The full text is available at pubmed.Nutr J. 2010 Oct 7;9:42.
Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review.
Lakhan SE, Vieira KF.
BACKGROUND: Over the past several decades, complementary and alternative medications have increasingly become a part of everyday treatment. With the rising cost of prescription medications and their production of unwanted side effects, patients are exploring herbal and other natural remedies for the management and treatment of psychological conditions. Psychological disorders are one of the most frequent conditions seen by clinicians, and often require a long-term regimen of prescription medications. Approximately 6.8 million Americans suffer from generalized anxiety disorder. Many also suffer from the spectrum of behavioural and physical side effects that often accompany its treatment. It is not surprising that there is universal interest in finding effective natural anxiolytic (anti-anxiety) treatments with a lower risk of adverse effects or withdrawal.
METHODS: An electronic and manual search was performed through MEDLINE/PubMed and EBSCO. Articles were not discriminated by date of publication. Available clinical studies published in English that used human participants and examined the anxiolytic potential of dietary and herbal supplements were included. Data were extracted and compiled into tables that included the study design, sample population, intervention, control, length of treatment, outcomes, direction of evidence, and reported adverse events.
RESULTS: A total of 24 studies that investigated five different CAM monotherapies and eight different combination treatments and involved 2619 participants met the inclusion criteria and were analyzed. There were 21 randomized controlled trials and three open-label, uncontrolled observational studies. Most studies involved patients who had been diagnosed with either an anxiety disorder or depression (n = 1786). However, eight studies used healthy volunteers (n = 877) who had normal levels of anxiety, were undergoing surgery, tested at the upper limit of the normal range of a trait anxiety scale, had adverse premenstrual symptoms or were peri-menopausal, reported anxiety and insomnia, or had one month or more of elevated generalized anxiety. Heterogeneity and the small number of studies for each supplement or combination therapy prevented a formal meta-analysis. Of the randomized controlled trials reviewed, 71% (15 out of 21) showed a positive direction of evidence. Any reported side effects were mild to moderate.
CONCLUSIONS: Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects. There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders. However, based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava and combinations of L-lysine and L-arginine as treatments for anxiety symptoms and disorders. Magnesium-containing supplements and other herbal combinations may hold promise, but more research is needed before these products can be recommended to patients. St. John's wort monotherapy has insufficient evidence for use as an effective anxiolytic treatment.
I found this to be a very easy article for a quick summary of kava kava, passionflower, L-lysine, magnesium, and St.Johns effectiveness for treating anxiety. I wanted to create this thread as a place for people to look for information on different herbs and nutritional supplements for treating anxiety. I'm interested in personal experiences, additional research, or anything else that helps our understanding of safer alternatives for treatment. I'm also happy to answer questions but I am not an expert.
I found this article while doing research on l-lysine and magnesium. I starting taking supplements about a week ago with the goal of reducing my Xanax use. I take l-lysine two-three times a day (1g each time) on an empty stomach and I take the magnesium (with calcium & Vitamin D) once a day with dinner. With minimal withdrawal symptoms and several positive benefits I've reduced my Xanax use by 33% (down from 1.5mg to 1mg). The first night I made the reduction I got less/worse sleep than normal. I also felt anxious the next day, although not nearly as badly as I usually feel (the absence of a headache was worth it alone). The second night was considerable better and I actually got much BETTER sleep than I did while on a higher dose of Xanax. In addition, I feel more high on Xanax when I do take it (that .5 or even .25 can go a long way). I plan to continue to take the l-lysine and magnesium and work toward reducing my dose down to .5mg once a day. I wanted to post this to help spread both my success story as well as the information.
I will continue to post personal progress & relevant journal abstracts to help fellow members of BL in their quest for HR.
NOTE: I did notice that it took several days for the nutrients to build up and gain effectiveness. If you plan to attempt this, you may want to give it a few days on the supplements before attempting to reduce your dose.
This is one of the articles looked in in the review from the first post. It is also perhaps the most interesting study concerning the effect of l-lysine on human health.Biomed Res. 2007 Apr;22):85-90.
Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans.
Smriga M, Ando T, Akutsu M, Furukawa Y, Miwa K, Morinaga Y.
Dietary supplementation with an essential amino acid L-lysine has been shown to reduce chronic anxiety in humans with low dietary intake of L-lysine. A combination of L-lysine and L-arginine has been documented to normalize hormonal stress responses in humans with high trait anxiety. The present study was carried out in one hundred eight healthy Japanese adults. The aim of study was to find out whether a week-long oral treatment with L-lysine (2.64 g per day) and L-arginine (2.64 g per day) reduces trait and stress-induced state anxiety and basal levels of stress hormones. We confirmed that, without regard to gender, the amino acid treatment significantly reduced both trait anxiety and state anxiety induced by cognitive stress battery. In addition, we found that the treatment with L-lysine and L-arginine decreased the basal levels of salivary cortisol and chromogranin-A (a salivary marker of the sympatho-adrenal system) in male subjects. These results of this double-blind, placebo controlled and randomized study confirm the previous findings in humans and animals and point to a combination of L-lysine and L-arginine as a potentially useful dietary intervention in otherwise healthy humans with high subjective levels of mental stress and anxiety.
This article looks at the health benefits of l-lysine in a population with lysine deficiencies.Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria.
Smriga M, Ghosh S, Mouneimne Y, Pellett PL, Scrimshaw NS.
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8285-8. Epub 2004 May 24.
Lysine is a limiting amino acid in diets based on wheat as the staple. In experimental animals, prolonged dietary lysine inadequacy increases stress-induced anxiety. If observed in humans, such a result would have a strong implication for the relationship between nutrition and communal quality of life and mental health. As part of a 3-month randomized double-blind study, we tested whether lysine fortification of wheat reduces anxiety and stress response in family members in poor Syrian communities consuming wheat as a staple food. In the lysine-fortified group, the plasma cortisol response to the blood drawing as a cause of stress was reduced in females, as was sympathetic arousal in males as measured by skin conductance. Lysine fortification also significantly reduced chronic anxiety as measured by the trait anxiety inventory in males. These results suggest that some stress responses in economically weak populations consuming cereal-based diets can be improved with lysine fortification.
J Nutr. 2002 Dec;132(12):3744-6.
Dietary L-lysine deficiency increases stress-induced anxiety and fecal excretion in rats.
Smriga M, Kameishi M, Uneyama H, Torii K.
Little is known about the psychobehavioral consequences of a dietary deficiency of the amino acid, L-lysine. This report demonstrates that a 4-d long L-lysine deficiency in rats interfered with the normal circadian release of the neurotransmitter serotonin, but not dopamine, measured by in vivo microdialysis in the central nucleus of the amygdala. L-Lysine deficiency was induced by feeding rats a L-lysine-deficient diet. Controls were pair-fed a L-lysine-sufficient diet. Footshock stress-induced anxiety, measured in an elevated plus-maze paradigm, and wrap-restraint stress-stimulated fecal excretion were significantly greater in the L-lysine-deficient rats than in the controls. We conclude that a severe deficiency of dietary L-lysine enhances serotonin release in the amygdala, with subsequent changes in psychobehavioral responses to stress.
PMID:12468617Nutr Neurosci. 2003 Oct;6(5):283-9.
A diet fortified with L-lysine and L-arginine reduces plasma cortisol and blocks anxiogenic response to transportation in pigs.
Srinongkote S, Smriga M, Nakagawa K, Toride Y.
We studied the effects of diet fortified with L-lysine HCl (Lys) and L-arginine (Arg) on stress (transportation) responses in male finishing pigs (Landrace x LargeWhite x Duroc). Pigs (n = 16) were randomly divided into two equally sized groups so that the average starting body weight in the groups was identical. For 1 week immediately preceding the transportation, the first group of pigs received a control diet while the second group received a Lys and Arg fortified diet. Plasma aminogram, cortisol and body weight were evaluated. Behavior of pigs was measured with the help of a video camera, recorded for 2 h at the same time, as on the day, before a day and immediately after transportation. The study revealed main stimulatory effects of transportation and main inhibitory effect of Lys and Arg on plasma cortisol (P < 0.05) without transportation x treatment interactions. Pigs fed with Lys and Arg diet tend to have higher body weight at the end of the experiment, when compared to their normally fed counterparts, but the difference did not reach a significant level (P < 0.21). Lys and Arg diet significantly inhibited stress-induced increase in locomotion (P < 0.05), without affecting feeding pattern. Transportation stress decreased plasma Lys and Arg. This decrease was reversed in the fortified group, and what is more the plasma Lys and Arg levels were significantly higher than in controls (P < 0.05). Lys and Arg enhanced plasma urea production (P < 0.05), without regards to stress. The behavioral results indicate a reduction in stress-induced anxiety in pigs fed with Lys and Arg fortified diet, that parallels similar observations in research with rats and broilers. The mechanism probably involves a decreased plasma cortisol, and/or normalized plasma Lys, Arg levels.
PMID: 14609314Prog Clin Biol Res. 1985;192:477-84.
On the brain endocoid for benzodiazepine recognition sites.
Guidotti A, Ferrero P, Costa E.
Human and rat brain contain a neuropeptide with 105 amino acid residues which inhibits the binding of 3H-diazepam and other specific benzodiazepine recognition site ligands to crude brain synaptic membranes. DBI injected intracerebroventricularly in thirsty rats which are subjected to a conflict test (Corda et al., 1983), lowers the threshold for behavioral suppression by punishment. In this test DBI acts like an anxiogenic endocoid for the benzodiazepine recognition sites. The large abundance of lysine and arginine residues in the DBI molecule suggest that this polypeptide functions as a precursor of a putative endocoid which regulates anxiety levels. This endocoid acts as an agonist for the benzodiazepine recognition site. Because of the anxiogenic properties of this endocoid, it is proposed that anxiolytic benzodiazepine should be classified as an antagonist and beta-carboline as an agonist at the receptor level.
PMID: 3001768Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):11043-8.
Inter- and intraspecies polymorphisms in the cholecystokinin-B/gastrin receptor alter drug efficacy.
Kopin AS, McBride EW, Gordon MC, Quinn SM, Beinborn M.
The brain cholecystokinin-B/gastrin receptor (CCK-BR) is a major target for drug development because of its postulated role in modulating anxiety, memory, and the perception of pain. Drug discovery efforts have resulted in the identification of small synthetic molecules that can selectively activate this receptor subtype. These drugs include the peptide-derived compound PD135,158 as well as the nonpeptide benzodiazepine-based ligand, L-740,093 (S enantiomer). We now report that the maximal level of receptor-mediated second messenger signaling that can be achieved by these compounds (drug efficacy) markedly differs among species homologs of the CCK-BR. Further analysis reveals that the observed differences in drug efficacy are in large part explained by single or double aliphatic amino acid substitutions between respective species homologs. This interspecies variability in ligand efficacy introduces the possibility of species differences in receptor-mediated function, an important consideration when selecting animal models for preclinical drug testing. The finding that even single amino acid substitutions can significantly affect drug efficacy prompted us to examine ligand-induced signaling by a known naturally occurring human CCK-BR variant (glutamic acid replaced by lysine in position 288; 288E --> K). When examined using the 288E --> K receptor, the efficacies of both PD135,158 and L-740, 093 (S) were markedly increased compared with values obtained with the wild-type human protein. These observations suggest that functional variability resulting from human receptor polymorphisms may contribute to interindividual differences in drug effects.
PMID: 9380756J Rheumatol Suppl. 1989 Nov;19:158-63.
Serum amino acids in fibrositis/fibromyalgia syndrome.
Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Wall K.
Free plasma tryptophan levels in patients with fibrositis syndrome were measured by Moldofsky and Warsh with the view that the pathogenesis of fibrositis syndrome might involve a functional deficiency of serotonin. The hypothesis was supported by the finding of an inverse relationship between tryptophan concentration and the severity of musculoskeletal pain. Our study examined the total serum amino acid pool in fibrositis syndrome. Twenty patients with primary fibrositis syndrome and matched normal controls were evaluated clinically. After denaturation of macromolecules, serum amino acids were quantitated by automated analysis. Patients with fibrositis syndrome exhibited significantly lower levels of total serum tryptophan (p = 0.002), as well as 6 other amino acids: alanine (p less than 0.0005), histidine (p = 0.001), lysine (p = 0.02), proline (p = 0.039), serine (p = 0.028 ), and threonine (p = 0.013). These findings support the serotonin deficiency hypothesis for fibrositis syndrome pathogenesis but also imply a more generalized defect in amino acid homeostasis among affected individuals.