Best with rhodiola

Pure Encapsulations Rhodiola Rosea

• Price: $$$$
• Dosage: 1 capsule 1-2 times per day
• Active ingredients: rhodiola extract

Rhodiola is an herb that, when taken in supplement form, has been linked to a variety of potential health benefits, including reduced depressive symptoms and an improved stress response (3).

Specifically, the herb is thought to benefit people with depression by reducing overactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis and affecting neurotransmitter receptors and molecular networks (3, 4, 5).

For example, studies focusing on adults with depression have found that taking rhodiola daily for 6 or 12 weeks led to clinically meaningful reductions in depressive symptoms (6, 7).

What’s more, while rhodiola treatment was less effective than the antidepressant medication Sertraline in one study, it caused many fewer side effects (6).

If you’re interested in taking a rhodiola supplement, this product from Pure Encapsulations is a great option.

The supplement contains 100 mg of rhodiola rosea, standardized to contain 3% rosavins and 1% salidrosides — bioactive components thought to be responsible for rhodiola’s therapeutic effects.

Plus, Pure Encapsulations is a company that takes product quality seriously.

The company exceeds standards set by United States Pharmacopeia (USP), an organization that sets strict product-specific standards for supplements.

Pure Encapsulations products are also third-party tested by independent laboratories such as Eurofins, Silliker, and Intertek.

Best with saffron

NOW Saffron 50 mg

• Price: $$$
• Dosage: 1 capsule two times per day
• Active ingredients: saffron

Saffron is a brightly colored spice that’s packed with antioxidant compounds, including the carotenoids crocin and crocetin. Interestingly, saffron has shown promise as a natural remedy for depression (8, 9).

Studies have observed that saffron increases levels of the mood-boosting neurotransmitter serotonin in the brain. While researchers do not know exactly how this process works, it’s possible that saffron inhibits serotonin reuptake, thereby keeping it in the brain longer (8, 9).

Two reviews from 2019 found that saffron significantly improved depression severity and was significantly more effective than placebo (8, 10).

What’s more, one review found that saffron supplements had similar effectiveness to antidepressant medication in reducing depressive symptoms (8)

NOW Saffron 50 mg provides a dose that has been shown to be effective for reducing symptoms of depression (11, 12).

What’s more, the supplement is affordable and easy to find at most nationwide pharmacies.

NOW supplements are made in a facility that’s certified by Underwriters Laboratory and exceeds the current good manufacturing practices (CGMPs).

The CGMPs are regulations set by the Food and Drug Administration (FDA) to ensure safe supplement manufacturing and processing.

Best with omega-3s

Nordic Naturals EPA Xtra

• Price: $$$$
• Dosage: 2 softgels per day
• Active ingredients: omega-3s (EPA, DHA, and other)

Omega-3 fats are essential fats, meaning you need to get them from your diet. Some studies show that omega-3 supplements may help reduce depressive symptoms in some people (13).

For example, one 2020 review of 10 studies including 910 people with MDD found that omega-3 supplements were superior to placebo treatments in reducing depressive symptoms and that higher dose omega-3 supplements were more effective than lower dose supplements (14).

Another 2020 review found that supplements with a higher ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) were particularly effective. EPA and DHA are two types of omega-3 fatty acids, both of which are concentrated in seafood (13).

While these findings are promising, more research is needed to investigate the effects of omega-3 supplements on depressive symptoms.

Research suggests that supplements with a greater amount of EPA are most effective for people with depression. Therefore, choosing an omega-3 supplement that delivers at least 1,000 mg of EPA may be best (14).

Nordic Naturals EPA Xtra meets this criteria, providing 1,060 mg of EPA and 260 mg of DHA per 2-softgel serving.

Nordic Naturals fish oil products are third-party tested to ensure the product meets strict standards for purity, potency, and freshness.

Plus, the company makes it easy to view the certificate of analysis (COA) for every batch of its supplements online for ultimate transparency.

Best with N-acetyl-L-cysteine

Pure Encapsulations NAC (N-acetyl-L-cysteine) 900 mg

• Price: $$
• Dosage: 1 capsule 1-2 times per day
• Active ingredients: N-acetyl-L-cysteine

NAC is a precursor to the amino acids L-cysteine and glutathione.

Glutathione is considered one of the most important antioxidants in your body and is critical for regulating inflammation and protecting cells from oxidative damage (15).

Taking NAC has been shown to offer several health benefits, including boosting your body’s glutathione levels (16).

Research shows that people with depression are more likely to have higher levels of inflammatory cytokines such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. Taking NAC may help reduce inflammation and ease depressive symptoms (17).

What’s more, NAC may improve neurotransmitter dysregulation in people with psychiatric disorders. The dysregulation of neurotransmitters such as dopamine and glutamate may be associated with mood disorders and schizophrenia, among other conditions (17).

Finally, a 2016 review of five studies concluded that treatment with NAC significantly reduced depressive symptoms and improved functioning in people with depression compared with placebo treatments. Plus, the NAC supplements were safe and well tolerated (18).

This supplement from Pure Encapsulations is a great NAC supplement because it contains just one active ingredient and is tested multiple times throughout manufacturing.

Best with vitamin D

Thorne Vitamin D/K2 Liquid

• Price: $
• Dosage: 2 drops 1-3 times per day
• Active ingredients: vitamin D3 and vitamin K2

Vitamin D is a critical nutrient that plays numerous essential roles in your body. However, many people don’t have sufficient vitamin D levels, often including people with depression.

Research shows that people with depression are more likely to be low or deficient in vitamin D. Those with the condition tend to have lower vitamin D levels than the general population, and people with the lowest levels tend to have the most significant depressive symptoms (19).

Vitamin D may reduce the risk of depression through several mechanisms, including by reducing inflammation, regulating mood, and protecting against neurocognitive dysfunction (19).

Several studies in people with depression suggest that taking vitamin D supplements may lead to significant improvements in depressive symptoms, quality of life, and illness severity (19, 20).

Keep in mind that more research is needed before vitamin D can be recommended as a universal treatment for depression. Additionally, it’s unclear whether vitamin D supplements are beneficial only for people with vitamin D deficiencies.

Thorne Vitamin D/K2 Liquid is a high quality vitamin D supplement that provides 1,000 IU (25 mcg) of vitamin D3, a highly absorbable form of vitamin D.

What’s more, each 2-drop serving also provides 200 mcg of vitamin K2, a nutrient that works together with vitamin D in the body (21).

Thorne is certified by NSF International, an organization that inspects manufacturing facilities and tests supplements for quality and potency.

Best with B vitamins

Klaire Labs B-Complex Plus

• Price: $$
• Dosage: 1 capsule per day
• Active ingredients: thiamine, riboflavin, niacin, vitamin B6, folate, vitamin B12, biotin, pantothenic acid, choline, inositol, and para-aminobenzoic acid

B vitamins play important roles in brain function and mood regulation.

B vitamins, including folate, B12, and B6, are necessary for the production and regulation of neurotransmitters such as serotonin, gamma-aminobutyric acid (GABA), and dopamine (22).

Older research suggests that deficiencies in vitamin B12 and folate may increase the risk of depression and that supplementing with these nutrients may help reduce depressive symptoms in certain populations (23, 24, 25, 26).

An older study also found B12 injections to be beneficial in people with MDD when used alongside antidepressant medication (27).

Additionally, a 2020 review suggested that taking vitamin B12 supplements earlier in life may delay the onset of depression and improve the effects of antidepressant medications (28).

Vitamin B6 has also been found to improve depressive symptoms when used in combination with other nutrients, including tryptophan and a form of vitamin B3 called nicotinamide (29).

Because several B vitamins may benefit people with depression, a B-complex supplement that contains all eight B vitamins may be the best choice.

Klaire Labs B-Complex Plus contains all eight B vitamins, including active forms of folate and B12 for better absorption. It’s also free of common allergens, including milk, shellfish, eggs, tree nuts, peanuts, gluten, and soy.

Klaire Labs supplements are made in a CGMP-compliant facility that meets FDA guidelines.

Best with zinc

Pure Encapsulations Zinc 15 mg

• Price: $
• Dosage: 1 capsule 1-4 times per day
• Active ingredients: zinc picolinate

Zinc is a mineral that’s critical to brain health and the regulation of neurotransmitter pathways. It also boasts antioxidant and anti-inflammatory properties (30).

Zinc deficiency is strongly linked to an increased risk of depression and depression symptom severity (30).

A 2020 analysis found that zinc supplementation significantly lowered symptom scores in people with depression (31).

Additionally, a 2021 analysis of 5 studies suggested that zinc supplementation may be useful for reducing depressive symptoms in people with clinical depression who are taking antidepressant medications. The studies used zinc doses of about 10-25 mg (32).

Pure Encapsulations offers a zinc supplement that’s made with high quality zinc picolinate and is tested multiple times throughout manufacturing.

The product is also available in a 30-mg zinc dose, so you can choose the dose that’s most appropriate for your nutrient needs.

Best with SAMe

Jarrow Formulas SAMe 400 mg

• Price: $$$$
• Dosage: 1 tablet per day
• Active ingredients: S-Adenosylmethionine

S-Adenosylmethionine (SAMe) is a sulfur-containing compound that has shown promise in the treatment of depression. It’s found naturally in your body and plays important roles in brain function.

A 2020 review of 8 studies found that SAMe, when used alone or with antidepressant medications, improved depressive symptoms in people with MDD. The studies used doses of 200-3,200 mg and treatment times of 2-12 weeks (33).

While this is promising, keep in mind that more research is needed before strong conclusions can be made.

Jarrow Formulas SAMe supplement delivers 400 mg of SAMe per tablet and is highly rated online.

Jarrow Formulas products are third-party tested by U.S. Department of Agriculture (USDA) accredited laboratories.

Best with magnesium

Bluebonnet Magnesium Glycinate

• Price: $$$
• Dosage: 4 capsules per day
• Active ingredients: magnesium bisglycinate

Magnesium is an important mineral that may benefit those with depression.

Magnesium deficiency is common among people with depression, and research shows that supplementing with it may reduce depressive symptoms (34).

A randomized study in 126 people with mild to moderate depression found that taking 248 mg of magnesium per day for 6 weeks significantly improved depressive symptoms compared with a placebo (35).

What’s more, very low magnesium intake has been significantly linked to an increased risk of depression, especially in younger adults (36).

Bluebonnet Magnesium Glycinate provides 100 mg of magnesium per capsule. You can adjust your dose depending on how much magnesium you need.

It’s also a good option because it contains magnesium glycinate, a highly absorbable form of magnesium (37).

Bluebonnet is certified by NSF International, and its products are certified gluten-free.

Best with creatine

Thorne Creatine

• Price: $$
• Dosage: 1 scoop (5 grams) per day
• Active ingredients: creatine monohydrate

Creatine is an organic acid that plays an important role in maintaining brain energy, among other functions. Altered brain energy levels are thought to be involved in the development of depression (38).

Some studies suggest that supplementing with 2-10 grams of creatine per day may reduce symptoms in people with MDD (39).

Also, a 2020 study that included data on 22,692 adults found that depression was 42% higher among adults with the lowest intake of creatine than among adults with the highest intake.

This protective effect seemed to be strongest in females, people ages 20-39, and those not taking antidepressant or anti-anxiety medication (40).

Thorne Creatine is a great creatine supplement because it contains just one ingredient and is NSF Certified for Sport — a third-party certification ensuring that the product is free of more than 270 substances banned by major athletics organizations.

Thorne Creatine is also unflavored, so it’s a versatile supplement that can be mixed with a beverage of your choice.