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Why repeated meta-analyses can show very different results?
1. Why repeated meta-analyses
and systematic reviews
may produce different
outcomes?
Recent meta-analyses on fat as an
example
Registered dietitian, M.Sc, MBA
Reijo Laatikainen
www.twitter.com/pronutritionist
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2. Why this slide deck?
• Early 2014 a meta-analysis by Chowdhury et al. in Annals of Intern
Medicine concluded that omega-6 fat intake is not associated with
coronary heart disease in prospective cohorts
• In contrast in August 2014 a meta-analysis by Farvid et al. in Circulation
concluded that linoleic acid is associated with reduced risk of coronary
heart disease both independently and in substitution model against
saturated fat
• In this slide deck I compare subtle differences in Chowdhury’s and
Farvid’s meta-analyses and their effect on the overall findings
• I only compare the representative analyses, ie. the reported fat intake
and risk of coronary heart disease (CHD). Chowdhury’s other analyses
on RCTs and circulating fatty acids are beyond the scope of this slide
deck.
2
3. Meta-analyses Chowdhury et al.
(2014) vs Farvid (2014) regarding
linoleic acid (omega-6 FA) intake
in prospective cohorts
3
4. High versus low intake of omega-6 fatty
acid/linoleic and risk of coronary heart
disease
Chowdhury
Risk of CHD
(omega-6 FA
intake as
variable)
95 %
Confidence
interval
0.98 0.90-1.06
Farvid
Chowdhury R et al. Association of dietary, circulating, and supplement fatty acids with coronary risk: a
systematic review and meta-analysis. Ann Intern Med. 2014 Mar 18;160(6):398-406.
Farvid M. et al. Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-
Analysis of Prospective Cohort Studies. Circulation. 2014 Aug 26. pii: CIRCULATIONAHA.114.010236.
4
Risk of CHD
(Linoleic acid
intake as
variable)
95 %
Confidence
interval
0.85 0.78-0.92
5. 1.
Re-use of the original studies
differ between meta-analyses
5
6. Farvid used original categorization of fat
intake but Chowdhury created new thirds
Chowdhury – new ”thirds” Farvid –original categories
Chowdhury R et al. Association of dietary, circulating, and supplement fatty acids with coronary risk: a
systematic review and meta-analysis. Ann Intern Med. 2014 Mar 18;160(6):398-406.
Farvid M. Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-
Analysis of Prospective Cohort Studies. Circulation. 2014 Aug 26. pii: CIRCULATIONAHA.114.010236.
6
7. You may lose the actual effect of
very high or low intake if you
transform quintiles/quartiles to
thirds (Chowdhury)
On the other hand, you don’t have
same metrics between individual
studies if you compare quintiles to
thirds (Farvid)
7
8. 2.
Meta-analyses include and
exclude studies differently
depending on the search strategy
defined before literature search
8
9. Studies included re: linolic acid intake
and risk of coronary heart disease
9
Studies
Only in Chowdhury
Studies
Only in Farvid
Included in both
Chowdhury and Farvid
MrFit*
Glostrup
KIHD
Monica (F)
Monica (M)
Aric (F)
Aric (M)
FMC (F)
FMC (M)
WHS
VIP
Morgen
NHS
HPFS
ATBC
MDC (ie. Malmö study)
*) MrFit was included also in Farvid’s CHD mortality analysis but not in overall analysis of CHD events
10. No wonder that results are
different.
Selection of studies is strikingly
different.
10
11. 3.
Only Farvid’s meta-analysis
included fat substitution
modelling
11
12. A 5% of energy increment in LA intake
replacing energy from saturated fat
intake was associated with a 9% lower
risk of CHD events in Farvid’s meta-analysis
Chowdhury Farvid
Chowdhury R et al. Association of dietary, circulating, and supplement fatty acids with coronary risk: a
systematic review and meta-analysis. Ann Intern Med. 2014 Mar 18;160(6):398-406.
Farvid M. et al. Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-
Analysis of Prospective Cohort Studies. Circulation. 2014 Aug 26. pii: CIRCULATIONAHA.114.010236.
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13. Conclusion
• Chowdhury’s and Farvid’s meta-analysis have less studies in common
than they do not have in common (5 vs 11 studies)
• Using the original categorization of data vs calculating new perhaps
more comparable categories may either highlight or dim the actual
effects
• It’s important to consider direct fat-by-fat substitutions. Increased intake
of carbohydrate or certain protein qualities can mask real effects of
saturated fat if fat is replaced by them rather than (certain) fatty acids.
Fat subsititution was done only in Farvid’s meta-analysis
• Researchers can intentionally or unintentionally manipulate the
outcomes of meta-analyses by (subtly) changing research methods and
words describing what is being done.
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14. Wellcome aboard!
http://twitter.com/pronutritionist
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http://www.pronutritionist.net
Reijo Laatikainen, RD, MBA
Images bought and licensed from BigStockPhoto. Snapshots from papers and sites referred to.
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