Could this simple vitamin be the missing link in hard to treat depression?

If you are one of the many people who suffer from depression or are a clinician that treats depression, you know how hard this can be to treat effectively. More than 70% of those treated for depression do not feel they are getting significant symptom relief. There are many things that contribute to depression. Stressful and traumatic life events, poor diet, lack of sleep, and genetics are all known risks factors for depression. If you seek help from your health care provider, you will often be offered an antidepressant medication and if that does not work another one will be tried or a combination of antidepressants. Yet still you do not get relief.


The ideal approach to treating depression would be to identify the root cause and address it at its source. Depression can result from neurotransmitter dysfunction or imbalance. Measuring neurotransmitter function and treating neurotransmitter imbalances with their precursors in the form of B vitamins and amino acids would be ideal. However, this option is not available to most people, nor is there an awareness that this option exists. Another root cause of depression most certainly is hidden in the digestive tract and is often referred to as the second brain. I think in many ways it is our brain’s brain. It is reported that anywhere from 70-95% of our serotonin is produced within the gut. If you are eating a poor diet devoid of vital amino acids, vitamins, and minerals, there is a greater probability you will suffer from some degree of depression. Throw in genetics and situational stressors and your odds of suffering from depression are even higher.

What if there was a simple missing link that could help turn on the switch to alleviating symptoms in those individuals who have a genetic glitch? Recently there was a very promising study done that showed that treatment resistant depression may improve significantly with the addition of Vitamin B9 in the form of L-methylfolate. L-methyfolate is important to the synthesis of cofactor tetrahydrobiopterin or BH4 activating amino acids involved in the synthesis and production of the neurotransmitters serotonin, norepinephrine, and dopamine. However if a key and critical enzyme, known as methylene tetrahydrofolate reductase (MTHFR) that activatesBH4 is lacking, this conversion does not happen thereby blocking the production of these key neurotransmitters passage across the blood-brain-barrier to the brain. So if you are taking an antidepressant to slow the uptake of any one of these key neurotransmitters and you lack MTHFR, you may well have little or no effect from your antidepressant.

Research presented at the European Congress of Psychiatry in 2011 (Papakostas GI et al, EPA 2011, Vienna, Austria; 13 March 2011) showed that when L-methylfolate (Deplin) was given to patients with hard to treat depression, there was a 50% reduction in depressive symptoms based on HAM-D score. Deplin 15mg per day was given to patients in conjunction with their Selective Serotonin Reuptake Inhibitor (SSRI). This was a small study and certainly raises the question, if more patients are offered this treatment with a safe medical food such as L-methylfolate (Deplin), would they benefit? Antidotally, I have had experience with only one patient that I know of who has tried Deplin. This individual felt their life change literally overnight expressing that a fog had been lifted and they felt normal again. It leaves me wondering if this is something that needs to be added to the arsenal to in the treatment of depression.

Could this simple vitamin be the missing link in hard to treat depression?

4 thoughts on “Could this simple vitamin be the missing link in hard to treat depression?

  1. My daughter saw Laura after a recommendation that maybe her thyroid was not functioning as she was too tired to make it through even an hour a day without wanting to collapse. she was also on the highest dosages of Abilify (15 mg) and Lexapro (40 mg) because none of the depression medications were keeping her from having panic attacks and attempting suicide. After 15 months of changing depression medications that only worked a little bit for 5 weeks, I was ready to look another direction.

    My daughter tested to have the MTHFR gene mutation and began taking 15 mg of Deplin. The results were stunning about 3 days in and then I confused the antibiotic she was taking with the Deplin so she did not take it for a few days. she didn’t seem to be doing any better. Once we started the Deplin again a few days later, it was like an awakening. Her mind was clear and those that knew her well said we got her back and even better than before!

    At this point, I’m trying to wean her off the high dosages of Lexapro and Abilify but doing it one medication at a time and seeing how she adjusts. Coming off of Lexapro has given her dizziness and headaches but other than that, I have a daughter who is happy and full of life. She has faced some stressful situations and no panic attacks after a couple of years of them. No signs of depression have surfaced. I have heard the word “miracle” used many times since she started taking this medication.

    I also have the genetic mutation but have had no signs of depression in my lifetime. The only symptom I could say I might have had due to this mutation would be 3 miscarriages. One was at 14 weeks of pregnancy, the other two were around 6-7 weeks gestation. Hard to say if there was any connection between the mutation and miscarriages though.

    I’m still shaking my head that a medicine food could make this much difference in my daughter’s life. She went from an appearance of someone dying to a vibrant young woman headed off to college in a few months. We are learning to read labels and avoid folic acid and choose the healthier alternatives when it comes to food. I guess my dad, the vitamin guru and health nut was way ahead of the medical community when it comes to a healthier lifestyle! Thank you Laura, you saved my daughter’s life literally.

    1. It is only through your persistent and courage to help your daughter that our lives were brought together. I am always humbled by the faith you and others have to journey down the path to find answers to get to the root cause, rather than just treating symptoms. It takes great courage. As you have experienced first hand it can be life changing in dramatic ways. Thank you for sharing this testimonial of your daughter’s journey as it can help and inspire others as well. Laura

  2. Laura, thanks so much for sharing this information.
    Chronic fatigue and fibromyalgia groups that are working with various trial supplement/diet protocols discuss this vitamin as a vital part of their programs. The primary issue they seem to have is the obtaining a pure source of it and deciding the safe dose for their particular condition and state of condition.
    Have you followed the information on sources for the supplement? I would be appreciative of your thoughts and knowledge on the topic.
    Again, thanks sincerely for this share.

    1. Janet, That is a good question. You do have to be careful about what form of folate that is used and certainly not use folic acid (synthetic form of folate). It needs to be natural, pure form of L-methylfolate at a dose of 15mg to be effective. Some resources I have come across state that it is safe up to 90mg. When synthetic folic acid is used, a dose of only 800-1000mcg is recommended. In the study on depression, a dose of 7.5mg of L-methylfolate was no more effective than placebo. Results were seen at the 15mg dose in reducing depression symptoms. You raise a very good question, would L-methylfolate be useful in the treatment of other conditions believed to be affected by the neurotransmitters of serotonin, norepinephrine, and dopamine? That would make for a great research study. The L-methylofolate used in the depression study is under the prescription name of Deplin (. I would theorize that for L-methylfolate to be effective to cross the blood-brain-barrier, 15mg was a therapeutic level for this to happen.
      There is a supplement out there called methylpro that has methyltetrahydrofolate in it, but this is closer to folic acid and more has to be done to break it down to become L-methylfolate. If you have the missing link of the MTHFR polymorphism, I suspect it may not convert and thus not get the same benefit.
      So I would caution any one from just going out any buying just any folate as there are different forms. There is Metafolin, but I believe the largest dose is only a fraction of what is in Deplin at only 1000mcg.

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