AACB July Webinar The Clinical Biochemistry of SUGAR A/Prof Ken Sikaris Melbourne Pathology BSc(Hons), MBBS, FRCPA, FAACB, FFSc A/Prof Ken Sikaris 9th July 2014 Prof. Robert H Lustig, San Francisco A/Prof Ken Sikaris 9th July 2014 Lustig R.H. “Obesity and the toxic environment”, Clin Biochem Rev. 2008 Nov; S120–S121 Lustig RH, Schmidt LA, Brindis CD, “The toxic truth about sugar.” Nature 2012;482:27-9 A/Prof Ken Sikaris 9th July 2014 I love sugar A/Prof Ken Sikaris 9th July 2014 Life loves ‘sugar’.... A/Prof Ken Sikaris 9th July 2014 Glucose – The Universal Fuel Archaea Bacteria / Eukaryotes Gluconeogenesis A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Humans and Glucose Glucose INSULIN A/Prof Ken Sikaris 9th July 2014 Carbohydrate ENERGY OXYGEN CARBON DIOXIDE CARBO ENERGY HYDRATE WATER Hydration A/Prof Ken Sikaris 9th July 2014 Seasonal Fruits A/Prof Ken Sikaris 9th July 2014 Plants and seed dispersal A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Carbohydrates • Mono-saccharides – Glucose, Fructose, Galactose • Di-saccharides – Sucrose, Maltose, Lactose • Sucrase, Maltase, Lactase A/Prof Ken Sikaris 9th July 2014 Sweetness A/Prof Ken Sikaris 9th July 2014 Carbohydrates • Mono-saccharides – Glucose, Fructose, Galactose • Di-saccharides – Sucrose, Maltose, Lactose • Sucrase, Maltase, Lactase • Polysaccharides – Starches, Fibre A/Prof Ken Sikaris 9th July 2014 Plants • Make Carbohydrate • But glucose can’t be stored – Esp because it dissolves in water • Glucose molecules linked together are not water soluable – can be stored • Stored in starch granules – fruit, seeds, rhizomes, tubers A/Prof Ken Sikaris 9th July 2014 Starch Granules Normal Maize Waxy Maize Cassava Potato Rice Potato Wheat Sorghum Sweet Corn Potato Amaranth High Amylose Maize A/Prof Ken Sikaris 9th July 2014 Digestion of Starch granules Waxy Normal High Amylose Corn (Salivary) Amylase (Pancreatic) Amylase + (Mucosal) a-glucosidase A/Prof Ken Sikaris 9th July 2014 Starch types A/Prof Ken Sikaris 9th July 2014 Starch digesting enzymes • Alpha amylase (amylose a1-4 linkage) – Bacteria, fungi, plants, animals • Beta amylase – Plants • Isoamylase (amylopectin a1-6 branch linkage) – Plants, bacteria A/Prof Ken Sikaris 9th July 2014 • Lactobacillus • Bifidobacterium • Streptococcus – Acidophilus – Longus – Salivarius – Delbrueckii • Infantis • Thermophilus • Lactis – Animalis • Escherichia • Bulgaricus • Lactis – Coli – Caucasicus – Breve • DSM17252 – Fermentem – Coagulans • Propionibacterium – Helveticus – Lichenformis – Freudenreichii – Leichmanii – Bifidum • Shermanii – Rhamnosus • Saccharomyces – Paracasei – Boulardii • paracasei – Plantarum – Reuteri A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 50 gm Glucose equivalent loads Potato Glucose Corn Bread GLUCOSE Rice Potato Dextrose Rice Corn Corn Bread Bread INSULIN Potato Rice Glucose A/Prof Ken Sikaris 9th July 2014 What is SUGAR: A/Prof Ken Sikaris 9th July 2014 The name tells it’s story; • Sakkarai (Tamil) • Sarkara (Sanskrit) • Shekar (Persian) • Sakkaris (Ancient Greek) • Sukkar (Arabic) • Acucar (Portugal) • Azucar (Spanish) • Zakhari (Modern Greek) • Zucchero (Italina) • Suchre (French) Sugar (English) A/Prof Ken Sikaris 9th July 2014 Sugar History • Papua New Guinea • Traded to India • Traded to ‘Spice Route’ – Controlled by empires • Persia, (Greeks, Romans) • Moslim, – Sicily, Spain, Portugal » South America • English, – (French/Europe Beet) • USA A/Prof Ken Sikaris 9th July 2014 Sugar Producers A/Prof Ken Sikaris 9th July 2014 The price of ‘sugar’ A/Prof Ken Sikaris 9th July 2014 1973 A/Prof Ken Sikaris 9th July 2014 Glucose to Fructose • Akabori S, Nehara K, Muramatsu I, – ‘Glucose Isomerase’, Chem Soc Jpn 1952;73:311 • Takasaki Y, Kosugi Y, Kanabayashi A, – “Fermentation Advances” New York: Academic Press, 1969 • Takayashi Y, Tanabe O, – “Enzyme method for converting glucose in glucose syrups to fructose.” US patent 3,616,221. 1971. A/Prof Ken Sikaris 9th July 2014 High Fructose Corn Syrup AMYLASE ISOMERASE 100% Glucose 55% Fructose A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Why HFCS? • Economic – Sugar cane price • Nixon 1973 declared war on poverty and rising food prices • Technical – 1975: HFCS – cheaper than sugar • Medical – LOW FAT FOOD (= high carb food!) • Dietary fat raises LDL cholesterol A/Prof Ken Sikaris 9th July 2014 1973 A/Prof Ken Sikaris 9th July 2014 The Food Pyramid A/Prof Ken Sikaris 9th July 2014 Cane Sugar = Sucrose = Gluc + Fruct A/Prof Ken Sikaris 9th July 2014 The fate of sugars (Glucose) LIVER 100 gm Glycogen MUSCLE 400 gm Glycogen A/Prof Ken Sikaris 9th July 2014 The fate of sugars (Fructose) LIVER MUSCLE A/Prof Ken Sikaris 9th July 2014 mmol/L umol/L A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 The fate of sugars • Glucose – 80% peripheral uptake – 20% hepatic uptake • 15% Glycogen • 5% Fat synthesis • Fructose – 100% hepatic uptake – 100% Fat synthesis • Esp + glucose & Insulin A/Prof Ken Sikaris 9th July 2014 0 Weeks 2 Weeks 4 Weeks 8 Weeks 16 Weeks A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Type 2 diabetes Fructose Glucose PANCREAS LIVER Insulin MUSCLE Fat A/Prof Ken Sikaris 9th July 2014 Fructose = Low GI (!) A/Prof Ken Sikaris 9th July 2014 Type 2 diabetes Fructose Glucose PANCREAS LIVER Insulin MUSCLE Blood Fat Fat Body Fat A/Prof Ken Sikaris 9th July 2014 How do we become obese? • Energy dense foods – Protein – Fats • Saturated Fats • Cholesterol – Carbohydrate • Refined • Sugar – Fructose? A/Prof Ken Sikaris 9th July 2014 Changes in Dietary Composition A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 US HFCS Consumption A/Prof Ken Sikaris 9th July 2014 Obesity in adults A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Obesity in Children A/Prof Ken Sikaris 9th July 2014 Overweight children in Australia: A/Prof Ken Sikaris 9th July 2014 Obesity • Energy Intake • Energy Output – Food – Exercise A/Prof Ken Sikaris 9th July 2014 Energy Expenditure (mainly NOT exercise) A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 How did we become obese? A/Prof Ken Sikaris 9th July 2014 Obesity in Babies ! Lack of Exercise? Kim 2006;15:1107. Obesity et al, Kim A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Type 2 diabetes Fructose Glucose PANCREAS LIVER Insulin MUSCLE Blood Fat Fat Body Fat A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Insulin Resistance and Dyslipidemia Liver Fructose FFA CE (hepatic TG VLDL (CETP) HDL lipase) TG Apo A-1 CE (CETP) TG Kidney SD LDL LDL (lipoprotein or hepatic lipase) A/Prof Ken Sikaris 9th July 2014 Modified LDL is atherogenic A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 LDL gradient gel electrophoresis ‘Lipoprint’ A/Prof Ken Sikaris 9th July 2014 Small Dense LDL Austin MA, King MC, Vranizan KM, Krauss RM, “Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease.” Circulation 1990;82:495-506. 0.5 1.0 1.5 2.0 2.5 3.0 (mmol/L) A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Triglycerides 3500 19% > 2.0 mmol/L 3000 9% > 2.0 mmol/L 2500 2000 Men Women 1500 1000 Thousands of Thousands People 500 0 <0.5 1.0 to <1.5 2.0 to <2.5 3 0.5 to <1.0 1.5 to <2.0 2.5 to <3.0 Triglycerides (mmol/L) A/Prof Ken Sikaris 9th July 2014 Triglycerides 3500 35% > 1.5 mmol/L 3000 22% > 1.5 mmol/L 2500 2000 Men Women 1500 1000 Thousands of Thousands People 500 0 <0.5 1.0 to <1.5 2.0 to <2.5 3 0.5 to <1.0 1.5 to <2.0 2.5 to <3.0 Triglycerides (mmol/L) A/Prof Ken Sikaris 9th July 2014 Small Dense LDL Austin MA, King MC, Vranizan KM, Krauss RM, “Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease.” Circulation 1990;82:495-506. 0.5 1.0 1.5 2.0 2.5 3.0 (mmol/L) A/Prof Ken Sikaris 9th July 2014 Interpretation of blood fats • 30 years ago – High cholesterol, Triglycerides unimportant • 20 years ago – Bad cholesterol (LDLC), Good cholesterol (HDLC) • 10 years ago – Modified LDL atherogenic • Oxidised, Glycated, Apo(a)/Lp(a), Small Dense LDL) • Today – Triglycerides are important! – Move away from LDLC: Non HDLC = LDLC + VLDLC A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Disaccharidases A/Prof Ken Sikaris 9th July 2014 Hydrogen Breath Test A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Glucose Transporters A/Prof Ken Sikaris 9th July 2014 Sweetness LACTULOSE A/Prof Ken Sikaris 9th July 2014 Case 1: Normal A/Prof Ken Sikaris 9th July 2014 Case 1: Normal A/Prof Ken Sikaris 9th July 2014 Case 2: Lactose Malabsorption A/Prof Ken Sikaris 9th July 2014 Case 3: Fructose Malabsorption A/Prof Ken Sikaris 9th July 2014 Case 4: Fructose Malabsorption A/Prof Ken Sikaris 9th July 2014 A/Prof Ken SikarisKen 9 A/Prof th July July 2014 Single Disorder Multiple Disorder Case 6: Carbohydrate Malabsorption A/Prof Ken Sikaris 9th July 2014 Case 6: Carbohydrate Malabsorption A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 A/Prof Ken Sikaris 9th July 2014 Major FODMAPS 1.