Finding an effective antidepressant medication can be challenging, since their effects often take weeks to manifest, efficacy rates are marginal, and individual responses can vary considerably. Moreover, common adverse side effects from SSRIs and SNRIs, the most widely prescribed antidepressants, include weight gain, gastrointestinal upset, sexual dysfunction, headaches, fatigue, insomnia, anxiety, dry mouth, and increased blood pressure.
(For an insightful review of why medications usually come with adverse side effects, why most doctors don’t prescribe more natural alternatives, and why a synergistic approach with nutritional supplements and lifestyle changes may be even more effective click here.)
For these and other reasons many who are placed on antidepressant meds wish there were other more natural and more effective remedies without the nasty side effects. The sad yet encouraging reality, as we hope you are finding in this review, is that such remedies exist, but most people have no idea where to find them! And it was for that reason that this website was build. So we hope you are encouraged by what you are finding here.
Earlier in this article we reviewed studies showing the efficacy of simply eating a healthier diet, with more fruit and vegetables. In this section we will share with you a variety of “food” supplements, that often bring quicker, safer and even more powerful results, especially when taken in combination.
1) SAMe (S-adenosyl methionine) This is a natural compound formed in our body from vitamin B-9 folic acid (from fruit and other foliage), vitamin B-12 from fish, eggs and various animal products and homocysteine, a marker of inflammation in the brain. SAMe levels tend to drop with age, and are especially low in Alzheimer’s patients. However, some research suggests SAMe could be more powerful as an antidepressant than any vitamin. In a 2009 Harvard study SAMe was found to be more effective—than a leading pharmaceutical drug alone for “treatment-resistant” patients. It helped improve mood and a host of other stress related conditions, without the side effects often associated with such drugs. (See a review of that study by clicking here.)
Moreover, SAMe’s mood-enhancing effects are generally seen much sooner than with standard antidepressants—often within 60 minutes of taking it, especially if taken on an empty stomach. However, because its initial effects can be a bit overwhelming—even dizzying the first time—if taken on an empty stomach, it’s suggested that it be taken initially with a meal, and only later on its own with juice. Effective doses are usually around 400 to 1200 mg.
In addition to relieving depressive symptoms, SAMe is effective in fighting liver toxicity (whereas some antidepressant drugs may contribute to liver problems) relieving arthritis pain, reducing aggression in older AD patients, and even supporting healthy arteries.
One of the reasons SAMe is so effective as an antidepressant is because it not only increases serotonin levels, but like other newer antidepressants on the market, it can also increase other mood-elevating neurotransmitters like dopamine and acetylcholine—which can enhance memory. And some research suggests it may increase the sensitivity of neuron receptors to these 3 neurotransmitters.
Therefore, SAMe may be helpful for either Type 1 (lethargic) or Type 2 (agitated) depression. Although it’s likely to be more effective with Type 2 men.
The one caution for SAMe is that it should not be taken by those with a history of mania or a “bi-polar” disorder. Fish oil high in DHA and EPA (see below) would likely be more helpful for them.
2) Vitamin B complex – These help provide an biological foundation for a healthy nervous system. They consists of nine water-soluble B vitamins that have related roles as cofactors in a diverse array of biochemical reactions, and are necessary for normal cellular metabolism and energy production. Vitamins B1 (thiamine), B3 (niacin), B6 (pyridoxine), B9 (folate), and B12 (cobalamin) are needed for normal nerve function, and deficiencies have been linked to depression. Adequate amounts of the trio of methylators, B6, B9, and B12, are required for the conversion of homocysteine into S-adenosyl methionine, or SAMe, a form of methionine involved in the synthesis of many critical biomolecules, including neurotransmitters. Deficiencies of any of these three B vitamins can raise homocysteine levels. High homocysteine levels have been associated with increased risk of depression, as well as cardiovascular, neurological, and other chronic diseases.
Once again the B-vitamins, are pretty basic and so should be helpful for either Type 1 or Type 2. However, they may be more helpful for Type 1’s as they tend to help boost energy.
Clinical trials have shown supplementing with B vitamins can lower levels of perceived stress and improve mood in healthy individuals. Long-term folate and B12 supplementation has been found to reduce the risk of relapse in individuals with major depression, and may help prevent the onset of major depression in people at high risk. (For study references See #11 Nutrients under the Life Extension Protocol for Depression and Depressive Disorders.)
3) L-Tryptophan or 5-HTP - L-tryptophan, is the amino acid precursor to the neurotransmitter serotonin, an important mediator of communication between the gut and the central nervous system. L-tryptophan is also a precursor to melatonin and vitamin B3 (niacin), as well as several other metabolites. Altered tryptophan metabolism may be a contributing factor in depression risk and may connect depression to other chronic conditions. Some evidence suggests stress can disrupt normal tryptophan metabolism, interfering with serotonin production and leading to increased inflammation and risk of depression. L-tryptophan levels have been noted to diminish with age.
A meta-analysis of studies found patients with major depression have lower levels of circulating tryptophan. Increased tryptophan intake is associated with reduced depressive symptoms and increased sociability, and randomized controlled trials indicate supplementing with up to 3 grams L-tryptophan daily may improve positive mood in healthy adults. Genetic factors that influence tryptophan metabolism appear to determine in part individual responsiveness to L-tryptophan supplementation.
However, research by Judith and Richard Wurtman, PhDs at MIT have shown that, L-tryptophan does not compete well with other proteins for entrance into the brain. Therefore, if one wants to raise serotonin levels it’s best to take L-tryptophan with a simple carbohydrate, like pasta, a muffin, or bread, with a bit of grape or apple juice independent of other protein rich food. That was more of it is likely to cross the blood brain barrier to create serotonin in the brain. Another alternative would be to take 5-HTP instead.
5-hydroxytryptophan (5-HTP) is a byproduct of tryptophan metabolism and the immediate precursor to serotonin. Supplementing with 5-HTP instead of L-tryptophan may avoid the high- jacking of L-tryptophan to form other metabolites and thus reduce the conversion of tryptophan to serotonin. Randomized controlled trials have found 5-HTP, mainly in doses of 200–300 mg per day, is more effective than placebo and comparable to first-line antidepressants in treating major depression. Some evidence suggests 5-HTP may also increase responsiveness to antidepressant therapy. 5-HTP can cause digestive upset in some users but has not been linked to serotonin syndrome or serious adverse effects.
5-HTP and the serotonin it enhances should be most helpful for those who are more agitated, crave carbs and have a hard time get enough sleep, etc.
Before we complete our list of natural mood boosters we need to identify one additional major player in depression and that is Dopamine. The lack or dysregulation of dopamine signaling may play an important though less-recognized role in depression. Dopamine plays a role in both learning and memory, and mediates feelings of pleasure and motivation. Deficits in dopamine signaling in specific brain regions may be associated with depression and are thought to contribute particularly to the loss of interest, pleasure, and motivation that are hallmark symptoms of depression. Older antidepressants called monoamine oxidase inhibitors (MAOIs) increase dopamine levels, as well as levels of serotonin and norepinephrine, by blocking their breakdown.
So if the depression you are addressing is characterized by a loss of interest, pleasure or motivation, as in Type 1 (lethargy) depression, then you may be low in dopamine, and you may want to watch this video by Dr. LeGrand on How to Increase Dopamine Levels Naturally. It contains some helpful insights as well as cautions, i.e. you likely need to be working with a doctor on this who is familiar with nutritional or Functional Medicine, especially if you are currently on a medication.
4) Mucuna Pruriens – Is a bean that contains L-Dopa the precursor to the neurotransmitter dopamine. It’s been used in Ayurveda medicine since 1500 B.C. For treating conditions like “melancholy” or mood disorders. It’s currently used to help individuals with Parkinson’’s symptoms. Research shows that supplementing with L-DOPA extracted from Mucuna Pruriens can be a good natural antidepressant if you are low in dopamine. User’s of Mucuna report that using Mucuna Pruriens helps in multi-tasking, improving motivation, more focus, less stress, and a sense of calm. According to Nootropics Expert. “You could find your energy levels increase, less brain fog, and a boost in overall mood. A more positive outlook on life. And an increase in libido.” (In contrast to some antidepressants that tend to inhibit libido. Nootropic is a term used for the study of natural remedies that promote brain health and cognitive function.)
5) Aniracetam— Is a prescribed medicine in some parts of the world, but in the US it does not require a prescription. It works to help balance both dopamine and glutamate receptors in the brain. Both of these help provide energy for various brain functions. According to the one Nootropic expert “Aniracetam is one of the most effective antidepressants I’ve ever tried. And its effects on dopamine in your brain can have a profound effect on anxiety symptoms as well.” Too learn more go to: https://nootropicsexpert.com/aniracetam/
(L-tyrosine, Rhodiola and L-theanine are also dopamine enhancers that are available at most any health food store. In fact L-theanine can help to boost both dopamine as well as GABA, to help reduce anxiety for Type 2 (agitated) individuals.
Note the additional co-factors mentioned by Dr. LeGrand, that may be lacking and needed as well - zinc, the B-vitamins, vitamin C and SAMe.
Additionally it’s important to note that there are a variety of other activities that can also aid in the production of dopamine. These include:
For a more complete list click on the link below.
The 36 Best Natural Ways to Increase Dopamine Levels in the Brain — Optimal Living Dynamics
6) Magnesium – Magnesium is essential to ensure the correct functioning of all human cells, including neurons in the brain; it is involved, in hundreds of enzymatic reactions, neuro transmissions, myelination (communication line protection), synapse formation and maintenance as well as in the regulation of nerve cell transmissions of serotonin, dopamine and acetylcholine. Any cramps in the body, like a restless leg are a sign of a possible magnesium deficiency. For these and other reasons, magnesium can play a major role in calming nerves and facilitating sleep at night. An thus could be very helpful for an individual suffering from Type 2 (agitated) depression. But it can also help individuals with energy issues in the morning.
A study was conducted with 5,708 people in Norway. The aim of the study was to examine the association between magnesium intake and depression and anxiety. The researchers found that indeed depression was correlated with low magnesium intake.
Other studies have reported higher magnesium intake and serum levels are associated with lower likelihood of depression and decreased depressive symptoms. Several uncontrolled trials have found magnesium supplementation is effective for reducing depressive symptoms. In one crossover trial that included 126 patients with mild-to-moderate depression, supplementing with 248 mg elemental magnesium (as magnesium chloride) per day for six weeks resulted in a significant reduction in symptoms compared with no treatment.
Another trial noted 500 mg of magnesium oxide daily for eight weeks reduced symptoms significantly more than placebo in 60 depressed patients with magnesium deficiency.
While magnesium oxide has been shown to be helpful for heart burn and constipation it does not appear to be as effective for the nervous system as magnesium glycinate, malate, citrate or other newer combo products.
In cell and animal research, magnesium L-threonate, a magnesium salt that more readily permeates the central nervous system, has been found to raise brain magnesium levels, improve brain structure and function, prevent nerve damage due to toxicity or low oxygen levels, and reduce symptoms of neurological diseases. In a study in rats, magnesium L-threonate reduced depression-like symptoms and improved memory more than other forms of magnesium.
References to the studies noted above and additional related research on depression can be found at: https://www.lifeextension.com/protocols/emotional-health/depression#
A new form combining magnesium with the protein Taurine, called Magnesium acetyl taurate, sold by Life Extension under the name CalmMag, has been shown to be even more effective for calming nerves, promoting sleep etc, especially for women with premenstrual syndrome.
After receiving 385 mg of magnesium acetyl taurate twice daily over a series of three consecutive menstrual cycles, scores for numerous symptoms were significantly reduced, including those for nervous tension, anxiety, irritability, headache, fatigue, and depression.
7) Probiotics - The gut microbiome has a close relationship with the brain and plays a fundamental role in regulating mood and cognitive function. People with depression have been found to have reduced gut microbial abundance and diversity, a pattern associated with poorer health in general. Eating probiotic-rich fermented foods was correlated with lower risk of major depression in one study.
Multiple clinical trials, reviews, and meta-analyses indicate probiotic supplements can be effective in treating depression. In an 8-week trial that included 110 patients being treated with antidepressant drugs for mild-to-moderate depression, those receiving a probiotic with 10 billion colony forming units (CFUs) of combined Lactobacillus helveticus R00052 and Bifidobacterium longum R00175 had greater reductions in scores on a test for depression than those receiving placebo.
A placebo-controlled trial that enrolled 90 subjects with mild-to-moderate depression found taking a probiotic supplement providing 1 billion CFUs of L. plantarum, along with 200 mg SAMe, daily for six weeks effectively reduced depression symptom scores as well as depression-related anxiety and cognitive changes. A probiotic supplement with 2 billion CFUs per day each of L. acidophilus, L. casei, and B. bifidum reduced depression symptoms and improved some markers of insulin resistance, oxidative stress, and inflammation better than placebo in 40 subjects with major depression after eight weeks.
The addition of a probiotic supplement containing Clostridium butyricum, at 60 mg per day, to standard antidepressant therapy resulted in a 70% response rate and 35% remission rate in an open trial in 40 patients with treatment-resistant depression. Another small open trial in treatment-resistant depression patients found the addition of a mixed probiotic with a total of 20 billion CFUs of L. acidophilus, B. bifidum, and Streptococcus thermophilus, plus 1,600 mg per day magnesium orotate, to antidepressant therapy led to improvement in depression and quality of life scores in eight of 12 participants (67%) after eight weeks. (References to the studies noted above and below can be found at: https://www.lifeextension.com/protocols/emotional-health/depression#)
8) Omega-3 Fatty Acids - The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important components of nerve cell membranes, affecting their fluidity and ability to send and receive signals. They are also used in the body to produce anti-inflammatory compounds that regulate nerve function by interacting with cannabinoid receptors. These effects have been correlated with improvement in major depression. Preclinical research further suggests EPA and DHA enhance neuroplasticity (the ability of brain cells to adapt).
Eating moderate amounts of fatty fish, the main dietary source of EPA, DHA, and other omega-3 fatty acids, have been shown to reduce the risk of depression. And in people with depression higher levels of omega-3 fatty acids have been correlated with less severe symptoms.
Numerous randomized controlled trials using supplements with EPA and DHA in proportions of 2:1 or 3:1 and at doses of 1–2 grams per day have been found to help alleviate depression. Omega-3 fats may be especially helpful for depressed individuals with metabolic disorders such as type 2 diabetes, obesity, and cardiovascular disease.
Based on the abundance of evidence, the International Society for Nutritional Psychiatry Research recommends the use of EPA in the treatment and prevention of major depression. However, many researchers feel the unique role of DHA in supporting emotional health should also be recognized.
DHA is the most prevalent fatty acid in the central nervous system. Not only is DHA incorporated into nerve cell membranes, where it is necessary for normal structure and function, it is also a critical component of other brain cells that use it to support neuron growth and formation of nerve connections. Furthermore, DHA is a source for other critical anti-inflammatory molecules called resolvins and protectins. Certainly, the Omega 3’s, are worth consideration for anyone suffering from mood swings (including bipolar) or other cognitive disorders.
9) DHEA (Dehydroepiandrosterone)— Sex hormones like testosterone and estradiol also play important roles in stress management and mood. DHEA is an adrenal hormone that our body uses to produce testosterone and estradiol. It also has immune-modulating and metabolic effects independently of its role as a sex hormone precursor. DHEA has been shown to contribute to mood modulation, is neuroprotective, and has anti-stress activity. Individuals with depression have been found to have low DHEA-sulfate (DHEA-s) levels, and the ratio of cortisol (the stress hormone) and DHEA-s has been suggested to be a measure of stress vulnerability in depression.
Persistent disturbance of the cortisol:DHEA ratio during remission from depression may be an indicator of recurrence risk – i.e. one is more likely to have a relapse into depression if that ratio is out of balance.
This ratio is particularly important for older individuals who are more prone to hormone decline. In a randomized controlled trial that included 17 participants with midlife-onset depression, taking 90 mg of DHEA daily for three weeks resulted in greater improvement in depression symptoms compared with placebo.
Similarly, a placebo-controlled trial involving 46 participants with major or non-major midlife-onset depression also noted the antidepressant effect of DHEA. In another trial, 22 participants with major depression, some of whom were being treated with antidepressant therapy, received either 90 mg DHEA per day for six weeks or placebo. Compared with the control group, more participants in the DHEA group experienced a treatment response, defined as a 50% reduction in depression symptoms
While DHEA might be helpful for either Type, the Type 1, may benefit most.
10) Acetyl-L-Carnitine (ALCAR)—This is a form of the amino acid L-carnitine, which is important for normal mitochondrial energy metabolism. Acetyl-L-carnitine readily crosses the blood-brain barrier to increase energy production in the brain. It is also thought to have brain-protective effects related to anti-inflammatory and antioxidative stress mechanisms, and promote neuroplasticity. Acetyl-L-carnitine levels in the blood have been reported to be lower in depressed than non-depressed subjects, and levels were noted to drop with decreasing age of depression onset and increasing severity; patients with treatment-resistant depression and a history of childhood trauma had the lowest levels.
A meta-analysis of 12 randomized controlled trials with a combined total of 791 participants found acetyl-L-carnitine was more effective than placebo and had similar efficacy to widely-prescribed antidepressant drugs for reducing depression symptoms. A 7-week placebo-controlled trial in 80 elderly patients with subthreshold depression found acetyl-L-carnitine was as effective as the antidepressant fluoxetine for reducing symptoms, but symptomatic improvements were more rapid with acetyl-L-carnitine than fluoxetine. Acetyl-L-carnitine in doses of 1,500 mg per day has been found to reduce depression symptoms and pain and improve quality of life in patients with fibromyalgia syndrome more effectively than placebo and similarly to the more addicting duloxetine (Cymbalta).
ALCAR would likely be most helpful for someone with Type 1 depression.)
One of the annoying problems with drug therapies, is the potential danger of adverse interactions. Anyone who works in this field is aware of the fact that whenever a person gets 4 or more meds on board, there is often a potential danger of these adversely impacting each other.
Just the opposite is true with nutrients however. Nutrients alone seldom adversely impact each other. To the contrary they tend to support and enhance the effectiveness of each other—so the more the merrier! That’s why in the British study people reported feeling better if they ate 7 servings of fruit and vegetables than when they ate just 2 or 3.
Applying that principle to the supplements above, 200 mg of SAMe alone might be helpful, but if a person took 5-HTP or DHEA, in conjunction with a good coenzyme B-complex, and probiotic, with a Calm Mag, Omega 3 fish oil, and Acety-l-Carnitine, maybe some Mucuna if they lacked motivation or haf trouble focusing, now they’d have a very powerful “Nootropic stack.”
Sure that will likely cost more than a cup of coffee and Cocoa-puffs, but the studies above suggest that within a month or two (if not a week), they should be feeling better, and then as their diet improves maybe they can start backing off of one or two these.
So while none of the supplements noted above are likely, on their own, to effect a major reversal of depressive symptoms, a wise blood test based combination of these, especially when taken in conjunction with a variety of dietary, cognitive and lifestyle initiatives like eating less sugar and more vegetables, increasing physical activity, especially in the sun, shifting focus from depressing thoughts to more hopeful possibilities, praying and practicing mindfulness, and getting a good night’s sleep can all work in concert to exert a very powerful synergistic effect.
(Note: References to the studies noted above and additional related research on depression can be found at: https://www.lifeextension.com/protocols/emotional-health/depression# . There are other nutrients there worth considering as well.)
But if all of that is a bit overwhelming for you right now, we would invite you to consider the following Simple Daily Strategy. And once you are feeling a bit better you can return to develop a more comprehensive and more powerful plan to improve your mind and mood.
Caution: If you are currently taking a medication for anxiety or depression, we suggest you consult with your physician before stopping or replacing any of your medications. Switching from meds to natural remedies can be tricky, and dangerous. We suggest you explore theroadback.org website and their free online book titled: How To Get Off Psychiatric Drugs Safely by James Harper, under the PROGRAM tab.
And we would encourage you to discuss your plans with a Functional Med Physician, or a professional health provider familiar with both the meds you are on and the nutrients you would like to try. Theroadback website offers other supplements not noted below, at nominal cost, that may also be of help.
