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This page contains a collection of scientific studies (and follow-up articles written by doctors based on these studies) that support the idea that INFLAMMATION is the cause of Restless Legs Syndrome.

The articles are in chronological order except for the first study listed, which is the groundbreaking work by Dr. Leonard Weinstein (et. al).

A team of scientists have written a scientific paper that contains overwhelming evidence that points to inflammation as the primary cause of Restless Legs Syndrome.

Leonard B. Weinstock, MD, Arthur S. Walters, MD, and Paisit Paueksakon, MD have written a paper titled "Restless Legs Syndrome: Theoretical Roles of Inflammatory and Immune Mechanisms."

Leonard B. Weinstock, MD Leonard B. Weinstock, MD, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO and the Specialists in Gastroenterology, LLC in St. Louis. Arthur S. Walters, MD Arthur S. Walters, MD, Dept of Neurology, Vanderbilt University School of Medicine, Nashville, TN. Paisit Paueksakon, MD Paisit Paueksakon, MD, Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN.


In the Restless Legs community, Dr. Weinstock is best known for his studies showing that a higher rate of RLS occurs with patients suffering from Crohn's Disease, SIBO (Small Intestinal Bacterial Overgrowth) and Irritable Bowel Disease. All three of these are inflamatory conditions.

In 1992, Dr. Walters organized the first medical advisory board for the Restless Legs Syndrome foundation (RLSF), a nationwide patient based support group organization. He served as the first chair of this board and remains a member. The RLSF has played a key role in educating both the public and physicians about RLS.

Dr. Paueksakon specializes in renal pathology involving mechanisms and pathophysiology of diabetic nephropathy and paraprotein related disease.

The title of their study is "Restless Legs Syndrome: Theoretical Roles of Inflammatory and Immune Mechanisms."

In the scientific community, and in the RLS community, this SHOULD be a groundbreaking work!

Here is an excerpt.

"A literature search for conditions highly-associated with RLS was performed. These included secondary RLS disorders and factors that exacerbate RLS. All of these conditions were reviewed with respect to potential pathogenesis including reports of iron deficiency, neuropathy, SIBO, inflammation and immune changes.

Overall, 36 of the 41 RLS-associated conditions (88%) have been associated with inflammatory and/or immune changes.

The fact that the majority of highly RLS associated conditions are also associated with inflammatory/immune changes suggests the possibility that RLS may be mediated or affected through these mechanisms."


CLICK HERE to read the FULL study.


For details on the 42 inflammatory conditions that display significantly higher occurences of RLS, please visit the Conditions that are Linked to RLS web page.

WHY IS IT NOT 100%?

You may have noticed in the above excerpt that only 88% of the conditions that have a distinct relationship with RLS were inflammatory.

If inflammation is really the issue, why are the results not 100%?

There's actually a simple explanation. Below are the conditions that the doctors have listed in their study as being non inflammatory:

Essential Tremor Movement Disorder is one of the conditions listed as not inflammatory. This is due to the fact that no real testing has been done to determine if it is an inflammatory condition or not.

A similar condition, Parkinson's Disease, is definitely known to be inflammatory. Also, studies have found that Essential Tremor Movement Disorder is significantly higher in elderly patients, and those with Azheimer's ... which are both inflammatory conditions.

Essential Tremor Movement Disorder is so closely linked to Parkinson's Disease that there is often difficulty determining which condition a person has:

Here's an exerpt from a recent study ...

Clinical distinction between advanced essential tremor and tremulous Parkinson's disease can be difficult.

"A new diagnostic test to distinguish tremulous Parkinson's disease from advanced essential tremor." Muthuraman M, Hossen A, Heute U, Deuschl G, Raethjen J. Mov Disord. 2011 Apr 25. doi: 10.1002/mds.23672.


Gastric resection is another condition listed as non inflammatory. However, it's not really a condition. It's more of a procedure.

Here's the definition ...

Gastric Resection
Etymology: Gk, gaster, stomach; L, re + secare, to cut
the surgical removal of part or all of the stomach, usually performed in the treatment of stomach cancer or intractable peptic ulcer.


Both cancer and ulcers are inflammatory conditions.

The third condition was Bruxism, which is the grinding of teeth at night.

Here's an excerpt from the Bruxism/RLS study:

In logistic regression, frequent bruxism (p < 0.05) and older age (p < 0.05) were significantly positively associated with RLS. Dissatisfaction with one's current workshift schedule (p < 0.05) and RLS (p < 0.05) were significantly positively associated with frequent bruxism, while age (p < 0.05) was significantly negatively associated. In conclusion, perceived bruxism may be a sign of a stressful situation or dissatisfaction, while RLS as a more stable trait may in itself negatively affect sleep quality and further enhance the problem.

"Reported bruxism and restless legs syndrome in media personnel with or without irregular shift work." Ahlberg K, Ahlberg J, K??n??nen M, Partinen M, Hublin C, Savolainen A. Acta Odontol Scand. 2005 Apr;63(2):94-8.


Again, not really a medical condition. It's more of a lifestyle/stress related condition.

You don't have to be a scientist to deduce that stress is directly responsible for the grinding of teeth. As you would expect, stress is a breeding ground for inflammation. Researchers have now found a definite link:

"A research team led by Carnegie Mellon University's Sheldon Cohen has found that chronic psychological stress is associated with the body losing its ability to regulate the inflammatory response. Published in the Proceedings of the National Academy of Sciences, the research shows for the first time that the effects of psychological stress on the body's ability to regulate inflammation can promote the development and progression of disease. Inflammation is partly regulated by the hormone cortisol and when cortisol is not allowed to serve this function, inflammation can get out of control. stress alters the effectiveness of cortisol to regulate the inflammatory response because it decreases tissue sensitivity to the hormone. Specifically, immune cells become insensitive to cortisol's regulatory effect. In turn, runaway inflammation is thought to promote the development and progression of many diseases."

How Stress Influences Disease: Carnegie Mellon Study Reveals Inflammation as the Culprit." Carnegie Mellon News (April 2012).

Their results showed that individuals who exhibited greater neural activity in the dorsal anterior cingulate cortex and anterior insula during social rejection in the brain scanner also exhibited greater increases in inflammatory activity when exposed to acute social stress in the lab.

"This is further evidence of how closely our mind and body are connected," Slavich said. "We have known for a long time that social stress can 'get under the skin' to increase risk for disease, but it's been unclear exactly how these effects occur. To our knowledge, this study is the first to identify the neurocognitive pathways that might be involved in inflammatory responses to acute social stress."


"Brain pathways linking social stress and inflammation identified." University of California - Los Angeles (2010, August 9). ScienceDaily. Retrieved June 22, 2011 http://www.sciencedaily.com??/releases/2010/08/100809133323.htm





Interleukin-17A is a protein that in humans is encoded by the IL17A gene. The protein encoded by this gene is a proinflammatory cytokine produced by activated T cells.
"IL17A" Wikipedia http://en.wikipedia.org/wiki/IL17A

As you will read below in the OBJECTIVE of Dr. Hennessey's study, dopamine, iron and inflammatory pathways are considered important to the development of RLS.

My belief, as I've stated and provided evidence for on this website, is that it is the inflammation that is affecting the dopamine and iron levels in RLS sufferers (as well as creating the uncomfortable sensations in the legs).

At the very least, what you can take out of this study is that inflammation is now being directly linked to RLS by scientists. There are many other factors that need to be explored in the scientific community, but they are now at least agreeing, due to the growing body of evidence, that inflammation is a primary component.

Here is the study:

"Polymorphisms of Interleukin-1 Beta and Interleukin-17Alpha Genes Are Associated With Restless Legs Syndrome."
Mary Dawn Hennessy, RN, PhD, Rochelle S. Zak, MD, Caryl L. Gay, PhD, Clive R. Pullinger, Kathryn A. Lee, RN, PhD and Bradley E. Aouizerat, MAS, PhD. Biol Res Nurs April 2016 vol. 16 no. 2 143-151. doi: 10.1177/1099800413478827


OBJECTIVE:

Dopamine, iron, and inflammatory pathways are considered important to the development of restless legs syndrome (RLS). Recent genetic studies support involvement of dopamine and iron; however, cytokine gene variation in the inflammatory component remains unexplored. A recent study reported a high prevalence of RLS among HIV-infected adults. We estimate occurrence of RLS in an ethnically diverse sample of HIV-infected adults and examine differences in demographic factors, clinical characteristics, and biomarkers relating to dopamine, iron, and inflammation between adults with and without RLS symptoms. Design: A prospective longitudinal study aimed at identifying biomarkers of RLS symptom experience among HIV-infected adults.

METHOD:

316 HIV-positive adults were evaluated using International RLS Study Group criteria. Genes were chosen for hypothesized relationships to dopamine (NOS1, NOS2), iron (HFE) or inflammation-mediated by cytokine genes (interferon [IFN], interleukin [IL], nuclear factor kappa-B [NFKB], and tumor necrosis factor alpha [TNFA]).

RESULTS:

Similar to general population estimates, 11% of the sample met all four RLS diagnostic criteria. Controlling for race, gender, and hemoglobin, carrying two copies of the minor allele for IL1B rs1143643, rs1143634, or rs1143633 or carrying the minor allele for IL17A rs8193036 was associated with increased likelihood of meeting RLS diagnostic criteria.

CONCLUSION:

This study provides preliminary evidence of a genetic association between IL1B and IL17A genes and RLS.

You can read the full study here:

brn.sagepub.com/content/16/2/143.abstract?rss=1


Dr. Hoe Bing Lo hosts a popular science and nutrition podcast that is based in Cairns, Australia. www.doctorbing.com

Dr. Bing has a Bachelor of Medicine and Surgery (M.B.B.S.) and Bachelor of Science Honours (BSc) from the University of Melbourne.

He has written several books on heart health including "Rekindling The Fire: Steps You Must take To Rebuild Your Heart Stronger Than Before Your Attack, One Heart: You Need Your Heart (And It Needs You)", "What You Don???t Know About Your Heart May Cost You Your Life" and "Renew Your Heart Puzzle: Uncommonly Known But Vitally Important Secrets That Will Keep Your Heart Ticking Strong."

He has also written many books promoting children's health including his popular "Maths Club" series. His new "Five Colour Series" is his unique yet simple introduction to the wonderful world of whole food nutrition.

In this podcast focusing on Restless Legs, Dr. Bing analyzes a scientific study that was published in 2013 by Dr. Leonard Weinstock (et. al) titled "Restless legs syndrome - Theoretical roles of inflammatory and immune mechanisms."

Dr. Bing extracts the dense scientific data from the study and presents it in easily understandable terms.

Dr. Bing agrees that inflammation is the root cause, and builds upon the findings of the study by talking about the importance of changing our diet - and gives scientific insights supporting these changes.

You can stream the podcast from the following website:

archive.org/details/episode-15---fire-an
(once you arrive on the website, click on the link that says "Stream" and the podcast will start playing) xxxxxxxxxxx



"Restless Legs Syndrome as a Comorbidity in Rheumatoid Arthritis"
John A. Gjevre and Regina M. Taylor Gjevre, Autoimmune Diseases. Volume 2013 (2013), Article ID 352782.

"While RLS may be in part considered neurologic disease, there is a significant interplay with the overall aspect of sleep and the immune system. Besides, the issue of iron deficiency often seen, rheumatoid arthritis is a chronic inflammatory condition with numerous proinflammatory cytokines and other immunomodulatory changes present. This likely explains the association of increased rates of primary sleep disorders seen in rheumatoid arthritis, including RLS."

You can view the whole study here:

www.hindawi.com/journals/ad/2013/352782/




In the CONCLUSION section of Dr. Patton's study, she confirms, as Dr. Weinstock suggested, that there is a strong case for considering inflammation as a key component of RLS.

"Proteomic analysis of the cerebrospinal fluid of patients with restless legs syndrome/Willis-Ekbom disease."
Stephanie M Patton, Yong Won Cho, Thomas W Clardy, Richard P Allen, Christopher J Earley and James R Connor. Fluids Barriers CNS. 2013; 10: 20. Published online Jun 7, 2013. doi: 10.1186/2045-8118-10-20

CONCLUSION:

Our results reveal a protein profile in the RLS/WED CSF that is consistent with iron deficiency, dopamine dysregulation and inflammation. The APO-A1 finding may be of relevance outside of CNS given the recently reported increased risk of cardiovascular disease in patients with RLS and cardiovascular dysfunction and reports of painful symptoms. The profiles in the CSF are also consistent with neuropathological findings of activation of HIF pathways and alterations in dopaminergic systems. The data indicate that the CSF protein profile, if confirmed in larger sample sizes, may provide support for existing hypotheses about a biological basis for RLS/WED which could prove clinically meaningful in evaluating therapeutic strategies and identifying new targets.

You can read the full study here:

www.ncbi.nlm.nih.gov/pmc/articles/PMC3680184



I ran across this article by Elizabeth Bowers on the Everyday Health website. One of the doctors quoted in the article, Dr. Michael Wald, suggests that inflammation may be the link between the two conditions.

WHY THESE TWO DISORDERS CO-EXIST

"There is a strong relationship between restless legs syndrome and irritable bowel syndrome," says Michael Wald, ND, MS, CDN, director of nutritional services at Integrated Medicine of Mount Kisco in Mount Kisco, N.Y. "In fact, when an individual has RLS along with IBS, it predicts more severe intestinal pain."

One reason is, put simply, tension. "If you have tension in your legs affecting the nerves and muscles causing restless legs syndrome symptoms, you can have similar tension in your gut affecting the muscles and nerves there, leading to IBS," Dr. Dean said.

Inflammation in the body may also be to blame. "A person may be affected by both conditions because the inflammatory process is a wide-body process ??? inflammatory chemicals literally circulate within the legs and the intestinal tract," Dr. Wald said.

Fortunately there are steps you can take to put both your digestion and your legs at ease.

1. Squelch stress. Stress is a risk factor for restless legs syndrome. It???s also thought to be one of the biggest contributors to IBS. So, reducing stress can help combat both conditions, Wald said. You might try relaxation techniques, such as meditation; counseling; attending support groups; physical activity such as walking or yoga; and getting enough sleep.

2. Improve your nutritional profile. The irritation and inflammation in the gut caused by IBS can translate to poor absorption of nutrients," Dean said. Supplements that may help treat both IBS and restless legs syndrome include melatonin, 5-HTP (5-hydroxy tryptophane), and magnesium. Discuss these options with your health care professional.

3. Eliminate irritants. With both IBS and the sleep disorder restless legs syndrome, certain food and drink may aggravate symptoms. "For restless legs syndrome, eliminating caffeinated beverages such as coffee, tea, and colas is essential," Wald said. Cutting out these beverages may also help symptoms of IBS, he added. Also restrict foods that produce excess gas, such as beans and cruciferous vegetables.

You can read the full article here:

www.everydayhealth.com/ibs/when-both-ibs-and-rls-strike.aspx


Scientists build truths based solely upon the studies of their peers. That???s the ONLY data that they will consider.

This is why Dr. Weinstock???s study on the relationship between RLS and inflammation was such a groundbreaking event. Even though Dr. Weinstock will not be continuing with further studies of the relationship between RLS and inflammation (due to a lack of funding) others are expanding on his findings.

That includes a study that was originally published in the Nov. 2012 edition of the scientific journal "Brain, Behavior and Immunity."

The study clearly demonstrates that there is a direct correlation between elevated C-reactive protein (an indicator of inflammation) and Restless Legs Syndrome.

Here is the study ...

"Elevated C-reactive protein is associated with severe periodic leg movements of sleep in patients with restless legs syndrome."
by Lynn Marie Trotti, Rye DB, De Staercke C, Hooper WC, Quyyumi A, Bliwise DL. Brain Behav Immun. 2012 Nov;26(8):1239-43. doi: 10.1016/j.bbi.2012.06.003. Epub 2012 Jun 26. Emory Program in Sleep, Department of Neurology, Emory University School of Medicine, Atlanta, GA


Abstract

BACKGROUND:

Restless legs syndrome (RLS) is a common sleep disorder in which urges to move the legs are felt during rest, are felt at night, and are improved by leg movement. RLS has been implicated in the development of cardiovascular disease. Periodic leg movements (PLMs) may be a mediator of this relationship. We evaluated systemic inflammation and PLMs in RLS patients to further assess cardiovascular risk.

METHODS:

137 RLS patients had PLM measurements taken while unmedicated for RLS. Banked plasma was assayed for high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha).

RESULTS:

Mean (SD) PLM index was 19.3 (22.0). PLMs were unrelated to TNF-a and IL-6, but were modestly correlated with logCRP (r(129)=0.19, p=0.03). Those patients with at least 45PLMs/h had an odds ratio of 3.56 (95% CI 1.26-10.03, p=0.02, df=1) for having elevated CRP compared to those with fewer than 45PLMs/h. After adjustment for age, race, gender, diabetes, hypertension, hyperlipidemia, inflammatory disorders, CRP-lowering medications, and body mass index, the OR for those with ? 45PLMs/h was 8.60 (95% CI 1.23 to 60.17, p=0.03, df=10).

CONCLUSIONS:

PLMs are associated with increased inflammation, such that those RLS patients with at least 45PLMs/h had more than triple the odds of elevated CRP than those with fewer PLMs. Further investigation into PLMs and inflammation is warranted.

You can read the full study here:

www.ncbi.nlm.nih.gov/pubmed/22750520





A lot of the studies I read through (actually almost all of them) are completely dense and I???m usually able to grasp a few sentences at best. The study I refer to below is no exception. Most of the information bounced off my head except for one VERY IMPORTANT line in the DISCUSSION area of the report.

It was first published in the scientific journal "Nephrology Dialysis Transplantation" in 2011.

Below is the excerpt from the DISCUSSION that concerns RLS sufferers.


"Restless legs syndrome enhances cardiovascular risk and mortality in patients with end-stage kidney disease undergoing long-term haemodialysis treatment."
Gaetano La Manna, Fabio Pizza, Elisa Persici, Olga Baraldi, Giorgia Comai, Maria Laura Cappuccilli, Francesca Centofanti, Elisa Carretta, Giuseppe Plazzi, Luigi Col??, Pasquale Montagna and Sergio Stefoni. Nephrol. Dial. Transplant. (2011) 26 (6): 1976-1983. doi: 10.1093/ndt/gfq681

DISCUSSION:

"This study showed that the presence of RLS and new cardiovascular events was associated with increased inflammatory markers, C-reactive protein and fibrinogen."


Simply put, his study found that there is a correlation between RLS and inflammation.

You can read the full study here:

ndt.oxfordjournals.org/content/26/6/1976.long




"Restless Legs Syndrome More Prevalent Among Hemodialysis Patients, Correlates With CRP (Inflammation) Levels" by Daniel M. Keller, PhD, Medscape
based on a lecture from the XLVII European Renal Association-European Dialysis and Transplant Association Congress.

Restless legs syndrome (RLS) affects patients on chronic hemodialysis with about 4 times the prevalence of that seen in the general population. An Italian research group presented their findings here at the XLVII European Renal Association-European Dialysis and Transplant Association Congress, which showed an association between RLS and levels of C-reactive protein (CRP) in chronic hemodialysis patients.

Giulio Romano, MD, professor of nephrology at the University of Udine in Italy, told Medscape Medical News that among RLS patients undergoing chronic hemodialysis, "the interesting conclusion of our work is that there is a correlation between restless legs syndrome and an increase of inflammatory cytokines and the increase of CRP." Total sleep time significantly negatively correlated with the level of serum CRP (r = .401; P < .004); the higher the CRP, the shorter the sleep time. The group of patients with RLS had serum CRP levels of 43.96 ?? 23.71 mg/L, compared with 15.24 ?? 3.94 mg/L for the non-RLS patients (P = .04).

Dr. Romano noted that several studies have shown that increased inflammation is associated with elevated cardiovascular risk in patients on chronic hemodialysis. Also, he said there is evidence that sleep disorders induce elevated levels of proinflammatory cytokines.

"We think that if patients have some sleep disorders, they evoke inflammation," he said; "if we treat the sleep disorders, we reduce a cardiovascular risk factor because CRP is a possible cause of increased cardiovascular risk." The hemodialysis patients without RLS, he noted, had much lower CRP levels. Similarly, the levels of transferrin saturation, another marker of inflammation, were different between patients with and without RLS.

Nageswara Reddy, MD, assistant professor of nephrology at Manipal University in India, who was not involved with the study, told Medscape Medical News that it makes sense to him that RLS is associated with inflammatory markers. Cardiovascular mortality, which is the main cause of death among hemodialysis patients, is associated with elevated levels of CRP, but it might be associated with other underlying causes as well.

"We have to find out all risk factors. Maybe lack of sleep is another risk factor," Dr. Reddy hypothesized, and suggested that other inflammatory markers, in addition to CRP, be investigated.


You can read the full article here:

http://www.medscape.com/viewarticle/724535




???Restless legs syndrome (RLS) is associated with an increased prevalence of small intestinal bacterial overgrowth: is RLS mediated by inflammatory and immunological mechanisms?"
Arthur S. Walters M.D and Leonard B. Weinstock MD. RLS and SIBO Abstract APSS. Vanderbilt University School of Medicine, Nashville, TN amd Washington University School of Medicine, St. Louis, MO. 2009.

CONCLUSION:

"Evidence of IBS and SIBO are common in RLS but there is not complete overlap. The high prevalence of SIBO in our RLS patients along with the fact that 75% of cases of secondary RLS are associated with inflammation suggests that RLS may be mediated through inflammatory or immunological mechanisms. Since inflammation is also associated with iron deficiency, these results are also in agreement with the iron deficiency hypothesis for RLS."


You can read the full research publication here:

www.gidoctor.net/RLS-and-SIBO-Abstract-APSS_.php




Yokukansan, also known as TJ-54, is composed of SEVEN herbs; Angelica acutiloba, Atractylodes lancea, Bupleurum falcatum, Poria cocos, Glycyrrhiza uralensis, Cnidium officinale and Uncaria rhynchophylla. Yokukansan is used to treat insomnia and irritability as well as screaming attacks, sleep tremors and hypnic myoclonia and neurological disorders which include dementia and Alzheimer???s disease.

Not only has Yokukansan proven in studies to have STRONG anti-inflammatory qualities, but EACH of the seven herbs that make up Yokukansan have anti-inflammatory qualities (references to these studies are below).


"Successful treatment of restless legs syndrome with the herbal prescription Yokukansan."
Hideto Shinno, Mami Yamanaka, Ichiro Ishikawa, Sonoko Danjo, Yasushi Inami, Jun Horiguchi and Yu Nakamura.
Progress in Neuro-Psychopharmacology and Biological Psychiatry. Volume 34, Issue 1, 1 February 2010, Pages 252???253.



CONCLUSION:

RLS improved in ALL 3 cases after the addition of Yokukansan. We speculate that actions on GABAergic, serotonergic and dopaminergic systems might account for some of the therapeutic effects of KS in the present cases. YKS, therefre, appears to be useful in RLS treatment.



"Use of Yokukansan (TJ-54) in the treatment of neurological disorders: A review."
S. de Caires, V. Steenkamp. Department of Pharmacology, Faculty of Health Sciences, University of Pretoria

"Ameliorative effects of yokukansan on behavioral deficits in a gerbil model of global cerebral ischemia."
Liu Y et al. Brain Res. 2016 Jan 16;1543:300-7. doi: 10.1016/j.brainres.2013.11.015. Epub 2013 Nov 19.
http://www.ncbi.nlm.nih.gov/pubmed/24269335

"Yokukansan promotes hippocampal neurogenesis associated with the suppression of activated microglia in Gunn rat."
Motohide Furuya et al. Journal of Neuroinflammation 2013, 10:145 doi:10.1186/1742-2094-10-145
http://www.jneuroinflammation.com/content/10/1/145

"Effects of Angelica acutiloba on mast cell-mediated allergic reactions in vitro and in vivo."
Kyungjin Lee et al. Immunopharmacology and Immunotoxicology, August 2012, Vol. 34, No. 4 : Pages 571-577
http://informahealthcare.com/doi/abs/10.3109/08923973.2011.636048

"Further Phenols and Polyacetylenes from the Rhizomes of Atractylodes lancea and their Anti-Inflammatory Activity."
M. Resch et al. Planta Med 2001; 67(5): 437-442. DOI: 10.1055/s-2001-15817
https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2001-15817

Bupleurum (Bupleurum falcatum)
http://www.herbosophy.com.au/bupleurum-bupleurum-falcatum

Assessment of anti-inflammatory activity of Poria cocos in sodium lauryl sulphate-induced irritant contact dermatitis.
Fuchs SM et al. Skin Res Technol. 2006 Nov;12(4):223-7.
http://www.ncbi.nlm.nih.gov/pubmed/17026651

"Antioxidant and Antiinflammatory Activities of Licorice Root (Glycyrrhiza uralensis): Aroma Extract."
Aki Tanaka and Takayuki Shibamoto. Chapter 20, pp 229???237. Chapter DOI: 10.1021/bk-2008-0993.ch020. ACS Symposium Series, Vol. 993.
http://pubs.acs.org/doi/abs/10.1021/bk-2008-0993.ch020

"Components of rhizome extract of Cnidium officinale Makino and their in vitro biological effects."
Bae KE et al. Molecules. 2011 Oct 21;16(10):8833-47. doi: 10.3390/molecules16108833.
http://www.ncbi.nlm.nih.gov/pubmed/22019572

"Uncaria rhynchophylla inhibits the production of nitric oxide and interleukin-1?? through blocking nuclear factor ?B, Akt, and mitogen-activated protein kinase activation in macrophages."
Kim JH et al. J Med Food. 2010 Oct;13(5):1133-40. doi: 10.1089/jmf.2010.1128.
http://www.ncbi.nlm.nih.gov/pubmed/20828308


You can read the full study here:

www.deepdyve.com/lp/elsevier/successful-treatment-of-restless-legs-syndrome-with-the-herbal-tIA5ur7GMK





A 2009 study performed at the University of Pennsylvania School of Nursing provided highly positive results when giving their RLS subjects valerian.

ALL of the subjects participating in the study showed a MARKED improvement with their RLS over an 8 week period.

Valerian is a herb with powerful anti-inflammatory properties. Valerian also helps to soften anxiety, insomnia and stress.


"Does valerian improve sleepiness and symptom severity in people with restless legs syndrome?"
Cuellar NG and Ratcliffe SJ. Altern Ther Health Med. 2009 Mar-Apr;15(2):22-8.

OBJECTIVE:

To compare the effects of 800 mg of valerian with a placebo on sleep quality and symptom severity in people with restless legs syndrome (RLS).

METHODS:

A prospective, triple-blinded, randomized, placebo-controlled, parallel design was used to compare the efficacy of valerian with placebo on sleep quality and symptom severity in patients with RLS. Thirty-seven participants were randomly assigned to receive 800 mg of valerian or placebo for 8 weeks. The primary outcome of sleep was sleep quality with secondary outcomes including sleepiness and RLS symptom severity.

RESULTS:

Data were collected at baseline and 8 weeks comparing use of valerian and placebo on sleep disturbances (Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale) and severity of RLS symptoms (International RLS Symptom Severity Scale) from 37 participants aged 36 to 65 years. Both groups reported improvement in RLS symptom severity and sleep. In a nested analysis comparing sleepy vs nonsleepy participants who received 800 mg ofvalerian (n=17), significant differences before and after treatment were found in sleepiness (P=.01) and RLS symptoms (P=.02). A strong positive association between changes in sleepiness and RLS symptom severity was found (P=.006).

CONCLUSIONS:

The results of this study suggest that the use of 800 mg of valerian for 8 weeks improves symptoms of RLS and decreases daytime sleepiness in patients that report an Epworth Sleepiness Scale (ESS) score of 10 or greater. Valerian may be an alternative treatment for the symptom management of RLS with positive health outcomes and improved quality of life.

You can read the full study here:

www.ncbi.nlm.nih.gov/pubmed/19284179





In the following study from 2005, researchers created a mixture of several healing ingredients and produced a syrup which the children with RLS took orally.

Out of the 14 ingredients in the mixture, 13 of them had ANTI-INFLAMMATORY properties (references for each are below).

The only ingredient that didn't have anti-inflammatory properities was Long Gu (Dragon's Bone) which is "ground bone" - a sedative to reduce stress and calm the mind.


"Fifty cases of child restless legs syndrome treated with the integrated method of Chinese Herbal drugs."
Wang W. and Fan H. J Tradit Chin Med. 2005 Dec;25(4):276-7.

Fifty cases of child restless syndrome were treated with oral administration of Chinese traditional herbal drugs plus auricular-plaster therapy from December 1998 to November 2001, and another 47 cases were treated with oral administration of methylphenidate as controls

METHODS OF TREATMENT:

For patients in the treatment group the ingredients of formula were prescribed as below:

Fu-Ling (Poria cocos) 40g
Shan Yao / Radix Dioscoreae (Chinese Yam Root) 40g
Radix Rehmanniae Praeparata 30g
Shan Zhu Yu (Fructus Corni) 30g
Shi Chang Pu (Rhizoma Acori Tatarinowii) 45g
Yuan Zhi / Radix Polygalae (Chinese Senega Root) 30g
Bai Ji Li (Fructus Tribuli) 30g
Long Gu (Dragon's Bone) 60g
Mu Li (Oyster shell) 60g
Jiang Can / Bombyx Batryticatus (Silkworm) 30g
Gou Teng (cat's claw) 30g
Yi Zhi Ren (Chinese Ginger) 30g
Da Zao (Jujube Fruit) 30g
Gan Cao / Radix Glycyrrhizae (Licorice Root) 25g

They were made into 250 ml of syrup in the pharmaceutics department of this hospital.

The syrup was orally administered to the patients under 9 years in a dose of 25 ml, three times daily, and to the patients over 9 years in a dose of 40 ml, three times daily.

RESULTS OF TREATMENT:

Of the 50 cases in the treatment group, 21 cases were markedly effective, 26 cases effective, and 3 cases ineffective, with a total effective rate of 94%. Among the 47 cases in the control group, 15 cases were markedly effective, 17 cases effective, and 15 cases ineffective, with a total effective rate of 68.09%. The difference in total effective rate between the two groups was statistically very significant (P<0.01).

DISCUSSION:

The results showed that the therapeutic effect of the treatment group was significantly superior to that of the control group


Fu-Ling (Poria cocos):
"Assessment of anti-inflammatory activity of Poria cocos in sodium lauryl sulphate-induced irritant contact dermatitis."
Fuchs SM et al. Skin Res Technol. 2006 Nov;12(4):223-7.
http://www.ncbi.nlm.nih.gov/pubmed/17026651

Shan Yao / Radix Dioscoreae (Chinese Yam Root):
"Ethanol extract of Alismatis Rhizoma reduces acute lung inflammation by suppressing NF-?B and activating Nrf2."
Han CW et al. J Ethnopharmacol. 2013 Mar 7;146(1):402-10. doi: 10.1016/j.jep.2013.01.010. Epub 2013 Jan 18.
http://www.ncbi.nlm.nih.gov/pubmed/23333748

Radix Rehmanniae Praeparata:
"2,5-dihydroxyacetophenone isolated from Radix Rehmanniae Preparata inhibits inflammatory responses in lipopolysaccharide-stimulated RAW264.7 macrophages."
Han Y. et al. J Med Food. 2012 Jun;15(6):505-10. doi: 10.1089/jmf.2011.1940. Epub 2012 Apr 17.
http://www.ncbi.nlm.nih.gov/pubmed/22510152

Shan Zhu Yu (Fructus Corni):
"Anti-inflammatory and analgesic effects of the aqueous extract of corni fructus in murine RAW 264.7 macrophage cells."
Sung YH et al. J Med Food. 2009 Aug;12(4):788-95. doi: 10.1089/jmf.2008.1011.
http://www.ncbi.nlm.nih.gov/pubmed/19735178

Shi Chang Pu (Rhizoma Acori Tatarinowii):
"Traditional Chinese Medicine: Scientific Basis for Its Use." by James David Adams (Jr.), Eric J. Lien. Page 209. RSC Publishing. March 30, 2013
http://www.chapters.indigo.ca/books/product/9781849736619-item.html


Yuan Zhi / Radix Polygalae (Chinese Senega Root):
"Traditional Chinese Medicine for Senile Dementia."
Zhihong Lin et al. Evidence-Based Complementary and Alternative Medicine. Volume 2012 (2012), Article ID 692621, 13 pages
http://www.hindawi.com/journals/ecam/2012/692621/

Bai Ji Li (Fructus Tribuli):
"Tribulus Fruit / Bai Ji Li." Golden Lotus Botanicals.
http://www.goldenlotusherbs.com/index.php?pageid=2&itemid=721

Long Gu (Dragon's Bone ):
Not an anti-inflammatory. A sedative to reduce stress and calm the mind.

Mu Li (Oyster shell): "Nutritional Value of Muli or Oyster." MDidea
http://www.mdidea.com/products/proper/proper04209.html

Jiang Can / Bombyx Batryticatus (Silkworm):
"Effect of silk fibroin peptide derived from silkworm Bombyx mori on the anti-inflammatory effect of Tat-SOD in a mice edema model."
Kim DW et al. BMB Rep. 2011 Dec;44(12):787-92.
http://www.ncbi.nlm.nih.gov/pubmed/22189681

Gou Teng (cat's claw): "Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content."
Sandoval M. et al. Phytomedicine. 2002 May;9(4):325-37.
http://www.ncbi.nlm.nih.gov/pubmed/12120814

Yi Zhi Ren (Chinese Ginger): "Chinese Ginger or Yi Zhi Ren - A Powerful Anti-inflammatory & Immune Boosting Agent." Dr. Paul Haider, OM Times Magazine. May 3, 2013.
http://community.omtimes.com/profiles/blogs/chinese-ginger-or-yi-zhi-ren-a-powerful-anti-inflammatory-immune

Da Zao (Jujube Fruit): "The jujube (Ziziphus jujuba Mill.) fruit: a review of current knowledge of fruit composition and health benefits."
Gao QH et al. Agric Food Chem. 2013 Apr 10;61(14):3351-63. doi: 10.1021/jf4007032.
http://www.ncbi.nlm.nih.gov/pubmed/23480594

Gan Cao / Radix Glycyrrhizae (Licorice Root): "Antioxidant and Antiinflammatory Activities of Licorice Root (Glycyrrhiza uralensis): Aroma Extract."
Aki Tanaka and Takayuki Shibamoto. Chapter 20, pp 229???237. Chapter DOI: 10.1021/bk-2008-0993.ch020. ACS Symposium Series, Vol. 993.
http://pubs.acs.org/doi/abs/10.1021/bk-2008-0993.ch020


You can read the full study here:

www.unboundmedicine.com/medline/citation/16447670/Fifty_cases_of_child_restless_syndrome_treated_with_the_integrated_method_of_Chinese_herbal_drugs_and_auricular_plaster_therapy_

















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