If you have an MTHFR variant and trouble sleeping, it can be tempting to assume that the answer to "Does MTHFR cause insomnia?" Is a simple "YES." Sadly, like everything else with MTHFR, it's complicated. MTHFR influences folate and one-carbon metabolism (methylation), which in turn affects homocysteine, methionine, S-adenosylmethionine (SAM), neurotransmitter biology and many methylation reactions throughout the body.Sleep itself also changes methylation patterns.