Phytosterols

Question 1

What are phytosterols? Where are they found?

Answer 1

• Plant-derived sterols that are similar to cholesterol

- Not synthesized by humans (only found in plant foods such as veggie/tree oils)

Question 2

What are the 3 most common phytosterols?

Answer 2

Β-sitosterol (24-ethylcholesterol)

Campesterol (24-methylcholesterol)

Stigmasterol (Δ22-24-ethylcholesterol)

Question 3

What are the 2 types of phytosterols? Explain the differences.

Answer 3

1. Sterols (Δ5-sterols)
   - Has double bond at position 5
2. Stanols
   - Has 5 α-reduction of double bond (saturated version of sterols)
   - Less common in foods than sterols
   - More often is a product of gut bacterial degradation of sterols
   - Can also be produced by hydrogenating sterols

Question 4

Explain the similarities and differences between cholesterol and phytosterols.

Answer 4

• Need high performance methods to distinguish phytosterols from cholesterol
• Cholesterol is found in animal foods only (eg. potato chips would have no cholesterol!)
• Both are atherogenic (can form plaque in our arteries)
• Phytosterols are not a problem as it is only 1-15% absorbed
• Blood levels of phytosterols are 200x lower than cholesterol

Question 5

Which diets have the highest intakes of phytosterols? Why is this relevant to know?

Answer 5

• Western < Vegetarian < Japanese Diet
• Even with the Japanese diet, we are only consuming mg amounts
• Cholesterol-lowering effects are present with low GRAM amounts

Question 6

What are the 3 main areas of focus?

Answer 6

1. CVD
2. Cancer
3. Immunity

Question 7

What is the biomarker of CVD risk?

Answer 7

LDL-cholesterol is a well-studied biomarker of CVD risk

Question 8

What do studies show about phytosterols and CVD?

Answer 8

• Many studies show effectiveness of phytosterols in reducing cholesterol
• 2 g of plant sterols/stanols lowered plasma LDL cholesterol (and therefore CVD risk) and had no effect on HDL or TG
• There is a dose-dependent effect on lowering LDL-cholesterol, but plateau past 3g/day
• No difference between plant sterols and stanols; but should be esterified
• Background diet does not matter; thought to be effective if consumed as part of a high fat meal that stimulates bile (endogenous cholesterol), but not necessary
• Form of administration does not matter (whether in margarine or a capsule)

Question 9

What is the mechanism at which phytosterols improve CVD?

Answer 9

• Phytosterols compete with dietary and endogenous (in our intestine from bile) cholesterol for limited space on mixed micelles in intestine
• More hydrophobic than cholesterol and has a higher affinity for micelles
• Displaces cholesterol from micelles which end up in feces
• However, they have no capacity to get absorbed so goes to feces

Question 10

What percentage of each type of cholesterol is reduced by phytosterols?

Answer 10

• Decreases cholesterol by 30-50%
• 20% dietary cholesterol ⟶ doesn’t really decrease dietary cholesterol which is good because it doesn’t really raise blood cholesterol anyway
• 80% (mainly) endogenous/biliary cholesterol

Question 11

Discuss the possibility of replacing lipid-lowering drugs with phytosterols.

Answer 11

• Avoid side effects and reduce cost
• HOWEVER, effect is less with plant sterols
• Might be able to have additive or synergistic (power of overall effect is more than just additive) effect with drugs and plant sterols

Question 12

What did the American Journal of Cardiology show in regards of additive/synergistic effects of drugs and phytosterols for CVD?

Answer 12

• American Journal of Cardiology showed an additive effect in lowering LDL cholesterol with drugs (inhibits HMG-CoA reductase that synthesizes cholesterol) and plant sterols (reduce cholesterol absorption, increases cholesterol synthesis and the above enzyme)
• Phytosterols may be used in combination with drugs to lower side effects

Question 13

What do we know about phytosterols and cancer right now?

Answer 13

• Unclear on relevance; we don’t absorb phytosterols, so how can it get to the tumour?
• Effects relate to membrane integrity, signal transduction, and apoptosis
• Cell culture studies show inhibition of prostate and colon cancer cells

Question 14

Where are phytosterols incorporated into in foods?

Answer 14

• Most often incorporated into fatty foods (margarine, cream cheese, salad dressing, yogurt)
• Does not affect the taste
• Benecol SoftGels is a capsule form with a higher dose

Question 15

What do we do to phytosterols to help incorporate them into foods?

Answer 15

• Ability to incorporate phytosterols into foods is limited due to low solubility in fats
• Therefore, often esterified with fatty acid to increase fat solubility
• When you consider the dose of plant sterol esters, you have to consider the weight of the fatty acid
• Often we are overestimating the biologically relevant dose (ie. flavonoid glycosides have carb moiety)

Question 16

What are the safety concerns regarding phytosterols in food? What are the conclusions?

Answer 16

• Studies show that phytosterols decrease absorption of fat-soluble micronutrients
• Decreases β-carotene, lycopene, vitamin E
• NOT vitamin A (not carried by LDL), vitamin K, or vitamin D
• Timing is a factor (affect foods consumed with phytosterols)
• However, Health Canada concluded it is only an acute effect
• Consuming >1 serving of vegetables high in carotenoids will maintain satisfactory blood levels during intake of sterol esters
• NO other side effects observed!

Question 17

What is phytosterolemia?

Answer 17

• Rare condition (only 40 patients worldwide)
• Inborn error of phytosterol metabolism
• Body is unable to distinguish between cholesterol and plant sterols
• Phytosterols in foods are absorbed ⟶ premature atherosclerosis
• Cholesterol absorption appears to be normal
• Patient cannot excrete sterols in the bile
• Reduced cholesterol 7-α-hydroxylase acitivity (less bile synthesis and therefore biliary excretion of plant sterols)
• Serum cholesterol levels are not highly elevated; reduced cholesterol synthesis

Question 18

When did phytosterols start being incorporated into foods in Canada?

Answer 18

• Started being incorporated into foods products in Canada since 2010 (thanks to Unilever)
• Before, was treated as a drug

Question 19

What did the Canadian safety assessment show?

Answer 19

• Safety assessment showed lack of adverse effects at doses as high as 6-8 g/d
• To be conservative, reference safe intakes were concluded at 3g/d for adults and 1g/d for infants (uncertain about any higher for long periods of time)
• Industry is allowed to add 1g free phytosterols per serving to an allowed list of foods
• Also, government must be informed of each new food product

Question 20

What did the Canadian health claim assessment show? What criteria must foods meet before making a health claim about phytosterols?

Answer 20

• Health claim assessment showed 8.8% LDL-cholesterol reduction with efficacy dose of 2g/d
• At this dose, effect was independent of food matrix
• Supports the claim about relationship between plant sterols and lower cholesterol
• Foods that carry claim must have composition criteria (ie. low saturated fat)