Evidence for beneficial effects of the trans fat, vaccenic acid, on health

1
Evidence for beneficial effects of the trans fat,
vaccenic acid, on health

• Catherine J. Field PhD RD
• Professor of Nutrition
• Dept of Agricultural, Food Nutritional Science
• Alberta Diabetes Institute Alberta Institute
  for Human Nutrition
• University of Alberta, Edmonton

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Outline

• Background on Vaccenic Acid (VA)
• Review of the Literature on Cancer Heart
  Disease
• Epidemiological
• Cell culture/animal studies
• Our work on VA in an animal model of metabolic
  syndrome
• Lipids
• Immune function

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Trans fats

• Heterogeneous group of fatty acids
• Formed during partial hydrogenation of plant oils
• Formed in the rumen during the biohydrogenation
  of unsaturated fats

Conjugated linoleic acid (CLA) Vaccenic acid (VA)
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Formation of Vaccenic acid
Linolenic
acid c9,c12,c15C183
isomerization
Linoleic acid c9,c12C182
isomerization
c9,t11,c15C183
hydrogenation
CLA c9,t11C182
t11,c15C182
hydrogenation
hydrogenation
VA t11C181
saturation
Stearic acid C180
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Vaccenic Acid (VA)

• Represent 1-12 of dairy fat 1.5-5 of beef fat
• Only dietary precursor of CLA in humans
• Increased in CLA-enriched foods
• But it is also in hydrogenated fats (13-17 of
  trans fat)
• Does VA contribute to some of the adverse health
  effects of industrially-derived TFA?

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Vaccenic Acid Risk of Cancer and Heart Disease
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Vaccenic Acid Cancer

• Epidemiological studies suggest
• Inverse relationship of plasma/intake of VA with
  cancer risk
• (Aro et al. 2000 McCann et al. Biomarkers Prev
  13 1480, 2004)
• Human tumour cell lines
• Incubation with VA is reported to reduce cell
  growth (Awad et al., 1995Miller et al., 2003)

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VA Animal Models of Cancer

• Chemical-induced models
• 2 w/w VA inhibited mammary tumours (Banni et al.
  2001, Corl et al. 2003)
• Hypothesized that the effects due to conversion
  to CLA
• Block the ?9 desaturase enzyme but did not
  completely block the effect of feeding VA (Lock
  et al. 2004a)

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Conclusions VA Cancer

• 4 of 5 epidemiological studies suggest an inverse
  relationship between intake cancer risk
• Suggestions from animal studies that VA may have
  some benefits (early in the cancer process)

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VA Heart Disease

• Epidemiological studies suggest
• No risk associated with CHD found
• (Ascherio et al. 341 581, 199 Roberts et al.,
  1995 Clifton et al., 2004 Hodgson et al., 1996
  )
• Animal study
• Hamster study fed a very high level (10 of
  energy) reported VA increased plasma
  cholesterol (Meijer et al., 2001)

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Conclusions VA Heart Disease

• Consumption does not appear to be associated with
  risk in epidemiological studies
• Lack of animal and human studies

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Our Research on VA Health
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Purpose

• To determine the effects of feeding VA on the
  metabolic (glycemic lipid) and immune
  (inflammatory/ functional) abnormalities that
  occur in the metabolic syndrome
• To use a unique animal model
• 3 week trial (short term)
• 16 week trial (long term)

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JCRLA-cp Rat
Corpulent Gene (cp) Stop Codon (recessive) No
functional Leptin Receptors
Elevated Leptin
Kidney damage glomerular sclerosis
Over eating and Obesity
Early Type-2 Diabetes and Metabolic Syndrome
Myocardial lesions Infarct
Elevated Insulin (pre-Type-2)
Vascular lesions atherosclerosis
Elevated Lipids (TGs, LDL, VLDL)
Vascular and endothelial dysfunction
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Experimental Design (short-term VA study)
Metabolic Syndrome JCR-La cp/cp

• Lean Control

3-week diet
Control Diet (N10)
VA 1.5 w/w (N10)
VA 1.5 w/w (N10)
Control Diet (N10)
Primary Endpoints body weight, food intake,
blood lipids, insulin sensitivity and inflammation
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Fatty acid composition of the diets
30
25
Control
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Percentage w/w of fat
VA
15
10
5
0
181 (9)
VA 181(t11)
182 (6)
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Short term feeding of VA

• VA does not cause detrimental health effects in
  either obese or lean animal

• Normal growth curve
• No change in weight gain
• No reduction in food intake
• No change in glycemic parameters
• No adverse effects on insulin sensitivity

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Effect of Feeding VA on Fasting Triglycerides

Control diet
VA diet
Lean
Obese
N10/group

19
Effect of Feeding VA on Fasting LDL-cholesterol
b
Control diet
b
VA diet
a
a
Obese
Lean
N10/group
20
Effect of Feeding VA on Fasting HDL-cholesterol
Control diet
b
VA diet
b
a
a
Lean
Obese
N10/group
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Effect of Feeding VA on Serum Haptoglobulin
3
Control diet
b
VA diet
b
2.5
2
mg/mL
1.5
a
a
1
0.5
0
lean CTL
lean TVA
obese CTL
obese TVA
22
Effect of Feeding VA on mitogen stimulated
cytokine production by splenocytes
Control diet
VA diet
350
b
b
300
ab
a
250
a
a
a
a
200
Cytokine Production (pg/mL)
150
100
50
0
lean
obese
lean
obese
TNF-a
IL-6
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Metabolic effects of short term feeding of
Vaccenic acid

• No adverse health effects
• weight gain or food intake
• fasting glucose or insulin
• response of glucose or insulin to a meal
  challenge
• inflammation
• Potential health benefits in our animal model
• Improved fasting triglycerides
• Normalized pattern of inflammatory cytokines
  after stimulation

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Experimental Design (long-term VA study)
Metabolic Syndrome Obese JCR-La cp/cp

• Lean Control

16-week diet
Control Diet (N10)
VA 1.0 w/w (N10)
Control Diet (N10)

• VA 9,11 CLA
• 1.01.0 w/w
• (N10)

Primary Endpoints body weight, food intake,
blood lipids, insulin sensitivity and inflammation
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Effect of Long term Feeding of VA Fasting
triglycerides
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Effect of Long Term Feeding of VA on postprandial
ApoB48
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Effect of Long term Feeding of VA Total plasma
cholesterol
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Effect of Long term Feeding of VA plasma
LDL-cholesterol
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Effect of Feeding VA on IL-2 production (Con A
stimulation)
Mesenteric Lymph Node Cells
Splenocytes
a
800
3000
a
2500
600
2000
400
1500
pg/mL
pg/mL
b
b
1000
200
500
0
0
control
control
VA
control
control
VA
Lean
Obese
Lean
Obese
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Summary

• Unlike other trans fats, VA does not appear to
  have negative health effects
• In an animal model of metabolic syndrome
• Feeding VA improves dyslipidemia
• Modulates immune function in what appears to be a
  beneficial direction
• Correct the reduced proliferative response to a T
  cell mitogen

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Acknowledgements

• Collaborators
• Spencer Proctor
• Donna Vine
• Martin Reaney
• Graduate student
• Megan Ruth
• Ye (Flora) Wang
• Post-Doctorate Fellow
• Heather Hosea
• Technicians
• Susan Goruk
• Kristina MacNaughton
• Sharon Sokolik

• Summer students
• Chris Gerdung
• Tara Martin
• Howe-Ming Yu
• Funding
• Beef Information Center
• Alberta Agriculture Research Institute Funding
  Consortium (AARI)
• Dairy Farmers of Canada
• AFMN-net

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Extra slides short term
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Body weight
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Glucose response to a meal challenge
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Insulin response to a meal challenge
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Serum IL-10
a
10
a
a
9
8
7
6
b
5
pg/mL
4
3
2
1
0
lean CTL
lean TVA
obese CTL
obese TVA
37
Extra slides long term study
38
lipids
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Total cholesterol
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Postprandial ApoB48