The Best Natural Antidepressants for Better Mood - Dr. Michael Ruscio, DC

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Do you want to start feeling better?

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Do you want to start feeling better?

Yes, Where Do I Start?

The Best Natural Antidepressants for Better Mood

How to Harness Diet, Lifestyle, and Supplements to Boost Your Mental Health

Key Takeaways:

  • Natural antidepressants include probiotics, St. John’s wort, and fish oils, but it’s best to start with the fundamentals of a gut-healthy anti-inflammatory diet, exercise, and sleep.
  • It used to be thought that genetically low serotonin levels caused depression, but newer research seems to suggest poor gut health and inflammation play a big role.
  • While genetics might still play a part in depression, we can work on poor gut health, nutrient deficiencies, and sedentary behaviors, which have the bigger impact on mood.
  • There are also lots of mood-boosting benefits to being outside and getting safe sun exposure.
  • Antidepressant medications have a role to play, especially with severe or debilitating symptoms, but you may get longer-term benefits by trying more natural approaches first if it makes sense for you.

Nearly one in twenty adults in America have regular bouts of depression [1], so it’s a mental health issue that most of us will have brushed up against some time during our lives. 

When you’re feeling really low — or have a friend or loved one who is — it’s hard to imagine that those feelings of sadness and despair can actually have a physical cause, but this is often the case.

More specifically, depression can be a symptom of poor gut health and inflammation, which may be treated with dietary and lifestyle changes and natural antidepressants. Some natural antidepressants, are similar to prescription antidepressants as they can alter neurotransmitter levels, but often do so to a lesser degree that can help avoid side effects.

The natural antidepressants we’ll consider in this article include: 

  • St. John’s Wort
  • Probiotics
  • Fish oils
  • Vitamin D/sunlight
  • S-adenosyl-l-methionine (SAMe)
  • Psychological therapies such as meditation 
  • Physical therapies such as saunas

Of course “fixing” depression isn’t always easy, but it’s empowering to know that by making small changes, you can feel significantly better over time.

Before we go into some of the specific natural therapies, let’s look at the more general underlying issues behind depression. Making changes here is a very positive way to start.

Depression, Gut Health, and Inflammation

Though anybody can be depressed, the chances may be higher if you have poor gut health, which is often linked to unhealthy eating patterns and inflammation. For example:

  • Compared to healthy people, those with depression were found to be more likely to have gut dysbiosis (an imbalance in the normal healthy balance of bacteria living in the digestive tract) [2].
  • Depression was noted more commonly in people with irritable bowel syndrome (IBS) and ulcerative colitis (a type of inflammatory bowel disease). 39% of ulcerative colitis patients and 33% of IBS patients had depression [3].

While it’s not clear whether gut issues directly cause depression (or vice versa), we do know that our gut environment and microbiome — the collection of trillions of microorganisms in our gut — has a powerful impact on the brain. Two-way gut microbiota-brain communication happens via the vagus nerve that passes from the gut to the brain [4].

Stress and anxiety can unbalance microbes in the gut, initiating a series of biochemical reactions that impact the central nervous system [5]. These changes in the vagus nerve and neurochemicals can be a contributing factor to experiencing depressive symptoms.

New Thoughts on The Serotonin Theory of Depression

For a long time, it was thought that a genetic disposition towards lower serotonin levels (a chemical messenger in the brain), was a common cause of depression. However, vast amounts of research based on the serotonin hypothesis of depression have NOT produced convincing evidence that depression is related to either serotonin-related biochemistry or serotonin-related genes.

A 2022 landmark umbrella meta-analysis of the serotonin/depression theory, which I review in more detail in this video, found that there was [6]: 

  • No association between blood plasma levels of serotonin and depression.
  • No clear trend between serotonin receptor binding and depression.
  • Weak or no association between low tryptophan (a serotonin precursor) and depression.
  • No association between serotonin-related genes and depression.

This doesn’t mean that drugs or herbs that temporarily increase levels of serotonin aren’t effective but it does mean that it’s not as straightforward as “high serotonin = good mood”, and “low serotonin = depression”.

It’s also actually good news that we are not totally at the mercy of our serotonin genes or chemistry when it comes to depression. We can’t change our genetics, but we can work on other factors like poor gut health, nutrient deficiencies, and sedentary behaviors that may be the real culprits behind depression [6]. 

Below we’ll walk you through how to heal your gut, damp down inflammation, and use natural antidepressants to lessen depressive symptoms. 

Diet, Exercise, and Sleep: The Antidepressant Big Guns

Probably the three most important things you can do to help tackle depression are to eat a gut-healthy anti-inflammatory diet, incorporate more physical activity in your daily routine, and get better quality sleep. However, it can be tempting to overexercise when dealing with symptoms of a mental illness, so always listen to your body and stick to the recommended amounts.

Eat to Quell Inflammation

Many observational studies have found an anti-inflammatory diet, the most studied of which is the Mediterranean diet, is associated with less depression. 

Anti-inflammatory diets eliminate pro-inflammatory foods and reduce inflammation, high levels of which appear to contribute to depression, possibly by changing the microbiome [7, 8, 9].

Here’s a table summarizing some of the research on the Mediterranean-style anti-inflammatory diet and depression.

Type of StudyPurpose of StudyWhat was Found?Ref
3-month randomized clinical trial involving 152 depressed adults.To research the effect of a Med-style diet plus fish oil, versus a control social group for 3 months.Depressed people on a Med-style diet had bigger drops in depression scores than depressed people who didn’t change their diet. In the Med-style group, the average depression score fell below the cutoff for extremely severe depression; in the control group, the average score stayed above this cut off.[10]
Meta-analysis (analysis of 41 separate observational studies).To examine the relationship between diet quality and depression in adults and teens.A Med-style diet was associated with a 33% lower risk of depression; diets with a lower inflammatory index were associated with a 24% lower risk of depression.[11]
Science literature reviewTo investigate the role of diet and nutrition in depression. Inadequate amounts of omega-3 fatty acids, vitamin B12, magnesium, folate, and zinc are associated with a higher risk of depression. Switching to a whole foods diet and replenishing nutrients if following a vegan/vegetarian diet can reduce depression.[12]

Although most research on diet and depression examines the Mediterranean diet, any wholesome inflammatory diet will likely be helpful. Such a diet might include seafood, olive oil, veggies, fruits, nuts, lean proteins, and whole grains, while limiting low-nutrient foods that are processed and high in calories, added sugars, and saturated fats.

One word of caution here: if you are taking MAOI (monoamine oxidase inhibitor) antidepressants, you should avoid eating fermented foods like kimchi, sauerkraut, pickles, and soy sauce. While these foods would normally be a useful part of a gut-healthy diet, if someone is taking MAOIs these foods can increase tyramine levels in the body to dangerous levels [2]. 

Many of my patients shift their eating patterns to be more ancestrally focused (i.e. the Paleo diet). In practice, this has lots of similarities to the Mediterranean diet (plenty of green veggies, oily fish, lean meats, and little to no processed foods), and is anti-inflammatory. But as it tends to be a little lower in carbs, and typically nixes dairy and wheat, it can sit better with those who have food intolerances and gut sensitivity.

Move to Improve Mood

Multiple studies point to an anti-depressant effect of exercise, and you’ll improve fitness and reduce the risk of other diseases (like heart disease and cancer) too.

One recent meta-analysis that analyzed 21 clinical trials (2,552 participants) compared the effectiveness of exercise, antidepressants, or a combination of both in adults with mild to moderate depression. On average, exercise was found to be a good alternative to antidepressants for treating mild to moderate depression. 

The only caveat was that people were more likely to drop out of exercise interventions than quit taking their antidepressants. So, exercise may require more effort and motivation to maintain [13].

Another meta-analysis on the effects of exercise found that it may help depression symptoms by improving circulating levels of brain-derived neurotrophic factor (needed for nerve cells to communicate with each other), and controlling levels of interleukin-6, involved in inflammation [14].

Most treatment guidelines for depression recommend doing 30–60 minutes of moderate-intensity exercise 2–3 times per week for 9–12 weeks.

To make regular exercise less daunting, many of my patients commit to just a month-long exercise program to start with but then find that they want to continue because of the mental and physical health benefits.

To turbocharge the benefits of exercise, it’s a good idea to get out into parks, forests, or next to the ocean as often as you can. Research has found that being in nature is a key way to reduce stress and lift low mood.

For example, a meta-analysis of clinical trials comparing the effects of walking or running in green outdoor spaces (versus urban outdoor environments), found better psychological effects from being in nature [15].

Yoga is another form of exercise that has been shown to have antidepressant effects [16, 17].

Sleep for Better Mental Health

People who are depressed often have severe sleep disturbances [18] but it’s also a two way street, with poor sleepers also being more likely to develop depressive symptoms.

One study found that people with insomnia were over 2.5x more likely than people who sleep well to develop depression [19].

The bottom line is that sleeping well is better for mental and overall health, and treating sleeping problems can reduce depression somewhat.

Some simple ways to improve sleep quality include:

  • Going to bed and getting up at the same time
  • Aiming to be asleep for at least 7 hours
  • Having a calming wind down schedule before retiring (for example, reading a book, taking a warm bath, and powering down electronic devices)
  • Sleeping in a cool, quiet room with blackout curtains

For more complex sleep issues cognitive behavioral therapy (specifically a program called CBT-I), can be very effective, as it teaches behaviors that encourage higher quality sleep.

Three different meta-analyses (reviews of many studies) have shown that CBT-I has [20, 21, 22]:

  • A moderate to large positive effect on insomnia 
  • A modest effect on self-reported depression symptoms 

Even though CBT for insomnia doesn’t seem to have a large effect on depression, tackling nighttime wakefulness can only have a benefit to your mental health in the long term. You can learn CBT-I from a therapist in person or online, and you can then apply the therapy yourself at home.

Other Helpful Natural Antidepressants

Once you’ve taken steps to improve your diet, exercise, and sleep, you can think about adding other habits and dietary supplements that build on these depression-fighting fundamentals. Perhaps the most important of these is probiotics, which will assist the work you’ve been doing to make your gut healthier.


The gut/brain axis is fundamental to good psychological health, and supplementing with good bacteria (probiotics) can play an important part at the gut end of this two-way communication.

This isn’t just theory either: studies looking at the mood-boosting capabilities of probiotics have found that:

  • Depression scale scores for major depressive disorder were improved in people taking probiotics [23].
  • Probiotics had a moderate to large positive impact on people with mild to moderate depression [24].
  • Psychiatric patients who took probiotics had improved scores on the Hamilton Rating Scale for Depression [25].

A recent study tried to tease out how probiotics benefit depression but could not say for definite whether they exert their effects by reducing inflammation or not. It’s also unclear as to what dosage is best and whether probiotics can prevent depression in people not currently depressed [26]. 

However, if you have combined gut issues and depressive symptoms, the evidence for the benefit of probiotics is compelling. 

In the clinic, we’ve found a good response in depressed patients from using three different strains of probiotics together.

Sun Exposure / Vitamin D 

Getting some safe UV exposure on any day the sun comes out is another natural antidepressant that we can all help ourselves to for free.

In a 2018 randomized clinical trial, a group of depressed women who were advised on the benefits of daily sun exposure had significant increases in vitamin D, became vitamin D sufficient, and went from being moderately depressed (depression score of about 24) to minimally depressed (depression score of about 13) [27].

Recommendations for sun exposure to enhance vitamin D levels vary by skin color, geographical location, and time of year. 

  • People with darker skin can typically make enough vitamin D by exposing their head, arms, and legs to sunlight for 25 minutes a day most days of the week [28]. 
  • People with lighter skin can typically make enough vitamin D by exposing their head, arms, and legs to sunlight for 10–15 minutes a day most days of the week [29].

Lighter-skinned people tend to easily make vitamin D, but they [28] can’t take as much sun without burning and other harmful effects [28]. 

Always remember to be sun safe and sensible. You should always apply sunscreen before your skin becomes reddened. Taking a vitamin D supplement is a good option if you can’t be out in the sun for any reason, but keep your dose around 2,000 IUs and/or get regular labwork to make sure you aren’t overdoing it.

St. John’s Wort 

St. John’s wort (Hypericum perforatum) appears to be as effective as selective serotonin reuptake inhibitor (SSRI) antidepressants for treating mild to moderate depression, and people generally tolerate this herbal supplement better than these drugs [30]. That said, there’s a lot more research on SSRIs than there is on St John’s wort.

The most popular theory is that St. John’s wort acts in the same way as serotonin reuptake inhibitor (SSRI) antidepressants, allowing more free serotonin to be available to go from nerve cell to nerve cell to deliver chemical messages [31].

If you decide to give St. John’s wort a go, start by taking one 300mg capsule with 0.3% hypericin content three times a day. However, you should consult with your doctor before commencing St. John’s wort as it can react with alcohol, other antidepressants, and many other medications. [31].

Saunas and Hot Baths

Though there isn’t a huge amount of research on the effects of sauna bathing on mood disorders, the practice does appear to have benefits for some people with depression.

One systematic review of 7 clinical trials found evidence pointing to a moderate to large positive effect on depressive symptoms after 1–6 weeks. Both infrared saunas and hot baths were included in this review [32].

A 2016 RCT of 93 adults with non-medicated major depressive disorder found that just one session of whole-body hyperthermia (heat delivered to the body by infrared lights) reduced depression for six weeks [33]. 

Most patients with depression seem to tolerate small increases in core body temperature without side effects unless they have physical conditions (check with your doctor if you are unsure) [34]. You will also want to be extra careful to stay hydrated if you are taking any prescription antidepressants to avoid fluctuations in blood levels.

How heat may help depression is unknown, but one possibility is that it improves the function of cell membranes in the skin, with the downstream effect being improved signaling to serotonin-specific nerve cells in the brainstem [32].

The best evidence-based suggestion we have is that you should aim — even for just one session — to slowly raise your core body temperature to between 100.4 and 102.2 degrees Fahrenheit [32].


We’ve already seen that a type of cognitive therapy (CBT-I) can be very effective for insomnia, which is a common symptom of depression.

However, for low mood symptoms, more specifically, the stronger weight of evidence lies with mindfulness meditation and mindfulness-based cognitive therapy (MBCT).

MBCT uses elements of mindfulness to tackle unhelpful thought patterns and CBT to reframe those thoughts and behaviors. 

Two meta-analyses and a randomized controlled trial found that MBCT is as effective as antidepressants for treating recurrent major depression and should be a go-to treatment for maintaining mental health after recovering from depression [35].

Two other meta-analyses found that mindfulness meditation improves depression in both young adults and older adults to a medium/large degree [36, 37].

MCBT may also help by teaching you to change your focus, make your memories more accurate, see yourself more as you are than how you wish you were, reduce your emotional reactivity to stress, and increase your experience of positive emotions [38].

Research suggests that doing guided mindfulness meditation for up to 5 weeks may be ideal for improving depression [37].

Fish Oil 

One of the benefits of the Mediterranean diet is its high levels of omega-3 from nuts, green leafy veggies, and particularly oily fish. 

Theoretically, omega-3s (EPA and DHA) could have anti-depressive effects by reducing inflammation and improving nerve formation (neurogenesis), neuroplasticity, and nerve communication in the brain [39, 40]. 

They may also improve the function of something called the hypothalamic-pituitary- adrenal (HPA) axis, improving resilience to stress [39].

A 2019 practice guidelines report by the International Society for Nutritional Psychiatry concluded that omega-3 fatty supplements can be useful for treating major depressive disorder in pregnant women, children, and the elderly (for whom medications may not be advisable), and for preventing it in those at high risk [40]. 

High-dose omega-3s (at least 2,000mg/day of EPA or DHA) had a greater (large to very large) positive effect on depression than low-dose omega-3s, which still had a medium to large effect [41].


S-adenosyl-l-methionine (SAMe) is made in the body from methionine, an amino acid found in protein.

It’s thought SAMe may have a role in beating depression by enhancing the activity of certain neurotransmitters associated with the onset and treatment of depression. Another theory is that it may influence the expression of genes that affect memory, behavior, learning, and cognition [42].

However, the evidence is somewhat contradictory. One meta-analysis that looked at SAMe supplements (1,600mg) in depressed patients found that they worked better than placebo but only if combined with an SSRI antidepressant [42]. 

Another small meta-analysis confirmed that SAMe seems to help antidepressants work better [43].

The consensus seems to be that SAMe appears to help some antidepressants do a better job of relieving depression, but the jury is still out on whether SAMe alone can improve depression scores [42]. Use of SAMe is not appropriate with all antidepressants, so check with your integrative healthcare provider to see if it is an option for you.


Although more research is needed to confirm, saffron (Crocus sativus) may be able to relieve depression in adults better than placebo and as well as some antidepressants [44, 45].

You can use saffron in cooking (for example, in Indian-style curries), but for therapeutic benefits, it is likely to be needed in more concentrated amounts in supplement form.

One meta-analysis suggested saffron could be about as effective as Prozac for treating depression. The quality of this research wasn’t good enough to say this with a good level of certainty though [44].

Nonetheless, saffron contains ingredients that have antioxidant, anti-inflammatory, and neuroprotective qualities, which may all positively impact mental health [46].

Although we don’t have clear data yet on the optimal dosing of saffron for antidepressant use, a reasonable range appears to be 30–50mg of saffron extract per day for about 6 weeks [44].

What About Antidepressant Drugs?

Though we’ve focused on natural antidepressants in this article, there’s obviously a time and place for prescription antidepressants too. 

In a large meta-analysis that evaluated 432 trials and a total of over 100,000 participants, 21 antidepressants were found to be better than placebo for treating adults with major depression [47].

For every 100 depressed adults who benefitted from placebo, 137 to 213 benefited from antidepressants. 

That said, all but two of the drugs were less tolerated than placebo, meaning people stopped taking them more often because of adverse effects than they stopped taking placebo. 

Just because antidepressants can be an effective treatment for depression in adults doesn’t mean everyone can accept or tolerate them.

They also don’t work for everyone – between not necessarily addressing the underlying cause of depression, causing side effects, or simply not improving symptoms, there are several possible issues with these medications. 

Many people also simply prefer a more natural approach. In most cases, I tend to take the approach of starting with more natural solutions that have been shown to be effective, before recommending medication. However, always talk to your doctor!

A Brighter Future with Natural Antidepressants

Though depression is hard to deal with, looking after your gut health, exercising, and getting good sleep can reduce your chances of being depressed and improve your mood if you do feel low. In addition, a wide range of natural antidepressants can be added to these fundamentals to improve your mental health. Not all of them are necessary or work for everybody, but with trial and error you should be able to find the ones that help you.

Pharmaceutical antidepressants are an option too, but you might want to try some natural remedies first, and always check with your functional healthcare provider when adding supplements onto prescription antidepressants.

If you are ever in a place where you feel you might harm yourself, it’s important to reach out for local medical attention immediately or to a national hotline.

Our highly experienced practitioners at the Ruscio Institute can also help with long-term lifestyle support for mental health issues, such as depressive symptoms, anxiety, and brain fog.

The Ruscio Institute has developed a range of high-quality formulations to help our patients and audience. If you’re interested in learning more about these products, please click here. Note that there are many other options available, and we encourage you to research which products may be right for you.

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