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Saturated fat induces inflammation via TLR4 activation. Please comment, fat lovers

saturated fat dha omega 3 fat tlr4 lps lipopolysaccharides inflammation firefly is good but overrated

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#1 StevesPetRat

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Posted 17 January 2015 - 08:51 PM


The Paleo / ancestral health / broader diet maverick community can't stop falling all over itself singing the praises of saturated fats (e.g.: here, here, here, here, etc.). I do agree that, on close examination, the evidence linking saturated fat consumption to heart disease shows a weak correlation at best. And ghee and coconut oil are so friggin' tasty that I sometimes eat a plain spoonful of them (not quite as great as a healthy swig of quality olive oil straight from the bottle, but close).

 

However, I'm not necessarily concerned with heart disease alone, but also general inflammatory conditions. And there is an overwhelming body of evidence that long and even the longer medium chain saturated fatty acids induce inflammation through my personal bugbear, TLR4 (and to some extent TLR2) agonism: in chronological order, 1, 2, 3, 4, 5, 6, 7, 8 (a couple of these are weaker than others but included for completeness). Furthermore, the sometimes loved, sometimes vilified omega-3 DHA mitigates this inflammation (See, no's 1, 4, 7). Any study I found that looked at pure MUFA seemed to show it had a neutral effect.

 

So could it be that longer chain saturated fat has benefits such as increasing LDL particle size and reducing oxidative stress that would offset its inflammatory effects in heart disease, while it might still contribute to other inflammatory diseases (e.g. autoimmune disease)? Oh, wait, here's an older study that shows the latter.

 

Sigh. Why does nutrition have to be so goddamned complicated? Makes me almost want to go back to eating Big Macs. (Just kidding, haven't eaten at McDonald's in maybe 6 years. I went for the Six Dollar Burger at Carl's Jr.) Guess it's time to fork over $1/oz for the "Bulletcultproof MCT".

 

Please comment if you think sat. fat is the greatest thing ever and explain why I'm a big fat poopy head. Thanks.



#2 pone11

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Posted 17 January 2015 - 10:27 PM

The problem with these studies is they are showing associations in vivo, not causation.   How do these studies explain that some people remain skinny on a high fat diet and have very low levels of inflammation?   How do these studies explain that some people get obese on high carbohydrate low fat diets, and exhibit very high inflammation?   I'm not denying the in vitro effects, but getting any kind of useful information about what to eat from these studies is not so simple.

 

Remember that a person who eats almost no saturated fat and eats huge carb loads with lots of high fructose corn syrup will get the very worst kind of VLDL generated by the liver, and the liver is the only pathway for the fructose metabolism.  So there are many dietary paths that will lead to a high fatty acid load.

 

What's key is that most of the in vivo data they have is about people who are already obese and already suffering from very high triglyceride levels and high inflammation levels.   They are looking at that person's high saturated fatty acid levels in the blood, and then trying to infer things about what that person eats.   I don't think it works that way.

 

I am skinny and have very low triglycerides.  I have low inflammation.   I eat high saturated fats.   What I have noticed in my own case, is that different saturated fats have a very different outcome on my LDL levels.   When I eat dairy cream, my LDL-P EXPLODES to very dangerous levels.   When I remove all dairy, and substitute just coconut milk and meat, I get much more moderate LDL-P.   I'm experimenting with ghee now and I don't know the effect on LDL-P yet.   Look at the Fat Profiles section here:

http://en.wikipedia....i/Saturated_fat

 

and the takeaway from that is that not all saturated fats are the same.   The relative compositions of Lauric, Myristic, Palmitic, and Stearic fatty acids greatly affect how you metabolize the food.   Cacao/Chocolate emphasizes Stearic and is probably the heart-healthiest form.   Coconut emphasizes Lauric, and is more neutral.   Palmitic is what you find in dairy, and this is the fatty acid that seems to cause some people serious LDL problems.

 

If you are obese or suffering from inflammation, maybe think about increasing monounsaturated fats.  Use macadamia oil on your salads.   If you are thin and not inflamed, but only suffering from high LDL, then try isolating which saturated fatty acid is causing the problem.   

 

I've realized in the last few years that there is no substitute for testing, experimenting with strict diet control, and then retesting.   It's all very individual.   Generalizations from diet studies that try to deliver one-size-fits-all advice are frankly almost worthless.


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#3 Darryl

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Posted 18 January 2015 - 04:42 PM

There's an active debate as to whether saturated fats directly activate Toll-like-receptors, or whether this is an artifact of low-level endotoxin contamination of most fatty acid sources.

 

Erridge, C., & Samani, N. J. (2009). Saturated fatty acids do not directly stimulate Toll-like receptor signalingArteriosclerosis, thrombosis, and vascular biology29(11), 1944-1949.

Huang, S., Rutkowsky, J. M., Snodgrass, R. G., Ono-Moore, K. D., Schneider, D. A., Newman, J. W., ... & Hwang, D. H. (2012). Saturated fatty acids activate TLR-mediated proinflammatory signaling pathwaysJournal of lipid research,53(9), 2002-2013.

 

What's uncontested at this point is that high saturated fat diets and meals increase plasma endotoxins, both by modulating the gut microbiota and by increasing intestinal permeability. I'll let the titles tell the story:

 

Erridge, C., Attina, T., Spickett, C. M., & Webb, D. J. (2007). A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammationThe American journal of clinical nutrition86(5), 1286-1292.

Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., & Burcelin, R. (2008). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in miceDiabetes57(6), 1470-1481.

Ghoshal, S., Witta, J., Zhong, J., De Villiers, W., & Eckhardt, E. (2009). Chylomicrons promote intestinal absorption of lipopolysaccharidesJournal of lipid research50(1), 90-97.

Ghanim, H., Abuaysheh, S., Sia, C. L., Korzeniewski, K., Chaudhuri, A., Fernandez-Real, J. M., & Dandona, P. (2009). Increase in plasma endotoxin concentrations and the expression of toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal implications for insulin resistanceDiabetes care32(12), 2281-2287.

Suzuki, T., & Hara, H. (2010). Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF ratsNutr Metab (Lond)7(1), 19.

Rabot, S., Membrez, M., Bruneau, A., Gérard, P., Harach, T., Moser, M., ... & Chou, C. J. (2010). Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolismThe FASEB Journal24(12), 4948-4959.

Laugerette, F., Vors, C., Géloën, A., Chauvin, M. A., Soulage, C., Lambert-Porcheron, S., ... & Michalski, M. C. (2011). Emulsified lipids increase endotoxemia: possible role in early postprandial low-grade inflammationThe Journal of nutritional biochemistry22(1), 53-59.

Pendyala, S., Walker, J. M., & Holt, P. R. (2012). A high-fat diet is associated with endotoxemia that originates from the gutGastroenterology142(5), 1100-1101.

Kim, K. A., Gu, W., Lee, I. A., Joh, E. H., & Kim, D. H. (2012). High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathwayPLoS One7(10), e47713.

Clemente-Postigo, M., Queipo-Ortuno, M. I., Murri, M., Boto-Ordonez, M., Perez-Martinez, P., Andres-Lacueva, C., ... & Tinahones, F. J. (2012). Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patientsJournal of lipid research53(5), 973-978.

Harte, A. L., Varma, M. C., Tripathi, G., McGee, K. C., Al-Daghri, N. M., Al-Attas, O. S., ... & McTernan, P. G. (2012). High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects.Diabetes care35(2), 375-382.

Shrestha, U. K. (2012). High-fat diet is associated with endotoxemia and low-grade inflammationNepal Journal of Medical Sciences1(2), 62-63.

Serino, M., Luche, E., Gres, S., Baylac, A., Bergé, M., Cenac, C., ... & Burcelin, R. (2012). Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiotaGut61(4), 543-553.

Laugerette, F., Furet, J. P., Debard, C., Daira, P., Loizon, E., Géloën, A., ... & Michalski, M. C. (2012). Oil composition of high-fat diet affects metabolic inflammation differently in connection with endotoxin receptors in mice.American Journal of Physiology302(3), E374-E386.

Mani, V., Hollis, J. H., & Gabler, N. K. (2013). Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemiaNutr Metab10(6).

Zaman, G. S., Zaman, F., & Rasul, M. G. (2014) Comparison of postprandial endotoxemia in male adolescents and male subjects above 50 years after a fat overload

 

Reviews:

 

Moreira, A. P. B., Texeira, T. F. S., Ferreira, A. B., do Carmo Gouveia Peluzio, M., & de Cássia Gonçalves Alfenas, R. (2012). Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemiaBritish Journal of Nutrition108(05), 801-809.

Herieka, M., & Erridge, C. (2014). High‐fat meal induced postprandial inflammationMolecular nutrition & food research58(1), 136-146.

Shen, W., Gaskins, H. R., & McIntosh, M. K. (2014). Influence of dietary fat on intestinal microbes, inflammation, barrier function and metabolic outcomesThe Journal of nutritional biochemistry25(3), 270-280.

 

High dietary fructose is also implicated in metabolic endotoxemia, through encouraging small intestinal dysbiosis. The whole metabolic endotoxemia story is one of the most interesting, and most underreported, stories from recent nutritional science.


Edited by Darryl, 18 January 2015 - 04:42 PM.

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#4 Darryl

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Posted 18 January 2015 - 07:53 PM

Correction to first line: there appears to be low level endotoxin contamination of much bovine serum albumin, which is ubiquitous in human cell culture experiments. Given endotoxin elicits inflammatory responses at picomolar concentrations, there are perhaps tens of thousands of cell culture studies of inflammation that may be compromised.


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#5 pone11

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Posted 18 January 2015 - 10:09 PM

There's an active debate as to whether saturated fats directly activate Toll-like-receptors, or whether this is an artifact of low-level endotoxin contamination of most fatty acid sources.

 

Erridge, C., & Samani, N. J. (2009). Saturated fatty acids do not directly stimulate Toll-like receptor signalingArteriosclerosis, thrombosis, and vascular biology29(11), 1944-1949.

Huang, S., Rutkowsky, J. M., Snodgrass, R. G., Ono-Moore, K. D., Schneider, D. A., Newman, J. W., ... & Hwang, D. H. (2012). Saturated fatty acids activate TLR-mediated proinflammatory signaling pathwaysJournal of lipid research,53(9), 2002-2013.

 

What's uncontested at this point is that high saturated fat diets and meals increase plasma endotoxins, both by modulating the gut microbiota and by increasing intestinal permeability. I'll let the titles tell the story:

 

Erridge, C., Attina, T., Spickett, C. M., & Webb, D. J. (2007). A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammationThe American journal of clinical nutrition86(5), 1286-1292.

Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., & Burcelin, R. (2008). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in miceDiabetes57(6), 1470-1481.

Ghoshal, S., Witta, J., Zhong, J., De Villiers, W., & Eckhardt, E. (2009). Chylomicrons promote intestinal absorption of lipopolysaccharidesJournal of lipid research50(1), 90-97.

Ghanim, H., Abuaysheh, S., Sia, C. L., Korzeniewski, K., Chaudhuri, A., Fernandez-Real, J. M., & Dandona, P. (2009). Increase in plasma endotoxin concentrations and the expression of toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal implications for insulin resistanceDiabetes care32(12), 2281-2287.

Suzuki, T., & Hara, H. (2010). Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF ratsNutr Metab (Lond)7(1), 19.

Rabot, S., Membrez, M., Bruneau, A., Gérard, P., Harach, T., Moser, M., ... & Chou, C. J. (2010). Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolismThe FASEB Journal24(12), 4948-4959.

Laugerette, F., Vors, C., Géloën, A., Chauvin, M. A., Soulage, C., Lambert-Porcheron, S., ... & Michalski, M. C. (2011). Emulsified lipids increase endotoxemia: possible role in early postprandial low-grade inflammationThe Journal of nutritional biochemistry22(1), 53-59.

Pendyala, S., Walker, J. M., & Holt, P. R. (2012). A high-fat diet is associated with endotoxemia that originates from the gutGastroenterology142(5), 1100-1101.

Kim, K. A., Gu, W., Lee, I. A., Joh, E. H., & Kim, D. H. (2012). High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathwayPLoS One7(10), e47713.

Clemente-Postigo, M., Queipo-Ortuno, M. I., Murri, M., Boto-Ordonez, M., Perez-Martinez, P., Andres-Lacueva, C., ... & Tinahones, F. J. (2012). Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patientsJournal of lipid research53(5), 973-978.

Harte, A. L., Varma, M. C., Tripathi, G., McGee, K. C., Al-Daghri, N. M., Al-Attas, O. S., ... & McTernan, P. G. (2012). High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects.Diabetes care35(2), 375-382.

Shrestha, U. K. (2012). High-fat diet is associated with endotoxemia and low-grade inflammationNepal Journal of Medical Sciences1(2), 62-63.

Serino, M., Luche, E., Gres, S., Baylac, A., Bergé, M., Cenac, C., ... & Burcelin, R. (2012). Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiotaGut61(4), 543-553.

Laugerette, F., Furet, J. P., Debard, C., Daira, P., Loizon, E., Géloën, A., ... & Michalski, M. C. (2012). Oil composition of high-fat diet affects metabolic inflammation differently in connection with endotoxin receptors in mice.American Journal of Physiology302(3), E374-E386.

Mani, V., Hollis, J. H., & Gabler, N. K. (2013). Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemiaNutr Metab10(6).

Zaman, G. S., Zaman, F., & Rasul, M. G. (2014) Comparison of postprandial endotoxemia in male adolescents and male subjects above 50 years after a fat overload

 

Reviews:

 

Moreira, A. P. B., Texeira, T. F. S., Ferreira, A. B., do Carmo Gouveia Peluzio, M., & de Cássia Gonçalves Alfenas, R. (2012). Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemiaBritish Journal of Nutrition108(05), 801-809.

Herieka, M., & Erridge, C. (2014). High‐fat meal induced postprandial inflammationMolecular nutrition & food research58(1), 136-146.

Shen, W., Gaskins, H. R., & McIntosh, M. K. (2014). Influence of dietary fat on intestinal microbes, inflammation, barrier function and metabolic outcomesThe Journal of nutritional biochemistry25(3), 270-280.

 

High dietary fructose is also implicated in metabolic endotoxemia, through encouraging small intestinal dysbiosis. The whole metabolic endotoxemia story is one of the most interesting, and most underreported, stories from recent nutritional science.

 

You have to be very careful with these studies.   First, since there are actually four different types of saturated fats (see my last post), you always have to ask which saturated fat are they testing?  It's almost always a dairy source, and the palmitic acid in those appears to have a dramatically different effect on many people (and animals) than the other types of saturated fats.

 

Second, you always have to ask are these studies showing the effects of dietary inputs, or are they actually reflecting high triglyceride loads in the blood caused by obesity or other lipid disorders?    When you overeat starchy carbs and high sugar foods, that gets stored as fats.   Those diets can make triglycerides soar.   Those triglycerides create high saturated fat loads at the cellular environment, which may or may not cause the endotoxin effects you are citing.

 

These are complex pathways and you have to invoke a lot of different causations to get from a dietary input to the final fact of inflammation.   Some people get high triglycerides from high palmitic acid diets.  Others get high triglycerides from high sugar/starch diets.   You find out your biology by testing, not by reading studies.

 

Again, I think diet studies are almost always worthless as "one-size-fits-all" advice.    There is no substitute for measuring YOUR triglycerides and HDL and LDL.  Then do very targeted dietary experiments, and re-measure those things until you get low triglycerides, high HDL, and low LDL-P (LDL particle count is a better marker than total LDL-C levels).    Some people will respond very well to high fat diets.   Some will crash on a high palmitic acid diet, but thrive on a high lauric acid diet.   Test and find out your specific genetics and dietary sensitivities.


Edited by pone11, 18 January 2015 - 10:10 PM.

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#6 Darryl

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Posted 19 January 2015 - 12:15 AM

The study protocols used a wide variety of fats:

 

butter: Erridge et al 2007,
coconut oil: Mani et al 2013
margarine and butter: Laugerette et al 2011
sausage muffin and hash browns: Ghanim et al 2009
lard and corn oil: Cani et al 2008, Serino et al 2012
lard and soybean oil: Suzuki & Hara 2010, Rabot et al 2010, Kim et al 2012
palm oil: Laugerette 2012
sunflower oil emulsion: Laugerette et al 2011
triolein: Ghoshal et al 2009
whipping cream: Harte et al 2012
lWestern-style diet: Pendyala et al 2012
 

The concern with saturated fats specifically is due to Laugerette et al 2012, which found that while all fats increased plasma endotoxin, palm oil diets caused the greatest transport of endotoxins to tissues via high LPS binding protein and low sCD14, and Mani et al 2013, which found that coconut oil increased postprandial plasma endotoxins by 60%, fish oil and cod liver oil reduced it by 50%, and olive and soybean oil had no effect.

 
High postprandial triglyceride levels are due to high fat meals, while high fasting triglycerides are associated with high-glycemic index starches, alcohol, and health conditions like obesity, diabetes, liver or kidney disease. As an aside, the usual fasting triglycerides measure on lipid panels may not be useful as a clinical predictor, as it strongly covaries with the stronger predictors HDL and non-HDL cholesterol. Similarly, genetic predispositions to higher fasting triglycerides which don't also effect HDL and LDL are not predictive of coronary heart disease, which casts additional doubt on a causal link between fasting triglycerides and cardiovascular risk. There has been some subsequent work on genetic predispositions for the less-studied non-fasting (ie, postprandial) triglyceride levels, which suggests a role in heart attack risk and all cause mortality
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#7 pone11

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Posted 19 January 2015 - 04:40 AM

 

The study protocols used a wide variety of fats:

 

butter: Erridge et al 2007,
coconut oil: Mani et al 2013
margarine and butter: Laugerette et al 2011
sausage muffin and hash browns: Ghanim et al 2009
lard and corn oil: Cani et al 2008, Serino et al 2012
lard and soybean oil: Suzuki & Hara 2010, Rabot et al 2010, Kim et al 2012
palm oil: Laugerette 2012
sunflower oil emulsion: Laugerette et al 2011
triolein: Ghoshal et al 2009
whipping cream: Harte et al 2012
lWestern-style diet: Pendyala et al 2012
 

The concern with saturated fats specifically is due to Laugerette et al 2012, which found that while all fats increased plasma endotoxin, palm oil diets caused the greatest transport of endotoxins to tissues via high LPS binding protein and low sCD14, and Mani et al 2013, which found that coconut oil increased postprandial plasma endotoxins by 60%, fish oil and cod liver oil reduced it by 50%, and olive and soybean oil had no effect.

 

Ignore the studies on polyunsaturated fats, because those have all kinds of health risks aside from endotoxin concerns.   The only study here that looks at Lauric acid is Mani 2013.   From that study:

"As expected, the CO (coconut oil) treatment significantly augmented the ileum endotoxin Papp compared to the saline control (P < 0.05). However, the endotoxin Papp was significantly reduced with the MβCD treatment compared to the saline control (1.54 vs. 0.07, P = 0.04). In the presence of MβCD and CO, the ileum Papp was attenuated three fold from the CO alone treatment (P < 0.05)."

 
Methyl-β-cyclodextrin (MβCD) is a kind of chemically produced amylose starch, so when they mixed in a starch that has lipid-lowering characteristics the coconut oil suddenly had fewer endotoxins than saline alone.  See the graph 4a in that study.   So what I take away from that study is that if you eat coconut oil and the right kind of starch together, you end up with less endotoxins than saline alone?   Where is the health impact of that?
 
This is why these kinds of isolated diet studies are almost worthless.   Foods interact with each other in complicated ways, further complicated by an individual's biology.   Even if I don't refer to studies that state the opposite conclusion, and just rely on this study itself, it already raises doubts about the usefulness of its observation.
 
The next problem with this study is that it does not measure endotoxins.    Instead, they use a proxy, which is the "serosal endotoxin transport permeability (Papp)" to endotoxins.   So we are supposed to conclude that endotoxins are higher because the gut is more permeable to endotoxins?   Again, the study contradicts its own results when it says:
"Importantly, ileum integrity and permeability as measured by transepithelial resistance was not altered by either short term coconut oil, MβCD, or the combination compared to the saline control (P = 0.98, Figure 4B)."
 
The author of the study himself calls out that other studies looking at the same effects come to opposite conclusions.  He tries to explain those differences away, unconvincingly I think but my opinion means nothing.
 
The next problem with this study is that it is a massively high carbohydrate load, made up of mostly corn and soybeans being fed to the pigs.   We don't really have any insight into the effects of dietary compositions, particularly from lowering the carbohydrate percentages in the diet.

 

The next problem with this study is that we don't have good research showing what *brief* periods of higher Papp permeability post-pandrial imply for actual inflammation in vivo.

 

Finally, I increased my saturated fat intake from 25% of calories ingested to 60% of calories ingested and my fasting triglycerides went from 74 to 51.    I was low and went even lower.  At the same time, my inflammation markers all went from very low to literally near zero.   So, like all dietary research, one size fits all advice is worthless.  Nothing substitutes measuring your own biology and response to different dietary inputs.    If I were suffering from inflammation I would test different types of saturated fat diets and then re-test the inflammation markers to see the actual effects.   And I guarantee you different individuals will get different results, and for many of us this study will have zero value in making any in vivo prediction.  

 

You can spend your whole life reading all of these contradictory nutrition studies and come out 20 years later even more confused than you were to start.  Or, you can spend two years running valid controlled experiments on your own body, and you can change your life dramatically for the better.

 

 

 

High postprandial triglyceride levels are due to high fat meals, while high fasting triglycerides are associated with high-glycemic index starches, alcohol, and health conditions like obesity, diabetes, liver or kidney disease. As an aside, the usual fasting triglycerides measure on lipid panels may not be useful as a clinical predictor, as it strongly covaries with the stronger predictors HDL and non-HDL cholesterol. Similarly, genetic predispositions to higher fasting triglycerides which don't also effect HDL and LDL are not predictive of coronary heart disease, which casts additional doubt on a causal link between fasting triglycerides and cardiovascular risk. There has been some subsequent work on genetic predispositions for the less-studied non-fasting (ie, postprandial) triglyceride levels, which suggests a role in heart attack risk and all cause mortality

 

The best new research suggests that 24 hour triglyceride area under the curve (AUC) correlates very strongly to fructose consumption.   There were some landmark studies by Kimber Stanhope at the Univ of California Davis where they took college students, locked them down in a hospital environment for weeks at a time, then alternated them on different diets.   In the video below she explains the protocol as it applies to a five year study they are currently undertaking.

 

There was no cheating on these diets, so they were able to tightly control fat intakes while they varied sugar intakes.   The other major advantage of the study protocol was that they could measure blood lipid levels constantly during the day, which made it possible to calculate a 24 hour area under the curve.  This is a much more meaningful metric than relying on either a postpandrial or fasting triglyceride!!    

 

They found when fructose was 25% of calories ingested, that most markers for heart disease deteriorated.   Here are two studies done by Stanhope's group or affiliates:

 

http://press.endocri...10/jc.2008-2192

http://www.ncbi.nlm....les/PMC2673878/

 

Some of the numbers in these studies are amazing.   When they made 25% of calories from glucose, the triglyceride 24 hr AUC was 242.3 +- 96.8.   When they substituted fructose 24 hr triglyceride AUC jumped to 704.3 +- 124.4 mg/dl.   (P < 0.0001).   These are enormous clinical changes, and as Kimber Stanhope has pointed out in interviews, these changes become visible within two weeks of starting these diets.    So you can dramatically and quickly change your blood lipid profiles by changing the type of carbohydrates in your diet.

 

This indirectly shows one of the problems with research that focuses on saturated fats.   95% of those studies do not control well for sugar.   So examining a diet where someone eats a fatty food that is loaded with high fructose corn syrup may see an association between higher fat intakes and higher triglycerides.   But the causality is significantly related to sugar, which they didn't measure or control in the study.

 

Just an aside:  no one should read these studies to say that fruit is bad.   The issue is not eating a few cups of fruit each day, which are loaded with fiber and other nutrients.   The issue is consuming massive amounts of fructose, particularly in the form of table sugar or high fructose corn syrup.   It's just common to find processed foods where each serving is 25 grams of carbs, and 15 grams of that is fructose.    You consume four sodas a day and six servings of processed food, and now you are eating 150 grams of fructose.   That's the target population that is at risk, not the person eating a few fruits at breakfast and lunch.

 

There was an interesting show on sugar on 60 Minutes, and a video summary of Stanhope's research starts at around 03:59 on the video:

http://www.dietdocto...r-on-60-minutes

(I grabbed this from third party web site because the resolution was better than the Youtube version...sorry about that.)    

 

Again, I think people who think they are going to read research studies suggesting that fat causes high triglycerides and learn anything about their personal biology are wrong.   There is no substitute for measuring your own biological parameters, designing careful experiments, and then retesting.

 

 

 


Edited by pone11, 19 January 2015 - 05:21 AM.

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#8 StevesPetRat

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Posted 21 January 2015 - 07:28 PM

Pone, while I do appreciate that saturated fat isn't bad for cardiovascular disease markers, and may even be beneficial in some cases, my concern is more with immune system activation through TLR4 agonism. While LDL, trigs, etc. can be sort of proxy measurements for systemic inflammation, they don't necessarily tell the full story. I've noticed brain fog, for instance, when I put too much coconut oil in my smoothies; this is a fairly reproducible result. Anyway, I do plan to test this all on myself, so your advice is well heeded.

Darryl, one of the studies I linked originally addresses your concern about contamination, I think. Further, a lot of the studies you've cited make it sounds like all fats are problematic for increasing LPS rather than just sat fat (though the coconut / fish / olive / soybean study would be more in line with what I thought was the case).

Seriously, can't I just kill off all the gram negative bacteria in my gut and stop worrying about it?

#9 pone11

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Posted 22 January 2015 - 03:09 AM

Pone, while I do appreciate that saturated fat isn't bad for cardiovascular disease markers, and may even be beneficial in some cases, my concern is more with immune system activation through TLR4 agonism. While LDL, trigs, etc. can be sort of proxy measurements for systemic inflammation, they don't necessarily tell the full story. I've noticed brain fog, for instance, when I put too much coconut oil in my smoothies; this is a fairly reproducible result. Anyway, I do plan to test this all on myself, so your advice is well heeded.

Darryl, one of the studies I linked originally addresses your concern about contamination, I think. Further, a lot of the studies you've cited make it sounds like all fats are problematic for increasing LPS rather than just sat fat (though the coconut / fish / olive / soybean study would be more in line with what I thought was the case).

Seriously, can't I just kill off all the gram negative bacteria in my gut and stop worrying about it?

 

Try an experiment just for kicks.   Take a breakfast with no starch (polysaccharides) and no sucrose or lactose (disaccharides).  Instead, any carbs should be from a form of fruit with minimal sucrose (e.g., blueberries or blackberries) and you can add in veggies that have no starch content.  You want fruit that contains the monosaccharides glucose and fructose as separate simple sugars.  Most honey has separate monosaccharides glucose and fructose and very little sucrose.   Record your digestion (e.g., gas) of that and your level of brain fog for each hour after the meal for about four hours.

 

Now the next day substitute sucrose and fruits like ripe banana that are high in sucrose.   Avoid the monosaccharides.   Do you observe a difference?

 

Third day just take in starches.   You might have to watch symptoms for six hours or so because these are slower to digest.

 

Most people with inflammatory bowel disease (IBD), and many with the more benign IBS, will see dramatically different results with the first case.  The monosaccharides will produce a very clean energy with minimal brain fog and intestinal disturbance.  The disaccharides - which in theory contain identical amounts of glucose and fructose - will create lots of intestinal symptoms and sometimes will increase inflammatory symptoms or brain fog.

 

The reason for the difference in the two cases is that many people with compromised gut functions lack either enough sucrase enzyme to break down the sucrose, or alternately their intestinal villi are compromised in such a way that the sucrase does not do its work completely.

 

I had an osteopath point this out to me and I immediately dismissed it since "I knew that sucrose is equal to fructose + glucose" but - sure enough - he was right and I was wrong.  In me - and in many people - the monosaccharides digest perfectly and the disaccharides create symptoms.   For me, learning this lesson was life changing.  I re-engineered my diet to remove all starches and to selectively minimize sucrose intake.  Wow, it's like being reborn, if you have this problem with disaccharide and starch digestion.

 

By any chance, are you taking in any supplements with alpha lipoic acid (ALA or R-ALA) on the ingredient list?   If yes, you might want to contact me by email.  

 

Brain fog is incredibly frustrating so I empathize with you.  It really compromises your ability to function at a basic level, and tracing back to the causes can be hideously difficult.


Edited by pone11, 22 January 2015 - 03:12 AM.

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#10 tunt01

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Posted 20 April 2018 - 09:04 AM

Evidence that TLR4 Is Not a Receptor for Saturated Fatty Acids but Mediates Lipid-Induced Inflammation by Reprogramming Macrophage Metabolism

 

 

Highlights

 

  • The long-chain saturated fatty acid palmitate is not a TLR4 agonist
  • Palmitate is unable to activate JNK in TLR4-deficient macrophages
  • Priming TLR4-deficient macrophages restores palmitate's inflammatory effects
  • Priming requires mTOR and is associated with altered lipid metabolism and ER stress

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Summary

Chronic inflammation is a hallmark of obesity and is linked to the development of numerous diseases. The activation of toll-like receptor 4 (TLR4) by long-chain saturated fatty acids (lcSFAs) is an important process in understanding how obesity initiates inflammation. While experimental evidence supports an important role for TLR4 in obesity-induced inflammation in vivo, via a mechanism thought to involve direct binding to and activation of TLR4 by lcSFAs, several lines of evidence argue against lcSFAs being direct TLR4 agonists. Using multiple orthogonal approaches, we herein provide evidence that while loss-of-function models confirm that TLR4 does, indeed, regulate lcSFA-induced inflammation, TLR4 is not a receptor for lcSFAs. Rather, we show that TLR4-dependent priming alters cellular metabolism, gene expression, lipid metabolic pathways, and membrane lipid composition, changes that are necessary for lcSFA-induced inflammation. These results reconcile previous discordant observations and challenge the prevailing view of TLR4's role in initiating obesity-induced inflammation.

 

 
I haven't had time to read this, but I thought it would be of interest here.

Edited by tunt01, 20 April 2018 - 04:27 PM.

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Also tagged with one or more of these keywords: saturated fat, dha, omega 3, fat, tlr4, lps, lipopolysaccharides, inflammation, firefly is good but overrated

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