Fiber and Cholesterol

HMG CoA reductase is the rate limiting enzyme for cholesterol synthesis
cholesterol de novo synthesis starts with acetyl CoA
liver is a major site for cholesterol synthesis
liver uses cholesterol to make bile acids
fecal disposal of bile acids is the major route for cholesterol to leave our body

study question:

synthesized by liver cells from cholesterol
- 7a-hydroxylase is the rate limiting enzyme
serve as emulsifiers/biological detergent
primary bile acids
- cholic acid
- chenodeoxycholic acid
conjugated (primary) bile acids
- conjugated with glycine (75%), taurine (25%)
- conjugation improves the ability to make micelles

study question:

secondary bile acids
- produced by colon bacteria from primary bile acids
higher [bile acids] = higher risk for colon cancer
secondary bile acids thought to promote colon cancer
fiber interferes with synthesis of secondary bile acids and increases fecal excretion

study questions:

what is the difference between primary and secondary bile acids?
other than increasing fiber, what other dietary changes may help decrease cholesterol and secondary bile acid production?

Dietary fiber

refers to NON-DIGESTIBLE carbohydrates and lignin that are intact and intrinsic in plants

Functional Fiber

consists of non-digestible carbohydrates that have been isolated, extracted, or manufactured and have been shown to have beneficial physiological effects in humans

In general:

gastric emptying and satiety

contributes to satiety
- nondigestible --> bulk --> GI distention --> feeling of fullness
viscosity and gel-forming slow gastric emptying
more processing in the stomach
more uniform presenetation in the small intestine

absorption in the small intestine (positive)

improves glucose tolerance
lower serum cholesterol
- related to attenuated glucose surge
- insulin activates HMG CoA reductase
- lower glucose surge --> lower insulin --> HMG CoA reductase is less active

absorption in the small intestine (negative)

nutrients may miss the best absorption sites
some minerals may bind to fiber and are not absorbed as easily
- adsorption
- negatively charged groups on polysaccharides bind to positively charged ions

study question:

Fermentation by bacteria in the colons
- provision of energy
  - butyrate provides energy for colon epithelial cells
  - propionate for liver (may inhibit HMG CoA reductase)
  - acetate for nonhepatic tissue
  - most acetate to cardiac muscle and skeletal muscle
- lowers pH in colon
  - free bile is less soluble
  - less secondary bile acids produced
  - Ca2+ more soluble
- fermentation also:
  - produces lactate, acetate (C2), propionate (C3), butyrate (C4)
  - generates hydrogen, CO2, CH4
  - increases water and Na absorption in colon
  - stimulates mucosal cell proliferation
Dilution potential
- nonfermentable fibers are effective bulking agents and fecal dilutors
- decreased carcinogen concentration
- fiber intake associated with lower colon cancer incidence

90-95% of bile acids and salts reabsorbed in the ileum by active transport
- goes back to liver, reconjugate, and secreted into duodenum
- remaining excreted in feces
important implications
- if circulation is interrupted, more bile acids will be excreted
- because bile acids are made from cholesterol, now more cholesterol will be used to make new bile acids
- decreases blood cholesterol

increased fecal excretion of bile and cholesterol --> less bile acids and cholesterol go back to liver --> more LDL removed from blood circulation and more cholesterol used for bile acid synthesis
altered bile acid profile inhibits HMG CoA reductase
SCFAs from fiber fermentation inhibit cholesterol synthesis; propionate enters liver and inhibits HMG-CoA reductase

study question:

if an 8th grader asked you to describe the relationship between fiber and cholesterol, how would you describe it?