20 Nutrient Deficiencies Proven to Cause Depression

Being depressed doesn’t mean you’re weak.

It’s not a defect in your personality. 

As I’m sure you know, it’s often caused by physiological changes in your body and brain.

So you need to think of it like any other illness. 

If you have a broken bone, you need to wear a cast to stabilize the bone while it heals. 

And if you have depression, you need to be kind to yourself, as you seek and address the underlying root causes. 

The good news is that you’re not powerless. 

I used to think that I’d be depressed forever.

That my depression was simply genetic, and I couldn’t do anything about it. 

In fact, I accepted that notion for a while.

I felt defeated and hopeless, and thought I'd feel that way for my entire life.

I told myself I’d simply have to rely on drugs to survive because that’s just “how I’m wired”. 

But then one day, I changed my mind and decided that I’d had enough. 

And I was actually going to get to the bottom of it instead of just accepting it.

I took action and searched far and wide for safer and healthier solutions to deal with my depression.

I came across a lot of different research and therapies.

I wasn’t sure if they would work, but then they did.

And I overcome my depression for good. 

One of my most important discoveries was that nutrient deficiencies can make your depression worse. 

And they could even be the root cause of it. 

It made so much sense.

But why hadn’t anyone ever brought it up?

I delved deeper into the scientific literature, and I found MANY nutrient deficiencies that can contribute to depression.

I started increasing my intake of them.

And I got better.

Much better.

This new post includes 20 nutrient deficiencies that could be making you feel depressed.

Read on to learn more. 

Depressed woman holds her forehead and wonders what nutrients she’s deficient in.

Vitamin Deficiencies That Can Cause Depression

1. 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.

And 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 (16-22). 

And B12 levels tend to be significantly lower in people who are depressed (13). 

In one study, subjects with Vitamin B12 deficiency were 2 times as likely to be severely depressed as non-deficient subjects (15). 

Even a mild decrease in B12 levels is associated with mood disturbances (14). 

Luckily, there are steps you can take to make sure you’re not deficient. 

Vitamin B12 is found primarily in animal foods, and beef liver is an excellent source. I take these beef liver capsules because I don’t like the taste of liver.

You may also want to supplement with Vitamin B12 because studies show that B12 supplementation significantly lowers homocysteine levels and reduces depressive symptoms (23-24). 

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.

 

2. Vitamin D (and Vitamin K2)

Sunlight shining through trees in a forest. Sunlight gives us Vitamin D, one of the main nutrient deficiencies that can cause depression.

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

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.

Researchers have found a very strong link between Vitamin D deficiency and depression (27-28). 

The lower your Vitamin D levels, the more symptoms of depression you are likely to have (35). 

Unfortunately, reports indicate that Vitamin D deficiency is widespread and a major health problem globally (25). 

Researchers estimate that 50 percent of the general population is at risk of Vitamin D deficiency (26). 

It’s best to get your Vitamin D by going outside and getting sunlight.

It’s especially important to make sure you get some sunlight in the morning to set your circadian rhythm. 

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

That’s why I recommend taking a Vitamin D supplement

Research does show that taking a Vitamin D3 supplement is effective at reducing symptoms of depression and seasonal affective disorder (29-31). 

This is likely because Vitamin D increases the production of numerous neurotransmitters, including serotonin, dopamine, norepinephrine and epinephrine (32-34). 

It's important to test and monitor your Vitamin D levels before and after supplementing with it. You can order an at-home Vitamin D test here.

Lastly, if you decide to supplement with Vitamin D3, you should consider taking it with Vitamin K2

A recent study found that Vitamin K2 reduces depression in animals (36). 

And Vitamin K2 is known to improve brain function in humans (37-38). 

 

3. Vitamin B6

A bunch of foods rich in Vitamin B6, including chicken, beef, bananas and potatoes. Vitamin B6 is one nutrient that can help you overcome depression.

Having a deficiency in Vitamin B6 can also contribute to your depression.

It’s a key nutrient that supports your entire nervous system.

It can boost your mood because it plays a key role in the production of neurotransmitters in your brain, including serotonin and dopamine. It also lowers homocysteine

Research shows that people with depressive symptoms tend to have low levels of Vitamin B6 (85-87). 

A Vitamin B6 deficiency also contributes to chronic inflammation, which is one of the main underlying root causes of depression (88). 

Fortunately, consuming more Vitamin B6 can help. 

One study found that women that eat more foods containing Vitamin B6 have a lower risk of depression (89). 

Some of the best food sources of Vitamin B6 include potatoes, bananas and chicken. 

But supplementation is often necessary to see quick improvements. 

One study found that supplementing with Vitamin B6 can reduce depressive symptoms by lowering homocysteine levels (90). 

When I took antidepressants for depression, multiple functional and integrative doctors suggested I supplement with Vitamin B6.

This is because these medications can actually further deplete Vitamin B6, increasing depression in the long run. 

Vitamin B6 is included in the Optimal Zinc supplement.

 

4. Vitamin C

Having low levels of Vitamin C can also make you feel depressed.

Researchers have found that poor Vitamin C status is associated with increased symptoms of depression (105). 

Animal research also shows that a Vitamin C deficiency can lead to low levels of dopamine and serotonin in the brain, which causes mice to act depressed (106-107). 

As you probably know, Vitamin C can be found in foods such as peppers, citrus fruits, green leafy vegetables, broccoli, tomatoes, and berries. These foods are included in my Free Grocery Shopping Guide for Optimal Mental Health.

In addition to getting Vitamin C from fruits and vegetables, I take at least 500 grams of this Vitamin C every day. 

I’ve experimented with taking up to 10 grams daily, and it definitely improved my mood and reduced my stress levels, especially when I was coming off antidepressants

Research backs this up, showing that supplementing with Vitamin C can actually improve mood in both unhealthy and healthy individuals (95, 102-103). 

Various other studies show that Vitamin C supplements reduce stress and anxiety and decrease the severity of depression (96-101, 104).

Studies even show that Vitamin C can increase the effectiveness of antidepressants (108-109). 

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5. Folate

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 (55-56). 

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 do not get enough folate from food because cooking and food processing destroy natural folates (54).

And supplementation is often needed. 

If you decide to supplement with folate, avoid synthetic folic acid, which is commonly found in standard multivitamins. Instead, you should take a 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 (51-53). 

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.

And the research backs up the use of methylfolate.

In one study, patients with depression took methylfolate for 6 months, and they witnessed a significant improvement in their depressive symptoms (57). 

Researchers have even suggested that folate supplementation should be a first-line treatment for depression (58). 

Methylfolate can be effective at treating depression because it helps lower homocysteine levels, helps produce serotonin and dopamine, and stimulates serotonin receptors in the brain (59-62). 

Methylfolate is included in this B vitamin complex that I take regularly. Or you can take it separately if you’d like. 

 

6. Thiamine

An assorted mix of nuts. Nuts are a rich source of thiamine, or Vitamin B1. People with depression often have low levels of Vitamin B1.

Thiamine, also known as Vitamin B1, is an essential water-soluble nutrient that cannot be made by the body. 

It’s used in nearly every cell in the body and especially important for supporting energy levels.

It’s also required by nerve cells and other supporting cells in the nervous system (167). 

Research shows that lower levels of Vitamin B1 are associated with a higher prevalence of depressive symptoms (168).

Vitamin B1 deficiency is also known to lead to irritability and symptoms of depression (170). 

Some doctors and researchers believe that postpartum depression is sometimes simply a Vitamin B1 deficiency (169). 

Luckily, consuming more Vitamin B1 can help.

A randomized, double-blind clinical trial found that Vitamin B1 supplementation reduces symptoms of depression within 6 weeks (171). 

And another concluded that Vitamin B1 supplementation improves mood, reduces brain fog, and speeds up reaction time (172).

In fact, researchers have even found that subjects’ mood improves if the amount of Vitamin B1 in their blood increases, and that the opposite occurs if the amount of Vitamin B1 in their blood decreases (173). 

Healthy food sources of Vitamin B1 include green peas, beef liver, asparagus, pecans, spinach, sunflower seeds, macadamia nuts, oranges, cantaloupe and eggs. 

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

 

7. Riboflavin

A handful of almonds. Almonds are an excellent source of Vitamin B2, a nutrient that is commonly depleted in people with depression.

Riboflavin, also known as Vitamin B2, plays a key role in energy metabolism throughout your entire body.  

As a result, a Vitamin B2 deficiency can affect the entire body, leading to low energy, weight gain, and depression.

In fact, lower levels of Vitamin B2 have been found in people with depression (91). 

Researchers have also found that Vitamin B2 consumption decreases risk of postpartum depression (92). 

Healthy food sources of Vitamin B2 include pastured eggs, leafy vegetables, beef liver, mushrooms, sunflower seeds, and almonds

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

If you’d like, you can also supplement with Vitamin B2.

Studies show that supplementing with Vitamin B2 helps lower homocysteine and reduces depressive symptoms (93-94). 

Vitamin B2 is included in the Optimal Zinc supplement. 

 

8. Inositol

Inositol is a naturally-occurring molecule found in nearly all plants and animals. It plays a key role in various biological processes.

The brain has the highest concentration of inositol, where it plays an important role making neurotransmitters (124). 

Inositol can be found in many foods, particularly fruit, especially cantaloupe and oranges (125). 

It used to be considered a B Vitamin, called Vitamin B8. But it currently is no longer considered an essential nutrient because your body can produce inositol from glucose (126). 

But I’m including it in this list anyway because individuals with depression have very low levels of inositol in their brains (127-129). 

And inositol supplementation has been shown to increase inositol levels and help treat depression (130, 132). 

It can also reduce symptoms of depression in women with premenstrual syndrome and premenstrual dysphoric disorder (131, 133). 

It’s even been shown to help patients who have discontinued their antidepressant medication (134). 

I took high doses of this inositol powder when weening off psychiatric medication.

I now take a normal amount found in this B complex.

Check out my full post about inositol to learn more about the benefits. 

Fun fact: Inositol is also used as a stand-in for cocaine in television shows and movies. 

 

9. Coenzyme Q10

Coenzyme Q10 (CoQ10) is a coenzyme and antioxidant located primarily in the mitochondria. It has numerous known health benefits and plays a critical role in producing energy for the body.

CoQ10 is produced within the body, but it’s also found within food and can be supplied to the body through food or supplementation. It resembles a fat-soluble vitamin.

Meat and fish are the richest sources of dietary CoQ10, including beef, pork, chicken heart, and chicken liver. Nuts and some oils also contain some CoQ10 (110). 

Research shows that CoQ10 levels are reduced in people with depression and chronic fatigue (111). 

One study also found that CoQ10 regulates serotonin levels and depressive symptoms in fibromyalgia patients (117). 

CoQ10 supplementation has also been shown to improve fatigue and reduce depression symptom severity (112-114). 

It also displays antidepressant-like activity in animals (115-116). 

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Mineral Deficiencies That Can Cause Depression

10. 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 today.  

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

Research shows that low magnesium levels contribute and worsen many neuropsychiatric problems, including depression (42). 

In fact, researchers have found that people with depression have lower magnesium levels than healthy people (49). 

They’ve also found a significant association between very low magnesium intake and depression (43). 

On top of this, animal research shows that removing magnesium from their diet results in depressive-like symptoms (50). 

So if you’re struggling with depression, it’s very important to make sure you’re getting enough magnesium so that you don’t have a deficiency.

Luckily, there are a number of ways to do this. 

First, make sure you’re eating magnesium-rich foods on a regular basis, including:

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

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

I also highly recommend a high-quality supplement that includes magnesium.

A number of studies have concluded that magnesium supplementation can reduce depressive symptoms in humans – sometimes within 7 days (44-48). 

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

 

11. Zinc

An image of zinc-rich foods, including pumpkin seeds of cashews. Zinc is one mineral that can help fight depression. Many people with depression often have low levels of zinc.

Zinc is an essential mineral for mental health.

Like magnesium, it plays a key role in neurotransmission and nervous system functioning.

Mounting evidence suggests a link between zinc deficiency and the development and severity of depression (66-68, 76).  

Depressed patients tend to have lower levels of zinc. And as their zinc levels drop, their depressive symptoms get worse (81-84). 

Unfortunately, it’s estimated that 2 billion people in the world are deficient in zinc, and several studies show that even subclinical deficiency of zinc impairs brain function in children and adults (63-65). 

So, if you struggle with depression, it’s quite possible that you’re deficient, and you’ll definitely want to optimize your zinc levels. 

Some of the best food sources of zinc include:

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

However, if you’re deficient like I was, I recommend taking a high-quality zinc supplement, at least for a short period of time. 

A meta-analysis and several studies have concluded that zinc supplementation has antidepressant effects and significantly reduces symptoms of depression. One way it improves mood is by significantly increasing BDNF levels (69-75, 77-80).

I created and take the Optimal Zinc supplement to make sure my zinc levels are optimal. 

Check out my previous post all about zinc if you’re interested in discovering more steps you can take to increase your zinc levels.

 

12. Iron

A spoonful of spirulina. Spirulina is rich in iron. Iron is one nutrient deficiency that can cause depression.

Iron is a trace mineral found in every living cell in our bodies.

It carries oxygen to all parts of your body, and low levels can leave you feeling tired, pale, irritable and foggy

Sounds like depression doesn’t it?

Several studies show that iron deficiency increases the risk of developing depression and increases the severity of depression (184-186, 188-190). 

Researchers have also conducted a meta-analysis and found that high iron intake reduces the chance of developing depression (183). 

In one study, iron supplementation resulted in a 25% improvement in depressive symptoms (187). 

Despite this, I don’t actually recommend supplementing with iron though because some research suggests that too much iron can cause health problems.

It’s definitely preferable to get your iron from food. 

I make sure I get enough iron simply by taking these grass-fed beef liver capsules.

Beef liver is one of the best sources of iron, but I don’t like the taste, so I go with the capsules. You can get them here or here.

Other good sources of iron include:

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

 

13. Selenium

Selenium is an essential trace mineral that is important for many bodily processes that affect your brain and mental health.

Researchers have found that depression is associated with low levels of selenium (191). 

But supplementing with selenium has been shown to significantly increase selenium levels and improve symptoms of depression (192). 

Other research shows that selenium intake is associated with a general elevation of mood (193). 

Brazil nuts are the richest dietary source of selenium, but it can also be found in wild-caught seafood, pastured chicken and eggs, and grass-fed meat.

I also make sure I’m not deficiency in selenium by taking selenomethionine, which is a highly-absorbable form of selenium.

 

14. Manganese

A table of foods that have high levels of manganese. Manganese deficiency can cause depression and make depression worse.

Manganese is an important trace mineral for human health. It acts as a cofactor, helping many enzymes carry out their functions in the body.

Research shows that having low levels of manganese can contribute to the development of depression (135). 

One study found that depressed patients had significantly lower levels of “manganese superoxide dismutase”, which is a manganese-dependent enzyme (136). 

Researchers have also found that women with higher manganese intake had a lower prevalence of depressive symptoms (137). 

Hazelnuts and macadamia nuts contain high levels of manganese, while leafy green vegetables, tea, chocolate and some fruits contain moderate levels (139). 

However, it’s important to note that you shouldn’t consume too much manganese.

In excess, manganese is neurotoxic and can lead to manganism, a neurodegenerative disorder that causes dopaminergic neuronal death and symptoms similar to Parkinson's disease (138). 

So I definitely don’t recommend supplementing with large doses of manganese. 

The small amount of manganese in Optimal Antiox is fine though. It’s what I take. 

 
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Fatty Acid Deficiencies That Can Cause Depression

15. Dihomo-Gamma-Linolenic Acid

Vials of Borage Oil, a fat that is rich in DGLA. DGLA has anti-inflammatory effects and can help beat depression.

Dihomo-Gamma-Linolenic Acid (DGLA) is an uncommon fatty acid.

It’s made in the body by the elongation of Gamma Linolenic Acid (GLA).

But small amounts can also be found in animal products (118). 

Last year, researchers found that people with depression are more likely to have low levels of DGLA levels (121). 

And increasing DGLA levels may lower the risk of developing depression (122). 

DGLA also has anti-inflammatory effects in the body (119). 

So it makes sense that levels would be low in depressed individuals because an increasing amount of evidence suggests that depression is a chronic inflammatory disease. 

DGLA can be increased by supplementing with dietary GLA (120). 

GLA can be found in Borage Oil, Evening Primrose Oil and Blackcurrant Seed Oil (123). 

 

16. Omega-3 Fatty Acids

Piece of cooked salmon on a plate. This salmon is full of omega-3 fatty acids that can help fight depression.

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 fight depression.

Several studies have shown that depressive patients have lower levels of omega-3 fatty acids (1-3).

Researchers even conducted a meta-analysis of 14 studies, and they found that levels of omega-3 fatty acids were significantly lower in people with depression (4). 

They concluded that having a deficiency in omega-3 fatty acids is a “contributing factor to mood disorders” (5). 

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 one.

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

This isn’t surprising because plenty of research shows that omega-3 supplements are effective at treating clinical depression – just as effective as antidepressants drugs – because they lower inflammation in the brain (6-10). 

 

Amino Acid Deficiencies That Can Cause Depression

17. Carnitine

Carnitine is an amino acid found in nearly every cell of the body. It plays a vital role in the production of energy.

Researchers have found significantly lower levels of carnitine in patients with depression. And their low carnitine levels are associated with the severity of their depression (11-12, 174-175). 

Carnitine is mainly found in meat, fish and poultry.

But you can also supplement with it. 

I recommend Acetyl-L-Carnitine (ALCAR), an acetylated form of carnitine. It’s best supplemental form of carnitine. 

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

But it’s also been shown to be very effective at quickly improving mood and treating depression (179-182). 

Six randomized clinical trials have demonstrated that ALCAR is better at treating depression than placebo (177). 

And two other studies found that ALCAR improved depressive symptoms in patients with chronic depression, and it was just as effective as antidepressant medications, but with less side effects (176, 178). 

ALCAR is included in the Optimal Brain supplement

 

18. Glutamine

Glutamine is the most abundant amino acid in the body, suggesting that it’s very important.

It’s also one of the few amino acids that can directly cross the blood-brain barrier.

Glutamine is a conditionally essential amino acid, meaning the body can usually produce sufficient amounts of it. But sometimes the body uses up so much glutamine that it becomes necessary to obtain it from the diet or supplements, particularly during periods of illness, stress, inflammation and injuries (156-157). 

Researchers have found that depressed adults have reduced levels of glutamine (158). 

And glutamine deficiency has been shown to increase depressive-like behaviour in animals (159). 

But glutamine supplementation has “clear anti-depressive properties” and has been shown to improve mood (160-161). 

High levels of glutamine can be found in protein-rich foods such as beef, chicken, fish and eggs. Beets, cabbage, spinach, carrots, parsley, brussel sprouts, celery, kale and fermented foods like miso also contain some glutamine.

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

Glutamine is also available in supplement form. 

Glutamine was one of the main supplements that helped me heal my leaky gut, but I no longer need to take it regularly. 

 

19. Tryptophan

Tryptophan is an essential amino acid that cannot be produced by the body. It must be consumed through diet or by taking supplements. 

Some healthy foods that contain tryptophan include bananas, chicken, turkey and dark chocolate (140). 

A doctor is talking to a turkey and says “I think I know what is causing your narcolepsy. You’re full of tryptophan. Tryptophan is an amino acid that can make you sleepy, but it can also improve mood and help treat depression.

Tryptophan helps produce the neurotransmitter serotonin. It’s converted to 5-hydroxytryptophan (5-HTP) in the brain, which then produces serotonin (141-142). 

Researchers have found that depressed patients have significantly lower levels of tryptophan in their blood than healthy control subjects (143-144). 

Studies also show that depressed patients have a decreased ratio of tryptophan to neutral amino acids in their blood. This suggests that tryptophan availability to the brain is likely reduced in depressed patients (145-146). 

Personally, supplementing with tryptophan never helped me. In fact, it always seemed to make me worse. It gave me asthma and acne and increased my depression.  

This is because depressed patients sometimes have problems creating serotonin from tryptophan. Instead, they create other metabolites from tryptophan, such as quinolinic acid, which can be toxic. For depressed patients like me, tryptophan supplementation won’t help, and may actually make their depression worse (150-151). 

However, some people do see their mood improve when they increase their intake of tryptophan. So it shouldn’t be completely disregarded. 

There are studies that show that consuming a high tryptophan diet and consuming additional dietary tryptophan can increase mood and lead to significantly less depressive symptoms (152-154). 

So supplementing with tryptophan is worth a shot if you’re struggling with depression and haven’t tried it yet. Just be aware of possible side effects. 

If you want, you can also try supplementing with 5-HTP instead of tryptophan. 5-HTP is the direct precursor to serotonin. 

5-HTP is included in this supplement

 

20. Glutathione

Glutathione is a small peptide made up of 3 important amino acids – glutamic acid, cysteine and glycine – each of which have several important roles in the human body.

Glutathione is found in the food supply and within the human body, where it acts as an antioxidant. It is used by every cell in the body.

It’s technically not an “essential nutrient” because the body can create it.

However, it’s still very important, and a glutathione deficiency leads to increased susceptibility to oxidative stress, which is thought to be involved in a number of diseases, including depression.

Studies show that patients with depression have significantly lower levels of glutathione. And the lower a person’s glutathione levels, the more depressed they are likely to be (162-164). 

Some practitioners and researchers have found that increasing glutathione intake and levels can successfully treat depression (165). 

Glutathione is also able to prevent behavioural depression in animals (166). 

It’s important to note that standard glutathione supplements are not very effective at increasing glutathione levels because they are not well absorbed by the body.

But I have found that high-quality liposomal glutathione supplements are effective. 

N-acetyl-cysteine (NAC) is another tried-and-true way of increasing glutathione levels because it’s the direct precursor to glutathione

Garlic, asparagus, and cruciferous vegetables, such as broccoli and kale, can also help boost glutathione levels, but liposomal glutathione and NAC supplements are more powerful. 

Other supplements that have been shown to help increase and maintain optimal glutathione levels include Selenium, Alpha Lipoic Acid, and S-adenosyl-methionine (Sam-E)

 

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Live Optimally,

Jordan Fallis

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References:

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

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31 Powerful Ways to Induce Autophagy in the Brain

Autophagy is an absolutely essential biological process that plays a key role in the normal functioning and survival of your brain cells.

The word autophagy is derived from the Greek words auto and phagein.

Auto translates to “self”.

And phagein translates to “devouring”.

So autophagy essentially means “self-devouring”, or “to eat oneself”.  

That may sound scary and something that you would want to avoid…

But it’s actually something you want to embrace and induce yourself.

Because autophagy is a self-cleaning mechanism within our cells, which helps your brain detoxify, repair and regenerate itself.

It destroys the old, damaged, and malfunctioning components of your cells – and rebuilds new and healthier ones instead!

It’s sort of like spring cleaning or replacing old parts of your car.

By inducing autophagy, we are clearing out worn-out and faulty cellular parts within our brain cells.

Our brain cells need to last a lifetime, so autophagy is our body’s unique way of naturally rejuvenating them and defending them from disease.

Autophagy.

How Does Autophagy Affect Your Brain and Mental Health?

What we’ve discovered is that autophagy protects against neurodegenerative diseases like Parkinson’s, Huntington’s and certain forms of dementia. If you switch on autophagy, you remove proteins rapidly, as well as protect against excessive inflammation. By learning how to influence this process, we are able to affect the progression of these diseases.
— Dr. David Rubinsztein, professor of molecular neurogenetics at the University of Cambridge and UK Dementia Research Institute

Research shows that autophagy supports the central nervous system, improves brain function and reduces neurological cellular breakdown (136-138).

And studies suggest that autophagy is a built-in defense mechanism that detoxifies and clears the central nervous system (139).

But the autophagy process becomes less efficient as we get older.

And over time, our brain cells accumulate a variety of damaged organelles, abnormal and pathogenic proteins, and oxidized particles (141-142).

This clogs up the brain, accelerates cognitive aging, and even contributes to the development of dementia (140).

But autophagy doesn’t just decline in older individuals.

Even younger people with depression and schizophrenia have been shown to have deficiencies in autophagy pathways (162-163).

In fact, researchers have found a link between autophagy dysfunction and many neurodegenerative, neurodevelopmental and neuropsychiatric disorders, including (143-161):

  • Alzheimer’s disease

  • Parkinson’s disease

  • Huntington’s disease

  • Schizophrenia

  • Depression

  • Bipolar disorder

  • Frontotemporal dementia

  • Amyotrophic Lateral Sclerosis

  • Autism spectrum disorders

  • Fragile X syndrome

  • Mood disorders

  • Psychotic symptoms

  • Behavioural change

The good news is that you can do something about this.

You have the power to activate autophagy.

There are several reliable and natural ways to increase it.

And by doing so, you can reduce neuroinflammation, protect the nervous system, improve cognitive function, encourage the growth of brain cells, and even fight depression and Alzheimer’s disease (164-174).

Read on to learn more about how you can induce autophagy.  

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Lifestyle Habits and Therapies That Induce Autophagy in the Brain

1. Exercise

Exercise is one of the best ways to boost autophagy in the brain.

Researchers have found that aerobic exercise induces neuronal autophagy (1).

They believe the reason why exercise improves cognitive function is perhaps because it increases autophagy in the brain (2).

Exercise is a stressor on the body, and the body induces autophagy so that your cells can recover from the stress. All it takes is 30 minutes of aerobic exercise to activate autophagy in the brain (3).

As a result, exercise increases neurogenesis and reduces neurodegeneration.

Many doctors and researchers recommend exercise as their number one piece of advice for optimal brain health.

You should find a sport or aerobic exercise routine that you enjoy, so that you’ll stick with it consistently.

2. Intermittent Fasting

One of the major benefits of fasting is a dramatic increase in autophagy, followed by a massive boost in stem cell production.
— Dr. Rhonda Patrick, PhD

Fasting is another biological stressor that promotes autophagy.

When you’re fasting, your body isn’t receiving nutrients, so it stresses out and triggers autophagy.

Researchers have found that fasting activates “profound autophagy” in the brain (24-26).

As a result, it can help treat neurological conditions and lowers the risk of cognitive decline and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (27-28).

So how long do you have to fast to trigger autophagy in the brain?

Research suggests 24 to 48-hour fasts are ideal and have the strongest effects (29).

But long fasts are not very realistic and practical.

Luckily, even shorter fasts have been shown to significantly promote neuronal autophagy (30-31).

That’s why I personally eat all my food for the day within an 8-hour window, and then fast for the other 16 hours of the day.

You don’t need to go that long, but you should try to fast for at least 12 hours at a time.

The best way to get started is simply by eating dinner around 6, not eating anything after that before bed, and then eating a regular breakfast the next day.

That should give you about 12-14 hours of fasting time.

3. A Ketogenic Diet

Ketogenesis is like an autophagy hack. You get a lot of the same metabolic changes and benefits of fasting without actually fasting.
— Dr. Colin Champ, MD

A ketogenic diet is a very high-fat, low-carb diet.

To follow the diet, you need to get most of your calories from healthy fats, and no more than 10 percent of calories from carbs (less than 50 grams of carbs per day).

When you restrict carbohydrate-rich foods – such as grains, sugar, and even potatoes, legumes and fruit – your body enters “ketosis”, a metabolic state in which your body and brain run on fatty acids and “ketones” instead of glucose.

And this be very beneficial and increase autophagy in the brain.

Researchers have found that ketosis is neuroprotective and reduces neurodegeneration by promoting autophagy in the brain (4-6).

Autophagy reduces amyloid beta, the main component of amyloid plaques found in the brains of patients with Alzheimer's disease (8-9).

An animal study also shows that ketosis reduces brain injury (during and after seizures) by activating autophagy (10).

I follow a ketogenic diet every so often.

Some of the best foods to eat if you follow a ketogenic diet include coconut oil, olive oil, pastured eggs, ghee, grass-fed meat, avocado, nuts and seeds.

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

I also take Optimal Ketones every day, which are exogenous ketones that get my body into a state of ketosis very quickly. That way I get the mental clarity of ketosis without having to follow a ketogenic diet all of the time.

Research shows that the ketone bodies in Optimal Ketones stimulates autophagy (7).

4. Circadian Rhythm, Melatonin and Deep Sleep

A baby sleeping. Sleep induces autophagy in the brain.

Getting enough high-quality sleep is very important if you want to increase autophagy.

I used to have very poor sleep and it was one of the main factors that contributed to my poor cognitive function.

Research shows that not getting enough sleep, and waking up intermittently throughout the night, negatively alters autophagy in the brain (11-12).

So it’s the length and quality of your sleep that matters.

That’s why I highly recommend getting at least 7 hours of uninterrupted sleep every night.

What can you do to improve your sleep?

  • Maintain a proper circadian rhythm

  • Promote the production and release of melatonin at night

Researchers have found that our circadian rhythm (sleep-wake cycle) controls autophagy and plays a role in cognitive decline (13-14).

Melatonin is a hormone released by your pineal gland, a small gland in your brain.

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

Melatonin has been shown to induce autophagy in the brain, and it reduces the risk of developing neuropsychiatric disorders (66-68).

Even mild changes in our external environment (i.e. blue lighting at night) can affect our circadian rhythm and reduce melatonin production, negatively altering autophagy and our cognition the next day (13-14).

Knowing this, here is what you can do to support melatonin production, maintain your circadian rhythm and maximize the quality of your sleep:

  • Expose your eyes to sun in the morning. This sets your circadium rhythm.

  • Keep a regular sleep schedule and go to bed at the same time every night.

  • Blue light significantly suppresses your body’s production of melatonin, leading to disrupted sleep patterns and abnormal functioning of your nervous system. As soon as it’s dark outside, you should avoid sources of blue light. Turn off household lights or install red light bulbs, install Iris on your computer and/or wear blue blocking glasses. These glasses block out blue light in your environment.

  • Don’t eat anything for 3 hours before bed, other than raw honey, bone broth and MCT oil, which are easy to digest and can actually support your sleep.

  • Avoid stimulating movies and TV before bed.

  • Avoid caffeine in the afternoon. Most people should completely avoid it after 2 pm. Some may have to cut it out even earlier. I can’t have any after 12 noon, otherwise the quality of my sleep suffers.

  • Sleep in a dark environment. Completely black out your room with curtains or wear a sleep mask overnight. Sleeping with lights on in your room decreases neurogenesis and impairs cognitive performance. If you need to have light in your room (nightlight or alarm clock), it’s better to have red, orange or amber lighting rather than blue.

  • Reduce stress before bed. I supplement with magnesium and lie on this acupressure mat for 10 minutes before bed.

  • Avoid alcohol before sleep, as it prevents getting into the deeper stages of sleep, which is when the body and brain heal.

  • Melatonin secretion can be disrupted by EMF exposure, so turn off cellphones, Wi-Fi and other electrical devices while you sleep.

If you’re still having trouble with sleep, try this sleep supplement. It contains natural compounds that I’ve used over the years to promote the production of melatonin.

5. Hot and Cold Exposure

Exposing yourself to both hot and cold temperatures can stress your cells and promote autophagy.

Several researchers have found that “heat stress” triggers autophagy and stimulates the autophagic process (15-18).

Autophagy and the heat-shock response are also tightly linked (19-20).

Researchers have found that cold exposure induces neuronal autophagy, and they believe it can reduce the risk of neurodegenerative diseases (21-22).

Research also shows that switching back and forth between cold and hot can induce autophagy (23).

So how does this translate into every day life?

Try switching back and forth between hot and cold in the shower.

Or spend time in a sauna or steam room, and then take a cold shower.

I personally like to go outside with minimal clothing in the winter, and then eventually come back inside and take a hot shower.

Cold plunges, cold baths and cryotherapy are some other ways to expose yourself to cold.

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6. Hyperbaric Oxygen Therapy

Hyperbaric oxygen therapy (HBOT) is a treatment that enhances healing and recovery after injury to the central nervous system.

Patients inhale 100% oxygen in a total body chamber.

Usually, oxygen is transported throughout the body only by red blood cells. But with HBOT, oxygen is dissolved into all body fluids, including the fluids of the central nervous system.

This leads to oxygen being carried to areas of the body where circulation is diminished or blocked. As a result, extra oxygen can reach all damaged tissues, including areas that need to heal.

Several studies have shown that HBOT elevates and enhances autophagy in the central nervous system (41-44).

You’ll need to find a practitioner or clinic in your area that provides this treatment.

HBOT can be expensive though. That's why I decided to buy my own oxygen concentrator. An oxygen concentrator is much less expensive than HBOT but it still helps a lot. My doctor recommended it to me and it has helped me recover.

I did a lot of research before buying my own and got this one. You can get it here or through Amazon. I use it almost every day. It's the best option on the market.

Check out my full article about oxygen therapy for more information.

7. Acupuncture

Acupuncture is an alternative treatment that has been shown to induce autophagy in the brain (69).

One study found that acupuncture improved learning and memory, and protected brain cells, by upregulating the autophagy pathway (70).

Another found that acupuncture promoted the “autophagic clearance” of proteins from the brain that contribute to Parkinson’s disease (71).

I’m a really big fan of auricular acupuncture. Auricular acupuncture is when needles are inserted into ear. I’d recommend trying to find a health practitioner in your area who provides it, especially if you’re weening off psychiatric medication. It really helped me the first time I came off antidepressants. I was surprised.

In my experience, ear acupuncture is more effective than regular acupuncture.

I also lie on this acupuncture mat at home to relax before bed.

Foods That Induce Autophagy in the Brain

8. Coffee and Caffeine

A cup of coffee on a plate with a spoon. Coffee induces autophagy in the brain.

Drinking coffee is another great way to induce autophagy in the brain.

Researchers have found that both regular and decaffeinated coffee rapidly trigger autophagy (32).

The polyphenols in coffee are also good for your brain health because they stimulate autophagy (32).

And other studies show that caffeine protects brain cells and lowers the risk of developing neurodegenerative diseases by inducing autophagy in the brain (33-35).

I drink one cup of this high-quality coffee every morning.

Coffee and caffeine can disrupt sleep though, so make sure you don’t drink it later in the day. I have my last cup sometime between 10 in the morning and noon. If I have it any later than that, it disrupts my sleep.

It’s also a good idea to try to consume the whole coffee fruit, instead of just the coffee bean or pure caffeine.

Traditionally, the coffee bean is extracted from the coffee fruit for roasting. And the surrounding fruit is discarded.

But that’s a problem because the coffee fruit contains several healthy compounds not found in coffee beans themselves.

And after years of careful clinical research, scientists have discovered that ingesting whole coffee fruit concentrate significantly increases brain function.

Coffee fruit concentrate is included in the Optimal Brain supplement.

9. Green Tea

Epigallocatechin-3-Gallate (EGCG) is the main polyphenol found in green tea.

It’s been shown to have anti-inflammatory and neuroprotective effects.

Researchers have found that EGCG stimulates autophagy in the brain, protects against brain cell toxicity and may help treat neurodegenerative disorders (36-38, 40).

It also improves learning and memory after chronic stress by restoring autophagic flux in the brain (39).

I personally drink organic green tea regularly, usually in place of coffee on days when I’m relaxing.

I also take Optimal Antiox, a supplement that includes green tea extract and EGCG.

10. Coconut Oil and Medium Chain Triglycerides (MCTs)

Coconut oil is one of the best foods for your brain.

It’s especially important if you want to support your thyroid.

But it can also stimulate autophagy in the brain by increasing ketone levels (45-46).

I eat one or two tablespoons of this coconut oil almost every day now, along with Optimal Ketones, to boost ketones and induce autophagy in my brain.

The medium-chain triglycerides (MCTs) within coconut oil are responsible for the ketone-increasing effects of coconut oil

If you don’t like coconut oil, you can supplement with pure MCT oil instead.

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11. Ginger

Ginger is one of the healthiest spices.

It contains lots of nutrients and bioactive compounds that have powerful, protective benefits for your brain (47-49).

6-shagol, one of the active compounds within ginger, induces autophagy (50-55).

12. Reishi Mushroom

Reishi mushroom (Ganoderma lucidum) is a powerful fungus with hundreds of bioactive compounds.

It has been used for thousands of years by Chinese medicine practitioners to support the immune system, regulate inflammation, lower anxiety and support brain function.

Research shows that reishi mushroom can induce autophagy (56).

It also protects the brain from oxidative stress by regulating autophagy (57-58).

I’ve supplemented with this reishi mushroom tincture in the past to support my immune system.

13. Turmeric (Curcumin)

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.

One reason is because it protects brain cells from damage by activating autophagy (59-61).

Curcumin is included in the Optimal Energy supplement.

14. Broccoli Sprouts (Sulforaphane)

Sulforaphane is a phytochemical found in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, cauliflower and kale.

It has potent antioxidant and anti-inflammatory actions, similar to curcumin.

Studies have shown that sulforaphane increases autophagy within brain cells (62-63).

As a result, researchers believe it can be a therapeutic tool in the treatment of neurodegenerative diseases (63).

Broccoli sprouts are the best source of sulforaphane.

You can also take sulforaphane in supplement form.

If you decide to take it in supplement form, make sure you get the "myrosinase-activated" form.

Myrosinase is the enzyme in broccoli that helps metabolize sulforaphane.

I once bought a supplement that didn't contain myrosinase and had to return it, and then ended up buying this one instead.

15. Galangal

Galangal is a spice.

It’s known as “Thai ginger” or “Siamese ginger” because it looks very similar to ginger.

But it’s actually a different spice altogether.

It's commonly found in Thai, Indonesian, and Malaysian cooking.

Galangin, a compound within galangal, has been shown to induce autophagy and protect dopaminergic neurons in the brain (64-65).

16. Extra Virgin Olive Oil (Oleuropein)

Olive oil on a picnic table. The antioxidants in olive oil can induce autophagy in the brain.

Olive oil has numerous health benefits, particularly because of its strong anti-inflammatory effects.

Oleuropein, a polyphenol found in olive oil, has been shown to induce autophagy and reduce cognitive impairment (92).

As a result, researchers propose that a diet with extra virgin olive oil might have potential benefits for Alzheimer’s patients because of its induction of autophagy (72).

I add olive oil to my salads and sometimes even just take a tablespoon of it straight.

Be careful though. A lot of cheap extra virgin olive oil in grocery stores are not actually “extra virgin.”

Investigations have found that there is a lot of fraud within the olive oil industry and many so-called extra virgin olive oils contains other cheaper, refined vegetable oils, such as soybean, corn and canola.

This is discussed more in the book Extra Virginity: The Sublime and Scandalous World of Olive Oil.

You don’t just have to eat olive oil to get the benefits of oleuropein though.

Oleuropein can also be found in olive leaf extract and argon oil.

17. Berries

Blueberries, strawberries, acai berries are included in my Free Grocery Shopping Guide for Optimal Brain.

And for good reason.

All three berries have been shown to significantly activate autophagy in the brain (74-74).

The polyphenols within them also protect brain cells from oxidative stress and inflammation and improve cognitive function.

I try to eat one cup of berries every day to support my brain health.

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18. Omega-3 Fatty Acids

Omega-3 fatty acids are essential fats that your body cannot produce itself, and they are absolutely necessary for 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 demonstrated that omega-3 fatty acids can increase BDNF signaling and enhance autophagy in the brain (108-112).

So increasing your intake of them is one of the most impactful actions you can take to support your brain.

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 Brain 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 feel off when I stop taking it. I actually notice the difference.

Some researchers believe that the beneficial effects of supplementing with omega-3 fatty acids may simply be due to their ability to activate autophagy (107).

Natural Supplements That Induce Autophagy in the Brain

19. Probiotics

Research suggests that certain probiotics can stimulate autophagy in the brain.

In one study, researchers gave the SLAB51 probiotic formulation to mice, and it partially restored autophagy in the brains of the mice (75).

The researchers also found that the SLAB51 probiotic reduced brain damage and decreased cognitive decline in the mice (75).

I tried to find the SLAB51 probiotic formulation online, but it doesn’t appear to be commercially available yet.

I personally take the Optimal Biotics supplement every day to support my gut and brain health.

I also like to drink kombucha and eat fermented foods regularly.

Check out this older article for several other ways to increase your good gut bacteria.

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

20. American Ginseng

American ginseng (Panax quinquefolius) is a powerful herb that enhances brain function.

Researchers have found that it induces autophagy, which then protects the brain from neurotoxicity and reduces mitochondrial dysfunction (76-78).

Because of this, researchers believe it can help treat neurodegenerative disorders (77, 79).

American ginseng is included in the Optimal Ketones supplement. I find it increases my mental clarity and energy.

21. 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, mood, mental energy and attention in both healthy and unhealthy individuals. It even reduces the risk of dementia and Alzheimer’s disease.

Researchers have also discovered it helps treat dementia and Alzheimer’s disease by activating and increasing autophagy in the brain (80-82).

Ginkgo Biloba is included in the Optimal Brain supplement.

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22. Acetyl-L-Carnitine

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 provides support to brain cells. It’s been shown to be very effective at alleviating chronic fatigue and improving mood.

Researchers have also found that it helps reverse cognitive decline and supports mitochondrial function by inducing autophagy in the brain (83-86).

I find that it personally gives me a big boost in mental energy and resilience.

ALCAR is included in the Optimal Brain supplement.

23. Vitamin D (and K2)

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

Unfortunately, researchers estimate that 50% of people are at risk of Vitamin D deficiency.

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

Research shows that Vitamin D, and activation of the Vitamin D receptor, induces autophagy (89-91, 93).

Vitamin D supplementation in mice also increases levels of autophagy (92).

One study found that Vitamin D can reduce neurological deficits caused by traumatic brain injury by restoring autophagy in the brain (95).

And some researchers have pointed out that Vitamin D deficiency is associated with many diseases that involve defective autophagy (94).

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 take this Vitamin D3 supplement.

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.

There is also some evidence that Vitamin K2 stimulates autophagy as well (87-88).

24. Lithium

Lithium is predominantly known as a medication given to bipolar patients to manage their symptoms.

However, it’s also an essential mineral.

Bipolar patients are often given high doses of lithium carbonate.

But low doses of lithium orotate can be safely supplemented to improve your brain health and increase the formation of myelin.

Research shows that lithium induces autophagy in the brain and enhances the breakdown and clearance of proteins that contribute to neuropsychiatric and neurodegenerative diseases.

Therefore, it may help treat Huntington’s disease, Alzheimer’s disease, Parkinson's disease, and dementia (96-97).

I used to take this lithium orotate. I don’t take it anymore because I don’t need it, but I remember it making me feel calm and stable.

25. Cannabidiol (CBD)

Cannabidiol (CBD) is one of the active cannabinoids found in marijuana.

Unlike tetrahydrocannabinol (THC), CBD isn’t psychoactive and doesn’t make you “high”.

But it can help treat a number of diseases because it reduces inflammation.

Researchers have found that CBD activates and enhances autophagy pathways in the brain (98-100).

I take this CBD oil and I highly recommend it. It significantly reduces my stress, makes me sleepy and knocks me out before bed.

You can get 15% off the same CBD oil by ordering through this page.

26. 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.

One study found that rhodiola can reduce neurodegeneration by inducing autophagy in the brain (101).

Other studies have found that the herb significantly upregulates autophagy (102-103).

I take this rhodiola supplement. I don't take it every day, only when I need a cognitive boost. You can get it here or here.

Check out this post all about rhodiola to learn more about this amazing herb.

27. Berberine

A bowl of berberine. Berberine induces autophagy in the brain.

Berberine is an alkaloid extracted from various plants.

It has anti-inflammatory, neuroprotective and possibly antidepressant effects. It can also improve intestinal health and lower cholesterol.

Researchers have also found that berberine reduces inflammation and protects the brain from damage by boosting autophagy in the brain (104-105).

One study even found it reduces neurological deficits and promotes neurogenesis by stimulating autophagy (106).

I’ve experimented with varying dosages of this berberine. I personally didn’t notice any profound brain and mental health benefits, but I have heard good things from other practitioners.

28. Nicotinamide

Nicotinamide, also known as niacinamide or nicotinic acid amide, is the water-soluble, active form of Vitamin B3.

It has been shown to reduce cognitive decline and halt the progression of Alzheimer’s disease by improving autophagy function in the brain (113-114).

It also improves cognitive performance and preserves mitochondrial integrity (113).

Nicotinamide is included in this supplement.

29. Schisandra

Schisandra is a berry commonly used by Traditional Chinese Medicine practitioners.

The seeds of the berry contain lignans, which have health-promoting properties.

It’s considered an adaptogen and traditionally used to treat depression, stress and menopause.

But lots of research shows that Schisandra can also benefit people struggling with Alzheimer’s disease and Parkinson’s disease (115-116).

This is because it reduces neurodegeneration and cognitive impairment by enhancing autophagy (117-120).

Besides promoting autophagy, it also has anti-inflammatory and neuroprotective effects upon brain cells (116).

You can also get Schisandra as dried whole berries or as juice.

But it usually isn’t used as a food.

Rather, it’s more commonly used as a supplement. It’s available in multiple forms, including dried powder and pills.

30. Spermidine

Spermidine is a polyamine compound with various metabolic functions.

It’s found in living tissues and within a wide range of foods, including aged cheese, fermented soy, chicken, mushrooms, pears and potatoes.

It can also be taken as a supplement.

Researchers have found that it’s neuroprotective and reduces synapse aging by enhancing autophagy in the brain (121-127).

As a result, it counteracts neurodegeneration, reduces memory impairment, and protects neurons from demyelination (121).

31. Resveratrol and Pterostilbene

Resveratrol is a beneficial antioxidant and anti-inflammatory compound found in grapes, red wine, raspberries and dark chocolate.

It’s known to help prevent the development of neurodegenerative diseases.

And researchers are starting to understand why.

Several studies have shown that resveratrol induces autophagy in the brain (128-132).

In two of the studies, it protected brain cells and helped brain cells recover after injury by enhancing autophagy (131-132).

Researchers propose it could even be used to help prevent and treat Alzheimer’s Disease due to its autophagy-enhancing effects (130).

To consume enough resveratrol to promote autophagy, you’ll need to supplement with it.

Resveratrol is included in the Optimal Energy supplement.

Pterostilbene, a compound found in blueberries, is very similar to resveratrol, and it has also been shown to induce autophagy (133-135).

I tried this pterostilbene and it was beneficial, but I didn’t find it any more helpful than resveratrol, so I’ve decided to just stick with resveratrol considering it has significantly more research to back it up.

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

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Jordan Fallis

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

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25 Powerful Ways to Boost Your Endocannabinoid System

The endogenous cannabinoid system, named after the plant that led to its discovery, is perhaps the most important physiologic system involved in establishing and maintaining human health.
— Dr. Dustin Sulak

It’s becoming increasingly clear that stimulating and supporting your endocannabinoid system is another way to improve your brain and mental health. 

But you don’t need to smoke marijuana to do this. 

There are a number of other options, and this articles explore them.

Marijuana leaf and the endocannabinoid system.

But first, what exactly is your endocannabinoid system? 

Well, your body actually creates its own cannabinoids, similar to those found in cannabis. 

And these naturally-occurring cannabinoids bind to cannabinoid receptors within your body and brain.

You can think of these receptors like little “locks”, and your body’s cannabinoids fit naturally into these locks like “keys”. Together, they make up your endocannabinoid system, which can influence your appetite, pain, inflammation, sleep, stress responses, mood, memory, motivation, reward, etc. (91-92). 

There are two main cannabinoid receptors – cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2). 

An illustration of CB1 and CB2 receptors in the body and brain.

CB1 receptors are mostly found in the brain and impact a number of neurotransmitters, including GABA, glutamate, dopamine and serotonin. CB2 receptors, on the other hand, are mostly found within the immune system and blood cells (93-99).

However, it’s important to note that some CB1 receptors are still located outside the brain, and some CB2 receptors can be found within the brain. So, there is some overlap. 

According to Martin Lee, author of Smoke Signals: A Social History of Marijuana, cannabinoid receptors are more abundant in the brain than any other type of neurotransmitter receptor.

There are two different types of cannabinoids that can activate these receptors in your body:

  • Phytocannabinoids – plant-derived cannabinoids, such as tetrahydrocannabinol (THC) and cannabidiol (CBD) found in marijuana

  • Endocannabinoids – as mentioned before, these cannabinoids are produced naturally within the body. Anandamide is the main endocannabinoid in your body. It can be found in humans, but also many other animals and plants. It binds to both CB1 and CB2 receptors and has similar effects as THC. 2-Arachidonoylglycerol (2-AG) is another critical endocannabinoid in your body that also binds to the CB1 and CB2 receptors. Its effects are similar to CBD (100-107).

What Are the Benefits of Stimulating and Supporting Your Endocannabinoid System?

Modulating the activity of the endocannabinoid system has turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson’s and Huntington’s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few.
— Dr. Pal Pacher, M.D., Ph.D

There is an increasing amount of research linking a number of illnesses and symptoms to low endocannabinoids levels, including:

Some researchers are convinced that when your body doesn’t produce enough endocannabinoids (anandamide and 2-AG), you’re more likely to develop these diseases.

They’ve even coined the term “Clinical Endocannabinoid Deficiency” to describe the problem (108). 

But if you have one of the above conditions, don’t worry!

You can stimulate and support your endocannabinoid system naturally, which can lead to a number of brain and mental health benefits:

CDB receptor synapses.

So without further ado, here are 25 ways to stimulate and support your endocannabinoid system naturally.

1. Cold Exposure

Cold exposure has been shown to increase endocannabinoid levels (1). 

Researchers have also found that cold exposure significantly increases the density of CB1 neurons (2). 

A man sitting outside in the freezing cold. Cold exposure stimulates the endocannabinoid system.

To support my endocannabinoid system, I take a cold shower every day, and often go outside with minimal clothing in the winter.

Try finishing your next shower with at least 30 seconds of cold water and see how you feel.

Then work your way up to longer periods of time.

It's painful to do, but the lingering effects are worth it.

You can also ease yourself into it by simply sticking your face in ice cold water.

Cold exposure also stimulates the vagus nerve.

2. Sex Hormones

Male and female sex hormones also stimulate and support the endocannabinoid system.

Both testosterone and estradiol have been shown to upregulate CB1 receptors (3-4). 

Estradiol also increases the synthesis and release of the endocannabinoids (anandamide), which activates CB1 receptors (5-6). 

And the plasma levels of anandamide correlate nicely with the levels of estrogen during the menstrual cycle in women (7). 

I recommend both men and women get their hormones checked regularly. I had low testosterone and testosterone replacement therapy (TRT) really improved my brain and mental health. I no longer need TRT though. 

3. Coffee

Drinking coffee is another way to stimulate and support your endocannabinoid system. 

Researchers believe that the cannabinoid system is involved in the psychoactive properties of caffeine (10). 

Regular caffeine consumption has been shown to enhance the activation of CB1 receptors by endocannabinoids (8). 

CB1 receptors are also downregulated after “social defeat stress”, but caffeine counteracts this effect (9). 

I drink one cup of this coffee most mornings.

Coffee and caffeine can disrupt sleep though, so make sure you don’t drink it later in the day. I have my last cup sometime between 10 in the morning and noon. If I have it any later than that, it disrupts my sleep.

It's also a good idea to try to consume the whole coffee fruit, instead of just the coffee bean or pure caffeine. 

Traditionally, the coffee bean is extracted from the coffee fruit for roasting. And the surrounding fruit is discarded. 

But that’s a huge problem! 

Because the coffee fruit contains several healthy compounds not found in coffee beans themselves.

And after years of careful clinical research, scientists have discovered that ingesting whole coffee fruit concentrate significantly increases brain function. 

Coffee fruit concentrate is included in the Optimal Brain supplement

4. Extra Virgin Olive Oil

Olive oil has numerous health benefits, particularly because of its strong anti-inflammatory effects.

It’s also been shown to upregulate CB1 receptors (11).

I add olive oil to my salads and sometimes even just take a tablespoon of it straight.

Be careful though. A lot of cheap extra virgin olive oil in grocery stores are not actually “extra virgin.”

Investigations have found that there is a lot of fraud within the olive oil industry and many so-called extra virgin olive oils contains other cheaper, refined vegetable oils, such as soybean, corn and canola. 

This is discussed more in the book Extra Virginity: The Sublime and Scandalous World of Olive Oil.

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5. Cannabidiol (CBD) Oil

Cannabidiol (CBD) is one of the active cannabinoids in cannabis. It is not psychoactive but has a wide range of medical applications.

Research shows that CBD enhances the expression of CB1 receptors in the brain (12-13). 

It also increases levels of 2-AG by preventing it from breaking down (14-15). 

I take this CBD oil and I highly recommend it.

It reduces my stress, makes me really sleepy and knocks me out before bed.

You can get 15% off by ordering it through this page.

6. Flavonoids

Flavonoids are a diverse group of plant compounds found in almost all fruits and vegetables.

Chocolate, tea, wine, and some beans, herbs, spices, nuts and seeds also contain them. Overall, the more colorful a food is, the richer it is in flavonoids.

Fruits and vegetables that are rich in flavinoids, which are known to stimulate the endocannabinoid system.

The following flavonoids inhibit fatty acid amide hydrolase (FAAH), which is the enzyme responsible for the breakdown of the endocannabinoids (anandamide) (16):

  • Genistein

  • Kaempferol

  • 7-hydroxyflavone

  • 3,7-dihydroxyflavone

I try to eat as many fruits and vegetables as possible on a daily basis so that I’m consuming plenty of flavonoids. It’s best to consume fruits and vegetables in their raw forms to receive the highest number of flavonoids, as cooked fruits and vegetables have less.

Check out my Free Grocery Shopping Guide for Optimal Brain Health for a bunch of flavonoid-rich foods. 

7. Tea

Tea contains catechins, which are antioxidant compounds that have anti-inflammatory and neuroprotective effects.

Researchers have found that catechins in tea target and bind to cannabinoid receptors in the central nervous system (25-26).

Epigallocatechin gallate (EGCG) is the most well known catechin. It’s found in green tea. I take a concentrated green tea extract with EGCG to support my endocannabinoid system. 

Drinking tea can also lower cortisol, and green tea increases BDNF

8. Kava

Kava is a plant located in the western Pacific. The root of the plant is used medicinally to treat anxiety and sleep disorders because it causes relaxation without impacting cognitive performance. Some people say it feels like drinking alcohol (30-31). 

Researchers have evaluated commercially available kava supplements to see whether they bind to cannabinoid receptors. They found that yangonin, a compound in kava, binds to the CB1 receptor, and concluded that kava’s anti-anxiety effects may be because it stimulates the endocannabinoid system (32). 

I searched for kava supplements that include yangonin and found this one. I personally don’t take kava anymore because I get a weird reaction and my functional medical practitioner confirmed I’m allergic to the plant. 

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9. Osteopathy

Osteopathy is a healing modality that emphasizes the treatment of disease by manipulating and massaging the bones, joints, and muscles. 

One study found that endocannabinoid levels increased by 168% on average after osteopathic treatment. (33). 

Practitioners of osteopathy are referred to as osteopaths. I saw an osteopath in Ottawa soon after my concussions in 2010. I had been suffering from constant dizziness, and his therapy completely reversed the dizziness. And it was permanent. The dizziness never came back. I was amazed and very grateful. 

I recommend finding an osteopath in your area if you’ve ever suffered a traumatic brain injury. If you happen to be in the Ottawa area, go to this one

10. Probiotics

Research suggests that some probiotics can stimulate and support the endocannabinoid system. 

In one study, researchers found that a specific strain of probiotic, lactobacillus acidophilus, increases the expression of CB2 receptors (53). 

Lactobacillus acidophilus is included in the Optimal Biotics supplement.

Probiotics have also been shown to stimulate the vagus nerve and help with depression

And here are five other ways to increase the good bacteria in your gut. 

11. Dark Chocolate

Most people know dark chocolate is rich in multiple antioxidants, such as flavonols and polyphenols, which reduce oxidative stress.

But interestingly, it also contains the endocannabinoid anandamide (54). 

And it includes other compounds that slow down the breakdown of anandamide, increasing the amount of anandamide that stimulates your endocannabinoid system (55-56). 

This is likely why eating chocolate makes people feel so good.

Dark chocolate also increases BDNF and reduces cortisol.  

Here is my favourite high-quality dark chocolate

This one is also very good. 

12. Reduce Stress

I highly recommend you try to do something every day to manage your stress because emotional stress has been shown to downregulate CB1 receptors (57-58). 

High cortisol levels for prolonged periods of time, such as those caused by chronically stressful circumstances, also reduces CB1 receptors and significantly reduces cannabinoid binding to CB1 receptors (59-62). 

On top of this, chronic psychological stress reduces endocannabinoid levels in the brain (63-66). 

A hand squeezing a stress ball. Reducing stress can support your endocannabinoid system.

Overall, researchers say there is strong evidence that the endocannabinoid system as a whole is required in order to properly deal with stress (67). 

My favourite ways to reduce stress include neurofeedback, meditation (using the Muse headband), massage, acupuncture, eye movement desensitization and reprocessing (EMDR), emotional freedom techniques (EFT), heart-rate variability (HRV) training, and this acupressure mat

Some supplements that can help you reduce stress include zinc, magnesium, ashwagandha and phosphatidylserine.

This anti-anxiety supplement also includes a number of natural compounds that have personally helped me manage my stress over the years (Use the the coupon code FIVE$45496275 for a 5% discount).

And here is an article with 20 other ways to lower your stress hormone, cortisol. 

13. Magnolia Officinalis

Magnolia Officinalis is a plant that has neuroprotective properties and relaxing effects.

It’s used in Chinese traditional medicine for the treatment of anxiety, depression and sleeping disorders. 

Researchers have found that Magnolia officinalis extract and its main bioactive constituents, magnolol and honokiol, can activate cannabinoid receptors (17). 

Here is a good extract

Alternatively, you can drink Magnolia tea. 

Both the tea and extract should be taken with a meal consuming fat because the active ingredients are fat soluble. 

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14. Exercise

Exercise is another great way to stimulate and support your endocannabinoid system.

Medium and high-intensity exercise has been shown to activate the endocannabinoid system (73). 

Research also shows that exercise significantly upregulates CB1 receptors and enhances CB1 receptor sensitivity, which is why exercise can protect against the consequences of stress (68, 72, 74). 

Exercise-related improvements in memory are also due to activation of the CB1 receptor. Blocking this receptor seems to prevent the memory benefits of exercise (69, 72). 

Several studies also show that exercise increases levels of anandamide and activates cannabinoid signaling (70-71). 

Illustration of people running. Exercise stimulates the endocannabinoid system.

And researchers now believe that endocannabinoids may actually be responsible for the “runner’s high” (euphoria) during exercise, and not endorphins (76-77). 

However, you shouldn’t force yourself to exercise. Forced exercise is seen by the endocannabinoid system as a type of stress, and therefore doesn’t increase endocannabinoid levels and can actually decrease CB1 signaling (75). 

So, you should find an aerobic activity that you enjoy so that it’s not a burden.

This is exercise routine I try to follow consistently:

  • Lift heavy weights 1-4 times per week

  • High-intensity interval sprinting 1-2 times per week

  • Walk as much as I can (ideally 30-60 minutes every day)

  • Run for 20-30 minutes before lifting weights

Many brain health experts recommend exercise as their number one piece of advice for optimal brain health. 

15. Palmitoylethanolamide

Palmitoylethanolamide (PEA) is a natural compound that has anti-inflammatory and neuroprotective effects, and low levels of PEA can contribute to chronic brain inflammation and pain (20). 

Research shows that PEA can alleviate pain and increase mood by enhancing endocannabinoid activity (18-19, 21-24).

PEA is naturally found within the body, but it’s also available as a supplement. It's even used for medical purposes in Italy and Spain. 

You can get it here.

16. Omega-3 Fatty Acids

Omega-3 fatty acids are essential fats that your body cannot produce itself. They are necessary for the normal electrical functioning of your brain and nervous system.

Research shows that they increase the synthesis of endocannabinoids and upregulate both CB1 and CB2 receptors (78-79). 

There is also a connection between low omega-3 fatty acid intake, poor endocannabinoid function and mood changes (80). 

Omega-3 fatty acids are found primarily in cold water fish such as salmon, black cod, sablefish, sardines and herring.

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

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

I take this one

You can also get very high-quality seafood and krill oil supplements here.

And you can read more about the importance of omega-3 fatty acids here

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17. Agmatine

Agmatine is a metabolite of the amino acid arginine. It can help reduce pain, treat drug addiction, and protect the brain from toxins (27-28). 

It has been shown to enhance the painkilling effects of cannabinoids. It does this by increasing cannabinoid action and signalling through the CB1 receptor (29). 

My personal experience with agmatine is that it made me agitated, so I stopped taking it. But I don’t have any symptoms of pain. If you do, I think it’s worth trying.

You can get it here.

18. Caryophyllene

Caryophyllene is a compound found in many plants and essential oils, including clove, rosemary, basil, oregano, lavender, and hops. It also contributes to the spiciness of black pepper (34). 

Caryophyllene has been shown to have anti-inflammatory, neuroprotective, antidepressant, anti-anxiety and anti-alcoholism effects (35, 40-41). 

These effects are likely because it binds to the cannabinoid receptors (36-37, 39, 42-43). 

It can also help reduce neuropathic pain through the CB2 receptor (38). 

19. Echinacea

Echinacea is a Native American medicinal plant and one of the most popular medicinal herbs.

People often use it to reduce flu symptoms and shorten the duration of the common cold. It is sometimes used to reduce anxiety and relieve fatigue as well.

Compounds in Echinacea, called alkylamides, have been shown to reduce inflammation by binding to the CB2 receptor (44, 46-47). 

Researchers have also found that alkylamides increase the effect of endocannabinoids (45). 

There are a large variety of Echinacea supplements available through Amazon.

20. Black Truffle

Tuber melanosporum, also called the black truffle, is an edible mushroom native to Southern Europe.

Researchers have found the endocannabinoid anandamide within black truffles (49). 

Black truffle peelings are available here. They can be added meals and go particularly well with mashed potatoes. 

21. Diindolylmethane (DIM)

Diindolylmethane (DIM) is an anti-carcinogenic compound found in cruciferous vegetables such as broccoli, cauliflower, Brussels sprouts, cabbage and kale.

DIM is one of the reasons why these foods are considered so healthy. 

Studies show that DIM reduces inflammation because it binds to CB2 receptors (50-51). 

It's also available in supplement form here.

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22. Ruta Graveolens

Ruta graveolens, commonly known as rue, is a medicinal herb.

Researchers have found that a compound within it binds to the cannabinoid receptors (52). 

Rue can be taken as an extract. You can get it here.

23. Acmella Oleracea

Acmella Oleracea, also known as Electric Daisy, is a medicinal herb originating from the Amazon region. 

It contains phytocannabinoids and other compounds that can reduce pain and inflammation (81-82). 

It’s available as an extract.

24. Helichrysum Umbraculigerum

Helichrysum Umbraculigerum is a plant with anti-inflammatory and antioxidant properties, originating from South Africa.

It’s been used medicinally for thousands of years, especially in countries like Italy, Spain, and Portugal. 

It’s been shown to have antidepressant effects likely because it contains cannabigerol, a phytocannabinoid that stimulates the endocannabinoid system (83-85). 

A number of different essential oils are available through Amazon

25. Radula Marginata

Radula Marginata is a plant commonly found in New Zealand.

It contains cannabinoids and cannabinoid-like compounds that bind to CB1 receptors, activating the endocannabinoid system (86-90). 

Conclusion

As you can see, there are many different ways to stimulate your endocannabinoid system besides smoking cannabis. 

And supporting this important system can lead to a number of brain and mental health benefits. 

I hope you implement some of these strategies into your regular routine and notice you feel better and live more optimally over time. 

If you think you know someone who might benefit from this article, please share it with them.

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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(116) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685476/

(117) http://www.leafscience.com/2013/11/04/study-memory-benefits-exercise-tied-cannabinoid-system/

(118) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817535/

(119) https://www.ncbi.nlm.nih.gov/pubmed/16224541

(120) https://www.ncbi.nlm.nih.gov/pubmed/16037095

(121) http://www.jci.org/articles/view/25509

(122) http://www.leafscience.com/2013/11/04/study-memory-benefits-exercise-tied-cannabinoid-system/

(123) https://www.ncbi.nlm.nih.gov/pubmed/15044630

(124) http://www.ncbi.nlm.nih.gov/pubmed/21480865

(125) https://www.ncbi.nlm.nih.gov/pubmed/10716447

(126) https://www.ncbi.nlm.nih.gov/pubmed/11156943

(127) https://www.ncbi.nlm.nih.gov/pubmed/8569415

(128) https://www.ncbi.nlm.nih.gov/pubmed/9813364

(129) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685476/

(130) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817535/

(131) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685476/

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(133) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817535/

(134) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685476/

(135) https://www.ncbi.nlm.nih.gov/pubmed/22265864

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

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16 Powerful Ways to Effectively Lower Homocysteine

Lowering and normalizing homocysteine levels is another key way to improve the health of your brain and manage your mental health. 

In fact, keeping homocysteine levels within normal range is good for overall health in general. 

But what exactly is homocysteine?

Homocysteine is an amino acid that is produced in the body as a by-product of methylation.

In healthy people, it’s properly metabolized and normal levels are maintained. 

But when homocysteine isn’t properly metabolized, it can build up inside the body and levels can become too high.

And that’s when homocysteine becomes dangerous and unhealthy. 

At high levels, homocysteine is inflammatory and neurotoxic, and increases oxidative stress and free radical damage in the brain by reducing levels of cysteine and glutathione (89-95, 138-139). 

Homocysteine and it’s chemical symbol.

It’s also been shown to contribute to mitochondrial damage and reduce energy production in the brain (96-98). 

Researchers have found that high levels of homocysteine disrupt the integrity of the blood-brain barrier, which allows substances that are normally kept out of the brain to cross over and contribute to neurological problems (99-102). 

And studies have found that people with high levels of homocysteine have lower levels of serotonin and SAMe, a nutrient involved in the production of many neurotransmitters that improve mood (103-104). 

Considering all this, it’s not too surprising that high levels of homocysteine have been linked to many chronic neurodegenerative and neuropsychiatric diseases, including:

  • Depression (105-111)

  • Dementia, Alzheimer’s disease, cognitive impairment/dysfunction/decline (119-133, 143)

  • Headaches and migraines (112-118, 148)

  • Hearing loss (136-137)

  • Brain atrophy (134, 144, 151)

  • Parkinson’s disease (145)

  • Stroke (154-155)

  • Postpartum depression (135)

  • Postmenopausal mental decline (146)

  • Schizophrenia and other affective disorders (147, 153, 156)

  • Alcoholism (149)

  • Brain damage and neurotoxicity (152)

  • Obsessive–compulsive disorder (157)

  • Multiple sclerosis (158-161)

People with nutritional deficiencies and MTHFR gene mutation are at an increased risk of high homocysteine levels. Homocysteine levels gradually increase as you age, and men are more likely than women to have high levels of homocysteine (140-142). 

Thankfully, there are a number of ways to lower homocysteine.

Here are 16 ways to keep your homocysteine levels in check. 

1. Trimethylglycine

Trimethylglycine (also known as betaine) is an amino acid derivative that can be found in plants such as beets and spinach. 

Trimethylglycine plays an important role in methylation, a process that is involved in the synthesis of melatonin, coenzyme Q10, and neurotransmitters such as dopamine and serotonin. 

An image of beets. Beets contain betaine, which has been shown to lower homocysteine levels.

Several studies show that supplementing with trimethylglycine can significantly lower homocysteine levels (1-5). 

One study found that the more trimethyglycine a person consumes, the lower their homocysteine levels (6).

According to the research, it appears that you need to supplement with at least three grams of trimethyglycine daily to significantly reduce homocysteine. Doing so will reduce homocysteine levels by 10% in persons with normal levels or by 20 to 40% in persons with elevated homocysteine levels (7-9).

However, even 500mg seems to lower homocysteine slightly (10). 

I took this trimethylglycine supplement after coming off psychiatric medication and noticed an improvement in mood and energy. 

2. Folate

The best way to lower homocysteine is by making sure you consume enough B vitamins on a regular basis.

Folate is one of the most important B vitamins because it helps metabolize homocysteine into methionine (51). 

When your body doesn’t have enough folate, elevated levels of homocysteine are the result (52). 

A pile of green, leafy vegetables. They contain folate, a key nutrient involved in lowering and normalizing homocysteine levels.

Good dietary sources of natural folate include leafy greens, asparagus, broccoli, cauliflower, strawberries, avocado, beef liver and poultry. These foods are included in my Free Grocery Shopping Guide for Optimal Brain Health.

However, folate-rich foods may not be enough to lower homocysteine. In fact, many people do not get enough folate from food because cooking and food processing destroy natural folates (57). 

That’s why I recommend supplementation. 

Supplementing with 800 mcg of folate has been shown to lower homocysteine by at least 28%. Even supplementing with just 113 mcg daily lowers homocysteine by about 15% (53-56, 58, 62). 

If you decide to supplement with folate, avoid synthetic folic acid, which is commonly found in standard multivitamins. Instead, you should take a biologically active form of folate (methylfolate, or 5-MTHF). 

5-MTHF is the most effective supplemental form of folate. 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.

Methylfolate supplements are almost seven times more effective than synthetic folic acid at increasing folate levels and lowering homocysteine levels. Regular synthetic folic acid has been shown to be quickly cleared from the central nervous system and poorly transported into the brain (59-61). 

3. Vitamin B12

Vitamin B12 is another nutrient that plays a role in methylation. It's also a necessary cofactor in the metabolism of homocysteine (75-77). 

Research shows that Vitamin B12 deficiency can contribute to rising homocysteine levels (78-80, 83-84). 

But in those with elevated homocysteine, supplementing with 1,000 mcg of B12 per day can significantly lower and normalize blood levels of homocysteine (81-82).

Ordinary B12 supplements don’t always cut it though.

If you decide to supplement, you should avoid the semisynthetic version of B12 (cyanocobalamin) and take the methylated form (methyl-B12) instead, which is better absorbed and more biologically active.

Methyl-B12 is included in this supplement

Vitamin B12 is also found primarily 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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4. Vitamin B6

Vitamin B6 is another homocysteine-reducing nutrient that boosts mood, deepens sleep, and supports your entire nervous system. 

It accomplishes this by playing a key role in the production of many neurotransmitters in your brain, including serotonin, GABA and dopamine.

Vitamin B6 is also a necessary cofactor in the metabolism of homocysteine, and having a deficiency can cause homocysteine levels to increase (14).

In fact, low blood levels of B6 are common, especially in people with higher homocysteine levels (15). 

Thankfully, supplementation has been shown to help lower and normalize homocysteine levels (11-13). 

Fruits and vegetables in the shape of B6. Vitamin B6 has been shown to lower homocysteine levels.

However, it’s important to point out that it’s best to supplement B6 along with both folate and B12 if you want to dramatically lower homocysteine levels. 

Supplementing with B6, B12 and folate has been shown to significantly lower homocysteine levels and reduce symptoms of depression (87). 

One study found that within three weeks, homocysteine levels could be reduced by 17% using folate alone, 19% using B12 alone, 57% using folate and B12, and 60% using folate, B12 and B6 (86). 

Another study found that combining B6 and folate reduces homocysteine 32% within five weeks (85).

That’s why I highly recommend supplementing with a high-quality B complex that contains all three B vitamins. 

Symptoms of Vitamin B6 deficiency include weakness, mental confusion, depression, insomnia and severe PMS symptoms.

Some of the best food sources of Vitamin B6 include potatoes, bananas and chicken. They are included in my free food guide.

5. Taurine

Taurine is an organic compound found in foods, particularly animal products. It has a wide variety of health benefits.

It can cross the blood-brain barrier and produces anti-anxiety effects, and acts as an antioxidant in the brain, protecting it from various substances including lead and cadmium (16-25). 

It’s also been shown to lower homocysteine. 

Research shows that taurine supplementation significantly reduces plasma homocysteine levels (26-28).

Taurine is included in the Optimal Zinc supplement

6. Creatine

Creatine is a molecule produced in the body and found in some foods, particularly meat, eggs, and fish.

Creatine is also available in supplement form. Athletes, bodybuilders, wrestlers, sprinters often take creatine supplement to gain more muscle mass. It’s an incredibly well-researched supplement and safe to take regularly. 

A scoop of creatine powder next to weights. Creatine lowers homocysteine levels.

Supplementing with creatine can also support the brain. It's been shown to have neuroprotective effects and it rapidly produces energy to support brain cell function (29). 

Research shows that creatine supplementation can also lower homocysteine in humans (32, 34). 

Animal studies show the same (30-31, 33).

Creatine gives me energy, which is why I included it in Optimal Energy.

I take extra creatine when I’m lifting weights regularly.

7. Green Coffee Extract

Green coffee extract is a supplement that is derived from green coffee beans. 

Green coffee beans are similar to regular coffee beans. However, they contain much more chlorogenic acid in them.

Chlorogenic acid is a phytochemical with cognitive health benefits

One study found that 140 mg of chlorogenic acid, which is 28% of the content of green coffee extract, can significantly lower homocysteine (39). 

Here is a good green coffee extract

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8. Reduce Stress

I highly recommend you try to do something every day to manage your stress because psychological stress has been shown to significantly increase homocysteine levels (70-71). 

A woman meditating on the beach near the water. Reducing stress can help you to lower your homocysteine levels.

My favourite ways to reduce stress include neurofeedback, meditation (using the Muse headband), massage, acupuncture, eye movement desensitization and reprocessing (EMDR), emotional freedom techniques (EFT), heart-rate variability (HRV) training, and this acupressure mat

Some supplements that can help you reduce stress include zinc, magnesium, ashwagandha and phosphatidylserine.

This anti-anxiety supplement also includes a number of natural compounds that have personally helped me manage my stress over the years.

And here is an article with 20 other ways to lower your stress hormone, cortisol.

9. Estrogen

Estrogen is the primary female sex hormone and responsible for the development and regulation of the female reproductive system.

Research shows that higher estrogen levels are associated with lower homocysteine levels, independent of nutritional status and muscle mass (72). 

And individuals on estrogen replacement therapy have significantly lower homocysteine levels (72-73). 

I recommend both men and women get their hormone levels checked regularly and optimize them because it can really improve your quality of life. 

10. Choline

Choline is an essential B vitamin that most people don’t consume enough of, because very few foods in the Western diet contain it.

Research shows that high homocysteine levels can be lowered with choline (40-42). 

Deviled eggs. Eggs contain choline, a nutrient that can lower homocysteine levels.

One study found that increased intake of choline led to lower levels of circulating homocysteine (43). 

And other studies have shown that choline deficiency in mice and humans is associated with increased homocysteine levels (44). 

Citicoline (also known as CDP-Choline) is my favourite source of choline for the brain. 

Citicoline also supports the blood-brain barrier and promotes the regeneration of myelin

Another good source of choline for brain health is Alpha GPC.

Both Citicoline and Alpha GPC are included in the Optimal Brain supplement

You can also find some choline in beef liver and egg yolks, but Citicoline and Alpha GPC have more noticeable effects on cognition. 

11. N-Acetyl-Cysteine

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.

I’ve previously discussed how NAC can help treat six different mental illnesses.

And it turns out that it can also help lower homocysteine levels. 

Research shows NAC supplementation can cause a “rapid and significant decrease” in homocysteine levels (49). 

Studies have found that NAC can decrease homocysteine anywhere from 25 to 45 per cent (47-48, 50).

Researchers believe NAC displaces homocysteine from its protein carrier in the blood, which lowers homocysteine and promotes the formation of glutathione (45-46). 

12. Omega-3 Fatty Acids

Is there anything omega-3 fatty acids can’t do?

They can promote the regeneration of myelin, stimulate the vagus nerve, help reverse brain damage, and support the endocannabinoid system

And now it appears they can also lower homocysteine levels. 

A randomized double-blind placebo-controlled clinical trial found that consuming three grams of omega-3 fatty acids daily for 2 months significantly decreases levels of homocysteine (63). 

Other researchers have reported that omega-3s can lower homocysteine by 36 to 48% (64-65). 

Salmon and walnuts. They contain omega-3 fatty acids, which have been shown to lower homocysteine levels.

And studies have also found that people using B vitamins to lower homocysteine should also have enough omega-3s to improve brain function. In fact, some clinical trials using B vitamins to improve brain function show benefits only in people with higher omega-3 levels (143-144). 

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

Omega-3 fatty acids are found primarily in cold water fish such as salmon, black cod, sablefish, sardines and herring.

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

That’s why I recommend people supplement with krill oil, a special kind of fish oil that contains omega-3s. 

I take this krill oil supplement. I feel slightly depressed when I stop taking it. I actually notice the difference.

You can also order very high-quality seafood and krill oil supplements here

And you can read more about the importance of omega-3 fatty acids here.

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13. Probiotics

Research suggests that probiotics may also be able to lower homocysteine.

Bacteria. Probiotic bacteria can lower homocysteine levels.

In one interesting study, researchers gave the probiotic VSL#3 to subjects with high homocysteine.

The researchers found that the probiotic increased the number of good bacteria in the gut, which then naturally increased Vitamin B12 and folate production in the gut. As a result, homocysteine levels dropped (66). 

You can get the VSL#3 probiotic used in the above study here.

I personally created and take the Optimal Biotics supplement to support my brain and mental health. 

Probiotics have also been shown to stimulate the vagus nerve and help with depression

And here are five other ways to increase the good bacteria in your gut. 

14. Avoid Alcohol

Alcohol is a neurotoxin that wreaks havoc on the brain by raising cortisol levels, disrupting the blood-brain barrier, and increasing inflammation and oxidative stress (67).

It also increases homocysteine. 

One study found that alcohol significantly reduces Vitamin B12 and folate levels and increased homocysteine levels (68). 

And another study found that alcohol consumption increased homocysteine levels regardless of Vitamin B levels (69). 

There are ways to protect your brain from alcohol, but you’re better off avoiding it completely or significantly reducing your consumption if you’re trying to heal. I personally don’t drink alcohol at all anymore.

If you do decide to drink it, this post explains that some types of alcohol are better than others

15. Eat “Head to Tail”

Whole plant foods tend to be much healthier when they’re left whole, as they tend to have various nutrients that work together synergistically. 

The same can be said about animal food.

Muscle meat (chicken breasts, lean beef) shouldn’t be your only source of animal protein. Our ancestors didn’t eat this way, so neither should we.

Your body prefers and expects to receive a balance of amino acids from different parts of whole animals.

That’s why I recommend “head-to-tail eating” – consuming a wide variety of proteins from the entire animal. 

Along with muscle meat, you should regularly cook and eat organ meats, such as liver, and bone broth.

One of the main reasons I recommend this is because lean muscle meat is high in methionine.

Methionine is an essential amino acid, but too much methionine increases homocysteine levels and increases your need for Vitamin B6, B12, folate and choline (74, 88, 162). 

But bone broth contains collagen, gelatin, and amino acids such as glycine and proline, which balance out the methionine in muscle meat, and helps your body better metabolize it. 

Bone broth can be inconvenient to make all the time, so I drink this pre-made, organic chicken bone broth

And if you’re actually interested in learning about how to cook and incorporate more whole animal proteins into your diet, I recommend checking out the book Odd Bits: How to Cook the Rest of the Animal by Jennifer McLagan.

16. Limit Medications and Compounds That Increase Homocysteine

A number of prescription drugs and natural compounds have been shown to increase homocysteine by interfering with folate absorption, or metabolism of homocysteine, including (35-38):

Various natural health supplements on table.
  • Cholestyramine

  • Colestipol

  • Fenofibrate

  • Levadopa

  • Metformin

  • Methotrexate

  • Niacin

  • Nitrous oxide

  • Pemetrexed

  • Phenytoin

  • Pyrimethamine

  • Sulfasalazine

Conclusion

High levels of homocysteine can be problematic and increase your risk of many brain and mental health disorders.

But fortunately, you can do something about it!

Implementing the above 16 strategies can provide powerful protection against homocysteine’s negative effects and improve your quality life. 

I’ve found great benefit in lowering my homocysteine levels, and I hope you experience the same. 

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

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