Dr. Tom Greenfield

Dear Dr. Greenfield,

I am a 42 year old woman with RLS. I have it since I was 20, with alternating good and bad periods.

It affects me especially in my sleep. I am a 0+, Gatherer.

Are there any natural supplements I can take which could make a difference?

Thanks and kind regards,

Petra

Restless legs syndrome (RLS) and periodic limb movement disorder are characterized during waking by an irresistible urge to move the legs while awake, and involuntary leg movements while asleep.

For people with a family history of RLS, it is worth considering whether there is a genetic influence on the condition: researchers have found several genetic loci associated with RLS in an autosomal dominant inheritance pattern [1].

One of the genetic influences may involve an increased need for folate [2]. Individuals with polymorphisms for folate metabolism often do better taking an active form of folic acid such as folinate, rather than the commonly available folic acid supplements. Although folic acid improves methylation in all GenoTypes, GT4 Explorers are more prone to folic acid deficiency anaemia; GT1 Hunters and GT6 Nomads may also need folate to slow down their rapidly aging genes [3].

Researchers have also found that iron supplementation may improve the symptoms of RLS [2], reducing fluctuations in dopamine levels in the brain at night. Patients with RLS have lower levels of dopamine and respond to iron administration [4]. Caffeine, nicotine, alcohol and medication that affects dopamine levels may induce RLS as a side effect. It is recommended to check ferritin (iron storage) levels before supplementing with iron, as ferritin levels are often lower than average in RLS sufferers. There are strong indications that a gene regulating dopamine beta hydroxylase activity is linked to the ABO blood group locus [5], and altered dopamine levels may be associated with blood type.

Finally, osteopathic manipulative therapy has been found to decrease spinal facilitation in a small pilot study, relieving symptoms in many patients with RLS [6].

References:
1. Dhawan V, Ali M, Chaudhuri KR. "Genetic aspects of restless legs syndrome." Postgrad Med J. 2006 Oct;82(972):626-9. PubMed
2. Lee KA, Zaffke ME, Baratte-Beebe K.J. "Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron." Womens Health Gend Based Med. 2001 May;10(4):335-41. PubMed
3. Dadamp, P. The GenoType Diet. Broadway Books, 2007, ISBN 978-0-7679-2524-2
4. Patrick LR. "Restless legs syndrome: pathophysiology and the role of iron and folate." Altern Med Rev. 2007 Jun;12(2):101-12. PubMed
5. Wilson AF, Elston RC, Siervogel RM, Tran LD. "Linkage of a gene regulating dopamine-beta-hydroxylase activity and the ABO blood group locus". Am J Hum Genet 1988;42:160-166. PubMed
6. Peters T W, "Restless Legs", Osteopathy Today, October 2001. P12-13.

The UK Food Standards Agency (FSA) has issued a press release advising pregnant mothers to limit their intake of coffee and caffeine-containing substances.[1] "Pregnant women are advised to limit their daily caffeine intake to 200mg a day – roughly two mugs of coffee a day" due to a potential link with Foetal Growth Retardation (FGR). This is a reduction from the previous advice of 300 mg per day, following an updated report from the FSA's independent Committee on Toxicity (COT).[2] According to the committee, if there is a causal link then there may be no lower 'safe' limit, but a caffeine intake of less than 200 mg per day during pregnancy may reduce the risk of FGR to less than 2%. FGR is defined as failure of the baby to attain its growth potential as determined by genetic and environmental factors.

The FSA funded research published by the British Medical Journal[3] which measured caffeine intake from all sources (coffee, tea, colas and medication) in pregnant women, and then measured their babies when they were born. The xenobiotic caffeine can be detoxified from the body in four main ways, 3-demethylation being quantitatively the most important: caffeine is converted to paraxanthine by the enzyme cytochrome P450 1A2 (CYP1A2). This is one of the enzymes which often has low activity in the GT4 Explorer GenoType, and is responsible for Explorers being up all night after drinking coffee. The researchers measured the CYP1A2 enzyme activity as the main form of caffeine clearance in the mothers taking part in the study. They found that the mothers with the highest CYP1A2 activity passed the most caffeine and caffeine metabolites to their foetus via the placenta. CYP1A2 activity is absent in the placenta and the fetus.[4] This means that like the GT4 Explorer, the unborn baby won't get much sleep after their mother has drunk coffee.

What is the problem with having smaller babies? It is a well known epigenetic risk factor, as the COT study says:

FGR is an important outcome because it is associated with an increased risk of perinatal mortality and morbidity, including perinatal asphyxia. Moreover, there is epidemiological evidence that FGR correlates with adverse effects in adult life. For example, affected individuals have an increased incidence of metabolic syndrome, manifesting as obesity, hypertension, hypercholesterolemia, cardiovascular disease, and type 2 diabetes.

Smoking and alcohol intake also have a significant effect on the risk of FGR.

References:

1. Food Standards Agency. "Food Standards Agency publishes new caffeine advice for pregnant women." Press release, Monday 3 November 2008.
2. Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. "Statement on the reproductive effects of caffeine". COT statement 2008/04
3. CARE Study Group. "Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study" BMJ 2008;337:a2332
4. Aldridge A, Aranda JV, Neims AH. "Caffeine metabolism in the newborn." Clin Pharmacol Ther. 1979 Apr;25(4):447-53. PMID: 428190