On oxidative stress and lipid peroxidation...
Lipid peroxidation as potential biomarker for oxidative stress generally, and the role of both in gene expression and cellular signaling. [Niki, 2008, 2009, 2012]
What raises/lowers oxidative stress:
- smoking, diabetes, BMI raise oxidative stress [Helmersson, et al 2004].
- female, C-reactive protein raise oxidative stress, but ascorbic acid lowers it [Block, Dietrich, 2002].
- higher glucose raises it [Menon, 2004].
- being homeless raises it [Kaldmae, 2012].
- saturated fat, transferrin saturase, heme iron from meat and fish raise it;
ferritin, vegetables, Vit C, non-heme iron from vegetables lowers it [Romeu, Aranda, et al, 2013].
- high fat meals, strenuous exercise raise it [McCarthy, Farney, 2013].
- a diet high in fruits and vegetables and their alpha- and beta-carotenes lower it [Asgard, Rytter, 2007].
- autoimmunity, mitochondrial dysfunction, mitochondrial stress, viral infection raise it. [Gerling, 2009].
Lipid peroxidation
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PhillyFree
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Silverlining
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Re: Lipid peroxidation
Philly, I'm really glad you posted this - thanks! There are a few things I might adjust...
Re: Lipid peroxidation
Excellent post, Philly; thank you for sharing. You most certainly have my attention. Because E4's clear lipids less effectively than E2s and E3s, my guess is that minimizing oxidized LDL is critical for us.
I question the notion that SFA increases oxidized LDL- just based on my basic understanding of lipids. SFA, because it’s a short chain fatty acid, is the MOST stable (least prone to oxidation) of all of the fatty acids. I read the full-text of the Mediterranean study that reached those conclusions. The researchers approached their examination by determining which foods produced the most iron, as iron is a pro-oxidant. Indeed, recent studies have demonstrated higher levels of serum ferritin stores are associated with Alzheimer’s (and CVD.) They used the TBARS essay, which is apparently a pretty unreliable in vitro tool, which may or may not hold true for how LDL (in the body) is affected. Actual testing of oxidized LDL in vivo is relatively new... and perhaps developing.
At first glance, this study appears to concur with the Mediterranean study.
Effect of Dietary Fat Saturation on LDL Oxidation and Monocyte Adhesion to Human Endothelial Cells In Vitro
http://www.ncbi.nlm.nih.gov/pubmed/8911273
The authors conclude: “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.” Notice how the PUFAs and SFA are both the MOST prone to oxidation per in vitro examination.
Not so fast. Other researchers, who’ve dissected the paper, found a buried graph that the authors chose to ignore.
When the participants actual oxidized LDL was studied in vivo, the effects were a little different. The PUFAs still led to higher oxidation, but the SFA and MUFA are almost equal in demonstrating significantly lower oxidized LDL.
Another study, examined oxidized LDL, when comparing two diets, both high in PUFAs; one high in vegetables, the other low in vegetables.
Changes in Dietary Fat Intake Alter Plasma Levels of Oxidized Low-Density Lipoprotein and Lipoprotein(a)
http://atvb.ahajournals.org/content/24/3/498.long
“The median plasma OxLDL-EO6 increased by 27% (P less than 0.01) in response to the low-fat, low-vegetable diet and 19% (P less than 0.01) in response to the low-fat, high-vegetable diet. Also, the Lp(a) concentration was increased by 7% (P less than 0.01) and 9% (P=0.01), respectively.” The antioxidant properties of vegetables appeared to have somewhat protected the women from increased oxidation, but what is most stunning to me; this is THE exact same diet that cardiologist have been recommending to patients to reverse and prevent heart disease. Indeed, a friend of ours (from 23 and Me) was following this diet when he learned his oxidized LDL was at the HIGHEST level.
The science and understanding here seems to be emerging. Nothing appears to be conclusive to me. Because our apoE is notoriously poor at clearing lipids, I suspect it is vital that we get this right. I’m keenly interested in learning more.
I question the notion that SFA increases oxidized LDL- just based on my basic understanding of lipids. SFA, because it’s a short chain fatty acid, is the MOST stable (least prone to oxidation) of all of the fatty acids. I read the full-text of the Mediterranean study that reached those conclusions. The researchers approached their examination by determining which foods produced the most iron, as iron is a pro-oxidant. Indeed, recent studies have demonstrated higher levels of serum ferritin stores are associated with Alzheimer’s (and CVD.) They used the TBARS essay, which is apparently a pretty unreliable in vitro tool, which may or may not hold true for how LDL (in the body) is affected. Actual testing of oxidized LDL in vivo is relatively new... and perhaps developing.
At first glance, this study appears to concur with the Mediterranean study.
Effect of Dietary Fat Saturation on LDL Oxidation and Monocyte Adhesion to Human Endothelial Cells In Vitro
http://www.ncbi.nlm.nih.gov/pubmed/8911273
The authors conclude: “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.” Notice how the PUFAs and SFA are both the MOST prone to oxidation per in vitro examination.
Not so fast. Other researchers, who’ve dissected the paper, found a buried graph that the authors chose to ignore.
When the participants actual oxidized LDL was studied in vivo, the effects were a little different. The PUFAs still led to higher oxidation, but the SFA and MUFA are almost equal in demonstrating significantly lower oxidized LDL.
Another study, examined oxidized LDL, when comparing two diets, both high in PUFAs; one high in vegetables, the other low in vegetables.
Changes in Dietary Fat Intake Alter Plasma Levels of Oxidized Low-Density Lipoprotein and Lipoprotein(a)
http://atvb.ahajournals.org/content/24/3/498.long
“The median plasma OxLDL-EO6 increased by 27% (P less than 0.01) in response to the low-fat, low-vegetable diet and 19% (P less than 0.01) in response to the low-fat, high-vegetable diet. Also, the Lp(a) concentration was increased by 7% (P less than 0.01) and 9% (P=0.01), respectively.” The antioxidant properties of vegetables appeared to have somewhat protected the women from increased oxidation, but what is most stunning to me; this is THE exact same diet that cardiologist have been recommending to patients to reverse and prevent heart disease. Indeed, a friend of ours (from 23 and Me) was following this diet when he learned his oxidized LDL was at the HIGHEST level.
The science and understanding here seems to be emerging. Nothing appears to be conclusive to me. Because our apoE is notoriously poor at clearing lipids, I suspect it is vital that we get this right. I’m keenly interested in learning more.
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Re: Lipid peroxidation
1996 study rather old news so it is typically ignored due to political reasons by medical societies I mean it takes typically 20 years or more to turn the thinking around but not for lack of evidence and collateral damage.
well has this been done in E4's?
and to what extent?
well has this been done in E4's?
and to what extent?
Re: Lipid peroxidation
Hey Spunky, I agree, we are far from proving anything conclusively in E4s. I can"t even find a study that examines oxydized LDL in our population.
I still find the study compelling...especially the information that was kept "hidden." It seems to be a small part of the lipid hypothesis, that is v-e-r-y slowly unravelling due to lack of scientific evidence.
I still find the study compelling...especially the information that was kept "hidden." It seems to be a small part of the lipid hypothesis, that is v-e-r-y slowly unravelling due to lack of scientific evidence.
Re: Lipid peroxidation
"supplementation with eicosapentaenoic acid, but not with other long-chain n−3 or n−6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y1,2,"
http://ajcn.nutrition.org/content/73/3/539.full
here it is but you can to sift out the implications of what factors for each genotype. yes there is more..but this can keep one busy for a while. do a search on each title to get started. then compare the results you get with HDLabs report on Genotype.
Impact of apolipoprotein E genotype and dietary quercetin on paraoxonase 1 status in apoE3 and ApoE4 people transgenic mice.
http://www.ncbi.nlm.nih.gov/pubmed/20307882
Quercetin promotes the anti-inflammatory PON1 in ApoE3 subjects but not ApoE4 subjects.
Plasma n-3 fatty acid response to an n-3 fatty acid supplement is modulated by apoE epsilon4 but not by the common PPAR-alpha L162V polymorphism in men.
Fish intake prevents cognitive decline in elderly ApoE3 subjects but not ApoE4 subjects.
A 12-week worksite health promotion program reduces cardiovascular risk factors in male workers with the apolipoprotein E2 and apolipoprotein E3 genotypes, but not in apolipoprotein E4 genotype.
Obesity correlates with plasma cholesterol & dietary cholesterol intake in ApoE3 subjects, but it correlates with dietary fat intake in ApoE4 subjects.
Serum lipid and antioxidant responses in hypercholesterolemic men and women receiving plant sterol esters vary by apolipoprotein E genotype.
Plant sterol esters reduce serum total cholesterol (TC) and LDL cholesterol (LDL-C) in ApoE2 &E3 subjects but not ApoE4 subjects.
Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein E3 and E4 in mice.
Western-type high fat diet impairs glucose tolerance and promotes fat overload in ApoE4 subjects but not ApoE3 subjects.
Apolipoprotein E polymorphism, life stress and self-reported health among older adults.
ApoE4 subjects have lower self-reported health than ApoE3 subjects.
Apolipoprotein E and lipoprotein lipase gene polymorphisms interaction on the atherogenic combined expression of hypertriglyceridemia and hyperapobetalipoproteinemia phenotypes.
Compared to apoE3 carriers, the ApoE4 allele significantly increases the risk of expressing the "hyperTG/hyperapoB" phenotype and ApoE2 decreases the risk.
[The role of epsilon 2/epsilon 3/epsilon 4 polymorphism of the apolipoprotein E gene in the development of dislipoproteinemia and its influence on the efficacy of the hypolipidemic therapy].
ApoE4 subjects have lower affinity to lipoprotein (LP) receptors and lipids than ApoE3 subjects or ApoE2 subjects. ApoE4 subjects are associated with hypercholesterolemia due to its impaired recycling in hepatocytes. Statins and physical training were more effective in ApoE2 subjects. Probucol and low-fat diet were more effective in ApoE4 subjects.
Apolipoprotein E genotype and plasma lipid levels in Caucasian diabetic patients.
Compared to diabetic ApoE3 subjects, total cholesterol, LDL cholesterol and Apo B levels were lower in diabetic ApoE2 subjects and higher in diabetic ApoE4 subjects. HDL-C was higher in ApoE2 subjects only.
Apolipoprotein E and atherosclerosis: beyond lipid effect.
ApoE polymorphism is particularly notorious for its role in neurodegenerative disorders and atherosclerotic arterial disease. Compared to ApoE3 subjects, ApoE4 subjects have higher LDL-C and are more proatherogenic, but ApoE2 subjects have lower LDL-C and are anti-atherogenic (although ApoE2 may be associated with increased plasma triglycerides and lipoprotein remnants).
Apolipoprotein E genotype in dyslipidemic patients and response of blood lipids and inflammatory markers to alpha-linolenic Acid.
ALA supplementation produced a small but significant decrease in HDL-C in ApoE3/3 subjects, but reduced serum amyloid A (SAA), CRP, macrophage colony-stimulating factor (MCSF), and IL-6. In ApoE3/4 subjects, ALA reduced SAA and MCSF. In ApoE2/3 subjects it had no effect.
Effect of apolipoprotein E4 allele on plasma LDL cholesterol response to diet therapy in type 2 diabetic patients.
Baseline plasma levels of LDL cholesterol were significantly higher in the ApoE4/3 group than in the apoE3/3 group. However, calorie-restricted diet therapy is more effective in reducing plasma LDL cholesterol in type 2 diabetic patients with the ApoE4 allele.
Alcohol intake and risk of dementia.
Intake of up to three daily servings of wine but not liquor or beer was associated with a lower risk of Alzheimer’s disease, but only for ApoE2 and ApoE3 subjects.
Interactions of apolipoprotein E genotype and dietary fat intake of healthy older persons during mid-adult life.
Lower fat diet may protect ApoE4 subjects from disorders of later life.
Evidence for differential effects of apoE3 and ApoE4 people on HDL metabolism.
Mice expressing ApoE3 on the Apoe(-/-) background had substantially lower VLDL levels than mice expressing ApoE4. ApoE4 mice had smaller HDL than ApoE3-expressing mice on both chow and high-fat diets. Also, ApoE4 was less efficient at transferring apoA-I from VLDL to HDL and at generating HDL in vitro than that from apoE3-expressing mice.
Effects of apolipoprotein E genotype on dietary-induced changes in high-density lipoprotein cholesterol in obese postmenopausal women.
ApoE2 & E3 postmenopausal women decreased HDL-C and increased triglycerides in response to a low-fat, low-cholesterol diet, while ApoE4 women had a smaller decrease in HDL-C and no change in plasma triglyceride. Also, ApoE2 & E3 women decreased HDL(2)-C by 32% , while ApoE4 women increased HDL(2)-C by 12% on a low-fat diet . It may be prudent to genotype older women before initiating low-fat diet therapy, as those with the ApoE4 allele benefit the most, while the lipid profile could worsen in women without the ApoE4 allele.
APOE polymorphism and the hypertriglyceridemic effect of dietary sucrose.
ApoE2 subjects had lower LDL-C and higher triacylglycerol ApoE3 subjects or E4. ApoE4 subjects have a greater serum cholesterol response to dietary changes in fat and cholesterol. ApoE2 CAD patients have a greater triacylglycerol response to high dietary sucrose intakes than ApoE3 or E4 patients.
Apoprotein E genotype and the response of serum cholesterol to dietary fat, cholesterol and cafestol.
The responses of LDL-C to saturated fat was larger in subjects with the APOE3/4 or E4/4 genotype than in those with APOE3/3. In contrast, responses of LDL-cholesterol to cafestol (from coffee) were smaller in subjects with the APOE3/4 or E4/4 genotype than in those with the APOE3/3.
APO E gene and gene-environment effects on plasma lipoprotein-lipid levels.
ApoE2 subjects have lower and ApoE4 subjects have higher total cholesterol and LDL-C than ApoE3 subjects. ApoE2 subjects, and possibly E3, subjects reduce plasma total and LDL cholesterol levels more than ApoE4 subjects with statin therapy. ApoE2 subjects are more likely to respond favorably to gemfibrozil and cholestyramine. With probucol, ApoE4 subjects improve plasma lipoprotein-lipid profiles more than ApoE3 subjects. ApoE2 and E3 perimenopausal women improve plasma lipoprotein-lipid profiles more with hormone replacement therapy than ApoE4 women. On the other hand, low-fat diet interventions tend to reduce plasma LDL cholesterol more in ApoE4 subjects than in ApoE2 or E3 individuals. ApoE2 and E3 individuals improve plasma lipoprotein-lipid profiles more with exercise training than APO E4 individuals.
Effects of ApoE genotype on ApoB-48 and ApoB-100 kinetics with stable isotopes in humans.
ApoE4 subjects have been shown to have higher LDL-C and apoB levels than ApoE3 & E2. Compared with the apoE3/E3 subjects, the ApoE3/E4 subjects had significantly higher levels of LDL ApoB-100. In addition, more VLDL apoB-100 was converted to LDL apoB-100 in ApoE3/E4 subjects than ApoE3/E3 subjects. One E4 allele was associated with higher LDL apoB-100 levels due to lower fractional catabolism of LDL apoB-100 and an increase in the conversion of VLDL apoB-100 to LDL apoB-100.
Apolipoprotein E isoform polymorphisms are not associated with insulin resistance: the Framingham Offspring Study.
There is no association between Apo(e) polymorphisms and insulin resistance. These appear to represent 2 completely independent risk factors for CHD.
Effect of apolipoprotein E genotype on lipid levels and response to diet in familial hypercholesterolemia.
ApoE4 subjects have higher basal total and LDL-C plasma levels and show an increased LDL-C response to dietary manipulation. The response to diet in subjects with familial hypercholesterolemia (FH) is also variable, but the influence of apo E genotypes on the dietary response of FH patients was minimal.
Apolipoprotein E genotype and exercise training-induced increases in plasma high-density lipoprotein (HDL)- and HDL2-cholesterol levels in overweight men.
APO E2 men have greater plasma HDL-C and HDL2-C increases with endurance exercise training versus E3 and E4 men
The apolipoprotein E4 allele is not associated with an abnormal lipid profile in a Native American population following its traditional lifestyle.
The increased LDL C levels associated with the E4 allele in previous studies were not observed in a Native American population with non-westernized habits.
[Apolipoprotein E and its alleles in healthy subjects and in atherosclerosis].
ApoE2 binds defectively to LDL- and to remnant-receptors. In Europe, E4 allele frequency increases from south to north along the cardiovascular disease frequency gradient. The ApoE4 role in atherosclerosis could be explained by its high solubility in ApoB lipoproteins. The average cholesterolemia of E4/E3 subjects is higher than E3/E3 subjects and E3/E3 subjects' cholesterolemia is higher than in E3/E2 subjects, probably because of a faster uptake of chylomicrons and VLDL remnants in E4/E3 subjects.
The effect of age and lifestyle factors on plasma levels of apolipoprotein E.
The mean plasma ApoE varies from 2.42 mg/dl in men with the E4/4 phenotype to 8.32 mg/dl in men in the E2/2 group. ApoE level is positively correlated to BMI and consumption of alcohol. The effect of age on the ApoE peaks in men aged 40-44 years, and is lower before & after. Subjects with BMI in the range 27-30 kg/m2 had a higher ApoE concentration than men in the group with BMI lower than 23 kg/m2. Smoking was only of borderline significance.
Apolipoprotein E phenotype and diet-induced alteration in blood pressure.
Two intervention diets were consumed by the study subjects for 4 wk at a time. Systolic, diastolic, and mean arterial pressures were significantly reduced during the low-fat diet period among the ApoE4 subjects only. Age was correlated with blood pressure response in ApoE4 subjects.
Prolonged postprandial responses of lipids and apolipoproteins in triglyceride-rich lipoproteins of individuals expressing an apolipoprotein epsilon 4 allele.
Postprandial clearance of intestinal and hepatogenous triglyceride-rich lipoprotein remnants is impaired in young ApoE3/4 men compared to ApoE3/3 men.
http://ajcn.nutrition.org/content/73/3/539.full
here it is but you can to sift out the implications of what factors for each genotype. yes there is more..but this can keep one busy for a while. do a search on each title to get started. then compare the results you get with HDLabs report on Genotype.
Impact of apolipoprotein E genotype and dietary quercetin on paraoxonase 1 status in apoE3 and ApoE4 people transgenic mice.
http://www.ncbi.nlm.nih.gov/pubmed/20307882
Quercetin promotes the anti-inflammatory PON1 in ApoE3 subjects but not ApoE4 subjects.
Plasma n-3 fatty acid response to an n-3 fatty acid supplement is modulated by apoE epsilon4 but not by the common PPAR-alpha L162V polymorphism in men.
Fish intake prevents cognitive decline in elderly ApoE3 subjects but not ApoE4 subjects.
A 12-week worksite health promotion program reduces cardiovascular risk factors in male workers with the apolipoprotein E2 and apolipoprotein E3 genotypes, but not in apolipoprotein E4 genotype.
Obesity correlates with plasma cholesterol & dietary cholesterol intake in ApoE3 subjects, but it correlates with dietary fat intake in ApoE4 subjects.
Serum lipid and antioxidant responses in hypercholesterolemic men and women receiving plant sterol esters vary by apolipoprotein E genotype.
Plant sterol esters reduce serum total cholesterol (TC) and LDL cholesterol (LDL-C) in ApoE2 &E3 subjects but not ApoE4 subjects.
Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein E3 and E4 in mice.
Western-type high fat diet impairs glucose tolerance and promotes fat overload in ApoE4 subjects but not ApoE3 subjects.
Apolipoprotein E polymorphism, life stress and self-reported health among older adults.
ApoE4 subjects have lower self-reported health than ApoE3 subjects.
Apolipoprotein E and lipoprotein lipase gene polymorphisms interaction on the atherogenic combined expression of hypertriglyceridemia and hyperapobetalipoproteinemia phenotypes.
Compared to apoE3 carriers, the ApoE4 allele significantly increases the risk of expressing the "hyperTG/hyperapoB" phenotype and ApoE2 decreases the risk.
[The role of epsilon 2/epsilon 3/epsilon 4 polymorphism of the apolipoprotein E gene in the development of dislipoproteinemia and its influence on the efficacy of the hypolipidemic therapy].
ApoE4 subjects have lower affinity to lipoprotein (LP) receptors and lipids than ApoE3 subjects or ApoE2 subjects. ApoE4 subjects are associated with hypercholesterolemia due to its impaired recycling in hepatocytes. Statins and physical training were more effective in ApoE2 subjects. Probucol and low-fat diet were more effective in ApoE4 subjects.
Apolipoprotein E genotype and plasma lipid levels in Caucasian diabetic patients.
Compared to diabetic ApoE3 subjects, total cholesterol, LDL cholesterol and Apo B levels were lower in diabetic ApoE2 subjects and higher in diabetic ApoE4 subjects. HDL-C was higher in ApoE2 subjects only.
Apolipoprotein E and atherosclerosis: beyond lipid effect.
ApoE polymorphism is particularly notorious for its role in neurodegenerative disorders and atherosclerotic arterial disease. Compared to ApoE3 subjects, ApoE4 subjects have higher LDL-C and are more proatherogenic, but ApoE2 subjects have lower LDL-C and are anti-atherogenic (although ApoE2 may be associated with increased plasma triglycerides and lipoprotein remnants).
Apolipoprotein E genotype in dyslipidemic patients and response of blood lipids and inflammatory markers to alpha-linolenic Acid.
ALA supplementation produced a small but significant decrease in HDL-C in ApoE3/3 subjects, but reduced serum amyloid A (SAA), CRP, macrophage colony-stimulating factor (MCSF), and IL-6. In ApoE3/4 subjects, ALA reduced SAA and MCSF. In ApoE2/3 subjects it had no effect.
Effect of apolipoprotein E4 allele on plasma LDL cholesterol response to diet therapy in type 2 diabetic patients.
Baseline plasma levels of LDL cholesterol were significantly higher in the ApoE4/3 group than in the apoE3/3 group. However, calorie-restricted diet therapy is more effective in reducing plasma LDL cholesterol in type 2 diabetic patients with the ApoE4 allele.
Alcohol intake and risk of dementia.
Intake of up to three daily servings of wine but not liquor or beer was associated with a lower risk of Alzheimer’s disease, but only for ApoE2 and ApoE3 subjects.
Interactions of apolipoprotein E genotype and dietary fat intake of healthy older persons during mid-adult life.
Lower fat diet may protect ApoE4 subjects from disorders of later life.
Evidence for differential effects of apoE3 and ApoE4 people on HDL metabolism.
Mice expressing ApoE3 on the Apoe(-/-) background had substantially lower VLDL levels than mice expressing ApoE4. ApoE4 mice had smaller HDL than ApoE3-expressing mice on both chow and high-fat diets. Also, ApoE4 was less efficient at transferring apoA-I from VLDL to HDL and at generating HDL in vitro than that from apoE3-expressing mice.
Effects of apolipoprotein E genotype on dietary-induced changes in high-density lipoprotein cholesterol in obese postmenopausal women.
ApoE2 & E3 postmenopausal women decreased HDL-C and increased triglycerides in response to a low-fat, low-cholesterol diet, while ApoE4 women had a smaller decrease in HDL-C and no change in plasma triglyceride. Also, ApoE2 & E3 women decreased HDL(2)-C by 32% , while ApoE4 women increased HDL(2)-C by 12% on a low-fat diet . It may be prudent to genotype older women before initiating low-fat diet therapy, as those with the ApoE4 allele benefit the most, while the lipid profile could worsen in women without the ApoE4 allele.
APOE polymorphism and the hypertriglyceridemic effect of dietary sucrose.
ApoE2 subjects had lower LDL-C and higher triacylglycerol ApoE3 subjects or E4. ApoE4 subjects have a greater serum cholesterol response to dietary changes in fat and cholesterol. ApoE2 CAD patients have a greater triacylglycerol response to high dietary sucrose intakes than ApoE3 or E4 patients.
Apoprotein E genotype and the response of serum cholesterol to dietary fat, cholesterol and cafestol.
The responses of LDL-C to saturated fat was larger in subjects with the APOE3/4 or E4/4 genotype than in those with APOE3/3. In contrast, responses of LDL-cholesterol to cafestol (from coffee) were smaller in subjects with the APOE3/4 or E4/4 genotype than in those with the APOE3/3.
APO E gene and gene-environment effects on plasma lipoprotein-lipid levels.
ApoE2 subjects have lower and ApoE4 subjects have higher total cholesterol and LDL-C than ApoE3 subjects. ApoE2 subjects, and possibly E3, subjects reduce plasma total and LDL cholesterol levels more than ApoE4 subjects with statin therapy. ApoE2 subjects are more likely to respond favorably to gemfibrozil and cholestyramine. With probucol, ApoE4 subjects improve plasma lipoprotein-lipid profiles more than ApoE3 subjects. ApoE2 and E3 perimenopausal women improve plasma lipoprotein-lipid profiles more with hormone replacement therapy than ApoE4 women. On the other hand, low-fat diet interventions tend to reduce plasma LDL cholesterol more in ApoE4 subjects than in ApoE2 or E3 individuals. ApoE2 and E3 individuals improve plasma lipoprotein-lipid profiles more with exercise training than APO E4 individuals.
Effects of ApoE genotype on ApoB-48 and ApoB-100 kinetics with stable isotopes in humans.
ApoE4 subjects have been shown to have higher LDL-C and apoB levels than ApoE3 & E2. Compared with the apoE3/E3 subjects, the ApoE3/E4 subjects had significantly higher levels of LDL ApoB-100. In addition, more VLDL apoB-100 was converted to LDL apoB-100 in ApoE3/E4 subjects than ApoE3/E3 subjects. One E4 allele was associated with higher LDL apoB-100 levels due to lower fractional catabolism of LDL apoB-100 and an increase in the conversion of VLDL apoB-100 to LDL apoB-100.
Apolipoprotein E isoform polymorphisms are not associated with insulin resistance: the Framingham Offspring Study.
There is no association between Apo(e) polymorphisms and insulin resistance. These appear to represent 2 completely independent risk factors for CHD.
Effect of apolipoprotein E genotype on lipid levels and response to diet in familial hypercholesterolemia.
ApoE4 subjects have higher basal total and LDL-C plasma levels and show an increased LDL-C response to dietary manipulation. The response to diet in subjects with familial hypercholesterolemia (FH) is also variable, but the influence of apo E genotypes on the dietary response of FH patients was minimal.
Apolipoprotein E genotype and exercise training-induced increases in plasma high-density lipoprotein (HDL)- and HDL2-cholesterol levels in overweight men.
APO E2 men have greater plasma HDL-C and HDL2-C increases with endurance exercise training versus E3 and E4 men
The apolipoprotein E4 allele is not associated with an abnormal lipid profile in a Native American population following its traditional lifestyle.
The increased LDL C levels associated with the E4 allele in previous studies were not observed in a Native American population with non-westernized habits.
[Apolipoprotein E and its alleles in healthy subjects and in atherosclerosis].
ApoE2 binds defectively to LDL- and to remnant-receptors. In Europe, E4 allele frequency increases from south to north along the cardiovascular disease frequency gradient. The ApoE4 role in atherosclerosis could be explained by its high solubility in ApoB lipoproteins. The average cholesterolemia of E4/E3 subjects is higher than E3/E3 subjects and E3/E3 subjects' cholesterolemia is higher than in E3/E2 subjects, probably because of a faster uptake of chylomicrons and VLDL remnants in E4/E3 subjects.
The effect of age and lifestyle factors on plasma levels of apolipoprotein E.
The mean plasma ApoE varies from 2.42 mg/dl in men with the E4/4 phenotype to 8.32 mg/dl in men in the E2/2 group. ApoE level is positively correlated to BMI and consumption of alcohol. The effect of age on the ApoE peaks in men aged 40-44 years, and is lower before & after. Subjects with BMI in the range 27-30 kg/m2 had a higher ApoE concentration than men in the group with BMI lower than 23 kg/m2. Smoking was only of borderline significance.
Apolipoprotein E phenotype and diet-induced alteration in blood pressure.
Two intervention diets were consumed by the study subjects for 4 wk at a time. Systolic, diastolic, and mean arterial pressures were significantly reduced during the low-fat diet period among the ApoE4 subjects only. Age was correlated with blood pressure response in ApoE4 subjects.
Prolonged postprandial responses of lipids and apolipoproteins in triglyceride-rich lipoproteins of individuals expressing an apolipoprotein epsilon 4 allele.
Postprandial clearance of intestinal and hepatogenous triglyceride-rich lipoprotein remnants is impaired in young ApoE3/4 men compared to ApoE3/3 men.
Re: Lipid peroxidation
Wow, Spunky, I was already playing catch-up from my recent trip. It will take me days to pour through this 
Luckily, some I have seen before.
A cursory glance doesn't reveal much that relates to lipid perixidation, but these are excellent studies. Would you mind if I moved them around to different categories? For instance, the first one would be great in the "Fish Oil" topic in the "Supplement" category. Many others would be excellent additions to the "ApoE4 Science & Research" category. Great stuff. Thank you for sharing.
Luckily, some I have seen before. A cursory glance doesn't reveal much that relates to lipid perixidation, but these are excellent studies. Would you mind if I moved them around to different categories? For instance, the first one would be great in the "Fish Oil" topic in the "Supplement" category. Many others would be excellent additions to the "ApoE4 Science & Research" category. Great stuff. Thank you for sharing.
Re: Lipid peroxidation
Increased LDL oxidation is just ONE reason to be cautious with a low fat/high carb diet...
Changes in lipoprotein(a), oxidized phospholipids and LDL subclasses with a low-fat, high-carbohydrate diet
http://www.jlr.org/content/early/2010/0 ... 9.full.pdf
CONCLUSIONS: In conclusion, the results demonstrate that a low-fat, high-carbohydrate diet results in increased plasma Lp(a) and its associated oxidized phospholipids, and suggest that these increases may be modified by changes in LDL metabolism leading to altered LDL subclass distribution. Additional studies are needed to understand the physiological and clinical impact of such changes.
COMMENTS: Just like we've seen in our NMR data sample, as fat goes down, small LDL goes up, as well as Lp(a) and oxidized LDL. My guess is that finding a balance is key for E4s. Too much could be detrimental, especially in the presence of inflammation. Too little, however, leads to an arthogenic profile; increased risk for metabolic syndrome, higher Lp(a), oxidized LDL, and elevated small LDL.
Changes in lipoprotein(a), oxidized phospholipids and LDL subclasses with a low-fat, high-carbohydrate diet
http://www.jlr.org/content/early/2010/0 ... 9.full.pdf
CONCLUSIONS: In conclusion, the results demonstrate that a low-fat, high-carbohydrate diet results in increased plasma Lp(a) and its associated oxidized phospholipids, and suggest that these increases may be modified by changes in LDL metabolism leading to altered LDL subclass distribution. Additional studies are needed to understand the physiological and clinical impact of such changes.
COMMENTS: Just like we've seen in our NMR data sample, as fat goes down, small LDL goes up, as well as Lp(a) and oxidized LDL. My guess is that finding a balance is key for E4s. Too much could be detrimental, especially in the presence of inflammation. Too little, however, leads to an arthogenic profile; increased risk for metabolic syndrome, higher Lp(a), oxidized LDL, and elevated small LDL.
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Gilgamesh
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Re: Lipid peroxidation
Just don't make half of it sugar/non-RS carbs! That's all this fairly badly written up (because so few details about what kind of carbs were eaten) tells us.Juliegee wrote:Increased LDL oxidation is just ONE reason to be cautious with a low fat/high carb diet...
From Table 1:
"Each diet was normalized to cholesterol content and ratio of simple versus complex carbohydrate (50/50)."
50% bad carbs, that is! (And we don't even know what the purported "good" carbs are.)
And, of course, it's not clear the diets were isocaloric....
(And it seems no one has cited the article in the last four years, aside from the authors, or their colleagues -- always a bad sign.)
Frustrating! We need to set up our own lab and start doing some high-quality studies!
GB
Re: Lipid peroxidation
Blast from the past, G
I agree that the composition of carbs matters; too bad we don't have more info in this paper. I may be going out on a limb here, but I still think the message generally holds true, even with "good" carbs. All carbs are metabolized into glucose; glucose oxidizes LDL. However, more complex carbs are metabolized more slowly and may contribute antioxidants and flavonoids that temper the oxidation process. My guess is that a diet too high in carbs (especially simple carbs) will increase LDL oxidation. High quality dietary fats, antioxidants and flavonoids may prove to be protective.
Here's two newer studies that demonstrate olive oil (and OEA- found abundantly in EVOO) attenuate LDL oxidation by two separate mechanisms: down-regulating CD40-ligand expression & inducing expressions of PPAR-α.
Protection of LDL from oxidation by olive oil polyphenols is associated with a downregulation of CD40-ligand expression and its downstream products in vivo in humans
http://ajcn.nutrition.org/content/95/5/1238.full
Atheroprotective Effect of Oleoylethanolamide (OEA) Targeting Oxidized LDL
http://www.ncbi.nlm.nih.gov/pmc/article ... po=38.8889
Heres a great one suggesting the flavonoid cocoa, with CR, reduces lipid per oxidation.
Oxidised LDL levels decreases after the consumption of ready-to-eat meals supplemented with cocoa extract within a hypo caloric diet
http://www.ncbi.nlm.nih.gov/pubmed/?ter ... loric+diet
Long live the nibs!
I agree that the composition of carbs matters; too bad we don't have more info in this paper. I may be going out on a limb here, but I still think the message generally holds true, even with "good" carbs. All carbs are metabolized into glucose; glucose oxidizes LDL. However, more complex carbs are metabolized more slowly and may contribute antioxidants and flavonoids that temper the oxidation process. My guess is that a diet too high in carbs (especially simple carbs) will increase LDL oxidation. High quality dietary fats, antioxidants and flavonoids may prove to be protective.
Here's two newer studies that demonstrate olive oil (and OEA- found abundantly in EVOO) attenuate LDL oxidation by two separate mechanisms: down-regulating CD40-ligand expression & inducing expressions of PPAR-α.
Protection of LDL from oxidation by olive oil polyphenols is associated with a downregulation of CD40-ligand expression and its downstream products in vivo in humans
http://ajcn.nutrition.org/content/95/5/1238.full
Atheroprotective Effect of Oleoylethanolamide (OEA) Targeting Oxidized LDL
http://www.ncbi.nlm.nih.gov/pmc/article ... po=38.8889
Heres a great one suggesting the flavonoid cocoa, with CR, reduces lipid per oxidation.
Oxidised LDL levels decreases after the consumption of ready-to-eat meals supplemented with cocoa extract within a hypo caloric diet
http://www.ncbi.nlm.nih.gov/pubmed/?ter ... loric+diet
Long live the nibs!
