Are Methylfolate Supplements and Insomnia Linked?

Methylfolate is an essential nutrient required for numerous biochemical processes in the body, namely those related to methylation. The nutrient itself is usually obtained from food or supplements containing folate or folic acid and then converted to methylfolate in the body. 

However, an MTHFR polymorphism can prevent the conversion of folic acid, resulting in negative health issues caused by low folate levels. Remedying these levels will usually require supplementation with a bioavailable form of folate called methylfolate. This is the form that can bypass an MTHFR polymorphism and enter the central nervous system. 

Although studies evaluating the safe upper limits of folate intake have found methylfolate to be a safe and beneficial nutrient, concerns have been raised regarding excessive intake and a possible link between methylfolate supplements and insomnia.

There is no clinical evidence to support the claim that methylfolate supplements and insomnia are linked. However, some reports show that high doses of methylfolate may increase agitation and potentially lead to mania.

This article will discuss whether methylfolate and insomnia are linked and other possible side effects from taking too large a dose of methylfolate.

Research suggests that methylfolate is generally a safe nutrient. The most commonly reported side-effects of taking methylfolate range from digestive complaints to headaches.

More severe side effects are usually linked to age. Older people appear to be more susceptible to unwanted reactions from many medications (not just methylfolate) due to reduced liver function or interactions with other medications.

The most common side-effects of methylfolate include:

• Irritability
• Sleeplessness and insomnia
• Sore muscles
• Joint pain
• Skin irritations (acne, rash)
• Severe anxiety
• Palpitations
• Nausea
• Headaches or migraines
• Burning or tingling nerves
• Runny nose
• Bronchospasms
• Difficulty concentrating
• Confusion
• Excitability
• Depression, malaise
• Taste impairment
• Reduced appetite
• Digestive issues: nausea, gas, abdominal bloating

Although the current data are limited, some research suggests that L-methylfolate may increase agitation or contribute to the onset of hypomania/mania. This may affect sleep patterns.

Methylation is required for numerous biochemical reactions in the body that regulate the activity of the cardiovascular, neurological, reproductive, and elimination systems. It is especially crucial for healthy liver function and detoxification.

Methylfolate plays an important role in phase II liver detoxification of estrogen. Phase II methylation of estrogen requires the COMT enzyme (catechol oxygen methyltransferase), which in turn requires a methyl group supplied by SAMe, the body’s methyl donor.

This process depends on the availability of the universal methyl donor SAMe (S-adenosylmethionine).  However, the system that produces SAMe also depends on the availability of methylfolate. The methylation cycle - and the detoxification process - will only work efficiently if adequate methylfolate and SAMe are present.

Low methylfolate caused by a mutation of the MTHFR gene can reduce your ability to methylate catechol estrogens. Poor methylation of these potentially genotoxic catechols is associated with a higher risk of postmenopausal breast cancer.

If you have been prescribed methylfolate or diagnosed with an MTHFR polymorphism, it is important that you do not stop taking it without first consulting your health professional. L-methylfolate has no known severe, serious, moderate, or mild interactions with other drugs. 

Sudden discontinuation of your methylfolate supplement may cause withdrawal symptoms or a return of previous health issues such as depression or elevated homocysteine. 

It is generally recommended to reduce your dose slowly until you find the dosage that suits you. This should be done over several weeks or months and only with the guidance of your medical professional. 

Reducing the risk of potential side effects when taking methylfolate is relatively simple.

• Always take the dosage prescribed by your doctor or as stated on the supplement itself. A quality supplement designed by experts will be formulated in a way that provides a specific dosage.
• Try to limit your intake of folic acid by avoiding foods such as fortified cereals, flours, and other products. The MTHFR mutation impairs the proper conversion of this substance in the body, which can lead to a buildup of unmetabolized folic acid.
• Supplement your diet with foods rich in vitamin B6 and B12. Both of these nutrients work alongside methylfolate in the methylation cycle. Deficiency in either nutrient can increase the risk of many adverse health issues.
• Advise your doctor if you are taking methotrexate, which is prescribed for psoriasis. Methylfolate appears to cause a flare-up of psoriasis symptoms when taken alongside methotrexate.
• Folate may trigger episodes of mania in those with bipolar disorder because it enhances the effect of certain antidepressant drugs. Screening for bipolar disorder is highly recommended before taking methylfolate.
• Methylfolate can interact with a range of drugs, albeit mildly. Discuss all your other medication and supplements with your medical practitioner before taking methylfolate and the possibility of any interactions.

Methylfolate is absolutely essential for normal bodily function due to its involvement in an enormous range of processes - the most important being methylation. 

Low levels of methylfolate can lead to a variety of health concerns, including elevated homocysteine, depression, and dementia. In turn, poor DNA methylation has been linked to many diseases, cancers, and health conditions. 

Adequate folate intake, on the other hand, is associated with numerous health benefits, including the reduction of neural tube defects, lower risk of cardiovascular disease, and prevention of certain cancers.

Methylfolate may be prescribed by doctors or natural health practitioners when required to correct a deficiency. Side effects of methylfolate supplementation are generally rare and can be avoided by checking whether there may be any interactions with your current medication or health conditions. 

A quality methylfolate supplement with an appropriate dosing schedule will also help to minimize the risk of side effects. Methylfolate supplements are often known or labeled as L-MTHF, L-5-Methylfolate, L-5-MTHF, and (6S)-5-Methylfolate.

Some of the most highly recommended methylfolate supplements are in the Methyl-Life® product range, which includes a variety of dosage level options: Methylfolate 7.5+, Methylfolate 10, and Methylfolate 15.

Each of the methylfolate products in the Methyl-Life® range contains the internationally-patented Magnafolate® PRO [(L)-5-methyltetrahydrofolate, Calcium, which is carried on an ultra-stable Type C Crystalline molecule (L-Methylfolate) for superior absorption]. 

This type is approximately three times more pure than other L-Methylfolate forms available on the health supplement market today. These top-rated products are formulated especially for people with a heightened need for bioavailable folate due to MTHFR defects, dietary deficiencies (such as vegans or vegetarians), or other conditions in which nutritional absorption is impaired.