14. LIPIDS & EFAs Flashcards
This module covers: • The structural characteristics of lipids. • The dietary sources, functions, bioavailability and metabolism of lipids, including essential fatty acids (EFAs). • Deficiency states and the therapeutic uses that apply to EFAs.
1
Q
What is the body fat composition of a lean healthy man compared to that of a severely obese individual?
A
The body of a lean healthy man is composed of roughly 16% fat, while the lipid content in severe obesity can account for up to 70% (or 57 kg) of body weight, mostly in adipocytes.
2
Q
Why were fats credited with heart disease in recent times? What did it lead to?
A
In the 1950s, Ancel Keys declared that eating a high saturated fat diet would increase serum cholesterol and consequently lead to heart disease.
The American Heart Association (AHA) then recommended a diet low in total fat, especially saturated fat and cholesterol, and high in carbohydrates from grains, substituting animal fats for seed oils. This also resulted in the introduction of statins - one of the pharmaceutical industry’s most profitable drugs.
3
Q
Name THREE functions of white adipose
tissue (WAT)?
A
- The secretion of hormones, growth factors, enzymes and cytokines
- the protection of organs
- a form of energy storage
- insulation to protect against temperature extremes.
4
Q
Name FIVE forms of lipids in the body.
A
- Individual fatty acids.
- Triglycerides.
- Phospholipids — in every cell membrane.
- Cholesterol and steroid-based compounds (e.g. oestrogen).
- Sphingolipids — found in nerve cell membranes, e.g. myelin.
- Glycolipids — involved in cell identity (like a cell ‘passport’).
- Cerebrosides — glycosphingolipids found in the brain.
- Fat-soluble vitamins — A, D, E, K.
5
Q
What are the functions of lipids?
A
- Energy (ATP) production — each gram of fat supplies the body with about 9 calories.
- Storage of energy reserves — fats are a more efficient form of storage energy than carbohydrates or proteins, so the body stores any excess energy as fat.
- Cell membrane structure — phospholipids and cholesterol stabilise cell membranes, whilst allowing a degree of fluidity which is crucial to the function of every cell.
- Thermal insulation in subcutaneous tissue and protection around organs.
- Steroid hormones — progestogens, androgens, glucocorticoids, mineralocorticoids and oestrogens are derived from cholesterol.
- Formation of eicosanoids — signalling molecules involved in a range of processes such as blood coagulation and inflammation.
- Growth and development — the brain is rich in arachidonic acid (AA) and docosahexaenoic acid (DHA).
- Constituents of nervous tissue structure (sphingomyelin).
- Aid to cell-signalling processes.
- Required for the absorption of fat-soluble vitamins.
6
Q
What is the chemical structure of fatty acids?
A
Fatty acids are hydrocarbon chains with an acid group at one end and a methyl group at the other.
7
Q
What is the difference in number of carbons between short-chain, medium-chain, long-chain and very long chain fatty acids?
A
Short-chain fatty acids - up to 5 carbons.
Medium-chain fatty acids - between 6–12 Cs; can travel directly to the liver where they can be used to create energy or ketones.
Long-chain fatty acids - between 14–22 Cs.
Very long-chain fatty acids - > 22 Cs; are used to build cell membranes.
8
Q
How are short-chain fatty acids (SCFAs) produced? What are the most common SCFAs?
A
SCFAs are produced when dietary fibre is fermented in the colon.
Acetate, propionate and butyrate are the most common SCFAs.
9
Q
Which short-chain fatty acid is particularly important for colon health and why?
A
- Butyrate is particularly important for colon health because it is the primary energy source for colonocytes. It supports the intestinal tight junctions.
- Butyrate is thought to have an anti-inflammatory effect on the colon.
10
Q
The omega-6 fatty acid, arachidonic acid, is referred to as 20:4 w6. What does it signify?
A
The omega system uses the number of carbon atoms, the number of double bonds, and the number of carbons from the omega end to the first carbon in the double bond.
11
Q
What is hydrogenation and its impact on health?
A
Hydrogenation is the process by which hydrogen atoms are added to unsaturated fats and oils.
When oils are made into solid spreads, hydrogenation turns the natural fatty acid into unnatural forms (i.e. trans fats) which are damaging to health.
12
Q
Describe the structure of saturated fatty acids.
A
Contain no C-C double bonds. All the carbons are completely saturated with hydrogen bonds. Solid at room temperature.
13
Q
Describe unsaturated fatty acids structure
A
Contain one or more double bonds between carbons. Liquid at room temperature.
14
Q
Monounsaturated fatty acids structure
A
Have one double bond in the chain.
15
Q
Polyunsaturated fatty acids structure
A
Have several double bonds
16
Q
Why is the number of double bonds in a fatty acid important?
A
The more double bonds there are in a fatty acid, the less stable it is, increasing susceptibility to oxidation.
17
Q
How are unnatural trans fatty acids produced and in which types of foods are they typically found?
A
Unnatural trans fatty acids are produced by high temperatures and hydrogenation. They are found in margarine, processed foods and refined vegetable oils.
18
Q
What are the effects of trans fats on the body?
A
- Trans fats stiffen cell membranes, making them prone to oxidation. This also alters their protective action and permeability, impeding normal cell function.
- Trans fats alter blood triglyceride and cholesterol profiles and are linked to an increased risk of cardiovascular disease, insulin resistance and cancer.
19
Q
Are trans fats saturated or unsaturated?
A
Trans fats are unsaturated, but behave like saturated fats because of their unkinked shape.
20
Q
What is the difference between the cis and trans fatty acids configuration?
A
– Cis configuration = the H atoms are on the same side of the double bond. The majority of natural fats are cis.
– Trans configuration = the H atoms are on opposite sides of the double bond.
21
Q
Give an example of a natural trans fat, its benefits and where it can be found.
A
Conjugated linoleic acid (CLA) is a natural trans fat found in grass-fed meat and dairy products. Studies indicate CLA helps increase lean muscle mass and decrease body fat.
22
Q
What is the major form of dietary fat, and the form in which fat is stored in the body?
A
Triglycerides (TGs). They circulate in the blood when released for energy.
23
Q
Describe triglycerides (TGs) structure
A
TGs are lipid molecules made up of one unit of glycerol and three fatty acids. The three fatty acids can differ in length (number of carbon atoms) and degree of saturation (number of hydrogen molecules attached).
24
Q
When does the body synthesise triglycerides and what has high levels of triglycerides in the blood been linked to?
A
The body synthesises triglycerides whenever caloric intake exceeds energy requirements.
High levels of triglycerides in the blood have been linked to atherosclerosis, and hence heart disease and stroke.
25
What is lipogenesis and where does it take place?
Lipogenesis is the process through which acetyl-CoA is converted to triglycerides for storage in fat. Three fatty acids are bound to glycerol and stored as triglycerides.
The sites of fatty acid synthesis are the liver, adipocytes, kidneys and lactating mammary glands.
26
What is lipolysis?
When dietary energy is limited, the fatty acids from triglycerides are mobilised from adipocytes into circulation.
Triglycerides are hydrolysed by lipase into fatty acids and glycerol for use in the body.
27
# Name the hormones that
a) stimulates lipolysis
b) antagonises lipolysis
**a) Stimulated by:**
- Adrenaline, noradrenaline.
- Adrenocorticotropic hormone (ACTH).
- Glucagon and growth hormone.
- Thyroid-stimulating hormone (TSH) and thyroxine.
**b) Antagonised by:**
Insulin (antagonises the lipolytic effects of these hormones). As a result, insulin resistance (e.g. Type 2 diabetes) = central adiposity.
28
Describe the process how fatty acids can be broken down to produce energy
1. Fatty acids cross the cell membrane (carnitine facilitates this), traverse the cytosol and reach the mitochondria.
2. The fatty acids undergo beta-oxidation and are broken down into 2-carbon blocks as acetyl-CoA, which is oxidised via the Krebs cycle to CO2 and H2O.
3. Energy is then generated using the electron transport chain.
29
What happens when carbohydrate levels are low in the body?
When carbohydrate levels are low, fat becomes the primary fuel for energy production (fatty acids or ketone bodies).
Ketone synthesis becomes necessary because the brain cannot metabolise fatty acids.
Ketones are made when glucose is in short supply. This occurs overnight, and during dieting or fasting
30
What is ketogenesis? Name TWO ketones.
A process when acetyl-CoA is converted to the ketones acetoacetate or β-hydroxybutyrate (β-OHB).
Acetoacetate can undergo decarboxylation to another ketone acetone.
31
How much carbohydrates needs to be consumed for the body to enter ketosis?
For most adults, this happens when carbohydrates are restricted to less than around 40 g a day.
32
What are the health benefits of ketosis?
Ketosis is linked with health benefits including weight loss, and the management of epilepsy, Parkinson’s and Alzheimer’s disease.
33
What is the difference between nutritional ketosis and ketoacidosis?
Low carbohydrate diets initiate a fundamental shift in the body’s primary fuel source from glucose to fat, a state known as ketosis.
This allows energy needs to be met by utilising fat (fatty acids / ketone bodies).
For most adults, this happens when carbohydrates are restricted to less than around 40 g a day.
Ketoacidosis is an unstable and dangerous condition that develops when your body doesn't have enough insulin to allow blood sugar into your cells for use as energy.
34
Describe the process of triglyceride digestion until its storage in adipose tissue.
In the stomach and small intestine, triglycerides are separated into glycerol and fatty acids. The resulting two free fatty acids and monoglyceride are transported into enterocytes, where they are rebuilt in the cell, packaged into chylomicrons and transported via the lymphatic system to the bloodstream.
The fatty acids can then be used or stored in adipose tissue.
35
What aids triglyceride digestion?
The digestion of triglycerides is aided by gastric lipase in the stomach and pancreatic lipase in the duodenum, which act to separate the glycerol and fatty acids.
This process is facilitated greatly by the emulsifying action of bile, which increases the surface area of fat droplets.
36
What can we do to optimise lipid digestion?
- Chew adequately and avoid drinking with meals.
- Increase bile production by optimising stomach acid levels via *zinc* and *B6*-rich foods, *bitter foods* (e.g. chicory, rocket); stress management.
- *Choleretics* (increase bile production) and *cholagogues* (increase bile flow); e.g. dandelion, artichoke and turmeric.
- Ensure good hydration to support bile flow.
- Increase *glycine* and *taurine*, which are components of bile. Good sources include legumes, sea vegetables, spinach and eggs.
- Olive oil can stimulate bile secretion.
37
What was the result of dietary guidelines recommendations for reducing the intake of total fat and dietary fat (>10% of energy)?
Low-fat diets led to fat in foods being replaced with refined carbohydrates and sugar.
Without adequate energy from fat, people struggle to be sufficiently satiated. This has resulted in the consumption of ultra-processed foods.
High carbohydrate diets led to the highest mortality rates.
38
What can we advise clients regarding fat intake in their diet?
Eating fats from natural, unrefined foods should be the priority. Fat in the diet should be a mixture of saturated, monounsaturated and polyunsaturated fats, but absent of trans fats.
Fat-soluble antioxidants, e.g. vitamin E (sunflower seeds, almonds and wheat germ), are important when including fats in the diet.
Focus on the quality of the fat and combine with foods naturally rich in antioxidants.
39
List THREE benefits of including good amounts of healthy fats in the diet.
* Greater satiety value.
* Sources of essential fatty acids.
* Sources of choline (needed to synthesise phosphatidylcholine).
* Sources of essential fat-soluble vitamins and phytonutrients.
* Greater flavour enhancement in cooked food.
40
Name FOUR dietary sources of healthy fats.
* Fruit — avocado, olives.
* Seeds — chia, flax, pumpkin, hemp, seed butters.
* Seed oils — flax oil, chia oil, hemp oil, sunflower oil, olive oil.
*Ensure oils are cold pressed*.
* Nuts — almonds, cashews, walnuts, Brazil nuts, nut butters.
* Other — coconut oil, grass-fed meat.
* Oily fish — salmon, mackerel, anchovies, sardines, herring.
41
# Tryglycerides, composition & application in practice:
What are the benefits of coconut oil?
Coconut oil contains *medium-chain triglycerides* (MCTs) that increase the number of calories burned compared to longer-chain fatty acids.
Coconut oil contains 50% *lauric acid*. *Monolaurin* is formed from lauric acid. Both substances have:
- antibacterial, antiviral and antifungal properties.
- ↑ HDL cholesterol, ↓ LDL cholesterol.
- Positive outcomes in epilepsy and Alzheimer’s disease.
42
What is the best fat for high temperature cooking? Give examples.
Due to the lack of double bonds in *saturated fatty acids*, they are considered more stable and less prone to oxidation / rancidity.
Coconut oil, butter and ghee contain saturated fats that can tolerate being heated and are preferable for cooking.
Frying foods in fat promotes free radical formation - ideally avoid.
43
What is the best fat for low temperature cooking?
Monounsaturated fats (extra virgin olive oil, avocado oil, macadamia) oxidise at higher temperatures but can be used for low-temperature cooking due to the naturally occurring antioxidants in these oils.
Do not use at temperatures above 180°C.
44
What oils should only be used in their raw, cold-pressed form?
Polyunsaturated fats (e.g. vegetable oils, flaxseed oil) oxidise when heated and produce free radicals that damage cells - should only be used in their raw, cold-pressed form for pouring over cooked or raw foods or in dressings.
Store in dark-coloured bottles in the fridge or freezer as they can go rancid quickly and can be oxidised simply through direct light exposure.
45
Fats are more prone to oxidation if they:
- Are high in polyunsaturated fat.
- Are exposed to prolonged heat, light or oxygen.
- Are naturally low in antioxidants.
- Are refined or heavily processed.
46
What happens when fatty acids within triglycerides go rancid?
They release the fatty acids from glycerol. Unsaturated fatty acids within triglycerides also go rancid when the double bonds are oxidised.
47
Name TWO fatty acids that cannot be made in the body and so are essential in the diet.
1. Linoleic acid LA (an omega-6 fatty acid).
2. Alpha-linolenic acid ALA (an omega-3 fatty acid).
From ALA and LA, the next in the sequence is manufactured in the body from the preceding fatty acid in the chain, with the help of special enzymes.
48
What is the most important enzyme that catalyses the chemical reaction to produce GLA and EPA?
Delta-6-desaturase
49
What is the EFAs recommended intake of EFAs and how can it be achieved?
250 mg EPA / DHA
consume 2–3 portions of oily fish per week or from an algal source.
50
Name FOUR Functions of EFAs.
* EFAs are vital components of all cell membranes and help to maintain *membrane fluidity*. The fluidity of the membrane must be maintained within a certain range for the cell to function properly.
* They act with cell membrane proteins thereby affecting the *transport of substances* into and out of the cell.
* EFAs are key *components of organelle membranes* such as those of the mitochondria.
* EFAs are necessary for *cell-to-cell communication*.
* They are essential for *foetal and child brain development*.
* EFAs are *precursors of eicosanoids*, which are ‘local’ hormones.
51
Clinical indicators of an EFA requirement: skin, nails, hair
- Dry, flaky, scaly, chapped lips (also dry eyes).
- Acne / eczema / psoriasis / dermatitis.
- Hyperkeratosis pilaris.
- Delayed wound healing.
- Nails: Dry / brittle, red / swollen cuticles.
- Hair: Dry / oily, split ends, alopecia.
52
Clinical indicators of an EFA requirement: endocrine system
- Weight imbalances (obesity / weight loss).
- PMS / painful menstrual cramps / sore breasts.
- Hyperinsulinaemia
53
Clinical indicators of an EFA requirement: reproductive system
- Infertility / impotence / history of repeated miscarriages.
- Ovarian cysts / fibrocystic breast disease
54
Symptoms of an EFA requirement: circulatory
- Frequent nosebleeds / bleeding gums.
- Easy bruising.
- Delayed recovery from exercise.
55
Clinical indicators of an EFA requirement: musculoskeletal
- Chronic joint pain / arthritis.
- Delayed recovery from injuries.
56
Clinical indicators of an EFA requirement: immune
Susceptibility to infections.
57
# name conditions
Clinical indicators of an EFA requirement: neurological
- Dementia / Alzheimer’s.
- Parkinson’s disease.
- Irritability / nervousness.
- Tingling arms and legs.
- Chronic Fatigue Syndrome / Myalgic encephalomyelitis.
58
Is Alpha Linolenic Acid (ALA) Omega-3 or Omega-6? Name THREE good food sources.
ALA is an omega-3 fatty acid, 18:3 n-3 (18-carbon polyunsaturated fatty acid).
Food sources include flaxseeds, hempseeds, soybeans, walnuts, dark green leaves, many edible plants.
59
What are the therapeutic uses for ALA: CVD
- *Decreases the risk of myocardial infarctions, atherosclerosis development and strokes*.
- *Reduces C-reactive protein levels* (an inflammatory marker used to evaluate CVD risk).
- *Anti-arrhythmic effect* – incorporation of ALA into the cell membranes of cardiomyocytes modifies ionic channel currents, stabilising electrical activity.
- *Anti-hypertensive* - ALA lowers the activity of angiotensin-converting enzyme (ACE).
- Shown to *lower LDL cholesterol* (whole flaxseed).
60
ALA therapeutic uses: neurological
- Strokes - ALA promotes vasodilation in the brain and increases brain-derived neurotropic factor (BDNF), exerting a neuroprotective effect.
- Depression – BDNF plays a critical role in neuronal maintenance, learning and memory. It has also been specifically implicated in mood-boosting effects.
61
In which conditions can the anti-inflammatory properties of ALA be beneficial?
The anti-inflammatory properties of ALA support its uses in cases such as inflammatory bowel disease, asthma and other autoimmune conditions.
These effects are likely dependent on its conversion to EPA & DHA.
62
ALA drug interactions
*Blood-thinning* medications:
– Omega-3 fatty acids may increase the anti-coagulant effects of blood-thinning medications, e.g. warfarin and aspirin.
Should only be taken together under GP supervision.
*Cholesterol-lowering* medications (i.e. statins):
– May have an agonist effect when combined with statins.
63
Name TWO fatty acids formed from alpha-linolenic acid (ALA)? What are their food sources?
Eicosapentaenoic acid (EPA) is an omega-3 fatty acid, 20:5 n-3.
Docosahexaenoic acid (DHA) is an omega-3 fatty acid, 22:6 n-3.
Main food sources include oily fish and human breast milk. Marine algae are a rich source of DHA.
64
# including supplemental dosage
EPA and DHA therapeutic uses: CVD
- EPA / DHA supplementation can significantly reduce blood triglyceride levels.
- Can lower blood pressure through the effects of series 3 prostaglandins.
- Preventative against the formation of atherosclerosis. Shown to lower blood fibrinogen levels (which are implicated in atherosclerosis development).
- The DART trial showed a reduction in myocardial reinfarction after a daily intake of 900 mg EPA / DHA.
Supplemental fish oil dosage: EPA + DHA 0.8 - 3g/day
65
# including supplemental dosage
EPA and DHA therapeutic uses: anti-inflammatory
- DHA and EPA have profound anti-inflammatory effects - *inhibiting NFκB, TNF-α* and *Interleukin-6*. Inflammation is modulated through changes to the PUFA content of cell membranes.
- Useful in inflammatory conditions, especially various forms of arthritis (e.g. osteo and rheumatoid), inflammatory bowel diseases, eczema and SLE.
- Studies show that supplementing >2.7 g / day of fish oils lowers NSAID use in those with arthritis.
Supplemental fish oil dosage: EPA 3 – 5g/day, DHA 0.8 – 2.7g/day.
66
# including supplemental dosage
EPA and DHA functions and therapeutic uses: neurological health
- EPA and DHA have neuroprotective properties and increase *BDNF* (brain-derived neurotrophic factor).
- Lower levels of EPA and DHA are associated with more learning and behavioural problems.
* Depression & ADHD
* Alzheimer’s disease
Dose: EPA 0.6 – 3g
DHA 0.15 – 2g/day
67
# including supplemental dosage
EPA and DHA functions and therapeutic uses: foetal health
- Support foetal brain development (language, visual, motor functions).
- There is evidence that mothers who supplement EPA and DHA during pregnancy and breastfeeding may protect their children against allergies.
- Pregnancy support (for foetal health)
Dose: EPA 800mg,
DHA 400mg/day.
68
Ways to meet EPA / DHA needs on a vegetarian or vegan diet?
- Include good sources of alpha-linolenic acid in the daily diet, such as flaxseed and hempseed.
- Support EFA conversion through increasing dietary intake of enzyme co-factors (zinc, magnesium and B6).
- Moderate the use of oils rich in omega-6 fatty acids, and avoid processed foods rich in these oils.
- Consider algal EPA / DHA supplements.
69
Name THREE factors that determine vegan omega oil quality.
- Extracted from microalgae of the schizochytrium species using water extraction methods (instead of hexane, alcohol and other solvents), to provide DHA.
- Extracted from echium seed oil which contains stearidonic acid (SDA) which is easily converted to EPA and DHA.
- Free from carrageenan which may induce inflammation in colonic cells.
- Cold-pressed, organic.
70
Discuss four possible EPA / DHA drug interactions
- *Anticoagulants* - EPA may increase bleeding time, so fish oil could make the effects of these drugs stronger.
- *Aspirin* - in combination with aspirin, fish oil could be helpful in the treatment of some forms of coronary artery disease. However, this combination may also increase the risk of bleeding.
- *Diabetes medications* - fish oil supplements may lower blood glucose levels and could make effects of diabetes drugs stronger.
- *Blood pressure medication* - DHA
may lower blood pressure (so monitor).
71
Name TWO omega-6 fatty acids and their food sources.
*LA* (linolenic acid) food sources: vegetable oils- safflower, sunflower, soybean, and corn oils. It is found in nuts, seeds and some vegetables.
*GLA* (gamma-linolenic acid) food sources: evening primrose oil, blackcurrant seed oil, hemp and borage oils.
72
What nutrients are required for the conversion of LA to GLA?
vitamin C, B3, B6, magnesium and zinc.
73
# name conditions
Name TWO GLA therapeutic uses and its mode of action.
*Rheumatoid arthritis*
- ↓ joint pain, swelling and morning stiffness in RA.
- GLA is converted to PG1, which has immune-regulatory and anti-inflammatory effects. This includes a reduction in NF-kB activity.
Dosage: 1.4 g / day of borage seed oil.
*ADHD*
- A combination of GLA and EPA shows
improvements in attention and impulsivity.
*Eczema*
- Reduced inflammation; improves skin symptoms.
Dosage: 320 mg GLA per day.
74
What are the therapeutic uses of Evening Primrose Oil (EPO)
*PMS*
* GLA is a precursor to PG1, which inhibits prolactin (↑ in women with PMS).
Dosage: 1500 mg daily for three months.
*Cyclical mastalgia* (breast pain)
* GLA forms PG1 which inhibits the synthesis of arachidonic acid metabolites (= anti-inflammatory).
Dosage: 1000 mg 3 x daily for four to six months.
*Female fertility*
* Increases and optimises cervical mucus, to sustain sperm during conception.
Dosage: 1500–2000 mg daily from day 1 of menses.
75
What caution should be taken when using GLA?
Borage seed oil, and possibly other sources of GLA, should not be used during pregnancy.
Dosages of greater than 3,000 mg / day may increase AA production.
76
Name THREE GLA drug interactions.
* Ceftazidime - it may increase the effectiveness of this antibiotic.
* Chemotherapy - it may increase treatment effects.
* Cyclosporine - it may increase the immunosuppressive effects.
* NSAIDs - NSAIDs may counteract the effects of GLA.
* Phenothiazines - they may increase the risk of seizures.
77
Name food sources of arachidonic acid (AA)
AA is primarily found in animal products such as meat, eggs and dairy, especially when those animals are intensively raised on grain.
Dihomo-gamma-linolenic acid (DGLA) can be converted to AA using delta-5-desaturase. However, this enzyme is used
preferentially for the omega-3 pathway, so the majority of AA in the diet is from animal products.
78
Why is AA seen as pro-inflammatory? What prevents excessive inflammation?
AA is metabolised by COX-1 and COX-2 enzymes to the *inflammatory prostaglandin series 2*.
This causes inflammatory effects including fever, vascular permeability and vasodilation, pain and oedema.
However, to prevent excessive inflammation PG2 induces 15-LOX activity that leads to the formation of lipoxins (anti-inflammatory).
79
How are eicosanoids made? Give THREE examples.
Eicosanoids are made by the *oxidation of omega-3 and 6 fats*. They are locally-acting hormone-like signalling molecules and have a short life span.
Eicosanoids include prostaglandins, leukotrienes, thromboxanes, resolvins and protectins.
80
What are eicosanoids involved in? Name three.
Eicosanoids = signalling molecules
– Inflammation.
– Blood vessel permeability and constriction.
– Blood coagulation.
– Immune cell behaviour.
– Lipid accumulation.
– Central nervous system signalling.
81
Describe how fatty acids are converted to eicosanoids, what they can be made of and what are their effects.
Fatty acids are released from the membrane phospholipids by the enzyme phospholipase A2.
These are converted to eicosanoids by cyclooxygenase (COX) and lipoxygenase (LOX) - this is dependent on the starting fatty acid and an outside stimulus.
Eicosanoids can be made from arachidonic acid (AA), eicosapentaenoic acid (EPA) and dihomo-y-linolenic acid (DGLA).
They can have both pro- and anti inflammatory effects.
82
Series 1 Prostaglandins (PG1) — what are they made of and what do they do in the body?
made from DGLA. ANTI-INFLAMMATORY.
- Keep blood platelets from sticking together.
- Remove excess sodium and water from the body.
- Relax blood vessels promoting circulation.
83
Series 2 Prostaglandins (PG2) — what are they made of and what do they do in the body?
made from AA. PRO-INFLAMMATORY.
- Mostly promote platelet aggregation.
- Promote sodium and water retention (↑ BP)
- Oppose functions of series-1 prostaglandins.
84
Series 3 Prostaglandins (PG3) — what are they made of and what do they do in the body?
made from EPA. ANTI-INFLAMMATORY.
- Some have weak platelet aggregating properties.
- Prevent the release of AA from cell membranes.
- EPA is the most important factor limiting PG2 production.
85
What determines which prostaglandins will predominate?
Cell membrane fatty acid composition determines which prostaglandins will predominate; e.g. a diet rich in arachidonic
acid leads to the formation of more pro-inflammatory PG2.
The more abundant fatty acids will occupy the enzyme active sites, which highlights the importance of omega-3 and -6 balance.
86
# in relation to AA
What can high consumption of EPA and DHA from omega-3 lead to?
A high consumption of EPA and DHA from omega-3 means that a higher proportion of fatty acids resides in the cell membrane at the expense of AA.
This can result in immune-suppression.
Hence, it is all about balance.
87
How can other omega-6 and omega-3 fatty acids be synthesised from ALA and LA?
By *desaturation* - addition of a double bond between two carbon atoms and / or *elongation* — addition of two carbon atoms.
Both LA and ALA compete for the same desaturase and elongase enzymes.
88
Delta-6-Desaturase is inhibited by
Magnesium, B6, zinc deficiency
Insulin resistance
Viruses
Refined sugars
Alcohol
Stress hormones, e.g. cortisol
High intake of EPA / DHA
Excess trans fats and cholesterol
89
Delta-5-Desaturase is inhibited by
Insulin resistance
Zinc deficiency
Alcohol
Excess trans fats and cholesterol
Stress hormones, e.g. cortisol
High intake of EPA / DHA
90
EFA testing includes
- Omega-3 index — a marker for cardiovascular risk.
- Omega-6:3 ratio — a marker for chronic illness.
- AA:EPA ratio — a marker of ‘silent’ inflammation.
91
What is cholesterol essential for?
Cholesterol is essential for the synthesis or action of:
– Vitamin D and calcium metabolism.
– Cortisol and related hormones.
– Aldosterone for mineral and fluid balance.
– Sex hormones — oestrogen, progesterone and testosterone.
– Bile salts and acids needed for digestion.
– Membrane integrity, especially in the brain.
– Lipoproteins, needed for triglyceride transport.
92
What stimulates cholesterol synthesis and where?
A diet rich in triglycerides stimulates cholesterol synthesis in the liver and small intestine.
93
How to optimise the excretion of cholesterol?
Cholesterol is excreted in the stool intact, mostly as bile products.
The excretion is increased by absorption onto non-digestible carbohydrates (fibre).
Gut bacteria from healthy microbiomes metabolise cholesterol = less reabsorption.
94
What substances (apart from cholesterol LDL and HDL) do lipoproteins carry?
A lot of substances are carried within them including CoQ10, beta-carotene and vitamin E.
95
# LDL, VLDL, HDL
Explain the difference between different lipoproteins that carry cholesterol.
*LDL* (low density) - takes cholesterol from the liver to cells.
*VLDL* (very low density) - takes triglycerides to cells.
*HDL* (high density) - collects cholesterol from cells to transport back to the liver.
96
What causes cholesterol deposition in atherosclerosis?
Atherosclerosis requires LDL cholesterol to deposit in the arterial wall and become oxidised.
Atherosclerosis is an inflammatory disease.
In the absence of *inflammation* or *injury to the endothelium*, cholesterol does not deposit.
97
What is a better health indicator for measuring total cholesterol?
There are varying sizes of LDL cholesterol.
*Measuring particle size* rather than total cholesterol is a better health indicator.
98
What is the difference of big and small LDL particles?
People whose LDL particles are predominantly small and dense have a threefold greater risk of coronary artery disease, whereas the large and fluffy type may be protective.
99
What are the benefits of large HDL particles?
Larger HDL particles:
- are more effective at *removing cholesterol* from the blood
- better exert *anti-inflammatory* and *anti-thrombotic effects*
- better at *promoting nitric oxide production* in endothelial cells.
100
Name THREE cardiovascular markers and what they might be indicative of.
*Lipoprotein (a)* - a blood clotting agent. It appears to be a key genetic risk factor in coronary artery disease. Higher levels are associated with greater risk.
*Lp-PLA2* - an enzyme that plays a role in endothelial inflammation and atherosclerosis.
*Fibrinogen* - raised levels are a risk factor for clot formation.
*C-reactive protein* - inflammatory marker associated with CVD.
*Lipid peroxides* - raised levels reflect oxidative damage to membranes.
101
What is the optimal cholesterol level and when does a GP prescribe a statin?
Serum cholesterol above 5 mmol / L - statin.
The optimal range is 0.79–1.24 mmol / L
102
What are phospholipids? Give THREE examples.
Phospholipids are the structural basis of all cell membranes.
- *Phosphatides* - contain glycerol, two long chain fatty acids, a phosphate group, and either inositol, choline or serine.
- *Phosphatidylcholine* - predominant phospholipid in the body.
- *Lecithin* - synthesised by the liver and plays a role in emulsification (fat digestion), increases the solubility of cholesterol and helps improve cognitive function.
103
Therapeutic uses of Inositol
Improves insulin sensitivity and can subsequently be used in cases of insulin resistance (e.g. Type 2 diabetes, PCOS).
104
Therapeutic used of phosphatidylserine
Improves neuronal membrane functioning and cognitive function. It can be used in cases of depression, insomnia and stress.
105
Therapeutic uses of phosphatidylcholine
- Neuro- and hepato-protective. It supplies choline for the synthesis of the neurotransmitter acetylcholine.
- Important for cognition, memory, immunity and hormone function.
