The Best Natural Antidepressants: An Evidence-Based Guide

Fighting depression and anxiety is a widespread malady in our society today. Not only are many people taking antidepressant medications, but many more are struggling with anxiety, negative thoughts, dark moods, and are struggling to find hope for the next day. And the medications come with unpleasant, often dangerous side effects. If you are looking for natural antidepressants that actually work, you’ve come to the right place.

While supplements and herbal remedies only address the physical aspects of this epidemic, they can be useful alongside the rest of the therapy. In a previous blog, I mentioned the four pillars of dealing with depression and anxiety. Those four pillars are: 

1. Physical health

2. Satisfying relationships

3. Finding meaning in life

4. Avoiding substance misuse and abuse 

Taking antidepressant drugs just blunts your emotions so that you can cope, but they don’t resolve the underlying issues in life that are causing your depression and anxiety.  However, it is hard to work on life when your brain is functioning poorly, i.e., it is anxious and depressed. So, here are the 8 best natural antidepressants for supporting emotional health. They’ve helped thousands of people feel calmer, happier, and more emotionally stable. And they can help you, too.

The items listed in this article have been tested in real human studies, not just in lab mice. And the proof undergirding this article comes from large systematic reviews that have examined dozens of studies with hundreds or even thousands of people.

1. EPA-Rich Fish Oil (Omega-3s)

• Best dose: 1,000–2,000 mg of EPA per day. Most fish oil contains more EPA than DHA, which the evidence says is best for depression. DHA is also excellent for cognitive health, so take fish oil that contains both.
• How to take it: With any meal that has fat (breakfast or dinner)
• Why it helps so much: Depression and anxiety create extra inflammation in the brain. EPA is like a fire extinguisher for that inflammation and also helps serotonin work better.
• Real proof:
  • A 2023 review of 10 high-quality studies (1,400+ people) showed that EPA-rich fish oil clearly lowered depression scores. The people who felt the biggest difference were the ones who started with low omega-3 levels.
  • Another 2023 review of 23 trials (2,189 people) found that when people took more than 2 grams of total omega-3 oil, it also calmed anxiety and racing thoughts. Lower doses had no significant effects. You have to get enough for it to work.
  • Many doctors now say EPA is the single most proven natural mood helper.
• Action Step: If you do nothing else, take fish oil with plenty of EPA in it to support a positive mood and emotional stability. This one step will move you in the right direction.

2. Vitamin D3

• Best dose: 5,000+ IU every evening with food
• Goal: Get your blood level to 60–80 ng/mL (verify with 25(OH)D blood test)
• Why it helps: Your brain is loaded with vitamin D receptors. When you’re low, serotonin (the feel-good chemical) drops. A real deficiency (25(OH)D < 20 ng/ml) results in a 2 to 3 times higher risk of depression. 
• Real proof:
  • A 2025 meta-analysis of 20 studies showed that, for many people, raising low levels of vitamin D made depression scores drop just as much as if someone started an antidepressant.
  • Another systematic review and meta-analysis of 31 studies (24,000+ people) from the end of 2024 concluded that vitamin D3 supplementation may reduce depressive symptoms, particularly in individuals with depression, with the greatest effect observed at 8,000 IU/day. The effect was more pronounced in short-term trials (less than 24 weeks) compared to longer trials.
  • People who get very little sunshine or who live far north or south of the equator are at higher risk for low vitamin D3 levels. These people see the biggest mood boost from taking supplemental vitamin D3.
• Action Step: If depressed, get a simple 25(OH)D test. Take 5,000 IU/day until you get tested, just to avoid being deficient. Best if taken with K2 at the same time. Look for a D3 / K2 formula.

3. Magnesium (amino acid chelate form, like glycinate or threonate)

• Best dose: 400-500 mg of magnesium daily, usually splitting morning and evening.
• Why it helps: Magnesium is the anti-stress, relaxing nutrient. It turns on the “relax” switch (GABA) and turns down the “stress” switch (cortisol). About half of the people with depression are deficient in magnesium, which ruins their sleep and makes it harder to control their emotions.
• Real proof:
  • A 2023 review of  7 randomized controlled studies (325 people) with diagnosed depression found that 4–6 weeks of magnesium lowered their scores on standard depression tests.
  • Results aren’t always instant, but many people notice they fall asleep faster and wake up less anxious within the first week.
• Action Step: Order a bottle of supplemental magnesium, and after taking the whole bottle (400 mg/day), evaluate whether you sleep better and are less anxious. 

4. Zinc (amino acid chelate or citrate form)

• Best dose: 25–30 mg with a meal (don’t take it on an empty stomach)
• Why it helps: “Think zinc,” is a motto I heard years ago, emphasizing the importance of zinc for brain health. And it is still true. One way zinc helps is by being a cofactor in reactions to recycle serotonin and grow new brain connections by supporting production of BDNF (brain-derived neurotrophic factor = growth hormone/fertilizer for brain cells).
• Real proof:
  • A large 2022 analysis showed that people who took zinc by itself felt about 4 points better on the usual depression rating scales—that’s enough for most people to say “I actually feel normal again.”
  • It works even better if a blood test shows you started low on zinc (very common in the U.S.).
• Action Step: Order a bottle of supplemental zinc and see how you feel after taking 25-30 mg per day.

5. L-Methylfolate (the active form of folic acid)

• Best dose: 5–15 mg once a day (start with 5 mg if you’re new to it)
• Who needs it most: People with the MTHFR gene change (about 4 out of 10 people) or anyone whose antidepressants never worked well.
• Why it helps: L-methylfolate is the bio-active form of folate. It participates in one-carbon methylation reactions that make neurotransmitters and clear out toxic homocysteine. Good methylation means a happy, fast, clean brain; poor methylation results in a sluggish, inflamed, depressed brain.
• Real proof:
  • A 2022 review found that adding L-methylfolate made twice as many people finally respond to their antidepressant.
  • Some people feel a lift in energy and mood within 1–2 weeks.
• Action Step: If you are taking antidepressants, but they haven’t worked well, get a bottle of methyl-folate to complement your antidepressant.

6. CurQfen Curcumin

• Best dose: 500–1,000 mg a day (CurQfen, Longvida, Meriva, or BCM-95 are the brands that actually get into your brain. Our review of the different advanced curcumin formulas shows that CurQfen has the best evidence supporting its efficacy.)
• Why it helps: Curcumin lowers inflammation and raises BDNF (mentioned above)—the “fertilizer” protein that helps your brain grow new cells and connections.
• Real proof:
  • A 2019 meta-analysis of 10 studies (over 500 people) showed curcumin worked about as well as Prozac for mild-to-moderate depression, and it also helped anxiety.
  • People who took the special high-absorption kinds saw results in 4–8 weeks.
• Action Step: Get a bottle of CurQfen Curcumin and take two capsules a day. Then evaluate your depression and anxiety at the end of that and see how you feel. See if it’s helpful to you. 

7. Saffron (standardized extract – look for affron® or 30 mg of 2% safranal)

• Best dose: 15 mg twice a day (morning and evening) or one 30 mg capsule
• Why it helps: It gently blocks the re-uptake of serotonin and dopamine, which is exactly what many prescription antidepressants do.
• Real proof:
  • A recent 2025 meta-analysis of 8 studies that compared saffron directly to drugs like Prozac, Zoloft, and Lexapro found that saffron worked just as well and caused far fewer side effects (no weight gain, no sexual problems).
  • It’s now one of the few herbs that doctors in Europe can officially prescribe for depression.
• Action Step: If you are taking a SSRI drug, work with your doctor to move over to a standardized saffron supplement. Get the benefits without the side effects.

8. Silexan (Standardized Lavender Oil) Capsules (optional – perfect if anxiety is your biggest problem)

• Best dose: 80–160 mg once or twice (1 or 2 capsules) a day
• Why it helps: The special lavender oil in Silexan calms the same brain receptors that Valium and Xanax use, but you stay clear-headed, and it’s non-addictive.
• Real proof:
  • A 2023 meta-analysis of five double-blinded randomized controlled trials (over 1,200 people) showed Silexan works as well as low-dose anxiety medicines, but people felt sharper the next day and had almost no side effects.
  • It’s approved in Germany as an actual anxiety medicine.
• Action Step: If you suffer more with anxiety than depression, Silexan may be a great addition to your protocol.

Here’s an eight-week starter plan:

If you aren’t sure where to start, here’s an idea to get you going. 

For the first month, add in the basics, what I call the “core four”: 

• Fish oil
• Vitamin D3
• Magnesium
• Zinc

Then, evaluate how you feel just adding those basics in. You might find that that’s enough right there, and you feel great with just that. Just keep on taking these supplements. These are core supplements for everybody anyway. 

In the second month, if you feel like you still need more help, fill up your stack:

• L-methylfolate
• Curcumin
• Saffron

When tested separately, all three of these supplements helped with depression and anxiety. Taken together, they should work very well. By the end of two months total, you should be able to tell if this is all making a difference for you.

If your anxiety is really high, go ahead and add in the Silexan standardized lavender oil right from the beginning. 

Wrapping It Up

Thousands of people, including a growing number of psychiatrists, are using versions of this same positive mood stack in 2025. They aren’t silver bullets, but they are the closest thing that we have so far that gives you a natural way to counter anxiety and general depressive disorder with much fewer side effects. 

Some of these items are just building blocks and cofactors (fish oil, magnesium, zinc, D3, L-methylfolate) that your body needs anyway. Nothing is wasted here. Then curcumin, saffron, and lavender oil have other natural benefits that go beyond their brain-boosting actions. No side effects, just side benefits. Welcome to natural medicine, where side benefits are normal, and side effects are nearly non-existent.

So talk to your doctor or a functional medicine practitioner to help you make informed treatment choices. And don’t forget, this helps with the physical health pillar of the four pillars that upholds mood stability. While you still need to work on other factors that contribute to your depression and anxiety, this can give you the emotional stability you need to effectively manage them.