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Lipids 2Learning 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 LipidsMaldigestion:

Pancreatic lipase or bile insufficiencyMalabsorption:

Defective epithelium, bacterial infectionCoeliac 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 acidsHuman body do not possess enzymes needed to synthesize. Body cant insert double bond before 9th carbon from -endN-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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EicosanoidsMetabolically active hormone-like substancesProstaglandins, thromboxanes, leukotrienesProduced in nearly every cell in bodyRegulate blood pressure, blood clotting, immune functionEicosanoids have different and sometimes opposing functions

Metabolic pathways of essential fatty acids

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Conversion to LCFAn-6 & n-3 compete for the same enzymesSlow process, varies considerably in humansFactors 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 balanceSufficient balance could help maintain or even improve healthRecommended balance (under debate) range from 2-5-10:1Western 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 balanceSome 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

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EFA deficiency in humansRare in humansImpaired growth in infantsReproductive failureSkin lesionsImpaired visual and cognitive functionCauses: Premature births Unsuitable breast milk substitute (e.g. skimmed milk) TPN with no PUFA Fat malabsorption disease

2 pools of lipidsStructural lipid pool

MembranesNot usually hydrolysed for energyHigher prop of LC-PUFAMore diverse rarely include TGreserve of fat sol vits and eicosanoid precursors35-45% cholesterol (more in skin and adrenal gland)

Storage lipid poolAdipose tissuePrincipally TG (82%) Palmitate Sterate Oleate Linoleate

Reflects dietary fat

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The energy paradoxFatty acids cannot be converted to glucose or amino acids, yet they remain our main stores of energyBrain 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

Figure 5.12

Sources of energy during moderate exercise (running)

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Dietary lipids & disease

Scientific evidence focus on:Blood lipid profileCVD (atherosclerosis)CancerObesity

CVD in NZCHD 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 = atherosclerosisTo 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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AtherosclerosisAtherosclerosis 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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CHDTrans 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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CHDMUFA 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 PUFAInterest 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 matterRetinal & brain development of fetus & babyDHAs role in structure & function of brain well supported by basic research: Incorporated into neural cell membranes

where affects various cellular and neuronalprocesses.

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 PUFAAffective disorders, e.g depression, attention-deficit 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).3mon-3+n-6 (80% fish oil, 20% evening primrose oil) (558mg EPA, 174mg DHA, 60mgGLA) motor skillsSignificant improvement in reading, spelling, behavior compared to placebo

N-3 PUFASinn & 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 (60%E) possibly deleterious effects: TG small dense LDL particles HDLC insulin resistance

Atherogenic lipoprotein phenotype

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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/overweightObesity multi-factorial. Fat not main cause

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Total fat (%E)* 20-35

SFA (%E)

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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.

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)

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PUFA, MUFA & cholesterol intake in NZ(2008/2009 NZ ANS)

PUFA, mean (95% CI): 4.9 (4.8 4.9)%EMUFA: 12.4 (12.2 12.6)%ECholesterol: 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 sources2008/2009 NZ ANS

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Dietary sources2008/2009 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%)