Methionine / Choline Chloride 25/50 mg/mL 10 mL Vial
Methionine / Inositol / Choline Chloride 25/50/50 mg/mL 30 mL Vial

Lipotropes are compounds that may aid in the breakdown of body fat by acting on lipid metabolism and synthesis pathways. When used in combination with lifestyle modifications such as exercise and diet, lipotropic compounds may promote fat and weight loss.

Lipotropic compounds including vitamins, nutrients, and other natural or pharmacological agents may be administered as injections or in the form of oral supplements. Injections provide the advantage of better bioavailability by avoiding enzymes in the gastrointestinal tract. In addition, injections may be especially beneficial in individuals with gastrointestinal absorption issues.

The lipotropic agents in this injection are methionine, inositol, and choline. While each may individually affect the mobilization of fats, the combination may provide synergistic benefits.123 The physiological role of each compound and the effects of supplementation are described below.

Methionine
A branched-chain amino acid with sulfur is methionine. Methionine is crucial for immune system function, lipid metabolism, polyamine production, heavy metal chelation, and redox balance since it is a precursor for cellular methylation processes.4 In contrast, methionine limitation in the diet decreased insulin resistance in rodents and promoted adipose tissue lipolysis and fatty acid oxidation.5

The metabolite S-adenosyl methionine (SAM) of methionine, which has lipotropic properties, may be responsible. Methionine is converted into SAM by a process that requires energy. For the treatment of depression, osteoarthritis, and liver conditions, SAM has been studied when taken orally or intravenously.6 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.789

Inositol
Inositol is a family of cyclic sugar alcohols consisting of nine stereoisomers of hexahydroxycyclohexane. The stereoisomers of the inositol family are myo-, scyllo-, muco-, neo-, allo-, epi-, cis-, and the enantiomers L- and D-chiro-inositol. Of these, myo-inositol and D-chiro-inositol are among the most abundant biologically active forms. The enzyme epimerase converts myo-inositol to the D-chiro-inositol isomer, maintaining organ-specific ratios of the two isomers. Physiologically, the concentration of myo-inositol is several times higher than D-chiro-inositol in most tissues.10

The myo-inositol derivative phosphatidylinositol is an important component of the lipid bilayer of cell membranes. Phosphatidylinositol and its phosphorylated forms act as second messengers that are involved in a host of cellular functions including membrane trafficking, autophagy, cell migration, and survival. Disruption of phosphoinositide lipid signaling is implicated in cancer, diabetes, and cardiovascular disorders.11

Inositol has shown clinical benefits in treating disorders associated with metabolic syndrome. Inositol supplementation has been effectively used to accelerate weight loss, reduce fat mass,12 improve serum lipid profiles and upregulate the expression of genes involved in lipid metabolism and insulin sensitivity13 in women with polycystic ovarian syndrome. Myo-inositol alone or in combination with D-chiro-inositol significantly reduced weight, BMI, and waist-hip circumference ratios in overweight/obese women with PCOS. Weight loss, reduction in fat mass and increase in lean mass were accelerated when inositol supplementation was accompanied by a low-calorie diet.14 In addition, inositol supplementation was associated with lower rate of gestational diabetes and preterm delivery in pregnant women.12 Currently, research is being performed to assess whether inositol may be used in treating various cancers.

Choline
Choline is an essential nutrient required for optimal functioning of various tissues including the liver, muscles, and brain.15 Since choline breaks down fat as an energy source, choline supplementation caused rapid fat and weight loss in female athletes.16 Only small amounts of choline are synthesized by the human body, necessitating its intake from external sources. In the body, about 95% of the total choline pool is converted to phosphatidylcholine – an essential component of the phospholipid bilayer and the predominant phospholipid in most mammalian cells.17 Choline also undergoes acetylation to form the neurotransmitter acetylcholine. Choline deficiency causes hepatic steatosis (fatty liver disease) and leads to loss of muscle membrane integrity. Chronic choline deficiency may also increase the risk of developing cancer.

Both choline and methionine are a source of methyl groups for the one-carbon transmethylation pathway and serve hepato-protective functions. Culturing hepatocytes in choline and methionine-deficient media impaired VLDL secretion.18 In addition, choline can donate methyl groups to support methionine regeneration, possibly contributing to their synergistic lipotropic effects.

Methionine
Methionine, an important amino acid containing sulfur, undergoes transmethylation processes to produce metabolic byproducts such S-adenosylmethionine (SAM) and homocysteine. SAM is an all-purpose methyl group donor that participates as a co-factor in a variety of physiological and cellular processes, including lipid homeostasis. S-adenosylhomocysteine (SAH) and homocysteine are produced when SAM donates its methyl group. SAM acts as a methyl donor, assisting in the synthesis of phosphatidylethanolamine and phosphatidylcholine. Phosphatidylcholine is stored in the liver as very low-density lipoproteins (VLDL), which are then transferred to other tissues. Low levels of SAM in the liver prevent the formation of VLDL and cause lipid accumulation in the liver, often known as fatty liver.19

SAM plays a critical function in epigenetic control by encouraging DNA methylation. A well-known method of repressing transcription is methylation close to gene promoters. Consequently, SAM might serve as a sensor for the nutritional condition of the cell and epigenetically modify the expression of genes that affect hunger, glucose metabolism, and lipogenesis.2021 In the synthesis of creatine, a high-energy molecule believed to enhance exercise, SAM serves as a methyl donor.22

Inositol
Structurally, all inositol stereoisomers are 6-carbon sugar alcohols with the same molecular formula as glucose (C6H12O6). Myo-inositol and D-chiro-inositol have insulin-mimetic effects. Inositol administration in diabetic rodents, rhesus monkeys, and humans lowers post-prandial blood glucose levels and improves insulin sensitivity.232425 These benefits may be attributed to the effects of inositol on the insulin signaling pathway. Stimulating the insulin receptor activates the phosphatidylinositol-3-kinase (PI3K) pathway. Phosphorylated forms of phosphatidylinositol act as second messengers that lead to downstream activation of Akt. Akt inactivates the enzyme glycogen synthase kinase-3, enhancing glycogen synthase activity. This increases translocation of the glucose transporter (GLUT4) to the surface of skeletal muscle cells, increasing glucose uptake and lowering blood glucose levels.26

Excess circulating glucose is often deposited as fat in the liver and around visceral organs. Dietary supplementation with inositol reduced weight gain and lipid accumulation in the liver of rats.2327 Inositol-mediated activation of PI3K/Akt signaling is believed to play a role in hepatic lipid metabolism and gluconeogenesis. Inositol also affects transcription of SREBP-1 and PPAR-α – genes involved in fatty acid synthesis, oxidation, and lipid transport.

Choline
In its unmodified form, or after oxidation to betaine, choline reduces fat deposition and accelerates the lipid transport. Like methionine, betaine can also methylate DNA and influence gene expression. Consequently, choline and betaine methylated the promoter region of PPAR-α,28 suppressing mRNA expression and possibly the lipogenic actions of the encoded protein. In addition, choline inhibited obesity-induced oxidative stress and prevented hepatic accumulation of triglycerides.28

In female athletes, choline supplementation significantly reduced body fat as well as levels of the hunger hormone leptin.16 Reduction in leptin levels are linked to greater food satiety. Thus, the dual advantage of consuming fewer calories while burning fats as an energy source may contribute to the lipotropic actions of choline.

Methionine
The liver is where methionine is predominantly processed. Through facilitative transport, it enters the hepatocytes.29 Three processes make up methionine metabolism: the methionine cycle, the transsulfuration route, and the salvage cycle.30 Methionine is converted to S-adenosyl methionine by the enzyme methyl adenosyltransferase in the first step of the methionine cycle (SAM). SAM gives up its methyl group to produce S-adenosyl homocysteine, which is then hydrolyzed to produce adenosine and homocysteine. Methionine can be produced from homocysteine through remethylation. The transsulfuration route is an alternative method of turning it into cysteine. SAM is decarboxylated in the salvage pathway and used as an aminopropyl donor for polyamine production. After ingesting 1-1.5 g of methionine orally, 9–15% of it was eliminated through the urine in healthy human volunteers. When the participants followed a high-fat diet, their urine excretion decreased.31

Inositol
Myo-inositol and inositol phosphate derivatives are primarily absorbed in the gut. Cellular uptake of inositol occurs via sodium ion-coupled transporters as well as sodium-glucose co-transporters. Because they compete for the same transporters for uptake into cells, high glucose levels can significantly inhibit the uptake of inositol.26 Kidneys are the main sites for breakdown of inositol. Renal cortical tubules express the enzyme myo-inositol oxygenase. This enzyme metabolizes myo-inositol via the glucuronate-xylulose pathway, converting it into the monosaccharides xylulose and ribulose. Inositol that is unmetabolized or not re-absorbed at the renal tubular level is excreted unchanged through urine.3233 Although most studies have evaluated the pharmacokinetics of inositol following oral administration, one study assessed the pharmacokinetics of myo-inositol following intravenous (IV) administration in preterm infants.34 In this study, the serum half-life of inositol following a single IV dose was 5.22 hours and after multiple IV dosing was 7.9 hours.

Choline
Choline obtained through the diet is absorbed by choline transporters in the intestine. Choline is primarily metabolized in the liver.35 Here, choline is converted to phosphatidylcholine via the cytidine diphosphate (CDP)-choline pathway. It may also be converted to betaine in a two-step irreversible reaction. Betaine contributes methyl groups to the one-carbon pathway, resulting in the regeneration of methionine from homocysteine. The metabolism of choline may be impaired by single nucleotide polymorphisms in genes encoding folate metabolizing enzymes. Furthermore, dietary choline is converted to trimethylamine by gut bacteria. Trimethylamine is oxidized to trimethylamine-N-oxide by flavin monooxygenase 3 (FMO3) in the liver. Trimethylamine-N-oxide is then excreted through urine.36 Impaired expression or function of FMO3 enzyme manifests as trimethylaminuria or Fish Odor Syndrome.

Methionine
There are no randomized, controlled trials studying the effect of Lipo-MIC injections on pregnant and lactating women or their offspring. Human and animal studies on each constituent compound may offer some insights.

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 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.38

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.39 However, high concentrations of D-chiro-inositol negatively affect the quality of oocytes.40 Therefore, D-chiro-inositol may not be used by women seeking to get pregnant. Effects of other inositol isomers are not well characterized.

Choline
Choline requirements are especially high in pregnant women and nursing mothers. In women of reproductive age, 425 mg/day of choline is considered adequate. Adequate choline intake increases to 450 mg/day during pregnancy and 550 mg/day in lactating women.41 Choline supplementation had beneficial effects on fetal neurodevelopment and maternal placental function. Randomized controlled studies have reported up to 900 mg/day of choline administered orally to be safe and free of adverse events in healthy pregnant women.4243 However, too low and excessively high levels of choline may adversely affect fetal health and development. Additionally, consuming more than 3.5 g/d of choline may cause fishy odor and hypotension in adults.44

Women who are pregnant, planning to be pregnant, or are breastfeeding must consult their physician regarding the use of lipotropic injections for weight loss.

Methionine
S-adenosyl methionine (SAM), a methionine metabolite, may interact with opioids, antipsychotics, amphetamines, and antidepressants to cause an overabundance of serotonin to accumulate in the body. Dextromethorphan, a cough suppressant, and St. John’s wort, a nutritional supplement, may interact with it, raising the risk of serotonin syndrome.45 Shivering and diarrhea are mild serotonin syndrome symptoms, but rigid muscles, fever, and seizures are severe symptoms.

Choline
Choline and inositol are not known to have any clinically relevant interactions with drugs, supplements, or foods.

Potential side effects of lipotropic injections include:

Pain or soreness at the site of injection
Diarrhea
Constipation
Anxiety
Increased heart rate
Incontinence
Insomnia
Dry mouth
Fatigue
Numbness of hands and feet
This is not a comprehensive list of adverse effects. If you experience rash, hives, itchiness, shortness of breath, or other symptoms of an allergic reaction, please discontinue use immediately and consult your physician. Side effects may vary from person to person.

Upcoming evidence indicates that the choline metabolite trimethylamine-N-oxide may be a risk factor for cardiovascular diseases. Studies in animal models suggest that TMAO may be atherogenic and prothrombotic. Therefore, Lipo-MIC injections are contraindicated in individuals with cardiovascular disorders. S-adenosyl methionine may worsen the symptoms of mania in people with bipolar disorder.6 Consult a physician before use.

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.