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  • Antidepressants work no better than placebo in terms of effectiveness. Studies now suggest their effectiveness can be boosted by adding certain supplements, but other studies suggest the supplements alone may do the trick
  • Fish oil, vitamin D, methylfolate (a form of folic acid/vitamin B9), and S-Adenosylmethionine (SAMe) were found to boost the impact of the antidepressants when compared to medication only
  • Other studies have shown that omega-3, vitamin D, and SAMe can help combat depression all on their own. In fact, both omega-3 and vitamin D are very important for mental health

Supplements Proven Beneficial for Depression

July 14, 2016 | 253,867 views
| Available in EspañolDisponible en Español

By Dr. Mercola

One in 20 Americans over the age of 12 struggles with depression1 and 11 percent of the U.S. population over the age of 12 is on antidepressant medication.2 This, despite overwhelming evidence showing that antidepressants are no better than placebo in terms of effectiveness.

As noted in a 2014 paper on antidepressants and the placebo effect, published in the journal Zeitschrift Fur Psychologie:3

"Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed, their supposed effectiveness is the primary evidence for the chemical imbalance theory.

But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect ...

Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind."

Serotonin Theory Has Been Proven Wrong

Research4,5 published in 2009 added further evidence to the pile indicating the low serotonin idea was incorrect, as they found strong indications that depression actually begins further up in the chain of events in the brain. Essentially, the medications have been focusing on the effect, not the cause.

More recent research into the mechanisms driving anxiety and social phobias has also turned conventional drug treatment with serotonin reuptake inhibitors (SSRIs) on its ear.

As it turns out, these mental health problems are actually linked to elevated levels of serotonin in the amygdala, not low levels.6,7,8,9 Your amygdala is the seat of primitive emotions such as fear. And the more serotonin produced in this area, the more anxious you feel.

This helps explain why some depressed patients end up feeling more anxious than before when taking a serotonin-boosting antidepressant. As noted in the paper above:

"The serotonin theory is as close as any theory in the history of science to having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future."

Vitamins and Supplements Boost Effectiveness of Antidepressants

A recent study10 raises even more questions about the effectiveness of antidepressants.

The meta-analysis, published in the American Journal of Psychiatry, found that certain nutritional supplements boosted the effectiveness of several classes of antidepressants, including SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants.

A total of 40 clinical trials were included in the review, and four supplements — fish oil, vitamin D, methylfolate (an effective form of folic acid), and S-Adenosylmethionine (SAMe) — were found to boost the impact of the medication when compared to medication only.

Fish oil — specifically the fat EPA — produced the most significant improvement. Studies investigating the use of creatine, zinc, vitamin C, tryptophan (an amino acid), and folic acid (B9) produced mixed results. As reported by Scientific American:11

"By some estimates, two-thirds don't respond to the first antidepressant they try and a third fail to get better after several treatment attempts.

'The implications are that clinicians and the public can consider [adding] therapeutic doses of nutrients such as omega-3s as a potential low-cost approach to reducing depression in people who are non-responsive to antidepressants,' (lead author Jerome Sarris) says."

Could Supplements Alone Be Responsible for Improvements?

According to the authors, "more patients in the studies showed an improvement in mood when prescribed omega-3 fish oil, methylfolate, vitamin D and SAMe supplements in combination with antidepressant medication, compared to those who took medication only."12

What's really missing here is a comparison between supplements only, medication only, and a combination of both.

Considering the fact that antidepressants have been proven to be no better than placebo, and can worsen depression in some people, perhaps patients would experience the same or even better results just by taking the supplement, without the drug.

If that's indeed the case, then why risk your health by taking an antidepressant? In fact, other studies have shown that both omega-3 and vitamin D can help improve mental health all on their own.

One likely theory as to why they work is because these supplements help combat inflammation and oxidative stress, not only in your brain but also in your gut.

Depression is often found alongside gastrointestinal inflammation, autoimmune diseases, cardiovascular diseases, neurodegenerative diseases, type 2 diabetes, and cancer.

Chronic low-grade inflammation is a significant contributing factor to all of these, leading researchers to suggest that "depression may be a neuropsychiatric manifestation of a chronic inflammatory syndrome," and that the primary cause of inflammation may be dysfunction of the gut-brain axis.13

An increasing number of clinical studies have indeed confirmed that treating gastrointestinal inflammation with probiotics, omega-3, and vitamins B and D can improve symptoms of depression by attenuating pro-inflammatory stimuli to your brain that originate in your gut.14

The Importance of Omega-3

Many Americans' diets are lacking in healthy fats, including the animal-based omega-3 fats EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Although omega-3s are most well known for their role in heart health, they also play an integral role in brain health and mental health.

The 2001 book, "The Omega-3 Connection," written by Harvard psychiatrist Dr. Andrew Stoll, was among the first works to bring attention to, and support the use of, omega-3 fats for depression.

There is no set recommended standard dose of omega-3 fats, but some health organizations recommend a daily dose of 250 to 500 milligrams (mg) of EPA and DHA for healthy adults. If you suffer from depression, higher doses may be called for.

In one study,15 an omega-3 supplement with a dose range of 200 to 2,200 mg of EPA per day was effective against primary depression. Omega-3 has also been shown to improve more serious mental disorders, including schizophrenia, psychosis, and bipolar disorder.16

Making sure you're getting enough omega-3s in your diet, either from wild Alaskan salmon, sardines and anchovies, or a high-quality omega-3 supplement, I believe, absolutely crucial for optimal health, including brain health, so it doesn't surprise me in the least that it was found to be the most effective addition against depression.

Low Vitamin D Repeatedly Linked to Depression

Vitamin D receptors appear in a wide variety of brain tissue early in the fetal development, and activated vitamin D receptors increase nerve growth in your brain. Researchers believe that optimal vitamin D levels may enhance the amount of important chemicals in your brain and protect brain cells by increasing the effectiveness of the glial cells in nursing damaged neurons back to health. As noted by the Vitamin D Council:17

"Exactly how vitamin D works in the brain isn't fully understood. One theory is that vitamin D affects the amount of chemicals called monoamines, such as serotonin, and how they work in the brain. Many anti-depressant medications work by increasing the amount of monoamines in the brain. Therefore, researchers have suggested that vitamin D may also increase the amount of monoamines, which may help treat depression."18

Regardless of the exact mechanism, a number of studies have linked low vitamin D to depression, including the following:

  • Seniors with the lowest levels of vitamin D have been found to be 11 times more prone to be depressed than those who had normal levels.
  • A study19 conducted by VU University Medical Center in Amsterdam found that people with minor and major depression had on average 14 percent lower vitamin D levels than non-depressed participants.
  • In another study,20 people with vitamin D levels below 20 ng/mL had an 85 percent increased risk of depression compared to those with vitamin D levels greater than 30 ng/mL.
  • Vitamin D deficiency has long been associated with Seasonal Affective Disorder (SAD)21 and, in 2007, researchers noted that vitamin D deficiency is associated with depression and fibromyalgia.22
  • A double-blind randomized trial23 published in 2008 also concluded that: "It appears to be a relation between serum levels of 25(OH)D and symptoms of depression. Supplementation with high doses of vitamin D seems to ameliorate these symptoms indicating a possible causal relationship."

Other Supplements and Habits Shown to Lessen Depressive Symptoms

SAMe is an amino acid derivative that occurs naturally in all cells. It plays a role in many biological reactions by transferring its methyl group to DNA, proteins, phospholipids and biogenic amines. Several scientific studies indicate that SAMe may be useful in the treatment of depression.

5-Hydroxytryptophan (5-HTP) is another natural alternative to traditional antidepressants. When your body sets about manufacturing serotonin, it first makes 5-HTP. Taking 5-HTP as a supplement may raise serotonin levels.

The evidence suggests 5-HTP outperforms a placebo when it comes to alleviating depression24 — more than can be said about antidepressants! However, keep in mind that anxiety and social phobias can worsen with higher levels of serotonin, so it may be contraindicated if your anxiety is already high. St. John's Wort has also been shown to provide relief from mild depressive symptoms.

While the featured study found some benefit from methylfolate, vitamin B12 deficiency can also contribute to depression, and affects about 1 in 4 people. If you're curious about methylfolate read through this quick summary of its side effects.25 Vitamin B12, on the other hand, is sorely needed by many, and if you're deficient, may help lessen symptoms of depression. Additionally to the best of my knowledge there have never been any overdoses of vitamin B12. It's incredibly safe.

Many also suffer from "exercise deficiency," and exercise is one of the most potent anti-depressants at your disposal. Research has confirmed it actually outperforms drug treatment. It's also a key treatment strategy for anxiety disorders.

Exercise primarily works by helping to normalize your insulin levels while simultaneously boosting "feel good" hormones in your brain. But researchers have also recently discovered that exercise helps your body eliminate kynurenine, a harmful protein associated with depression.26

And, confirming the link between inflammation and depression, your body metabolizes kynurenine in the first place via a process that is activated by stress and inflammatory factors. Additionally, exercise increases BDNF (brain-derived neurotropic factor) and is a powerful activator of mitochondrial biogenesis.

Key Factors to Overcoming Depression and Anxiety Without Drugs

It's important to realize that your diet and general lifestyle are foundational factors that must be optimized if you want to resolve mental health problems such as depression or anxiety, because your body and mind are so closely interrelated. For example, while many think of their brain as the organ in charge of their mental health, your gut may actually play a far more significant role.

The drug treatments available today for depression fail miserably in addressing people's mental health problems. While adding one or more supplements to the treatment protocol is a step in the right direction, it still falls short, as the side effects of these drugs can be worse than the original complaint, running the gamut from sexual side effects to lack of emotions or "emotional flatness," restlessness, sleep disturbances, brain damage, and even to suicide and homicide.

Antidepressants can also result in chronic, long-term, and worsening depression, so ideally, you'll want to avoid them unless absolutely necessary.

Since antidepressants are on par with placebo in terms of effectiveness, wouldn't it make sense to try something else first? Your diet is an obvious place to start. Research tells us that the composition of your gut flora not only affects your physical health, but also has a significant impact on your brain function and mental state, and your gut microbiome can be quickly impacted by dietary changes — for better or worse.

Research has also revealed there are a number of other safe effective ways to address depression that do not involve hazardous drugs. So, if you suffer from an anxiety or depression-related disorder, please consider addressing the following diet and lifestyle factors before you resort to drugs:

Eat real food, and avoid all processed foods, sugar (particularly fructose), grains and GMOs

High sugar and starchy carbohydrates lead to excessive insulin release, which can result in falling blood sugar levels, or hypoglycemia. In turn, hypoglycemia causes your brain to secrete glutamate in levels that can cause agitation, depression, anger, anxiety, and panic attacks.

Sugar also fans the flames of inflammation in your body. In addition to being high in sugar and grains, processed foods also contain a variety of additives that can affect your brain function and mental state, especially MSG, and artificial sweeteners such as aspartame.

Gluten sensitivity is also a common, hidden cause of depression, so going on a gluten-free diet can be part of the answer. Recent research also shows that glyphosate, used in large quantities on genetically engineered crops like corn, soy, and sugar beets, limits your body's ability to detoxify foreign chemical compounds.

As a result, the damaging effects of those toxins are magnified, potentially resulting in a wide variety of diseases, including brain disorders that have both psychological and behavioral effects.

Increase consumption of traditionally fermented and cultured foods

Reducing gut inflammation is imperative when addressing mental health issues,27 so optimizing your gut flora is a critical piece. To promote healthy gut flora, increase your consumption of probiotic foods, such as fermented vegetables, kimchee, natto and kefir.

Get adequate vitamin B12

Vitamin B12 deficiency can contribute to depression and affects one in four people.

Optimize your vitamin D levels

Vitamin D is very important for your mood. Remember, Seasonal Affective Disorder is a type of depression related to sunshine deficiency, so it would make sense that the perfect way to optimize your vitamin D is through UV exposure. Be sure to check your levels (via blood test) at least once or twice a year. You'll want to be within the therapeutic range of 40 to 60 ng/ml year-round.

If you cannot get sufficient sun exposure to maintain this level, taking an oral vitamin D3 supplement would be advisable. Just remember to also increase your vitamin K2 when taking oral vitamin D.

Get plenty of high-quality animal-based omega-3 fats

Your brain is 60 percent fat, and DHA, an animal-based omega-3 fat, along with EPA, is crucial for good brain function and mental health28,29 Unfortunately, most people don't get enough from diet alone, so make sure you take a high-quality omega-3 fat.

Evaluate your salt intake

Sodium deficiency actually creates symptoms that are very much like those of depression. Make sure you do NOT use processed salt (regular table salt), however. You'll want to use an all natural, unprocessed salt like Himalayan salt, which contains more than 80 different micronutrients.

Get adequate daily exercise

Studies have shown there is a strong correlation between improved mood and aerobic capacity. There's also a growing acceptance that the mind-body connection is very real, and that maintaining good physical health can significantly lower your risk of developing depression in the first place.

Exercising creates new GABA-producing neurons that help induce a natural state of calm. It also boosts your levels of serotonin, dopamine, and norepinephrine, which help buffer the effects of stress.

Get enough sleep

You can have the best diet and exercise program possible but if you aren't sleeping well you can easily become depressed. Sleep and depression are so intimately linked that a sleep disorder is actually part of the definition of the symptom complex that gives the label depression.

Energy psychology

Energy psychology techniques such as the Emotional Freedom Techniques (EFT) can also be very effective for reducing symptoms of depression or anxiety by correcting the bioelectrical short-circuiting that causes your body's reactions — without adverse effects.

Recent research has shown that EFT significantly increases positive emotions, such as hope and enjoyment, and decreases negative emotional states. EFT is particularly powerful for treating stress and anxiety because it specifically targets your amygdala and hippocampus, which are the parts of your brain that help you decide whether or not something is a threat.30,21

For serious or complex issues, seek out a qualified health care professional that is trained in EFT32 to help guide you through the process.

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