Lettuce (Lactuca sativa) as an anxiolytic Treatment

Lactuca sativa is a culinary form of lettuce that belongs to the Asteraceae (daisey) family of plants. The plant is often grown as a vegetable for use in salads and is completely non-toxic. Medicinally the plant has a number of uses, and these stem from its anti-inflammatory effect. These effects, for example, allow lettuce to effectively treat a number of gastrointestinal problems. In terms of mental health, Lactuca sativa is known to affect the central nervous system and this may explain its mood elevating effects. For example, in one study dried extract from Lactuca sativa were administered to mice orally and the animals were exposed to a number of experimental stressors that were designed to cause behavioural changes relating to mood. The results of the experiment showed that lettuce treated animals exhibited significantly less anxious behaviour compared to controls and that this anxiolytic effect became greater between 15 and 30 days of treatment. Lettuce may therefore possess anxiolytic effects in animals. 

lactuca sativa anxiety depression mood

Lactuca sativa contains a latex within its tissues that has been analysed for its chemical composition. In this regard a number of potentially therapeutic phytochemicals have been identified including 15 oxalyl- and 8 sulfate- conjugates of the guaianolide sesquiterpene lactones, lactucin, deoxylactucin and lactucopicrin. In addition, extracts of the plant also contain polyphenols including chlorogenic acid, vanillin, epicatechin, caffeic acid, rutin hydrate, sinapic acid, quercetin-3-rhamnoside, p-coumaric acid and quercetin. These polyphenols may confer significant antioxidant effects to the consumer.

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Harsha, S. N. and Anilakumar, K. R. 2013. Anxiolytic property of Lactuca sativa, effect on anxiety behaviour induced by novel food and height. Asian Pacific Journal of Tropical Medicine. 532-536
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Neuroprotective Effects for Hericium erinaceus

Hericium erinaceus is a fungus used in traditional medicine, and studies suggest that it possesses a number of medicinal properties. These effects include mood elevating effects. The mood elevating effects of the fungus may stem from its neuroprotective ability. For example a number of studies have reported that Hericium erinaceus has the ability to prevent nerve damage in animals. One way it may achieve this is by promoting the release of endogenous nerve growth factor. This has led authors to suggest that the fungus may be useful in the treatment of dementia. This view is supported by observations that Hericium erinaceus can improve short term memory. In culture studies extracts of Hericium erinaceus were able to promote the growth of myelin sheaths that protect nerves. The high antioxidant content of the fungus may explain some of the neuroprotective effects, and it is thought that polysaccharides within the mushroom confer its antioxidant effects to the consumer. 

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Khan, M. A., Tania, M., Liu, R. and Rahman, M. M. 2013. Hericium erinaceus: an edible mushroom with medicinal values. Journal of Complementary and Integrative Medicine. 10(1): 253-258
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Lion’s mane (Hericium erinaceus) As An Anxiolytic and Antidepressant

Hericium erinaceus is an edible fungi that has a number of medicinal effects in animals and humans. Common names for Hericium erinaceus include lion’s mane. The fungus belongs to the tooth fungus group (Basidiomycota) and is found in North America, Europe and Asia. The fungus grows on hardwood trees and is identified by its spines that dangle down from a central clump. Lion’s mane is evidenced to act on the central nervous system of humans and animals and this interaction may produce mood elevating effects. For example, in one study, researchers administered extracts of lion’s mae to mice and then exposed them to experimental stress. This stress was designed to elicit anxious and depressive-like behaviour in the mice. The results of the study showed that administration of the lion’s mane extract caused significant anti-anxiety and antidepressive behaviour in the mice. The researchers suggested that these effects were due to the creation of new neurones in the hippocampal region of the brain’s of the mice. 

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Ryu, S., Kim, H. G., Kim, J. Y., Kim, S. Y. and Cho, K. O. 2018. Hericium erinaceus Extract Reduces Anxiety and Depressive Behaviors by Promoting Hippocampal Neurogenesis in the Adult Mouse Brain. Journal of Medicinal Food. 21(2): 174
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Anthocyanins are Neuroprotective

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The Bioavailability of Anthocyanins

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Creatine Transport

Creatine is synthesised in the liver and kidney. From here the creatine is transported to where it is required, mainly the skeletal muscle and brain. Creatine passes into the blood from the sites of synthesis and then into cells down its concentration gradient through sodium and chloride dependent transporters. The location and amount of these transporters matches the cellular expression of creatine kinase, the enzyme that is responsible for the formation of creatine phosphate (phosphocreatine) from creatine and ATP. The skeletal muscle and brain therefore have high amounts of these transporters as they have a high requirement for creatine phosphate. As type 2 skeletal fibres have a higher requirement for creatine phosphate compared to type 1 fibres, they have higher expressions of creatine kinase and creatine transporters to allow them to accumulate more creatine phosphate. Adrenaline, insulin-like growth factor 1 (IGF-1), insulin, and exercise can influence the uptake of creatine into skeletal muscle.

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Persky, A. M. and Brazeau, G. A. 2001. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacological Reviews. 53(2): 161-176
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Creatine Synthesis 

Dietary creatine from a typical mixed diet is equivalent to around 1 gram per day with a further 1 gram per day synthesised mainly in the liver and kidney. Creatine is synthesised from the amino acids glycine, arginine and methionine. The rate limiting step in the formation of creatine, the enzyme arginine:glycine amidino-transferase (AGAT) prevents synthesis rates exceeding 1 gram per day. Once produced, creatine negatively inhibits AGAT to slow further creatine formation, and synthesis of creatine is also regulated by thyroid hormone, growth hormone, testosterone, ornithine, vitamin E deficiency and fasting. Diet and endogenous synthesis equals the phosphocreatine degradation rate of around 2 grams per day. Any intake over 1 gram per day leads to accumulation of creatine, which is distributed 95 % in skeletal muscle and 5 % in the brain. Total body stores of creatine for a 70 kg male are equivalent to 120 grams. Creatine is excreted through the kidney and dietary creatine increases excretion and blood creatine levels. 

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Persky, A. M. and Brazeau, G. A. 2001. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacological Reviews. 53(2): 161-176
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Creatine Monohydrate And Membrane Stabilisation

Creatine monohydrate has a number of less well known pharmacological effects in cells. In this regard it is considered that creatine may have the ability to stabilise cell membranes. Creatine accumulates in cells where it can act as a zwitterion (positively and negatively charged molecule) in the form of phosphocreatine. Phosphocreatine has a negatively charged phosphate and positively charged guanidino groups. Studies suggest that phosphocreatine binds to the head group of phosphates in the cell membrane, and thereby decreases membrane fluidity. This may also decrease any loss of cytoplasmic proteins such as intracellular enzymes. Studies on animals suggest that phosphocreatine can reduce the damage to cardiomyocytes during experimentally induced damage due to a stabilisation of the membrane. In studies that have investigated membrane stabilisation for phosphocreatine in exercise induce damage no effect has been found, and so the exact role creatine plays in exercise induce membrane changes is not known. 

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Persky, A. M. and Brazeau, G. A. 2001. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacological Reviews. 53(2): 161-176
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More on the Insulin Creatine Connection

Creatine monohydrate supplements have become popular with athletes because they can confer strength gains. Studies suggest that creatine monohydrate absorption and uptake are dependent on the function of the insulin system. In this regard insulin may be required for the effective uptake of creatine to skeletal muscle cells. Studies have investigated this relationship in humans and observed a significant contribution of the insulin system to creatine accumulation in skeletal muscle. For example, in one study researchers found that insulin increased the amount of creatine that was found in skeletal muscle. However, the insulin could only elicit this effect at levels above the normal range for insulin release. They concluded that insulin had this effect by increasing the transport of creatine through a sodium dependent transporter on the cell membrane. If insulin is required for the uptake of creatine, it stands to reason that creatine may stimulate the release of insulin itself, something that has been reported in other studies. 

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Steenge, G. R., Lambourne, J., Casey, A., Macdonald, I. A. and Greenhaff, P. L. 1998. Stimulatory effect of insulin on creatine accumulation in human skeletal muscle. American Journal of Physiology-Endocrinology And Metabolism. 275(6): E974-E979
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Creatine Monohydrate Stimulates Protein Synthesis

The most well known explanation for the performance enhancing effect of creatine monohydrate is that it allows improvements in energy metabolism by causing accumulation of creatine in skeletal muscle, which increases the buffering capacity for ATP. However, there may be other mechanisms by which creates can improve exercise performance. In particular, creatine monohydrate supplements may stimulate muscle protein synthesis. In one study, creatine caused an increase in muscle fibre size of around 35 % with resistance training, but the training alone caused an increase in fibre size of only 15 %. It is possible that this effect stems from an anti catabolic effect as creatine has been shown to prevent leucine oxidation in skeletal muscle. Some authors have suggested that as creatine is an end product of contraction, it may be possible that creatine is a stimulus for protein synthesis. In fact creatine can stimulate action and myosin fibres in animal models. Some evidence therefore suggests that creatine may cause muscle growth.  

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RdB

Persky, A. M. and Brazeau, G. A. 2001. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacological Reviews. 53(2): 161-176
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