Lipids 2

Learning outcomes:
By the end of this session you will be able to:
To describe possible causes and effects of essential fatty
acid deficiency in humans.
Outline the use of fat in energy metabolism.
Discuss nutritional regulation of fatty acid profiles and
cholesterol levels (as a biomarker for CVD).
Summarise the role of lipids in health and disease
especially with regard to CHD, obesity and cancer.

Maldigestion/malabsorption of Lipids
Maldigestion:
Pancreatic lipase or bile insufficiency
Malabsorption:
Defective epithelium, bacterial infection
Coeliac disease (gluten sensitisation).
Results in - sprue - loss of villi:
steatorrhoea unabsorbed fat + bacteria in faeces
low EFAs
low fat-soluble vitamins
low energy (possibly)
Can be treated with medium-chain TG diet

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Essential fatty acids

Human body do not possess enzymes needed
to synthesize. Body cant insert double bond
before 9th carbon from -end
N-6 PUFA: Linoleic acid (LA) (C18:2n-6)
N-3 PUFA: Alpha-linolenic acid (ALA) (C18:3n-3)
Function:
Structural component of cell membranes
Precursors for the synthesis of LCFA and eicosanoids
Essential for growth and development of fetus and
baby (DHA retina, brain and nervous system; AA
growth)

Essential fatty acids

Synthesis of LCFA from EFA conditionally
essential:
Arachidonic acid (AA) (C20:4n-6)
Eicosapentaenoic acid (EPA) (C20:5n-3)
Docosahexaenoic acid (DHA) (C22:6n-3)

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Eicosanoids
Metabolically active hormone-like substances
Prostaglandins, thromboxanes, leukotrienes
Produced in nearly every cell in body
Regulate blood pressure, blood clotting, immune
function
Eicosanoids have different and sometimes
opposing functions

Metabolic pathways of essential fatty acids

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Conversion to LCFA
n-6 & n-3 compete for the same enzymes
Slow process, varies considerably in humans
Factors that might influence conversion:

Diet high in n-6 conversion to n-3 LCFA

Diet high in SFA, trans fatty acids
Age
Disease (e.g. diabetes)

Reported conversion rates highly variable

Some ALA converted to EPA, but very little to DHA

n-6:n-3 balance
Sufficient balance could help maintain or even
improve health
Recommended balance (under debate) range from 25-10:1
Western diet: 10-20:1
Because of technological and agricultural
development over last 100 years increased
intake of n-6 at expense of n-3.
Debate among academics re the importance of
balance
Some suggest n-3 without changing n-6
n-6 associated with decrease in CHD risk
Most Western populations, including NZ low intake
of n-3

151.232 2014 (Lipids 2)

EFA deficiency in humans

Rare in humans
Impaired growth in infants
Reproductive failure
Skin lesions
Impaired visual and cognitive function
Causes:

Premature births
Unsuitable breast milk substitute (e.g. skimmed milk)
TPN with no PUFA
Fat malabsorption disease

2 pools of lipids
Structural lipid pool
Membranes
Not usually hydrolysed for
energy
Higher prop of LC-PUFA
More diverse rarely
include TG
reserve of fat sol vits and
eicosanoid precursors
35-45% cholesterol (more in
skin and adrenal gland)

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Storage lipid pool

Adipose tissue
Principally TG (82%)

Palmitate
Sterate
Oleate
Linoleate

Reflects dietary fat

The energy paradox

Fatty acids cannot be converted to glucose or
amino acids, yet they remain our main stores of
energy
Brain requires 500 kcals/d of water soluble fuel
(usually glucose)
How do we deal with this?

Oxidation of FA to spare glucose

Fasting lipolysis also glycerol glucose
FA oxidation (liver)
ATP for gluconeogenesis
FA can be converted to ketone bodies

Sources of energy during moderate exercise (running)

Figure 5.12

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Dietary lipids & disease

Scientific evidence focus on:
Blood lipid profile
CVD (atherosclerosis)
Cancer
Obesity

CVD in NZ
CHD one of the leading causes of death among
New Zealanders.
The OECD 2008 Health Data report ranked NZ
first for deaths from acute myocardial infarction.
Most common cause = atherosclerosis
To decrease CVD aim to:
TC, LDL-C, TG
HDL-C

DHAH-study: 68% high cholesterol (>5mmol/L);

9.4% low HDL-C; 26% high TG (>1.7mmol/L)
(DHAH: Diabetes, Heart and Health study in Auckland, 2002-2003)

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Atherosclerosis
Atherosclerosis
Development of fatty plaque
within intima and media of
medium and large arteries
causing thickening of the
arterial wall and obstruction
of blood flow to the heart and
other tissue.
Occlusion of arteries
ischaemia & damage to
tissue Angina, Myocardial
infarction (heart attack),
stroke (brain)
Slow progressive disease
starting in childhood,
decades to develop.

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CHD
SFA
LDL-C, TC, HDL-C, TG
Positively associated with CHD
Chol raising SFAs:
lauric (C12:0) myristic (C14:0), palmitic (C16:0).
Stearic acid (C18:0) no effect on cholesterol.
However, pos. association with CHD (possibly
thrombotic)

Changes in CHD risk of replacing 5%E from SFA

with carbohydrate and other fats (Hu et al., 1997).

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CHD
Trans fatty acids
Positive association with CHD
LDL-C, TC, TG, HDL-C, inflammatory markers

Butter vs margarine
Studies comparing butter with margarine (containing
trans FA) showed that butter cholesterol compared
to margarine intake.
Combined effect of SFA + trans fatty acids +
cholesterol in butter (higher than in margarine).

CHD
Dietary cholesterol
LDL-C, TC
Response smaller than for SFA
Response differ in individuals. Some individuals more
vulnerable for effect of dietary cholesterol e.g. HL,
diabetics.

Plant sterols
LDL-C, TC
Meta-analysis of RCT - 2-3g/d (20-25g fortified
margarine) - LDLC with 10-15%.

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CHD
MUFA
Neg associated with CHD
Mediterranean diet high in fat (>40%E), especially
olive oil associated with lower incidence of CHD
/ TC, LDL-C, / HDL-C, / TG

PUFA: Neg associated with CHD

N-6:
TC, LDL-C, TG
HDL-C ( with PUFA >10%E),

N-3 (EPA, DHA):

TG (consistent effect of n-3)
HDL-C
/ LDL-C ( n-3 in HL patients)

N-3 PUFA
Interest in n-3 stimulated in 1970s Eskimos
high fat intake, rarely develop CHD.
Eat what sea provides (whale meat, seal
meat, sea birds, sea fish - high n-3 LCPUFA
content)
Today huge body of scientific evidence
dietary n-3 and health benefits, especially for
EPA + DHA. Less evidence for ALA.

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N-3 PUFA
risk for CHD
TG, cardiac arrhythmia (major cause of sudden
death - irregular electrical activity of the heart
muscle), blood clotting, blood pressure, inflammation,
improve endothelium function

Beneficial role in inflammatory disease (EPA

and DHA in particular)
(e.g. rheumatoid arthritis)

N-3 PUFA (Brain function)

N-3 PUFA (DHA) major PUFA in brain grey matter
Retinal & brain development of fetus & baby
DHAs role in structure & function of brain well supported
by basic research:
Incorporated into neural cell membranes
where affects various cellular and neuronal
processes.
Maintains optimal state of neural membrane fluidity and
thickness which in turn affects cell signally.
Increase neuroplasticity of nerve membranes and
synaptogenesis.
Protects brain tissue from lipid peroxidation.
May control brain glucose uptake and energy supply to the brain.

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N-3 PUFA
Affective disorders, e.g depression, attentiondeficit hyperactivity disorder, dyslexia.
Oxford-Durham Study (Richardson & Montgomery, May 2005):
117 children with Development Coordination Disorder (DCD)
(symptoms overlap with ADHD, dyslexia, problems with
motor function, learning, behavior, psychosocial adaptation).
3mo
n-3+n-6 (80% fish oil, 20% evening primrose oil) (558mg
EPA, 174mg DHA, 60mgGLA)
motor skills
Significant improvement in reading, spelling, behavior
compared to placebo

N-3 PUFA
Sinn & Bryan (2007): PUFA & micronutrients
learning and behaviour problems associated
with ADHD (Australia):
132 (104) children 7-12 years with ADHD
Randomized placebo controlled double-blind
intervention over 15 weeks.
Treatments: PUFA or PUFA + micronutrients or
placebo
PUFA: Eye qTM 400mg fish oil + 100mg evening
primrose oil). 6 capsules/day
PUFA improved ADHD symptoms (inattention,
hyperactivity / impulsivity) using Conners Parent
Rating Scale
Micronutrients no additional effect

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N-3 PUFA
Age-related cognitive decline & dementia
Alzheimer's disease:
Prospective epidemiology studies - decrease risk
RCT no effect in AD patients (limited evidence).

Mild cognitive impairment & age-related

cognitive decline: n-3 may slow cognitive
decline (limited evidence).
Healthy populations: limited evidence. May
improve reading, spelling, memory, reaction
time.

Very low-fat diets

Very low fat diets (<15%E), where fat is replaced
with CHO (>60%E) possibly deleterious effects:
TG
small dense LDL particles
HDLC
Atherogenic lipoprotein
phenotype
insulin resistance

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Dietary fat & cancer

Association between total fat intake and cancer
(breast, colon, prostate cancer).
Some studies relationship between some types
of cancer and animal fat or meat.
Populations (ecological studies) with diets high
in MUFA (olive oil) or PUFA (fish oil) protect
against colon cancer compared to animal fats.
Results mostly inconclusive.
Strongest association between dietary fat and
cancer is for prostate cancer.

Dietary fat & obesity/overweight

Pos association between %E fat and
obesity/overweight
Obesity multi-factorial. Fat not main cause

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Dietary guidelines for adults

Total fat (%E)*

20-35

SFA (%E)

<7-10

Trans FA (%E)

<1.0

MUFA (%E)

>10

PUFA (%E)*

LA: 4-5 10%

ALA: 0.4-0.5 1%
EPA+DHA+DPA#:
Men: 610mg/d
Women: 430mg/d

N-6:N-3

2-5-10:1

Cholesterol (mg/day)

<300mg/dag

*Acceptable macronutrient distribution ranges (AMDR) to reduce

chronic disease + ensure adequate micronutrient status
#Suggested dietary target

Recommendations: LC n-3 PUFA

NRVs Australia & NZ (adults):
AI: Men: 160mg/d; Women: 90mg/d
Based on median intakes of Australian/NZ
population.
SDT: Men: 610mg/d; Women: 430mg/d
Set when convincing evidence of reduced chronic
disease risk
Based on 90th percentile of intakes of Australia/NZ
population

UL: 3000mg/d
US FDA: GRAS (Generally Recognised As Safe)
for inclusion in diet.

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Total fat intake (%E) in NZ

(2008/2009 NZ ANS)

University of Otago, Ministry of health. A Focus on Nutrition: Key findings of the 2008/2009 New Zealand
Adult Nutrition Sruvey. Wellington: Ministry of Health, 2011.

SFA intake (%E) in NZ

(2008/2009 NZ ANS)

University of Otago, Ministry of health. A Focus on Nutrition: Key findings of the 2008/2009 New Zealand
Adult Nutrition Sruvey. Wellington: Ministry of Health, 2011.

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PUFA, MUFA & cholesterol intake in NZ

(2008/2009 NZ ANS)
PUFA, mean (95% CI): 4.9 (4.8 4.9)%E
MUFA: 12.4 (12.2 12.6)%E
Cholesterol: 281 (285 385)mg/d
Men: 333 (299 333)mg/d
Women: 219 (206 232)mg/d

University of Otago, Ministry of health. A Focus on Nutrition: Key findings of the 2008/2009 New Zealand
Adult Nutrition Sruvey. Wellington: Ministry of Health, 2011.

Dietary sources
2008/2009 NZ ANS

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Dietary sources
2008/2009 NZ ANS
From total fat: Butter & margarine (9%);
Potatoes, kumara & taro (6%); Bread-based
dishes (6%); Poultry (6%); Milk (5%); Beef &
veal (5%); Bread (4%); Cakes & muffins (4%);
Cheese (4%); Grains & Pasta (4%).
From SFA: Butter & margarine (8%); Milk (8%);
Bread-based dishes (6%); Cheese (6%);
Potatoes, kumara & taro (6%); Cakes & muffins
(5%); Poultry (5%); Beef & veal (5%); dairy
products (5%); sausages & processed meats
(4%)

151.232 2014 (Lipids 2)