How to Treat Depression Naturally: Top 3 Supplements Backed by Science

If you’ve been exploring natural ways to manage depression, this is a great place to start. And the good news is, there are evidence-based options that go beyond psychotherapy and prescription meds. While there’s no magic bullet, certain supplements can genuinely help improve mood, energy, and emotional resilience. In this post, I’m sharing three natural supplements I use all the time with my patients: SAM-e, vitamin d, and omega-3 fatty acids.These are some of the most well-studied and effective tools for supporting depression naturally; whether you're just starting out or looking to enhance what you're already doing.

SAME-e

SAM-e (short for S-adenosylmethionine) is a compound your body makes naturally. It plays a key role in methylation, a process that helps regulate your nervous system, detox pathways, and most importantly neurotransmitters like serotonin, dopamine, and norepinephrine.

In fact, SAM-e has been linked to increased serotonin turnover and elevated dopamine and norepinephrine levels, which is exactly why it’s often used to support mood. Some even refer to it as the supplement version of the medication duloxetine (Cymbalta) because of its dual role in treating both depression and pain.

What the research says:

• A 2016 Cochrane review looked at eight clinical trials and found that while high-quality studies are still limited, SAM-e often showed similar effects to SSRIs in reducing depressive symptoms. Other reviews note that it “holds promise” as a complementary or alternative treatment.

• Earlier studies, like a 2002 American Journal of Psychiatry trial, found that SAM-e outperformed placebo and performed similarly to tricyclic antidepressants, but with fewer side effects.

• A 2010 study in the Journal of Clinical Psychopharmacology showed that adding SAM-e to SSRIs improved symptoms in people with major depression who hadn’t responded well to medication alone.

It works especially well in people with folate cycle issues or methylation imbalances—this is often seen in individuals with MTHFR variants.

I’ve personally used SAM-e many times with patients who either didn’t want to start medication or needed extra support alongside it and it often works really well. That said, it’s not for everyone (like if you have bipolar depression), and I think the biggest downside is that it can get pricey, especially at higher doses.

What to know before trying it:

• Typical dose: 400–1600 mg/day, usually in divided doses.

• Start low—SAM-e can feel a little stimulating at first, especially for those prone to anxiety.

• Take on an empty stomach for best absorption.

• Works best when paired with methylated B vitamins (like B12 and folate).

• Avoid if you have bipolar disorder unless supervised, as it can increase the risk of mood swings.

Vitamin D: Sunshine in a Capsule (Seriously)

You’ve probably heard of vitamin D as the “sunshine vitamin” and for good reason! Your body makes it when you're exposed to sunlight, and it’s involved in hundreds of bodily processes, including hormone balance, immune health, and yes, you guessed it—mood regulation.

Why it helps with depression:

Low vitamin D levels are incredibly common, especially in women, and have been consistently linked to higher rates of depression. One 2023 meta-analysis of 41 randomized controlled trials found that vitamin D supplementation significantly improved depressive symptoms, particularly in people who were deficient.

And when it comes to pregnancy and postpartum mental health, the research gets even more interesting:

• A U.S.-based study published in Evidence-Based Practice (2021) found that vitamin D deficiency during pregnancy was associated with an increased risk of postpartum depression, suggesting it may be a modifiable risk factor.

• Another study from the MGH Center for Women’s Mental Health observed that lower prenatal vitamin D levels correlated with higher postpartum depression symptoms in African American women, especially when inflammation was also present.

If you’re thinking, “well my vitamin D was normal and I’m still struggling.” Here's the part most people don’t realize, even your provider:

Many labs consider levels of 30 ng/mL “normal,” but research suggests optimal levels for mental health are closer to 50–75 ng/mL. That’s a big difference and one reason why it's worth getting your levels checked and interpreted through a mental health lens.

What to know:

• Most adults benefit from 2,000–5,000 IU/day, especially if their levels are under 50 ng/mL.

• Take it with a fat-containing meal (think avocado, eggs, or olive oil) to help your body absorb it.

• Going too high without supervision can lead to unwanted side effects. That’s why testing your levels is key to personalizing your dose.

Omega 3

Maybe you’ve heard that omega-3s can help with depression. Or maybe you’ve even tried a fish oil supplement yourself and didn’t notice much of a difference. The truth is, not all omega-3s are created equal, and the formula you took might not have been the right one for mood support. Let’s dig a little deeper into the two main types of omega-3s: EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Both are important for brain health, but when it comes to supporting mood, EPA is the one that really makes the difference.

There’s a lot of research out there, but study is worth highlighting:

A large 2019 meta-analysis published in Translational Psychiatry pooled data from 26 randomized controlled trials involving 2,160 participants and found that EPA, and not DHA, was the omega-3 that consistently helped improve symptoms of depression. The greatest benefit was seen when supplements contained at least 60% EPA, or were pure EPA formulations.

So what makes EPA more effective?

• Stronger anti-inflammatory effects: Depression is often linked to chronic inflammation. EPA helps reduce inflammatory markers more efficiently than DHA, which may explain why it’s more mood-lifting.

• Neurotransmitter support: EPA seems to play a bigger role in helping your brain make and regulate serotonin and dopamine (those feel-good brain chemicals we all rely on).

• More immediate action: While DHA is great for long-term brain structure (especially during pregnancy and early development), EPA seems to have a more functional role in day-to-day brain signaling and mood regulation.

What to know:

• Read your labels: Many fish oils are too low in EPA or too heavy on DHA, which isn’t as effective for mood. Look for formulas with at least 60% EPA—that’s the form shown to help most with depression.

• Target dose: Aim for around 1,000 mg of EPA per day.

• Skip the 3-6-9 blends: You likely get enough omega-6 and 9 from food—stick with a pure omega-3.

• Consistency is key: Daily use for 8–12 weeks is when results tend to show.

• Bonus points: Eating fatty fish 3x/week like salmon or sardines helps too!

Ready to Try a More Natural Approach To Depression?

You’ll always hear about the latest natural supplements for depression, but not every supplement works for every person. Genetics, gut health, nutrient levels, and medication interactions all influence how your body responds. That’s why a personalized, integrative approach to mental health makes such a difference. If you're in Florida and tired of traditional psychiatry, seeking a natural way to treat depression, or struggling with depression during pregnancy or postpartum, schedule a consult. We’ll talk about how integrative psychiatry can better support your mood, energy, and overall well-being—in a way that’s actually tailored to you. You don’t have to figure it out alone.

References

1. Liao, Y., Xie, B., Zhang, H., He, Q., Guo, L., Subramanieapillai, M., Fan, B., Lu, C., & McIntyre, R. S. (2019). Efficacy of omega-3 PUFAs in depression: A meta-analysis. Translational Psychiatry, 9, Article 190. https://doi.org/10.1038/s41398-019-0515-5

2. Bolland, M. J., Grey, A., Avenell, A., Gamble, G. D., & Reid, I. R. (2023). Effect of vitamin D supplementation on depression: Systematic review and meta-analysis. Critical Reviews in Food Science and Nutrition, 63(4), 616–628. https://doi.org/10.1080/10408398.2020.1865003

3. Vaziri, F., Nasiri, S., Tavana, Z., Dabbaghmanesh, M. H., Sharif, F., & Jafari, P. (2016). A randomized controlled trial of vitamin D supplementation on perinatal depression in Iranian pregnant mothers. BMC Pregnancy and Childbirth, 16, 239. https://doi.org/10.1186/s12884-016-1032-y

4. Sarris, J., Papakostas, G. I., & Schweitzer, I. (2016). SAMe for depression: A review of clinical studies. CNS & Neurological Disorders - Drug Targets, 15(4), 538–544. https://doi.org/10.2174/1871527315666160425110520

5. Sharma, A., Madaan, V., & Petty, F. D. (2006). Efficacy of S-adenosyl-L-methionine (SAMe) for treating major depression: A meta-analysis of randomized controlled trials. Journal of Clinical Psychopharmacology, 26(5), 507–511. https://doi.org/10.1097/01.jcp.0000235436.74822.2e

6. Cooney, G. M., Dwan, K., Greig, C. A., Lawlor, D. A., Rimer, J., Waugh, F. R., McMurdo, M., & Mead, G. E. (2013). Exercise for depression. Cochrane Database of Systematic Reviews, (9). https://doi.org/10.1002/14651858.CD004366.pub6

7. MGH Center for Women’s Mental Health. (2022). Exploring the relationship between vitamin D, inflammation, and postpartum depression. https://womensmentalhealth.org/posts/exploring-the-relationship-between-vitamin-d-inflammation-and-postpartum-depression/