Midterm 3 (Lecture 14) Flashcards
Phytosterols
Plant derived sterols
Structurally similar to cholesterol
NOT synthesized by humans - therefore all derived from diet
Over 40 identifier but most common are:
- beta- sitosterol
- campesterol
- stigmasterol
So similar to cholesterol that it requires advanced laboratory methods to distinguish them
Phytosterol structure
Subdivided into:
- sterols: indicates a double bond at position 5
- stanols: reduction of the double bond (no longer there), less common than sterols
Phytosterol structure very similar to cholesterol
Phytostanol simply the saturation of the double bond (no double bond)
Phytosterol vs cholesterol and intake
Cholesterol: animal foods
Phytosterol: plant foods
Both are atherogenic (produce fat plaques) but is not a concern with Phytosterol because very little is absorbed (only 1-15%)
Blood levels of.phytosterols are lower than cholesterol
Western diet: 80 mg/day
Vegetarian diet: 345 mg/day
Japanese diet: 400 mg/day
- supplementation is often only way to get sufficient amount of Phytosterols
- cholesterol lowering effects apparent with low GRAM amounts
Phytosterols/stanols and health: CVD
Numerous human clinical trials demonstrate effectiveness of Phytosterols in reducing blood lipids (primarily total and LDL cholesterol)
- blood cholesterol is a great biomarker for this
2 grams plant sterols or plant stanols per day:
- decrease plasma LDL cholesterol
- no effects on HDL cholesterol or TG
- estimated to reduce heart disease risk by 25%
Occurs in various foods, no difference between stanols and sterols - plateau at about 3 g per day
Phytosterols/stanols and CVD mechanisms important slide
Mechanism for reduction of blood total and LDL cholesterol:
- compete with cholesterol for limited space on the mixed micelles in the intestines
- more hydrophobic than cholesterol, therefore higher affinity for micelles
- displace cholesterol from the micelles into feces BUT phytosterols are NOT absorbed
- decreases cholesterol absorption by 30-50% : 1/5 dietary cholesterol and 4/5 biliary (endogenous) cholesterol
UN ABSORBED CHOLESTEROL GOES TO FECES
Phytosterol and cholesterol lowering: factors to consider
Plant sterols versus plant stanols (makes no difference though)
Dose response relationships
- dose response effect no longer apparent after 2-3 grams
Form of administration (makes no difference though etc: margarine or orange juice or capsule all same))
Does background diet matter (no)
- originally thought to only be effective as part of high cholesterol diets ; NOT the case
CVD: Phytosterols and drugs
Could the use of phytosterols replace a lipid lowering drug
- avoids side effects, costs less, but less effect
Could there be an additive or synergistic effect together (reduce dose of medications?)
STUDY:
American journal of cardiology: additive effect of plant sterols ester margarine and Cervistatin in lowering LDL cholesterol in primary hypercholesterolemia
Background:
plant sterols/stanols reduce cholesterol absorption followed by a compensatory increase in cholesterol synthesis
- thus a concurrent use of HMG-CoA reductase inhibitor may yield a synergistic effect
Methods:
4 parallel treatment arms 37-39 per group
- cervistatin plus sterol ester margarine (synergistic group)
- cervistatin plus regular margarine (additive group)
- placebo plus sterol ester margarine (additive)
- placebo plus regular margarine (control)
- 4 weeks
Results:
Magnitude of effect of plant sterols was similar
- sterol ester alone
- sterol ester plus statin
Therefore although no synergistic effect, there is an additive effect of phytosterols and this specific statin drug in blood lipids
Phytosterols/stanols in foods
Ability to incorporate phytosterols and phytostanols in food is limited
- due to low solubility in fats; ester frying them to a fatty acid increases their incorporation into fat soluble foods by up to 10 fold
- therefore often esterified with a fatty acid to increase their fat solubility
- allows for their incorporation into foods
1.6 plant sterol/stanol esters provides appximatrly 1.0 g plant sterol/stanol and 0.6 FA
most often incorporated into fatty foods
- margarine is the main one (1.7 g), cream cheese, yoghurt, dressings
- does not affect taste
- MINUTE MAID premium heart wise: 1 serving contains 1 gram of plant sterols
Phytosterols/stanols and health: cancer and immune function
Not as important/studied (overall just know there’s been some cancer reducing properties)
Prostate cancer:
- b-sitosterol inhibited the growth of prostate cancer cells
Colon cancer:
- Phytosterols inhibit colon cancer cell proliferation
In general, effects relate to:
- membrane structure
- membrane fluidity
- membrane integrity
- membrane bound enzymes
- signal transduction
- apoptosis
- specific to colon cancer: effects on neutral and acidic sterols in the colon
Immune function: some/little evidence supports a role- mechanisms of action currently being explored
Phytosterol safety: effects on fat soluble nutrients
Relates to safety
- Could they reduce absorption of key fat soluble micronutrients?
- studies do show they decrease absorption
Three key factors to consider
- TIMING
- would affect food consumed WITH the Phytosterols
- acute effect
Studies have shown
- decreased plasma carotenoids ; beta carotene by 25%, alpha carotene by 10%, lycopene
- no evidence of decreased vitamin A, K, D
Consuming at least 1 serving of vegetables high in carotenoids will maintain satisfactory blood levels during intake of Phytosterols/stanol esters
recognize three factors above are what contributes
OVERALL FAT SOLUBLE VITAMINS NOT A MAJOR CONCERN
Phytosterolemia
Inborn error of phytosterol metabolism
- Very rare condition - 40 people worldwide
- cholesterol appears normal
Metabolic abnormalities
intestinal inability to distinguish between cholesterol and plant sterols
- result is excessive plant sterol absorption (up to 65 mg/dL, 50-60 times higher than normal)
Inability to excrete sterols rapidly in bile
Reduced cholesterol 7 hydroxylase activity
- rate limiting step in bile acid synthesis
- likely due to inhibit on by sitosterol
- reduced biliary excretion of plant sterols
Reduced whole body cholesterol synthesis
- serum cholesterol levels are not highly elevated
OVERALL RESULT IS INCREASED BLOOD PLANT STEROL CINCENTRATIONS - LEADS TO PREMATURE ATHEROSCLEROSIS
Phytosterols in Canada
May 17, wpqp letter from food directorate of health Canada to industry to allow for sale of foods containing added Phytosterols/plant sterols
- completed a safety assessment
- completed a health claim assessment; reviewed scientific evidence for blood chol lowering
Foods with added Phytosterols have a long history of regulatory status
- evolved from isolated form to drug to natural health product to food
Canadian safety assessment
Phytosterols and phytostanols as a group
- toxicological assessment: lack of adverse effects at high doses BUT uncertainty for doses higher than 3 grams per day for long periods
- therefore reference safe intake concluded at: 3 g per day for adults, 1 g per day for children
(JUST DONT GO ABOVE 3)
Conclusion
- industry allowed max of 1 g free Phytosterols per serving to a list of allowed foods (spreads, mayo, margarine, yoghurt etc)
- only certain foods to avoid over consumption
- petitioner must notify the food directorate of each new product
Canadian health claim assessment
At the average intake of 2 g plant sterol per day, the effect was independent of food matrix
Most studies were done in moderately to highly hypercholesterolemic subjects
Conclusion:
- support the claim about the relationship between consumption of plant sterol enriched foods as foods and blood cholesterol lowering
- daily amount will be 2 grams
- foods that carry claim will have specific composition criteria (usually healthy foods, etc low saturated fats)
