Supplements for Depression that Actually Work

Supplements that help with depression, e.g. St. John's wort, N-acetyl cysteine

Some people claim that vitamins and minerals can cure serious mental illness. That’s not what I’m talking about here. While in general, there’s not a ton of research funding for supplements and herbal products, there are a number of supplements that do have some research evidence to support their effectiveness in depression.

For people with mild depression, a supplement may be helpful on its own, but for people with moderate to severe depression, supplements can serve as an add-on to another primary form of treatment. These are some of the examples from complementary and alternative medicine chapter in my new book Managing the Depression Puzzle.

St. John’s wort

St. John’s wort is a herbal product that has shown some effectiveness in mild depression. SJW contains a number of different compounds, several of which affect the neurotransmitter serotonin. It’s not clear which particular compounds are responsible for the beneficial effect. The strength of SJW is described in terms of the compound hypericin. There can be considerable variation from one formula to the next.

SJW can interact with a number of different psychiatric medications, so if you’re taking meds don’t use SJW without consulting a health professional.

Omega-3 fatty acids

Omega-3s are a type of unsaturated fatty acid found primarily in fish oils, and they have anti-inflammatory effects. Some, but not all, studies in depression have shown a benefit. There are two primary types of omega-3s, EPA and DHA. EPA appears to be the most important in depression, so pick out an omega-3 formula with a high EPA content.

I’ve been taking an omega-3 supplement for several years now. I honestly have no idea if it’s doing anything for me or not, but at this point, I really need any little bit of help that I can get, so I’m sticking with my omega-3s.


Curcumin is a compound that’s part of turmeric, a spice that’s commonly used in Indian and Southeast Asian cuisine. It has anti-inflammatory and antioxidant properties, and some research has shown it to be helpful for a variety of different inflammatory conditions as well as depression.

There appears to be a link between depression and inflammation in a subset of people with depression, which may account for some of the beneficial effect seen in depression.

I started taking a curcumin supplement a couple of months ago. Much like with the omega-3s, I have no idea if it’s actually helping, but I figure might as well keep going with it.


L-methylfolate is an activated form of folic acid. It’s considered activated because it’s able to donate a single-carbon methyl group to the process of synthesizing new neurotransmitters like serotonin, norepinephrine, and dopamine. Some studies have shown a beneficial effect from L-methylfolate use in depression, particularly among people with elevated levels of inflammation.

The dose needed to achieve the effect on depression is 15mg. It’s available in 15mg tablets in the U.S., but for some reason, in Canada, it’s only available as 1mg tablets. Popping 15 of those a day would get rather expensive rather quickly. I used to get it as an injection from a naturopath, but that was also expensive, so I stopped it even though it was helpful.

S-adenosyl methionine (SAMe)

S-adenosyl methionine (SAMe) is involved in the synthesis process for serotonin and other neurotransmitters. It may be useful as an add-on to another form of treatment for depression.

The recommended dose is 1600 mg/day. SAMe tends to be fairly pricey, so you might not get the best bang for your buck with this option.

What’s most important when considering the use of supplements in depression, or any illness for that matter, is to keep in perspective what they can and can’t do. I’ve ranted about this before, but just because something is “natural” doesn’t mean it’s safe or effective, and it doesn’t mean that the natural products industry has your best interests at heart. But if you’re looking for something else to add into your overall plan for managing your illness, a supplement or two might be worth a try.

Have you ever tried any supplements to help with managing your own illness?

book cover: Managing the Depression Puzzle, 2nd Edition, by Ashley L. Peterson

Managing the Depression Puzzle takes a holistic look at the different potential pieces that might fit into your unique depression puzzle.

It’s available on Amazon and Google Play.

35 thoughts on “Supplements for Depression that Actually Work”

  1. I take omega-3 tablets. I don’t think it does much for my depression, but as I don’t eat much fish, being semi-vegetarian, I figure I probably need a supplement. Someone also recommended zinc for depression. I don’t know whether that helps either. It’s hard to tell.

      1. They were funny in that they were both good and bad. Looking back, I think I tend to think of them more as bad. But, there were some good times that emerged out of those years. I’ll have to write more about them. 🙂

  2. I tried Ashwaghanda for better sleep and low and behold it did made me sleep longer and a little more relaxed. That was before the diagnosis and the start of medication.
    I used to take ‘Sedinal’ which are ‘natural’ medications made out of a mix of herbs. It did help a little but didn’t made a difference. I sometimes use it as an addition when I anticipate stressful times. I try to focus more on eating regularly and a little more healthy and I hope I can get some more vitamins in that way.

  3. I take omega 3’s, but never really noticed a difference in my depression or my inflammation/chronic pain (another reason I take it). I keep taking it just in case it is helping though lol. At least it is good for you I guess.

  4. I appreciate this writing. My doc put me on deplin (which is the L-methylfolate). I was afraid and thought he was out of his mind, although I tried it. I was actually taking it up to about a week ago when I ran out and the pharmacy had to order more. It is the most expensive drug that I take. I take that…Zoloft and rexulti. He also wanted me to take the n-acetyl cysteine but that scared me. I read up on all the stuff..and of course it said something about being used for Tylenol overdose (something like that). Again, I didn’t trust him, so I stopped at all the other drugs and didn’t add it. He knows that I am not taking it. I think I had to order it online…couldn’t find it anywhere. I look forward to reading your book about all of this. Thank you for this blog.

  5. We definitely have gut issues. Maybe being so much in fight/flight/etc. keeps our gut leaky. We have tried probiotics. Could not tell a difference, so stopped taking them because they were so expensive. We didn’t like fermented foods and liquids (taste). We are intolerant of so many foods. We follow FODMAP diet to a large extent. It’s something about sugar intolerance.

    We avoid all processed sugars, including honey but can tolerate maple syrup and molasses in small amounts. Sugar makes us so sick and sleepy and hungover. Have avoided it since the ’80s. We avoid lactose (goat cheese is okay) and gluten. If we cheat on gluten, we are often fine. If we cheat on dairy, the results can be very dramatic. The last affair with pizza ended so awfully that we may never try it again (sniff). Foods we miss that cause us harm include onions and cherries. But definitely pizza. And gluten-free goat cheese pizza tastes awful to us, so it’s no replacement. In Santa Fe, New Mexico, the trauma center provided gluten-free cracker crust with pizza sauce and then like 4,000 tons of pepperoni. It was edible, if salty lol. That was almost like medicine…

      1. We do the cooking so everyone else must bend to our whim bwahahahaha. Actually, they choose to eat our cooking probably because cooking is time-consuming and they’re pretty busy. It fulfills us to feed them, too. And we get poisoned less.

  6. I’ve tried St. Johns Wort but it didn’t help for me so I quit that. I am not sleeping well these days and have headaches. Maybe, I can take melantoline meds or something to sleep don’t know.

  7. Great post! SAMe was fantastic, in my experience. Except when it blasted me through the ceiling and into mania. This is probably why manufacturers don’t recommend it for those with bipolar disorder. I think N-acetylcysteine has some utility as an adjunct supplement for treating depression, although the positive effect is short-lived, from what I understand.

  8. Thanks for the interesting post.
    Pre-diagnosis I tried valerian root for anxiety, but it didn’t do much. Nowadays I take an omega 3 and 6 supplement with my other medications, but like you, I’m not sure if it has an effect.
    My partner had situational depression before I met him and he swears by St John’s Wort.

  9. I take a whole bunch of things like iron, vitamin d, zinc, magnesium, etc. But, some are to help with migraines and all are things I’m naturally deficient in. Being vitamin deficient can exacerbate depression, and standard panels don’t usually test for most of the things I’m deficient in. They don’t even test for ferritin as well as hemoglobin. So, it’s always worth making sure there aren’t underlying deficiencies that could be exacerbating depression in general (even if “supplementing” by itself for that same given thing wouldn’t necessarily help someone struggling with depression who *wasn’t* also deficient.) Especially if someone also has a chronic physical illness in addition to depression.

  10. Hi, Ashley. While reading this entry I kept thinking back to all the supplements my mother and/or friends were telling me about before I went into the hospital. SAMe, Turmeric, and SJW were the ones I tried over a period of 5 months. It did actually help with inflammation in a small way. However, it may have helped me if I wasn’t drinking, duh?
    I still take Turmeric along with my other medications, as well as Melatonin. I did mention in my entry yesterday that I plan on speaking to my psychiatrist in regards to being over medicated and maybe cutting down on some of it, or for that matter change something.
    I’m happy that I came across this entry and will ask my doctor if I can eventually change ove to some of what you shared here.
    Thank you!

  11. This was really informative, thank you for sharing. I’ve never actually tried supplements for depression but I’ve heard good things from a number of my friends who have – St John’s Wort being the most popular. Definitely some food for thought!

  12. Thank you for posting this. Times get so hard sometimes, You reach for something, ANYTHING that might help, but are more often than not, left with nothing. I want these options to help. I need them to help. ..I hope that they can help.

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