Transcript Omega-3 Nutrition-Fish versus Supplements

Omega-3 Nutrition- Fish versus Supplements
CSIRO FOOD AND NUTRITION
Manny Noakes Research Director
n-3 LC PUFA intake
• LC PUFA n-3 reputed wide-ranging
health benefits.
• Humans limited capacity to
synthesize n-3 LC.
• Consumption of preformed n-3LC
PUFA s needed.
• Seafood best dietary source.
~20% Australians consumed fish
& seafood
(Aus Health Survey 2011/12)
Vegan, vegetarian and non fish
consumers may be very low in n-3
LC PUFA
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Slide from W Stonehouse
Median n-3 LC PUFA intakes (mg/day)
Year of data
collection
Country
Population
Greenland
Eskimos
1976
13,000
Canada
Inuit of Nunavik
1992
2115
James Bay Cree
1992
800
∼2008
207
Kyushu<comma> SW island of Japan
1999
905
INTERLIPID study Aito Town
2003
810
INTERLIPID study Japanese living in Hawaii
2003
310
France
All regions of France
1995
364
Nth Sth Europe
7 Centres in Europe
2003
239
Belgium
Women living in Flanders
2009
199
Australia
1995 National Nutrition Survey
Germany
German Nutrition Survey
USA
USDA
Netherlands
Rotterdam coronary calcification study
Quebec
Japan
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Meyer et al 2011
Median intakes (mg/day)
1995
1998
1994–1996
1993
170
160
∼115
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Current Australian Guidelines
• NHMRC nutrient reference values (NRVs) in 2006 for omega-3
LCPUFA recommending both an adequate intake 160mg/day
(men) and 90mg/day (women) and a suggested dietary target to
prevent chronic disease – 600mg/day for men and 400mg/day for
women.
• FSANZ also supports the consumption of omega-3 LCPUFA by
allowing general-level health claims for heart health on
commercially available food products. The food must contain a
minimum of 50 mg EPA+DHA combined in a serving of food.
• Australian Dietary Guidelines recommend at least 2 serves of (any)
fish per week.
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Slide from W Stonehouse
Health Claims for Heart Health
FSANZ
EPA & DHA contribute to heart health
EFSA
• DHA & EPA contribute to normal function of the heart (0.25 g/d)
• DHA & EPA contribute to maintenance of normal blood pressure (3
g/d)
• DHA & EPA contribute to maintenance of normal blood triglyceride
levels (2 g/d)
• DHA contributes to maintenance of normal blood triglyceride
levels (2 g/d in combination with EPA)
FDA
Supportive but not conclusive research shows consumption of EPA &
DHA omega-3 fatty acids may reduce risk of coronary heart disease.
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Slide from W Stonehouse
2008
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Recommendations
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Systematic reviews – literature between 2007-2013
FISH OIL SUPPLEMENTS
• Are omega-3 LCPUFA supplements effective in the primary prevention of coronary heart
disease?
• Are omega-3 LCPUFA supplements an effective intervention for the secondary prevention
of CHD?
• Are omega-3 LCPUFA supplements effective in the prevention or treatment of heart
failure?
• Are omega-3 LCPUFA supplements an effective intervention for lowering plasma
triglycerides in hypertriglyceridaemic patients?
FISH
• Is the reported consumption of omega-3 LCPUFA from fish associated with lower incidence
of CHD events in primary prevention?
• Is the reported consumption of fish associated with a lower incidence of CHD in patients
with existing CHD (i.e. secondary prevention)?
• Is the reported consumption of fish, or dietary patterns high in omega-3 LCPUFA
associated with lower incidence of heart failure?
Fish Oil Studies
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Are omega-3 LCPUFA supplements effective in the
primary prevention of coronary heart disease?
There
no current
evidence that omega-3 LCPUFA
Kotwal etis
al 2012
Level 1
• Omega 3 Fatty acids and cardiovascular
outcomes:
supplementation
is
beneficial
or the primary
systematic review and meta-analysis
Rizos et al 2012 Level
1CHD
prevention
of
• Association between omega-3 fatty acid supplementation
and risk of major cardiovascular disease events: a systematic
review and meta-analysis
Bosch et al 2012 Level 11
• n-3 fatty acids and cardiovascular outcomes in patients with
dysglycemia
Itakura et al 2011 Level 11
• Relationships between plasma fatty acid composition and
coronary artery disease
Roncaglioni et al. 2013 Level 11
• n-3 fatty acids in patients with multiple cardiovascular risk
factors
doses of EPA/DHA was 1-2 g
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Kotwal et al 2012 a systematic review and meta-analysis
Level 1 Evidence
20 trials and >60 000 patients
No effect of ω-3 fatty acids on composite cardiovascular outcomes
Copyright © American Heart Association, Inc. All rights reserved.
Are omega-3 LCPUFA supplements effective in the
secondary prevention of coronary heart disease?
5 Level 1ismeta-analyses
included: Kotwal
et al.; Rizos LCPUFA
There
no currentwere
evidence
that omega-3
et al.; Kwak et al.; Zhao et al., and Marik et al.
supplementation
is beneficial for the secondary
The two meta-analyses published prior to 2010 provided
prevention
of CHD
evidence of benefit
in patients with existing CHD, but the
meta-analyses published after 2010 did not.
3. Level II RCTs included the OMEGA study (2010), Alpha to
Omega study (2010) and GISSI Heart Failure (GISSI-HF)
trial
2 trials provided 1 g EPA/DHA, one for 1 year (OMEGA and
GISSI-HF), while the Alpha-Omega trial provided 400 mg
EPA/DHA. The OMEGA trials did not find evidence of a
beneficial effect
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Might statins inhibit LC PUFA n-3?
– possible mechanisms
• de Lorgeril et al BMC Medicine 2013
• Statins increase arachidonic acid, the main
n-6 fatty acid in cell membranes .
• This may in turn inhibit the protective
effects of n-3 because n-6 and n-3 fatty
acids are in competition through various
pathways involved in the development and
complications of CHD.
• Thus statins may inhibit n-3 by interfering in
the n-3/n-6 interplay and favoring n-6.
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Does Statin Use Mitigate the Benefit of Omega-3
Fatty Acids?
• Seth et al. 2014 Meta-Regression of
Randomized Trials
• 23 studies with 38,910 n-3 LCPUFA;
38,866 controls .
• Lower control group statin use (b =
0.222, P = 0.027) and higher DHA/EPA
(b = -0.105, P = 0.033) ratio was
associated with higher reduction in
total mortality.
Statin use may mitigate, and higher DHA/EPA ratio is associated
with the beneficial effect of PUFA supplementation.
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Are omega-3 LCPUFA supplements effective in the
prevention or treatment of heart failure?
GISSI-HF
7,000benefit
patientsfrom
with functional
There
is trial
modest
1g n-3 Class
II to IV heart
failurefailure
were randomised
to 1 g/day
LCPUFA
in heart
and in particular
or placebo. Over a 3.9-year median follow-up,
in those with greater absolute CHD risk.
supplementation resulted in an absolute 9%
reduction in mortality or admission to hospital
(p=0.04).
Benefit was greater in elderly and diabetic
patients and those with impaired left ventricular
function (sub-groups with greater absolute risk).
Around 300,000 Australians are living with heart failure, and every
year around another 30,000 people are newly diagnosed with it
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Are omega-3 LCPUFA effective for lowering plasma
triglycerides in hypertriglyceridaemic patients?
2 These
positivedata
meta-analyses
confirm high doses n-3
• LCPUFA
Hartweg et
andfor
Reiner
et al. 2011
asala 2007
means
lowering
plasma triglyceride levels .
Effective Dosage:
•Starting with 1200 mg/day DHA+EPA
Increase if needed to:
• 4000 mg/day
• Checking patient’s response every 3-4 weeks
when the dose is changed, until target TG
levels reached.
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Do Omega-3 LCPUFA Alter the Risk or Incidence of
High Blood Pressure?
• 3 meta-analyses Appel et al 1993, Geleijnse
et al 2002, Morris et al 1993 have shown
that omega-3 LCPUFA reduce BP with the
greatest effect in hypertensive patients
-3.4 to -5.5 mmHg systolic BP
-2.0 to -3.5 mmHg diastolic BP
• Dokholyan et al. 2004 also suggested that
greater than >3 g/day n-3 LCPUFA is
required to reduce BP in patients with highnormal diastolic BP or stage 1 hypertension.
Mori et al. showed that in overweight, mildlyhypercholesterolaemic patients, 4 g/day of encapsulated DHA, but
not EPA, reduced 24-hour BP by -5.8/-3.3 mmHg.
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EPA/DHA and blood pressure: a meta-analysis.
Miller et al 2014
• Effect of EPA+DHA on blood pressure
in RCTs.
• 70 RCTs were included.
• The strongest effects in untreated
hypertensives
systolic blood pressure = -4.51 mm Hg
diastolic blood pressure = -3.05 mm Hg
• BP also lowered among
normotensives
Provision
of EPA+DHA
systolic
blood pressure
= -1.25reduces
mm Hg systolic BP, while
provision
of ≥2g omega3
LCPUFA
reduces diastolic BP.
diastolic
blood pressure
= -0.62 mm
Hg
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Omega-3 and LCPUFA Rheumatoid Arthritis
• Patient-assessed pain,
morning stiffness, number of
painful and/or tender joints
and non-steroidal antiinflammatory drug (NSAID)
consumption
• Large dosages EPA+DHA
(>3g/d) needed for 3 months
to see symptomatic benefits.
• 1yr trial, 5.5 g EPA+DHA/d
–
st
lower failure rate of 1 -line
therapy (Proudman et al. 2015)
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n-3 LCPUFA and
Cognition
Suggestive evidence DHA
enhances learning and cognitive
development in children;
memory and reaction time
• 3 Meta-analyses – n-3 LCPUFA
particularly:
improved memory, attention &
• Individuals with low habitual intake
processing speed in adults with
of LC n-3
mild cognitive impairment /
• Children with low literacy ability
age-related cognitive decline
• Age-related cognitive decline
Stonehouse et al 2013
Stonehouse et al 2014
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Slide from W Stonehouse
Yurko-Mauro et al 2015
Mazereeuw et al 2012
Cooper et al 2015
n-3 LCPUFA & Depression
Meta-analysis (Martins, 2009):
• Symptoms of depression significantly
reduced with pure ethyl-EPA and
high EPA (>50%) supplements.
• No effects seen with pure DHA or high
DHA (>50%) supplements.
• Greatest effects in therapeutic populations
(bipolar disorder and major depression) vs.
mild-to-moderate depression
• Dose-response effect.
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n-3 LCPUFA in depression
• Sublette et al 2011 - 15 trials 916 participants
• % EPA in the supplements was the fixed-effect
predictor, dichotomized into 2 groups:
EPA < 60% or EPA ≥ 60% of the total EPA + DHA
• Supplements with EPA ≥ 60% showed benefit on
standardized mean depression scores (effect size =
0.532; P < .001) versus supplements with EPA <
60% (effect size = -0.026; P = .756)
• Supplements with EPA < 60% were ineffective.
Supplements containing EPA ≥ 60% of total EPA + DHA, in a dose
range of 200 to 2,200 mg/d of EPA in excess of DHA, were
effective against primary depression.
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Fish/Dietary Studies
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Is consumption of omega-3 LCPUFA from fish associated with
lower incidence of CHD events in primary prevention?
Prospective cohort studies
• de Goede et al , 2010 Marine (n-3) fatty acids, fish
consumption, and the 10-year risk of fatal and
nonfatal coronary heart disease in a large population
of Dutch adults with low fish intake
• Joensen et al 2011 Marine n-3 polyunsaturated fatty
acids in adipose tissue and the risk of acute coronary
syndrome
• Mozaffarian et al 2013 Plasma phospholipid longchain omega-3 fatty acids and total and causespecific mortality in older adults: a cohort study
• Musa-Veloso et al. 2011 Impact of low v. moderate
intakes of long-chain n-3 fatty acids on risk of
coronary heart disease
– benefit with >250 mg omega-3 LCPUFA from fish
reducing the risk of sudden cardiac death by 35%
• Streppel et al 2008 Long-term fish consumption and
n-3 fatty acid intake in relation to (sudden) coronary
heart disease death: the Zutphen study
There is good evidence that increased consumption of
fish or dietary patterns with omega-3 LCPUFA are
associated with the primary prevention of coronary
heart disease (Level 111)
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Is consumption of fish associated with lower
incidence of heart failure?
Prospective cohort studies
observational
data are
supportive
•These
Meta-analysis
-7 prospective
cohort
studies - of a modest
inverse
fish
176,441association
subjects withbetween
5,480 cases
of consumption
heart failure. and
High fish
intakeLevel
protective
heart
failure.
III against developing HF.
• Cardiovascular Health Study - 4,738 US adults
>65y. Highest quintile had 32% lower risk
compared to those who consumed fish < or = to
1/month (p trend 0.009).
• A 14.3-year follow-up -The Atherosclerosis Risk in
Communities (ARIC) study - plasma phospholipid
omega-3 LCPUFA (especially EPA) at baseline
inversely correlated with heart failure in women
but not in men (P<0.001).
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Is consumption of fish associated with lower CHD in
patients with existing CHD (i.e. secondary prevention)?
Evidence support s the consumption
Evidence from prospective cohort studies
of
fish
oilystudies.
fish for
Only
twoincluding
applicable new
secondary prevention of CHD. Level III
Manger et al. 2010, Dietary intake of
n-3 long-chain PUFA and coronary
events in Norwegian patients with
coronary artery disease.
Pottala et al 2010 Blood EPA and
DHA predict all-cause mortality in
patients with stable coronary heart
disease: the Heart and Soul study.
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Are Omega-3 LCPUFA from Fish Associated with
Lower Stroke Risk?
• Mozaffarian et al. (2013) reported total plasma
phospholipid
omega-3
LCPUFA
were
inversely
These
data
suggest
that
fish
intake
related to ischaemic stroke risk (p=0.043) with a
associated
with
lower
stroke
risk.
37% reduction in
the highest
versus
the lowest
quintile, but there was no significant effect on
haemorrhagic stroke (p=0.86).
• DHA most strongly associated with reduction in
ischaemic stroke and DPA with reduction in stroke
death.
• Larsson et al., meta-analysis of fish consumption
and stroke in 15 prospective studies, - increment
of 3 servings of fish/week associated with a 6%
lower incidence of total stroke.
• Interventions with fish oil supplementation have
not demonstrated any reduction in stroke.
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is
Key Findings:
Omega-3 LCPUFA supplements - neither a beneficial nor adverse
effect demonstrated in primary or secondary prevention of CHD.
•The evidence continues to be positive for the role of omega-3
LCPUFA in the treatment of hypertriglyceridaemia
•The evidence continues to be positive for the role of omega-3
LCPUFA as a benefit to prevent heart failure.
•Higher fish intake was associated with lower incident rates of
heart failure in addition to lower sudden cardiac death, stroke and
myocardial infarction.
2015
Recommendations
FISH
• Dietary intake of fish consistently found to be of benefit for the
protection from heart disease and stroke. Higher fish intake was
associated with lower incident rates of heart failure,o lower sudden
cardiac death, stroke and myocardial infarction.
• Heart Foundation recommends all Australians include 2-3 three serves
fish (including oily fish)/week as part of a heart healthy eating pattern.
• This amount of fish provides between 250-500 mg per day of combined
docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).
SUPPLEMENTS
• Omega-3 LCPUFA supplements can be considered in patients with heart
failure in additional to standard therapy.
• Omega-3 LCPUFA supplements are effective in the treatment of
hypertriglyceridaemia.
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