Botanicals for Blissful Mental Wellness

Possibly the best-known botanical in the mood support toolbox is St. John’s wort (Hypericum perforatum). A review in the October 2008 Cochrane Library noted St. John’s wort appears to work just as well as prescription antidepressants for treating patients with major depression, with German patients realizing the best results.¹ Lead reviewer Klaus Linde, from the Centre for Complementary Medicine Research at Technical University, Munich, commented: “The most striking trial from our review is that trials from German-speaking countries have clearly more positive effects, both compared to placebo and standard antidepressants, than trials from elsewhere.” This review included 29 studies and a total of 5,489 patients, with daily dosages between 500 and 1,200 mg. Linde and colleagues published an earlier review in 2005 that focused exclusively on St. John’s wort’s ability to reduce symptoms of mild to moderate depression.²

Comparative trials support St. John’s wort’s efficacy in treating depression. For example, Harvard researchers saw similar responses in improving symptoms in patients with major depression who received St. John’s wort or fluoxetine for 12 weeks; both interventions had similar effects in the timing of clinical improvement and symptom severity at the end of the trial.³ A trial at Vienna Medical University, Austria, involving 332 women with mild to moderate depression found St. John’s wort (600 or 1,200 mg/d) was safer and more effective than placebo in treating symptoms.⁴

The Austrian research team has also found St. John’s wort can help prevent relapse as a long-term maintenance treatment for patients recovering from recurrent depression.⁵ In a double blind, placebo-controlled, multicenter trial, adult outpatients with recurrent moderate major depression received 900 mg/d of St. John’s wort or placebo; those on the active intervention had a significantly lower chance of depression recurrence, particularly among patients with early onset of depression or a high degree of recurrence.

And while St. John’s wort is best-known for its efficacy in addressing depression, it may also help in treating anxiety. A study out of Panjab University, Chandigarh, India, examined the therapeutic impact of St. John’s wort on behavior and oxidative damage induced by sleep deprivation in mice.⁶ Mice were administered either St. John’s wort or imipramine for five days, starting two days prior to a 72-hour period of sleep deprivation. Sleep deprivation produced anxiety-like behavior and oxidative damage, which was reduced by either intervention. Combining the treatments had a synergistic effect on anxiety and oxidative damage.

Regardless of its efficacy, St. John’s wort does have pharmacological activity in the body, which has raised concerns about its possible impact on the efficacy of other substances, particularly pharmaceuticals that are absorbed via the same pathway, called cytochrome P450 (CYP3A). A research review noted St. John’s wort may lower the efficacy of several drugs, including certain statins and oral contraceptives, suggesting induction of P-glycoprotein and/or CYP3A enzymes could be the reason.⁷ Researchers suggest a comprehensive understanding of clinical drugs that interact with St. John’s wort is important, as drugs could be designed to minimize the interaction, or St. John’s wort formulas developed that avoid the interaction.⁸

There has also been controversy around the herb kava (Piper methysticum) traditionally used by in the South Pacific for mood enhancement. A review out of the Fiji School of Medicine, Suva, noted kava’s lactones exert sedative, anxiolytic, anti-stress and neuroprotective properties; however, there have been some concerns about possible hepatotoxicity.⁹ Specifically, back in 2001, there were reports and advisories out of Europe and Canada purporting to link kava ingestion to liver damage. In the United States, FDA never issued a ban on the botanical, in part due to active outreach by the botanical industry, which even hired a board-certified toxicologist to review more than 50 adverse event reports (AERs) on kava. Donald Waller, Ph.D., found the AERs generally did not provide adequate clinical information, and noted, “Based on the data available to me at this time, there is no clear evidence that the liver damage reported in the U.S. and Europe was caused by the consumption of kava.”

With the toxicity question addressed, studies have continued to support kava’s role in safely treating anxiety. A Cochrane Library review looked at 12 studies with more than 700 patients, and found kava had a significant treatment effect in relieving anxiety, with few adverse events reported.¹⁰ German researchers conducted a meta-analysis that included six placebo-controlled, randomized trials, which found kava extracts are effective in addressing anxiety disorders and remain alternatives to pharmaceutical treatments.¹¹ And a review from the Universities of Exeter Plymouth, England, concluded “kava has been shown beyond reasonable doubt to have anxiolytic effects in humans.”¹²

Another popular European botanical is valerian (Valeriana officinalis), a perennial plant native to Europe and Asia. Its active compounds are valerenic acid and its derivatives, and it has a seriously unpleasant odor (akin to sweaty socks) when dried, due to degradation of volatiles in the plant. Antoine Dauby, group marketing manager, Naturex Inc., noted valerian has been used since ancient times as a sedative, anti-convulsant and for relaxation; the company developed a specialty deodorized ingredient (ValeriPure®), standardized for valerenic acids.

In vitro trials have shown there are specific binding sites on GABA(A) receptors with affinity for valerian constituents, suggesting the botanical exerts an anxiolytic effect by affecting the neurons expressing GABA.^13,14 It has also been shown in animal studies to not exert sedative effects but, instead, exert anxiolytic and antidepressant activity.¹⁵

Valerian may have greater impact when paired with other botanicals. For example, a combination therapy of St. John’s wort and valerian was seen to more quickly treat anxiety symptoms in humans without side effects, compared to monotherapy.¹⁶ Similarly, combining valerian and lemon balm (Melissa officinalis) ameliorates anxiety induced by stress testing in healthy adults.¹⁷

Lemon balm alone may also exert anti-anxiety effects. Karine Nardon, NAT’Life, noted, “Lemon balm has been used since antiquity to counter nervous disorders. Comparative studies notably showed that lemon balm possesses relaxing properties.” Naturex developed a specialty ingredient, Cyracos®, which has been shown to have antistress activity. In a 15-day unpublished, double blind, placebo-controlled clinical study, 30 people showing symptoms of anxiety and suffering from sleep disturbances received 600 mg/d of Cyracos. Even with such short-term supplementation, there was a 32-percent reduction in the state of stress, 72-percent reduction in anxiety-associated symptoms, and a 60-percent decrease in initial insomnia.

Another proprietary botanical formulation, Relora®, from Next Pharmaceuticals, combines Magnolia officinalis and Phellodendron amurense. In animal research, the combination of botanicals was shown to be an effective, non-sedating anxiolytic in a common stress test.¹⁸ Human studies have reported similar results. An unpublished open label study on Relora, which included 1,291 participants who suffered from stress, sleeplessness and/or stress-related eating, was conducted at the LaValle Metabolic Institute in Cincinnati. Ninety-one percent of the subjects reported Relora helped them relax, 90 percent said it helped them have a restful sleep, and 86 percent reported Relora helped prevent stress-related eating. And a six-week, placebo-controlled clinical study conducted by Miami Research Associates examined the impact of Relora (250 mg/d) in healthy, overweight premenopausal females (n=40) who said they typically eat more in response to stressful situations and scored above the national mean for women on self-reporting anxiety.¹⁹ In comparison to the placebo, Relora was effective in reducing temporary, transitory anxiety, although it was not effective in reducing long-standing feelings of anxiety or depression.

An Asian botanical used for emotional well-being is Apocynum venetum L. In vitro trials suggest Apocynum venetum have significant antioxidant effects, which may inhibit lipid peroxidation in the central nervous system.²⁰ Animal trials investigating the impact of the botanical extract have found it exerts antixolytic activity mediated by the GABAergic system,²¹ and also reduces norepinephrine and dopamine concentrations, similar to the action of imipramine.²² Further, studies have shown Apocynum venetum extract does not impact the CYP3A pathway the way St. John’s wort does, eliminating the possibility of drug interactions.²³

OptiPure offers a patented form of Apocynum venetum called Posinol™, which contains no less than 4 percent of the flavonoid glycosides isoquercitrin and hyperoside, which support mental relaxation. Case study reports, provided by the ingredient producer Tokiwa Phytochemical Co., show 50 mg/d of Posinol can help reduce symptoms of mild to moderate depression. Company studies also show Posinol shortens the immobility time in an animal model for antidepressant activity.

References:

1. Linde K, Berner MM, Kriston L. “St. John’s wort for major depression.” Cochrane Database Syst Rev. 2008 Oct 8;(4):CD000448.2. Linde K et al. “St. John’s wort for depression.” Cochrane Database Syst Rev. 2005 Apr 18;(2):CD000448.3. Papakostas GI et al. “Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder. A replication of findings with the use of a double-blind, placebo-controlled trial of Hypericum perforatum versus fluoxetine.” Neuropsychobiology. 2007;56(2-3):132-7. Epub 2008 Feb 7.4. Kasper S et al. “Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298].” BMC Med. 2006 Jun 23;4:14.5. Kasper S et al. “Continuation and long-term maintenance treatment with Hypericum extract WS((R)) 5570 after recovery from an acute episode of moderate depression - A double-blind, randomized, placebo controlled long-term trial.” Eur Neuropsychopharmacol. 2008 Aug 9. [Epub ahead of print]6. Kumar A, Singh A. “Protective effect of St. John's wort (Hypericum perforatum) extract on 72-hour sleep deprivation-induced anxiety-like behavior and oxidative damage in mice.” Planta Med. 2007 Oct;73(13):1358-64. Epub 2007 Oct 4.7. Izzo AA. “Drug interactions with St. John’s wort (Hypericum perforatum): a review of the clinical evidence.” Int J Clin Pharmacol Ther. 2004;42(3):139-48.8. Di YM et al. “Clinical drugs that interact with St. John's wort and implication in drug development.” Curr Pharm Des. 2008;14(17):1723-42.9. Gounder R. “Kava consumption and its health effects.” Pac Health Dialog. 2006 Sep;13(2):131-5.10. Pittler MH, Ernst E. “Kava extract for treating anxiety.” Cochrane Database Syst Rev. 2003;(1):CD003383.11. Witte S, Loew D, Gaus W. “Meta-analysis of the efficacy of the acetonic kava-kava extract WS1490 in patients with non-psychotic anxiety disorders.” Phytother Res. 2005 Mar;19(3):183-8.12. Ernst E. “Herbal remedies for anxiety - a systematic review of controlled clinical trials.” Phytomedicine. 2006 Feb;13(3):205-8. Epub 2005 Aug 15.13. Benke D et al. “GABA(A) receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts.” Neuropharmacology. 2008 Jun 17. [Epub ahead of print]14. Khom S et al. “Valerenic acid potentiates and inhibits GABA(A) receptors: molecular mechanism and subunit specificity.” Neuropharmacology. 2007 Jul;53(1):178-87. Epub 2007 May 13.15. Hattesohl M et al. “Extracts of Valeriana officinalis L. s.l. show anxiolytic and antidepressant effects but neither sedative nor myorelaxant properties.” Phytomedicine. 2008 Jan;15(1-2):2-15.16. Müller D, Pfeil T, von den Driesch V. “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. 2003;10 Suppl 4:25-30.17. Kennedy DO et al. “Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory induced stress.” Phytother Res. 2006 Feb;20(2):96-102.18. Sufka KJ et al. Anxiolytic properties of botanical extracts in the chick social separation-stress procedure. Psychopharmacology (Berl). 153, 2:219-24, 200119. Kalman DS et al. “Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial.” Nutr J. 2008 Apr 21;7:11.20. Shirai M et al. “Approach to novel functional foods for stress control 5. Antioxidant activity profiles of antidepressant herbs and their active components.” J Med Invest. 2005 Nov;52 Suppl:249-51.21. Grundmann O et al. “Anti-anxiety effects of Apocynum venetum L. in the elevated plus maze test.” J Ethnopharmacol. 2007 Apr 4;110(3):406-11. Epub 2006 Oct 13.22. Butterweck V et al. “Long-term effects of an Apocynum venetum extract on brain monoamine levels and beta-AR density in rats.” Pharmacol Biochem Behav. 2003 Jun;75(3):557-64.23. Kobayashi M et al. “Apocynum venetum extract does not induce CYP3A and P-glycoprotein in rats.” Biol Pharm Bull. 2004 Oct;27(10):1649-52.