1. The Isotonix Advantage The Isotonix ® Advantage Mark Lange, Ph.D. Director, Quality Control Market America

2. OVERVIEW Understanding Your Digestive System Understanding Your Digestive System Transporting Nutrients into Cells Transporting Nutrients into Cells The Isotonix Delivery System The Isotonix Delivery System Isotonix Advantage #1,2,3….. Isotonix Advantage #1,2,3…..

6. STOMACH Secretes 5 substances mainly: Water – diluent Water – diluent Chloride ions Chloride ions Hydrogen ions Hydrogen ions Pepsin – proteolytic enzyme (proteins) Pepsin – proteolytic enzyme (proteins) Intrinsic factor – vitamin B-12 binding protein released by parietal cells Intrinsic factor – vitamin B-12 binding protein released by parietal cells Hydrochloric acid HCl = pH 1.0 – 2.8

9. Isotonix Advantage #1 Nutrients are not exposed to acidic environment of stomach, where they would otherwise degrade. Customer money is not wasted.

10. Isotonix Advantage #2 Reduced delivery time. Example: B vitamins for energy Minutes to uptake – not hours

11. SMALL INTESTINE ACIDIC FOOD SOLUTION stimulates pancreas to release numerous digestive enzymes in a sodium bicarbonate solution ACIDIC FOOD SOLUTION stimulates pancreas to release numerous digestive enzymes in a sodium bicarbonate solution NEUTRALIZATION pH of food solution changed from acidic to nearly neutral NEUTRALIZATION pH of food solution changed from acidic to nearly neutral

12. SMALL INTESTINE BILE is a product of the liver, collected in the gall bladder, and secreted onto the food solution. BILE is a product of the liver, collected in the gall bladder, and secreted onto the food solution. Contains surfactants that disperse fat. Contains surfactants that disperse fat. Lipases act on triglycerides, releasing fatty acids. Lipases act on triglycerides, releasing fatty acids.

16. Isotonix Advantage #3 Carbon dioxide created by the effervescent reaction reduces the thickness and viscosity of the mucus layer of the intestinal tract, promoting absorption into the cells. Pharm. Res. 1998, vol 15, pp 925-930. “Mechanistic studies on effervescent-induced permeability enhancement.”

17. FOLDS IN THE SMALL INTESTINE Villi Mucosa Sub - Mucosa

19. The Cell Membrane

20. Cell Membrane Barriers Lipid bi-layers are impermeable to most essential molecules and ions. Oxygen, Water, & Carbon Dioxide can freely pass. Many nutrients cannot freely pass.

21. Movement through Differences in Concentration Diffusion is moving molecules from a region of higher concentration to a region of lower concentration.

22. Simple Diffusion

23. Higher concentrations move nutrients into cells Membrane (lipid bi- layer)

24. Isotonix Advantage #4 Favorable concentration gradient for absorption of some nutrients. Example: Calcium/Magnesium Nutrients are delivered to the small intestine in a concentrated solution.

25. Facilitated Diffusion Takes place through channels embedded in the membrane. Example: Fructose moved into cell by facilitated diffusion.

26. Active Transport Pumping of molecules or ions through a membrane into a region of higher concentration. It requires a trans- membrane protein and energy input. Example: Amino Acids, ATP, Sodium, Potassium moved into cell by Active Transport.

28. SMALL INTESTINE Absorption of nutrients occurs throughout entire length of small intestine (90 – 95% efficient) Absorption of nutrients occurs throughout entire length of small intestine (90 – 95% efficient) Calcium absorption occurs as late as ileo- cecal juncture (appendix)  transport into cells via calcium channels Calcium absorption occurs as late as ileo- cecal juncture (appendix)  transport into cells via calcium channels Under neutral pH, intrinsic factor binds to vitamin B-12 to form a complex Under neutral pH, intrinsic factor binds to vitamin B-12 to form a complex

29. SMALL INTESTINE Intrinsic factor/vitamin B-12 complex binds to receptors (specialized docking structures) on intestinal membranes Intrinsic factor/vitamin B-12 complex binds to receptors (specialized docking structures) on intestinal membranes Last 1/3 rd of small intestine is main absorptive site Last 1/3 rd of small intestine is main absorptive site

30. COLON Most nutrients will have been absorbed by the time they reach the large intestine —an additional 3-5% possible. Most nutrients will have been absorbed by the time they reach the large intestine —an additional 3-5% possible. Major functions of colon: Major functions of colon: Site of bacterial cell growth and residence Site of bacterial cell growth and residence An estimated 300-400 species or strains of bacteria continue digestion of waste products An estimated 300-400 species or strains of bacteria continue digestion of waste products Regulates water in body Regulates water in body Some vitamins produced in low amounts by bacteria and absorbed Some vitamins produced in low amounts by bacteria and absorbed

31. COLON Bacteria adjust the pH of the colon into the acidic range – prevents overgrowth of harmful bacteria. Continued growth of friendly bacteria help maintain healthy balance.

32. What does “isotonic” mean? ISO = SAME TONIC = Tension or Pressure An Isotonic Cell is a Happy Cell.

33. Cells act like little bags of salty water….. The movement of water in and out of a cell is called “Osmosis.” Cells want the same concentration of dissolved particles (salt) on both sides of the membrane.

35. ISOTONIC (NORMAL) HYPOTONIC (WATER GOING IN) HYPERTONIC (WATER GOING OUT)

36. Isotonix Advantage #5 Isotonic solutions are the optimal delivery system. Isotonix products work with – not against – normal body physiology.

37. Composition of Isotonix Delivery System Active ingredients: vitamins, minerals, oligomeric proanthocyanidins (OPC), flavonoids, coenzyme Q10, etc. Active ingredients: vitamins, minerals, oligomeric proanthocyanidins (OPC), flavonoids, coenzyme Q10, etc. Base ingredients: fructose, glucose, citric acid, malic acid, calcium sulfate, maltodextrin, silica, potassium bicarbonate Base ingredients: fructose, glucose, citric acid, malic acid, calcium sulfate, maltodextrin, silica, potassium bicarbonate

38. Composition of Isotonix Delivery System Glucose and fructose: Glucose and fructose: Sweet-tasting simple sugars Sweet-tasting simple sugars Add significant osmotic pressure Add significant osmotic pressure Caloric value (~ 8 cal/serving) Caloric value (~ 8 cal/serving) Fructose: principle sugar in formula scores 20 out of 100 on glycemic index (i.e., relatively low value) Fructose: principle sugar in formula scores 20 out of 100 on glycemic index (i.e., relatively low value)

39. Composition of Isotonix Delivery System Citric acid and malic acid: Citric acid and malic acid: Adjust pH to acid range (about 3.5 – 5.0) Adjust pH to acid range (about 3.5 – 5.0) Adjust taste to “citrus” flavor Adjust taste to “citrus” flavor Minor osmotic pressure adjustment Minor osmotic pressure adjustment

40. Composition of Isotonix Delivery System Calcium sulfate: Calcium sulfate: Desiccant (takes up moisture in powder) / free-flow agent Desiccant (takes up moisture in powder) / free-flow agent Minor osmotic pressure adjustment Minor osmotic pressure adjustment Minor nutritive value Minor nutritive value

41. Composition of Isotonix Delivery System Maltodextrin: Maltodextrin: Glucose polymer has minor caloric value Glucose polymer has minor caloric value Powder — bulking agent Powder — bulking agent Prevents citric acid from reacting with potassium bicarbonate and water Prevents citric acid from reacting with potassium bicarbonate and water Thickening and suspending agent in solution Thickening and suspending agent in solution

42. Composition of Isotonix Delivery System Potassium bicarbonate: Potassium bicarbonate: Potassium and bicarbonate ions have significant osmotic pressure Potassium and bicarbonate ions have significant osmotic pressure Helps adjust and buffer pH Helps adjust and buffer pH Release of CO 2 stirs liquid Release of CO 2 stirs liquid

43. Isotonix Advantage #6 Isotonix offers an alternative to pills. Survey shows 40% of American adults have experienced difficulty swallowing pills The survey of 679 adults (513 ages 18-64, 166 age 65 and older) was funded by the US affiliate of Germany's Schwarz Pharma.

44. Isotonix Advantage #7 People with stomach and esophageal challenges benefit from Isotonix delivery. Acid reflux sufferers Bariatric patients Hiatal Hernia (stomach protrudes up through diaphragm) People who have trouble swallowing Elderly (reduced acid production)

45. Conclusion Isotonix ® product line offers customers a wide selection of nutrient combinations with the advantages of isotonic delivery. Isotonix ® is the logical choice of those seeking fast and optimal nutrient uptake.