Impact of IE fats on
health
Post-prandial effects lipoprotein
metabolism and plasma
concentrations, glycemic control
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Tom Sanders
Professor of Nutrition & Dietetics
Diabetes & Nutritional Sciences
Division, King’s College London
Disclosure of interest
• Research funding
– UK Food Standards Agency/Department of
Health
– Malaysian Palm Oil Board (mpob.gov.my)
• Member of Scientific Advisory Committee
of the Global Dairy Programme
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Available data
Small studies n<=16 – not RCTs
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Summers LK, Fielding BA, Herd SL, Ilic V, Clark ML,
Quinlan PT, Frayn KN. Use of structured triacylglycerols
containing predominantly stearic and oleic acids to
probe early events in metabolic processing of dietary
fat. J Lipid Res 1999;40:1890-8.
Yli-Jokipii K, Kallio H, Schwab U, Mykkanen H, Kurvinen
JP, Savolainen MJ, Tahvonen R. Effects of palm oil and
transesterified palm oil on chylomicron and VLDL
triacylglycerol structures and postprandial lipid
response. J Lipid Res 2001;42:1618-25.
Yli-Jokipii KM, Schwab US, Tahvonen RL, Kurvinen JP,
Mykkanen HM, Kallio HP. Chylomicron and VLDL TAG
structures and postprandial lipid response induced by
lard and modified lard. Lipids 2003;38:693-703.
Zampelas A, Williams CM, Morgan LM, Wright J, Quinlan
PT. The effect of triacylglycerol fatty acid positional
distribution on postprandial plasma metabolite and
hormone responses in normal adult men. Br J Nutr
1994;71:401-10.
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RCTs with n>16
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Sanders TA, Oakley FR, Cooper JA, Miller GJ. Influence
of a stearic acid-rich structured triacylglycerol on
postprandial lipemia, factor VII concentrations, and
fibrinolytic activity in healthy subjects. Am J Clin Nutr
2001;73:715-21.
Sanders TA, Berry SE, Miller GJ (2003). Influence of
triacylglycerol structure on the postprandial response
of factor VII to stearic acid-rich fats. Am J Clin Nutr
77: 777-782.
Berry SE, Miller GJ, Sanders TA. The solid fat content
of stearic acid-rich fats determines their postprandial
effects. Am J Clin Nutr 2007;85:1486-94.
Berry SE, Woodward R, Yeoh C, Miller GJ, Sanders TA.
Effect of interesterification of palmitic acid-rich
triacylglycerol on postprandial lipid and factor VII
response. Lipids 2007;42:315-23.
Sanders TA, Filippou A, Berry SE, Baumgartner S,
Mensink RP (2011). Palmitic acid in the sn-2 position of
triacylglycerols acutely influences postprandial lipid
metabolism. Am J Clin Nutr 94: 1433-1441.
Problems with previous studies
• Small numbers of subjects studied in many studies <16
• Study participants – healthy, young and predominantly
female
• Lack of standardized test meal protocol
• Fats often contained a high proportion of high melting point
fats >40⁰C
• No measure remnant particles (apolipoprotein B48)
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Research on dietary fats
• Most research measures the effects of dietary
fats in the fasting state
• Most of the time we are in the fed state
(postprandial)
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Exogenous Pathway
INTESTINAL
CELL
GO LGI
HDL
B4 8
E
C
I PA S
E
B48
CHYLOMICRON
ER
L IV
C
LYSOSOME
8
B4
E
E
REMNANT
NEFA
LI P O
PRO
T EIN
L
TAG
FFA
MAG
ADIPOCYTE
TAG
MUSCLE
Impaired postprandial lipaemia has adverse effects
on lipoprotein metabolism by generating more
atherogenic particles
Effect of different chain length fatty acids
on postprandial lipaema
Change in plasm a triglycerides after test m eal
mmol/l
3
18:1 cis
18:1trans
18:0
16:0
MCT
Low fat
2
1
0
0
1
2
3
4
5
6
7
8
hours
10
Sanders et al Atherosclerosis 2000, 149: 413-420
Postprandial lipaemia
Sanders et al. Atherosclerosis. 2000; 149:413-20.
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SALATRIM STUDY
Mean change in plasma TAG
from fasting with 95%CI
mmol/l
0.75
Oleate
Salatrim
Cocoabutter
0.50
0.25
0.00
3h
6h
12
Sanders et al. Am.J.Clin.Nutr. 2001, 73, 715-721.
SALATRIM meal decreased FVIIc and
FVIIa
FVIIc
change in FVIIc activity %
Oleate
30
SALATRIM
Cocoabutter
20
10
*
*
0
6h
3h
change in FVII a concentration ng/ml
Hours following test meal
FVIIa
2
*
1
*
0
3h
6h
Hours following test meal
Sanders, Oakley & Miller. Am J Clin Nutr. 2001; 73:715-21
Randomized vs Unrandomized cocoabutter
P<0.001
300
200
Unrandomized CCB
Randomized CCB
Plasma TAG (mmol/L)
2.5
100
2.0
0
Unrandomized
CCB
1.5
Randomized
CCB
Incremental area under curve
1.0
Diet x time effect P=0.003
0.5
0
1
2
3
4
5
6
Time (h)
Sanders et al. (2003)Am J Clin Nutr 77: 777-782
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Effect of randomization of palm
oil on postprandial lipaemia
Plasma TAG (mmol/L)
2.5
2.0
1.5
1.0
Randomised palm
Unrandomised palm
0.5
0
1
2
3
4
5
6
Time (h)
Berry et al Lipids 2007, 42, 315-323.
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Solid fat index curve determined by NMR
analysis
75
Unrandom ized CCB
Solids (%)
Random ized CCB
Random ized HOS
50
Unrandom ized shea
Random ized shea
25
0
30
35 37
40
45
50
Temperature (°C)
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Study methodology
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An intake of at least 50g fat is needed to produced reproducible
postprandial lipemia
Characterise the test fat with regard to chemical composition and physical
characteristics
Meals high in fat and exercise should be avoided on the day before the
test meal
The test meal should be able to be consumed within 10 minutes
Cannulation is preferred over repeated venepuncture
Blood should be samples up until a minimum of 6h up to 8h
Participants should have access to sip water throughout the procedure
Report incremental area under curve
Conduct study double-blind if possible
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Measurement of glucose and insulin
responses
• 75-80g carbohydrate in test meal is
equivalent to that use in an oral glucose
tolerance test
• Glycemic index testing uses 50g
• Measure c-peptide as an index of insulin
secretion
• Sample at 0,15,30,60,90,120 min also at 45
min if feasible
• Consider measuring gut peptide GIP, GLP-1
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Hypothesis
Fats with a high proportion of palmitic
acid in the sn-2 position will decrease
postprandial lipemia.
Outcome
• Primary outcome
Sample size calculations were based on 90%
power at P=0.01 to detect a 0.5 SD unit change in
the area under the curve for plasma triglycerides
which gave a sample size of 48
• Secondary outcomes were changes in apoprotein
B48 and non-esterified fatty acids (NEFA) and
insulin secretion and glucose
• Exploratory outcomes were postprandial changes
in inflammatory cytokines, GIP and PYY
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Study design
• A randomized cross-over design
conducted at 2 centres (London and
Maastricht)
• The study was conducted double-blind
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Participants and setting
• Healthy men and women recruited in two
centres
– Maastricht n=24
– London n=26
Cross-over design with treatment allocation
according to a Latin square design
Participants and investigators were blinded to the
treatment allocation
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Muffin and milkshake test meal
TAG fatty acid composition (wt %)
Test fats
SFA
MUFA
PUFA
sn-2 palmitic
acid (%)
Native palm olein (PO)
45
42
12
13
Interesterified palm olein (IPO)
45
42
12
41
Lard
44
43
10
55
7
81
11
0
High oleic sunflower oil (HOS)
Test meal macronutrient composition
Energy (kcal)
Carbohydrate (g)
Fat (g)
Protein (g)
905
91
50
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Solid fat content of the test fats (%)
Lard
Interesterified High Oleic Palm Olein
Palm Olein Sunfloweroil
(IV 56)
10°C
49.7
52.7
20°C
35.9
30.1
4.4
25°C
27.5
20.5
0.7
30°C
15.7
12.4
0.0
35°C
6.2
7.7
40°C
4.4
4.5
0.0
33.2
STUDY PROTOCOL
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4
a,b
3
iAUC
GM ± 95% CI
% change in plasma TAG
mean with 95% CI
80
Linear trend P=0.001
a,b
60
b,c
c
2
1
0
HOS
40
PO
Lard
IPO
20
0
1
2
3
4
5
Time (h)
-20
6
7
8
Postprandial changes in plasma nonesterified fatty acids (NEFA)
1.0
Lard
HOS
PO
IPO
Meal x time interaction P=0.0001
Plasma NEFA (mmol/L)
GM ± 95% CI
0.8
0.6
2nd meal
0.4
0.2
3
1
2
0.0
0
1
2
3
4
5
Time (h)
6
7
8
ApoB48
proportionate change from fasting
Postprandial changes in apolipoprotein B48
concentrations
1.0
0.8
0.6
Lard
High oleic sunflower oil
Palm olein
Interesterified palm olein
0.4
0.2
Meal x times P=0.006
0.0
0
1
2
3
4
5
Time (h)
6
7
8
Glucose-dependent insulinotropic polypeptide (GIP)
550
Meal x time P<0.0001
500
450
400
GIP (ng/L)
350
300
250
80
200
70
iAUC
a
150
a
b
60
b
50
100
40
50
HOS
PO
IPO
Lard
0
0
60
120
180
Time (min)
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C-peptide secretion
200
iAUC C-peptide
C-peptide (µg/L)
2500
2000
1500
175
150
125
HOS
PO
IPO
Lard
100
1000
500
0
0
60
120 180 240 300 360 420 480
Time (min)
Postprandial glucose no difference between treatments
but significant gender effect P<0.00001
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Other interesting observations
• Women showed much smaller increases in
plasma triglyceride than men
• Women secreted more insulin and had
lower postprandial blood glucose levels
than men
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Implications for long-term health/disease risk
• No evidence to indicate increased remnant
concentrations following IE fats
• Decreased postprandial lipemia following
higher melting points may have an
advantage in terms of decreased
postprandial activation of FVII
• Interesterified C16 fats do not differ from
naturally occurring C16 fats with regard to
postprandial effects on glucose homeostasis
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Risk-benefit considerations
• Benefit – IE can replace TFA
• Risk – none identified for IE fats with
regard to postprandial lipemia
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Gaps and research needs
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There is a lack of information regarding the effects of interesterified shorter chain
(C12-C14) fatty acids.
Need for head to head comparison of stearic rich vs palmitic rich interesterified
fats
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There is a lack of information regarding the effects of enzymically interesterified
fats rich in stearic acid.
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Most studies have been conducted on healthy subjects in the normal body weight
range. In view of the high prevalence of obesity and overweight and the growing
burden of type 2 diabetes, there is a need to evaluate the effects of interesterified
fats in the overweight/obese groups.
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There is emerging evidence that changing higher melting point fats as produced by
interesterification may influence the secretion of gut peptides that are involved in
hormonal signalling in postprandial period.
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