Supplements for depression: Do they work?

Depression is a common mental health disorder that affects many people worldwide. Effective treatments are available, but they do not work for everyone, so some people look to dietary supplements to try and alleviate symptoms. But do they have any effect? Medical News Today looked at the latest research and asked experts whether supplements might be of benefit to people with depression.

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What does the latest research say about using supplements to help treat depression? Image credit: Kseniya Ovchinnikova/Getty Images.

Depression is a lasting feeling of sadness, emptiness, or an inability to feel pleasure that usually happens for no obvious reason. According to the World Health Organization (WHO), it is different from regular mood changes, it lasts for a long time, and it may interfere with a person’s normal functioning.

According to the WHO, global estimates suggest that 3,8% of people experience depression. Women are more likely than men to experience depressive episodes, and the risk of depression is slightly higher in those over 60 years old.

The number of people with depression has been steadily increasing: In the United States, in 2020, almost 1 in 10 people experienced depression.

Major depressive disorder (MDD), in which a person experiences depressive episodes, is one of the most common mood disorders. Depressive episodes in major depressive disorder each last at least 2 weeks, with symptoms that cause “clinically significant distress or impairment in social, occupational, or other important areas of functioning.”

These symptoms often include:

  • depressed mood
  • loss of interest in almost all activities
  • significant unintentional weight loss/gain, or decrease/increase appetite changes
  • sleep disturbance
  • tiredness
  • a sense of worthlessness
  • impaired ability to think or concentrate
  • suicidal thoughts.

Depression may be treated with medications and/ or psychological therapies. The type of treatment depends on the severity of the depressive symptoms.

Antidepressant medications are generally effective for more severe depression. They work by modifying the action of neurotransmitters — chemicals that enable nerve cells to communicate with each other. Different antidepressants affect neurotransmitters in different ways.

The first line of treatment is usually selective serotonin reuptake inhibitors (SSRIs), which include fluoxetine (Prozac) and citalopram. As their name suggests, these drugs inhibit the reuptake of the neurotransmitter serotonin. The exact mechanism of action is unknown, but they do help symptoms of depression in many people.

Although these drugs are better tolerated than the older tricyclic antidepressants, some research has highlighted adverse effects, such as insomnia, agitation, gastrointestinal symptoms, sexual dysfunction, and suicidal ideation, particularly in adolescents.

If SSRIs are ineffective, doctors may prescribe other antidepressants, but some of them carry an even greater risk of side effects.

Psychological therapies can also be very effective for depression, used alone or in combination with antidepressants. They include cognitive behavioral therapy (CBT), interpersonal therapy, and supportive therapy.

However, people often find it difficult to access these therapies, with a study from the University of Oxford reporting that fewer than 5% of people with depression and anxiety were receiving them in the United Kingdom.

Some 68% of people fail to respond to the first-line antidepressant treatment, and 15–30% will not respond after two adequate trials. So could dietary supplements — vitamins, minerals, or probiotics — help relieve symptoms or enhance the effectiveness of antidepressants?

“There is some evidence suggesting that certain dietary supplements may have a beneficial effect in alleviating depressive symptoms. However, it’s important to note that supplements should not be considered a standalone treatment for depression, and their effectiveness may vary among individuals.”

– Sebnem Unluisler, genetic engineer at the London Regenerative Institute

The evidence for benefits from supplements varies widely, with some showing no benefit and studies suggesting that others may have a beneficial effect in the treatment of depression.

The MooDFOOD study looked at supplements and depression in 1,000 people with overweight and obesity at elevated risk of depression.

In 2019, it concluded that daily intake of nutritional supplements containing folic acid, vitamin D, zinc, and selenium was no better at preventing major depressive episodes than a placebo.

They suggested instead that for people with overweight and obesity, weight loss and following a healthy diet, such as the Mediterranean diet, could help with symptoms of depression.

Some supplements, however, have been shown to help alleviate symptoms, particularly when used as an adjunct to other treatments, such as psychological therapies or antidepressants.

A 2022 meta-analysis of 41 studies suggested that vitamin D might benefit people with depression. Although there was variation between studies, in general, 50 micrograms or more of vitamin D per day were more effective than a placebo in alleviating depression symptoms.

Unluisler explained to Medical News Today why vitamin D might have a positive effect.

“One possible mechanism is that vitamin D may influence the production and regulation of neurotransmitters, such as serotonin, which play a role in mood regulation,“ she told us. “Furthermore, vitamin D receptors are present in brain regions associated with depression.”

Another study showed that high doses of vitamin B6 may have a small beneficial effect on depression. However, the study sample size was small, and the majority of people included had self-reported anxiety, against which B6 was more effective, rather than depression.

Studies have also suggested that low iron may accentuate depressive symptoms, with links observed between anemia and depression.

One 2016 study found a significant association between iron deficiency anemia and depression. Research suggests that low iron alters dopamine metabolism and may also affect serotonin levels, both of which can result in mood changes.

Iron deficiency does not always cause anemia, but may still cause other symptoms including depression, so for those with low iron levels and depression, iron supplementation may be beneficial.

Other studies have looked at the effect of pro- and prebiotics — foods and food supplements that enhance a person’s gut microbiome. Recent research has highlighted the importance of the gut-brain axis, and the effects of the gut microbiota on mood and mental health.

“Prebiotics and probiotics can modulate the gut microbiota, which in turn can influence the production of neurotransmitters and other signaling molecules that affect brain function and mood. Additionally, the anti-inflammatory effects of prebiotics and probiotics may contribute to their potential impact on mental health.”

– Sebnem Unluisler

A 2019 review of studies concluded that pre- and probiotics might have some benefit in the management of depression. The researchers suggest that, pending further investigation, such dietary supplements could be used as an adjunctive treatment for people with depression.

Now, a study published in June 2023 provides further evidence that probiotics may help the treatment of depression. Although it had a small sample size, this double-blind study of people who were not responding to antidepressant treatment found a clear improvement in symptoms in those taking probiotics.

In the 8-week study, half the sample (24 people) received capsules 4 times a day containing 14 different probiotics. The rest received identical placebo capsules.

There was some reduction in depression symptoms in both groups, but after 4 weeks on the treatment, the probiotic group showed a greater response.

As the probiotic was well tolerated, with no serious adverse effects, the researchers suggest it could be a useful additional therapy for those with major depressive disorder.

There is some evidence that supplements may be helpful to people with depression, but Dr. Thomas MacLaren, consultant psychiatrist at Re:Cognition Health, cautioned:

“It’s important that you don’t take supplements as a substitute for the medical treatment of your depression. However, they may be taken as a complementary approach in conjunction with medical treatment, such as medication or therapy.”

“Research on the use of supplements for depression is ongoing. Recent studies have provided mixed results, highlighting the need for further investigation to determine the effectiveness and safety of specific supplements,” he added.

Even natural supplements can have safety concerns, particularly for those taking other medications. Studies have found that the herbal remedy St. John’s wort may be as effective as SSRIs for treating mild to moderate depression, but it can have similar adverse effects and must not be taken with a number of commonly prescribed drugs.

Other supplements that have shown some benefit in studies can also have adverse effects. Vitamin D and vitamin B6 can be toxic at high doses, and an excess of iron can lead to liver damage.

Dr. MacLaren advised: “People should be aware of potential side effects, interactions with medications, and the lack of sufficient scientific evidence supporting the benefits of supplements for depression. It is crucial to consult with a healthcare professional before starting any new supplements.”

Unluisler agreed that consulting a doctor is vital: “Healthcare professionals need to be aware of all the supplements a person is taking to assess their safety and potential interactions with prescribed medications. Some supplements may interact with certain antidepressants or other medications, affecting their effectiveness or causing adverse effects.”

It looks like the strongest evidence for benefit without risk of side effects is for probiotics, but following a healthy, varied diet that is high in fruit, vegetables, and fermented foods may also possibly have beneficial effects by encouraging a healthy microbiome.

Some people may find taking a supplement reassuring — and whether it has any actual benefit, the placebo effect can be enough to help alleviate symptoms. Provided people follow the advice of their healthcare professional, supplements are unlikely to do harm.

However, as Dr. MacLaren told us: “The overall evidence is still inconclusive. It is therefore important to think twice before investing money in a special supplement. Focus on a balanced and healthy diet.”

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