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Evidence-based Guide to Supplements for Anxiety

by | November 23, 2020

Evidence-based Guide to Supplements for Anxiety

In our fast paced, high-tech world, stress is the norm for most of us. Life stressors including jobs, relationships, health, and financial stressors often contribute to worrying and fear. These combined with other triggers and predisposing factors can cause anxiety. The uncertainty, isolation and restrictions caused by the current Covid-19 pandemic exacerbate any underlying anxiety an individual may experience. It is estimated that 40 million adults in the US suffer from anxiety. This can include fear, excessive worry, as well as panic disorders and phobias. While feeling unease and having a healthy dose of concern over our wellbeing is normal, you might ask, at what point should one be concerned about anxiety and seek treatment?

What Is An Anxiety Disorder?

For the purpose of this article, I am going to focus on generalized anxiety disorder. Other major anxiety disorders include panic disorder, specific phobias, obsessive compulsive disorder, separation anxiety, and post-traumatic stress disorder.

DSM-5 criteria that need to be satisfied for diagnosis of generalized anxiety disorder (GAD) require that excessive anxiety and worry have lasted for at least 6 months, the individual finds it difficult to control the worry, and has had 3 or more of the following symptoms for the past 6 months (in children only 1 of the following symptoms is required):

 1. Restlessness or feeling on edge

 2. Being easily fatigued

 3. Difficulty focusing

 4. Irritability

 5. Feeling muscle tension

 6. Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep)

In addition to above, the anxiety or the accompanying physical symptoms are so great that the person’s social functioning, work/school or other important areas of life are impaired. It is also necessary that a doctor rules out medical causes that could be contributing to anxiety (e.g., hyperthyroidism – overactive thyroid) or substances that could be causing it.

If symptoms can be identified early, an intervention should be considered as soon as possible, so that the individuals can gain a deeper insight into their feelings, thoughts and behavior, and learn the tools to cope effectively. Cognitive behavioral therapy is the standard of treatment for individuals who are diagnosed with anxiety disorder. Mindfulness-based stress reduction, yoga, daily meditation, exercise and healthy nutrition (as well as avoidance of substances that can worsen anxiety – e.g., coffee) have also been found to be effective for alleviating symptoms of anxiety. To learn more about mindfulness-based stress reduction, you may go here. While these strategies may not always replace other treatment modalities, they can be a helpful addition.

Pharmacotherapy recommended as first line typically includes serotonergic antidepressants (also known as selective serotonin reuptake inhibitors, or SSRI’s, and serotonin norepinephrine reuptake inhibitors, SNRI’s). There are other pharmacotherapy strategies for anxiety, however they are outside of the scope of this article (if you’d like to know more, let me know and I will write about it in one of my upcoming articles!). I should note that benzodiazapines, a class of medications that is commonly used for anxiety and panic disorders is addictive and has the potential to be misused, abused and cause physical dependence, and withdrawal symptoms if stopped abruptly. It has the potential to cause drowsiness, and is therefore best avoided in the elderly, or in combination with other sedating medications. 

Supplements for Anxiety

What about supplements? Anxiety is one of the conditions for which individuals frequently seek complementary and alternative therapies, and it is therefore important to understand what treatment options are available, especially for individuals who may want to forgo pharmaceutical therapy or seek ways to complement it. As an integrative medicine physician, I often get asked about supplement use. While it is important to discuss your anxiety with your primary care physician, therapist and/or psychiatrist, who can help identify the strategies that will be most helpful to you, I am sharing a list of supplements that have been supported by research and clinical experience to help alleviate symptoms of anxiety. I am also sharing commonly used supplements that do not have sufficient evidence for use, as it is important to understand safety and efficacy before making a decision about treatment. If you are considering a supplement, I recommend talking to your physician first, as the risk/benefit ratio of taking a supplement must be considered. Supplements and botanical remedies are not without side effects, and many interact with medications and other supplements. It is therefore important to understand the level of evidence supporting supplement use, possible side effects as well as contraindications. For instance, some supplements for depression may exacerbate mania in individuals with bipolar disorder. One needs to be under the supervision of a physician when considering supplement use.

A review in the American Family Physician concluded that inositol and kava have evidence for use in anxiety. Let’s examine this evidence and discuss several other commonly used supplements.

Inositol

Inositol is an organic compound in the sugar family, and is found in many foods (cantaloupe, citrus fruit, beans, brown rice, and many others). This nutrient is needed for healthy metabolic function, the formation of cell membranes, nerve transmission, and the body’s stress response.

Inositol has been found to reduce the frequency and severity of panic attacks in a small double-blind, placebo-controlled crossover trial, in people with panic disorder. It is also more effective at reducing panic attacks, than fluvoxamine – a medication used for anxiety disorders and depression. Myo-inositol has also been found to ameliorate symptoms of depression and anxiety in women with polycystic ovarian syndrome (PCOS), however the publisher and editors of the journal where this paper was published expressed concern with respect to the integrity of the research.

Given encouraging results, it is reasonable to consider use of inositol to support individuals with anxiety, however more data is needed to elucidate the effects of inositol, and its appropriate use.

Though it can cause gastrointestinal symptoms at higher doses, inositol is generally well-tolerated. If your doctor recommends inositol, it is important to get it from a high-quality supplement brand. ConsumerLab is one resource that provides an independent analysis of supplements. In order to achieve doses that were studied (up to 12-18g/day), inositol powders are typically used. If you are wondering whether inositol is appropriate for you, and what dose to take, talk to your doctor first. Integrative and functional medicine physicians are generally knowledgeable with respect to use of inositol and its dosing.

Kava

Kava kava is an herbal preparation derived from Piper methysticum, a plant native to the South Pacific Islands. It contains compounds called kavalactones which are biologically active, and exert a calming effect via several mechanisms.

There are over 50 published human clinical trials that support the use of Kava. A Cochrane systematic review of 11 clinical trials with 645 participants concluded that kava is a safe and effective treatment for anxiety. The treatment in these studies lasted 1-24 weeks. An 8-week clinical trial with 129 patients (randomized double blind clinical trial) found that Kava-kava is as effective as anti-anxiety medications buspirone and opipramol, and safe. A 6-week clinical trial with 58 patients with generalized anxiety disorder found that kava was effective treatment for anxiety. While it did cause more headaches, no liver damage was found in the participants. Another study of 60 adult participants supported the use of kava for management of anxiety.

It is important to note that over 100 cases of liver damage have been attributed to intake of kava. Some experts claim that the damage may have been due to other drugs or alcohol taken together with kava, while in other instances, excessive dose may be the culprit. Other experts believe that the extraction method (alcohol or acetone extraction) may extract toxic compounds from the plant, which cause liver damage. Use of suboptimal raw material (e.g., the inappropriate part of the plant) has also been postulated as the cause of liver toxicity.

Three case reports of liver failure, some resulting in death, are described here.

While kava has been found to be effective for anxiety, it is important to discuss potential risks and benefits with your physician, prior to taking it. It can interact with medications and supplements, and it is important to check for interactions prior to taking it.

Ashwagandha

Another supplement that has been studied for anxiety is Ashwagandha, or Withania somnifera. This Ayurvedic herb has been used as a remedy in India for centuries.

A review of 5 clinical trials found that ashwagandha resulted in greater improvement in stress and anxiety than placebo.

While ashwagandha is generally well tolerated at therapeutic doses, there was a case published of ashwagandha causing increase in thyroid hormones. Furthermore, large doses may cause diarrhea, nausea, and vomiting.

German Chamomile

German Chamomile, or Matricaria recutita, has been widely studied and used due to its anxiolytic and antidepressant properties.

A study done in 2009 showed that when 57 adults with generalized anxiety disorder were randomized to receiving German chamomile vs. placebo for 8 weeks, the individuals who received chamomile had a significant decrease in anxiety and depression. A larger study of 179 patients with moderate to severe generalized anxiety disorder confirmed the clinically meaningful reduction in generalized anxiety disorder symptoms with an 8-week course of pharmaceutical grade chamomile. Almost 60% of individuals, treated with 1500mg/day of German chamomile daily, met criteria for clinical response. Nearly 12% of the patients reported mild-moderate side effects including gastrointestinal symptoms, drowsiness, fatigue and herbal taste that was lingering.

It is also important to note, however, that there is a risk of allergic reaction to chamomile, especially for those sensitive to chrysanthemums, ragweed or other members of the Compositae family.

L-Theanine

L-Theanine is another supplement that can be used for anxiety. This amino acid occurs naturally in both green and black tea.

As a supplement, it has been found to be better than placebo at ameliorating symptoms of anxiety, depression and result in improved sleep in healthy individuals who were suffering from stress-related symptoms. It also resulted in improved cognitive function in these individuals. In this particular study, L-theanine was administered for 4 weeks at 200mg/day.

In contrast, when patients with generalized anxiety disorder were administered L-theanine in addition to their current treatment for anxiety, in a 10-week study, no additional benefit was found with L-theanine addition, compared to placebo, with respect to anxiety. Interestingly, subjects reported better sleep quality with L-theanine.

L-theanine does not cause drowsiness or impaired concentration and has not been found to cause dependence. L-theanine may lower blood pressure and should therefore be used with caution in individuals taking medications for high blood pressure.

Lavender

For most, the scent of lavender, or Lavendula angustifolia, is a relaxing one. It is believed that just the smell of it, or even topical application through a cream, can reduce both stress and anxiety.

A study done in Austria found that a lavender oil capsule preparation, silexan, showed a greater improvement in anxiety compared to placebo, when 80mg was administered daily. A meta-analysis found that silexan 160mg daily was found to be more effective than an anti-anxiety medication paroxetine and 80mg daily was found to be just as effective as paroxetine.

While helpful for adults, use lavender on children sparingly. For them, it is believed to be an endocrine disruptor with continuous use. Please contact your doctor before using lavender regularly.

Lemon Balm

Lemon balm (Melissa officinalis) is a member of the mint family and has been used historically to ease anxiety and stress. It has been shown to lower anxiety and improve working memory at 1 and 3 hours after ingestion, at a dose of 1.8g (standardized to 2% rosmarinic acid). In patients with heart disease, 3g of lemon balm daily for 8 weeks was found to be more effective at alleviating anxiety, stress and improving sleep, compared to placebo. Another study found that a single 600mg dose of Melissa officinalis extract was associated with worsening memory processing and a dose of 900mg was also associated with decreased alertness.

The typical dose range for lemon balm is 2g-4g of the powdered herb, or 300-600mg of the standardized extract (standardized to 5% rosmarinic acid). It is important to be aware of the sedative effect at higher doses and start and titrate supplement doses only under the supervision of a physician.

N-acetylcysteine (NAC)

NAC is a supplement derived from amino acid L-cysteine. It is the precursor to glutathione, the body’s powerful antioxidant, and is typically used to treat respiratory congestion: it loosens mucus in airways and acts as an antioxidant and anti-inflammatory agent. There is growing evidence that it has anxiety-lowering properties as well. NAC reversed anxiety-like behavior and oxidative damage observed in stressed zebrafish. A literature review on uses of NAC in humans concluded that it is beneficial in several psychiatric and neurological disorders, including obsessive-compulsive disorder, depression, and bipolar disorder, and that there is preliminary evidence supporting its use in anxiety, however larger confirmatory studies are needed.

NAC interacts with multiple medications, so it is important to check with your doctor if NAC interacts with your medications before taking it.

Rhodiola

Rhodiola is grown in the cold, mountainous regions of Europe and Asia. This adaptogen stimulates the body’s stress response to support stress resiliency. A small study found that participants who were given 340mg rhodiola daily for 10 weeks, experienced significantly less anxiety at the end of the study. Adverse events were mild to moderate, the most common being dizziness and dry mouth. Another study showed that rhodiola administered daily for 6 weeks at 340-680mg/day improved symptoms of depression. Rhodiola also reduces stress-related fatigue and improves mental performance when administered at 576mg extract/day.

Though most will tolerate this herb well, some have experienced dizziness, dry mouth, agitation, and irritability. It can also interfere with some medications; therefore, always consult your doctor before taking it.

Where Do I Start?

Though you may feel that dealing with anxiety can be overwhelming or even embarrassing, it doesn’t have to be. Know that you are not alone – many people worldwide are dealing with this condition. Finding a way to cope with it successfully and alleviate its symptoms is an empowering experience that will deliver long term benefits. Talk to your doctor and therapist, seek expertise and support, identify and address triggers, practice healthy lifestyle habits, and you will gain control of the anxiety.  

Note: many supplements have not been investigated in women who are pregnant, nursing and in children, therefore speaking to a physician about safety and efficacy profiles of supplements, as well as contraindications in these situations is imperative prior to their use.

Additional and related resources:

Dr. Bojana Weatherly on the Benefits of Mindfulness, Overcoming Victimhood, and Mindfulness Techniques

5 Easy Ways to Be Mindful Every Day

6 Ways to Declutter Your Mind

How to Live a Happier Healthier Life in 5 Steps

How to Be Your Best Self? Embrace Your Imperfection

Kava Is an Effective and Safe Treatment of Anxiety

Disclaimer

Nothing stated or posted in this article is intended or should be taken to be the practice of medical or counseling care. The information made available in this article, including, but not limited to, interviews, text, graphics, images, links to other articles, websites, and other material contained in this article, is strictly for informational and entertainment purposes only. The information in this article is NOT (and should not be used as) a substitute for professional psychiatry, psychology, medical, nursing, or professional healthcare advice or services, nor is it designed to suggest any specific diagnosis or treatment. Please always seek medical advice from your physician or a qualified health care provider regarding any medical questions, conditions or treatment, before making any changes to your health care regimen, medications or lifestyle habits. None of the information in this article is a representation or warranty that any particular drug or treatment is safe, appropriate or effective for you, or that any particular healthcare provider is appropriate for you. Never disregard professional medical advice or delay seeking help from a health care provider due to something you have read or seen in this article. Your reading/use of this article does not create in any way a physician-patient relationship, any sort of confidential, fiduciary or professional relationship, or any other special relationship that would give rise to any duties. This article does not recommend or endorse any specific tests, healthcare providers, procedures, or treatments, and if you rely on any of the information provided by this article, you do so solely at your own risk.

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About the Author

Dr. Bojana

Dr. Bojana

Dr. Bojana (Boy•ana) Jankovic Weatherly is an award winning physician, double board certified in internal and integrative medicine. After completing internal medicine residency, she did a fellowship in integrative medicine, trained in functional medicine, nutrition and mindfulness. Her approach is rooted in evidence-based medicine that is personalized to each individual she works with.

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