4. NORMAL CHOLESTEROL
METABOLISM
Synthesis
Primary synthetic sites are extrahepatic, but liver is key
regulator of homeostasis
Absorption
Largest source is biliary secretion, not diet.
Normal absorption: 50%
For cholesterol to be absorbed it must:
undergo hydrolysis (de-esterification by esterases)
be incorporated into micelles
be taken up by cholesterol transporter
be re-esterified and incorporated into chylomicrons
9. NORMAL TRIGLYCERIDE
METABOLISM
Absorption
Dietary triglyceride must be hydrolyzed to fatty acids,
mono-glycerides and glycerol prior to absorption.
Fatty acids must partition to micellar phase for
absorption.
For transport, triglyceride must be reconstituted from
glycerol and fatty acid and incorporated into
chylomicrons.
22. Therapeutic Lifestyle Changes
A dietary pattern recommended by
NCEP/ATP III, to control
hypercholesterolemia.
It also includes Weight control, Physical
activity, and not smoking
TLC are recommended even if, under
cholesterol lowering drugs.
23. Therapeutic Lifestyle Changes
Nutrient Composition of TLC Diet
Nutrient Recommended Intake
Saturated fat Less than 7% of total calories
Polyunsaturated fat Up to 10% of total calories
Monounsaturated fat Up to 20% of total calories
Total fat 25–35% of total calories
Carbohydrate 50–60% of total calories
Fiber 20–30 grams per day
Protein Approximately 15% of total calories
Cholesterol Less than 200 mg/day
Total calories (energy):
Balance energy intake and expenditure to maintain desirable body
weight/prevent weight gain
ATP III lipid Guideline
24. Reinforce reduction
in saturated fat and
cholesterol
Consider adding
plant stanols/sterols
Increase fiber intake
Consider referral to
a dietitian
Initiate Tx for
Metabolic
Syndrome
Intensify weight
management &
physical activity
Consider referral
to a dietitian
6 wks 6 wks Q 4-6 mo
Emphasize
reduction in
saturated fat &
cholesterol
Encourage
moderate physical
activity
Consider referral to
a dietitian
Visit I
Begin Lifestyle
Therapies
Visit 2
Evaluate LDL
response
If LDL goal not
achieved, intensify
LDL-Lowering Tx
Visit 3
Evaluate LDL
response
If LDL goal not
achieved, consider
adding drug Tx
A Model of Steps in
Therapeutic Lifestyle Changes (TLC)
Monitor
Adherence
to TLC
Visit N
ATP III lipid Guideline
25. LDL–C Lowering
1. Intake of vegetables, fruits, and whole grains; includes low-
fat dairy products, poultry, fish, legumes, non-tropical
vegetable oils and nuts; and limits intake of sweets, sugar-
sweetened beverages and red meats.
Adapt this dietary pattern to appropriate calorie requirements,
personal and cultural food preferences, and nutrition therapy for
other medical conditions (including diabetes mellitus)
Achieve this pattern by following plans such as the DASH dietary
pattern, the USDA Food Pattern, or the AHA Diet
2. 5% to 6% of calories from saturated fat
3. Reduce percent of calories from saturated fat
4. Reduce percent of calories from trans fat
2013 AHA/ACC Lifestyle Management Guideline
26. BP Lowering
1. Intake of vegetables, fruits, and whole grains; includes low-fat dairy
products, poultry, fish, legumes, non-tropical vegetable oils and nuts;
and limits intake of sweets, sugar-sweetened beverages and red meats.
Adapt this dietary pattern to appropriate calorie requirements, personal
and cultural food preferences, and nutrition therapy for other medical
conditions (including diabetes mellitus)
Achieve this pattern by following plans such as the DASH dietary
pattern, the USDA Food Pattern, or the AHA Diet
2. Lower sodium intake
a. No more than 2,400 mg of sodium/day;
b. 1,500 mg/day is desirable, even greater reduction in BP;
c. Reduce intake by at least 1,000 mg/day since that will lower BP, even if
the desired daily sodium intake is not yet achieved.
3. Combine the DASH dietary pattern with lower sodium intake
2013 AHA/ACC Lifestyle Management Guideline
29. PHYSICALACTIVITY
Lipids
1. Aerobic physical activity to reduce LDL–C and non-HDL–
C:
3 to 4 sessions a week, lasting on average 40 minutes per session,
and involving moderate-to-vigorous intensity physical activity.
BP
1. Aerobic physical activity to lower BP:
3 to 4 sessions a week, lasting on average 40 minutes per session,
and involving moderate-to-vigorous intensity physical activity
2013 AHA/ACC Lifestyle Management Guideline
30. The Bad Fats
Saturated Fat
Solid at room temperature.
Found mostly in meats, dairy and tropical oils
(palm oil, cocunut oil).
Increases LDL and decreases HDL
It raises blood cholesterol more than anything else
in the diet
To lower blood cholesterol:
Keep your saturated fat intake to less than 7% of your
calories for the day.
31. The Bad Fats
Trans unsaturated fats
Formed when liquid oils are made into solids
by the process of hydrogenation
Trans fats extend shelf life and help
consistency
Trans fats raise LDL cholesterol and
decrease HDL cholesterol.
Limit Trans fats to <2 gm/day
33. Dietary Effects on Lipids
Several studies showed
Significant correlation between saturated fat intake and
blood cholesterol levels.
Meta-analysis of RCTs showed
Lowering saturated fat and cholesterol reduced total and
LDL-C by 10-15%
For every 1% increase in intake of saturated fat, blood
cholesterol increases 2 mg/dl
Soluble fiber intake may provide additional LDL-C
response over that of a low-fat diet.
34. Dietary Cholesterol
The cholesterol in diet raises the cholesterol
level in the blood – but not as much as
saturated fat
The two are often found in the same foods.
Eg. Eggs, Beef, Poultry, Cheese, Milk,
Fish/shellfish.
36. Dietary cholesterol
In a 2013, meta-analysis of 8 prospective
cohort studies (4,74,000)
No association between egg consumption and
risk for coronory heart disease or stroke
The evidence indicates that for most
individuals, only minor emphasis on
reducing dietary cholesterol (eg from eggs) is
needed.
37. Dietary Fibre?
Soluble Fibre
-Lowers LDL cholesterol
-Aim for 7-13 grams per
day
Insoluble Fibre
- Relieves and prevent
constipation
• Psyllium
• Legumes
• Barley
• Oats, oatbran, oatmeal
• Some fruits
• Some vegetables
• Wheat bran
• Whole grain foods
• Whole fruits and
vegetables
38. Good Fats:
Use in Moderation
Fat Type Sources Effect
Poly-
Unsaturated
Omega-3 fat
Seafood and fatty fish (mackerel, sardines,
salmon, herring, trout), wild game
Canola oil, ground or crushed flaxseed,
flax oil, hemp seed and oil, and non-
hydrogenated margarine made with these
oils.
Walnuts, pumpkins seeds, and soybean
products.
Functional Foods: Omega-3 eggs, Omega-
Pro liquid eggs, omega-3 milk, omega-3
yogurt, omega-3 cheese
Decreases
triglycerides
May
increase
HDL
Thins the
blood
Many heart
health
39. Good Fats:
Use in Moderation
Fat Type Sources Effect
Poly-
unsaturate
d
Omega-6 fat, Omega-9 fat
Oils: grapeseed, corn, safflower,
sunflower, soybean.
Sunflower seeds, wheat germ, non-
hydrogenated margarine made with these
oils.
Decrease
s LDL
May
decrease
HDL
Mono-
unsaturate
d
Oils: olive, canola, peanut, sesame.
Nuts: chestnuts, hazelnuts, pistachios,
almonds, macadamias, pecans, peanuts,
and their butters.
Other: fish, seafood, olives, avocado,
mayonnaise, sesame seeds, non-hydrog.
margarine (with these oils)
Decrease
LDL
May
increase
HDL
40. Los Angeles VA study
846 men in Veterans Home, 5-8 years, 1969
Groups randomized to diets in which
2/3 of fat given either as vegetable oil (corn,
cottonseed, safflower, soybean) or animal fat
Saturated fat 11% vs. 18%,
Polyunsaturated fat 16% vs. 5% of calories
31% decrease in CVD endpoints
41. Oslo Diet Heart Study
412 men (30-64yr) with CHD, 5 year study, 1970
Treatment group randomized to
low saturated fat (8.4% of calories), low cholesterol (264
mg/day), and high polyunsaturated fat (15.5%) diet
Serum cholesterol reduced 14%
33% reduction in MI,
26% decrease in CHD mortality
Dietary counseling every 3 months
42. Stanford Coronary Risk
Intervention Project (SCRIP)
300 men and woman with CHD, baseline and 4
year follow-up angiograms,1994
Randomized to
<20% fat, <6% saturated fat, <75 mg cholesterol/day,
and exercise (Rx group) vs
Usual care
LDL-C and TG decreased 22% and 20%, and HDL-
C increased 20%
Rx group had 47% less progression than control
group, P<0.02
43. Lyon Diet Heart study
302 men and women with CHD, 1999
Treatment group randomized to
low saturated fat, high canola oil margarine (5% alpha
linolenic, 16% linoleic, and 48% oleic acid, also 5%
trans)
46 month follow-up
65% lower CHD death rate in treatment group
(6 vs. 19 death)
44. Benefits of fish oil
supplementation
Diet and Reinfarction Trial (DART) 1989
2033 men with CHD increased intake of fish or use of 2
fish oil caps/day
reduced CHD mortality 29% over 2 years
GISSI-P 1999
11324 men and woman with CHD, use of 1 gm/day of
omega-3 PUFA within 3 months of MI
decreased CVD events including mortality by 15% over
3.5 year follow up.
45. Nuts, Soy, Phytosterols, Garlic
Nurses’ Health Study:
five 1ounce servings of nuts per week a/w
40% lower risk of CHD events
Metaanalysis of 38 trials of soy protein, (NEJM 1995)
47g/d intake
lowered Total, LDL-C, and TG, 9%, 13%, and 11%
Phytosterol-supplemented foods (e.g., stanol ester margarine)
lowers LDL-C avg. 10%
Meta-analysis of garlic studies (1/2 to 1 clove per day) 1993
9% total cholesterol reduction
No advantages seen in recent metaanalysis done in 2009
46. Carbohydrates
Diets low in refined carbohydrates is best
Choose whole grain breads, cereals, pasta, rice
and keep intake moderate (not too much.)
Eat more vegetables, and some fruits such as
apples and pears.
48. Reisell et al., Am J Clin Nutr 1966;19:84
Fast for average 5 days, then consume low CHO diet.
Effect of Carbohydrate Restriction on
Carbohydrate-induced
Hypertriglyceridemia
49. Dietary Effects on Thrombosis
Omega-3 fatty acids
antithrombogenic and antiarrhythmic effects,
decreased platelet aggregation, and
lower triglycerides
50. Healthy Eating
Cholesterol
Reduce the total amount of fats and oil
Limit egg yolk to not more than 2-3 per week
Limit your use of organ meats (e.g. liver, heart,
kidney) and of shell fish (e.g. shrimp, lobster,
conchs)
Avoid foods that are high in saturated fat –
bacon, sausages, pastry, gravies, salad dressings,
mayonnaise
Limit use of red meats
instead use more fish, chicken, turkey or dried peas,
beans, lentils
51. Healthy Eating
Cholesterol
Trim all visible fat from meats
remove skin and pour off the fat that melts during cooking
Use low fat and skim milk products
instead of full cream milk and dairy products
Include foods that are high in fibre
e.g. dried peas and beans, nuts, whole wheat bread, whole grain
cereals especially oats, oat bran, fresh fruits and vegetables and
ground provisions.
Choose fats wisely - use vegetable oils and margarines that
are high in polyunsaturated fats
e.g. olive oil, canola oil, corn oil, sunflower oil
52. Healthy Eating
Cholesterol
Improving the diet is the most effective way to
maintain good cholesterol levels
IMPORTANT FACT:
It IS NOT the cholesterol found in foods that causes
high blood cholesterol.
It IS the FAT in food, particularly the
SATURATED FAT and TRANS FAT that raises
blood cholesterol
54. References
Updates on the Management of Dyslipidemia
A Review of the 2013 ACC/AHA
Cholesterol Guidelines
Dyslipidemia ATP III 2004
Lippincott biochemistry, 6th
edition
The AHA 2013 Diet and Lifestyle
Recommendations
Editor's Notes
HMG (Hydroxy-methyl-glutaryl)
ATP-binding cassette (ABC) transporters G5/G8
Sitosterolemia (&quot;Phytosterolemia&quot;) is a rare autosomal recessively inherited lipid metabolic disorder. It is characterized by hyperabsorption and decreased biliary excretion of dietary sterols (including the plant phytosterol beta-sitosterol).
Healthy persons absorb only about 5% of dietary plant sterols, but sitosterolemia patients absorb 15% to 60% of ingested sitosterol without excreting much into the bile.
The phytosterol campesterol is more readily absorbed than sitosterol.
Sitosterolemia patients develop hypercholesterolemia, tendon and tuberous xanthomas, premature development of atherosclerosis, and abnormal hematologic and liver function test results
Eicosa-pentaenoic-acid (EPA)
Five subfractions of HDL. Largest (most effective in cholesterol removal) to smallest (least effective), the types are 2a, 2b, 3a, 3b, and 3c
Lecithin-cholesterol-acyl-transferase (LCAT), also called (phosphatidylcholine-sterol-O-acyl-transferase) is an enzyme that converts free cholesterol into cholesteryl-ester (a more hydrophobic form of cholesterol)
Tangier disease (Familial alpha-lipoprotein deficiency or Hypo-alpha-lipoproteinemia) is a rare inherited disorder characterized by a severe reduction in the amount of HDL.
Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins.
NCEP (national cholesterol education program)
ATP (adult treatment program)
Dietary Approaches to Stop Hypertension (DASH)
However, some patients who either consume very large amount of cholesterol or whose serum LDL-C response to moderate cholesterol intake is unfavourable, may benefit from from reduction in their cholesterol intake.
VA (veteran administration)
Gruppo Italiano per lo Studio della Sopravvivenza nell&apos;Infarto Miocardico (GISSI)