FNH 350: Lipids - Effect of dietary and lifestyle factors on blood lipids

Why is LDL called potentially “bad” cholesterol? (how can it lead to atherosclerosis?)

Usually, LDL transports cholesterol to cells, but if they aren’t taken up, they continue to circulate in the blood. The longer LDL circulates in the blood, the higher its chance of becoming oxidized which can cause macrophages to take them up and can become swollen foam cells, resulting in formation of fatty plaques that narrow blood vessels, thus causing atherosclerosis

what can atherosclerosis cause?

1. CVD

2. Heart attack

3. stroke

what is dyslipidemia?

an abnormal blood lipid profile associated with an increased risk of atherosclerosis

causes of dyslipidemia include:

1. genetic predisposition (e.g., familial hypercholesterolemia)

2. lifestyle factors

what is genetic predisposition and how can it can dyslipidemia?

• This is the increase of developing a disease due to inherited genetics

• This can include familial hypercholesterolemia, which causes low expression of LDL receptor or reduced binding capacity of LDL receptor, resulting in lower cholesterol uptake by cells

what lifestyle factors can contribute to dyslipidemia?

• Consuming calorie intake is higher than energy expenditure

• Low physical activity

• Stress

• Overweight or obesity

Which metabolic conditions can contribute to dyslipidemia?

Insulin resistance and diabetes mellitus

How is lipid status measured?

By a fasting blood test that measures lipids in plasma or serum

How often is lipid status testing recommended for healthy adults aged 40 or older?

Every 5 years

List the parameters that are measured in blood lipid profile

1. total cholesterol

2. LDL cholesterol

3. HDL cholesterol

4. triacylglycerols

What blood lipid levels are desirable to reduce atherosclerosis risk?

1. Low total cholesterol

2. Low LDL cholesterol

3. High HDL cholesterol

4. Low triacylglycerols

Which is more clinically significant: the LDL:HDL ratio or total cholesterol alone?

Seeing a lower LDL : HDL ratio is a greater validity and significance in clinical diagnosis than measuring total cholesterol

The dietary and lifestyle factors impacting lipoprotein metabolism in healthy adults include:

1. quality/composition of dietary fat

2. dietary cholesterol

3. fiber intake

4. source of protein (animal vs plant protein)

5. coffee consumption

6. lifestyle factors

How do saturated fatty acids (SFAs) generally affect LDL cholesterol?

SFAs can increase LDL cholesterol, although their effects differ depending on the specific fatty acid

SFAs are major nutritional determinants of ____

progression of coronary artery disease

LDL is now used as a surrogate marker for what?

CVD risk in intervention studies

how can SFAs increase LDL cholesterol?

1. increase SFAs causes for LDL structure to become stiffer,

2. this reduces apoB-100 interaction with LDL receptors,

3. therefore decreasing cholesterol uptake by cells

When trying to lower LDL cholesterol, what can replace sources of palmitic acid (16:0)?

Carbohydrates or stearic acid (18:0)

When considering both LDL cholesterol and blood glucose, what can replace palmitic acid and carbohydrates?

Replace palmitic acid with stearic acid, and replace carbohydrates with stearic acid or MUFAs. (e.g., follow a Mediterranean diet)

how do SFAs from dairy foods affect LDL?

do not increase LDL

How does cheese affect LDL cholesterol compared with butter of equal fat content?

Cheese intake lowers LDL cholesterol compared with butter intake of equal fat content

How do monounsaturated fatty acids (MUFAs) affect blood cholesterol?

They decrease LDL cholesterol and increase HDL cholesterol

What are sources of MUFAs?

Nuts, dairy fats, and olive oil

What were the effects of consuming 2–3 oz of pistachios daily for 4 weeks in the study?

Lower LDL and higher HDL were observed, alongside higher PUFA intake, lower SFA intake, and higher fibre intake

How do omega-6 PUFAs affect cardiovascular disease risk?

They have various beneficial effects on cardiovascular disease risk

How can omega-3 PUFAs reduce atherosclerosis risk?

They have anti-atherogenic properties. They reduce triacylglycerols, inhibit platelet aggregation, and reduce the release of pro-inflammatory cytokines from cells involved in plaque formation

Omega-3-fatty acids, have numerous various beneficial effects on what?

1. metabolic

2. cardiovascular

3. cognitive disease risk

How do trans fats affect LDL and HDL cholesterol?

Trans fat have a greater hypercholesterolemic effect compared to SFAs. They cause more extensive increase in LDL concentration and cause no change or reduction in HDL cholesterol

How does a diet rich in trans fats affect the LDL:HDL ratio compared with a diet rich in SFAs?

It results in a higher LDL:HDL ratio

What determines whether dietary cholesterol increases plasma cholesterol levels?

A person's baseline dietary cholesterol intake and whether they are a cholesterol responder

How does baseline dietary cholesterol intake affect the response to increased dietary cholesterol?

People with low baseline intake tend to have a greater increase in blood cholesterol, while those with high baseline intake tend to have a smaller increase

What proportion of people are hyper-responsive to dietary cholesterol, and why? How do most people regulate blood cholesterol when dietary cholesterol intake changes?

• About 20–30% are hyper-responsive because they do not adequately down-regulate endogenous cholesterol synthesis when dietary cholesterol increases

• About 70% adjust their endogenous cholesterol synthesis in response to dietary cholesterol intake, helping regulate blood cholesterol levels

How does fibre intake lead to a reduction of plasma cholesterol?

1. Insoluble fibers speed up movements in GI and soluble fibers reduce mixing of chyme with digestive enzymes (gels - ‘physical barrier’).

   • Both effects lead to increase bile/cholesterol excretion, leading the liver to take LDL cholesterol from the blood to produce new bile.

2. Bile composition changes

   • liver pulls LDL from blood for new bile production, which inhibits HMG CoA reductase enzyme required for cholesterol synthesis

3. Production of short chain fatty acids by colonic fermentation of soluble fibers → inhibits cholesterol + fatty acid synthesis

4. Replacement of high-fat foods

How can animal and plant protein sources differ in their effects on blood cholesterol?

Animal protein sources may be associated with increased cholesterol due to their saturated fat content that contain cholesterol, while plant protein sources may lower cholesterol because they contain plant sterols and fibre

How can coffee affect LDL cholesterol?

Coffee contains cafestol, which stimulates an increase in LDL cholesterol

How does coffee preparation affect its cafestol content and LDL cholesterol?

Unfiltered coffee, such as French press coffee, contains more cafestol and can increase LDL cholesterol, while paper-filtered coffee removes most cafestol

where are FAs synthesized?

cytosol

How are FAs synthesized?

FAs are synthesized by using an enzyme system called fatty acid synthase system which consists of condensing enzyme and acyl carrier protein. Acetyl-CoA is used as a substrate and palmitic acid (16:0) (SFA) is the final product

what can palmitic acid (16:0) be elongated to form?

Palmitic acid can be elongated to form stearic acid (18:0) which is also a SFA

What happens when palmitic acid and stearic acid undergo Δ9 desaturation?

Palmitic acid (16:0) forms palmitoleic acid (16:1), while stearic acid (18:0) forms oleic acid (18:1). Both products are MUFAs.

From which end is the Δ9 desaturation position counted?

From the carboxyl end of the fatty acid

Why can't humans synthesize omega-3 and omega-6 fatty acids from scratch?

Humans lack Δ12-desaturase and Δ15-desaturase, which are needed to introduce the double bonds that produce these fatty acids. Thus, these FAs are considered essential because we can only obtain them from our diet.

What are the essential fatty acids for humans, and what are their abbreviations?

1. Alpha-linolenic acid (ALA), an omega-3 fatty acid

2. linoleic acid (LA), an omega-6 fatty acid

what does omega-3 fatty acid function in?

1. Brain and cognitive development

2. Cardiovascular health

3. Inflammation control

What are dietary sources of ALA (omega-3)?

Flaxseed, walnuts, canola oil, and fish.

Omega-6 is also called linoleic acid (LA)

Found in vegetable oils

What is a dietary source of LA (omega-6)?

vegetable oils

What are EPA and DHA, and how can the body produce them?

They are long-chain omega-3 fatty acids that the body can produce from omega-3 FA using desaturase and elongase enzymes

Why are EPA and DHA not considered essential fatty acids?

The body can convert ALA into EPA and DHA, although the conversion rate is low (2-5%)

How does omega-6 intake affect the conversion of ALA into EPA and DHA?

Omega-3 and omega-6 pathways compete for the same desaturase and elongase enzymes. Higher omega-6 intake can therefore limit the conversion of ALA into EPA and DHA

What is the ideal omega-6:omega-3 ratio from a metabolic perspective?

Ideally consume 1:1 (omega-6 : omega-3)

What omega-6:omega-3 ratio is recommended for dietary intake?

Less than 4:1

What is the typical omega-6:omega-3 ratio in the Western diet?

Approximately 15:1

Why is the dietary omega-6:omega-3 ratio important?

Omega-3 and omega-6 fatty acids compete for the same enzymes, so higher omega-6 intake can reduce the conversion of ALA into EPA and DHA

Why is regular fish consumption recommended?

Regular fish consumption is recommended because fish provides EPA and DHA, which support cardiovascular health

How much fish is recommended, and what daily EPA and DHA intake does this provide?

At least two servings of fish per week, providing approximately 0.3–0.45 g of EPA and DHA per day

How may omega-3 fatty acids reduce cardiovascular disease (CVD) risk?

1. Cause vasodilation, which helps regulate blood pressure.

2. Provide anti-arrhythmic effects, which help stabilize heart rhythm

3. Reduce inflammation and triacylglycerol (TAG) concentrations

what are eicosanoids?

Eicosanoids are hormones that function as signaling molecules derived from the oxidation of 20-carbon FAs

What are the functions of eicosanoids that are formed from the omega-3 pathway?

• In this pathway, we can form EPA, which can become:

  • Prostaglandin, which provides anti-inflammatory effect

  • Leukotrienes, which provides anti-inflammatory effect

• In this pathway, we can form DHA, which can become:

  • Resolvins, which provides anti-inflammatory effect

• Overall effects: anti-arrhythmic, anti-inflammatory, and vasodilation

What are the functions of eicosanoids that are formed from the omega-6 pathway?

• In this pathway, we can form arachidonic acid, which can become:

  • Prostaglandin, which provides pro-arrhythmic effect

  • Leukotrienes, which provides pro-inflammatory effect

• Overall effects: pro-arrhythmic, pro-inflammatory, and vasoconstriction

Describe how PUFAs may impact cardiovascular disease risk.

1. Reduce triacylglycerol (TAG) concentrations.

2. Promote vasodilation, helping regulate blood pressure.

3. Provide anti-arrhythmic effects, helping stabilize heart rhythm.

4. Reduce inflammation by decreasing the release of pro-inflammatory cytokines involved in plaque formation.

5. Inhibit platelet aggregation, reducing blood clotting