor should first try to treat any underlying medical conditions that may be causing restless legs.
• If medications may be causing RLS, the doctor should try to prescribe alternatives, if possible.
• If the cause cannot be determined, it is best to first try sleep hygiene and relaxation methods. Such approaches provide added benefits, even if drug therapy is later required.

Helpful Tips

Some people report help or relief from RLS with the following behaviors or devices:

• Hot baths or cold compresses.
• Ergonomic measures. For example, patients might find it useful to work at a high stool, where they can dangle their legs. In meetings or during air travel, it is helpful to obtain an aisle seat.
• Changing sleep patterns. Some patients report that symptoms don't occur if they sleep late in the morning, so, if feasible, changing sleep patterns may also be helpful.
• Avoiding caffeine, alcohol, and nicotine.

Alternative treatments that are sometimes advocated for RLS include acupuncture and massage. These treatments, however, have not been rigorously studied.

Vitamins and Minerals

Some people have reported benefits from:

• Vitamin E (800 - 1200 IU per day)
• Calcium, magnesium, or potassium supplements
• Folic acid supplements for people with folate deficiencies

Dietary Iron

Because RLS is associated with iron insufficiency, people with the condition should be sure they have a diet that provides iron. [For more information, see In-Depth Report #57: Anemia.] Iron found in foods is either in the form of heme or non-heme iron:

• Heme Iron. Foods containing heme iron are the best for increasing or maintaining healthy iron levels. Such foods include (in decreasing order of iron-richness) clams, oysters, organ meats, beef, pork, poultry, and fish.
• Non-Heme Iron. Non-heme iron is less well absorbed. About 60% of the iron in meat is non-heme (although meat itself helps absorb non-heme iron). Eggs, dairy products, and iron-containing vegetables have only the non-heme form. Vegetable include dried beans and peas, iron-fortified cereals, bread, and pasta products, dark green leafy vegetables (chard, spinach, mustard greens, kale), dried fruits, nuts, and seeds.

The Effects of Food on Iron Absorption. The absorption of non-heme iron often depends on the food balances in meals. The following are foods that enhance absorption of non-heme iron.

• Meat and fish not only contain heme iron, the best form for maintaining stores, but they also help absorb non-heme iron.
• Increasing intake of vitamin-C rich foods can enhance absorption of non-heme iron during a single meal. In any case, vitamin-C rich foods are healthful and include broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries. One orange or 6 ounces of orange juice can double the amount of iron your body absorbs from plant foods. (Taking vitamin C supplements does not appear to have any significant effect on iron stores.)
• Foods containing riboflavin (vitamin B2) may help enhance the formation of hemoglobin from iron. Sources include liver, dried fortified cereals, and yogurt.

Certain nutrients impede the body's absorption of dietary iron. They include:

• Polyphenols (found in tea, coffee, red wine, berries, apples).
• Phytates (found in foods such as seeds, dried beans, soy, and bran). Such foods are typically high in fiber. (It is often believed that fiber itself impedes iron absorption, but researchers report that it has little or no effect.)
• Calcium. Calcium impairs the absorption of heme and non-heme iron. However, calcium intake must be quite high to cause any significant problems. For example, a 2002 study reported that cheese had no effect on iron absorption from meals rich in heme and non-heme iron.

The Effects of Cooking Methods on Iron. Cooking methods can enhance iron stores. Cooking in cast iron pans and skillets is well-known to increase the iron content of food. According to one study, boiling, steaming, or stir-frying in utensils composed of any material significantly increased the release of non-heme iron stored in vegetables.

Iron Supplements

In people with RLS who are also iron deficient, iron supplements can produce a significant reduction in symptoms. They should be used in these patients, however, only when dietary measures have failed. They do not appear to be useful for patients with normal or above normal iron levels.

Supplement Forms. To replace iron, the preferred forms of iron tablets are ferrous salts, usually ferrous sulfate (Feosol, Fer-In-Sol, Mol-Iron). Other forms include ferrous fumarate (Femiron, FerroSequels, Feostat, Fumerin, Hemocyte, Ircon), ferrous gluconate (Fergon, Ferralet, Simron), polysaccharide-iron complex (Niferex, Nu-Iron), and carbonyl iron (Elemental Iron, Feosol Caplet, Ferra-Cap). Specific brands and forms may have certain advantages. The following are some examples:

• Prolonged-release ferrous sulfate (Slow Fe) may enhance iron absorption with fewer side effects than standard ferrous sulfate pills.
• FerroSequels contains a stool softener, which helps prevent constipation.
• Polysaccharide-iron complex has fewer side effects and equal absorption rates compared to ferrous salts. It is very expensive, however.
• Carbonyl iron is composed of very fine tiny uniform spheres of iron powder and may prove to be less toxic than ferrous iron.
• Coated or combination pills do not appear to offer any additional advantages and may hinder absorption of the iron.

Regimen. A reasonable approach for patients with RLS is to take 65 mg of iron (or 325 mg of ferrous sulfate) along with 100 mg of vitamin C on an empty stomach three times a day.

IMPORTANT: As few as three adult iron tablets can poison, and even kill, children. This includes any form of iron pill. No one, even adults, should take a double dose of iron if one is missed.

Tips for taking iron are:

• For best absorption, iron should be taken between meals. (Iron may cause stomach and intestinal disturbances, however, and some experts believe that low doses of ferrous sulfate can be taken with food and absorbed without side effects.)
• Always drink a full 8 ounces of fluid with an iron pill.
• Tablets should be kept in a cool place. (Bathroom medicine cabinets may be too warm and humid, which may cause the pills to disintegrate.)

Side Effects. Common side effects of iron supplements include the following:

• Constipation and diarrhea are very common. They are rarely severe, although iron tablets can aggravate existing gastrointestinal problems such as ulcers and ulcerative colitis.
• Nausea and vomiting may occur with high doses, but can be controlled by taking smaller amounts. Switching to ferrous gluconate may help some people with severe gastrointestinal problems.
• Black stools are normal when taking iron tablets. In fact, if they do not turn black, the tablets may not be working effectively. This tends to be a more common problem with coated or long-acting iron tablets.
• If the stools are tarry looking as well as black, if they have red streaks, or if cramps, sharp pains, or soreness in the stomach occur, gastrointestinal bleeding may be causing the iron deficiency and the patient should call the doctor promptly.
• Acute iron poisoning is rare in adults, but can be fatal in children who take adult-strength tablets.

Interactions With Other Drugs. Certain medications, including antacids, can reduce iron absorption. Iron tablets may also reduce the effectiveness of other drugs, including the antibiotics tetracycline, penicillamine, and ciprofloxacin and the anti-Parkinson's disease drugs methyldopa, levodopa, and carbidopa. At least 2 hours should elapse between doses of these drugs and iron supplements.

Supplementary Treatments. The following supplements may improve iron absorption:

• Adding either ascorbic acid (vitamin C) or succinic acid to ferrous sulfate therapy will improve absorption of iron stores. Ascorbic acid added to iron therapy, however, may worsen some of the side effects. Succinic acid added to ferrous sulfate does not appear to increase side effects.
• Some studies have found that the addition of zinc to iron supplements increases hemoglobin levels more than iron alone. (Some evidence for this suggests that zinc affects a hormone called insulin-like growth factor-I (IGF-I), which plays a role in the regulation of red blood cell production.)

Exercise

Exercise earlier in the day may be one of the best ways to achieve healthy sleep. However, vigorous exercise and stimulation (including sexual activity) within 1 - 2 hours of bed time may worsen RLS. A study found that people who engaged in brisk walking for 30 minutes, four times a week, improved minor sleep disturbances after 4 months. Regular, moderate exercise, healthful in any case, may help prevent RLS. Patients report that either bursts of excessive energy or long sedentary periods worsen symptoms.

What Are Nocturnal Leg Cramps? Benign nocturnal leg cramps, sometimes known as a charley horse, are muscle spasms in the calf that can occur one or many times during the night. Cramping may also occur in the soles of the feet. They typically last from a few seconds to a few minutes. Some people experience them regularly, others only on isolated occurrences. Causes of Nocturnal Leg Cramps In many cases, the cause of nocturnal leg cramps remains unknown. Among the conditions that might cause leg cramps are: Calcium and phosphorus imbalances can cause cramping, particularly during pregnancy. Imbalances in these minerals can also occur when fluid levels in the body become low, for example from taking diuretics, excessive perspiration, vomiting, or diarrhea. Low potassium or sodium (salt) levels. Deficiencies of a nutrient called hesperidin, an antioxidant flavonoid found in oranges and other citrus fruits, have also been linked to nocturnal leg cramps. Overexertion, standing on concrete for long periods, or prolonged sitting (especially with the legs contorted) may contribute to nighttime cramps. Having structural disorders in the legs or feet (such as flat feet) may increase the risk for cramps. Among the many medical causes of muscle cramping include hypothyroidism, Addison's disease, uremia, hypoglycemia, anemia, and certain medications. Various diseases, such as Parkinson's, that affect nerves and muscles cause leg cramps. Peripheral neuropathy, a complication of diabetes in which the nerves in the extremities are impaired, can cause cramp-like pain, numbness, or tingling in the legs. Patients with kidney disease undergoing dialysis are also prone to leg cramps. Individuals at Higher Risk for Nocturnal Leg Cramps Nocturnal leg cramps occur at all ages but peak at different times. They are particularly common in adolescence, during pregnancy, and in older age, affecting up to 70% of adults over age 50 at some point. Pregnant women and those taking diuretics are also at risk for leg cramps because of low calcium levels and an imbalance in calcium and phosphorus . Consequences of Nocturnal Leg Cramps Nocturnal leg cramps, like restless legs syndrome, rarely have any serious consequences. However, they can be extremely painful and long-lasting. In some cases, severe and persistent symptoms can cause chronic insomnia and considerable mental distress. Managing Nocturnal Leg Cramps Once a cramp begins, straighten the leg, flex the foot upward toward the knee, or grab the toes and pull them toward the knee. Walking or shaking the affected leg, then elevating it, may also help. If soreness persists, a warm bath or shower or an ice pack may bring relief. Preventing Nocturnal Leg Cramps Lifestyle Tips. Nighttime leg cramps are generally treated with lifestyle changes. Everyone with leg cramps should drink plenty of water (at least 6 - 8 glasses daily) to maintain adequate fluid levels. Pregnant women and others who get legs cramps due to low calcium levels should reduce milk intake, because drinking milk does not correct the underlying imbalances in calcium and phosphorus. Instead, they should boost calcium levels by taking nonphosphate calcium supplements. To prevent cramps from occurring, nightly stretching exercises may be the best preventive measure. Patients should stand about 30 inches from a wall and, keeping the heels flat on the floor, lean forward and slowly move the hands up the wall to achieve a comfortable stretch. A few minutes on a stationary bicycle at bedtime may also help. While in bed, loose covers should be used to prevent the toes and feet from pointing, which causes calf muscles to contract and cramp. Propping the feet up higher than the torso may also help. During the week, swimming and water exercises are a good way to keep muscles stretched, and wearing supportive footwear is also important. Quinine. Quinine had been widely used to prevent leg cramping but was banned by the FDA for over-the-counter pharmacy sales because it was reported to cause some serious, although rare, side effects, including bleeding problems and heart irregularities. Other, less serious side effects include headaches, vision problems, and rash The FDA has since banned the marketing of most quinine drugs, cautioning against the off-label use of the drug to treat RLS. Only one form of the drug, Qualaquin, is approved for treatment of some types of malaria. Pregnant women and those with liver problems should avoid quinine in any form. Supplements. Some small studies indicate that the mineral magnesium, taken as magnesium citrate or magnesium lactate, may provide some benefit, including in pregnant women with leg cramps. In one small study, taking vitamin B complex was helpful. Other supplements tried for leg cramps include vitamin E, calcium, and potassium or sodium chloride, but these do not appear to be very effective. Sodium chloride (salt) may be helpful, but Western diets already contain excessive sodium.

• Review Date: 10/18/2006
• Reviewed By: Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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