Lipids - thecnm.com

© CNM: Nutrition Year 1: Lipids. MK.

Lipids

1

Naturopathic Nutrition Year 1


Learning Outcomes

In this lesson you will learn about:

• 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.

2


Introduction

3

• 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.

• Dietary fat intake is a hotly-debated issue and is a major

point of interest in nutrition today.

• Fats are not just a source of energy. They form part

of every cell and are vital for physiological and

biological processes (e.g. hormone production).

• Farming and food processing have increased

the amount and types of fat in human diets,

most notably trans fats and vegetable oils.

adipo = fat

cyte = cell

© CNM: Nutrition Year 1: Lipids. MK.4

The Fat Debate

Fat intake has changed in recent times, most notably

since fats were credited with causing heart disease.

• In the 1950s, Ancel Keys declared that eating a high saturated fat

diet would increase serum cholesterol and consequently

lead to heart disease. His experiments significantly changed

society’s perception on fats.

• 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 most profitable pharmaceutical industry drugs.


Fat For Health

5

Due to the association with cardiovascular disease, and the

cosmetic and psychological burden of excess body fat, the

role of adipocytes in the body is hugely misunderstood.

• Far from being inert, white adipose

tissue (WAT) is a complex,

metabolically-active endocrine tissue.

• Functions include: The secretion of

hormones, growth factors, enzymes

and cytokines; the protection of organs;

a form of energy storage; and to provide

insulation to protect against temperature extremes.

cytokines = cell

signalling proteins

(Coelho et al. 2013)

© CNM: Nutrition Year 1: Lipids. MK. 6

Lipids in the Body

Lipids exist in the body in various forms

with each form having a different structure

and function. Lipids include:

• 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.

phospholipid = phosphate + fatty acidsglycolipid = carbohydrate + lipidcerebroside = waxy lipid + sugarsphingolipid = long chain amino alcohol + fatty acid + sugar

(Geissler & Powers, 2005)


Function of Lipids

• Energy (ATP) production — each gram of fat supplies the

body with about nine 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.8

Function of Lipids

Myelin

sheath

eicosanoids =

signalling molecules

(Geissler & Powers, 2005)


Fatty Acids

Fatty acids are hydrocarbon chains with an acid

group at one end and a methyl group at the other.

• Short-chain fatty acids (up to 5 Cs) and medium-chain fatty acids

(6–12 Cs) travel directly to the liver where they can be used to

create energy or ketones. Medium-chain triglycerides (MCTs)

can be used as a source of energy before exercise (e.g.1 tbsp).

• Long-chain fatty acids (14–22 Cs) and very long chain fatty acids

(> 22 Cs) are used to build cell membranes.

Methyl or

omega end

(-CH3)

Alpha or

carboxylic

end (-COOH)

C = Carbon

(Geetha et al. 2005)


Short-Chain Fatty Acids

Short-chain fatty acids (SCFAs) have fewer than six carbon atoms.

• SCFAs are produced when dietary fibre is fermented in the colon.

• Acetate, propionate and butyrate are the most common SCFAs.

• Butyrate is particularly important for colon health because

it is the primary energy source for colonocytes.

It supports the intestinal tight junctions.

• SCFAs are speculated to have a role in

the microbiota-gut-brain axis crosstalk.

• Butyrate is thought to have an

anti-inflammatory effect on the colon.(Dalile et al. 2019)


Fatty acids are named using their common names and the omega

nomenclature system.

• 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.

• The omega-6 fatty acid, arachidonic acid, is referred to as 20:4 w6.

• Unsaturated fats can be saturated by the

addition of hydrogen — as in hydrogenation

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.

No. of

carbons

No. of double bonds

No. carbons

to first

double bond

Fatty Acidshydrogenation =

addition of hydrogen



• Saturated fatty acids: Contain no C-C double

bonds. All the carbons are completely saturated

with hydrogen bonds. Solid at room temperature.

• Unsaturated fatty acids: Contain one or more double

bonds between carbons. Liquid at room temperature.

• Monounsaturated fatty acids:

Have one double bond in the chain.

• Polyunsaturated fatty acids:

Have several double bonds.

• The more double bonds there are in a fatty acid, the

less stable it is, increasing susceptibility to oxidation.

Fatty Acids



Unnatural trans fatty acids are produced by high

temperatures and hydrogenation.

• They are found in margarine, processed

foods and refined vegetable oils.

• 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.

Unnatural Trans Fats

13

hydrogenation = the

addition of hydrogen

to solidify an

unsaturated fat

(Mozaffarian et al. 2010; Zhu et al. 2019)


Cis and Trans Fatty Acids

14

At each double bond, two possible isomeric forms exist.

– 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 separate sides of the double bond.

• 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.

Trans fats are

unsaturated, but

behave like saturated

fats because of their

unkinked shape.


Triglycerides

Triglycerides (TGs) are the major form of dietary fat, and the

form in which fat is stored in the body. They circulate in the

blood when released for energy.

• 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).

• High levels of triglycerides in the blood have been linked to

atherosclerosis, and hence heart disease and stroke.15

Triglycerides are also referred to as triacylglycerols (TAGs)


Synthesis and Storage of Triglycerides

16

The body synthesises triglycerides whenever caloric intake

exceeds energy requirements.

• Excess dietary energy is

converted to triglycerides via

lipogenesis, and excess ingested

fat is taken up by adipose tissue.

• Lipogenesis takes place in adipose

tissue and the liver.

• Adipocytes are supplied by an extensive network of blood vessels.

• They acquire TGs from circulating lipoproteins,

chylomicrons and very low density lipoproteins.lipo = fat

genesis = formation


Lipogenesis is the process through which acetyl-CoA is

converted to triglycerides for storage in fat.

• Fatty acids are synthesised when there

is an excess of carbohydrates.

• Acetyl-CoA, created from glucose during

glycolysis, as well as from fats and

amino acids, is built up with the addition of

2-carbon units to form palmitic acid (C16).

• 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.17

Lipogenesisacetyl-CoA = a component of cell respiration that adds acetyl groups to reactions


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.

• Lipolysis is stimulated by:

- Adrenaline, noradrenaline.

- Adrenocorticotropic hormone (ACTH).

- Glucagon and growth hormone.

- Thyroid-stimulating hormone (TSH) and thyroxine.

• Insulin antagonises the lipolytic effects of these hormones. As a

result, insulin resistance (e.g. Type 2 diabetes) = central adiposity.18

Lipolysislipo = fat

lysis = breakdown

Adrenaline Free

fatty

acids

Glycerol


Fatty Acid Catabolismsee

Biochemistry II

catabolism

= breakdownFatty acids can be broken down to produce energy.

• Fatty acids cross the cell membrane, traverse

the cytosol and reach the mitochondria.

• Carnitine facilitates the transport

of fatty acids across the

mitochondrial membrane.

• 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.

• Energy is then generated using the electron transport chain.

Mitochondrial

matrixCytosol



When carbohydrate levels are low, fat becomes the primary

fuel for energy production. 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.

• By a process known as ketogenesis,

acetyl-CoA is converted to the ketones

acetoacetate or β-hydroxybutyrate (β-OHB).

• Acetoacetate can undergo decarboxylation

to another ketone acetone.

• Acetone build-up gives a characteristic sweet smell to the breath.20

Ketosisdecarboxylation = removal of a carboxyl group

Acetone


Ketosis

Low carbohydrate diets initiate a fundamental shift in the body’s primary fuel source from glucose to fat. • This allows energy needs to be met by utilising fat

(fatty acids or by ketone bodies).

• For most adults, this happens when carbohydrates are restricted to less than around 40 g a day.

• Ketosis is linked with health benefits including weight loss, and the management of epilepsy, Parkinson’s and Alzheimer’s disease.

• Nutritional ketosis is different from ketoacidosis — an unstable and dangerous condition that occurs when there is insufficient pancreatic insulin response to regulate serum β-OHB.


Lipid Digestion

22

Triglycerides form the bulk of fat in a Western diet.

• 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.

• 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 be used or stored in adipose tissue.

enterocyte = intestinal cellmonoglyceride = glycerol + 1 fatty acid



Lipid Digestion

23

Optimising 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.


Lipid Recommendations

Type of fat: Amount

(% of

energy):

Amount in grams

(female, 2000

calories / day):

Total fat 20–35 44‒78

Saturated fatNo more than

1022

Polyunsaturated

fat6–11 13–24

Omega-3 0.5–2 1.1–4.4

Generic recommendations:


The UK Government’s Scientific Advisory Committee on

Nutrition (SACN) Review (2019) recommended that saturated

fats should not exceed >10% of energy.

• The Eatwell Guide advises:

- Choose low-fat dairy options.

- Choose unsaturated oils and

spreads, and eat in small amounts.

• There is no emphasis on healthy fats such as oily fish, avocado,

nuts, seeds, extra virgin olive oil, egg yolk and grass-fed meat.

• Low-fat dairy options often contain high levels of sugar.

Unsaturated oils may be highly refined and contain trans fats.



In past decades, dietary guidelines have advocated

reducing the intake of total fat and dietary fat:

• 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.

• The PURE study in 2017 found that high carbohydrate diets led

to the highest mortality rates. People consuming more fat, 35%

of daily energy, were less likely to die than those consuming

10% daily energy.


(Dehghan et al. 2017)


Healthy Dietary Fats

The importance of fat as a macronutrient in

the diet has been understated and demonised.

• 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, are important

when including fats in the diet. Foods rich in vitamin

E include sunflower seeds, almonds and wheat germ.

• Focus on the quality of the fat and combine with foods

naturally rich in antioxidants.


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.



Healthy dietary fats’ food sources:

• 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.



Compare the fat content using a macro counter app, e.g. ‘My Fitness Pal’ for a 10 stone / 63 kilo, 30-year old female.Which meal has a higher fat content? A higher caloric value?

30

Exercise

Breakfast50 g porridge, 100 ml whole

milk, 100 g Greek yoghurt + 1 tbsp seeds.

50 g cornflakes, 100 ml skimmed milk and 1 tsp

sugar.

Snack2 tbsp hummus with 1 large

carrot.2 chocolate digestive

biscuits.

LunchChicken breast / avocado

salad, 1 tbsp olive oil.2 tbsp mixed nuts.

Turkey sandwich (low fat spread). Low fat crisps.

Pack of Maltesers.

DinnerSalmon fillet, spinach and

roast tomatoes.300 g spaghetti bolognese.


Saturated Fat

Saturated fat intake has been a fiercely-debated topic.

• A lot of studies about high saturated fat diets and health, have

reported on dietary intake of saturated fats from junk foods.

• A recent review by the Journal

of the American College of

Cardiology found that there was

inadequate scientific evidence

to keep advising against foods

high in saturated fats, including

coconut, unprocessed meat,

eggs and dark chocolate.(De Souza et al. 2015)


Saturated Fat

Coconut oil contains medium-chain triglycerides

(MCTs) which the body uses as a source of fuel

or turns them into ketones.

• MCTs 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.

• Preliminary studies show positive outcomes

in epilepsy and Alzheimer’s disease. (Kabara et al. 1972; Assunção et al. 2009;

Boateng et al. 2016)


Saturated Fats in Food

Butyric acid

4-C:

Caprylic acid

8-C:

Lauric acid

12-C:

Palmitic

acid 16-C:

Stearic acid

18-C:

Butter, dairy Coconut Coconut Coconut Beef, pork

Produced in the gut

Palm kernel Palm Lamb, mutton

Breast milk Palm kernel Cocoa and shea butterAnti-fungal

properties Butter


Palmitoleic acid

Omega-7:

Oleic acid

Omega-9:

Sea buckthorn berries Olive, avocado

Coconut Almond, peanut, pistachio

Coconut, palm kernel Brazil nuts, pecan, cashew

Macadamia nuts Hazelnut, neem, macadamia

Animal fat, butter

34

Monounsaturated Fats in Food


Polyunsaturated Fats Omega-3

Alpha-linolenic acid

(ALA):

Stearidonic

acid (SDA):

EPA and DHA:

Flaxseeds (richest source —

50% of its fatty acids are ALA)

Blackcurrant

seeds

Cold-water fish oil

Chia seeds, hemp seeds,

dark green leaves

Salmon, trout, tuna,

anchovies, mackerel

Pumpkin seeds, soybean,

rapeseed (canola)

Sardines, herring

Spirulina, chlorellaWalnuts,

wheat germ


Linoleic acid

(LA):

Gamma linolenic

acid (GLA):

Arachidonic acid

(AA):

Safflower Borage oil Meat

Sunflower, hemp,

soybean, walnut

Evening primrose and

hemp oil

Other animal products

Pumpkin seed, sesame,

almond, chia, cashew

Blackcurrant seed oil

Rapeseed,

wheat germ,

avocado,

Brazil nut

36

Polyunsaturated Fats Omega-6


Cooking with Fats

Coconut oil, butter and ghee contain saturated fats that can

tolerate being heated and are preferable for cooking.

• They have a high smoke point and should be

chosen for high temperature cooking.

• Frying foods in fat promotes free radical formation — ideally avoid.

• 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.

smoke point = temp. at which an oil starts to smoke and burn


Cooking with Fats

Polyunsaturated fats (e.g. vegetable oils, flaxseed oil) oxidise

when heated and produce free radicals that damage cells.

• Polyunsaturated oils should only be used in their raw, cold-pressed

form for pouring over cooked or raw foods or using 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.

• As a general rule it is best to purchase

polyunsaturated fats with a pressing

date as well as a use-by date.


Rancidity and Toxicity

Dietary lipids are prone to rancidity, generating compounds

which are highly detrimental to health.

• Fatty acids within triglycerides go rancid by releasing the fatty

acids from glycerol. Unsaturated fatty acids within triglycerides

also go rancid when the double bonds are oxidised.

• 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.


Rancidity and Toxicity

Rancidity results in unpleasant odours and flavours.

• Fats break down into compounds that are

subsequently transformed into products such

as aldehydes, ketones and hydrocarbons.

• Oxidation of the double bonds generally leads

to the production of malondialdehyde.

• Malondialdehyde is a potential mutagen and is

found in some hydrogenated or overheated fats.

• Due to the lack of double bonds in saturated fatty acids,

they are considered more stable and less prone to oxidation /

rancidity. This explains why coconut oil is stable for cooking.

malondialdehyde = a very reactive compound that induces oxidative stress


There are two fatty acids that cannot be made in

the body and so are essential in the diet. They are:

1. Linoleic acid (an omega-6 fatty acid).

2. Alpha-linolenic acid (an omega-3 fatty acid).

• Arachidonic acid was once thought to be essential in the

diet, but we now know it can be made from linoleic acid.

• Humans lost the ability to introduce

double bonds into fatty acids between

the carbon atoms 6‒7 and 3‒4,

making LA and ALA essential in the diet.41

Essential Fatty Acids (EFAs)

arachidonic = From ‘arachidic’= of the groundnut (the Greek for peanut is arachis), which has a similar fatty acid structure


ALA and LA have to be obtained from foods so are ‘essential’.

• From ALA (omega-3) and LA

(omega-6), the next in the

sequence is manufactured in

the body from the preceding

fatty acid in the chain, with

the help of special enzymes.

The most important enzyme

that catalyses the chemical

reaction to produce GLA and

EPA is Delta-6-desaturase.42

Essential Fatty Acids

a-Linolenic acid (ALA)


This shows the

omega-3 and

omega-6

pathways, and

the potential

food sources

of the EFAs

— ALA and LA.



A typical western diet is abundant in omega-6

fatty acids (plant oils, grain-fed meat and dairy),

and low in omega-3 fatty acids from ALA

sources (flaxseeds, pumpkin seeds) and

EPA / DHA sources (oily fish).

• Human beings evolved on a diet with an omega-6:omega-3 of 1.

• In Western diets the ratio is generally around 16:1.

• The relatively low rate of conversion of ALA to EPA / DHA

suggests that EPA and DHA are conditionally essential nutrients.

• To achieve the EFSA recommended intake of 250 mg EPA / DHA,

consume 2–3 portions of oily fish per week or from an algal source.

EFSA = EuropeanFood Safety AuthorityEssential Fatty Acids

(Simopoulos, 2002)


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.45


(Rolfes et al. 2006)


Clinical indicators of an EFA requirement:

Skin • Dry, flaky, scaly, chapped lips (also dry eyes).

• Hyperkeratosis pilaris.

• Delayed wound healing.

• Nails: Dry / brittle, red / swollen cuticles.

• Hair: Dry / oily, split ends, alopecia.

• Acne / eczema / psoriasis / dermatitis.

Endocrine system

• Weight imbalances (obesity / weight loss).

• PMS / painful menstrual cramps / sore breasts.

• Hyperinsulinaemia.

Reproductive system

• Infertility / impotence / history of repeated miscarriages.

• Ovarian cysts / fibrocystic breast disease.


(Kiecolt-Glaser et al. 2011; Rocha et al. 2011)


Clinical indicators of an EFA requirement (cont.):

Circulatory • Frequent nosebleeds / bleeding gums.

• Easy bruising.

• Delayed recovery from exercise.

Musculo-skeletal

• Chronic joint pain / arthritis.

• Delayed recovery from injuries.

Immune • Susceptibility to infections.

Neurological • Dementia / Alzheimer’s.

• Parkinson’s disease.

• Irritability / nervousness.

• Tingling arms and legs.

• CFS / ME.


(Puri et al. 2004)


Omega 3:

Alpha Linolenic Acid (ALA)

ALA is an omega-3 fatty acid, 18:3 n-3.

• Food sources include flaxseeds,

hempseeds, soybeans, and walnuts.

It is also found in dark green leaves.

• Many edible plants produce this

18-carbon polyunsaturated fatty acid.

48

lino- = Greek for ‘flax’ (linseed)


ALA therapeutic uses:

Cardiovascular disease (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).

Omega 3:


(Bemelmans, et al. 2004; Takeuchi, 2007; Pan et al. 2009;

Edel et al. 2015; Khalesi et al. 2015; Del Gobbo et al. 2016)


50

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.

Anti-inflammatory

• 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.

Omega 3:


(Blondeau et al. 2015; Mocking et al. 2016)


Drug interactions:

• Blood-thinning medications:

– Omega-3 fatty acids may increase the

anti-coagulant effects of blood-thinning

medications, e.g. warfarin and aspirin.

– While the combination of aspirin and

omega-3 fatty acids may actually be

helpful, under certain circumstances (such as CVD),

these should only be taken together under GP supervision.

• Cholesterol-lowering medications (i.e. statins):

– May have an agonist effect when combined with statins.51

Omega 3:



Omega 3 :

EPA and DHA

• Formed from alpha-linolenic acid (ALA).

• 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.

52

eicosa = Greek for 20 (meaning 20 carbons)penta = from ‘pentagon’ / 5 (meaning 5 double bonds)-enoic acid = a carboxyl group (-COOH)

docosa = Greek for 22 (meaning 22 carbons)hexa = from ‘hexagon’ / 6 (meaning 6 double bonds)-enoic acid = a carboxyl group (-COOH)


53

EPA and DHA (i.e. fish oil) therapeutic uses:

Cardiovascular disease

• 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

Omega 3 :

EPA and DHAThere is much research into the benefits of omega-3s. The

majority of this focuses on EPA and DHA as opposed to ALA.

(Sala‐Vila et al. 2016; Rangel-Huerta & Gil, 2018)


54

Omega 3 :

EPA and DHA

EPA and DHA (i.e. fish oil) 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 NSAID use in those with arthritis.

Supplemental fish oil dosage: EPA 3 – 5g/day,

DHA 0.8 – 2.7g/day.(Maroon & Bost, 2006; Calder, 2010; Akbar et al. 2017)


55

Omega 3 :

EPA and DHA

EPA and DHA functions: Therapeutic uses:

Neurological health

• EPA and DHA have neuroprotective properties and increase BDNF.

• 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

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.

(Krauss-Etschmann et al. 2008;

Bloch, 2011; Liao et al. 2019)


A vegetarian or vegan diet can meet EPA / DHA needs:

• 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.

Omega 3 :

EPA and DHA


Factors that determine Omega Fish oil quality:

• It is important to assess the sustainability practices of a

company when selecting a fish oil. Check if it is made from

sustainably caught fish approved by the Marine Stewardship

Council, where bycatch of non-targeted species is minimised.

• Check that the oil is independently tested

for purity and toxins, This will ensure

minimal levels of toxic chemicals such

as dioxins, PCB’s and heavy metals.

• When selecting a fish oil, make sure that

the EPA and DHA content is listed on the label.

Omega 3 :

EPA and DHA


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.

Omega 3 :

EPA and DHA

(James et al. 2003)


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).

Omega 3 :

EPA and DHA


Omega 6:

Linoleic Acid (LA)

LA is an omega-6 fatty acid, 18:2 n-6.

• Food sources include vegetable oils safflower,

sunflower, soybean, and corn oils. It is found in

nuts, seeds and some vegetables.

• Conversion of LA to GLA requires vitamin C, B3,

B6, magnesium and zinc.

60

lino- = Greek for ‘flax’ (linseed) –indicating its presence also in flaxseeds

-oleic = olive oil (‘oleic acid’)

Flax and hemp oil are

considered ‘nutritionally

superior’ to safflower

oil because they also

contain omega-3.


Omega 6:

Gamma-Linolenic Acid (GLA)

GLA is an omega-6 fatty acid, 18:3 n-6.

• Main food sources include evening

primrose oil, blackcurrant seed oil,

hemp and borage oils.

61


GLA therapeutic uses:

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 / d of borage seed oil.

ADHD • A combination of GLA and EPA shows

improvements in attention and impulsivity.

Eczema • Reduced inflammation; improves skin symptoms.

• Just be careful not to raise the levels of AA.

• Dosage: 320 mg GLA per day.

Omega 6:


(Zurier et al. 1996; Bamford et

al. 2013; Chung et al. 2013)


63

Omega 6:

Evening Primrose Oil (EPO)EPO is abundant in LA, and contains GLA which is also

present in borage, blackcurrant seed and hemp seed.

EPO therapeutic uses:

Premenstrual syndrome (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.

(Horrobin, 1983; Pruthi et al. 2010; Mahboubi, 2019)


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.

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.64

Omega 6:



Omega 6:

Arachidonic Acid (AA)

Arachidonic acid (AA) is an omega-6 fatty acid, 20:4 n-6.

• Arachidonic acid 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.65


Arachidonic acid is often seen as inflammatory, but:

• Inflammation is a key part of the immune system’s

response to injury and infection.

• 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).

Arachidonic acid

Omega 6:

Arachidonic Acid (AA)


Eicosanoids are made by the oxidation of omega-3 and 6 fats.

They are locally-acting hormone-like signalling molecules.

• They have a short life span and are involved in:

– Inflammation.

– Blood vessel permeability and constriction.

– Blood coagulation.

– Immune cell behaviour.

– Lipid accumulation.

– Central nervous system signalling.

• Eicosanoids include prostaglandins, leukotrienes,

thromboxanes, resolvins and protectins.67

Eicosanoidseicosa = 20

(carbon atoms)


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.68

Eicosanoids


Series 1 Prostaglandins

(PG1) — made from DGLA


(PG2) — made from AA


(PG3) — made from EPA

Keep blood platelets from

sticking together.

Mostly promote platelet

aggregation.

Some have weak platelet

aggregating properties.

Remove excess sodium

and water from the body.

Promote sodium and

water retention (↑ BP)

Prevent the release of AA

from cell membranes.

Relax blood vessels

promoting circulation.

Oppose functions of

series-1 prostaglandins.

EPA is the most important

factor limiting PG2

production.

ANTI-INFLAMMATORY PRO-INFLAMMATORY ANTI-INFLAMMATORY

69

Prostaglandins fall into three families or series,

depending on which fatty acid they are made from:

Eicosanoids


Eicosanoids made from arachidonic acid produce initial

inflammation. This is ‘shut off’ by the introduction of

eicosanoids made from DGLA and EPA.

Eicosanoids

(Boer et al. 2012)


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.

• 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.

EFA Metabolism

How might this

be applicable in

clinical

practice?


Genetic variability affects the synthesis of EPA

and DHA. Polymorphisms are common in the

genes coding for delta-6 and delta-5 desaturase.

• Other omega-6 and omega-3 fatty acids can

be synthesised from ALA and LA respectively.

• 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.

• Only 1–20% of ALA is converted to EPA.

• Women of reproductive age convert ALA 2.5 times better than men.72

polymorphism =

a genetic variationEFA Metabolism


EFA Metabolism

a-Linolenic acid (ALA) 18:3n-3


Delta-6-Desaturase 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

Delta-5-Desaturase inhibited by:

Insulin resistance

Zinc deficiency

Alcohol

Excess trans fats and cholesterol

Stress hormones, e.g. cortisol

High intake of EPA / DHA

Inhibitors of EFA Metabolism



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.

Maintaining the balance of omega-3 and omega-6

can be addressed by supplementing EPA / DHA, along with

addressing any co-factor deficiencies needed for interconversion.

• Fatty acid profile testing options:

– Genova — essential and metabolic fatty acids test (blood test).

– Wiley’s Finest — omega-3 index test (blood spot).

– Igennus — Opti-O-3 (blood spot).

Omega Testing


Cholesterol is an important compound for cell structure and

function. Beneficial properties are often overlooked because

of negative perceptions around cardiovascular disease risk.

• 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.

Cholesterol


77

Cholesterol

A diet rich in triglycerides stimulates cholesterol

synthesis in the liver and small intestine.

• It 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.

• Dietary cholesterol does not significantly affect

plasma cholesterol levels in most people as they are

primarily influenced by genetic and nutritional factors.(Lecerf & De Lorgeril, 2011; Kenny et al. 2020)


Doctors and other health officials often refer to cholesterol as

‘good’ and ‘bad’, especially in reference to heart health.

• LDL and HDL cholesterol are in fact carriers. Cholesterol sits

within these lipoproteins to be transported to wherever needed.

• A lot of other substances are carried within them

including CoQ10, beta-carotene and vitamin E.

• 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.

Cholesterol


Governments have led us to believe that saturated fat and

cholesterol simply clog up arteries and cause heart attacks.

• This led to a global cholesterol-lowering industry,

with around 200 million people taking statins.

• In 2009, a study found that ‘bad’ cholesterol

was lower in people with heart disease.

• Over a period of 10 years the percentage of

men aged 65–74 with high cholesterol dropped

from 87 to 54, whereas CHD remained at 20%.

• In 2004, the definition of low plasma cholesterol

dropped from below 6.5 mmol / L to below 5 mmol / L.

BHF advert

‘fat arteries’ https://www.yout

ube.com/watch?

v=cDAN7Oi62e0

Cholesterol

https://www.youtube.com/watch?v=cDAN7Oi62e0


Increases in cholesterol may indicate an increased demand for

cholesterol’s anti-inflammatory function or an increased need

for cholesterol to repair membranes, make hormones, etc.

• 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.

• There are varying sizes of LDL cholesterol.

Measuring particle size rather than total

cholesterol is a better health indicator.

Cholesterol


Cardiovascular Markers

• LDL particle size — 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.

• HDL particle size — larger HDL particles are more effective at removing cholesterol from the blood. Larger particles better exert anti-inflammatory and anti-thrombotic effects, as well as promoting nitric oxide production in endothelial cells.

What are the

physiological

effects of nitric

oxide?

(Eren et al. 2012)


• Lipoprotein (a) — lipoprotein (a) is 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.


(Sachdeva et al. 2009)


A GP cholesterol test – what does this tell us?

• Serum cholesterol above 5 mmol / L — GP prescribed a statin.

• Triglycerides (TGs) are high, but this is a non-fasting sample.

The optimal range is 0.79–1.24 mmol / L.



A functional test tells us much more about CV health.

↑LDL-P and normal

or ↓LDL-C levels =

higher CV risk.

LDL-P correlates

with carotid

atherosclerosis

and is more closely

associated with

obesity, diabetes and

insulin resistance

than LDL-C.



Phospholipids are the structural basis of all cell membranes.

Different types of phospholipids perform roles in cellular

function, such as insulin signalling.

• 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).

Lecithin increases the solubility of cholesterol

and helps improve cognitive function.

Phospholipids

(Blusztajn et al. 2017)


86

Therapeutic uses of key phospholipids:

Inositol • Improves insulin sensitivity and can subsequentlybe used in cases of insulin resistance

(e.g. Type 2 diabetes, PCOS).

Phosphatidylserine • Improves neuronal membrane functioning and cognitive function. It can be used in cases of depression, insomnia and stress.

Phosphatidylcholine • Neuro- and hepato-protective. It supplies choline for the synthesis of the neurotransmitter acetylcholine.

• Important for cognition, memory, immunity and hormone function.

Phospholipids Covered in more detail in the orthomolecular nutrients lecture

(Hellhammer et al. 2004; Moré et al.

2014; Blusztajn et al. 2017)


Case Study: Exercise

Troy 57 years, male. Works fulltime as a bus driver.

Aside from a bit of gardening is relatively inactive.

• Presenting with: Fatigue, especially on exertion and mild

hypertension. Troy’s GP wants him to take statins. Total

serum cholesterol 6.6, LDL 3.8, non fasting TGs 2.5mmol/L.

• Observations: Troy has a ruddy complexion and appears a little

breathless. He is overweight with obvious central adiposity.

• Dietary evaluation: High refined carbohydrates, non-organic /non

grass-fed red meat, processed omega-6 fatty acids and presence

of trans fats. Low complex carbohydrates, fibre and omega-3 fatty

acids. Low water intake, coffee x 4 day, 3 or 4 beers 2 x week.


Case Study: Exercise

Questions:

1. What lifestyle factors and signs / symptoms indicate

that Troy is at risk of cardiovascular disease?

2. What dietary factors are likely to be contributing

to his health concerns?

3. In regards to lipids, what are THREE

recommendations you would make and why?

4. Outline THREE other dietary recommendations

you would make and provide a rationale.

5. Are there any functional tests that you feel would provide a

clearer picture of the state of Troy’s health? If so, what are they?


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