Substances for treatment of fatty liver-related conditions
Inventors
Mardinoglu, Adil • Borén, Jan • Uhlén, Mathias
Assignees
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Publication Number
US-11813236-B2
Publication Date
2023-11-14
Expiration Date
Abstract
There is provided a composition comprising: A) serine, glycine, betaine, N-acetylglycine, N-acetylserine, dimethylglycine, sarcosine and/or phosphoserine; B) N-acetyl cysteine, cysteine and/or cystine; C) optionally carnitine, deoxycarnitine, gamma-butyrobetaine, 4-trimethylammnoniobutanal, 3-hydroxy-N6,N6,N6-trimethyl-L-lysine, N6,N6,N6-trimethyl-L-lysine and/or lysine; and D) nicotinamide riboside, quinolinate, deamino-NAD+, nicotinate D-ribonucleotide, nicotinamide D-ribonucleotide, nicotinate D-ribonucleoside, nicotinamide and/or nicotinate, wherein the molar ratio of A) to D) is between 250:1 and 1.5:1 and the molar ratio of A) to B) is between 16:1 and 1:4. The composition may be used in a method of treatment of a medical condition selected from the group consisting of non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), type 2 diabetes, obesity, insulin resistance and dyslipidemia.
Core Innovation
A composition and a method are provided for fatty-liver diseases by combining glycine-group nutrients and amino-alcohol-related nutrients with sulfur and carnitine-related cofactors and with a nicotinamide riboside and/or nicotinamide component. The composition includes serine, betaine and/or glycine (A), N-acetyl cysteine and/or cysteine (B), L-carnitine (C), and nicotinamide riboside and/or nicotinamide (D), with constrained molar ratios of A to D and A to B.
The nutrient regimen is linked to altered NAD+ metabolism and glutathione (GSH) metabolism as a mechanistic basis for non-alcoholic fatty liver disease (NAFLD) and related fatty liver conditions. The mechanistic basis ties the combined regimen to changes in NAD+ and GSH metabolism, with effects on hepatic steatosis and liver function markers.
Proof-of-concept is reported in both mouse and human contexts where supplementation with the serine/NAD+ and GSH precursor components decreases hepatic steatosis and improves liver function markers. The compositions are described as being formulated as solid compositions or aqueous solutions/suspensions, and are administered orally as a regimen.
Claims Coverage
Two independent claims are directed to a composition and a method of treating a medical condition. Each independent claim uses the same core component groupings and constrains molar ratios, including a defined A to D ratio and a defined A to B ratio, to establish the inventive combination.
Ratio-constrained multi-nutrient fatty-liver composition
A composition comprising serine, betaine and/or glycine; N-acetyl cysteine and/or cysteine; L-carnitine; and nicotinamide riboside and/or nicotinamide, wherein the molar ratio of A) to D) is between 50:1 and 3:1 and the molar ratio of A) to B) is between 16:1 and 1.5:1.
Ratio-constrained fatty-liver treatment by multi-nutrient administration
A method of treating a medical condition in a subject comprising simultaneous, separate or sequential administration to the subject of serine, betaine and/or glycine; N-acetyl cysteine and/or cysteine; L-carnitine; and nicotinamide riboside and/or nicotinamide, wherein the molar ratio of A) to D) is between 50:1 and 3:1 and the molar ratio of A) to B) is between 16:1 and 1.5:1.
Across the independent claims, the inventive coverage centers on a specified four-group combination (A: serine/betaine/glycine; B: N-acetyl cysteine/cysteine; C: L-carnitine; D: nicotinamide riboside/nicotinamide) with constrained molar ratios (A to D and A to B), applied both as a composition and as a multi-component treatment regimen for fatty-liver and related metabolic conditions.
Stated Advantages
Decreases hepatic steatosis.
Improves liver function markers.
Documented Applications
Treating fatty liver diseases including non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD).
Treating non-alcoholic steatohepatitis (NASH).
Treating metabolic conditions selected from type 2 diabetes, obesity, insulin resistance, and dyslipidemia.
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