MIC Capsules

Overview of Methionine / Inositol / Choline Bitartrate Capsules

Dosage Strengths of Methionine / Inositol / Choline Bitartrate Capsules

Methionine / Inositol / Choline Bitartrate 150/300/300 mg

General Information

Methionine

Methionine is a branched-chain amino acid that contains sulfur. Methionine, a precursor for cellular methylation processes, is crucial for lipid metabolism, polyamine production, immune system function, heavy metal chelation, and redox balance maintenance.1 On the other hand, dietary methionine limitation in rodents decreased insulin resistance, increased energy expenditure, and improved adipose tissue lipolysis and fatty acid oxidation.2

Methionine's metabolite S-adenosyl methionine may be responsible for the lipotropic effects of methionine (SAM). Methionine is converted into SAM through an energetic process. SAM has been studied as a potential treatment for depression, osteoarthritis, and liver conditions when taken orally or intravenously.3 SAM may act as a methyl donor in the metabolic processes that control lipid homeostasis, DNA stability, gene expression, and neurotransmitter release, which may account for the benefits it confers. 456

Inositol

Nine stereoisomers of the cyclic sugar alcohol known as inositol make up this family of compounds. Myo-, Scyllo-, Muco-, Neo-, Allo-, Epi-, Cis-, and the enantiomers L- and D-chiro-inositol are the stereoisomers of the inositol family. Myo-inositol and D-chiro-inositol are two of the most prevalent biologically active versions of these compounds. Myo-inositol is transformed into the D-chiro-inositol isomer by the enzyme epimerase, preserving the ratios of the two isomers in different organs. In most tissues, myo-inositol concentration is physiologically many times higher than D-chiro-inositol concentration.7

The lipid bilayer of cell membranes contains phosphatidylinositol, a derivative of myo-inositol. A variety of cellular processes, such as membrane trafficking, autophagy, cell migration, and survival, depend on phosphatidylinositol and its phosphorylated variants to function. Phosphoinositide lipid signaling disruption has been linked to cardiovascular, metabolic, and cancerous diseases.8

In treating diseases connected to the metabolic syndrome, inositol has demonstrated clinical advantages. Supplementing with inositol has been proven to improve weight loss, reduce fat mass, 9 raise the expression of genes involved in lipid metabolism and insulin sensitivity, and enhance serum lipid profiles10with polycystic ovarian syndrome in females. In overweight/obese women with PCOS, myo-inositol alone or in combination with D-chiro-inositol dramatically decreased weight, BMI, and waist-hip circumference ratios. When inositol supplementation was combined with a low-calorie diet, weight loss, a decrease in fat mass, and an increase in lean mass were all expedited.11 Additionally, supplementing with inositol was linked to a decreased incidence of gestational diabetes and preterm birth in pregnant women.9 Research is currently being done to determine whether inositol may be utilized to treat different tumors.

Choline

Choline is an essential nutrient that is naturally present in certain foods and available as a supplement. Additionally, a tiny quantity can be produced by the body on its own in the liver, but not enough to meet daily requirements. Acetylcholine, a neurotransmitter that is produced from choline, aids in the contraction of muscles, triggers pain perception, and aids in memory and thought processes. The liver is where most choline is metabolized; there, it is changed into phosphatidylcholine, which aids in the formation of proteins that carry fat and the breakdown of cholesterol. 12

Mechanism of Action

Methionine

Methionine, an important sulfur-containing amino acid, undergoes transmethylation processes to produce homocysteine and S-adenosylmethionine (SAM), which are metabolic byproducts. SAM is a ubiquitous methyl donor and a co-factor in many physiological and cellular processes, including lipid homeostasis. SAM is transformed into S-adenosyl homocysteine (SAH) and ultimately homocysteine by giving up its methyl group. SAM functions as a methyl donor in the synthesis of phosphatidylethanolamine, which then results in the production of phosphatidylcholine. Phosphatidylcholine is carried to other tissues via very low-density lipoproteins (VLDL), which are formed in the liver. A fatty liver or hepatic accumulation of triglycerides results from insufficient levels of SAM in the liver, which interferes with VLDL assembly.13

SAM is essential for the control of epigenetic regulation because it encourages DNA methylation. One well-known method of transcriptional suppression is methylation close to gene promoters. As a result, SAM may serve as a sensor for the nutritional condition of the cell and alter the expression of genes that affect hunger, glucose metabolism, and lipogenesis epigenetically.1415 SAM serves as a methyl donor in the production of creatine, a high-energy molecule that is believed to enhance exercise performance.16

Inositol

All inositol stereoisomers share the same chemical formula as glucose and are all six-carbon sugar alcohols structurally (C6H12O6). Both myo-inositol and D-chiro-inositol mimic the effects of insulin. In diabetic rodents, rhesus monkeys, and humans, inositol treatment reduces post-prandial blood glucose levels and enhances insulin sensitivity.171819 These advantages might be credited to inositol's impact on the insulin signaling system. Phosphatidylinositol-3-kinase (PI3K) is activated when the insulin receptor is stimulated. In order to activate Akt later on, phosphatidylinositol's phosphorylated forms function as second messengers. Glycogen synthase activity is increased by Akt because it deactivates the enzyme glycogen synthase kinase-3. Via boosting the translocation of the glucose transporter (GLUT4) to the surface of skeletal muscle cells, this lowers blood glucose levels by increasing glucose uptake.20

Excess glucose in the blood is frequently stored as fat in the liver and the area around visceral organs. Inositol supplementation in the diet prevented rats from gaining weight and from accumulating lipids in their livers.212223Hepatic lipid metabolism and gluconeogenesis are thought to be influenced by inositol-mediated activation of PI3K/Akt signaling. SREBP-1 and PPAR-, which are involved in fatty acid synthesis, oxidation, and lipid transport, are likewise impacted by inositol on their transcription.

Choline

The polar head group of phosphatidylcholine contains a significant amount of choline. All of the fundamental biological functions, including information transfer, intracellular communication, and bioenergetics, depend on phosphatidylcholine's involvement in the preservation of cell membrane integrity. All these processes would be adversely impacted by inadequate choline consumption. Sphingomyelin, a different membrane phospholipid that is crucial for maintaining cell shape and function, has a significant amount of choline as well. The fact that choline deprivation in cell culture results in apoptosis, or programmed cell death, is interesting and not surprising. This appears to be caused by changes in the amount of phosphatidylcholine in cell membranes as well as a rise in ceramide, a precursor and metabolite of sphingomyelin. Ceramide buildup, brought on by choline deprivation, seems to stimulate Caspase, a particular type of enzyme that controls apoptosis. Choline undergoes an oxidation process to produce betaine, also known as trimethylglycine. One element that helps keep homocysteine levels low is betaine, which creates L-methionine from homocysteine. A substantial risk factor for atherosclerosis, as well as other cardiovascular and neurological conditions, is elevated homocysteine levels. One of the main neurotransmitters, acetylcholine, is synthesized with the help of choline. It is thought that enough acetylcholine levels in the brain can fend against dementia, especially Alzheimer's disease. 24

Pharmacokinetics

Methionine

The liver is where methionine is processed predominantly. Facilitative conveyance is used to deliver it to the hepatocytes.25 Methionine metabolism consists of three parts: the methionine cycle, the transsulfuration pathway, and the salvage cycle.26 Methionine is converted to S-adenosyl methionine in the first phase of the methionine cycle by the enzyme methyl adenosyltransferase (SAM). S-adenosyl homocysteine is created when SAM contributes its methyl group, and it is then hydrolyzed to produce adenosine and homocysteine. Methionine can be produced by remethylating homocysteine. Alternately, it can undergo the transsulfuration route to become cysteine. SAM is decarboxylated and used as an aminopropyl donor for polyamine production in the salvage route. Following oral consumption of 1-1.5 g of methionine, 9–15 percent of it was eliminated through urine in healthy human volunteers. A high-fat meal caused the individuals' urine excretion to decrease.27

Inositol

The gut is where myo-inositol and its byproducts, inositol phosphate, are largely absorbed. Both sodium-glucose co-transporters and sodium ion-coupled transporters are involved in inositol cellular absorption. High glucose levels can greatly reduce the uptake of inositol because they compete for the same transporters for uptake into cells.20Inositol is primarily broken down in the kidneys. Myo-inositol oxygenase is expressed in renal cortical tubules. Through the glucuronate-xylulose pathway, this enzyme breaks down myo-inositol into the monosaccharides xylulose and ribulose. In the renal tubular level, inositol that has not been digested or reabsorbed is expelled unaltered in the urine.2829 One study examined the pharmacokinetics of myo-inositol after intravenous (IV) administration in preterm newborns, whereas the majority of studies have examined the pharmacokinetics of inositol after oral administration.30 The serum half-life of inositol in this investigation was 5.22 hours after a single IV dosage and 7.9 hours after several IV doses.

Pregnancy

Methionine

A maternal diet high in methionine may be harmful to the development of the fetus. This is due to the possibility that more glycine and serine may be needed to catabolize the extra methionine, thereby leading to a shortage in these amino acids. Homocysteine can also be produced when methionine levels are too high. Preeclampsia, spontaneous abortion, placental rupture, and miscarriage are all linked to elevated plasma homocysteine levels.31

Inositol

Given its use in the treatment of polycystic ovarian syndrome and gestational diabetes, myo-inositol may be considered relatively safe during pregnancy. In a meta-analysis of randomized controlled trials, 2 g of myo-inositol administered orally twice daily was reported to be safe during pregnancy.32 However, high concentrations of D-chiro-inositol negatively affect the quality of oocytes.33 Therefore, D-chiro-inositol may not be used by women seeking to get pregnant. Effects of other inositol isomers are not well characterized.

Choline

Most prenatal vitamins lack choline, which is present in egg yolks, lean red meat, fish, poultry, legumes, nuts, and cruciferous vegetables, and more than 90% of expecting mothers consume less than the advised quantity. According to a recent Cornell study, moms who took twice the recommended quantity of choline throughout their pregnancies had children who fared better on a difficult activity demanding continuous attention. In the Cornell research, all pregnant women ate a prepared diet containing a specific amount of choline throughout the duration of the third trimester. The adequate intake (AI) limit of 450 mg/day was slightly exceeded by one-half of these women, who ingested 480 mg of choline daily. The daily choline consumption of the other half was 930 mg, or roughly double the AI threshold. 34

Breastfeeding

Methionine

Methionine intake by mothers may be too high and harm the development of the fetus. This is due to the possibility that more glycine and serine may be needed to properly catabolize the extra methionine, unintentionally leading to a shortage in these amino acids. Homocysteine can also be produced by the metabolism of excess methionine. Preeclampsia, placental rupture, spontaneous abortion, and miscarriage are all linked to elevated plasma homocysteine levels.31

Inositol

Given its use in the treatment of polycystic ovarian syndrome and gestational diabetes, myo-inositol may be considered relatively safe during pregnancy. In a meta-analysis of randomized controlled trials, 2 g of myo-inositol administered orally twice daily was reported to be safe during pregnancy.32 However, high concentrations of D-chiro-inositol negatively affect the quality of oocytes.33 Therefore, D-chiro-inositol may not be used by women seeking to get pregnant. Effects of other inositol isomers are not well characterized.

Storage

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.

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