In the face of the quite strong evidence that PUFAs n-6 lower CHD risk when they ewplace SFAs, it seems we are a few here trying to figure out how this can be since it's quite contradictorry with common knowledge that developed in the recent year : n-6 promote inflammation and oxidation and hence should exacerbate CHD risk factor.
Whereas I agree that utimilatly the how might not matter that much in the face that we know they lower the risk, I was nontheless curious of finding the evidence that n-6 really promote oxidation and inflammation in healthy human - and as pointed out by JLL in another thread, if there could not be important counfonding factor in studies where PUFAs seems to be beneficial.
So, I will share what i've found, and if anyone find something else it would be interesting to add it here
Oxidation:
Dietary intakes of polyunsaturated fatty acids and indices of oxidative stress in human volunteers.
OBJECTIVE: To assess whether nutritionally-relevant changes in polyunsaturated fatty acid (PUFA) intake alter indices of oxidative stress in human volunteers DESIGN: A split plot/change over dietary study where half the volunteers consumed a diet containing 5% PUFA (low PUFA) as food energy for 4 weeks and after a 6 week washout period consumed a 15% PUFA (high PUFA) diet for another 4 weeks. The second group of volunteers completed this protocol in reverse. Total fat, carbohydrate, protein and vitamin E contents of the diets were constant. SUBJECTS: 10 healthy, non-smoking, male volunteers aged 32.6 +/- 1.7 y RESULTS: There was a significant increase in whole blood oxidised glutathione (P < 0.05), an index of oxidative stress, after consumption of the high PUFA diet. Moreover, urinary thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, significantly increased (P = 0.038) following consumption of the high PUFA diet and decreased (P = 0.031) after consuming the low PUFA diet. However, there was no change in non specific plasma indices of lipid peroxidation, conjugated dienes and TBARS, nor in red cell antioxidant enzymes glutathione peroxidase, glutathione reductase, and catalase. However, superoxide dismutase significantly decreased (13%, P=0.018) after consumption of the low PUFA diet. Total cholesterol increased by 13% (P=0.014) after consumption of the low PUFA diet. CONCLUSIONS: This study indicates that although increasing dietary levels of PUFA may favourably alter cholesterol profiles, the same dietary changes may adversely affect some indices of lipid peroxidation. Care should be taken when providing dietary advice on PUFA intake and an adequate intake of antioxidants to match any increased PUFA may be important for preventing oxidative stress.
A high linoleic acid diet increases oxidative stress in vivo and affects nitric oxide metabolism in humans.
Evidence from in vitro studies shows that increased intake of polyunsaturated fatty acids leads to increased oxidative stress, which may be associated with endothelial damage. We measured the urinary levels of 8-iso-PGF2alpha and nitric oxide metabolites as well as plasma sICAM-1 levels from healthy subjects after strictly controlled diets rich in either linoleic acid (LA, C18:2 n-6) or oleic acid (OA, C18:1 n-9). Thirty-eight volunteers (20 women and 18 men, mean age 27 years) consumed a baseline diet rich in saturated fatty acids (SFA) for 4 weeks and were then switched to either a high LA diet (11.5 en%) or a high OA diet (18.0 en%) also for 4 weeks. During the LA and OA diets, nearly all food was provided for the whole day. A control group of 13 subjects consumed their habitual diet throughout the study. Urinary excretion of 8-iso-PGF2alpha was significantly increased after the LA diet (170 vs 241 ng/mmol creatinine, P=0.04), whereas the urinary concentration of nitric oxide metabolites decreased (4.2 vs 2.6 mg/mmol creatinine, P=0.03). No significant changes were seen in the OA group. Significant differences between the LA and control group were found for both 8-oxo-PGF2alpha (P=0.03) and NO (P=0.02), whereas the OA and LA groups did not differ with respect to any parameter. Also plasma sICAM-1 remained unchanged in both groups throughout the study. In conclusion, the high-LA diet increased oxidative stress and affected endothelial function in a way which may in the long-term predispose to endothelial dysfunction.
Dietary polyunsaturates and peroxidation of low density lipoprotein
Oxidative modification of low density lipoprotein is influenced by dietary polyunsaturates. Omega-6 polyunsaturated fatty acids enhance the susceptibility of low density lipoprotein to oxidation compared with monoenes. Most studies on omega-3 fatty acids also exhibit increased peroxidation of low density lipoprotein, although these data are more conflicting. Future studies should focus on additional information concerning dietary intake of antioxidants, fatty acids and lipid peroxides, as well as on the importance of low density lipoprotein oxidation in vivo.
Effect of dietary fat saturation on LDL oxidation and monocyte adhesion to human endothelial cells in vitro.
Forty-two healthy men and women were subjected to four consecutive dietary periods differing in the fat content of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (n-6) [PUFA(n-6)] and (n-3) [PUFA(n-3)]. Plasma lipids, vitamin E, and in vitro LDL oxidation were examined during each period. Adhesion of human monocytes to cultured human endothelial cells was used as a functional test to identify differences in the biological properties of LDL from each dietary period. Consumption of an SFA-rich diet resulted in higher LDL cholesterol (4.06 +/- 0.85 mmol/L, P < .05) than did consumption of MUFA- (3.59 +/- 0.75 mmol/L), PUFA(n-6)- (3.44 +/- 0.77 mmol/L), or PUFA(n-3)- (3.31 +/- 0.8 mmol/L) rich diets. HDL cholesterol was lower during both PUFA-rich diets (1.24 +/- 0.28 and 1.27 +/- 0.28 mmol/L for n-6 and n-3, respectively) than during the SFA-(1.32 +/- 0.36 mmol/L) and MUFA- (1.32 +/- 0.34 mmol/L) rich diets. LDL resistance to copper-induced oxidation, expressed as lag time, was highest during the MUFA-rich diet (55.1 +/- 7.3 minutes) and lowest during the PUFA(n-3)- (45.3 +/- 7 minutes) and SFA- (45.3 +/- 6.4 minutes) rich diets. LDL induction of monocyte adhesion to endothelial cells was lower during the MUFA-rich diet than the other periods. The highest monocyte adhesion was obtained during the PUFA(n-3) and SFA dietary periods. In conclusion, an MUFA-rich diet benefits plasma lipid levels compared with an SFA-rich diet. Furthermore, this diet results in an increased resistance of LDL to oxidation and a lower rate of monocyte adhesion to endothelial cells than the other dietary fats examined.
Safety considerations of polyunsaturated fatty acids
The n-6 and n-3 polyunsaturated fatty acids (PUFAs) are essential nutrients; intake of relatively small amounts of these fatty acids prevents nutritional deficiencies. Replacing dietary saturated fat with PUFAs may confer health gains. Experimental data support the notion that high intake of n-6 PUFAs may increase in vivo lipid peroxidation. This effect may be counteracted by dietary antioxidant supplementation. The influence of a high n-3 PUFA intake on measures of lipid peroxidation has been equivocal. In clinical trials, subjects who consumed diets rich in n-6 or n-3 PUFAs had fewer atherothrombotic endpoints than did control groups. In this report, data regarding the influence of PUFAs on lipid peroxidation as well as on cholesterol and glucose metabolism, hemostasis, and other aspects of interest are reviewed and discussed. Currently, daily intake of PUFAs as >10% of total energy is not recommended. Below this ceiling there is little evidence that high dietary intake of n-6 or n-3 PUFAs implies health risks.
Modified egg composition to reduce low-density lipoprotein oxidizability: high monounsaturated fatty acids and antioxidants versus regular high n-6 polyunsaturated fatty acids
Eggs high in n-6 PUFA, predominant in Western markets, were found to increase blood LDL oxidation, suggesting a new health concern beyond raising cholesterol. Protective composition was explored by increasing egg antioxidants and MUFA and reducing n-6 PUFA. Lag times to plasma LDL oxidation were significantly shortened with two eggs/day of high-PUFA compositions compared to a low-egg (2-4/week) regime, by 28.8% following "HPUFA-regular" ( p < 0.01) and by 27.2% following antioxidant-fortified "HPUFA-HAOX" ( p < 0.01). However, two "HMUFA-HAOX" eggs/day with reduced egg n-6 PUFA FA% (LA by 30.7%) and PUFA:MUFA ratio (LA:OA by 45.8%) plus increased antioxidants (vitamin E 500%, carotenoids 260%), resulting in increased plasma OA 33.3%, vitamin E 22.4%, and carotenoids 55.0% ( p < 0.01), were associated with lag-time only 6.6% shorter than low-egg (NS). Among health-oriented egg modifications, here for the first time they reduced associated LDL oxidization, consistent with anti-inflammation and antioxidant paradigms, warranting further research on functional advantages of antioxidative egg composition.
Effect of meals rich in heated olive and safflower oils on oxidation of postprandial serum in healthy men.
The present randomised, crossover study sought to determine the effect of meals rich in safflower oil and olive oil (60 g) which had been heated for 8 h at 210 degrees C and the corresponding unheated oils on copper ion oxidation of dilute serum from 16 healthy men. Four hours after the meals rich in the heated oils, there were significant decreases of similar magnitude (-12%) in the lag time in conjugated diene formation during diluted serum oxidation. In the 12 subjects who consumed meals containing unheated oils, the lag time also decreased (-11%) significantly after the meal rich in unheated safflower oil (US) and did not change significantly after the unheated olive oil (UO) meal and these changes were different between the meals at a marginal level of significance (P=0.05). Our data suggest that susceptibility to oxidation of lipoproteins in low antioxidant environments similar to dilute serum may be increased in the postprandial period following meals rich in heat-modified vegetable oils and unheated oils rich in polyunsaturated fatty acids but not following meals rich in native olive oil. These findings may be relevant to the choice of fat to replace saturated fats in lipid-lowering diets and to low risk of coronary heart disease in communities which have a high consumption of olive oil.
Acute effects of different types of oil consumption on endothelial function, oxidative stress status and vascular inflammation in healthy volunteers.
Consumption of different types of oil may have different effects on cardiovascular risk. The exact role of maize oil, cod liver oil, soya oil and extra virgin olive oil on endothelial function, oxidative stress and inflammation is unknown. We evaluated the effect of acute consumption of these types of oil on endothelial function, oxidative stress and inflammation in healthy adults. Thirty-seven healthy volunteers were randomised to receive an oral amount of each type of oil or water. Endothelial function was evaluated by gauge-strain plethysmography at baseline and 1, 2 and 3 h after consumption. Oxidative stress status was determined by total lipid peroxides (PEROX), while inflammatory process was estimated by measuring the soluble form of vascular adhesion molecule 1. Serum levels of the two previous markers were measured at baseline and 3 h after oil consumption. Reactive hyperaemia (RH) was significantly decreased after maize oil consumption compared with controls (P < 0.05). However, the consumption of cod liver oil and soya oil induced a significant improvement of RH after 1 h, compared with controls (P < 0.05). There was no significant effect of any type of oil consumption on endothelium-independent dilatation, total lipid PEROX and vascular adhesion molecule 1 serum levels. Consumption of maize oil leads to impaired endothelial function, while soya oil and cod liver oil slightly improve endothelial function. However, all types of oils did not affect inflammatory process and systemic oxidative stress, suggesting that their effect on endothelial function may not be mediated by free radicals bioavailability.
The result from the last one are interesting. Still, the vast majority seems to report that oxidation is increase on a higher PUFAs-6 diet (and probably n-3 too).
Considering that ox-LDL is a marker of risk for CHD, again, i'm clueless about how n-6 can be protective if they promote LDL oxidation and LDL oxidation is a risk factor.
Maybe that people eating a lot of PUFAs also eat much healthier and hence get more antioxidant and are protected from this side effect - and then benefits from the lowering of LDL?
I'll be back for the inflammation part i'm out of time. Anybody can find anything else that could help complete this puzzle? Again, I know utimatly it's not so important, but I want to know if the oxidation argument hold in place.
Edited by oehaut, 28 January 2010 - 01:59 PM.
