Lipo-C + B12

Choline Deficiency and Fatty Liver

Choline deficiency is a well-characterized cause of hepatic steatosis. Human depletion studies demonstrate that removing dietary choline rapidly induces fatty liver in susceptible individuals, particularly postmenopausal women and those with specific genetic polymorphisms (PEMT, MTHFD1). The mechanism is impaired VLDL-mediated triglyceride export. This established biochemistry underlies the rationale for choline supplementation.

Methionine and One-Carbon Metabolism

Methionine is rate-limiting for hepatic phosphatidylcholine synthesis via the PEMT pathway when choline intake is insufficient. The transsulfuration pathway also converts methionine-derived homocysteine to cysteine for glutathione synthesis, linking methylation capacity to antioxidant status.

Inositol and Insulin Signaling

Myo-inositol functions as a precursor to phosphatidylinositol derivatives that serve as second messengers in insulin signaling. Meta-analyses in PCOS populations have characterized modest improvements in insulin sensitivity and ovulatory function. Effects in general metabolic dysfunction outside PCOS are less established.

B12 and Homocysteine Recycling

Methylcobalamin is essential for methionine synthase activity. B12 deficiency impairs homocysteine remethylation, depleting methionine pools and disrupting the methylation cycle. Adequate B12 status is prerequisite for efficient one-carbon metabolism.

Choline Supplementation in NAFLD (2025 RCT)

A 12-week randomized controlled trial in patients with non-alcoholic fatty liver disease evaluated phosphatidylcholine supplementation (2400 mg/day). Treated patients showed significant improvements in hepatic steatosis measured by controlled attenuation parameter, fibrosis scores, oxidative stress markers, and liver enzymes compared to placebo. This provides direct clinical evidence for choline's role in hepatic lipid handling beyond deficiency correction.

The evidence base for this formulation differs from peptide compounds:

• Individual components: Well-characterized biochemistry with clear mechanistic roles in hepatic lipid handling, methylation, and one-carbon metabolism. Choline now has direct RCT support in NAFLD populations.
• Combination product: Clinical trial evidence for the MIC + B12 combination specifically remains limited. Most published research examines components in isolation.
• Deficiency correction vs enhancement: Evidence is strongest for correcting deficiency states and supporting hepatic function under metabolic load; enhancement effects in fully replete individuals are less characterized.

This framing matters: the mechanisms are established biochemistry, and emerging clinical data supports choline's hepatic benefits directly — but combination-specific efficacy data remains an open question.

Rigorous placebo-controlled trials evaluating the combination for defined metabolic outcomes (weight loss, liver fat reduction, body composition) are largely absent. The lipotropic combination is a longstanding formulation in functional medicine practice, but evidence remains at the level of biochemical rationale plus individual component data rather than combination-specific clinical trials. Effects likely depend on baseline nutritional status — correction of marginal deficiency differs from supplementation in replete individuals.

• Zeisel SH. Choline: critical role during fetal development and dietary requirements in adults. Annu Rev Nutr 2006.
• Corbin KD, Zeisel SH. Choline metabolism provides novel insights into NAFLD. Curr Opin Gastroenterol 2012.
• Unfer V, et al. Myo-inositol effects in women with PCOS: a meta-analysis. Endocr Connect 2017.
• Sedhom SS, et al. The impact of choline supplementation on oxidative stress and clinical outcomes among patients with non-alcoholic fatty liver disease: a randomized controlled study. Ther Adv Chronic Dis 2025.

For laboratory research use only.