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Supplements for Anxiety: Evidence-Based Review of Natural Remedies

Supplements for Anxiety: Evidence-Based Review of Natural Remedies

Introduction

Anxiety disorders are among the most prevalent mental health conditions worldwide, affecting millions of people. While conventional treatments like therapy and medication are effective, many individuals also turn to natural supplements to help manage their anxiety symptoms. Supplements for anxiety have gained popularity as people seek alternative or complementary approaches to support their mental well-being.

This article provides a comprehensive review of the scientific evidence on supplements for anxiety. We will explore the potential benefits, safety considerations, and limitations of various herbal and nutritional supplements that have been studied for their anxiolytic effects. By examining the available research, we aim to help readers make informed decisions about incorporating supplements into their anxiety management plan.

It is important to note that supplements should not replace proven therapies like cognitive-behavioural therapy and prescribed medications when needed. Consulting with a healthcare professional is crucial before starting any supplement regimen, as they can interact with medications and cause side effects. With that in mind, let’s delve into the evidence behind some of the most promising supplements for anxiety.

Herbal Supplements for Anxiety

Passionflower (Passiflora incarnata)

Passionflower, a climbing vine native to the Americas, has been traditionally used for its calming effects. Several randomised controlled trials (RCTs) have investigated the anxiolytic properties of passionflower. A double-blind study by Akhondzadeh et al. (2001) found that passionflower extract was as effective as the benzodiazepine oxazepam in treating generalised anxiety disorder (GAD). The study included 36 patients with GAD who received either passionflower extract (45 drops/day) or oxazepam (30 mg/day) for 4 weeks. Both treatments significantly reduced anxiety symptoms, with no significant difference between the two groups (Akhondzadeh et al., 2001).

Passionflower has also shown benefits for reducing anxiety in specific populations. In a double-blind, placebo-controlled study, Movafegh et al. (2008) found that oral passionflower reduced anxiety in patients undergoing spinal anaesthesia for surgery. Ninety patients received either passionflower (500 mg) or placebo 90 minutes before surgery. The passionflower group experienced significantly lower anxiety levels compared to the placebo group (Movafegh et al., 2008). Similarly, a controlled study by Bourin et al. (1997) demonstrated that a combination of passionflower and other plant extracts effectively reduced anxiety in outpatients with adjustment disorder.

While passionflower is generally well-tolerated, mild side effects such as dizziness and confusion have been reported (Miroddi et al., 2013). More research is needed to establish the optimal dosage and long-term safety of passionflower for anxiety.

Kava (Piper methysticum)

Kava, a plant native to the South Pacific islands, has a long history of traditional use for its relaxing and anxiety-reducing properties. The anxiolytic effects of kava have been attributed to its active compounds, known as kavalactones, which modulate neurotransmitter activity in the brain (Sarris et al., 2013).

Numerous RCTs have investigated the efficacy of kava for various anxiety disorders. A meta-analysis by Pittler and Ernst (2003) reviewed 11 RCTs involving 645 participants and found that kava extract significantly reduced anxiety symptoms compared to placebo. The studies included patients with GAD, non-psychotic anxiety, and anxiety related to menopause.

One double-blind, placebo-controlled study by Volz and Kieser (1997) evaluated the efficacy of kava extract WS 1490 in 101 outpatients with anxiety disorders. After 25 weeks of treatment, the kava group experienced significant improvements in anxiety symptoms compared to the placebo group, as measured by the Hamilton Anxiety Scale (HAMA) (Volz & Kieser, 1997). Similar positive results were found in RCTs investigating kava for GAD (Boerner et al., 2003; Sarris et al., 2009) and anxiety in perimenopausal women (Cagnacci et al., 2003).

However, not all studies have found significant benefits of kava over placebo. A placebo-controlled study by Connor and Davidson (2002) involving 75 patients with GAD found no significant differences between kava and placebo in reducing anxiety symptoms. Similarly, an internet-based RCT by Jacobs et al. (2005) found no significant effects of kava on anxiety or insomnia compared to placebo.

It is important to note that concerns have been raised about the potential hepatotoxicity of kava, particularly at high doses or with long-term use. Rare cases of liver toxicity have been reported, leading to restrictions or warnings in some countries (Teschke et al., 2011). However, a systematic review by Sarris et al. (2013) concluded that the risk of liver toxicity from kava is low when used at recommended doses and in the absence of other risk factors.

St. John’s Wort (Hypericum perforatum)

St. John’s wort (SJW) is a flowering plant that has been extensively studied for its antidepressant effects. While primarily used for depression, SJW has also been investigated for its potential anxiolytic properties.

The evidence for SJW in treating anxiety disorders is mixed. An open-label trial by Taylor and Kobak (2000) found that SJW (900-1800 mg/day) significantly reduced symptoms of obsessive-compulsive disorder (OCD) in 12 patients over 12 weeks. However, a subsequent double-blind RCT by Kobak et al. (2005) found no significant differences between SJW and placebo in reducing OCD symptoms.

Similarly, a placebo-controlled pilot study by Kobak et al. (2005) investigated SJW for social anxiety disorder (SAD). Forty patients with SAD received either SJW (600-1800 mg/day) or placebo for 12 weeks. While both groups showed improvements in anxiety symptoms, there were no significant differences between SJW and placebo (Kobak et al., 2005).

More promising results have been found for SJW in treating depression with comorbid anxiety. A double-blind, randomised trial by Müller et al. (2003) evaluated a combination of SJW and valerian extract in 149 patients with depression and anxiety. After 6 weeks, the herbal combination significantly reduced anxiety and depression scores compared to placebo (Müller et al., 2003). Similarly, a placebo-controlled study by Volz et al. (2002) found that SJW extract (600-1200 mg/day) effectively reduced anxiety symptoms in patients with somatoform disorders.

SJW is generally well-tolerated, with mild side effects such as gastrointestinal upset and dizziness reported in some cases (Rahimi et al., 2009). However, SJW can interact with various medications, including antidepressants, contraceptives, and anticoagulants, so caution is advised (Henderson et al., 2002).

Nutritional Supplements for Anxiety

L-Lysine and L-Arginine

L-lysine and L-arginine are amino acids that have been studied for their potential anxiolytic effects. Two RCTs have investigated the combination of L-lysine and L-arginine for anxiety.

Jezova et al. (2005) conducted a double-blind, placebo-controlled study involving 29 healthy volunteers with high trait anxiety. Participants received either an amino acid mixture containing L-lysine (2.64 g/day) and L-arginine (2.64 g/day) or placebo for 10 days. The amino acid mixture significantly reduced anxiety and perceived stress levels compared to placebo. Additionally, the L-lysine/L-arginine combination attenuated the stress-induced increase in cortisol levels (Jezova et al., 2005).

Another double-blind, placebo-controlled study by Smriga et al. (2007) evaluated the effects of L-lysine and L-arginine on anxiety and stress responses in 108 healthy Japanese adults. Participants received either L-lysine (2.64 g/day) and L-arginine (2.64 g/day) or placebo for 1 week. The amino acid combination significantly reduced both state and trait anxiety scores compared to placebo. Furthermore, the L-lysine/L-arginine group exhibited lower levels of salivary cortisol and chromogranin-A, markers of stress response (Smriga et al., 2007).

No adverse effects were reported in these studies, suggesting that L-lysine and L-arginine may be a safe and effective option for reducing anxiety. However, more research is needed to confirm these findings and determine the optimal dosage and duration of use.

Magnesium

Magnesium is an essential mineral that plays a crucial role in the regulation of neurotransmitters involved in anxiety and stress response (Kirkland et al., 2018). Magnesium deficiency has been linked to increased risk of anxiety and depression (Serefko et al., 2013).

Several RCTs have investigated the anxiolytic effects of magnesium supplementation. A double-blind, placebo-controlled study by Hanus et al. (2004) evaluated the efficacy of a magnesium-containing supplement in 264 patients with generalised anxiety. Participants received either a combination of magnesium (75 mg/day), hawthorn extract, and California poppy extract or placebo for 3 months. The magnesium-containing supplement significantly reduced anxiety scores compared to placebo, as measured by the Hamilton Anxiety Rating Scale (HAMA) (Hanus et al., 2004).

Another double-blind, placebo-controlled study by Tarleton et al. (2017) investigated the effects of magnesium supplementation on anxiety and stress in 126 adults with mild to moderate anxiety. Participants received either magnesium (248 mg/day) or placebo for 6 weeks. Magnesium supplementation significantly reduced subjective anxiety and stress levels compared to placebo (Tarleton et al., 2017).

A randomised, double-blind, cross-over study by Boyle et al. (2017) evaluated the effects of magnesium supplementation on anxiety and stress in 40 healthy adults. Participants received either magnesium (300 mg/day) or placebo for 6 weeks, with a 2-week washout period between treatments. Magnesium supplementation significantly reduced self-reported anxiety and stress compared to placebo (Boyle et al., 2017).

While these studies suggest that magnesium may be beneficial for reducing anxiety, it is important to note that they used magnesium in combination with other nutrients or herbal extracts. More research is needed to evaluate the efficacy of magnesium monotherapy for anxiety. Magnesium supplements are generally safe, but high doses can cause gastrointestinal side effects such as diarrhoea (Schwalfenberg & Genuis, 2017).

Limitations and Future Directions

While the studies discussed in this article provide promising evidence for the anxiolytic effects of certain herbal and nutritional supplements, several limitations should be acknowledged. Many of the studies had small sample sizes, short durations, and used varying dosages and formulations of the supplements. Some studies lacked placebo controls or had mixed results.

Furthermore, the long-term safety and efficacy of these supplements for anxiety need to be established through larger, well-designed clinical trials. The potential interactions between supplements and medications should also be carefully considered.

Future research should aim to identify the optimal dosages and standardise the formulations of herbal and nutritional supplements for anxiety. Investigating the mechanisms of action and active compounds responsible for the anxiolytic effects could lead to the development of more targeted and effective interventions.

It is crucial for individuals with anxiety to work closely with healthcare professionals when considering the use of supplements. A personalised approach that takes into account an individual’s medical history, symptoms, and potential drug interactions is essential for safe and effective anxiety management.

Conclusion

In conclusion, this comprehensive review has explored the scientific evidence behind various herbal and nutritional supplements for anxiety. The findings suggest that certain supplements, such as passionflower, kava, L-lysine/L-arginine, and magnesium, may offer anxiolytic effects and could potentially serve as complementary treatments for anxiety disorders.

However, it is crucial to approach the use of supplements with caution and under the guidance of healthcare professionals. While some studies have shown promising results, the evidence is not always consistent, and more high-quality research is needed to establish the long-term efficacy and safety of these supplements. Additionally, supplements can interact with medications and cause side effects, emphasising the importance of a personalised approach to anxiety management.

In summary, herbal and nutritional supplements may provide a complementary approach to managing anxiety symptoms, but they should not replace evidence-based treatments such as cognitive-behavioural therapy and prescribed medications when needed. By working closely with healthcare providers and considering the available scientific evidence, individuals with anxiety can make informed decisions about incorporating supplements into their treatment plans. As research continues to evolve, a better understanding of the potential benefits and limitations of supplements for anxiety will emerge, ultimately leading to more targeted and effective interventions for this prevalent mental health condition.

Key Highlights and Actionable Tips

  • Passionflower, kava, and combinations of L-lysine and L-arginine show strong evidence as effective treatments for anxiety symptoms and disorders, with mild to moderate side effects.
  • Magnesium-containing supplements and other herbal combinations may be promising for anxiety, but more research is needed to confirm their effectiveness.
  • St. John’s wort monotherapy has insufficient evidence as an effective anxiolytic treatment.
  • Consult with a healthcare professional before starting any nutritional or herbal supplements for anxiety to ensure safety and appropriateness for your individual needs.
  • Look for high-quality, standardised herbal extracts from reputable brands to ensure potency and minimise risk of side effects.

What are some of the most promising nutritional and herbal supplements for anxiety based on current research?

According to this systematic review, passionflower, kava, and combinations of L-lysine and L-arginine have the strongest evidence as effective treatments for anxiety symptoms and disorders. Magnesium-containing supplements and some herbal combinations also show promise but require more research to confirm their anxiolytic effects.

Are there any potential side effects or risks associated with using supplements to treat anxiety?

While most of the reviewed studies reported only mild to moderate side effects, some supplements may interact with medications or have risks for certain individuals. Kava, for example, has been linked to rare cases of liver toxicity. It’s crucial to consult with a healthcare professional before starting any supplement regimen to ensure safety and appropriateness for your specific needs and medical history.

How do nutritional and herbal supplements compare to conventional treatments for anxiety, such as therapy and medication?

The evidence suggests that certain supplements, like passionflower and kava, may be as effective as some conventional anxiety medications with potentially fewer side effects. However, supplements should not necessarily be viewed as a replacement for therapy or medication, as an integrated approach may be most beneficial. More head-to-head studies are needed to directly compare the effectiveness of supplements versus conventional treatments.

What should I look for when choosing a nutritional or herbal supplement for anxiety?

Quality and standardisation are key factors when selecting a supplement. Look for products from reputable brands that undergo third-party testing to ensure purity and potency. For herbal supplements, choose those with standardised extracts to guarantee a consistent level of active compounds. It’s also advisable to choose supplements with minimal fillers or additives.

Can nutritional and herbal supplements be used long-term for managing anxiety, or are they more appropriate for short-term use?

The long-term safety and efficacy of many supplements for anxiety have not been extensively studied. Some, like kava, may be more appropriate for short-term use due to potential risks with prolonged use. Others, like magnesium and certain herbal combinations, may be safer for long-term use but still require periodic monitoring. Consult with a healthcare professional to determine an appropriate duration of use based on your individual circumstances and response to treatment.

References

Akhondzadeh, S., Naghavi, H. R., Vazirian, M., Shayeganpour, A., Rashidi, H., & Khani, M. (2001). Passionflower in the treatment of generalized anxiety: A pilot double-blind randomized controlled trial with oxazepam. Journal of Clinical Pharmacy and Therapeutics, 26(5), 363-367. https://doi.org/10.1046/j.1365-2710.2001.00367.x

Boerner, R. J., Sommer, H., Berger, W., Kuhn, U., Schmidt, U., & Mannel, M. (2003). Kava-Kava extract LI 150 is as effective as Opipramol and Buspirone in Generalised Anxiety Disorder–an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patients. Phytomedicine, 10 Suppl 4, 38-49. https://doi.org/10.1078/1433-187x-00309

Bourin, M., Bougerol, T., Guitton, B., & Broutin, E. (1997). A combination of plant extracts in the treatment of outpatients with adjustment disorder with anxious mood: Controlled study versus placebo. Fundamental & Clinical Pharmacology, 11(2), 127-132. https://doi.org/10.1111/j.1472-8206.1997.tb00179.x

Cagnacci, A., Arangino, S., Renzi, A., Zanni, A. L., Malmusi, S., & Volpe, A. (2003). Kava-Kava administration reduces anxiety in perimenopausal women. Maturitas, 44(2), 103-109. https://doi.org/10.1016/s0378-5122(02)00317-1

Connor, K. M., & Davidson, J. R. (2002). A placebo-controlled study of Kava kava in generalized anxiety disorder. International Clinical Psychopharmacology, 17(4), 185-188. https://doi.org/10.1097/00004850-200207000-00005

De Souza, M. C., Walker, A. F., Robinson, P. A., & Bolland, K. (2000). A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: A randomized, double-blind, crossover study. Journal of Women’s Health & Gender-Based Medicine, 9(2), 131-139. https://doi.org/10.1089/152460900318623

Hanus, M., Lafon, J., & Mathieu, M. (2004). Double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders. Current Medical Research and Opinion, 20(1), 63-71. https://doi.org/10.1185/030079903125002603

Jacobs, B. P., Bent, S., Tice, J. A., Blackwell, T., & Cummings, S. R. (2005). An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia. Medicine, 84(4), 197-207. https://doi.org/10.1097/01.md.0000172299.72364.95

Jezova, D., Makatsori, A., Smriga, M., Morinaga, Y., & Duncko, R. (2005). Subchronic treatment with amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety. Nutritional Neuroscience, 8(3), 155-160. https://doi.org/10.1080/10284150500162937

Kobak, K., Taylor, L., Bystrisky, A., Kohlenberg, C. J., Greist, J. H., Tucker, P., Warner, G., Futterer, R., & Vapnik, T. (2005). St John’s wort versus placebo in obsessive-compulsive disorder: Results from a double-blind study. International Clinical Psychopharmacology, 20(6), 299-304. https://doi.org/10.1097/00004850-200511000-00003

Kobak, K., Taylor, L., Warner, G., & Futterer, R. (2005). St. John’s wort versus placebo in social phobia: Results from a placebo-controlled pilot study. Journal of Clinical Psychopharmacology, 25(1), 51-58. https://doi.org/10.1097/01.jcp.0000150227.61501.00

Malsch, U., & Kieser, M. (2001). Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Psychopharmacology, 157(3), 277-283. https://doi.org/10.1007/s002130100792

Movafegh, A., Alizadeh, R., Hajimohamadi, F., Esfehani, F., & Nejatfar, M. (2008). Preoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: A double-blind, placebo-controlled study. Anesthesia and Analgesia, 106(6), 1728-1732. https://doi.org/10.1213/ane.0b013e318172c3f9

Müller, D., Pfeil, T., & von den Driesch, V. (2003). Treating depression comorbid with anxiety–results of an open, practice-oriented study with St John’s wort WS 5572 and valerian extract in high doses. Phytomedicine, 10 Suppl 4, 25-30. https://doi.org/10.1078/1433-187x-00305

Sarris, J., Kavanagh, D. J., Byrne, G., Bone, K. M., Adams, J., & Deed, G. (2009). The Kava Anxiety Depression Spectrum Study (KADSS): A randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology, 205(3), 399-407. https://doi.org/10.1007/s00213-009-1549-9

Smriga, M., Ando, T., Akutsu, M., Furukawa, Y., Miwa, K., & Morinaga, Y. (2007). Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans. Biomedical Research, 28(2), 85-90. https://doi.org/10.2220/biomedres.28.85

Taylor, L. H., & Kobak, K. A. (2000). An open-label trial of St. John’s Wort (Hypericum perforatum) in obsessive-compulsive disorder. The Journal of Clinical Psychiatry, 61(8), 575-578. https://doi.org/10.4088/jcp.v61n0806

Volz, H. P., & Kieser, M. (1997). Kava-kava extract WS 1490 versus placebo in anxiety disorders–a randomized placebo-controlled 25-week outpatient trial. Pharmacopsychiatry, 30(1), 1-5. https://doi.org/10.1055/s-2007-979474

Volz, H. P., Murck, H., Kasper, S., & Möller, H. J. (2002). St John’s wort extract (LI 160) in somatoform disorders: Results of a placebo-controlled trial. Psychopharmacology, 164(3), 294-300. https://doi.org/10.1007/s00213-002-1171-6



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