New genetic factor identified in worsening of MASLD, with vitamin B3 as the most effective therapeutic agent (Niacin)

Approximately 30% of the global population is affected by metabolic-associated fatty liver disease (MASLD), a condition that previously lacked targeted treatments. Researchers have now identified a genetic factor that exacerbates the disease, and remarkably, the FDA-approved drug that most effectively targets this factor is vitamin B3.

A research team has elucidated the role of microRNA-93 (miR-93), which is expressed in the liver, as a key genetic regulator in the development and progression of MASLD.

MiR-93 is a specialized RNA molecule expressed in hepatocytes that functions to suppress the expression of specific target genes. The team observed abnormally elevated levels of miR-93 in both patients with fatty liver disease and animal models. Through molecular analysis, they demonstrated that miR-93 promotes lipid accumulation, inflammation, and fibrosis by inhibiting the expression of SIRT1, a gene involved in lipid metabolism within liver cells.

In experiments using gene-editing techniques to eliminate miR-93 production in mice, researchers observed a marked reduction in hepatic fat accumulation, along with significant improvements in insulin sensitivity and liver function indicators. Conversely, mice with overexpressed miR-93 exhibited worsened hepatic metabolic function.

Furthermore, screening of 150 FDA-approved drugs revealed that niacin (vitamin B3) most effectively suppresses miR-93. Mice treated with niacin showed a significant decrease in hepatic miR-93 levels and a notable increase in SIRT1 activity. The activated SIRT1 restored disrupted lipid metabolism pathways, thereby normalizing liver lipid homeostasis.

The research team explained, "This study precisely elucidates the molecular origin of MASLD and demonstrates the potential for repurposing an already approved vitamin compound to modulate this pathway, which has high translational clinical relevance. Given that niacin is a well-established and safe medication used to treat hyperlipidemia, it holds promise as a candidate for combination therapies targeting miRNA pathways in MASLD."

Are you taking enough?

Taking high doses of niacin has been shown to produce the following improvements in blood cholesterol and lipids:

Increase HDL (good) cholesterol. It prevents the breakdown of apolipoprotein A1, which is used to make HDL (good) cholesterol. It can increase HDL (good) cholesterol by up to 20–40%.
Reduce LDL (bad) cholesterol. Niacin speeds the breakdown of apolipoprotein B in LDL (bad) cholesterol, causing less to be released by the liver. It can reduce LDL (bad) cholesterol by 5–20%.
Lower triglycerides. Niacin interferes with an enzyme that’s essential for making triglycerides. It can lower triglycerides in the blood by 20–50%.

People only experience these positive effects on blood fats when they take therapeutic doses of niacin in the range of 1,000–2,000 mg per day.

you might consider Tru Niagen, a branded form of nicotinamide riboside chloride ... it’s not cheap, but doesn’t flush ... it is also direct precursor to NAD+, which is what niacn is eventually converted to after additional bioconversion steps ...

here’s what grok3 has to say about the two forms:

how is nicotinamide riboside chloride related to niacin?

Nicotinamide riboside chloride (NR) and niacin (vitamin B3) are both precursors to nicotinamide adenine dinucleotide (NAD+), a critical coenzyme in cellular metabolism. Here’s how they are related:

Chemical Relationship:

Niacin, also known as nicotinic acid, is a form of vitamin B3. Nicotinamide, another form of vitamin B3, is closely related to niacin and is a direct precursor to NAD+.
Nicotinamide riboside (NR) is a derivative of nicotinamide, consisting of nicotinamide bound to a ribose sugar. The chloride form is a stabilized salt used in supplements.
Both niacin and NR are converted into NAD+ in the body through different biochemical pathways.

NAD+ Synthesis Pathways:

Niacin: Converted to NAD+ via the Preiss-Handler pathway. Niacin is first transformed into nicotinic acid mononucleotide, then to nicotinic acid adenine dinucleotide, and finally to NAD+.

Nicotinamide Riboside: Converted to NAD+ through a shorter pathway involving nicotinamide mononucleotide (NMN). NR is phosphorylated by nicotinamide riboside kinases (NRKs) into NMN, which is then converted to NAD+ by NMN adenylyltransferases.

Both pathways ultimately boost NAD+ levels, but NR is considered a more efficient precursor because it bypasses some of the steps required for niacin.

Functional Similarities:

Both compounds support NAD+ production, which is essential for energy metabolism, DNA repair, and cellular signaling.
They are used in supplements to address NAD+ decline associated with aging, metabolic disorders, or deficiencies.

Differences:

Side Effects: Niacin can cause flushing (redness and warmth of the skin) at high doses due to its effect on blood vessels, while NR is generally better tolerated with fewer side effects.

Bioavailability: NR may be more efficiently absorbed and utilized in certain tissues compared to niacin or nicotinamide.

Forms: Niacin exists as nicotinic acid or nicotinamide, while NR is a distinct molecule often sold as a chloride salt for stability.

In summary, nicotinamide riboside chloride and niacin are related as vitamin B3 derivatives that both serve as precursors to NAD+, but they differ in their chemical structure, metabolic pathways, and physiological effects. NR is often marketed as a more direct and efficient way to boost NAD+ levels compared to niacin.

Grok 3

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