Update 7/20/22. As I write these words it's coming up the 20 years since my mom and dad passed away. As you can guess, it doesn't help it's Christmas time either. While I try to stay busy, I know depression during Christmas/Hanukkah is very common. I also know sometimes we may need a little help during this time, such as natural solutions for depression. But which supplements for depression work? In this review, I'll show you 6 popular supplements that have been clinically shown to help depression. I'll also show you some of their side effects too. Below that, I'll tell you which I think is best. Leave a comment below if you have questions or just want someone to listen to you. I'm listening.
1. St. John's Wort
St. Johns's wort is probably the most famous natural antidepressant. Also known by its scientific name Hypericum perforatum, St. Johns wort has been studied more than any other supplement for depression. In my review of the research, I discovered 19 clinical studies on St. John's wort showing it helped alleviate mild to moderate levels of depression. There may be more. I stopped counting at 19.
Depression Symptoms
Mild / Moderate Depression | Major Depression |
loss of interest in things you once enjoyed | suicidal thoughts |
lack of motivation | attempting suicide |
sudden lack of socializing | hallucinations |
fatigue/insomnia | |
changes in body weight | |
reckless behavior – sex, drugs, alcohol, etc. |
In one investigation researchers in Germany randomly gave 263 people either:
- St. John's wort (1050 mg per day)
- a placebo
- depression drug (Tofranil)
for 8 weeks.
Results showed St. John's wort was more effective than the placebo -and just as effective as the antidepressant drug.
Other studies comparing St. Johns's wort to antidepressant medications have also found it works as well as anti-depressant drugs. The benefits appear to be similar in both men and women.
Even in those who suffer from really bad, major depression, some research finds St. Johns's wort can help. That said, it's always best to get professional help when you think you or a loved one has major depression.
St. Johns's wort may be taken as a capsule or as a liquid extract. Like many natural treatments, results may take a couple of weeks to see a difference. Here's a quick video on this herb:
How Much St. John's Wort Works?
Several studies have used 300 mg, taken 3 times per day (900 mg total per day). Some supplements indicate how much hypericin they contain. Hypericin is considered one of the active ingredients in St. John's wort. Look for supplements containing a 0.3% hypericin extract.
St. John's Wort Precautions
Some things to consider before taking St. Johns's wort are as follows. This list is not complete:
- Start with less than is recommended for the first week
- Don't take if you are pregnant or breastfeeding
- Speak to your doctor and pharmacists first if you take ANY medications
- Speak to your doctor first if:
- you have ANY health problems
- you take other dietary supplements
- you have bipolar disorder, schizophrenia or similar issues
- Stop taking St. Johns wort at least 2 weeks before having surgery
St. John's wort & Birth Control Pill Warning
Watch on my Youtube channel if you prefer.
2. SAMe
SAMe (pronounced “SAMMY”) is short for S-adenosyl-L-methionine. It's a substance we make in the body. Generally, we make a lot of SAM-e when we are young. It tends to decrease with age. Both vitamin B12 and folic acid are needed to make SAMe.
At least 9 human clinical trials have documented SAM-e to be effective for depression. Various trials have noted SAM-e supplements help depression by itself and some have even shown it to be more effective than anti-depression medications called tricyclics.
Like most natural therapies, not all studies find SAM-e works. But there are more investigations finding SAM-e helps depression than not. Here's a video describing the supplement
As an added bonus, multiple studies have noted SAMe appears to be a natural COX2 inhibitor, helping reduce osteoarthritis pain. In theory, this may be another way SAM-e helps.
In other words, if you have less arthritis pain, you are more likely to go outside and do more stuff. More exercise/activity and more socializing with people can also help reduce depression.
How Much SAM-e Do I Take For Depression?
SAMe clinical trials tend to use 800-1600 mg per day, divided into equal dosages. For example, if the capsule is 400 mg, use it 2 to 4 times per day. For best results, take SAMe on an empty stomach.
SAMe Precautions
For most people, SAMe seems generally safe. Some things to consider first include the following. This list is not complete:
- Start with less than is recommended for the first week
- Stop taking at least 2 weeks before surgery
- Talk to your doctor if you are pregnant or nursing
- Talk to your doctor if you have bipolar disorder
- SAM-e may be inappropriate if you are taking certain antidepressant medications
- SAM-e may interact with medications or supplements which raises serotonin levels
- Use caution if you have Parkinson's disease
3. Eicosapentaenoic Acid
Most know eicosapentaenoic acid by its other name – EPA. The name is pronounced “I-kona-pen-ta-ah-know-ick acid.” EPA, along with DHA, are the fish oils that form the basis of most fish oil supplements.
Fish oils are a type of polyunsaturated fatty acid (PUFA).
Besides the reputation fish oils have for being heart-healthy, several studies have noted EPA may alleviate feelings of depression. Some investigations have noted that fish oil supplements -composed mostly of EPA – work better than supplements containing equal amounts of EPA and DHA (DHA is the other fish oil).
To be fair, not all studies have shown EPA helps depression symptoms. For example, in a clinical trial involving 196 people, neither 1000 mg EPA or 1000 mg DHA helped relieve symptoms.
How Much EPA Helps Depression?
Studies have used 500 mg to 1000 mg per day. Most supplements contain a combination of EPA and DHA. If using a combination of both, look for supplements having more EPA than DHA.
EPA Precautions
In healthy people, EPA -and DHA – are considered safe. A typical piece of salmon has about 1000 mg of EPA and DHA. Here are some things to consider when taking fish oil supplements. This list is not complete:
- Start with less than is recommended for the first week
- Talk to your pharmacist/doctor if you take any medications like blood thinners or cancer medicine.
- Talk to your doctor if you are pregnant/breastfeeding
- EPA might lower blood pressure. Speak to your doctor if you take blood pressure medicine
- Stop taking fish oil supplements at least 2 weeks before surgery
- In theory, EPA may bolster the effects of other supplements with blood thinner properties
Here's the EPA/DHA Supplement I Take
4. 5-Hydroxy-Tryptophan (5-HTP)
The substance 5-HTP (sometimes called L 5-HTP) comes from the amino acid tryptophan. When we take 5-HTP, it's converted to serotonin, a mood-enhancing brain chemical. This is how 5-HTP is thought to work. Several studies, many carried out in the 1970s found 5-HTP supplements given to people can reduce anxiety and depression symptoms.
In one investigation, researchers in India conducted an 8-week study where they gave 60 people either 5-HTP supplements or Prozac, a popular SSRI anti-depressant drug. People were given up to 400 mg of 5-HTP. Those taking 5 -HTP started showing improvements in depression after only 2 weeks.
5-HTP was seen to be about as effective as Prozac.
In the past, 5-HTP was only available by prescription. When the supplement law was revamped in the 1990s, this changed. You can now purchase 5-HTP as a supplement. Some supplements contain it as an ingredient too. Many supplements get their 5-HTP from Griffonia simplicifolia, which is native to Africa and other areas.
How Much 5-HTP Do You Take?
While the optimal dosage is not known, studies showing positive results often use 100-800 mg per day. Studies tend to find improvements in mood and anxiety after 2-6 weeks. Of course, this can vary from person to person.
5-HTP Precautions
We can't talk about 5-HTP and tryptophan without discussing eosinophilia-myalgia syndrome (EMS). What's that? Eosinophilia myalgia syndrome is a rare disorder marked by a rise in blood cells called eosinophils.
Eosinophilia myalgia syndrome is serious. Symptoms can include:
- Severe and debilitating muscle pain and cramps
- Difficulty breathing
- Muscle weakness
- Hair loss
- Swelling of the arms, legs and face
In 1989 over 1500 people were afflicted with EMS. Of those, over 30 people died. Sometimes the symptoms of EMS can last for years. Back then, the cause of EMS was traced to a contaminated tryptophan supplement. Since 5-HTP comes from tryptophan, some wonder if it too might cause eosinophilia-myalgia syndrome?
I've been keeping track of EMS since the 1990s. I don't hear much about tryptophan causing it anymore. This tells me the risk is probably low for most people. That is probably true for 5HTP also.
However, because of the gravity of EMS, I think you should discuss this with your doctor and pharmacist before trying 5-HTP or tryptophan supplements.
If you decide to try 5-HTP, here are a few things to consider. This list is not complete:
- Start with less than is recommended for the first week
- Stop taking tryptophan /5-HTP supplements at least 2 weeks before having surgery
- Don't take while pregnant or breastfeeding
- Talk to your doctor if you have any heart problems or blood pressure problems
- Speak to your doctor first before you combine tryptophan or 5-HTP with antidepressant medications. It's possible the supplements may interact with medications, causing your serotonin level to go too high. This is called serotonin syndrome. It's very dangerous.
- Speak to your doctor if you take other serotonin-enhancing supplements. Both tryptophan and/or 5-HTP may be used in sleep supplements, weight loss supplements, and brain-enhancing supplements (nootropics).
- Use caution if you have ever had rhabdomyolysis. It's probably rare but there are some cases of rhabdo after 5HTP supplement use.
- Don't drive while taking 5-HTP as it may cause sleepiness
- Speak to your doctor first if you have bipolar disorder, schizophrenia or similar medical issues
Can BlueBerries Help Depression?
Watch on my Youtube channel if you prefer
5. Saffron
Saffron (Crocus sativus) is often called the world's most expensive spice. One reason for this may be the many benefits of saffron. One of those benefits appears to be alleviating depression symptoms. At least 5 clinical studies have found saffron supplements can elevate mood levels.
For example, researchers in Iran randomly gave 40 people either a placebo or 60 mg of saffron per day (30 mg 2x per day. After 6 weeks, those taking saffron reported better mood than those taking the placebo.
Other reviews have also shown saffron to be as effective as some antidepressant medications. Still, other studies have noted saffron improves the effectiveness of anti-depressant medicine when they are taken together. Saffron has also been shown to reduce anxiety levels too.
Crocin is an extract of saffron. Some research has shown that crocin extract can help depression too. As such, some supplements may tell you how much crocin they contain.
Crocin has not been compared to the whole saffron spice to see which is better. It's possible saffron (the spice) may provide a more broad-spectrum effect than a single extract like crocin.
Until more is known, it may take some experimenting to see which -saffron or crocin – works best for you.
People who are depressed tend to gain weight due to increased appetite. Various studies have also shown saffron can decrease appetite. As such, saffron supplements are also marketed for weight loss.
How long does saffron take to work? This is difficult to pin down because we are all different. The time frame might depend on the severity of the depression you have. As a rule, 4-6 weeks, may be required before saffron kicks in. In other studies, up to 12 weeks may be needed.
How Much Saffron Do I Take For Depression?
Studies have used 30-60 mg per day. If the supplement highlights its crocin content, look for supplements that have 15-30 mg per serving.
Saffron Precautions
Saffron is considered safe, especially when used as a spice. When taken as a supplement, here are some things to consider. This list is not complete:
- Start with less than is recommended for the first week
- Don't take saffron while pregnant
- Talk to your doctor if you take medicine for high blood pressure or heart disease.
- Saffron might lower blood pressure and interact with some heart medications such as calcium channel blockers.
What About Magnesium And Depression?
Watch on my Youtube channel if you prefer
6. Folic Acid
Folate (Folic acid) is one of the B vitamins (vitamin B9). Another name for this vitamin is folacin. Folate is the natural form of the vitamin while folic acid is the synthetic form.
Researchers as far back as the 1960s noticed depressed people have lower folate levels than those who were not depressed. But how does folate work?
Folate helps us make at least 3 important neurotransmitters:
- serotonin
- dopamine
- norepinephrine
These 3 brain chemicals play a role in mood. So, the idea is if we consume more folate, our levels of these neurotransmitters will increase, leading to us having a better outlook on life.
That's the theory anyway.
Most studies on folate tend to combine it with antidepressant medications like SSRIs. These studies tend to show folate helps depression medications work better.
While more research is needed, folic acid supplements – by themselves- may not work. That was the finding of at least one study involving 121 younger people with mood disorders. This study compared 2.5 mg of folic acid per day (a mega dose) to a placebo.
Many people – especially women – tend to be deficient in folate. This is bad because folate is very important because folic acid prevents birth defects.
Foods high in folate include fruits and veggies. An advantage of eating the foods – over taking supplements – is the food provides more than just folic acid. The health benefits of a mostly plant-based diet are too numerous to list here.
Some supplements contain methyl folate. This is another version of folic acid. It's often touted as being superior but it's unclear if the methyl form is better than regular folic acid or folate in foods.
How Much Folic Acid For Depression?
Aim for at least the RDA which is 400 micro-grams (mcg) per day. Many multivitamins contain this amount (check to make sure). We don't store folate so we have to consume this vitamin regularly. Women who are pregnant and breastfeeding need more folate – 600 mcg and 500 mcg per day respectively.
Good food sources of folate include:
- Spinach (~120 mcg per 1/2 cup)
- Broccoli (~90 mcg per 1/2 cup)
- Brussels sprouts (~80 mcg per 6 sprouts)
- Romaine lettuce (~60-80 mcg per 1 cup)
Folic Acid Precautions
Folate from food is safe. When taking folic acid supplements, some general considerations are as follows. This list is not complete:
- Talk to your doctor if you are receiving chemotherapy
- Talk to your doctor if you have seizure problems
- Avoid taking large doses (1000 mg or more). Some studies have linked high-dose folic acid supplements to prostate, lung, and colon cancer. Is it possible some types of cancer need folic acid to grow? This does not happen when consuming folate in foods.
- Talk to your doctor and pharmacist if you take any medications
The Best Depression Supplement
This review contained a LOT of information and I know what you're thinking – just tell me what's best!
OK. Here's my pick. It's a tie between:
Honerable mention also goes to magnesium too. See the video above for why.
Both of these supplements have several clinical studies testifying to their benefits for depression. While St. John's may have more clinical studies under its belt, that may be because it's been around longer. On the downside, St. John's wort also has many drug interactions, so talk to your doctor first if you are going to take it.
Both are intriguing supplements when it comes to mood elevation.
Final Thoughts
As I approach 20 years since the death of my mom and dad, I'd be lying if I said I was 100% OK. While I am much better than when it first happened, now that time has passed, I find myself wondering strange things I didn't before such as would they be proud of me? and would they recognize me?
Depression is complected.
That's why I think depression is best battled holistically. In other words, I don't think supplements alone will work for everybody. For some, counseling and medications may be required. For others exercise and talking to friends can be godsends. Please remember this as you consider a natural therapy that's right for you.
Remember, it's OK to ask for help. We all need help sometimes.
Wendy E says
I tried SAMe about 10 years ago. Each day I used SAMe, about 90 minutes to 2 hours after ingesting, I got stomach/gut cramps that were very uncomfortable; they lasted about an hour. I thought maybe my body would adjust if I kept using it and the cramping would go away, but the pain was bad enough that I had to quit after just a few days use.
Joe Cannon says
Hi Wendy, did you take SAMe on an empty stomach? Tummy issues can pop up when some supplements are taking on an empty stomach.
Jen says
Hey Joe, saw your posting about this on Instagram. What about Kava? I didnt see this listed here. What are your thoughts?
Joe Cannon says
Hi Jen, Kava (also called kava kava) is more for anti-anxiety than depression. Some studies have shown kava can help reduce anxiety levels. If kava is used too much it can have some side effects such as liver problems and being allergic to sunlight (photosensitivity).
Because kava can put people to sleep, dont drive or operate machinery while taking it. There are reports of police pulling people over for DUI. they were “drunk” on kava.
I know there are kava bars out there. Sometimes they mix kava with another herbal drug called kratom. Kratom has its own share of issues.
See the kratom review for much more information
Death from kratom: Reports of cases