How to Support Your Mitochondria for Better Brain Health

Picture of several mitochondria.

It’s becoming increasingly clear that chronic dysfunction of mitochondria is another underlying factor that contributes to poor brain function and mental illness. 

Mitochondria are unique structures within every cell of your body. You have trillions and trillions of them, making up approximately 10% of your total body weight. They are considered the “powerhouses of the cell,” generating most of the energy in your body by converting your nutrition into adenosine-5’- triphosphate (ATP). ATP is your body’s main source of cellular fuel. You are constantly using it, and your brain needs enough of it to work properly (106-107). 

Along with your gut bacteria, your mitochondria are critically important and need to be supported to overcome depression and anxiety, and reach optimal brain and mental health.

Mitochondria are especially abundant in your brain cells and involved in many important biological processes in the brain, including the regulation of free radicals and neurotransmitters. In fact, monoamine oxidase (MAO), the enzyme responsible for the metabolism of monoamine neurotransmitters, is localized within the outer mitochondrial membrane (91-93). 

So not surprisingly, numerous studies show that there is a correlation between impaired mitochondrial functioning in the brain and many psychiatric and neurodegenerative diseases, including bipolar disorder, major depressive disorder, multiple sclerosis, Parkinson’s disease, Alzheimer's disease, chronic fatigue syndrome, schizophrenia, psychosis, panic disorder, social anxiety, generalized anxiety and other stress-related diseases (82-90, 94-100, 102-104). 

Yes, you read that right. Every single one of those conditions has been linked to mitochondrial dysfunction. In fact, many researchers are convinced that mitochondrial dysfunction is involved in almost every chronic disease (108-110). 

Mitochondria dysfunction decreases ATP energy production and increases oxidative stress, which are commonly found in the brains of people suffering from brain and mental health disorders. Cognitive symptoms of mitochondrial dysfunction can also include impairments in attention, executive function and memory. Unfortunately, a number of psychiatric drugs damage the mitochondria and worsen dysfunction (105). 

But luckily, there are ways to halt and reverse mitochondrial decay.

Below are a number of strategies I’ve used over the years to support my mitochondria and you can use them to regain optimal brain and mental health.

Eat Nutrient-Dense, Whole Foods

Not surprisingly, eating lots of fresh, nutrient-dense whole foods is the most impactful action you can take to power your mitochondria. 

In order to thrive, your mitochondria need phytonutrients, antioxidants, healthy fats and proteins.

Dr. Terry Wahls, MD, clinical professor of medicine at the University of Iowa, is a leading expert on the relationship between nutrition and mitochondrial health.

Dr. Terry Wahls standing in front of her wheelchair.

She was diagnosed with multiple sclerosis (MS) more than a decade ago but reversed the neurodegenerative brain disease by repairing her mitochondria with an intensive nutritional strategy. She outlines how she recovered her health in her book The Wahls Protocol

Research on her protocol shows that patients witness a “significant improvement in fatigue” (67). 

She recommends eating six to nine cups of vegetables and fruits every day, including green veggies (kale, spinach), brightly colored vegetables (beets, carrots, peppers), and sulfur-rich veggies (broccoli, cauliflower).

My Free Grocery Shopping Guide for Optimal Brain Health also contains a bunch of foods that you should be eating on a regular basis for optimal mitochondrial health. 

Dr. Wahls also has a fascinating TED talk that you can watch below if you're interested in learning more. 

Avoid Certain Foods and Ingredients

Eating poor-quality foods can also wear down your mitochondria. 

Pizza, burgers and fries. Fast, processed food impairs mitochondria health.

Genetically, your mitochondria were not designed to deal with our current food environment and lifestyle habits. 

On top of this, your mitochondria are expected to perform proficiently for much longer, as our ancestors rarely lived to the age of 80.

That’s why you should avoid refined sugars, processed flours, industrial oils and trans fats. They can damage your mitochondria and prevent them from properly producing energy.

Dr. Wahls also recommends you avoid all gluten, dairy and soy products for optimal mitochondrial health. I feel much better avoiding them completely. 

Eat More Essential Fats

Healthy fats, including omega-3 fatty acids, help build and strengthen the membranes of your mitochondria. They’ve also been shown to improve mitochondrial functioning in brain (5-7). 

That’s why Dr. Wahls recommends eating organic grass-fed beef or wild-caught fish, such as salmon, every day. Avocados, nuts, seeds, coconut and olive oil are also rich in healthy fats. 

Supplementing with krill oil is another option. I’ve discussed the overwhelming benefits of krill oil before here

Exercise

Not surprisingly, exercise strengthens your mitochondria by increasing oxygen and blood flow and activating biochemical pathways that produce new mitochondria (8). 

Runners have more high-functioning mitochondria than non-runners, and strength training and high-intensity interval training also increase the number of mitochondria and improve the efficiency of your existing mitochondria (9, 10).

Many experts recommend exercise for brain health, and as I’ve mentioned before, it can also increase brain-derived neurotrophic factor (BDNF), your brain’s growth hormone

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Low-Level Laser Therapy (LLLT)

Low-level laser therapy (LLLT) is a treatment that uses low-level (low-power) lasers or light-emitting diodes (LEDs) to stimulate brain cells, helping them heal and function better. 

There is strong evidence to suggest that LLLT supports the mitochondria. 

Research shows that it reduces oxidative stress and increases the production of ATP energy in mitochondria (39, 40). 

These mitochondrial benefits have also been seen directly within the brain. Studies show that LLLT increases mitochondrial activity within brain cells, and this leads to beneficial effects in behaviour (41). 

On top of all this, LLLT treatment has been shown to increase the number of mitochondria and mitochondrial oxygen usage within the brain (42, 43).

Frankly, it’s ridiculous that this therapy is not more well-known and promoted by doctors.

But if you’ve read my blog for a while now, I’m sure you understand why.

You don’t have to wait for conventional medicine to catch up, and you can experiment with it yourself since it’s known to be very safe (44).

I use these two devices :

  • Platinum Therapy Lights Bio-450 (Combo Red/NIR) - This is a powerful all-one-device that shines 660 nm of red light and 850 nm of infrared light. I shine it on my forehead for 5-10 minutes every day or every other day. I also shine it on other parts of my head, and on my thyroid, thymus gland and gut. If you decide to get this device, you can use the coupon code OPTIMAL for a 5% discount.

  • Vielight 810 – This is an intranasal device with 810 nm of near infrared light that I use regularly. It penetrates deeper into brain tissue and is absorbed better by the central nervous system. If you decide to get this one, you can use the coupon code JORDANFALLIS for a 10% discount. Some research has shown a 20-fold higher efficiency of light delivery to the deep brain through the nose instead of transcranial application (125).

You can learn more about LLLT in this post

Infrared saunas are another excellent way to expose yourself to infrared light. Check out my post about the benefits here

And you should also limit your exposure to artificial blue light, as it can also wear down your mitochondria. You can learn more about the risks of too much blue light in this post

Resveratrol

Resveratrol is a beneficial antioxidant compound found in grapes and red wine. 

Not only does it increase BDNF levels, but it also activates the SIRT1 gene. This gene triggers a number of positive biochemical reactions that protect and improve the functioning of your mitochondria. Caloric restriction and intermittent fasting also trigger the SIRT1 gene (11, 12, 13).

In 2006, Harvard researchers found that resveratrol may increase lifespan by protecting the mitochondria (14).

That’s why I take this resveratrol on a regular basis and will continue to do so for the rest of my life.

Caloric Restriction and Intermittent Fasting

Restricting your calories is one the best actions you can take to improve mitochondrial function.

Empty plate, fork and knife. Intermittent fasting boosts mitochondrial function.

Studies show that eating less food reduces the demand and damage on your mitochondria. 

But reducing calories is tough to do and absolutely no fun. 

That’s why I intermittent fast instead. 

Fasting activates your mitochondria and triggers autophagy, which is an intracellular process that essentially allows the mitochondria to clean themselves by removing unwanted and damaged debris, proteins and reactive oxygen species (1, 2, 4).

This process has been shown to reduce the risk of cancer, Parkinson’s disease and Alzheimer’s disease (3). 

Nicotinamide Adenine Dinucleotide (NADH)

NADH is a naturally-occurring compound found in the cells of all living organisms.

It plays a key role in the production of energy within the cell and is highly concentrated within your mitochondria (45). 

Depletion of NADH has been linked to a number of diseases, including depression, chronic fatigue syndrome, Alzheimer’s and Parkinson’s, and stabilized oral NADH has been shown to improve all of these conditions (46, 47, 48). 

Although I don’t take it anymore, I’ve witnessed a beneficial effect from supplementing with this NADH through Amazon

LLLT also increases NADH in your mitochondria. 

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Ketogenic Dieting

A ketogenic diet is a very low-carb diet. 

When you restrict carbohydrate-rich foods, your body enters ketosis, a metabolic state in which your body and brain run on fatty acids and “ketones” instead of glucose (36).

Ketones are an alternative source of energy for your brain cells and their mitochondria. 

When your mitochondria are dysfunctional, following a ketogenic diet can be an effective strategy to fuel the mitochondria. 

When mitochondria are fueled by ketones instead of glucose, their ability to produce ATP is enhanced and free-radical byproducts are reduced.
— Dr. Jong Rho, MD, Professor of Pediatrics and Clinical Neurology at the Alberta Children’s Hospital

Ketogenic diets may help treat many different brain and mental health diseases including Alzheimer’s, Parkinson’s, epilepsy and autism. 

Exogenous ketones can help you get into ketosis quickly.

I take Optimal Ketones, and it immediately increases my mental clarity (even when I'm eating carbohydrates). 

B Vitamins

All of the B vitamins play an essential role in maintaining mitochondrial function, and your mitochondria will be compromised if you have a deficiency of any B vitamin (37). 

Deficiency is more likely if you take certain medications

I take this B complex. It includes the bioactive forms of all of the B vitamins. 

Ribose

Ribose is a five carbon sugar created naturally by your body. Even though it’s a sugar, research suggests it does not raise blood sugar levels. Instead, your body stores it in the mitochondria (49, 50). 

Ribose is used by the mitochondria to produce ATP and if you don’t have enough, you’ll experience low energy (51). 

Chronic stress can deplete ribose, and certain conditions have been linked to chronic ribose deficiency, including depression and chronic fatigue syndrome. That’s why I recommend people supplement with ribose if they struggle with these disorders because it can help reduce mental and physical lethargy (52, 53).

I don’t take it every day, but I do cycle this ribose with other mitochondrial enhancers. 

Coenzyme Q10 (CoQ10)

Coenzyme Q10 (CoQ10) is an antioxidant molecule found in every cell of your body. It’s particularly concentrated in the mitochondria, playing a key role in the production of energy and protecting the mitochondria from oxidative damage. 

Without CoQ10, your body cannot synthesize ATP because CoQ10 is an essential component of the mitochondrial electron transport chain.

Many doctors are unaware that CoQ10 is an excellent treatment for many brain health issues, including depression, chronic fatigue, and Alzheimer’s disease. 

Low levels of CoQ10 can cause brain fog, mental fatigue, difficulty concentrating, memory lapses, depression and irritability (68-70). 

Researchers have found that CoQ10 levels are significantly lower in the depressed patients (71). 

Unfortunately, chronic oxidative stress and medications can further deplete CoQ10

But supplementing with CoQ10 can increase your mitochondrial energy production and reduce symptoms of depression and chronic fatigue (71). 

I took this CoQ10 supplement after coming off psychiatric medication

Ubiquinol is a lipid-soluble form of CoQ10. I haven’t taken it but it is the most active form of CoQ10. 

If you decide to supplement with CoQ10, you should take it with a healthy fat source such as coconut oil to increase absorption because it is fat soluble. 

Food sources with high natural concentrations of CoQ10 include organic red palm oil and grass-fed beef heart (72, 73). 

Pyrroloquinoline quinone (PQQ)

Pyrroloquinoline quinone (PQQ) is a vitamin-like enzyme and potent antioxidant found in plant foods with a wide range of brain health and mitochondrial benefits.

It’s been shown to preserve and enhance memory, attention, and cognition by protecting the mitochondria from oxidative damage and promoting the growth of new mitochondria in the brain (56-59). 

Since it helps grow new mitochondria, it may help you if you suffer from depression, since fewer mitochondria have been found in people with depression (63). 

Reactive nitrogen species (RNS) and reactive oxygen species (ROS) cause severe stress on brain cells and mitochondria, and PQQ has also been shown to suppress RNS and ROS (60-62). 

Researchers have found that supplemental PQQ can be neuroprotective by increasing mitochondrial activity levels (64-66). 

I recommend taking 10-20 mg each day along with CoQ10, as they are synergistic. Taking them together leads to further improvements in cognitive function (57).

You can get it here

It's also included in this supplement

Check out the “Neuroprotective” section of the PQQ Wikipedia page for more information on the brain health benefits of this compound. 

Magnesium

Magnesium is a vital mineral within your body, and the mitochondria are considered magnesium “storage units” because they hold onto a lot of your body’s magnesium. 

Magnesium protects the mitochondria and plays a role in the production and transfer of ATP within the mitochondria. And research shows that if you have a deficiency in magnesium, your brain cells will have fewer mitochondria, and they will be less healthy (54, 55). 

This is just another reason to supplement with at least 200 mg of magnesium every day. It’s one of the most important nutrients for optimal brain health. I take this one through Amazon

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Acetyl-Carnitine (ALCAR) and Alpha Lipoic Acid

Acetyl-Carnitine (ALCAR) is an acetylated form of the amino acid carnitine.

Carnitine is an amino acid that improves mitochondrial activity and plays an important role in energy production by transporting fatty acids directly into the mitochondria of your brain cells. It is required to produce ATP and deficiencies are associated with reduced mitochondrial function in the brain (74). 

Supplementing with ALCAR makes it easier for fatty acids to cross your blood-brain barrier and nourish the mitochondria within your brain. This can improve your mood, memory and energy levels.

Several studies show that ALCAR eases depressive symptoms and improve quality of life in patients with chronic depression (75-78). 

Scientific representation of brain and brain blood flow.

And individuals with autism often have reduced levels of carnitine within their brain (79). 

ALCAR is included in the Optimal Brain supplement

ALCAR is also synergistic with Alpha Lipoic Acid (ALA), meaning that when you take them together, they are more effective at supporting the mitochondria in your brain.

ALA is a mitochondrial enzyme and antioxidant. It is fat soluble and can easily cross your blood-brain barrier.

It’s been shown to improve cognition by reducing oxidative stress, and protecting existing mitochondria and creating new mitochondria in the brain (80, 101).

Other helpful nutrients that support your mitochondria and provide raw materials for them to produce ATP:

Conclusion

Picture of mitochondrion, the energy producer of brain cells.

Paying attention to your mitochondria is crucial for optimal brain and mental health, and luckily there are a number of dietary and lifestyle habits that can protect and support mitochondrial function.

The following steps will ensure your body and brain have healthier and more abundant mitochondria: 

Over time, if you follow these strategies, you can improve your mitochondrial health and naturally restore your mood and energy levels.

Please share this post with one of your friends or family members who you think might benefit from protecting and supporting their mitochondria, because it really is an underappreciated and unknown aspect of optimal brain and mental health. 

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

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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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Medically reviewed by Dr. Terry Wahls, MD

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Rhodiola: The Very Best Herb for Depression and Fatigue

This herb increased your resilience to physical and mental stress. It can calm you down, or increase your energy, depending on the needs of your body. In other words, it helps the body normalize itself and reach a state of physical and mental balance

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

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