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Cholesterol Absorption:

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Cholesterol Absorption: Some New Concepts and Applications ... Company with Offices in Chesterfield Center, MO. ... Wheat Germ Muffin Breakfast phytosterols ... – PowerPoint PPT presentation

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Title: Cholesterol Absorption:


1
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
2
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.
3
Model for Cholesterol Absorption
4
Whole Body Cholesterol Metabolism Contrasted
with Lipoproteins in Plasma Compartment Whole
Body Cholesterol 72 g Plasma Compartment
Cholesterol 5 g
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6
  • Controlling Cholesterol Absorption
  • Regulation by Transport Proteins
  • Regulation by Oxysterols
  • Regulation by Phytosterols
  • Regulation by drugs (Ezetimibe / Zetia)

7
Phytosterols Perform Membrane Functions of
Cholesterol in Plants Structurally Similar to
Cholesterol Not Absorbed Block Cholesterol
Absorption
8
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9
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
10

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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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15
Phytosterol Absorption in Humans
16
Absorbability of Steroids in Humans Determined
with Stable Isotopes Cholesterol 56 12
Sitosterol (sterol) 0.51 0.04 Sitostanol
(stanol) 0.04 0.004
17
Purified Phytosterols Are Biologically Inert
Phytosterols Must be Formulated For Clinical
Use
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19
In Vitro Solubilization of Sitostanol Into
Artificial Bile by Lecithin
20
  • 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.

21
Activation of Phytosterols by Esterification and
Solubilization in Fat (Benecol /
TakeControl) Solubility in Triglyceride Free
Phytosterols 2 Esterified Phytosterols 20
Glycosylated Phytosterols nil
22
Reduction in LDL by Phytosterols in Oil 26
Studies
23
Stanol/Lecithin in Fat-Free Foods
24
High Absorbers Respond Better to Phytos
25
Effect of Stanol Tablets on LDL in
Statin-Treated Patients
26
Are Natural Abundance Dietary Phytosterols
Important? Little Economic Interest thus
far Much Nutritional Interest
27
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.
28
Increased Cholesterol Absorption After Removal
of Phytos from Muffins
29
Trace Components of Food Oils Need Further Study
30
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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32
Is Cholesterol Absorption Specific or Protein
Mediated? Reduction in Absorption Ezetimibe
54 Phytosterols 35
33
Cholesterol Enantiomer ent-Cholesterol
34
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

38
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
39
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