The Best Amino Acid for Depression, Anxiety and Pain

An illustration of a woman worrying and ruminating.

Today I want to talk to you about one of the best amino acids that has really helped me manage feelings of depression, anxiety and trauma.

I write about many different helpful nutrients and supplements, and I know it can be overwhelming. 

So I want to dedicate this post to one amino acid, because I feel like it’s helped me more than any other (even more than n-acetyl-cysteine). 

As soon as I realize I'm running low and have just a few capsules left, I order it immediately because it gives me so many benefits.

Even though I can live without it, I’d rather not.

A man sitting on the edge of a cliff, depressed and worrying. Clouds are above him and raining down on him.

Taking it every so often helps my mood and significantly improves the quality of my life. 

A subtle sense of “impending doom” starts to creep in when I’ve gone too long without it. 

If you struggle with chronic anxiety and depression, you probably know what I’m talking about.

This feeling used to be a lot worse for me. 

It felt like a dark cloud was following me around all day, and I just couldn’t shake it.

It’s now gone.

And thankfully, I know exactly how to keep it away.

But life can be tough at times, and things happen.

And that’s why I’m glad I have access to DL-Phenylalanine (DLPA) whenever I need it.

It helps me get through stressful times.

It can get me out of a deep hole like nothing else.

And if you struggle with feelings of trauma, anxiety and depression on a regular basis, it may help you too. 

What is DL-Phenylalanine (DLPA) and How Does It Work?

I first learned about phenylalanine in the book The Mood Cure by Julia Ross. 

It’s an essential amino acid that plays a key role in the proper functioning of your nervous system.

If you're deficient in phenylalanine, you can have the following symptoms:

  • Fatigue

  • Confusion

  • Memory problems

  • Decreased alertness

  • Loss of appetite

DL-Phenylalanine, or DLPA for short, is a combination of two different forms of phenylalanine – D-Phenylalanine and L- Phenylalanine.

The D and L forms of phenylalanine have different beneficial effects on your body and brain. 

L-Phenylalanine is used as a building block by your body to create a number of important proteins, hormones and neurotransmitters. 

This includes dopamine, norepinephrine and thyroid hormone – all of which are necessary for optimal brain and mental function.

Dopamine in particular is very important as it’s the main neurotransmitter that supports your attention and motivation, and plays a key role in the “reward system” of your brain.

D-Phenylalanine, on the other hand, inhibits the breakdown of endorphins.

Endorphins are pain-relieving compounds that originate within your body. 

Your brain produces and releases these natural painkillers during times of strenuous exercise, emotional stress and pain. 

But D-Phenylalanine has been shown to slow the action of enzymes that destroy these morphine-like substances. By doing this, it can prolong the activity of your endorphins within your nervous system, allowing you feel better for longer (1-6). 

How It Can Help You

Together, D and L-Phenylalanine can support your brain and mental health by increasing both dopamine and endorphins levels.

My research and personal experience suggest it can help treat a number of different conditions, including:

  • Depression

  • Anxiety disorders

  • Chronic pain conditions, such as fibromyalgia and arthritis

  • Chronic fatigue syndrome

  • Bipolar disorder

  • Parkinson’s disease

  • Premenstrual syndrome (PMS)

  • Attention deficit-hyperactivity disorder (ADHD)

  • Drug withdrawal, including alcohol, opiates and psychiatric medication (antidepressants, benzodiazepines, antipsychotics). If you struggle with any sort of addiction and cravings, I recommend the book End Your Addiction Now by Dr. Charles Gant, MD.

Personally, it helped me the most with depression and anxiety, and there are several studies that show it can improve your mood.

In one study, 20 depressed patients took 200 mg of DLPA everyday. At the end of the 3-week study, 12 patients no longer had depression, and 4 patients experienced mild to moderate improvements in their mood (8). 

This makes sense considering that researchers have found that people struggling with depression often have low levels of phenylalanine, and supplementation significantly elevates their mood (9). 

In fact, one study found that DLPA is just as effective as standard antidepressants (but without side effects), and another found that people who don’t respond to common antidepressants often get significantly better when they take DLPA (10, 11). 

And even if you take medication, research shows that combining DLPA with antidepressants leads to greater increases in mood than simply taking an antidepressant alone (12).

Yet unlike antidepressants, you can feel the effects of DLPA quickly (within a few hours) and in some cases, it can “terminate depression within 2 to 3 days” (13).

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My Experience

By building up your natural endorphin production, DLPA doesn’t just help reduce physical pain – but mental pain as well.

I'm currently taking this DLPA.

I'm currently taking this DLPA.

When I first started taking DLPA, it was such a relief. I was so glad I had found it. 

I notice it makes me:

  • More comfortable, happy and satisfied with my life;

  • More relaxed and calmer every time I take it;

  • Less moody and irritable;

  • Less likely to take things so seriously; and

  • Less reactive to negative events and situations.

Overall, it lifts my mood and reduces emotional sensitivity. Life becomes less intense. I’m not as sensitive to the world around me. I would definitely recommend it to others who also have “sensory processing sensitivity”. 

And eventually, DLPA helped me successfully wean off multiple psychiatric medications. Along with some other supplements, it played a critical role in making the withdrawal process as smooth as possible. 

I used to take 500 mg every day. Currently, I only need 500 mg once or twice each week, mainly because neurofeedback, low-level laser therapy and EMDR have helped me so much.

Other Success Stories

I understand that you might be thinking that perhaps DLPA won’t help you like it helped me.

And I can't guarantee that it will. 

But I did some digging and found a number of other people online who say that DLPA has also helped them manage or overcome their mental health issues. 

I’ve gathered their comments below and bolded anything that I can personally relate to or I have experienced while taking it:

  • “Suffering from severe post-traumatic stress, I've tried any number of natural products as the chemical cocktails handed out by conventional medicine are simply not acceptable to me. After my first dose of 1000mg DLPA, my depression lifted and trauma reactions (flashbacks and hyperviligence) significantly reduced. I've been taking this for a couple months now and there is definitely a light at the end of the tunnel. It has almost completely reversed my suicidal tendencies which were increasing regularly; they are now practically nonexistent. This product has truly saved my life.”

  • “My brain finally feels at rest and the anxiety has greatly decreased, and I can get on with my life. DLPA is my lifesaver. I will be taking this for as long as I need to.”

  • DLPA has been a huge help to me. I have type 1 bipolar and this has helped me more than anything I have ever tried. I will buy more and I also take more than 1. I take 2 to 3 a day and it calms my mind like nothing else ever has.”

  • “My husband is mildly bipolar. We've decided to try to treat him naturally and phenylalanine is one of the treatments. He only takes this on an "as needed" basis, which turns out to be at least two days per week. He has other regular supplements he takes daily. This is only for "extra support" on bad days. And it really works.”

  • DLPA is a key factor in improving my anxiety, depression and ADHD more than any of the several medications I have taken over the last 10 years.”

  • “I take DLPA first thing in the morning and it literally helps me get out of bed, get focused and get the day going with a positive attitude.”

  • “I honestly felt a difference right away. I was suddenly happy and smiling non-stop. I truly had a sparkle in my eye and I felt talkative and social. After a few hours the feeling wore off but I still felt an inner sense of content. It has helped with feelings of anxiety as well which is a plus.”

  • “Wow, what a difference! I have been so relieved from all those false moods that I can honestly say I am happy, alive and free.”

  • “I use this daily for the treatment of mild depression. I do notice a difference while on it. I went off of it briefly and felt as if someone had let some air out of my balloon, just kind of deflated.”

  • “I have suffered with extreme depression and anxiety since I was 13 (I’m now 42). I have gone through many different prescription/herbal/clinical therapies, and this product has been life-changing in a very short time. This has given me energy and focus I never had, a zest for life, an ability to handle stresses. I tell my husband (who keeps mentioning what a huge difference he has noticed) that this must be how "normal" people live.”

It absolutely blows my mind that more people aren’t aware of DLPA’s incredible and diverse benefits.

Clearly, it should be a first-line treatment for depression and anxiety. 

Yet I was never told about it, and it took me years to finally discover it.

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Where to Get It and How to Take It

I currently take this DL-Phenylalanine

I've also taken this one at one point.

I've also taken this DLPA and it works. It's currently less expensive than others through Amazon.

I've also taken this DLPA and it works. It's currently less expensive than others through Amazon.

Both work very well in my experience.

There are a number of other brands with good reviews, but I personally can’t vouch for them.

Make sure you get a combination of both D and L-Phenylalanine. I tried L-Phenylalanine alone once and it didn’t help me as much. 

In theory, it’s also a good idea to take it alongside Vitamin B6 and Vitamin C because they help with the conversion of phenylalanine to dopamine.

You should start with 500-750 mg each day and monitor how you feel. You will have to experiment and figure out your ideal DLPA dosage. The DLPA dosage for depression, pain or anxiety can vary. You may even need up to 1,500 mg daily.

But the benefits seem to increase over the time. The more you take it, the more you can feel it’s effects. 

Also, make sure you take it on an empty stomach. Do not take it with high-protein foods. Other amino acids (such as tryptophan) can compete with phenylalanine, and reduce its absorption and transportation across the blood-brain barrier.

Lastly, this anti-anxiety supplement includes several other natural compounds and amino acids that have helped me manage my anxiety over the years. It can also help reduce stress and anxiety, along with DL-Phenylalanine

Conclusion

Antidepressants and benzodiazepines are not your only options for depression and anxiety. 

Unfortunately, much of the so-called “science” behind mainstream psychiatric drugs is untrustworthy and fraudulent, and other safe and effective treatment options are often ignored by conventional medicine. 

A person’s hand and it says “I am stronger than depression.”

DL-Phenylalanine is one of these other options.

I can’t promise it will work for everyone, but since it’s easily accessible through Amazon, it’s worth a try if you suffer from depression and anxiety. Experiment with it and listen to how you feel. 

And like I have, I encourage you to use as many tools as you can to help yourself, including nutrition, supplements, exercise, neurofeedback, light therapy, etc. The list goes on and on. 

None of them have to work completely.

But all together, they can make a huge difference and change the course of your life like they have mine.

Enjoy This Article? You Might Also Like My FREE Food Guide for Optimal Brain and Mental Health!

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Live Optimally,

Jordan Fallis

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The 25 Best Natural Supplements Proven to Reduce Depression

Eight years ago, I was prescribed an antidepressant and started taking it every day. 

Knowing what I know now, I wouldn’t have done it. 

It helped a little bit. 

But then some serious side effects kicked in over time... 

Weight gain, sexual dysfunction, insomnia, emotional numbness, drowsiness, personality changes, and even cognitive decline

So if I could go back in time, I would rely on natural supplements first before jumping on pharmaceuticals.  

That’s not to say prescription antidepressants don’t help people.  

They do. 

They can save lives. 

But for some people (like me), they can end up doing more harm than good.  

So in this post, I want to share with you my favourite natural supplements for relieving depression.  

Research shows that there are many natural antidepressants that are just as effective as prescription antidepressants, but without adverse effects. 

After I came off medication, I relied on many of them to reduce depression and improve my mood and energy.  

Depression is complex, and there are often numerous underlying root causes.  

But these natural options will support you and prop you up while you seek and resolve the root causes of your depression.  

I’ve tried hundreds of natural supplements over the years, and these are the most effective ones for depression.  

They’ve really helped me, and I’ve seen other people get better with them as well. 

Read on to discover the best evidence-based supplements for treating depression. 

A smiley face made out of supplement capsules.
 

1. Probiotics

As you probably already know, the health of your gut (and the bacteria within it) significantly influence your brain and mental health.  

In fact, people who have been diagnosed with gut diseases are more likely to be diagnosed with depression (1).  

But luckily, there’s a solution. 

High-quality research shows that probiotic supplements can significantly reduce depressive symptoms in both healthy and depressed individuals (2-4).  

Studies also show that the neurotransmitter serotonin is produced in the gut.  

By taking a probiotic supplement, you can enhance the diversity of the bacteria in your gut, create a better environment for the synthesis of serotonin, and therefore increase serotonin levels and activity in your brain (5).  

Probiotics also reduce inflammation, which tends to be elevated in people with depression (6).  

The best probiotics for depression are Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum, and Lactobacillus casei. 

All five of them are included in the Optimal Biotics supplement.  

Check out this post for five other ways to increase the good bacteria in your gut.  

And if you struggle with anxiety, here are 9 probiotic strains that can help. 

 

2. Rhodiola

Rhodiola, also known as golden root or arctic root, is a Traditional Chinese and Scandinavian herb.  

It’s one of the most popular adaptogens used to increase physical and mental stamina. 

It can also reduce depression (9).  

In one study, rhodiola significantly reduced symptoms of depression and emotional instability in people with mild and moderate depression (7).  

Another study found that it was almost as effective as Zoloft, a commonly prescribed antidepressant, but it was better tolerated and it didn’t cause nearly as many side effects (8).  

Plenty of animal research also shows that rhodiola has antidepressant effects by lowering cortisol, and restoring serotonin, dopamine and norepinephrine (10-16).  

I personally take this rhodiola supplement. I don't take it every day, only when I need a boost in mood and energy.  You can get it here or here.  

Be sure to check out this post to learn more about the benefits of rhodiola, above and beyond just reducing depression. 

 

3. Acetyl-L-Carnitine (ALCAR)

Acetyl-L-carnitine (ALCAR) is an acetylated form of the amino acid carnitine. It’s been shown to have neuroprotective and cognitive-enhancing effects. 

It’s often used as a natural brain booster because it increases alertness and supports brain cells.  

Researchers have found that ALCAR is quite effective at alleviating chronic fatigue, improving mood and treating depression (17-18).  

In one study, supplementing with ALCAR for 1 to 2 months reduced depression in elderly individuals (19). 

And another study showed that ALCAR can reduce depression in people with chronic depression. Twelve weeks of supplementation reduced their depressive symptoms just as effectively as an antidepressant (20).  

It works because it supports mitochondrial function, and increases BDNF levels and serotonin levels in the brain (21-22).  

I find that ALCAR personally gives me a big boost in mood, motivation, mental energy and resilience. 

That’s why I included it in the Optimal Brain supplement

 

4. Theanine

A cup of green tea. Theanine is found in green tea and has been shown to help reduce depression.

Theanine is a unique amino acid found in tea. It has a number of mental health benefits. 

I take theanine alongside my morning coffee. It definitely improves my mood. It also helps me focus and cancels out the jitters of caffeine. 

In one study, theanine supplementation reduced depressive symptoms and anxiety, and improved sleep and cognitive function in patients with major depression (23).  

Animal research also shows that theanine can alleviate depression in mice that are exposed to chronic stress (24).  

This mental health supplement contains theanine, along with several natural compounds that have helped me manage depression and anxiety over the years. 

Theanine can also be found in green tea, which has also been shown to help reduce depression (25). 

 

5. Magnesium

Magnesium is a vital mineral that participates in more than 300 biochemical reactions in your body.  

Unfortunately, a lot of people are deficient in magnesium.  

This is a shame because magnesium is absolutely essential for the proper functioning of your nervous system and optimal neurotransmitter activity

Research clearly shows there are links between low magnesium intake, magnesium deficiency, and depression and suicide (26-28, 34-35).  

Several studies also show that magnesium supplementation improves depressive symptoms in people with depression, including people with postpartum depression, premenstrual syndrome, and chronic fatigue syndrome (29-32).  

Sometimes even just one week of supplementing with magnesium can improve mood and reverse symptoms of depression (33).  

Since most people are deficient, magnesium is one of the three supplements that I think everyone should be taking every day. 

Epsom salt baths are another great way to increase your body’s intake of magnesium.  

You should also make sure you’re eating enough magnesium-rich foods on a regular basis, including: 

These foods are included in my Free Grocery Shopping Guide for Optimal Mental Health.  

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6. Vitamin D

Vitamin D is a fat-soluble vitamin that your skin synthesizes when exposed to the sun.  

Unfortunately, Vitamin D deficiency is widespread and has become a major global health problem. Researchers estimate that 50% of people are at risk of Vitamin D deficiency

This is a huge concern because every tissue in your body has Vitamin D receptors, including the brain, so a deficiency can lead to costly physiological and psychological consequences, including depression. 

Research shows that there is a strong link between Vitamin D deficiency and depression and suicide (36-37).  

Thankfully, several studies shown that Vitamin D3 supplementation reduces depressive symptoms, treats seasonal affective disorder, and lowers suicide risk (38-40).  

Vitamin D helps fight depression because it plays a key role in the production of dopamine and norepinephrine, and protects against the depletion of dopamine and serotonin in the brain (41).  

Ideally, you should get your Vitamin D by going outside and getting sun.  

I try to get sunlight every day during the spring and summer months.  

But most people still don’t get enough Vitamin D from the sun, especially during the winter.  

During the winter months, when there isn't enough sun, I use this Vitamin D sunlamp.

I also take this Vitamin D supplement as needed, depending on my blood test levels.  

Vitamin D is so critical for optimal brain health, so make sure to check your levels regularly. You can order a test here.  

If you decide to take a Vitamin D3 supplement, it’s a good idea to take it along with Vitamin K2. They are synergistic and mix well together. 

 

7. Zinc

Zinc is an essential mineral for mental health, as it plays a key role in neurotransmission and nervous system functioning. 

Unfortunately, it’s estimated that 2 billion people in the world are deficient in zinc, and several studies show that even subclinical zinc deficiency impairs brain function (42-44). 

Researchers have also found that a zinc deficiency increases the likelihood of developing depression, as well as increasing the severity of depression (45).  

But zinc supplementation can definitely help.  

A meta-analysis concluded that taking a zinc supplement is an effective treatment for depression (46).  

In one study, 50 people took 30 mg of zinc for 12 weeks, and their mood significantly improved, and their BDNF levels increased as well (47-49).  

So if you struggle with depression, it’s quite possible you’re deficient, and you’ll want to consider taking a zinc supplement to optimize your levels. 

I created and take the Optimal Zinc supplement to make sure my zinc levels are optimal. I created it because I want to give my clients and readers the very best zinc supplement so that they can experience superior results. I have found that many zinc supplements on the market fall short. Optimal Zinc includes several other nutrients (co-factors) that increase the absorption of zinc. 

Some of the best foods you should eat to optimize your zinc levels include: 

These foods are included in my Free Grocery Shopping Guide for Optimal Brain and Mental Health

Check out my previous post all about zinc for more steps you can take to increase your zinc levels. 

 

8. DL-Phenylalanine

Phenylalanine is an essential amino acid, meaning that your body cannot create it, and you must obtain it from your diet. 

It plays a key role in the production of dopamine, a critical neurotransmitter that can improve your mood (50).  

People struggling with depression have been shown to have low levels of phenylalanine in their blood and urine (55).  

You can find phenylalanine in from protein-rich foods, such as: 

These foods are included in my Free Grocery Shopping Guide for Optimal Brain and Mental Health

But I find that supplementing with DL-Phenylalanine (DLPA), a special supplemental form of phenylalanine, is much more effective than simply eating foods with phenylalanine. 

In one study, 23 depressed patients took DLPA every day for 15 days. At the end of the 15 days, 17 of them had completely overcame their depression, and they didn't experience adverse side effects (51).  

Another 3-week study found very similar results (52).  

Researchers have even concluded that DLPA is just as effective as prescription antidepressants. And people who don’t respond to pharmaceutical antidepressants often get significantly better when they take DLPA (53-54).  

Even if you take medication, research shows that combining DLPA with antidepressants leads to greater increases in mood than simply taking an antidepressant alone (56).  

Yet unlike antidepressants, you can feel the effects of DLPA quickly (within a few hours) and in some cases, it can “terminate depression within 2 to 3 days” (57). 

Not surprisingly, I absolutely love DL-Phenylalanine. It was probably the most important supplement that I took while I transitioned off of antidepressants

If you’d like to learn more about DLPA, read this post

 

9. N-Acetyl-Cysteine (NAC)

N-Acetyl-Cysteine (NAC) is a modified form of the amino acid cysteine.  

It’s also the precursor to glutathione, your body’s master antioxidant

Nowadays, we’re exposed to so many environmental toxins, which cause oxidative stress in the body and deplete our reserves of cysteine and glutathione.  

But supplementing with NAC can increase and normalize your cysteine and glutathione levels. 

This can combat and reduce oxidative stress in your brain, which can then help treat several mental illnesses, including depression.  

In one study, 149 people with moderate depression were given NAC or placebo for eight weeks. The individuals who received NAC experienced a significant reduction in their depression, as well as improvements in their overall functioning and quality of life (58).  

In another six-month study, NAC significantly reduced symptoms of depression in patients with bipolar disorder. It also significantly improved their social and occupational functioning. The researchers concluded that NAC is a safe and effective strategy for depressive symptoms (59).  

Several other studies have examined the effects of NAC on bipolar disorder and found that taking NAC daily can significantly improve and even cause a full remission of depressive symptoms (60-62).  

 

10. Omega-3 Fatty Acids

Omega-3s fatty acids are the highest quality fats for the brain and increasing your intake of them is one of the most impactful actions you can take to promote the normal functioning of your brain and nervous system. 

They have been shown in many studies to significantly reduce brain inflammation; improve memory, mood and cognition; and protect against mild cognitive impairment, dementia and Alzheimer's disease

Researchers have also found that levels of omega-3 fatty acids are significantly lower in individuals with depression (63-64).  

It’s important to consume enough omega-3 fatty acids because they are essential fats that your body cannot produce itself. 

Omega-3 fatty acids are found primarily in cold water fish, including: 

  • Salmon  

  • Black cod  

  • Sablefish  

  • Sardines  

  • Herring 

These foods are included in my Free Grocery Shopping Guide for Optimal Mental Health.  

Unfortunately, most people don't consume enough omega-3 fatty acids through their diet. 

That’s why I recommend supplementing with krill oil, a special kind of fish oil that contains the essential omega-3 fatty acids.  

I take this krill oil supplement.  

I feel more depressed when I stop taking it. I actually notice the difference. 

Studies show that omega-3 fatty acid supplements are effective at treating clinical depression. They also improve mood in people who haven’t been diagnosed with depression, but have depressive symptoms (65-66. 68-69).  

One way they work is by reducing inflammation in the brain, which is strongly linked to depression (67).

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11. Ginseng

Ginseng is known for its anti-stress effects. 

But it also has antidepressant effects (70).  

More than one study has shown that ginseng reduces depression and increases quality of life (71-72).  

Ginseng has been shown to work because it reduces inflammation and increases dopamine, serotonin and BDNF in the brain (73-76).  

Ginseng is one of my favourite herbal supplements for brain function and depression.

 

12. S-adenosyl-L-methionine

S-Adenosyl-l-methionine (SAM-e) is a compound that naturally occurs in the body.  

It’s also available as a supplement.  

It’s most commonly used for treating depression because lowered SAM-e levels are associated with depression. 

Researchers have concluded that SAM-e is an effective and safe option for the treatment of depression. It has beneficial effects similar to conventional antidepressants (77-78, 82-83).  

In one study, people who hadn't responded to SSRI antidepressants took SAM-e for six weeks, and it significantly reduced their symptoms of depression (79).  

In another study, 20 healthy individuals received infusions of SAM-e or a placebo for seven days. The researchers scanned and studied the brains of the participants during the study. And it was confirmed that SAM-e is an antidepressant because it targets and supports brain regions involved in depression (81).  

It has also been shown to increase serotonin and dopamine activity in the brain, and inhibit the reuptake of norepinephrine (80).  

The great thing about SAM-e is that it works fairly quickly, as people usually notice benefits within the first few days of taking it, and it doesn’t cause severe side effects like pharmaceutical antidepressants (83).  

I took this SAM-e supplement after coming off psychiatric medication and it significantly helped me by improving my mood and energy.

 

13. Curcumin

A picture of turmeric. Curcumin is the main compound in turmeric that has been shown to reduce depression.

Curcumin is the most heavily researched compound within turmeric, the spice that gives curry its yellow colour.  

It’s one of my favourite natural compounds for the brain

Researchers have repeatedly found that curcumin reduces depressive symptoms in patients with major depression (84-86). 

In one study, curcumin reduced depression in more than 100 people after six weeks of supplementation (87).   

It also reduces inflammatory markers and cortisol levels, and increases BDNF levels, all of which are involved in depression (87). 

 

14. Methylfolate

Folate (Vitamin B9) is an essential B vitamin that plays a key role in methylation, one of the most important processes in your body and brain for optimal energy and nervous system function.  

Researchers have found that if you are depressed, you likely have lower levels of folate circulating in your blood, and people with low blood folate are at greater risk for developing depression (88).  

Good dietary sources of natural folate include: 

  • Leafy greens  

  • Asparagus  

  • Broccoli  

  • Cauliflower  

  • Strawberries  

  • Avocado  

  • Beef liver  

  • Poultry

These foods are included in my Free Grocery Shopping Guide for Optimal Brain and Mental Health

However, eating folate-rich foods sometimes isn’t enough. In fact, many people don't get enough folate from food because cooking and food processing destroy natural folates (103). 

People with depression often need to supplement with methylfolate to get the full benefits.  

In one study, six months of methylfolate supplementation reduced symptoms of depression in patients with clinical depression and schizophrenia (92).  

Research also shows that taking methylfolate alongside an antidepressant makes the antidepressant more effective (93).  

Researchers have even suggested that folate supplementation should be a first-line treatment for depression (104). 

Methylfolate works because it lowers homocysteine levels, stimulates serotonin receptors in the brain, and plays a key role in the production of dopamine (94-102).  

Whatever you do, avoid synthetic folic acid, which is commonly found in standard multivitamins. Instead, you need to take the biologically active form of folate (methylfolate or 5-MTHF). 

Methylfolate supplements are almost seven times more effective than synthetic folic acid at increasing folate levels. Regular synthetic folic acid has been shown to be quickly cleared from the central nervous system and poorly transported into the brain (89-91).  

On top of this, many people have genetic mutations in the enzyme that converts folic acid into methylfolate in the body. Therefore, folic acid is a waste and can actually cause harm if you have this genetic mutation.  

I take this B vitamin complex, and it includes methylfolate. Or you can take methylfolate separately at a higher dose.  

 

15. Vitamin B12

Lack of understanding of B12 is one of the greatest tragedies of modern medicine.
— Dr. James Greenblatt, Integrative Psychiatrist

Having sufficient levels of Vitamin B12 is necessary for optimal brain and mental health.  

Unfortunately, a deficiency is very common, especially in older individuals and vegetarians and vegans.  

Even if you eat meat and you’re young, you may still have a deficiency.  

Poor gut health and even psychiatric medications can cause a deficiency

In fact, it’s estimated that almost 40% of Americans are deficient today. 

Numerous studies have shown that having a deficiency in Vitamin B12 leads to symptoms of depression (136-142). 

But supplementation can help. 

Research shows that supplementing with Vitamin B12 for six weeks can reduce depressive symptoms in depressed patients (143).  

In one study, Vitamin B12 supplementation lowered homocysteine levels and reduced depression in more than 200 people (144).  

If you decide to supplement, avoid the semisynthetic version of B12 (cyanocobalamin) and instead take the methylated form (methylcobalamin or methyl-B12).  

Methyl-B12 is better absorbed and more biologically active. 

Besides methyl-B12 and methylfolate, you should also consider supplementing with the rest of the B vitamins. 

There is evidence to suggest that many people with depression are also deficient in Vitamin B1, B2, B3 and B6, and supplementing with them can help reduce, prevent and lower the risk of depression (145-151).  

I take this B complex supplement, which includes all the bioactive forms of the B vitamins, including B9, B12, B2 and B6.  

Vitamin B12 is also found in animal foods, and beef liver is a really good source. I take these beef liver capsules because I don’t like the taste of liver. 

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16. St. John’s Wort

St. John’s Wort (Hypericum Perforatum) is a natural medicinal herb with antidepressant effects. It's often prescribed for depression in European countries.  

Researchers have concluded that it’s as effective as pharmaceutical antidepressants for treating depression but has fewer adverse effects (105-107). 

A double-blind, randomized control trial showed that St John’s Wort can prevent depression from developing, and delay relapses in depression (108).  

It's been found to work by increasing dopamine signaling and increasing serotonin receptors (109-111). 

I took this St. John’s Wort supplement years ago for my depression. It helped me, but I eventually stopped taking it and working on fixing the true, underlying causes of my depression instead. 

In my experience, it’s best for people who are struggling with mild or moderate depression.  

It’s important to note that you shouldn’t take St. John’s Wort if you’re already taking antidepressant medication. They don’t mix well.  

 

17. Melatonin

Melatonin is a hormone released by your pineal gland, a small gland in your brain. You can also take it as a supplement.  

It helps control your circadian rhythm, and adequate levels of melatonin are necessary to fall asleep quickly and sleep deeply throughout the night. 

Researchers have found that people with depression often have low levels of melatonin and a compromised circadian rhythm (257-259). 

Studies also show that supplementing with melatonin at bedtime can lower symptoms of depression. It can also improve the circadian rhythm of various neurotransmitters that are disturbed in people with depression (260-261).  

You can get melatonin here.  

Or you can take this sleep supplement. It contains magnesium and other natural compounds that I’ve used over the years to promote the production of melatonin. You can use the coupon code FIVE$45496275 for a 5% discount. 

 

18. Uridine

Four glasses of beer. Beer contains uridine, which has been shown to reduce depression.

Uridine is a natural compound commonly found in beer.  

I definitely don’t recommend drinking beer, but supplementing with pure uridine can protect the brain, enhance cognition, and increase mood and motivation. 

Uridine supplementation has been shown to reduce depression in young people with bipolar disorder (113).  

Animal studies also show that uridine supplements alleviate depression and increases dopamine in the brains of rats (114-115).  

It’s important to note that uridine in food is not bioavailable, and no food has been shown to increase blood levels of uridine (112). 

So you’ll need to supplement with it.

 

19. Sarcosine

Sarcosine is an amino acid derivative that is naturally found in egg yolks, turkey, ham, vegetables and legumes. 

Supplementing with sarcosine has been shown to significantly reduce symptoms of depression without side effects (116, 119).  

In one study, sarcosine was found to be significantly more effective at treating major depression than citalopram (a common SSRI antidepressant). 

Patients who received sarcosine were much more likely to improve, improved much more quickly, and were less likely to drop out of the study than patients that received citalopram (117).  

Animal research also shows that sarcosine has antidepressant effects (118).  

You’ll have to supplement with sarcosine for it to improve your mood. The amount of sarcosine in food is too small to have a beneficial effect. 

I take this sarcosine powder.  

It has impressive antidepressant and anti-anxiety effects, but without any of the nasty side effects that are common with pharmaceutical antidepressants and benzodiazepines.  

 

20. Phosphatidylserine

Phosphatidylserine is a fat-soluble amino acid that is known to support cognitive function.  

High amounts of phosphatidylserine are in the brain, and supplementation has been shown to improve attention, learning and memory

But researchers have also found that phosphatidylserine can also reduce depression. 

In one study, supplementing with phosphatidylserine induced consistent improvement of depressive symptoms, memory and behaviour in elderly individuals with depression (121).  

Animal research also shows that phosphatidylserine has antidepressant effects. In fact, the antidepressant effects are more prominent in rats than the cognitive-enhancing effects (122).  

I personally take phosphatidylserine every day. It's included in the Optimal Brain supplement

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21. Lion’s Mane Mushroom

Hericium Erinaceus – better known as lion’s mane mushroom – is an edible mushroom with numerous health benefits.  

It’s another one of my favourite supplements for brain health because it reduces inflammation and has antioxidant effects

One study found that it reduced depression in 30 women after 4 weeks of supplementation (120).  

This lion’s mane mushroom supplement is the highest-quality that I could find. I spent a lot of time researching and looking into different sources because not all lion's mane supplements are high-quality and effective, and I settled on this one.  

You can get it here or here

 

22. Ginkgo Biloba

Ginkgo Biloba is a plant that has been used in China for thousands of years to treat a number of health problems. 

It’s one of the top-selling natural supplements in the world, and it’s even a prescription herb in Germany. 

It’s most commonly used to improve brain health because it increases brain blood flow and improves memory, mental energy and attention in both healthy and unhealthy individuals. It even reduces the risk of dementia and Alzheimer’s disease

But researchers have also found that Ginkgo Biloba reduces depression in elderly individuals (123-127).  

Ginkgo Biloba is included in the Optimal Brain supplement.

 

23. Saffron

Saffron plant. Saffron has been shown to reduce depression.

Saffron is a spice derived from the Crocus sativus plant.  

It has a number of health benefits due to the medicinal compounds within it. 

Researchers have found that saffron is effective at reducing depression in people with mild to moderate depression (127-128).  

More than one study shows that saffron works just as well as SSRI antidepressants, reducing depression without side effects (129-131).  

Saffron has also been shown to inhibit the reuptake of serotonin, dopamine and norepinephrine, similar to pharmaceutical antidepressants (132). 

 

24. Pregnenolone

Pregnenolone is a steroidal hormone naturally manufactured by the body, but it can also be taken as a supplement.  

It’s the precursor to almost all other steroid hormones, including DHEA, progesterone, testosterone, estrogens, and cortisol.  

It’s been shown to enhance memory and reduce fatigue. 

But researchers have found that it can also reduce depression.  

Depressed patients often have low pregnenolone levels, but replenishing pregnenolone levels with supplementation significantly reduces symptoms of depression (133-135).  

Whenever I take pregnenolone, it gives me a big boost in brain function and mental energy. It definitely has an effect. But it doesn’t really improve my mood. In fact, if I take it every day, it starts to make me irritable. So I save it and only take it when I need it.   

Plenty of other people have excellent, consistent results with it though. 

If you want to try it, you can get it here

 

25. Dehydroepiandrosterone

Dehydroepiandrosterone (DHEA) is one of the most abundant circulating steroid hormones in humans. It’s produced in the adrenal glands, the gonads, and the brain, and it’s a precursor to other hormones, including estrogen and testosterone. 

It's also available as a supplement

Research shows that low DHEA levels are significantly associated with increased depressive symptoms, and low DHEA levels are often found in depressed patients (270-271).  

And in multiple studies, supplementing with DHEA has been shown to improve mood and reduce depression (272-273).  

Researchers have found that it works because it impacts the activity of several neurotransmitters involved in depression, including dopamine, serotonin and GABA (274).  

 

26. BONUS: Other Natural Supplements That Can Reduce Depression

An image of several different natural supplements

Here are numerous other natural supplements that have also been shown to reduce depression and improve mood in humans.

I didn’t include them in the main list because they aren’t my favourite “go-to” solutions for depression.

Plus, they can be “hit-and-miss” and don’t always work for everyone in every situation.

But research still shows they can be quite effective, so they’re worth considering and giving a shot.  

 

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Live Optimally,

Jordan Fallis

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About the Author

Jordan Fallis is a health and science journalist and researcher, and the founder of Optimal Living Dynamics, a website that has helped more than 1.5 million people improve their brain and mental health. His work has been featured in the Canadian Broadcast Corporation, the Canadian Medical Association Journal, and the Canadian Pharmacists Journal. Jordan has also interviewed, consulted, and worked with more than one hundred medical doctors, health practitioners and leading researchers. He spends a lot of time scouring medical research, writing about what he finds, and putting the theories to the test on himself.

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(241) ttp://www.ncbi.nlm.nih.gov/pubmed/21771745

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Medically reviewed by Dr. Fred Hui, MD, CCFP, CAFC

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