Some natural and dietary supplements—such as folic acid, GABA, SAMe, tryptophan, and vitamin D—may help ease mild symptoms of depression like fatigue, low mood, and sleep problems. However, claims from supplement manufacturers are not always backed by strong scientific evidence, and their ingredients can vary in potency and quality.

Severe depression typically requires medical treatment, which may or may not include antidepressants.

1. Folic Acid

Folic acid is the synthetic form of folate (vitamin B9), found in leafy greens, fruits, and other foods. It influences neurotransmitters in the brain such as monoamines. Low folate levels have been linked to an increased risk of depression.

However, more recent research suggests that vitamin B12 may have a stronger connection to depression than folate. Folic acid might be more beneficial when used alongside antidepressant medication.

Forms like 5-MTHF and L-methylfolate could also be helpful, but caution is advised when purchasing non-prescription supplements labeled as “optimized folate.”

2. GABA

GABA (gamma-aminobutyric acid) is a neurotransmitter that promotes relaxation and reduces stress. People with depression and anxiety often have lower GABA levels.

Animal studies have shown that GABA may have antidepressant-like effects, though more human research is needed. GABA is available in capsule, tablet, or powder form.

3. Omega-3 Fatty Acids

Omega-3s such as EPA and DHA are important for brain and heart health. They are commonly found in fish oil supplements. While some research supports the use of omega-3s for depression, results are mixed, and no clear consensus exists.

Despite this, omega-3s generally have few side effects and may offer additional cardiovascular benefits. They may be worth considering—with guidance from a healthcare provider.

4. Saffron

Saffron, a spice derived from crocus flowers, has been used in traditional medicine to treat mood disorders. Supplements are available online, though they are not yet widely available in stores.

Studies suggest saffron may be more effective than a placebo for mild to moderate depression but not more effective than prescription antidepressants like fluoxetine or citalopram.

Further research is needed to confirm its exact effectiveness.

5. SAMe

SAMe (S-adenosylmethionine) is a naturally occurring compound in the body that influences serotonin and dopamine. Low levels of SAMe are associated with depressive symptoms.

SAMe may be more effective when combined with other treatments. In one study, it was paired with a probiotic (L. plantarum HEAL9), and participants reported symptom improvement after two weeks.

However, SAMe may trigger mania in people with bipolar disorder, so consult a doctor before using it.

6. Tryptophan

Tryptophan is an amino acid that helps the body produce serotonin. It’s available over the counter as L-tryptophan or 5-HTP, which are both steps in the serotonin production process.

Studies have shown that low tryptophan levels may worsen emotional processing in people with depression. However, safety concerns have arisen in the past: In 1989, contaminated L-tryptophan supplements were linked to a rare blood disorder and several deaths.

L-tryptophan should be used cautiously and not for extended periods without medical supervision.

7. Vitamin D

Vitamin D is produced naturally by the body in response to sunlight, and it's also found in food and supplements. It’s essential for bone health and may influence emotional regulation.

Some studies suggest that people diagnosed with depression may benefit more from vitamin D supplementation than those who only have mild symptoms.

8. Zinc

Zinc is a vital nutrient involved in immune function, wound healing, and cellular growth. A deficiency in zinc has been linked to a higher risk of depression since the 1980s.

Research suggests that people with low zinc levels may be more susceptible to developing depressive symptoms. Zinc supplements may be useful in supporting mood and emotional health.

How To Choose the Right Supplements

Always consult a healthcare provider before starting any supplements. Effectiveness varies depending on the type, dose, duration, and whether it interacts with medications you’re already taking.

Things to consider include:

  • Cost: Compare different brands and options to get good value.

  • Form: Choose the most convenient form—capsules, powders, or tablets.

  • Ingredients: Read labels carefully for allergens, additives, or preservatives.

  • Drug interactions: Make sure the supplement doesn’t interfere with any prescription drugs or other supplements you use.

The FDA does not tightly regulate dietary supplements. Choose products that are third-party tested by reputable organizations like NSF International, USP, or ConsumerLab.

When To Contact a Healthcare Provider

You should contact a healthcare provider if you have three or more symptoms of depression that last longer than two weeks. Some signs to watch for include:

  • Crying without a clear reason

  • Taking medications that may be linked to depression

  • Signs of alcohol use disorder (such as guilt after drinking)

  • Hearing or seeing things that aren’t there

  • Suspecting that a child or teenager may be depressed

Suicide Prevention

Suicidal thoughts can be a complication of depression. If you or someone you know is in crisis, call 911 immediately. You can also contact the 988 Suicide & Crisis Lifeline:

Quick Summary

Folic acid, GABA, SAMe, tryptophan, and vitamin D are natural supplements that may support mental health and reduce symptoms of mild depression. Speak with a doctor before taking any supplements to ensure safety and effectiveness. Clinical treatments such as medication and therapy may also be necessary depending on your condition.

Other supportive treatments include light therapy, mindfulness, and physical activity like yoga.