Methylfolate and Anxiety

MTHFR gene mutations can increase your risk of developing mental health conditions, including depression and anxiety.

For those with a MTHFR genetic mutation and anxiety and/or depression, antidepressant medication is often ineffective. This is because the lack of the MTHFR enzyme results in impaired methylfolate metabolism, which means the brain cannot produce the neurotransmitters required for antidepressant medication to function ⁴.

Supplementing with B vitamins has shown promise in improving the symptoms of anxiety and other issues associated with MTHFR ⁵.

At present, there are limited studies on treating anxiety with folate, folic acid, or methylfolate supplements. However, there is substantial evidence that depression can be treated with methylfolate, and the World Health Organization has shown that anxiety and depression are the most common coexisting psychological problems in primary care ⁶.

One study found that rats with depression and anxiety-like behavior were successfully treated with folic acid supplements. The folic acid improved neuro-oxidative damage and neuro-inflammation caused by nicotine withdrawal, which then helped to reduce their anxiety ⁷.

Folic acid and antipsychotics have also been successfully used to treat negative symptoms in schizophrenia patients ⁸. Anxiety symptoms can occur in up to 65% of patients with schizophrenia, which may mean that methylfolate would also be helpful ⁹.

It’s also worth noting that many patients with depression have self-reported improvement in their anxiety symptoms after taking Deplin®, a prescription methylfolate product ¹⁰.

For those who cannot obtain Deplin®, over-the-counter methylfolate supplements are available from Methyl-Life®.

How does methylfolate help anxiety?

Methylfolate is the active form of folate, one of the key nutrients necessary for the production of neurotransmitters such as serotonin and dopamine. These ‘brain chemicals’ are involved in supporting healthy mood, cognition, and normal stress response ¹¹.

Methylfolate is required for the methylation of homocysteine, which forms methionine and S-adenosylmethionine (SAMe). SAMe plays an essential role in neurotransmitter synthesis ¹².

Methylfolate and other B vitamins are also involved in the conversion of alpha-linolenic acid to Omega 3 fatty acids. Sufficient levels of omega 3 fatty acids are associated with a lower risk of anxiety ¹³.

Dosage of methylfolate for anxiety

At present, there is no specific dosage recommendation for treating anxiety with methylfolate. However, as anxiety often coexists with depression, it may be helpful to consider the methylfolate dosage guidelines recommended for depressive symptoms.

Studies have shown that methylfolate dosages of 15mg are effective in improving symptoms of depression and anxiety ¹⁴.

Always consult with your healthcare professional before starting any new supplement, including methylfolate, especially if you're currently on other medications or have a medical condition.

Follow the recommended dosage provided by your healthcare provider, as excessive intake without professional guidance may lead to adverse effects.

Taking vitamin B12 and/or vitamin D is effective in improving the symptoms of depression and anxiety, especially in patients who are low in these nutrients ¹⁵. Vitamin B12 is another crucial nutrient involved in the production of neurotransmitters. 

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. It works alongside the excitatory neurotransmitter glutamate to control many processes, including anxiety and stress regulation, sleep patterns, memory, mood, and even the perception of pain.

Research suggests that the MTHFR mutation can affect levels of glutamate and GABA, possibly due to the brain trying to counter the excitatory effects of homocysteine ¹⁶. Too much glutamate and too little GABA can result in anxiety, restlessness, brain fog, insomnia, mental exhaustion, and other symptoms.

Studies have shown that people who have very little MTHFR activity tend to have higher levels of glutamate and reduced levels of GABA, which could explain anxiety symptoms ¹⁷.

It is for this reason that some pharmacological treatments of anxiety disorders and insomnia usually involve benzodiazepines, which help to increase GABA.

Recent studies have shown that GABA from supplements, probiotics, and GABA-rich fermented foods may increase GABA levels in the brain. One clinical trial found that GABA not only induces relaxation but also reduces anxiety ¹⁸.

CALMING is a supplement from Methyl-Life® specifically formulated to reduce anxiety and support the nervous system. CALMING contains GABA, Saffron, and N-acetyl cysteine (NAC), which work together to improve neurotransmitter activity in the brain and soothe feelings of anxiety.