I have been treating a lot of women with premenstrual dysphoric disorder (PMDD) lately. The more I see of this debilitating condition, the more I am becoming convinced it’s an MTHFR and methylation issue (you can read more about MTHFR here)

What we currently understand about PMDD is that your brain chemicals or neurotransmitters such as serotonin and dopamine are affected by the fluctuations of oestrogen and progesterone that occurs in the luteal phase of the menstrual cycle. The luteal phase is from ovulation to menstruation.

All women experience fluctuations in hormones, but women with PMDD suffer with more severe symptoms including severe depression, anxiety, cognitive impairment, and severe fatigue. What is happening is that these women’s central nervous system and neurotransmitters can’t cope with the fluctuations in hormones. Exactly why this happens is still largely unknown. What we do know is that the production of S-Adenosly-Methionine (SAMe) via the methylation cycle plays a crucial role in the production and balancing of neurotransmitters. What we also know is that women with an MTHFR gene mutation and methylation cycle issues may not be producing enough SAMe.

Clinically I have seen many women significantly reduce the symptoms of PMDD within one cycle by supplementing with SAMe. 

A big statement?  Possibly….but I have seen it numerous times.

A possible mechanism of action is that if you have MTHFR and methylation issues and are not producing enough SAMe, it is possible that you already have low levels of serotonin in the brain. Then, during the luteal phase when oestrogen drops you suddenly have very low serotonin levels. Serotonin is important for maintaining a sense of wellbeing and a happy positive mood.

There can be other nutrient deficiencies at play including low zinc, B6 and iron, which are important for the production of neurotransmitters. Inflammation can also can cause a reduction in neurotransmitters and women with PMDD do have higher levels of inflammatory markers during the luteal phase. Correcting these nutrient deficiencies and reducing inflammation can help, but if there is a genetic MTHFR gene mutation issue and low SAMe levels, then this needs to be corrected for best clinical outcomes.

Joanne has treated many women PMDD, allowing them to live a life free from depression, anxiety and fatigue.


Appointments can be made online, or by emailing Joanne at or by phone on 0400 658 003.

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Author: Joanne Kennedy

Joanne Kennedy is a degree qualified Naturopath practising in the Sydney CBD. Areas of speciality include: MTHFR, Women’s hormones; stress, fatigue and insomnia; anxiety & depression; gut/digestive health; and histamine intolerance. Jo has helped hundreds of patients with chronic and complicated health issues gain control of their health and finally heal.

Jo is currently seeing patients in the Sydney CBD at Sydney Health & Wellness Centre and via Skype. For appointments call Jo on 0400 658 003 or email