Sunday, October 28, 2012

Fats and LDL Oxidation

The fat composition of the diet highly influences the fat composition of adipose tissue, phospholipids and cholesterol esters.  Changes in fat composition of adipose tissue to changes in the diet are slow and take a few years to approximates the proportions of fats in the diet [1] 

The following studies fed humans a variety of diets rich in a particular type of fat for 5 weeks then sampled their blood and oxidised the lipids.  Malondialdehyde and conjugated dienes are products of lipid peroxidation and lag time refers to how long it takes for oxidisation to occur. 

[2]
SFA
MUFA
PUFA
(n-6)
PUFA
(n-3)
Vitamin E (molecules/ LDL particle)
10.6
12.4
14.2
14
TBARS MDA (nmol/mg LDL protein)
1.15
1.15
1.51
1.69
Conjugated dienes (nmol/mg LDL protein)
266
256
301
331
Lag time (min)
45.3
55.1
47.1
45.3

[3]
SFA
MUFA
PUFA
(n-6)
PUFA
(n-3)
Vitamin E (molecules/ LDL particle)
9.8
11.0
13.2
13.9
TBARS MDA (nmol/mg LDL protein)
0.89
1.06
1.56
1.70
Conjugated dienes (nmol/mg LDL protein)
254
251
295
348
Lag time (min)
45.9
53.4
47.9
47.1

(What’s interesting about the two studies above is the SFA group had higher linoleic acid in their phospholipids than the MUFA group despite a roughly equal amount in the diet.) 

[4]
MUFA
PUFA (n-6)
Max rate of conjugated diene formation per minute
0.0025
0.0035
Lag Time (min)
~30
~60
TBARS before oxidation (ns)
(nmol MDA/mg protein)
8.8
5.5
TBARS after oxidation (ns)
(nmol MDA/mg protein)
37.6
43.6
Macrophage degradation before oxidation
(µg LDL x 5h-1 x mg cell protein)-1 (ns)
2.8
2.1
Macrophage degradation after oxidation
(µg LDL x 5h-1 x mg cell protein)-1
6.8
11.9

[5]
Baseline
MUFA
PUFA
Vitamin E (nmol/mg)
3.26
3.41
3.94
Vitamin LDL bound (µM)
8.86
7.57
7.33
Inhibition time (min)
11.21
12.70
13.10
Peroxidation rate (nmol O2/min)
20.01
20.95
25.19

These studies suggest the linoleic acid to oleic acid ratio in phospholipids and the amount of vitamin E correlated very strongly with LDL oxidation rate.  And also that SFA and MUFA rich diets produce less lipid peroxidation products than PUFA rich diets.  As fat composition in adipose tissue takes a while to change, I expect the differences between SFA/MUFA and PUFA rich diets would be greater if these studies lasted longer than five weeks. 

However, the previous four studies used copper ions to oxidise LDL in vitro, which is artificial and would not happen in vivo.  To support their findings a study found a low fat and high PUFA diet increased LDL oxidation and Lp(a) compared to the participants normal diet [6] 

[6]
LDL Oxidation
Lp(a)
Low Fat, High PUFA, High Vegetable
+19%
+9%
Low Fat, High PUFA, Low Vegetable
+27%
+7%

An interesting finding of this study is that the low fat, high PUFA diet decreased LDL-C, but increased Lp(a) – a marker of LDL-P [6] 

* Oxidised lipoproteins are rapidly cleared and plasma concentrations of oxidised LDL in healthy humans are extremely low [7] 

Further Reading:
(1) The Diet-Heart Hypothesis: Oxidized LDL, Part II

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