Masterclass Liver Care - Vitafoods 2016
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The liver performs many essential functions including detoxification, protein synthesis, production of biochemicals for digestion, storing glycogen, and decomposing red blood cells. Liver disease can result from alcohol use, viruses, autoimmune conditions, genetic disorders, or non-alcoholic fatty liver disease (NAFLD). NAFLD occurs when excess fat accumulates in the liver and is increasing worldwide due to the rise in obesity and metabolic syndrome. Poor diet and lifestyle factors contribute to NAFLD progression. Choline plays an important role in liver health by supporting phospholipid membranes, lipoprotein synthesis, and methylation reactions, and higher intakes may be needed to prevent NAFLD.
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Masterclass Liver Care - Vitafoods 2016
- 2. Liver, what do you know? • Food – Liver – Foie gras • Alcohol use
- 3. Liver anatomy • 1,5 kg • Supplied by blood from – Hepatic artery – Portal system (gut, pancreas, spleen) • Liver sinusoids => central vene • Bile duct
- 4. Liver function • Detoxification of various metabolites – Reduction, oxidation, conjugation, excretion – Drugs, alcohol • Protein synthesis • Production of biochemicals necessary for digestion • Bile • Numerous functions in the human body • Glycogen storage • Decompensation of red blood cells • Hormone production
- 5. Liver function • Detoxification of various metabolites – Reduction, oxidation, conjugation, excretion – Drugs, alcohol • Protein synthesis • Production of biochemicals necessary for digestion • Bile • Numerous functions in the human body • Glycogen storage • Decompensation of red blood cells • Hormone production
- 6. Liver disease • Alcohol • Steatosis (NASH/NAFLD) • Chronic Hepatitis (B/C) • Auto-immune hepatitis • Primairy Biliair Cholangitis (PBC) • Primairy Sclerosing Cholangitis (PSC) • Metabolic diseases • Hemochromatose • M. Wilson • Alfa-1-antitrypsine deficiëncy • Drugs • Infections • Cryptogenic
- 7. Liver fibrosis -> cirrhosis
- 8. Complications livercirrhosis • Portal hypertension – Oesofageal varices – Splenomegaly en hypersplenism – Ascites en Spontaneous Bacterial peritonitis (SBP) – Hepatorenal Syndrome – Hepatic encefalopathy • Liver failure – Clotting problems – Hypoalbuminaemia • Hepatocellulair carcinoma
- 9. End stage
- 10. NAFLD / NASH • 2016 worldwide more obesity than malnutrition – 500.000.000 • 2016 more deaths related to obesity than malnutrition • 15% world population obese • 40% world population overweight • NAFLD 17-46% of adults in western population • Steatosis No1 indication for liver transplantation (US) USA Steatosis No1 indication for liver transplantation
- 11. NAFLD / NASH • WHO: 2016 worldwide more obesity than malnutrition – 500.000.000 • 2016 more deaths related to obesity than malnutrition • 15% world population obese (BMI >30) • 40% world population overweight (25< BMI<30) • NAFLD 17-46% of adults in western population – NAFL & NASH • NASH 3 -5% prevalence
- 12. Dimension of the problem General population NAFLD 20-40% NASH 2-5% Obesity NAFLD NASH 15-55% DM type 2 NAFLD NASH 20-80% DM: >380 million >550 in 2030 1 billion
- 13. NAFLD / NASH • Characterised by – Excessive hepatic fat accumulation – Associated with insulin resistance • Definition: – Steatosis in 5% of hepatocytes (histology or proton magnetic resonance spectroscopy 1H-MRS or MRI) • Exclusion: – Alcohol daily >30g(♂) and >20g (♀)
- 14. Risk factors • Obesity • Hypertension • Dyslipidemia • Type 2 diabetes • Metabolic syndrome
- 15. Pathophysiology
- 16. NAFLD / NASH Pathogenesis • High-calorie diet • Excess (saturated) fats • Refined carbohydrates • Sugar-sweetened beverages • High fructose intake • Western diet • Genetic factors? Weight gain Obesity NAFLD
- 17. Identification • Identify risk factors of NAFLD • Imaging – US, (MRI) • Markers of inflammation – ALAT • Markers of fibrosis – NFS, FIB-4, ELF, Fibrotest • Transient elastography - liverbiopsy
- 19. Treatment • Liver transplantation ($600.000)
- 20. Treatment • Bariatric surgery – ($ 6.000 - 30.000)
- 21. Treatment Diet and lifestyle changes • Small amounts of weight loss! – reduce liver fat and improve hepatic IR • 7% histological improvement • Progressive increase in exercise
- 22. Treatment • Insulin sensitizers – Metformine – Pioglitazone – Rosiglitazone – Incretin mimetics • Antioxidants, cytoprotective and lipid lowering agents – Vit E (800IU/day) – UDCA – Obeticholic acid – N-3 polyunsaturated fatty acids (PUFA) • Iron depletion
- 23. Treatment Experimental therapies • Anti-inflammatory • Antifibrotic agents • Insulin sensitizing • Fatty acid/ bile acid conjugates • Choline (Vitacholine)
- 24. Future perspective • Fighting steatosis • Lifestyle changes • Drugs • Supplements
- 26. Choline, an essential nutrient for humans • Required to make essential membrane phospholipids. • Precursor for biosynthesis of neurotransmitter acetylcholine • Source of labile methyl groups. • Choline NOT considered a vitamin (body synthesizes small amounts) still considered an essential nutrient in humans because choline MUST be consumed to maintain health. • Design: – Healthy male volunteers fed choline-free diet with 500 mg/day choline X1wk. – Randomized into 2 groups, with choline (control) & without (deficient) for 3wk. – Final wk – all received choline. • Results: – choline-deficient group, plasma choline and phosphatidylcholine concentrations 30%; plasma and RBC phosphatidylcholine 15%; no such changes occurred in the control group. – In choline-deficient group, serum alanine aminotransferase activity • Observations support conclusion and choline is an essential nutrient for humans when excess methionine and folate are not available in the diet. Zeisel S.H., et al; FASEB J. 1991 Apr;5(7):2093-8.
- 27. 1. Phosphorylated down cytidine diphosphate-choline (CDP-choline) pathway to produce phosphatidylcholine (PC) for cell membranes and circulating lipoproteins. or 2. Oxidized to betaine, as a source of methyl groups for the synthesis of methionine & S-adenosyl-methionine (SAM), principal methylating agent in mammalian cells. and 3. Generate PC via the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, & catalyzes SAM-dependent sequential trimethylation of phosphatidyl ethanolamine. Yan, J., et al; Am J Clin Nutr December 2013 vol. 98 no. 6 1459-1467 Choline Metabolic Pathways
- 28. Betaine (Trimethyl glycine) Choline Glycine MethionineHomocysteine Methyl glycine S-Adenyl Methionine Methyl tetrahydrofolate Folate DNA RNA Protein Lipid Choline Oxidation Pathway
- 29. What Pregnancy can teach us about Choline • Large amounts of PC needed for cellular division, tissue expansion, and lipoprotein synthesis. • 12-wk feeding study examining impact of pregnancy on biomarkers of choline metabolism – 26 healthy, third-trimester, singleton pregnant women – 21 non-pregnant women – 2 choline intake levels (380mg from diet) and • 100mg & 550mg (Balchem Vitacholine). – All participants also took a multivitamin • 600ug folate, 2.6ug B12, 1.9mg B6 • 200mg DHA (Neuromins, Natures Way). Yan, J., et al; Am J Clin Nutr December 2013 vol. 98 no. 6 1459-1467
- 30. PC-DHA 480mg linoleic (18:2n−6) oleic (18:1n−9) Yan J, et al; Am J Clin Nutr December 2013 vol. 98 no. 6 1459-1467 DHA (22:6n−3) ARA (20:4n−6)
- 31. PC-DHA VLDL DHA PC-DHA cytidine diphosphate 930mg PEMT Yan J, et al; Am J Clin Nutr December 2013 vol. 98 no. 6 1459-1467 40% Genetic Polymorphism in PEMT gene – unresponsive to estrogen
- 32. Betaine CholineGlycine MethionineHomocysteine Methyl glycine S-Adenyl Methionine SAM Methyl tetra hydrofolate Folate Methyl Cobalamin Vitamin B12 DNA RNA Protein Lipid X X B12 Deficiency & Choline Steal Tetra hydrofolate X X CH3- B12 B12X39% US pop subclinical deficiency
- 33. Corbin KD & Zeisel SH. Curr Opin Gastroenterol. 2012 Mar; 28(2): 159–165. http://www.histology.leeds.ac.uk/cell/plasma_membrane.php
- 34. Maintaining the Balance 34 Membrane Integrity Phosphatidylcholine Packaging of Triglyceride rich VLDL VLDL Choline Gene Silencing & Activation Protein Synthesis Lipid Synthesis Methylation Cystein
- 35. Imbalance = Choline Steal 35 Leaky Membrane Triglyceride Trapping Fatty Liver Cirrhosis Liver Cancer VLDL Liver Enzymes Stealing Choline from membranes Liver Enzymes Insulin Resistance Metabolic Syndrome Deficiency in USA 0.5% 39% Methylation Survival Mode Robs Peter (liver) to Pay Paul (methylation) Gene Silencing & Activation Protein Synthesis Lipid Synthesis Muscle Enzymes Muscle Enzymes Gene
- 36. • Choline intake exceeding current recommendations may be needed to support both PC production via CDP-choline pathway and choline-mediated one-carbon metabolism. • The competing demands for choline by the phosphorylation or oxidative pathways and the critical importance of this compound in a variety of key metabolic functions make the necessity for ensuring at least recommended intakes of choline, and preferably more.
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