Cholesterol Absorption:

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Cholesterol Absorption Some New Concepts and
Applications for Human Treatment Richard E.
Ostlund M.D. Professor of Medicine Division of
Endocrinology, Diabetes and Lipid
Research Washington University
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NIH / NHLBI Lifeline Technologies, Inc. ADM
Company Dr. Ostlund and Dr. Curtis Spilburg are
the Founders Of Lifeline Technologies, Inc., a
University Spinoff Company with Offices in
Chesterfield Center, MO. Lifeline Licenses
Washington University Patents in Phytosterol
Formulation.
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Model for Cholesterol Absorption
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Whole Body Cholesterol Metabolism Contrasted
with Lipoproteins in Plasma Compartment Whole
Body Cholesterol 72 g Plasma Compartment
Cholesterol 5 g
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• Controlling Cholesterol Absorption
• Regulation by Transport Proteins
• Regulation by Oxysterols
• Regulation by Phytosterols
• Regulation by drugs (Ezetimibe / Zetia)

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Phytosterols Perform Membrane Functions of
Cholesterol in Plants Structurally Similar to
Cholesterol Not Absorbed Block Cholesterol
Absorption
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Types of Phytosterols Sterols ?5-Phytosterols
TakeControl Margarine and Natural
Foods Examples Sitosterol, Campesterol,
Stigmasterol Stanols 5-?-Reduce
d Sterols (From Soy or Wood) Benecol Margarine
and Natural Foods Examples Sitostanol,
Campestanol
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• Phytosterols are Chemically Underestimated in
  Foods
• 25-35 of Phytosterols in Common Diets are
  Glycosylated and not Measured in Conventional
  Assays
• 2. Glycosylated Phytosterols May Explain LDL
  Lowering by Foods Such as Soy Protein (gt90
  Glycosylated)

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Phytosterol Absorption in Humans
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Absorbability of Steroids in Humans Determined
with Stable Isotopes Cholesterol 56 12
Sitosterol (sterol) 0.51 0.04 Sitostanol
(stanol) 0.04 0.004
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Purified Phytosterols Are Biologically Inert
Phytosterols Must be Formulated For Clinical
Use
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In Vitro Solubilization of Sitostanol Into
Artificial Bile by Lecithin
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• Bioactivity of Phytosterols
• Crystalline Phytosterols are Inert
• 2. Phytosterols are Insoluble in Water and
  Poorly-Soluble in Fat.
• Phytosterol Esters are Very Soluble in Fat.
  Benecol and TakeControl are Phytosterol Esters in
  Fat.
• 4. Phytosterols Can be Emulsified in Lecithin
  or Monoglyceride and are Bioactive. Phytosterols
  can be added to Nonfat Foods Such as Lemonade,
  EggBeaters, Yogurt.

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Activation of Phytosterols by Esterification and
Solubilization in Fat (Benecol /
TakeControl) Solubility in Triglyceride Free
Phytosterols 2 Esterified Phytosterols 20
Glycosylated Phytosterols nil
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Reduction in LDL by Phytosterols in Oil 26
Studies
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Stanol/Lecithin in Fat-Free Foods
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High Absorbers Respond Better to Phytos
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Effect of Stanol Tablets on LDL in
Statin-Treated Patients
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Are Natural Abundance Dietary Phytosterols
Important? Little Economic Interest thus
far Much Nutritional Interest
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Single-Meal Tests of Cholesterol Absorption
Defined Test Breakfast 30 g corn oil Wheat Germ
Muffin Breakfast phytosterols Deficient and
Replete Meals Differ Only by 300 mg of
phytosterols Include 30 mg Heptadeuterated
Cholesterol in Meals and Measure Cholesterol
Enrichment in Plasma after 4-5 Days.
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Increased Cholesterol Absorption After Removal
of Phytos from Muffins
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Trace Components of Food Oils Need Further Study
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Left, commercial corn oil. Right, purified corn
oil. PE, phytosterol long chain esters TG
triglycerides T, vitamin E F, phytosterol
ferulates P free phytosterols O, origin of
chromatography.
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Is Cholesterol Absorption Specific or Protein
Mediated? Reduction in Absorption Ezetimibe
54 Phytosterols 35
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Cholesterol Enantiomer ent-Cholesterol
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Absorption of ent-Cholesterol
Gavage Mixture of Tracers in Hamsters Natural
cholesterol-d7 ent-Cholesterol-d2 Measure
Excretion of Cholesterol Tracers Natural
Cholesterol Absorption 52.6 3.9 Ent-Cholesterol
Absorption 0 (lt3.0)
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• Conclusions
• 1. Cholesterol Absorption is a Key Regulatory
  Point in Lipid Metabolism and Controls the
  Reverse Transport of Cholesterol
• Phytosterols Both in Natural Foods and
  Supplements Reduce LDL Levels when Formulated
  Properly
• Phytosterols are Underestimated by Conventional
  Analytical Methods
• 4. Cholesterol Absorption is Sterically Specific
  and Not Diffusion-Mediated. Both the Enterocyte
  and the Liver Confer Specificity

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Collaborators
Xiaobo Lin Lina Ma Anne Goldberg Janet
McGill William Stenson Catherine Anderson Emily
Westover Douglas Covey Curtis Spilburg Alfred
Okeke Bruce Patterson Fong Hsu David Hachey
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