Last updated November 6, 2023.
Edited and medically reviewed by Patrick Alban, DC. Written by Deane Alban.
These proven supplements have a history of effectiveness and safety for depression vs prescription drugs. Learn how they work and get recommended dosages.
In recent years, the use of prescription antidepressants has continued to increase steadily.
But these drugs are not right for everyone.
Children, teens, pregnant women, and the elderly are not good candidates.
Prescription antidepressants work only about half the time, can have unacceptable side effects, and do not mix safely with many other medications and even some supplements.
While the safety and effectiveness of antidepressant drugs are in question, there is an array of supplements that are both safe and effective for treating depression.
The Top Herbal Supplements for Depression
Herbs have been used traditionally to treat depression in every culture.
Apparently, depression is not just a modern problem.
Here’s a look at some of the best herbal supplements for depression — those with a long history of safe use that have also been scientifically proven to be effective.
Caution: If you currently take a prescription antidepressant, talk to your doctor before making any changes to your medication.
1. Arctic Root (Rhodiola rosea)
Arctic root is found mainly in cold Arctic regions of Europe, Asia, and North America.
It’s been used since the time of the ancient Greeks to boost overall physical and mental vitality.
This herb is a top-rated adaptogen, a natural substance that increases resilience to physical and emotional stress.
It works by increasing the activity of brain chemicals that impact mood, such as serotonin, norepinephrine, and dopamine.
It also decreases inflammation, an underlying cause of depression.
Arctic root has been shown to reduce depression symptoms faster than antidepressant medications.
It’s particularly useful for depression accompanied by anxiety and fatigue, or when you need results quickly.
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2. Ashwagandha (Withania somnifera)
Ashwagandha is one of the most important herbs in the Indian Ayurvedic healing tradition.
Like Arctic root, it’s an adaptogenic herb.
What makes ashwagandha a standout is its ability to reduce levels of the stress hormone cortisol.
Ashwagandha is an excellent choice if you have depression together with stress, anxiety, and insomnia.
3. Chamomile (Matricaria recutita or Chamaemelum nobile)
Chamomile is a cheery, daisy-like plant that’s an excellent multipurpose relaxing herb.
It can be served as a tea, taken in capsule or tincture form, or used as a relaxing essential oil.
It’s so safe that it was traditionally used to treat childhood ailments such as diarrhea, colic, croup, and fevers.
Chamomile is particularly beneficial for those dealing with both depression and anxiety.
There are two main species of chamomile used medicinally — German or wild chamomile (Matricaria recutita) and Roman or English chamomile (Chamaemelum nobile).
German chamomile is more commonly used, but both offer similar health benefits.
4. Curcumin (Curcuma longa)
Curcumin is the main active ingredient in the Indian spice turmeric (Curcuma longa) which is renowned for its anti-inflammatory and brain-boosting properties.
Curcumin works by increasing levels of two feel-good neurotransmitters, serotonin and dopamine.
One clinical trial found it to be as effective for depression as the popular antidepressant Prozac.
It’s beneficial for obsessive-compulsive disorder (OCD) and major depressive disorder.
Both turmeric and curcumin supplements can be taken for depression indefinitely.
And, unlike some natural antidepressant supplements, curcumin can be safely combined with antidepressant drugs and actually enhances their effectiveness.
5. Ginkgo (Ginkgo biloba)
Ginkgo biloba is an ancient Chinese herb that’s now one of the most popular herbal supplements in the world.
Traditionally it has been used to improve memory; however, scientific research has found that this is not ginkgo’s best use.
But what ginkgo does do well is help with depression by reducing oxidative stress in the brain and modulating dopamine and serotonin.
Additionally, researchers have found through MRI imaging that ginkgo increases blood flow to the brain.
" A healthy brain is the first line of defense against depression and other mood disorders. Some vitamins are necessary for the formation of mood-boosting neurotransmitters, while others provide energy to brain cells or protect them from damage.
Ginkgo is another adaptogenic herb that reduces stress and anxiety by lowering levels of cortisol.
6. Saffron (Crocus sativus)
Saffron is one of the rarest and most expensive culinary spices.
It comes from the tiny red stigmas of the purple saffron crocus and must be harvested by hand.
A little-known benefit of saffron is that it’s one of the most promising herbal supplements for depression.
Several studies have found it to be as effective for depression as Prozac.
Saffron is also helpful for anxiety, stress, obsessive-compulsive disorder, and premenstrual syndrome.
The exact mechanism isn’t fully understood yet, but saffron seems to work by acting on serotonin metabolism.
One other notable benefit of saffron is that it reduces hunger and the urge to snack.
While saffron is generally considered safe, the only caveat is that high doses should be avoided by pregnant women since it can stimulate uterine contractions.
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When buying any supplement, quality matters — and with saffron, quality matters more than usual since saffron fraud is rampant.
Look for a supplement that’s manufactured by a reputable company and contains a standardized extract of Crocus sativus.
Historical note: Saffron fraud is nothing new. People have been faking saffron since the time of the ancient Greeks.
The Top Vitamin Supplements for Depression
Vitamin deficiency is not the first thing you think of when considering the underlying causes of depression.
Doctors and psychiatrists rarely recommend vitamins for depression either.
But clearly, your brain can’t operate at its peak when essential nutrients are missing.
A healthy brain is the first line of defense against depression and other mood disorders.
Some vitamins are necessary for the formation of mood-boosting neurotransmitters, while others provide energy to brain cells or protect them from damage.
Here’s a look at the most important vitamins for depression and their recommended dosages.
1. Vitamin B6 (Pyridoxine): A Serotonin Cofactor
Serotonin is the main brain chemical responsible for feeling happy, relaxed, and confident.
It also plays an important role in sleep, sex drive, and digestive health.
The most prevalent theory of depression is that it’s caused by a lack of serotonin.
This is why the most commonly prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs) which work by increasing serotonin levels in the brain.
Normally, serotonin is created in the brain and body from tryptophan, an amino acid commonly found in meat, poultry, fish, and dairy products.
Tryptophan provides the basic building blocks used to synthesize serotonin, but certain cofactors — vitamin B6, folic acid, vitamin C, iron (Fe), magnesium (Mg), calcium (Ca), and zinc (Zn) — must be present for this reaction to take place.
You can see that vitamin B6 is used twice in this two-step conversion process, which helps explain the correlation between low blood levels of vitamin B6 and depression.
Vitamin B6 is also needed to make dopamine, another neurotransmitter associated with depression.
Additionally, large doses of vitamin B6 have been found to alleviate both depression and anxiety by increasing GABA, the neurotransmitter of relaxation.
Low levels of vitamin B6 contribute to chronic inflammation, an underlying cause of many health conditions, including mood disorders and neurological diseases.
There’s a growing body of evidence that chronic brain inflammation may be a root cause of depression.
Vitamin B6 Supplement Dosages
The RDA (Recommended Dietary Allowance) for vitamin B6 is 1.3 mg daily for most adults.
Pregnant women need more (1.9 mg), as do seniors (1.5 mg for women, 1.7 mg for men).
If you take supplements like 5-HTP or tryptophan for depression, look for one that includes B6 in the supplement’s formulation.
Without this vitamin, these ingredients can’t do their intended job of increasing serotonin.
2. Vitamin B9 (Folate): Enhances Antidepressant Drugs
Vitamin B9 is usually called folate or folic acid.
People with major depression consistently have low blood levels of folate.
Folic acid acts as an antidepressant by affecting serotonin receptors in the brain.
It enhances the effects of antidepressant medications such as Prozac and the natural antidepressant SAM-e.
The potential benefits of taking folic acid for depression are so great that one study concluded that all patients with depression should be treated with folic acid.
Also, folate protects the brain from environmental neurotoxins and from the buildup of the toxic brain plaques that are a factor in Alzheimer’s.
Vitamin B9 Supplement Dosages
The terms folate and folic acid are used interchangeably but are not exactly the same.
Folate occurs naturally in foods, while folic acid is a synthetic form found in supplements and fortified foods.
The recommended dietary allowance of folic acid is 400 mcg for most adults and 600 mcg for pregnant women.
Some people have a mutation in the MTHFR (methylenetetrahydrofolate reductase) gene that makes it hard to process vitamin B9.
If you know or suspect that you have this gene, look for folate supplements that use the methylated folate form rather than the usual folic acid form of vitamin B9.
3. Vitamin B12 (Cobalamin): For Nerve and Brain Health
Vitamin B12 is found in everyday foods, yet vitamin B12 deficiency is surprisingly common, affecting approximately 40% of all adults.
B12 is critical for a healthy nervous system and for the formation of serotonin and dopamine.
Symptoms of inadequate B12 include depression, anxiety, brain fog, memory loss, mental confusion, and schizophrenia.
Vitamin B12 deficiency can be quite serious and should not be taken lightly.
If left untreated, it leads to irreversible nerve damage and can be life-threatening.
There are many reasons for widespread B12 deficiency — vegetarian diets, acid-suppressing drugs, and malabsorption issues.
If you suspect you are deficient in this important nutrient, get your vitamin B12 blood level checked and supplement accordingly.
Vitamin B12 Supplement Dosages
You’ll find several forms of B12 in supplements — cyanocobalamin, methylcobalamin, adenosylcobalamin, and hydroxocobalamin.
There seems to be little difference in absorption or bioavailability for most people.
The RDA for vitamin B12 is 2.4 mcg/day, but if you look at supplement labels, you’ll find that most supplements contain much more.
Manufacturers provide megadose levels of B12 since only about 2% of it is actually absorbed.
There are no known adverse effects from taking these large doses.
Interestingly, for those with compromised digestive systems, supplemental B12 is absorbed more efficiently than B12 from food, where it’s bound to protein.
4. Vitamin C (Ascorbic Acid): A Natural Antidepressant
Vitamin C isn’t just for colds; it’s also a proven stress reducer and antidepressant.
It slows the release of cortisol which, in excess, increases susceptibility to depression.
People with low vitamin C levels are often depressed and fatigued.
One study found that participants who took vitamin C reported feeling happier, often within as little as one week.
Vitamin C is yet another serotonin cofactor that acts as a natural antidepressant.
Severe vitamin C deficiency causes mice to act depressed by reducing serotonin and dopamine levels in their brains.
Researchers found that vitamin C enhanced the effectiveness of the antidepressant Prozac in children who were depressed.
Vitamin C is required to produce norepinephrine, a chemical that acts as both a stress hormone and a neurotransmitter.
Some antidepressants like Wellbutrin and Cymbalta work, in part, by raising norepinephrine levels.
Vitamin C is also a potent antioxidant.
Antioxidants protect the brain by reducing free radical damage and inflammation, potential causes of depression.
Vitamin C Supplement Dosages
The RDA for vitamin C is 75-90 mg/day, but most experts believe this amount to be ridiculously low.
Most studies use much higher dosages.
One study on depression had participants taking 3,000 mg per day.
If you don’t normally take vitamin C, 250-500 mg per day is a reasonable place to start.
You can safely take more, but doses over 2,000 mg per day can cause digestive upset in some people.
5. Vitamin D: The Sunshine Vitamin
Vitamin D has profound effects on the brain during all stages of life, from infancy through senior years.
Insufficient vitamin D is linked to an array of mental disorders in seniors, including depression, bipolar disorder, schizophrenia, dementia, and Alzheimer’s.
A major meta-analysis of studies that included over 31,000 participants linked low levels of vitamin D to depression.
It’s not fully understood how vitamin D helps depression, but a prevailing theory is that it boosts levels of serotonin, dopamine, and norepinephrine — all feel-good brain chemicals necessary for a positive mood.
Vitamin D may alleviate depression by being anti-inflammatory.
One study found that suicidal patients had low vitamin D levels and high concentrations of compounds that promote inflammation.
One systematic review of studies concluded that vitamin D compares favorably to fluoxetine (Prozac) as an antidepressant.
This is not surprising since vitamin D regulates the conversion of tryptophan into serotonin.
Additionally, vitamin D has been shown to enhance the effectiveness of Prozac.
Vitamin D Deficiency Is Epidemic
Vitamin D deficiency is an “ignored epidemic” that affects over 1 billion people worldwide.
Vitamin D is synthesized when skin is exposed to sunlight.
But most of us spend too much time indoors or covered with sunscreen to manufacture appreciable amounts, even during the summer months.
Low levels of vitamin D, rather than fewer hours of daylight, may be the underlying cause of seasonal affective disorder, a type of depression that affects millions during the winter.
By far the best way to increase vitamin D is from exposure to the sun.
But if you live north of the 37th parallel (see the red line in the image below) in the northern hemisphere or south of that in the southern hemisphere, the sun’s rays are too weak to trigger vitamin D production most of the year.
It’s only when the UV index is greater than 3 that the needed UVB wavelengths are present in sufficient amounts to produce vitamin D.
You can find your current local UV index at Weather.com or Accuweather.com, or by using a reputable UV index app.
Food Is Not an Effective Way to Get Vitamin D
It’s very difficult to get all the vitamin D you need from food.
There are only a few foods that contain vitamin D3, the best-utilized form.
The top food sources are salmon, mackerel, tuna, and sardines.
Small amounts are found in beef liver, cheese, and egg yolks.
Some foods contain vitamin D2, such as mushrooms, fortified milk, and orange juice, but the body does not utilize the D2 form well.
This makes vitamin D supplementation the only viable option for most people unless you spend time outside in a location that’s warm and sunny year-round.
Vitamin D Supplement Dosages
Vitamin D dosages were previously labeled in IU (International Units).
But the US Food and Drug Administration now requires that food and supplement labels list the amount in micrograms (mcg) as well.
Note that 1 mcg is equivalent to 40 IU.
The current RDA for vitamin D is 15 mcg (600 IU) per day, but this amount is hotly contested.
Some experts believe that we need ten times this amount for good health.
The only way to know your vitamin D status for sure is to take a 25-hydroxy vitamin D test.
You can see your doctor or order a vitamin D test online here.
If you have depression, this is a worthwhile investment in your mental health.
Vitamin D is so important for depression that your doctor should ideally run this test before prescribing you an antidepressant.
And since vitamin D is fat-soluble and gets stored in the body’s fat cells and liver, it is possible to accumulate too much of it — another good reason to get your level checked.
Interestingly, excessive sun exposure does not result in vitamin D toxicity since the body has a way of regulating vitamin D production.
When choosing a supplement, be sure to buy from a reputable company you can trust.
A study on 55 brands of vitamin D supplements found that the contents diverged wildly, containing as little as 9% and as much as 146% of the vitamin D listed on the label.
6. Multivitamin Supplements (really!) for Depression
Modern life is full of vitamin drains.
Alcohol, caffeine, smoking, stress, sugar, toxins, prescription medications, and malabsorption issues are among the many factors that increase the brain’s demand for vitamins.
Don’t underestimate the power of a good multivitamin supplement for boosting brain health and function.
Numerous studies confirm that taking a high-quality multivitamin alone can improve mood by reducing stress, anxiety, and depression while improving memory, attention, and overall cognitive function.
There are occasions when a single-nutrient supplement is warranted.
But starting with a reputable multivitamin and mineral supplement is a convenient, economical way of covering your basic nutritional needs.
Taking a multivitamin supplement as insurance can help you be healthier and happier and may even help you live longer.
Two Depression Supplements to Use With Caution
Just because a supplement is natural doesn’t necessarily mean that it’s without risks.
Here are two supplements often taken for depression that don’t meet the criteria of being both safe and effective.
St. John’s Wort (Hypericum perforatum)
St. John’s wort is one of the most popular herbal supplements for depression, but it’s not one we recommend.
It has a deserved reputation for causing side effects and negative interactions.
Ironically, reported side effects of St. John’s wort can be very similar to those of SSRI antidepressants — anxiety, dizziness, confusion, nausea, dry mouth, sexual dysfunction, and anxiety.
Compared with other herbal supplements, St. John’s wort is more likely to have negative drug interactions.
It has known interactions with several hundred medications.
When taken with antidepressants, it can cause serotonin syndrome, a potentially fatal condition.
St. John’s wort should not be taken by women who are taking birth control pills since it can render them less effective.
5-HTP
5-HTP is another popular supplement for depression that we recommend only as a last resort.
A meta-analysis of over 100 studies concluded that there is insufficient evidence that 5-HTP helps depression.
Importantly, 5-HTP is not recommended for long-term use since it often stops working after a few months.
Additionally, it increases serotonin at the expense of other equally important neurotransmitters.
And finally, it is not safe to mix 5-HTP with antidepressants or numerous natural remedies, including St. John’s wort.
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