Salvia (Sage) Plants: Anxiety Treatments?

weight lossSalvia (sage) plants are a perennial plant that belongs to the Lamiaceae or mint family of plants. The most well known of these plants is possibly Salvia officinalis, which is also called common sage or garden sage. Salvia plants tend to grow to about 1 meter in height and possesses hairy leaves and a long stem that often possesses purple or lavender flowers. Salvia plants have a widespread distribution being found in both tropical and temperate region, and are often grown in gardens. Many of the plants in this group are aromatic. The aromatic nature of this group of plants comes from the presence of an essential oil in the plant tissues. These plants are often used in cooking because of their distinctive taste properties. Salvia species of plants have been used for a number of medicinal effects, For example, the aerial parts of Salvia officinalis is used as a blood sugar lowering agent, Salvia sclare is used as a tonic, Salvia macrosiphon is used as an antimicrobial and Salvia aegyptica is used as an anti-inflammatory.

sage anxiety mood

Salvia miltiorrhiza, also called red sage, Chinese sage, Tan shen or danshen, is another salvia plant that may have medicinal properties. Analysis of Salvia miltiorrhiza revealed that it contains a large number of phytochemicals that may explain its pharmacological activity. The phytochemicals present in Salvia miltiorrhiza include the phenolic acids protocatechuic acid, ptotocatechuic aldehyde, caffeic acid, isoferulic acid and Danshensu (3,4- diydroxyphenyllactic acid). There are also a number of polyphenols that are mainly conjugates of the phenolic acid, danshensu or caffeic acid. Other polyphenolic acids are rosmarinic acid, lithospermic acid and salvianolic acid A-G.

However, some of the salvia plants may have beneficial effects in the treatment of anxiety. For example, in one study, the neurochemical effects of lilac sage (Salvia reuterina, also called whorled clary) was investigated using animal models. Administration of lilac sage resulted in significant reductions in the anxious behaviour exhibited by mice when they were exposed to experimental stress. In addition, mice administered lilac sage also displayed significant reduction in movement, suggesting that the herb was an effective sedative. The mood elevating effects of Salvia has also been investigated in humans. In one study, human subjects were administered essential oil extract from Salvia lavandulaefolia. The results of the study showed that at 50 μL dose, the essential oil significantly improved the memory of the subjects. The same researchers also showed improvements in memory with 25 and 50 μL doses of Salvia officinalis and improvements in alertness, calness and centrentedness in the 50  μL dose group.

sage anxiety depression mood

Analysis of Salvia reterana showed that the volatile constituents of the plant included 21 components in the essential oil including β-ocimene (32 %), α-gurjunene (14 %), germacrened (11 %) and hexyl acetate (8 %). Analysis of Salvia reterana showed that the volatile constituents of the plant included 31 components in the essential oil including β-caryophyllene (42 %), germacrene-B (21 %), caryophyllene oxide (7 %), cis-β-farnesene (6 %) and germacrene-D (6 %). Garden or common sage (salvia officinalis) (pictured) may have similar phytochemical constituents.

In another study, the effects of Salvia officinalis (garden sage or common sage) were investigated on the mood, anxiety and under-stress performance of healthy young subjects. Subjects were administered 300 or 600 mg of sage leaf and their mood was then evaluated on the Bond-Lader mood scale and the State Trait Anxiety Inventory. At both doses, administration of salvia officinalis led to improvements in mood. At the lower dose the herb was effective at reducing anxiety and at higher doses increasing alertness, calmness and contentedness. However administration of stress to the subjects did modify these effects, as might be expected. The researchers showed that the sage leaf extracts were able to inhibit acetylcholinesterase in the tissue cultures. This suggests that one of the mechanisms by which sage may work is through the inhibition of the enzyme that breaks down acetylcholine. This may increase acetylcholine levels in the brain, producing elevations in mood and memory.

anxiety sage mood depression

Extracts of sage may inhibit the enzyme acetylcholinesterase and in doing so, increase brain levels of the neurotransmitter acetylcholine. This may then in turn increase memory and mood. In one study, a single dose 50 μL of salvia lavandulaefolia essential oil was administered to healthy participants. Oral consumption of the essential oil of Salvia lavandulaefolia was effective at improving memory and attention in the subjects, notably at 1 hour post consumption. In contrast improved alertness and reduced mental fatigue were more pronounced at 4 hours post consumption. This essential oil was made up almost exclusively of monoterpenoids. It was confirmed using tissue studies, that the essential oil was a potent inhibitor of acetylcholinesterase. Therefore the monoterpenes in the essential oil of Salvia lavandulaefolia may be partly responsible for the memory and mood elevating effects of the herb.

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Rabbani, M., Sajjadi, S. E., Jafarian, A. and Vaseghi, G. 2005. Anxiolytic effects of Salvia Reuterana Boiss. on the elevated plus-maze model of anxiety in mice. Journal of Ethnopharmacology. 101(1): 100-103
De Palma, A., Rossi, R., Carai, M., Cabras, C., Colombo, G., Arnoldi, L., Fuzzati, N., Riva, A., Morazzoni, P. and Mauri, P. L. 2008. Pharmaceutical and biomedical analysis of terpene constituents in Salvia miltiorrhiza. Current Pharmaceutical Analysis. 4(4): 249-257
Mirza, M., & Sefidkon, F. 1999. Essential oil composition of two Salvia species from Iran, Salvia nemorosa L. and Salvia reuterana Boiss. Flavour and Fragrance Journal. 14(4): 230-232
Kennedy, D. O., Pace, S., Haskell, C., Okello, E. J., Milne, A. and Scholey, A. B. 2006. Effects of cholinesterase inhibiting sage (Salvia officinalis) on mood, anxiety and performance on a psychological stressor battery. Neuropsychopharmacology. 31(4): 845-852
Tildesley, N. T., Kennedy, D. O., Perry, E. K., Ballard, C. G., Savelev, S. A. W. K., Wesnes, K. A. and Scholey, A. B. 2003. Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers. Pharmacology Biochemistry and Behavior. 75(3): 669-674
Tildesley, N. T. J., Kennedy, D. O., Perry, E. K., Ballard, C. G., Wesnes, K. A. and Scholey, A. B. 2005. Positive modulation of mood and cognitive performance following administration of acute doses of Salvia lavandulaefolia essential oil to healthy young volunteers. Physiology and Behavior. 83(5): 699-709
Kennedy, D. O., Dodd, F. L., Robertson, B. C., Okello, E. J., Reay, J. L., Scholey, A. B. and Haskell, C. F. 2011. Monoterpenoid extract of sage (Salvia lavandulaefolia) with cholinesterase inhibiting properties improves cognitive performance and mood in healthy adults. Journal of Psychopharmacology. 25(8): 1088-1100
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Are Low Energy Neuroprotective?

weight lossFasting has been known to produce anticonvulsant effects since the 1920’s. In fact low energy diets and fasting are recorded at effective treatments for epilepsy by mainstream medicine. As understanding of this process has increased, it has become clear that low energy diets and fasting may have general neuroprotective effects in animals and humans. On interesting aspect of this research is that ketogenic diets and the presence of ketone bodies in the blood appears to be neuroprotective, and this may explain the neuroprotective effects of fasting and low energy diets. Further, it is known that low energy diets are protective of both Parkinson’s disease and Alzheimer’s disease and that obesity increases the risk of dementia. Low energy diets may also increase energy pathways in the brain providing cognitive benefits. It is also known that energy restriction can improve mood. In animals, the normal deterioration seen with age in cognitive function is also reduced with energy restriction.

energy restriction mood

The sirtuins are a group of enzymes that regulate gene expression. Increasing the expression of sirtuins increases longevity in animals and may increase neuroprotective factors in the brain. In mammals, energy restriction increases expression of sirtuins. Resveratrol, a polyphenol found in grapes and red wine also increases expression of sirtuins. This may explain why red wine has been shown to increase the age-related memory decline seen in mammals.

It was originally thought that the improvements in mood, memory and other cognitive functions seen in energy restrictive diets may be due to improved mitochondrial function and ultimately decreases free radical generation, or through gene regulation that increases the production of neuroprotective factors. These mechanisms may contribute to the beneficial neurochemical effects of energy restrictive diets. A more recent theory suggests that the stress placed upon the cells of the brain by energy restriction, may increase the efficiency of the energy production of the cell. Energy restricted diets may also increase antioxidant defences by upregulating antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and catalase. Coupled with the decrease in free radicals generated by the improved mitochondrial function, this may decrease oxidative stress in the tissue of the brain and decrease lipid peroxidation of cell membranes, improving neuronal transmission and thereby improving mood.  

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Maalouf, M., Rho, J. M. and Mattson, M. P. 2009. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Research Reviews. 59(2): 293-315
Wing, R. R., Marcus, M. D., Blair, E. H. and Burton, L. R. 1991. Psychological responses of obese type II diabetic subjects to very-low-calorie diet. Diabetes Care. 14(7): 596-599
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Linalool: A Plant Terpene with Anxiolytic Effects

weight lossLinalool is a phytochemical belonging to the terpene group. Linalool is a component of the essential oils of a number of aromatic plants and it may have particular medicinal effects. Essential oils are concentrated volatile phytochemicals that produce a strong odour. They often contain high amounts of hydrocarbons, mainly terpenes and terpene derivatives as well as non-hydrocarbons such as alcohols, ketones, aldehydes, phenols, oxides and esters. Such essential oils are used nutritionally in traditional medicine and are also used as treatments in aromatherapy. Essential oils have been shown to possess a number of therapeutic effects, and in some cases can be useful in the treatment of mood disorders. Essential oils containing linalool have traditionally been used for their relaxing and calming properties. Linalool is found in a number of medicinal plants including Lavandula angustifolia (lavender), Melissa officinalis (lemon balm), Rosmarinus officinalis (rosemary) and Cymbopogon citratus (lemon grass).

lavender anxiety depression

The essential oils of plants contain two groups of phytochemicals. The first group are hydrocarbons that comprise mainly of terpenes and terpene derivatives such as monoterpenes, sesquiterpenes, and diterpenes. In addition, there are a group of non-hydrocarbons that include oxygenated chemicals that include oxides, phenols, aldehydes, ketones, esters and alcohols. Linalool is a terpene, bt linalool oxide is a monocyclic alcohol. Linalool is present in a number of plant essential oils. Pictured is lavender, which contains linalool. The essential oil from lavender may be relaxing and calming because of its linalool content.

Inhaled linalool has been shown to possess sedative effects in mice. At 1 % and 3 % saturation of air with linalool, mice experienced increase sleeping time when exposed for 60 minutes. In addition, the inhalation of linalool decrease body temperature in the mice. At the higher 3 % dose, the mice also experienced reductions in locomotion. All of these effects taken together suggest that linalool possesses sedative effects in mammals. In another study on mice, the behavioural effects of inhaled linalool were investigated. Again mice were exposed to air saturated with 1 % and 3 % linalool and their behavior was observed. The addition of linalool to the air decreased the anxious behaviour exhibited by the mice. In addition, the linalool increased social interaction and decreased aggressive behaviour. The authors concluded that inhaled linalool may be an effective way of inducing relaxation and decreasing anxiety. This sort of administration of linalool is inline with the use of certain essential oils in aromatherapy.  

lemon grass anxiety depression

Research has shown that linalool has particular central nervous system effects in mammals. In particular linalool has been shown to have sedative, hypnotic and anxiolytic effects in rats and mice. Linalool may work by binding to glutamate receptors in the brain. In experiments of rats, linalool has been shown to inhibit the glutamate receptor in a similar way to the barbiturate drug phenobarbital. Glutamate receptors are excitatory, and activation of them increases excitation in the brain. By inhibiting the receptors, linalool may exert its calming effects. Pictured is lemon grass. Lemongrass my be calming and relaxing because of the linalool content of its essential oil.

In another study, researcher investigated the effects of linalool on the behaviour of rats. The researchers reported that the linalool, administered as an injection, reduced the movement exhibited by the rats, suggesting that it had a sedative effect. However the researchers injected the linalool into the rats, rather than by using inhalation, which may explain the lack of effects. Linalool can be oxidised to another chemical called linalool oxide. Linalool oxide is also found in certain plants essential oils, albeit at a lower concentration that linalool. The behavioural and mood elevating effects of linalool oxide have also been investigated. In one study, researchers administered linalool oxide to mice by inhalation in a chamber, through mixture with air. Mice receiving the linalool oxide exhibited a reduction in anxious behaviour, suggesting that the linalool oxide had conferred anxiolytic effects on the mice. At some concentrations of linalool oxide, the effects were close to those of the benzodiazepine drug diazepam.

rosemary anxiety depression

Administration of linalool to mice improves their memory and learning. This has made linalool an interesting compound for researchers investigating treatments for Alzheimer’s disease. Linalool appears to have potent antioxidant and anti-inflammatory effects in brain tissue, and this may explain its neurochemical effects. Mice administered linalool also demonstrate behavioural changes that are indicative of elevated mood, particularly, with regard to reductions in anxiety. Rosmarinus officinalis (rosemary), pictured, contains linalool.

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Souto-Maior, F. N., de Carvalho, F. L., de Morais, L. C. S. L., Netto, S. M., de Sousa, D. P. and de Almeida, R. N. 2011. Anxiolytic-like effects of inhaled linalool oxide in experimental mouse anxiety models. Pharmacology Biochemistry and Behavior. 100(2): 259-263
de Moura Linck, V., da Silva, A. L., Figueiró, M., Piato, A. L., Herrmann, A. P., Birck, F. D., Caramao, E. B., Nunes, D. S., Moreno, P. R. H. and Elisabetsky, E. 2009. Inhaled linalool-induced sedation in mice. Phytomedicine. 16(4): 303-307
Linck, V., da Silva, A., Figueiró, M., Caramão, E. B., Moreno, P. R. H. and Elisabetsky, E. 2010. Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice. Phytomedicine. 17(8): 679-683
Cline, M., Taylor, J. E., Flores, J., Bracken, S. and McCall, S. 2008. Investigation of the anxiolytic effects of linalool, a lavender extract, in the male Sprague-Dawley rat. AANA Journal. 76(1): 1-6
Elisabetsky, E., Marschner, J. and Souza, D. O. 1995. Effects of linalool on glutamatergic system in the rat cerebral cortex. Neurochemical Research. 20(4): 461-465
Maria, S. G. A., Edison, O. and Patricia, C. G. G. 2016. Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer’s mice. Neuropharmacology. 102: 111-120
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Lippia Plants: Anti-anxiety herb

weight lossLippia refers to a Genus (group) of flowering plants from the Verbenaceae (vervain or verbena) family. The Genus contains between 200 and 400 different species and these are characterised by their fragrant aroma, which is due to the presence of a unique essential oil. However, there is a great deal of dispute about exactly which plants belong to this group, with some authors including certain plants and others excluding them. Lippia plants are found mainly in South and Central American and in Tropical Africa. The leaves of many species of Lippia can be used as a herb in cooking for their flavour. One species of plant, Lippia dulcis Trevir, has exceptionally sweet licorice-flavoured leaves that can be used as an alternative to sugar, and is often added to beverages for this reason. The essential oil of Lippia species may have particular medicinal properties. The chemical composition of Lippia species appears to be relatively consistent with minor variation, which suggests that many plants are interchangeable in their medicinal role.

lippia verbena anxiety

The chemical composition of the essential oils of Lippia plants has been extensively reported. Commonly, Lippia essential oils include phytochemicals such as limonene, β-caryophyllene, p-cymene, camphor, linalool, α-pinene and thymol. However the essential oils may differ between species. For example, the essential oil of Lippia citriodora contains neral and geranial (citral) as well as the mono­terpenoids limonene, carvone, dipentene, linalool, nerol and geraniol. Whereas the essential oil of Lippia graveolens contains mainly thymol with lesser amounts of p-cymene. The essential oils in Lippia plants may also differ slightly between the flowers and leaves of a specific species, and further may vary depending on the season in which the analysis is performed.

The most common medicinal role for Lippia species is in the treatment of respiratory disorders.  such as coughs, colds, bronchitis, influenza, shortness of breath and asthma. Medicinally the leaves, stems and other aerial parts of Lippia plants tend to be used therapeutically in the form of a tea or other decoction. However, some evidence suggests that Lippia species of plants may possess anxiolytic and sedative effects. For example researchers have investigated the effects of Lippia alba on the behaviour of rats exposed to experimental stress designed to induce generalised anxiety and panic disorder. The results of the study showed that Lippia alba conferred anxiolytic effects on the rats, and the behaviour exhibited by the rats administered Lippia was comparable to that of the benzodiazepine drug diazepam. A similar anxiolytic behavioural response was seen in rats administered the Lippia essential oil component carvone, suggesting that this compound may have been responsible in part for the effects of Lippia.

Lippia citriodora (Also called Aloysia triphylla; commonly lemon verbena) is a member of the Lippia genus that has been investigated for its anxiolytic effects. For example, in one study, the anxiolytic and sedative effects of Lippia citriodora leaf extracts were investigated on mice. The results of the study showed that the extracts of Lippia citriodora conferred behavioural effects on the mice that was indicative of an anti-anxiety effect. In addition, the herbal extract increased the sleep time of the mice, suggesting that it had sedative effects. These effects were also seen for verbascoside, a phytochemical present in Lippia citriodora leaves. Therefore verbascoside may have been partly responsible for the effects. The sedative effects of the leaf extract and verbascoside were inhibited by the benzodiazepine blocker flumazenil, suggesting that sedation may have occurred through activation of the benzodiazepine receptor. The verbascoside in Lippia citriodora has also been shown to possess neuroprotective effects in rats.  

lippia verbena anxiety

The sweet compound in Lippia dulcis Trevir has been identified as the sesquiterpenes hernandulcin and epihernandulcin. Other species of Lippia also contain sesquiterpenes including lippifoli-1(6)-en-5-one. Lippia plants also contain polyphenolic substances including derivatives of the hydroxy cinnamate caffeic acid (including verbascoside and acteoside), derivatives of the phenolic acids p-coumaric acid and ferulic acid, and a wide range of flavonoids, the majority of which are flavones (including, luteolin, luteolinhispidulin, 6-hydroxyluteolin, luteolin 7-O-β-glucoside, cismaritin, diosmetin, cirsiliol, chrysoeriol apigenin and pectolin-arigenin). Some flavanones (including naringenin and pinocembrin) are also present. Lippia also contains a number of triterpene and steroidal derivatives that are most commonly saponins. A number of alkaloids are also present in the aerial parts of the Lippia plants.

In another study Lippia alba leaf extracts were shown to possess both sedative and muscle relaxant effects in mice. These effects were highest in the extracts containing the most flavonoids, suggesting that the flavonoid concentrations may be an important determinant of the sedative effects of Lippia alba leaf extracts. In another study, the essential oil of Lippia alba containing either 55 % citral, 10 % myrcene, 63 % citral and 23% limonene, or 55 % carvone and 12 % limonene was investigated on the behaviour of mice. All of the extracts caused significant sedation, and also caused anxiolytic effects in mice exposed to stress tests. Citral, myrcene and limonene all appeared to have sedative effects in the mice. However the anxiolytic and sedative effects were not as great as for with the benzodiazepine drug diazepam. Other researchers have measured the binding capacity of flavonoids extracted from Lippia alba on the benzodiazepine receptor and found that the flavone luteolin 7-digucuronide was the most active.

lippia verbena anxiety

The leaves of Lippia alba plants has been shown to possess significant antioxidant properties. This is likely due to the presence of polyphenolic compounds including hydroxycinnamates and flavonoids in the leaves. Antioxidants have been shown to be beneficial against mood disorders because they prevent the detrimental lipid peroxidation of brain tissue that can be a causative factor in neurodegeneration.

In another study researchers investigated the mood elevating and behavioural effects of another Lippia plant, Lippia graveolens. Mice were administered leaf extracts of Lippia graveolens and then exposed to experimental stress. The researchers observed significant anxiolytic effects in the Lippia graveolens group, an effect that was similar to that of the benzodiazepine drug diazepam. Therefore Lippia species of plants appear to demonstrate anxiolytic and sedative effects in mammals. Lippia studies on humans are very limited and so it is difficult to determine the usefulness of the herb in the treatment of mood disorders. One study investigated the effects of Lippia citriodora on human subjects, but found no evidence of anxiolytic effects. However, many of the phytochemicals contained within Lippia plants have been shown to have significant effects against mood disorders in experimental models and in humans. Therefore the traditional use of Lippia plants as a treatment for anxiety is likely a real effect, but more studies are needed.

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Pascual, M. E., Slowing, K., Carretero, E., Mata, D. S. and Villar, A. 2001. Lippia: traditional uses, chemistry and pharmacology: a review. Journal of Ethnopharmacology. 76(3): 201-214
Santos-Gomes, P. C., Fernandes-Ferreira, M. and Vicente, A. M. 2005. Composition of the essential oils from flowers and leaves of vervain [Aloysia triphylla (L’Herit.) Britton] grown in Portugal. Journal of Essential Oil Research. 17(1): 73-78
Argyropoulou, C., Daferera, D., Tarantilis, P. A., Fasseas, C. and Polissiou, M. 2007. Chemical composition of the essential oil from leaves of Lippia citriodora HBK (Verbenaceae) at two developmental stages. Biochemical Systematics and Ecology. 35(12): 831-837
Hatano, V. Y., Torricelli, A. S., Giassi, A. C. C., Coslope, L. A. and Viana, M. B. 2012. Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze. Brazilian Journal of Medical and Biological Research. 45(3): 238-243
Ara, N. and Nur, H. 2009. In vitro antioxidant activity of methanolic leaves and flowers extracts of Lippia alba. Research Journal of Medicine and Medical Sciences. 4(1): 107-110
Razavi, B. M., Zargarani, N. and Hosseinzadeh, H. 2017. Anti-anxiety and hypnotic effects of ethanolic and aqueous extracts of Lippia citriodora leaves and verbascoside in mice. Avicenna Journal of Phytomedicine. 7(4): 353-365
Liang, J. Q., Wang, L., He, J. C. and Hua, X. D. 2016. Verbascoside promotes the regeneration of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra. Neural Regeneration Research. 11(1): 101-106
Zétola, M., De Lima, T. C. M., Sonaglio, D., González-Ortega, G., Limberger, R. P., Petrovick, P. R. and Bassani, V. L. 2002. CNS activities of liquid and spray-dried extracts from Lippia alba—Verbenaceae (Brazilian false melissa). Journal of Ethnopharmacology. 82(2): 207-215
Vale, T. G., Matos, F. J. A., De Lima, T. C. M. and Viana, G. S. B. 1999. Behavioral effects of essential oils from Lippia alba (Mill.) NE Brown chemotypes. Journal of Ethnopharmacology. 67(2): 127-133
Do Vale, T. G., Furtado, E. C., Santos, J. G. and Viana, G. S. B. 2002. Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) NE Brown. Phytomedicine. 9(8): 709-714
Hennebelle, T., Sahpaz, S., Gressier, B., Joseph, H. and Bailleul, F. 2008. Antioxidant and neurosedative properties of polyphenols and iridoids from Lippia alba. Phytotherapy Research. 22(2): 256-258
Hennebelle, T., Sahpaz, S., Joseph, H. and Bailleul, F. 2008. Ethnopharmacology of Lippia alba. Journal of Ethnopharmacology. 116(2): 211-222
González-Trujano, M. E., Hernández-Sánchez, L. Y., Muñoz Ocotero, V., Dorazco-González, A., Guevara Fefer, P. and Aguirre-Hernández, E. 2017. Pharmacological evaluation of the anxiolytic-like effects of Lippia graveolens and bioactive compounds. Pharmaceutical Biology, 55(1): 1569-1576
Wannmacher, L., Fuchs, F. D., Paoli, C. L., Fillman, H. S., Gianlupi, A., Lubianca, N., Hassegawa, C. Y. and Guimaraes, F. S. 1990. Plants employed in the treatment of anxiety and insomnia: II. Effect of infusions of Aloysia triphylla on experimental anxiety in normal volunteers. Fitoterapia. 61(5): 449-453
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Raspberry Leaves to Treat Mood Disorders

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Common Sage (Salvia officinalis)

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Sweet Flag (Acorus calamus) Against Anxiety

weight lossSweet flag (Acorus calamus) is a wetland grass-like monocotyledon plant of the Acoraceae family. Sweet flag can be found growing in northern and subtropical regions, particularly in parts of Europe, Asia, Russia and North America. Sweet flag can grow to up to 100 cm tall in tufts of leaves that spread from a central creeping rhizome. The tufts also give rise to tall flower stems which flower in spring and summer. The rhizomes of the plant contain α- and β-asarone and these may provide mood elevating effects. For example, in one study researchers investigated the mood elevating effects of sweet flag extracts on subjects with generalised anxiety disorder. Subjects received 500 mg per day of Acorus calamus extract twice daily for up to 60 days. The researchers reported that the subject experienced significant reduction in their anxiety as measured by the Hamilton’s Brief Psychiatric Rating Scale and clinical examination. Therefore sweet flag may have therapeutic use as an anxiolytic agent in human subjects.  

In addition, the Acorus calamus extract also significantly reduced the stress of the subjects and the depression that is associated with stress. Therefore as well as an anxiolytic effects Acorus calamus may have anti-stress and antidepressant effects. Other studies have also observed significant reductions in depression with administration of Acorus calamus extracts to human subjects. The antidepressant effects of Acorus calamus may derive from the ability of the herb to alter the electrical activity in the brain, and its ability to increase monoamine levels in the brain. In rats, Acorus calamus extracts have been shown to modify levels of noradrenaline, dopamine and serotonin, in different parts of the brain, with some regions experiencing increases, and some decreases. Further, the alpha brain wave activity in the brain also increased. These results are consistent with activation of the GABA receptors in the brains of the rats. Activation of GABA receptors would be expected to modify monoamine release and increase an alpha wave state.   

sweet flag acorus calamus anxiety depression

A number of bioactive phytochemicals have been isolated from sweet flag, including asarones, shyobunones, acorones, octanoic acid, α-cedrene, α-phellandrene, β-farnesene and γ-elemene. These phytochemicals may be responsible for the mood elevating effects of sweet flag. Sweet flag rhizome has been shown to contain 1.8 to 9.3 % of a volatile oil composed of monoterpenes, sesquiterpenes, and phenylpropanoids. Researcher have shown that a number of sesquiterpenes from sweet flag and the chemical β-asarone can bind to the GABAA receptors. As GABA receptors are involved in producing anxiolytic effects in animals, this may be the mechanism by which sweet flag is able to exert its mood elevating effects. Image is of sweet flag (Acorus calamus). Image from: By J.F. Gaffard, Autoreille, France (photo J.F. Gaffard, Autoreille, France, mai 2004,) [GFDL (http://www.gnu.org/ copyleft/ fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/ licenses/by-sa/ 3.0/) or CC BY-SA 1.0 (https:// creativecommons.org/ licenses/ by-sa/1.0)], via Wikimedia Commons.

Acorus calamus extracts may also have sedative effects, and it has been suggested that the α- and β-asarone may be responsible for these effects. Evidence also suggests that Acorus calamus may have memory enhancing effects, and in this regard may inhibit the enzyme acetylcholinesterase, thereby increasing brain levels of acetylcholine. The anxiolytic effects of α-asarone from Acorus gramineus has been investigated in rats. Rat were administered different concentrations of α-asarone prior to exposure of the rats to stressful conditions. The extract of α-asarone significantly decreased the anxious behaviour of the rats, suggesting that this compound may be responsible for the anxiolytic effects of plants which contain it, including Acorus calamus. Stress hormone release is known to cause an upregulation of tyrosine hydroxylase which subsequently increase brain production of noradrenaline and dopamine. Extracts of α-asarone have been shown to attenuate these stress induced changes to tyrosine hydroxylase.   

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Bhattacharyya, D., Sur, T. K., Lyle, N., Jana, U. and Debnath, P. K. 2011. A clinical study on the management of generalized anxiety disorder with Vaca (Acorus calamus).Indian Journal of Traditional Knowledge. 10(4): 668-671
Gupta, V., Bansal, P., Kumar, S., Sannd, R. and Rao, M. M. 2010. Therapeutic efficacy of Phytochemicals as anti-anxiety-a review. Journal of Pharmaceutical Research. 3: 174-179
Pattanaik, J., Kumar, Y. and Khatri, R. S. 2013. Acorus calamus Linn.: A herbal tonic for central nervous system. Journal of Scientific and Innovative Research. 2(5): 950-954
Zaugg, J., Eickmeier, E., Ebrahimi, S. N., Baburin, I., Hering, S. and Hamburger, M. 2011. Positive GABAA receptor modulators from Acorus calamus and structural analysis of (+)-dioxosarcoguaiacol by 1D and 2D NMR and molecular modeling. Journal of Natural Products. 74(6): 1437-1443
Hazra, R. and Guha, D. 2003. Effect of chronic administration of Acorus calamus on electrical activity and regional monoamine levels in rat brain. Biogenic Amines. 17(3): 161-169
Lee, B., Sur, B., Yeom, M., Shim, I., Lee, H. and Hahm, D. H. 2014. Alpha-asarone, a major component of Acorus gramineus, attenuates corticosterone-induced anxiety-like behaviours via modulating TrkB signaling process. The Korean Journal of Physiology and Pharmacology. 18(3): 191-200
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Docosahexaenoic Acid Improves Cognition

weight lossA number of fatty acids from the omega 3 family are essential to health. Deficiencies of these fatty acids can lead to a number of clinically relevant symptoms including inflammation and cognitive decline. Generally the Western diet is deficient in omega 3 fatty acids and this leaves the consumer at risk of developing Western lifestyle diseases. The addition of omega 3 fatty acids to the diets of those that normally consume the typical Western diet can reverse many of the symptoms associated with omega 3 deficiency. A number of studies have investigated the ability of omega 3 fats from algal oils to reverse cognitive problems. For example in one study, researchers supplements a number of elderly individuals with algal oil that contained the omega 3 fatty acid docosahexaenoic acid (DHA, C22:6, n-3)). The results of the study showed that those subjects talking the DHA supplement for 6 months experienced significantly fewer errors in tests of cognitive ability compared to subjects taking the placebo.

dha memory

Docosahexaenoic acid has unique structural properties that allow it to confer specific functional properties that are necessary for cellular and tissue health in the brain. In particular, DHA can accumulate in the cell membranes of neuronal cells where it acts as a reservoir for the production of a number of unique molecules including the resolvins and the protectins. These compounds, collectively called the docosanoids, may play a particular role in the protection and regeneration of neurons through their regulation of inflammation. In addition, the DHA molecule is considered long chain fatty acid, and the presence of double bonds in the molecule gives it a pronounced kink. When packed into the cell membrane, this increases the intermolecular spaces and produces a more fluid membrane. This can alter the membrane function with regard to the propagation of neuronal signals, and this may facilitate more efficient memory and learning. It may also alter behaviour through more efficient use of neurotransmission routes.

In another study, researchers administered 2 grams of algal oil containing DHA to a group of patients with Alzheimer’s disease. The results of the study suggested that the supplement was able to slow the cognitive decline of the subjects compared to a placebo. However, this was only apparent in subjects who possessed the apolipoprotein E3 (ApoE3), but not ApoE4 variant of the apolipoprotein gene. Therefore some genetic variation may account for variation in the response to DHA supplements in patients with dementia. However, it is not just the elderly that benefit from DHA supplementation, as DHA supplements have been shown to benefit children by improving cognition and behaviour, and particularly in school performance. In a review of the studies to date one group of researchers reported that over half of the studies observed improvements in one area of cognition or behavior. Children may be particularly sensitive to deficiencies of DHA because the growing brain requires omega 3 fats for correct development.    

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Yurko-Mauro, K. 2010. Cognitive and cardiovascular benefits of docosahexaenoic acid in aging and cognitive decline. Current Alzheimer Research. 7(3): 190-196
Cole, G. M., & Frautschy, S. A. 2010. DHA may prevent age-related dementia. The Journal of Nutrition. 140(4): 869-874
Quinn, J. F., Raman, R., Thomas, R. G., Ernstrom, K., Yurko-Mauro, K., Nelson, E. B., Shinto, L. and Nair, A. K. 2009. A clinical trial of docosahexaenoic acid (DHA) for the treatment of Alzheimer’s disease. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. 5(4): P84
Kuratko, C. N., Barrett, E. C., Nelson, E. B. and Salem, N. 2013. The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: a review. Nutrients. 5(7): 2777-2810
Bradbury, J. 2011. Docosahexaenoic Acid (DHA): An Ancient Nutrient for the Modern Human Brain. Nutrients. 3: 529-554
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Omega-3 Fatty Acids and Depression

weight lossAnimals cannot synthesise some of the omega 3 fatty acids they require for correct metabolic function. These fats are therefore essential and must be supplied in the diet, in a similar way that vitamins must be supplied in the diet. As with vitamins, a dietary deficiency of the essential fatty acids leads to a deficiency disease. The parent omega 3 fatty acid is alpha linolenic acid (ALA, C18: 3, n-3)) and this is derived from plant sources such as walnuts, green leafy vegetables and flax seeds and hemp seeds. However, metabolites of ALA, including docosahexaenoic acid (DHA, C22:6, n-3)) and eicosapentaenoic acid (EPA, C20:5, n-3)) can also fulfill the omega 3 fatty acid requirement and these can be obtained from algae, or animals that feed on algae such as krill and fish. Increasingly, it is being shown that a deficiency of the omega-3 fatty acids may be associated with the development of depression. This association may relate to the important functions that omega 3 fats play in brain development and plasticity.

For example, evidence suggests that as consumption of fish and seafood increases, there is a concomitant reduction in the prevalence of depressive disorder and bipolar depression. As seafood and fish contain high amounts of DHA and EPA, it has been suggested that this could be the reason for the associations. In other studies, it has been shown that supplementation with EPA can improve the symptoms of major depressive disorder. For example, in one study, 22 patients with major depressive disorder that were supplemented with 2 grams of EPA per day for 4 weeks experienced significant clinical improvements in their depression by week 3 of treatment as measured by the Hamilton Depression Rating Scale. Those receiving the EPA had a 12.4 point reduction in depression rating, whereas those on the placebo had a 1.6 point improvement. In total 60 % of the patients receiving the EPA had a 50 % reduction in their depression rating. The authors also reported that no clinically relevant side effects were reported.

DHA EPA depression

Postmortem analysis of the orbitofrontal cortex of patients has shown that DHA levels are 22 % lower in the brains of patients suffering from major depressive disorder, compared to the brains of control subjects. In females, the deficit in DHA concentrations was highest with a 32 % deficit, compared to a 16 % deficit in males. This supports the theory that DHA is a major structural component of the brain and that it may be required for the correct function of normal mental faculties. In particular, DHA is required for the correct fluidity of the neuronal cell membranes, and may be a precursor to important factors that maintain the health of neurones. A deficiency of DHA or its metabolites in the diet, may therefore be a cause of depression and other mood disorders. Fish oils contain EPA and DHA, but they can also be obtained through consumption of algal oils.

In another study, patients already receiving pharmaceutical treatment for depression were administered 1 gram of EPA per day for 12 weeks. The patients administered the EPA experienced significantly greater improvements in their depression compared to the placebo, as measured on the Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale. The clinical benefits of the EPA was evident by week 4 of the study. Of those receiving the EPA, 59 % experienced a 50 % reduction in their rating of depression, suggesting the EPA has had caused a substantial improvement. The authors noted that strong beneficial effects were seen regarding feelings of depression, anxiety, sleep, lassitude, libido and suicidality in the EPA group. Interestingly, higher doses of EPA (2 gram per day and 4 gram per day) were not as effective as 1 gram per day, suggesting that more is not better with regard the mood elevating effects of EPA supplementation.

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McNamara, R. K., Hahn, C. G., Jandacek, R., Rider, T., Tso, P., Stanford, K. E. and Richtand, N. M. 2007. Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder. Biological psychiatry. 62(1): 17-24
Hibbeln, J. R. 2002. Seafood consumption, the DHA content of mothers’ milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. Journal of affective disorders. 69(1): 15-29
Noaghiul, S. and Hibbeln, J. R. 2003. Cross-National Comparisons of Seafood Consumption and Rates of Bipolar Disorders. American Journal of Psychiatry. 160: 2222-2227
Nemets, B., Stahl, Z. and Belmaker, R. H. 2002. Addition of Omega-3 Fatty Acid to Maintenance Medication Treatment for Recurrent Unipolar Depressive Disorder. American Journal of Psychiatry. 159(3): 477-479
Peet, M. and Horrobin, D. F. 2002. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Archives of General Psychiatry. 59(10): 913-919
Posted in Algal DHA, Alpha Linolenic Acid, Anxiety, Depression, Docosahexaenoic Acid, Eicosapentaenoic Acid, Fish Oils | Comments Off on Omega-3 Fatty Acids and Depression

Ashwagandha (Withania somnifera): Human Studies on Anxiety

weight lossThe prevalence of anxiety or anxiety related disorders has been reported to be as high as 30 % in the United States. Estimates suggest the prevalence is at similar levels in other Western countries. The high prevalence of anxiety has increased the desire for effective and safe anxiety treatments, particularly those from the traditional forms of medicine. Ashwagandha, also called withania or Withania somnifera, is a herb used in traditional Ayurvedic medicine as a general tonic. Ashwagandha is thought to possess adaptogenic properties on account of the presence of phytochemicals called saponin lactones in the plants tissues. By an unknown mechanism these phytochemicals are able to reduce the detrimental effects of external stressors and thus help the consumer to maintain normal homeostatic function. Ashwagandha can therefore be thought of as an anti-stress agent, and this anti-stress effect likely has downstream beneficial effects on the parameters normally negatively affected by stress, including mental health and mood.

ashwagandha anxiety

Ashwagandha is a herb that possesses anti-stress effects. The ability of the herb to modulate the stress response may explain its anti-anxiety, antidepressant, anti-fatigue and immunomodulatory effects. Ashwagandha is considered safe and has been used in traditional Indian medicine for centuries without issue.

The anti-anxiety of many herbs has only been experimentally tested in animals. However, ashwagandha is an exception as a number of clinical trials have been performed in humans. For example, in one study, researchers administered 500 mg of ashwagandha extract per day or a placebo to patients who required treatment for anxiety. After 6 weeks the ashwagandha group showed significantly greater improvements in their anxiety as rated on the Hamilton Anxiety Scale, when compared to the placebo. This study found that the ashwagandha was well tolerated and did not create any more adverse effects than the placebo. In another study, researchers administered standardised ashwagandha root and leaf extract to chronically stressed individuals for up to 60 days. The results of the study showed that the ashwagandha group experienced significantly greater reductions in anxiety as rated by the Hamilton Anxiety Scale, and also significantly greater reductions in cortisol, inflammation and blood pressure.

In another study, researchers compared the anti-anxiety effect of naturopathic care, psychotherapy or a placebo in a group of patients that had diagnoses with and suffered from anxiety for more than 6 weeks. Subjects in the naturopathic group received a number of treatments including dietary counseling, deep breathing relaxation techniques, a multivitamin and mineral supplement, as well as 300 mg ashwagandha root extract standardized to 1.5 % withanolides. The treatments were followed for 8 weeks or more. The results of the study showed that compared to the placebo, the anxiety of the subjects decreased by 56.5 % in the naturopathic group and by 30.5 % in the psychotherapy group, as measured on the Beck Anxiety Index. In addition, the mental health, concentration, fatigue, social functioning, vitality, and overall quality of life were significantly decreased in the group receiving naturopathic care compared to the group receiving psychotherapy and the placebo.

ashwagandha anxiety

Mainstream treatments for anxiety are controversial because often the side effects of the drugs are more debilitating than the anxiety itself. For those with low grade chronic anxiety this creates a dilemma that results in mainstream treatment often being passed by. However, herbal alternatives like ashwagandha provide a viable alternative because as well as being highly effective, they are also free from adverse effects. As a result there is an increased interest in their use. Image is withania. Image from: Wowbobwow12 at English Wikipedia [GFDL (http://www.gnu.org/ copyleft/fdl.html) or CC BY-SA 3.0 (https://creativecommons.org/ licenses/by-sa/3.0)], via Wikimedia Commons.

In another human study, researchers administered 300 mg of ashwagandha root extract or a placebo to a group of chronically stressed individuals for a period of up to 60 days. The results of the study showed that the ashwagandha group experienced improvements in all scores of stress assessment, compared to the placebo. In addition, the cortisol levels of the ashwagandha group were reduced significantly more in the placebo group. In yet another study, researchers administered 4 grams of ashwagandha granules or a placebo to a group of patients suffering from the generalised anxiety disorder (GAD). The results of the study showed that the ashwagandha group experienced greater reductions in anxiety, although the results did not reach statistical significance. In a reviews of these trials, one group of authors suggested that the weight of evidence suggests that there was substantial evidence from human clinical trials that ashwagandha was effective as a treatment for anxiety and had significant anti-stress effects.   

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Pratte, M. A., Nanavati, K. B., Young, V., & Morley, C. P. 2014. An alternative treatment for anxiety: a systematic review of human trial results reported for the Ayurvedic herb ashwagandha (Withania somnifera). The Journal of Alternative and Complementary Medicine. 20(12): 901-908
Andrade, C., Aswath, A., Chaturvedi, S. K., Srinivasa, M. and Raguram, R. 2000. A double-blind, placebo-controlled evaluation of the anxiolytic efficacy ff an ethanolic extract of withania somnifera. Indian Journal of Psychiatry. 42(3): 295-301
Auddy, B., Hazra, P. J. and Mitra, P. A. 2008. A Standardized Withania Somnifera Extract Significantly Reduces Stress-Related Parameters in Chronically Stressed Humans: A Double-Blind, Randomized, Placebo-Controlled Study. Journal of the American Nutraceutical Association. 11: 50-56
Cooley, K., Szczurko, O., Perri, D., Mills, E. J., Bernhardt, B., Zhou, Q. and Seely, D. 2009. Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974. PLoS One. 4(8): e6628
Chandrasekhar, K., Kapoor, J. and Anishetty, S. 2012. A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults. Indian Journal of Psychological Medicine. 34(3): 255-262
SudKhyati, S. and Anup, B. T. 2013. A randomized double blind placebo controlled study of ashwagandha on generalized anxiety disorder. International Ayurvedic Medicine Journal. 1: 1-7
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