Compared to soybean oil and olive oil coconut oil results in endotoxemia and fatty liver

[Kvothe]

Consumption of soybean or olive oil at recommended concentrations increased the intestinal microbiota diversity and insulin sensitivity and prevented fatty liver compared to the effects of coconut oil​

Author links open overlay panelValeriaLópez-Salazarab1
Mónica SánchezTapiab1SandraTobón-CornejobDanielDíazcGabrielaAlemán-EscondrillasbOmarGranados-PortillobLiliaNoriegabArmando RTovarbNimbeTorresb

The Journal of Nutritional Biochemistry​

Volume 94, August 2021, 108751

Diets rich in mono or polyunsaturated fats have been associated with a healthy
phenotype, but there is controversial evidence about coconut oil (CO), which is rich
in saturated medium-chain fatty acids. Therefore, the purpose of the present work
was to study whether different types of oils rich in polyunsaturated (soybean oil,
SO), monounsaturated (olive oil, OO), or saturated fatty acids (coconut oil, CO)
can regulate the gut microbiota, insulin sensitivity, inflammation, mitochondrial
function in wild type and PPAR KO mice. The group that received SO showed the
highest microbial diversity, increase in Akkermansia muciniphila, high insulin
sensitivity and low grade inflammation, The OO group showed similar insulin
sensitivity and insulin signaling than SO, increase in Bifidobacterium, increase in
fatty acid oxidation and low grade inflammation. The CO consumption led to the
lowest bacterial diversity, a 9-fold increase in the LPS concentration leading to
metabolic endotoxemia, hepatic steatosis, increased lipogenesis, highest LDL-
cholesterol concentration and the lowest respiratory capacity and fatty acid
oxidation in the mitochondria. The absence of PPARdecreased alpha diversity
and increased LPS concentration particularly in the CO group, and increased
insulin sensitivity in the groups fed SO or OO. These results indicate that
consuming mono or polyunsaturated fatty acids produced health benefits at the
recommended intake but a high concentration of oils (three times the
recommended oil intake in rodents) significantly decreased the microbial alpha-
diversity independent of the type of oil.

"the results of the Western blot analysis revealed that
consuming 7% SO or 7% OO led to significantly lower TLR-4 and NF-kB protein
abundance than 7% CO, but the PPARKO mice showed a significant increase in
the abundance of these proteins, primarily in the group that received 21% CO"

"Increasing the % of dietary fat increased the serum
LPS concentration, but the consumption of 21% CO, increased the concentration
of LPS in the serum by 90-fold compared to the 7% SO group" (ouch )

Discuss. Intersting points are:

- Increased TLR4 in coconut oil groups (@haidut )
- Decreased lactobacillus reuteri in coconut oil group. (This study showed the direct opposite)
- Lower bacterial diversity resulting in inflammation following coconut oil (@Amazoniac )
- Mice at 7% cocnut oil had higher BW gain compared to SO or OO, while 21% coconut oil made animals leaner.

 

[Razvan]

Oh I thought you were a very pro peat individual,even got irritable when attacked of peaty stuff in other threads:))

 

[Perry Staltic]

Interesting about the coconut oil. The last time i used it I developed an irritated gut. I don't know if that was the reason, but I've been afraid to do a test. I usually use olive oil. Maybe the gut gets used to one and doesn't like the other.

 

[haidut]

Consumption of soybean or olive oil at recommended concentrations increased the intestinal microbiota diversity and insulin sensitivity and prevented fatty liver compared to the effects of coconut oil​

Author links open overlay panelValeriaLópez-Salazarab1
Mónica SánchezTapiab1SandraTobón-CornejobDanielDíazcGabrielaAlemán-EscondrillasbOmarGranados-PortillobLiliaNoriegabArmando RTovarbNimbeTorresb

The Journal of Nutritional Biochemistry​

Volume 94, August 2021, 108751

Diets rich in mono or polyunsaturated fats have been associated with a healthy
phenotype, but there is controversial evidence about coconut oil (CO), which is rich
in saturated medium-chain fatty acids. Therefore, the purpose of the present work
was to study whether different types of oils rich in polyunsaturated (soybean oil,
SO), monounsaturated (olive oil, OO), or saturated fatty acids (coconut oil, CO)
can regulate the gut microbiota, insulin sensitivity, inflammation, mitochondrial
function in wild type and PPAR KO mice. The group that received SO showed the
highest microbial diversity, increase in Akkermansia muciniphila, high insulin
sensitivity and low grade inflammation, The OO group showed similar insulin
sensitivity and insulin signaling than SO, increase in Bifidobacterium, increase in
fatty acid oxidation and low grade inflammation. The CO consumption led to the
lowest bacterial diversity, a 9-fold increase in the LPS concentration leading to
metabolic endotoxemia, hepatic steatosis, increased lipogenesis, highest LDL-
cholesterol concentration and the lowest respiratory capacity and fatty acid
oxidation in the mitochondria. The absence of PPARdecreased alpha diversity
and increased LPS concentration particularly in the CO group, and increased
insulin sensitivity in the groups fed SO or OO. These results indicate that
consuming mono or polyunsaturated fatty acids produced health benefits at the
recommended intake but a high concentration of oils (three times the
recommended oil intake in rodents) significantly decreased the microbial alpha-
diversity independent of the type of oil.

"the results of the Western blot analysis revealed that
consuming 7% SO or 7% OO led to significantly lower TLR-4 and NF-kB protein
abundance than 7% CO, but the PPARKO mice showed a significant increase in
the abundance of these proteins, primarily in the group that received 21% CO"

"Increasing the % of dietary fat increased the serum
LPS concentration, but the consumption of 21% CO, increased the concentration
of LPS in the serum by 90-fold compared to the 7% SO group" (ouch )

Discuss. Intersting points are:

- Increased TLR4 in coconut oil groups (@haidut )
- Decreased lactobacillus reuteri in coconut oil group. (This study showed the direct opposite)
- Lower bacterial diversity resulting in inflammation following coconut oil (@Amazoniac )
- Mice at 7% cocnut oil had higher BW gain compared to SO or OO, while 21% coconut oil made animals leaner.

If you look at Figure 3, they show that in mice that lack PPAR-alpha, coconut oil (CO) was actually the healthiest of all 3 oils and it was specifically the expression/activation of PPAR-alpha to varying degrees by the 3 oils that accounted for the difference in their effects on mice. There seems to be species difference between rodents and humans in both the expression (mRNA) and responsiveness of PPAR-alpha to agonists such as fatty acids, making humans behave more similarly to PPAR-alpha lacking mice, in which CO was the healthiest

Differential Gene Regulation in Human Versus Rodent Hepatocytes by Peroxisome Proliferator-activated Receptor (PPAR) α

We compared the ability of rat and human hepatocytes to respond to fenofibric acid and a novel potent phenylacetic acid peroxisome proliferator-activated receptor (PPAR) α agonist (compound 1). Fatty acyl-CoA oxidase (FACO) activity and mRNA were increased after treatment with either fenofibric...

www.jbc.org

The PPAR alpha-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha - PubMed

To determine the impact of the species difference between rodents and humans in response to peroxisome proliferators (PPs) mediated by peroxisome proliferator-activated receptor (PPAR)alpha, PPAR alpha-humanized transgenic mice were generated using a P1 phage artificial chromosome (PAC) genomic...

pubmed.ncbi.nlm.nih.gov

Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators - PubMed

We have isolated a human peroxisomal proliferator activated receptor (hPPAR) from a human liver cDNA library. Based on sequence analysis, we have determined that this cDNA encodes the human PPAR alpha. When assayed in a reconstituted hPPAR responsive transcription system in mammalian CV-1 cells...

pubmed.ncbi.nlm.nih.gov

While I don't discount this study's findings, the benefits of CO specifically for human liver have been confirmed multiple times by various studies with cirrhotic chronic alcoholics in India, and by the studies of Nanji et al who demonstrated not only lack of liver inflammation from CO but actual reversal of liver fibrosis in both humans and rodents, while PUFA was the most detrimental.

 

[Kvothe]

If you look at Figure 3, they show that in mice that lack PPAR-alpha, coconut oil (CO) was actually the healthiest of all 3 oils and it was specifically the expression/activation of PPAR-alpha to varying degrees by the 3 oils that accounted for the difference in their effects on mice. There seems to be species difference between rodents and humans in both the expression (mRNA) and responsiveness of PPAR-alpha to agonists such as fatty acids, making humans behave more similarly to PPAR-alpha lacking mice, in which CO was the healthiest

Differential Gene Regulation in Human Versus Rodent Hepatocytes by Peroxisome Proliferator-activated Receptor (PPAR) α

We compared the ability of rat and human hepatocytes to respond to fenofibric acid and a novel potent phenylacetic acid peroxisome proliferator-activated receptor (PPAR) α agonist (compound 1). Fatty acyl-CoA oxidase (FACO) activity and mRNA were increased after treatment with either fenofibric...

www.jbc.org

The PPAR alpha-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha - PubMed

To determine the impact of the species difference between rodents and humans in response to peroxisome proliferators (PPs) mediated by peroxisome proliferator-activated receptor (PPAR)alpha, PPAR alpha-humanized transgenic mice were generated using a P1 phage artificial chromosome (PAC) genomic...

pubmed.ncbi.nlm.nih.gov

Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators - PubMed

We have isolated a human peroxisomal proliferator activated receptor (hPPAR) from a human liver cDNA library. Based on sequence analysis, we have determined that this cDNA encodes the human PPAR alpha. When assayed in a reconstituted hPPAR responsive transcription system in mammalian CV-1 cells...

pubmed.ncbi.nlm.nih.gov

While I don't discount this study's findings, the benefits of CO specifically for human liver have been confirmed multiple times by various studies with cirrhotic chronic alcoholics in India, and by the studies of Nanji et al who demonstrated not only lack of liver inflammation from CO but actual reversal of liver fibrosis in both humans and rodents, while PUFA was the most detrimental.

Interestingly, LPS and TLR4 were highest in the coconut animals lacking PPARα. The fact that other studies comparing coconut oil and soybean oil have found distinctly different results, make the negative effects of coconut oil in this one intriguing.

Soybean Oil Is More Obesogenic and Diabetogenic than Coconut Oil and Fructose in Mouse: Potential Role for the Liver
Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice

PPAR

 

[haidut]

Interestingly, LPS and TLR4 were highest in the coconut animals lacking PPARα. The fact that other studies comparing coconut oil and soybean oil have found distinctly different results, make the negative effects of coconut oil in this one intriguing.

Soybean Oil Is More Obesogenic and Diabetogenic than Coconut Oil and Fructose in Mouse: Potential Role for the Liver
Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice

View attachment 30359
PPAR

Yep, definitely interesting results. I wonder why they selected specifically PPARa as a target to modulate in their mice. It is also strange that in the PPARa-null mice LPS rose 90+ times in the CO group yet that group had the lowest weight/fat gain. If LPS is responsible for liver issues/inflammation and obesity, which the study also stated/agreed, the group with the highest LPS should fare the worst. Maybe enxotoxin/LPS is only/mostly dangerous by increasing fatty acid oxidation (FAO) through PPARa?? Could be worth emailing the authors with these questions, and maybe suggest repeating the study with the same design but administering the CO group a FAO blocker such as Mildronate, or maybe even niacinamide, and checking if that changes the outcome.

 

[Kvothe]

Yep, definitely interesting results. I wonder why they selected specifically PPARa as a target to modulate in their mice. It is also strange that in the PPARa-null mice LPS rose 90+ times in the CO group yet that group had the lowest weight/fat gain. If LPS is responsible for liver issues/inflammation and obesity, which the study also stated/agreed, the group with the highest LPS should fare the worst. Maybe enxotoxin/LPS is only/mostly dangerous by increasing fatty acid oxidation (FAO) through PPARa?? Could be worth emailing the authors with these questions, and maybe suggest repeating the study with the same design but administering the CO group a FAO blocker such as Mildronate, or maybe even niacinamide, and checking if that changes the outcome.

They explain in their introduction that fatty acids act as a ligand for PPARα, and that it is involved in regulating the gut microbiota. In the discussion they mention that several PPARα-agonist are tested as treatments for liver disease. They state that unsaturated fats have a higher affinity for the nuclear receptor, but other studies have shown that lauric acid in particular acts as natural ligand for PPARα, and that this is part of coconut oil's curative properties.
They do mention that"only at 21% CO that we observed an increase in the expression of fatty acid synthase (FAS)". Again this stands in contrast to other studies showing coconut oil lowers the expression of that enzyme. Maybe natural flavonoids present in the soy and olive oil, but not in the (refined?) coconut oil had some short-term beneficial effect on fatty acid metabolism.

"Dietary supplementation of VCO decreased tissue lipid levels and reduced the activity of the enzymes involved in lipogenesis, namely acyl CoA carboxylase and fatty acid synthase (FAS) (P< 0·05). Moreover, VCO significantly (P< 0·05) reduced the de novo synthesis of fatty acids by down-regulating the mRNA expression of FAS and its transcription factor, sterol regulatory element-binding protein-1c, compared with the other oils."

Influence of virgin coconut oil-enriched diet on the transcriptional regulation of fatty acid synthesis and oxidation in rats - a comparative study

 

[lampofred]

I didn't read the study in detail, but my first reaction to skimming OP is that eating coconut oil is analogous to how taking progesterone increases estrogen in the bloodstream initially but actually lowers the body's stores of estrogen over time, whereas a low progesterone person will seem to have low estrogen in the blood but is actually more estrogenic than the high progesterone person because the estrogen is accumulating hidden inside the cells where it is much more active and toxic than when it is being visibly dumped into the bloodstream by progesterone.

That might sound a bit convoluted but the progesterone-estrogen relationship itself is pretty convoluted; you shouldn't trust what you see on the surface but you shouldn't read overly into it either...

Another point I see in favor of coconut oil is that it didn't increase inflammation like soy oil or olive oil, and Peat considers inflammation to be one of the most important factors to look at.

However interestingly Peat seems to be recommending butter more than coconut oil nowadays; he doesn't seem to be as much of a fan of CO as he used to be.

 

[tca300]

Probably has a lot to do with fat chain length and how shorter fat chain lengths are absorbed differently. Endotoxin probably piggy backs on the shorter chain fats during absorbtion. I think the endotoxin getting into the bloodstream would explain the liver Inflammation etc..

.." dietary medium-chain triglycerides (MCT), which bypass mesenteric lymph and directly enter portal blood.."

Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice

The prevalence of peanut allergies is rising. Peanuts and many other allergen sources contain significant amounts of triglycerides, which affect absorption of antigens but have unknown effects on sensitization and anaphylaxis. We recently reported that ...

www.ncbi.nlm.nih.gov

 

[Kvothe]

Probably has a lot to do with fat chain length and how shorter fat chain lengths are absorbed differently. Endotoxin probably piggy backs on the shorter chain fats during absorbtion. I think the endotoxin getting into the bloodstream would explain the liver Inflammation etc..

.." dietary medium-chain triglycerides (MCT), which bypass mesenteric lymph and directly enter portal blood.."

Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice

The prevalence of peanut allergies is rising. Peanuts and many other allergen sources contain significant amounts of triglycerides, which affect absorption of antigens but have unknown effects on sensitization and anaphylaxis. We recently reported that ...

www.ncbi.nlm.nih.gov

Still, it's odd because other studies, even the ones with mice, show no liver inflammation when coconut oil is fed. They don't show any endotoxemia in the long-term, either. Endotoxin is probably transported by the same transport mechanisms as are long-chain-fatty-acids, by incorporation into chylomicrons. Therefore, fats with more LCFA should be more potent transporters than coconut oil. MCTs are taken up by chylomiocrons to a much lesser degree. (2)

1) Lipopolysaccharides transport during fat absorption in rodent small intestine
2) Medium-chain fatty acids: evidence for incorporation into chylomicron triglycerides in humans

​

 

[Amazoniac]

It is also strange that in the PPARa-null mice LPS rose 90+ times in the CO group yet that group had the lowest weight/fat gain. If LPS is responsible for liver issues/inflammation and obesity, which the study also stated/agreed, the group with the highest LPS should fare the worst.

Spoiler

"[..]we observed marked hepatic steatosis in wild type mice receiving 7% CO, whereas the livers in mice that consumed 7% OO showed slight interstitial inflammation and the liver of mice that consumed 7% SO showed a normal morphology. Mice receiving 21% SO showed macrovesicular steatosis due to the presence of large lipid droplets, but mice consuming 21% OO showed microvesicular steatosis due to the presence of multiple small lipid droplets. Mice that were given 21% CO showed severe microvesicular steatosis with the characteristic foamy cytoplasmic appearance (Figure S2A)."​

Given that things went worse for higher fat intakes, a stress response must explain their lower weight, maybe animals decreased food consumption when it got overwhelming.

---

Perhaps extra killcium mitigates these issues.

- Why Ray Recommends Eating Lots Of Calcium

"LPS molecules are made up of a polysaccharide chain and several saturated fatty acids and have low permeability for hydrophobic compounds."

(This study showed the direct opposite)

"As suggested by de Wit et al [18] this could be due to the overflow of dietary fat to the distal parts of the intestine induced by a diet high in saturated fat but not by unsaturated fat diets."​

​

[18] Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine​

 

[Kvothe]

"As suggested by de Wit et al [18] this could be due to the overflow of dietary fat to the distal parts of the intestine induced by a diet high in saturated fat but not by unsaturated fat diets."[18] Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine

The saturated fat used in Wit et al was palm oil. I'm less than certain this is a useful choice to make generalizations about saturated fat, and palm oil comes with lots of carotene as a confounding variable. In their study, the palm oil caused a significant reduction in proteobacteria, the ones most associated with saturated fats in some studies we discussed.
I don't see why more fatty acids from coconut oil should overflow to distal parts of the intestine, when most of the fatty acids in it have a very short chainlength and are rapidly absorbed.

 

[Amazoniac]

The saturated fat used in Wit et al was palm oil. I'm less than certain this is a useful choice to make generalizations about saturated fat, and palm oil comes with lots of carotene as a confounding variable. In their study, the palm oil caused a significant reduction in proteobacteria, the ones most associated with saturated fats in some studies we discussed.
I don't see why more fatty acids from coconut oil should overflow to distal parts of the intestine, when most of the fatty acids in it have a very short chainlength and are rapidly absorbed.

I don't expect a direct effect. Coconut oil affects lipids, degradation of atherosclerol to bile acids can be a means for this to occur, and the impact should be greater if it's not refined.

On a side note, it's a shame that Cu and Mn are lost in obtaining the oil because they could be of benefit for lipid metabolism. They're probably extractable when coconut pulp is consumed since the milk retains them.

 

[Kvothe]

and the impact should be greater if it's not refined.

Why?

 

[Kvothe]

Could be worth emailing the authors with these questions

I reached out to the two main authors. I got a mail delivery failed, and her site at the Helmholz institute no langer exists. I'll see whether one of the other guys replies. I asked them what kind of coconut oil they used exactely (brand, source, grade of refinement)

 

[Amazoniac]

Why?

- Problems With Sulphur

- Anatomical and Physiological Parameters that Influence Gastrointestinal Absorption

Spoiler

 

[Dave Clark]

Doesn't palmitoylethanolamide, PEA, activate PPAR? May be a good compound to use with coconut oil.

 

[Kozak]

I'd say monolaurin (natural antibiotic) from CO was killing pathogenic bacteria. LPS (as you know) are the remnants of the pathogenic bacteria membranes.

 

[Birdie]

Another article from this esteemed journal:

Omega-3 polyunsaturated fatty acids promote SNAREs mediated GLUT4 vesicle docking and fusion​

 

[Birdie]

Would be interesting to see who controls this journal.