Restless Legs Syndrome Foundation Blog

What's Really under the Bun?

The Impossible Burger is a plant-based burger that has been widely praised for looking, smelling and – luckily for burger lovers – tasting just like the real thing. But if you have RLS and low iron stores, you may be wondering: Can it boost your iron?

Iron is essential for all living cells in the body. One of its main roles is as a component of hemoglobin (heme), the molecule in red blood cells that carries oxygen throughout the body. Iron deficiency is a known contributing factor to RLS, so maintaining a healthy iron level is especially important for those with the disease.*

According to a 2018 Gallup poll, 5% of Americans report they are vegetarian, and another 3% are vegan. (Vegetarians don’t eat meat; vegans don’t eat any animal products.) Individuals choose to limit their diet for a variety of reasons, but no matter why, removing meat from one’s diet can drastically reduce iron intake. To combat this iron deficiency, vegetarians have to work to fit other high-iron food choices (such as tofu, lentils and beans into their diets. Could the Impossible Burger be an iron-rich choice for vegetarians and vegans alike?

The Impossible Burger is a nationwide phenomenon. This 100% plant-based burger is known to taste like the real thing and even bleed. But how can a burger bleed if it isn’t meat? Scientists at Impossible Foods claim that heme is the molecule that makes meat taste and bleed like meat. The company genetically engineers yeast to make heme for the Impossible Burger.

However, the burger’s benefit as a source of dietary iron is up for debate. James Connor, PhD, a member of the RLS Foundation Scientific and Medical Advisory Board and a leading expert in brain iron metabolism, says that although the Impossible Burger contains heme iron, it is not clear to experts if this genetically altered molecule acts the same in the body as regular heme.

Additionally, Connor explains that soy protein actually inhibits iron absorption. Since the heme in the Impossible Burger is fermented in a soy plant, it is unlikely that any iron in the burger is absorbed into the body, according to Connor.

Overall, the Impossible Burger may be a tasty option for vegetarians or vegans who are craving a burger. Also, Impossible Foods states its main goal is “to reduce humanity’s destructive impact on the global environment by replacing the use of animals as food production technology.” However, choosing an Impossible Burger over a regular burger is probably not going to have much impact on your iron level.

The moral of the story is to do your research as a consumer. With so many products on the market and so much information on the internet and social media, it is sometimes hard to know if a product or service will provide the benefits you are expecting. Whether it is a new diet, a new drug or a new RLS treatment, make sure you understand the details and consult with your doctor before making any changes to your treatment plan.

Editor’s note: James Connor, PhD, is founder and chair of the board of Sidero Science, a competing specialty biotechnology company with an iron- based medical food product under development.

Study Funded by RLS Foundation Reveals Results

Scientists are one step closer to developing a working animal model of RLS. In a study funded by the RLS Foundation, Yuan-Yang Lai, PhD, and her team at the University of California – Los Angeles (UCLA), researchers manipulated the diet of rats to make them iron deficient, and the animals demonstrated symptoms of RLS. These symptoms improved when the rats were given the drug pramipexole, and when they received more iron in their diets – two therapies known to improve RLS in humans.

“Dopamine drugs are one of two first-line treatments for RLS; however, they can lead to adverse effects, such as augmentation, after use,” says Dr. Lai. “Using our animal model, we should be able to test alternative drugs that are developed for the potential treatment of RLS that is caused by iron-deficiency anemia.”

The model may also enable researchers to identify the specific brain regions, circuits and chemicals involved in RLS and periodic limb movements disorder (PLMD). The study, “Motor Hyperactivity of the Iron-Deficient Rat – An Animal Model of Restless Legs Syndrome,” was published August 2017 in the journal Movement Disorders.

Studies have shown that RLS is common in people with iron-deficiency anemia, affecting up to 32 percent of people with this condition. The researchers fed rats an iron deficient diet to create anemia, then recorded their motor activity, or movement, through implanted electrodes – before and after treatment with pramipexole. They also monitored the animals after feeding them a normal diet to restore their iron stores, representing the process of iron therapy in humans.

The researchers found that the iron-deficient animals had symptoms similar to those seen in RLS patients, including motor hyperactivity in quiet wake and in sleep, frequent awakening from sleep, and daytime sleepiness. These symptoms were relieved when the rats received pramipexole, as well as when they received a normal diet containing iron.

These findings build on those of a previous RLS Foundation-funded study in which Dr. Lai found that iron-deficient rats given thioperamide, an H3 receptor antagonist, showed reduced period limb movements (PLMs). As a next step, Dr. Lai’s team is currently using the animal model to study why pramipexole treatment causes augmentation, and which areas and chemicals of the brain are involved in RLS.

What You Should Know about Iron and RLS

Iron deficiency is a known contributing factor to RLS, and many find some symptom relief from supplemental iron in pill form or by intravenous (IV) infusions.

Healthcare providers have new guidance for treating RLS patients whose iron stores are low. A paper published in the January 2018 issue of Sleep Medicine provides information on how to evaluate RLS patients for low iron, when to offer iron therapy as a treatment, and which type of treatment is most likely to be helpful for individual patients, including children.

“Iron treatment, despite its importance, is not well understood,” says co-author Richard P. Allen, PhD, a researcher at the Johns Hopkins Center for Restless Legs Syndrome. “Iron treatment is complicated by current iron status, and the various oral and IV iron treatments available. Understanding the benefits of IV iron in particular for some patients is relatively new, and this paper provides reasonable guidance for its use that is not available elsewhere.”

Past research has shown that iron deficiency in the brain is an underlying abnormality of RLS. “RLS treatments are basically palliative – they reduce symptoms but do not reduce any basic biological abnormality,” Allen says. “Iron treatment differs. It serves to reduce, for some, a biological abnormality in RLS of reduced brain iron.”

The new report was developed on behalf of the International Restless Legs Syndrome Study Group (IRLSSG). In recent years, a number of research studies on iron for RLS and periodic limb movement disorder (PLMD) have been published. To evaluate these findings, the IRLSSG formed a task force of 12 medical experts in RLS, sleep medicine, neuroscience and other fields, to evaluate published research on the topic and develop a set of recommendations for clinical practice.

This group searched the medical literature and examined 299 related articles. The group’s analysis also included clinical recommendations based on expert clinical opinion. The resulting report includes evidence- and consensus-based guidelines that confirm iron should be a first-line treatment option for RLS. The report also recommends treating people with RLS and iron deficiency with oral iron first, unless there is a medical reason why oral iron cannot be used. The article presents updated treatment algorithms for iron use to treat RLS in adults, and both RLS and PLMD in children.

Importantly, the article delves into the differences among five different IV iron formulations available. “Not all IV iron formulations are alike, and some appear to work better than others,” says Dr. Allen. In addition, specific guidance about when and how to use oral iron is presented, including the recommendation that taking oral supplements once a day is preferable to taking them twice a day.

The article, “Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis- Ekbom disease in adults and children: an IRLSSG task force report,” is available online at www.sleep-journal.com.

This and other clinical publications are the outcome of dedicated work by members of the RLS medical and scientific community to help healthcare providers worldwide offer the best possible medical treatment to RLS patients.

Iron and RLS: What you need to know

Every individual with RLS should have their blood iron levels (serum ferritin) checked, as keeping ferritin levels mid-range – at 75 micrograms per liter and above – correlates to RLS symptom improvement.

If your iron levels are low, your doctor may recommend ways to replenish your iron stores, including:

• Increased consumption of iron-rich foods, especially meat, fish and liver. Leafy green vegetables also contain iron but may not be broken down adequately by your digestive tract to deliver significant amounts of iron to your body.
• Oral iron supplements. For best iron absorption, iron pills should be taken at night on an empty stomach with vitamin C. They should not be taken with food, milk, antacids, calcium supplements or medications used to treat acid reflux and thyroid.
• IV iron therapy. Your RLS doctor should be aware of the potential for IV iron treatment, and if you are an appropriate candidate, can refer you to a hematology center or RLS program that provides iron treatments for RLS.

Iron supplements should only be taken under the supervision and care of a physician to ensure proper monitoring and help prevent iron overload.

Learn more

To learn more about iron and RLS, please view the webcast “Iron and RLS” or see the handout Understanding Iron and Restless Legs Syndrome, available in the Member Portal at www.rls.org.

What You Need to Know

Iron deficiency without anemia has been associated with increased fatigue, depression, cognitive impairment, decreased work capacity and restless legs syndrome (RLS). Prior to diagnosis, an RLS healthcare provider may check a patient's iron (ferritin) levels to see if they have low iron.

"Keeping iron levels mid-range (75mcg/L and above) correlates to RLS symptom improvement," RLS Foundation Executive Director Karla Dzienkowski, RN, BSN, said. "Every individual with RLS needs to know their ferritin level, as it is a key component in the management of RLS symptoms."

Iron is essential for all living cells in the body. It works with the oxygen in your body to produce energy for your cells. When an individual has low iron stores, the amount of iron going into the bone marrow increases. When someone is severely iron deficient, as much as 99 percent of the body's iron will go directly into bone marrow, effectively starving other organs, including the brain, of iron.

There are a number of ways for someone with RLS to ensure that they keep their iron stores up. Eating meat, fish and liver provide the most absorbable form of iron for the body. While leafy green vegetables also contain iron, it is not always broken down adequately by the human digestive tract. Thus, the same amount of iron in a vegetable may not deliver the same amount of iron as in meat or liver.

Additionally, many RLS sufferers turn to supplementation to assist with their iron intake. Iron pills should not be taken with food, milk, antacids, calcium supplements or medications used to treat acid reflux, as they drastically reduce iron's absorption into the body. Some individuals increase this absorption by taking their iron pills with either Vitamin C or orange juice. It is essential for someone with RLS to consult with their physician before taking any supplements or altering their current RLS treatment plan, as this helps ensure the proper monitoring of iron levels, as well as looking out for the development of iron overload known as hemochromatosis.

In severe cases, some individuals with RLS use intravenous iron infusions. Currently, there are five different formulations of IV iron available for use:

• iron dextran
• iron sucrose
• iron gluconate
• ferumoxytol
• ferric carboxymaltose

It is important to note that the low molecular iron formulations present a low risk for allergic reaction, and therefore IV iron usually only considered if iron pills fail to improve iron stores.

The Foundation has a number of publications available in the Member Portal that cover iron and RLS, including our brand new Medical Bulletin. Not a member but need information? Send us an email at info@rls.org and we'll get you what you need!