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S-Adenosyl-L-methionine (SAMe) and synthesis of neurotransmitters. The neurotransmitter serotonin (5-hydroxytryptophan; 5-HT) is synthesized from the amino acid tryptophan in a series of chemical reactions, of which the rate-limiting step is catalyzed by the enzyme tryptophan hydroxylase (EC 1.14.16.4). Similarly, the neurotransmitters dopamine (DA) and norepinephrine (NE) are synthesized from the amino acid tyrosine in a series of chemical reactions dependent on tyrosine hydroxylase (EC 1.14.16.2). SAMe functions as a methyl-donating cofactor in the rate-limiting step in these synthetic reactions. BH 4 , tetrahydrobiopterin. Adapted from reference 11.
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Major depression remains difficult to treat, despite the wide array of registered antidepressants available. In recent years there has been a surge in the popularity of natural or alternative medications. Despite this growing popularity, there is limited evidence for the effectiveness of many of these natural treatments. S-adenosyl-L-methionine (SA...
Citations
... Measurements in cerebral spinal fluid (CSF) performed by Bottilgieri et al. [107] showed low SAMe levels associated with depression. Additionally, the enzyme responsible for SAMe production is lower in patients with depression and schizophrenia [108]. ...
... No observational studies for SAMe have been conducted, as SAMe is not normally obtained through diet; however, a deficiency in SAMe has been linked to depression [108], as a result of low levels of folate and vitamin B12, which are precursors to SAMe [109]. ...
The nutritional management of depression has long been discussed, due to the perceived benefit of a nutritional product having less side effects than pharmaceutical agents. Candidate nutrients for managing depression include vitamin D, B vitamins, tryptophan, branch chain amino acids, probiotics, omega-3 fatty acids, folate/methylfolate (also known as vitamin B9), and s-adenosylmethionine. This paper provides a narrative review of three nutrients which have significant scientific support for the management of depression. A deficiency in each nutrient is associated with depression, and interventional studies indicate that the correction of the nutritional deficiency may provide clinical benefit. We present epidemiological evidence, a mechanistic explanation and a review of interventional studies for these nutrients. Finally, relevant nutritional guidelines are presented with their conclusion for the role of each nutrient in the management of depression.
... Arginine plays a critical role in cell division, wound healing, ammonia removal, immune function, and hormone release (Sharma et al., 2013). Methionine is key in improving wound healing, and is also used to treat liver disorders, depression and Parkinson's disease (Mischoulon and Fava, 2002). Amino acids such as glutamic acid, aspartic acid, alanine, and glycine are responsible for flavor and taste (Ruiz-Capillas and Moral, 2004) and therefore play a significant role in determining consumer taste preferences. ...
Fish is an important seafood that provides quality nutrients to human beings which is vital for health and development. This is especially critical in the diets of children under two years old and reproductive women (pregnant and lactating). Selected fish species were sampled from both Lake Victoria and fish farms, and their weight was determined using a sensitive weighing balance and fish-based products (powder and gelatin) developed to food-grade standards. The proximate composition of minerals, amino acid, and fatty acid profile were assessed in the laboratory, and data were analyzed using R statistic tool version 4.2.2 to understand the differences between the variables at a significance level of p < 0.05. Results indicated that crude fat ranged from 3-23%, crude protein was highest in Nile perch gelatin at 81.22±1.43 while omena and haplochromine spp. had the highest concentration of calcium at 6347.1±428.5 and 4522.0±233.3 mg/Kg respectively. The highest concentration of essential amino acids was found in omena and Nile perch powder. Among the fatty acids; oleic and palmitic were the dominant fatty acid in the fish products at 25.12±0.56% - 45.12±0.65% and 20.52±0.69% - 44.23±0.74% respectively. The moisture content of the final products was between 4.64 ±0.08% - 8.82±0.35%, which was within limits ensuring little microbial activity thus enhancing the shelf-life of the final products. The developed products had nutrients that are beneficial to human health at desirable concentrations and are recommended for inclusion in the diet of vulnerable groups for a prosperous community free from hunger and malnutrition.
... Eleotris fusca was found to have the highest glycine (3.10 ± 0.28 g/100 g) followed by the shellfish Macrobrachium malcolmsonii (2.53 ± 0.14 g/100 g) in the present study. Previously, the glycine content of the European seabass, turbot, gilthead seabream, Channa micropeltes, Channa striatus, and Channa lucius was reported to be high [32,44]. Histidine has multiple functions in protein interaction [45] and is also a precursor of histamine. ...
Amino acids are significant biomolecules that govern the major metabolic processes and act as precursors for macromolecules such as proteins that are crucial to life. Fish is an integral component of human nutrition and a dietary source of high-quality animal proteins and amino acids. In this context, the crude protein and amino acid compositions of food fish from different landing stations of the Ganga river have been determined. The Kjeldahl method was utilized to determine the crude protein content and the amino acids were analyzed using high-performance liquid chromatography (HPLC); data on 30 food fish were assessed. The study showed that among the fish studied, Eleotris fusca, Macrobrachium malcomsonii, and Mystus cavasius were rich in most of the amino acids important for human nutrition, such as glycine, glutamic acid, cysteine, threonine, phenylalanine, methionine, lysine, leucine, isoleucine, histidine, and valine. Further, it was observed that the daily consumption of these fish (approximately 50 g) can fulfil the daily requirement of these individual amino acids for an adult human with a body weight of 60 kg. Therefore, the amino acid composition analyzed in the present study could be utilized for recommendation by clinicians according to the requirement for specific amino acids, and fish can be prescribed as a natural supplement against the amino acid requirement.
... Notably, we found significant alterations of adenosine and adenosine monophosphate in the serum under SD, and they are the precursors that participate in the biosynthesis of SAM [50] . SAM is a naturally occurring molecule mainly present as a methyl donor in all living cells [51] . During the past several decades, SAM has been proven to have nearly equal efficacy as antidepressants for treating depression in human trials [52][53][54] . ...
Gut microbiome is indispensable for maintaining normal brain function. Specifically, gut microbiota plays a causal role in sleep deprivation (SD)-induced cognitive impairment. In this study, neurobehavioral effects of the Bifidobacterium breve strain (CCFM1025) were assessed in sleep-deprived mice. CCFM1025 improved the body weight and food and water intake of the mice. It also alleviated SD-induced cognitive behavioural abnormalities (in the novel object recognition test), but did not show beneficial effects on mood- and spatial memory-related behaviours. CCFM1025 significantly altered the gut microbial composition and genome function. Key microbial metabolites that may regulate sleep function were also identified, such as isovaleric acid and γ-aminobutyric acid in the gut and purine metabolites in the serum. Those metabolites may participate in gut-brain communication by acting on the striatal melatonin system, for example to increase melatonin levels, and by regulating the expression of circadian clock genes such as those encoding the adenosine A2A receptor and period circadian regulator 1. Collectively, administration of probiotics alleviated cognitive impairment and circadian rhythm disturbance induced by SD via modulation of gut microbiome and its metabolites. These findings may help guide the treatment of insomnia or other sleep disorders via dietary strategies.
... These neurotransmitters are synthesized by enzymes that take the methyl group from SAM for their enzymatic activity and are implicated in regulating mood and emotion beside other functions in the brain [94,95]. Although the relationship between these monoamine neurotransmitters and mood disorders is complex, it is suggested that SAM may have antidepressant-like effects by influencing the synthesis of these neurotransmitters [96]. In individuals with major depressive disorder (MDD), elevated plasma homocysteine levels are observed alongside reduced serum and cerebrospinal fluid (CSF) levels of SAM and folate, as well as decreased CSF levels of the monoamines dopamine, norepinephrine and serotonin [97]. ...
The relationship between nutrition and brain health is intricate. Studies suggest that nutrients during early life impact not only human physiology but also mental health. Although the exact molecular mechanisms that depict this relationship remain unclear, there are indications that environmental factors such as eating, lifestyle habits, stress, and physical activity, influence our genes and modulate their function by epigenetic mechanisms to shape mental health outcomes. Epigenetic mechanisms act as crucial link between genes and environmental influences, proving that non-genetic factors could have enduring effects on the epigenome and influence health trajectories. We review studies that demonstrated an epigenetic mechanism of action of nutrition on mental health, focusing on the role of specific micronutrients during critical stages of brain development. The methyl-donor micronutrients of the one-carbon metabolism, such as choline, betaine, methionine, folic acid, VitB6 and VitB12 play critical roles in various physiological processes, including DNA and histone methylation. These micronutrients have been shown to alter gene function and susceptibility to diseases including mental health and metabolic disorders. Understanding how micronutrients influence metabolic genes in humans can lead to the implementation of early nutritional interventions to reduce the risk of developing metabolic and mental health disorders later in life.
... Methionine in mammals is also used to treat depression, alcoholism, allergies, asthma, copper poisoning, radiation side effects, schizophrenia, drug withdrawal, Parkinson's disease, and liver diseases (Mischoulon and Fava., 2002). ...
... Moreover, higher plasma levels of these amino acids were associated with better EF after exercise. These amino acids (Leu, Ile, Val, Lys, Phe, and Met) are precursors for neurotransmitters (dopamine, norepinephrine, and glutamate) [25][26][27][28][29] . Brain glutamate is synthesized from Leu and Lys 25,26 . ...
... Dopamine and norepinephrine are synthesized from Tyr, whose precursor is Phe 27 . The intake of S-adenosyl-L-methionine, which is synthesized in the body from Met, increases dopamine and norepinephrine in the brain 29 . Then, the rate of synthesis and release of these neurotransmitters is thought to be directly modulated by brain concentrations of their amino acid precursors, BCAA, Phe and Lys, and Met is also influenced by their availability from the blood [27][28][29] . ...
... The intake of S-adenosyl-L-methionine, which is synthesized in the body from Met, increases dopamine and norepinephrine in the brain 29 . Then, the rate of synthesis and release of these neurotransmitters is thought to be directly modulated by brain concentrations of their amino acid precursors, BCAA, Phe and Lys, and Met is also influenced by their availability from the blood [27][28][29] . To our best of knowledge, there are no studies that investigate whether supplementation of Leu, Ile, Val, Lys, Phe and Met acutely increases neurotransmitters (dopamine, norepinephrine, and glutamate) in the brain. ...
Aerobic exercise acutely improves cognitive function (e.g., executive function (EF); memory recognition (MR)) and increases circulating brain-derived neurotrophic factor (BDNF). In addition, branched-chain amino acids (BCAA) ingestion acutely shortens the choice reaction time and increases brain BDNF. We examined whether the ingestion of essential amino acid (EAA) supplements (mainly composed of BCAA) would positively impact on cognitive function and circulating BDNF after moderate-intensity aerobic exercise. Twenty-two healthy young men received either an EAA supplements or the placebo (PL) 30 min before undergoing aerobic exercise. The participants performed a cycling exercise at 60% of peak oxygen uptake for 30 min. EF after aerobic exercise was better after the EAA treatment than after the PL treatment (P = 0.02). MR (P = 0.38 for response accuracy; P = 0.15 for reaction time) and circulating BDNF (P = 0.59) were not altered by EAA supplements. EF improvement was correlated with increases in some amino acids (leucine, isoleucine, valine, lysine, phenylalanine; all Ps < 0.05) that are potential substrates for synthesizing neurotransmitters in the brain. These results suggest that EAA supplements ingestion had a positive effect on EF after moderate-intensity aerobic exercise, while MR and BDNF were not altered.
... L-MET is the immediate precursor of SAMe and the end product of the one-carbon cycle [64]. SAMe is a major donor of the methyl groups required for DNA methylation, which is one of the most studied epigenetic mechanisms that alter gene expression without changing the DNA sequence. ...
... 5-HT is synthesized from the amino acid tryptophan, and the rate-limiting step is catalyzed by tryptophan hydroxylase. SAMe functions as a methyl-donating cofactor in the rate-limiting step of the synthesis of the monoamines DA and 5-HT [64]. Enhancement of SAMe levels permits it to act as a cofactor of COMT, decreasing COMT enzyme activity and thereby the degradation of catecholamines [67]. ...
... Therefore, SAMe can be regarded as a treatment option for depressive disorders that increase monoamines since low levels of SAMe, elevated homocysteine, and low 5-HT, DA, and NA are usually found in depressive patients [68]. Indeed, SAMe is an effective antidepressant drug [64,69] as it is well tolerated and may have a relatively faster onset of action than conventional antidepressants [64]. In addition, an antiepileptic and memoryenhancing effect of SAMe administration in a PTZ-induced kindling model of epilepsy has also been demonstrated [70]. ...
Depression is a severe and widespread psychiatric disease that often accompanies epilepsy. Antidepressant treatment of depression comorbid with epilepsy is a major concern due to the risk of seizure aggravation. SAMe, a universal methyl donor for DNA methylation and the synthesis of brain monoamines, is known to have high antidepressant activity. This study aimed to find out whether L-methionine (L-MET), a precursor of SAMe, can have antidepressant and/or anxiolytic effects in the WAG/Rij rat model of depression comorbid with absence epilepsy. The results indicate that L-MET reduces the level of anxiety and depression in WAG/Rij rats and suppresses associated epileptic seizures, in contrast to conventional antidepressant imipramine, which aggravates absence seizures. The antidepressant effect of L-MET was comparable with that of the conventional antidepressants imipramine and fluoxetine. However, the antidepressant profile of L-MET was more similar to imipramine than to fluoxetine. Taken together, our findings suggest that L-MET could serve as a promising new antidepressant drug with anxiolytic properties for the treatment of depression comorbid with absence epilepsy. Increases in the level of monoamines and their metabolites—DA, DOPAC, HVA, NA, and MHPG—in several brain structures, is suggested to be a neurochemical mechanism of the beneficial phenotypic effect of L-MET.
... A deficit in SAMe concentration was found in the 2 of 19 cerebrospinal fluid (CSF) of depressed patients and was normalized by intravenous or oral SAMe administration [7]. SAMe adjunct treatment facilitates and enhances the action of tricyclic antidepressants (TCA) and SSRIs in poor responders with MDD [8][9][10][11]. ...
The role of hippocampal monoamines and their related genes in the etiology and pathogenesis of depression-like behavior, particularly in impaired sociability traits and the meaning of changes in USVs emitted by pups, remains unknown. We assessed the effects of prenatal administration of S-adenosyl-methionine (SAMe) in Sub mice that exhibit depressive-like behavior on serotonergic, dopaminergic and noradrenergic metabolism and the activity of related genes in the hippocampus (HPC) in adulthood in comparison to saline-treated control Sub mice. During postnatal days 4 and 8, we recorded and analyzed the stress-induced USVs emitted by the pups and tried to understand how the changes in the USVs’ calls may be related to the changes in the monoamines and the activity of related genes. The recordings of the USVs showed that SAMe induced a reduction in the emitted flat and one-frequency step-up call numbers in PND4 pups, whereas step-down type calls were significantly increased by SAMe in PND8 pups. The reduction in the number of calls induced by SAMe following separation from the mothers implies a reduction in anxiety, which is an additional sign of decreased depressive-like behavior. Prenatal SAMe increased the concentrations of serotonin in the HPC in both male and female mice without any change in the levels of 5HIAA. It also decreased the level of the dopamine metabolite DOPAC in females. There were no changes in the levels of norepinephrine and metabolites. Several changes in the expression of genes associated with monoamine metabolism were also induced by prenatal SAMe. The molecular and biochemical data obtained from the HPC studies are generally in accordance with our previously obtained data from the prefrontal cortex of similarly treated Sub mice on postnatal day 90. The changes in both monoamines and their gene expression observed 2–3 months after SAMe treatment are associated with the previously recorded behavioral improvement and seem to demonstrate that SAMe is effective via an epigenetic mechanism.
... As in the case of cognitive decline, the link between B vitamins and depression is a correlation proposed several times without a definitive mechanistic explanation (Alpert & Fava, 1997). The possible mechanism could involve the antidepressant action of SAM (Mischoulon & Fava, 2002). ...
B vitamins are crucial nutrients for nervous system functions. This is particularly evident in the case of nutritional B vitamin deficiency (mainly folate and cobalamin), with the onset of neurological dysfunction in the advanced stages of shortage. Homocysteine is a functional marker of B vitamins, and higher blood homocysteine concentrations were seen among people with cognitive disorders, including dementia and Alzheimer's disease. However, it is not so clear if homocysteine can be a marker of dementia or a mere consequence of vitamin deficiency linked to secondary phenomena. Interventional trials with folic acid and cobalamin gave mixed results so it can be crucial to understand if monitoring of B vitamins could prevent or postpone dementia signs. This chapter deepens the link between B vitamins and dementia, focusing on folate, vitamin B12, and their functional marker homocysteine.
