Mitigating PUFAs anti metabolic effect with increased calories intake

[rockarolla]

I've tried PUFA in isolation as a supplement and it brought a lot of stress response(fatigue, insomnia, etc) like I was eating some sort of toxin. Does PUFA raises endotoxemia as an antibiotic?

Anyway I've overcame the effect next time eating an extra 500 carb-calories, i.e. it seems that negative effects from PUFA could be mitigated via increased glucose calories intake, as if extra toxicity spikes requirements for glucose drastically.

Anyone noticed the same thing?

New Defense Against Bacterial Superbugs: Taking Fish Oil May Reduce Antibiotic Resistance

For the first time, Australian scientists have confirmed a link between the role of regular fish oil to break down the ability of 'superbugs' to become resistant to antibiotics. The discovery, led by Flinders University and just published in international journal mBio, found that the antimicrobia

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[Momado965]

Interesting so bump.

 

[dabdabdab]

I've done this, it doesn't help with postprandial endotoxin. I know that since whenever I eat even a small amount of pufas, my heels start to pain.
I've always had that pain since childhood, the only time it stopped was when I ate something purgatuve like a large amount of hot peppers and ran into the bathroom , or when I changed my diet and cooking oil to a mufa, sat type of oil.

nuts usually have less effect on me due to high vitamin e and fiber.

 

[rockarolla]

Maybe its due to corresponding insulin increase.


Acute modulation of toll-like receptors by insulin
Acute modulation of toll-like receptors by insulin - PubMed
Results: Insulin infusion significantly suppressed TLR1, -2, -4, -7, and -9 mRNA expression in MNCs within 2 h of the infusion, with a maximum fall at 4 h by 24 +/- 9%, 21 +/- 5%, 30 +/- 8%, 28 +/- 5%, and 27 +/- 10% (P < 0.05, for all), respectively, below the baseline. TLR2 protein was suppressed by 19 +/- 7% (P < 0.05) below the baseline at 4 h. The DNA binding of PU.1, a major transcription factor regulating many TLR genes, was concomitantly suppressed by 24 +/- 10% (P < 0.05) by 4 h in MNCs. There was no change in TLR expression or DNA binding by PU.1 following dextrose or saline infusion in the control groups.
...
Since TLR4 mediates the inflammatory response to endotoxin, it is possible that insulin may potentially reduce the inflammatory response to endotoxin by reducing the receptor population binding to endotoxin, provided we can demonstrate a reduction in TLR4 protein expression with longer infusions in the future. This effect would be in addition to the more direct anti-inflammatory effect of its own through the suppression of NFκB and early growth response factor-1, two major proinflammatory transcription factors. Such an additional effect may be of considerable importance since inflammation triggers an increase in TLR expression and thus provides a positive feedback for inflammation. This positive feedback, which may lead to a more protracted and intense inflammation, would potentially be prevented by insulin. A direct anti-inflammatory effect of insulin and its additional ability to suppress TLR expression provide it a profoundly potent combination in combating inflammatory processes. The suppression of TLR2 expression at mRNA and protein level by insulin is relevant to gram-positive bacterial infections. These actions of insulin may have contributed to the beneficial effects of insulin observed by Langouche et al. (22) in patients in critical care. It is also relevant that a similar low dose of insulin infusion causes a reduction of 40% in plasma CRP and SAA concentrations within 24 h in acutely ill patients with acute myocardial infarction (3) and in patients undergoing coronary artery bypass surgery (4). Whether a significant part of this suppression of CRP and SAA and the cardioprotection observed in acute myocardial infarction receives a contribution from a reduction in TLR2 expression needs to be carefully assessed in the future.

Recent work (23) has shown that in atherosclerosis, the expression of TLR1, -2, and -4 in the arterial intima is increased, especially in areas with inflammatory infiltration. The increase in TLR2 and TLR4 expression is associated with an increase in intranuclear NFκB. Several TLR4 ligands, such as oxidized LDL, human heat shock protein-60 and -70, and peptidoglycan are found in atherosclerotic plaques. They may activate NFκB and cause a release of cytokines and matrix metalloproteinases. This indicates that insulin action on TLR expression might play a role in atherosclerosis suppression and potential prevention of plaque rupture.

Active pharmaceutical research aiming to reduce TLR4 expression to prevent the proinflammatory action of LPS is currently being undertaken. This includes an attempt to generate antibodies against TLR4. The rapid suppression of TLR2 and TLR4 expression by insulin implies that insulin can be used clinically in endotoxemia and gram-negative (TLR4) and gram-positive (TLR2) infections to limit their inflammatory effects. Furthermore, the involvement of TLR2 in ischemia-reperfusion injury (11) and that of TLR4 in atherogenesis further justifies the use of insulin in acute and chronic atherosclerotic syndromes. In this context, the ability of insulin to suppress CRP is also relevant, since CRP mediates injury during ischemia-reperfusion of the heart and synthetic small molecules (phasphotidyl choline derivatives), which bind to and block CRP action and reduce the size of myocardial injury (24).

In conclusion, insulin suppresses TLR expression and the activity of the transcription factor PU.1. The suppressive effect of insulin on TLRs also has important potential implications in the treatment of inflammatory conditions including endotoxemia, other infections, and acute coronary syndromes in which TLR2-related mechanisms are involved. The suppressive effect of insulin on TLR4 is also important in understanding the relationship of inflammation to obesity and insulin resistance and atherosclerosis.

Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
LPS injection induced a rapid increase in plasma concentrations of nitric oxide metabolites, nitrite and nitrate (NOM), and thiobarbituric acid–reacting substances (TBARS), an increase in reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNLs), and marked increases in plasma free fatty acids, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibition factor (MIF), C-reactive protein, resistin, visfatin, lipopolysaccharide binding protein (LBP), high mobility group-B1 (HMG-B1), and myoglobin concentrations. The coinfusion of insulin led to a total elimination of the increase in NOM, free fatty acids, and TBARS and a significant reduction in ROS generation by PMNLs and plasma MIF, visfatin, and myoglobin concentrations. Insulin did not affect TNF-α, MCP-1, IL-6, LBP, resistin, and HMG-B1 increases induced by the LPS.
...
Insulin reduces significantly several key mediators of oxidative, nitrosative, and inflammatory stress and tissue damage induced by LPS. These effects of insulin require further investigation for its potential use as anti-inflammatory therapy for endotoxemia.
...
Insulin has been shown to suppress inflammatory changes in vitro and in vivo. It suppresses intranuclear NFκB and Egr-1 binding and the expression of several proinflammatory mediators including intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9, C-reactive protein (CRP), and serum amyloid A (3,4). In addition, it suppresses the expression of several Toll-like receptors (TLRs) (5). It also suppresses reactive oxygen species (ROS) generation and p47phox expression.
...
Our data clearly show for the first time a potent and rapid suppressive effect of a low dose of insulin infusion on the expression of TLR1, -2, -4, -7, and -9 by 20–30%, evident at 2 h, continuing until 4 h, and reverting back to baseline 2 h after the cessation of infusion. This low-dose infusion of insulin has previously been shown to exert a rapid and profound anti-inflammatory effect within 2 h, as reflected in the suppression of NFκB binding and an increase in inhibitor of κBα expression. The fall in TLR2 mRNA was also associated with a reduction in the expression of TLR2 protein. The absence of a clear suppression of TLR4 protein level may be due to the relatively short period of infusion. This issue should be addressed in the future by longer periods of infusion. Our data also demonstrate clearly for the first time that insulin rapidly suppresses the DNA binding of PU.1 to a specific sequence of TLR4 gene promoter. PU.1 is a key transcription factor in the regulation of TLR transcription, and, thus, its suppression is reflected in the suppression of many of TLRs to a similar extent. The pattern of fall in TLR mRNA expression was similar to that observed with other proinflammatory mediators like MCP-1 and sICAM-1, which fell at 2 h, remained low for the duration of the infusion, and returned to baseline at 6 h, 2 h after the cessation of the insulin infusion. This is also consistent with our previous data on the suppressive effect of insulin on other indexes of inflammation. Thus, there is a remarkable consistency in the pharmacodynamics of the various aspects of the anti-inflammatory effects of insulin.

 

[dabdabdab]

I ate two plates of rice and bread, it didn't help with that. it actually worsened my problem.
maybe the study speaks about increases sugar not complex carbs like starch.

 

[Hugh Johnson]

I've tried PUFA in isolation as a supplement and it brought a lot of stress response(fatigue, insomnia, etc) like I was eating some sort of toxin. Does PUFA raises endotoxemia as an antibiotic?

Anyway I've overcame the effect next time eating an extra 500 carb-calories, i.e. it seems that negative effects from PUFA could be mitigated via increased glucose calories intake, as if extra toxicity spikes requirements for glucose drastically.

Anyone noticed the same thing?

New Defense Against Bacterial Superbugs: Taking Fish Oil May Reduce Antibiotic Resistance

For the first time, Australian scientists have confirmed a link between the role of regular fish oil to break down the ability of 'superbugs' to become resistant to antibiotics. The discovery, led by Flinders University and just published in international journal mBio, found that the antimicrobia

scitechdaily.com

Because it gets stored as fat, so you won't notice an immediate effect.

 

[rockarolla]

I ate a two plates of rice and bread, it didn't help with that. it actually worsened my problem.
maybe the study speaks about increases sugar not complex carbs like starch.

Starch seems to have dual effect - it raises both glucose and insulin where glucose is pro inflammatory while insulin is anti - so the net effect could differ by per case basis - for me sometimes starch actually palliates symptoms...

Enhancement of LPS-Induced Microglial Inflammation Response via TLR4 Under High Glucose Conditions
Enhancement of LPS-Induced Microglial Inflammation Response via TLR4 Under High Glucose Conditions
Background: Microglia activation mediated by toll-like receptor 4 (TLR4) plays an important role in neuroinflammation and postoperative cognitive dysfunction (POCD). Diabetes mellitus (DM) has been recently suggested as an independent risk factor for POCD. In this study, we investigate the potential exacerbation of the inflammatory response in primary microglia due to high glucose conditions. Methods: Primary microglial cells were exposed to normal glucose (25 mmol/L) and high glucose (35 mmol/L) levels alone or with lipopolyscaccharide (LPS 0, 2, 5, 10 ng/mL). The pro-inflammatory response of the cells was assessed by measuring changes in cytokine levels and the evaluation of associated signaling pathways. Results: Neither high glucose nor low LPS (≤5ng/ml) alone had an effect on TNF-a and IL-6 levels, but the combination of low LPS and high glucose stimulated the inflammatory response. Analyses of the associated signaling pathways demonstrated that high glucose enhanced the LPS-induced microglial activation via the TLR4/JAK2/STAT3 pathway. Conclusion: This study demonstrates that high glucose, one of the key abnormalities characteristic of DM, can augment LPS-induced microglial activation and inflammatory cytokine levels through the TLR4/JAK2/STAT3 pathway, offering new insight into the pathophysiological relationship between DM and POCD.

 

[dabdabdab]

Starch seems to have dual effect - it raises both glucose and insulin where glucose is pro inflammatory while insulin is anti - so the net effect could differ by per case basis - for me sometimes starch actually palliates symptoms...

Enhancement of LPS-Induced Microglial Inflammation Response via TLR4 Under High Glucose Conditions
Enhancement of LPS-Induced Microglial Inflammation Response via TLR4 Under High Glucose Conditions
Background: Microglia activation mediated by toll-like receptor 4 (TLR4) plays an important role in neuroinflammation and postoperative cognitive dysfunction (POCD). Diabetes mellitus (DM) has been recently suggested as an independent risk factor for POCD. In this study, we investigate the potential exacerbation of the inflammatory response in primary microglia due to high glucose conditions. Methods: Primary microglial cells were exposed to normal glucose (25 mmol/L) and high glucose (35 mmol/L) levels alone or with lipopolyscaccharide (LPS 0, 2, 5, 10 ng/mL). The pro-inflammatory response of the cells was assessed by measuring changes in cytokine levels and the evaluation of associated signaling pathways. Results: Neither high glucose nor low LPS (≤5ng/ml) alone had an effect on TNF-a and IL-6 levels, but the combination of low LPS and high glucose stimulated the inflammatory response. Analyses of the associated signaling pathways demonstrated that high glucose enhanced the LPS-induced microglial activation via the TLR4/JAK2/STAT3 pathway. Conclusion: This study demonstrates that high glucose, one of the key abnormalities characteristic of DM, can augment LPS-induced microglial activation and inflammatory cytokine levels through the TLR4/JAK2/STAT3 pathway, offering new insight into the pathophysiological relationship between DM and POCD.

that explains it, thanks

 

[OccamzRazer]

I've tried PUFA in isolation as a supplement and it brought a lot of stress response(fatigue, insomnia, etc) like I was eating some sort of toxin. Does PUFA raises endotoxemia as an antibiotic?

Anyway I've overcame the effect next time eating an extra 500 carb-calories, i.e. it seems that negative effects from PUFA could be mitigated via increased glucose calories intake, as if extra toxicity spikes requirements for glucose drastically.

Anyone noticed the same thing?

New Defense Against Bacterial Superbugs: Taking Fish Oil May Reduce Antibiotic Resistance

For the first time, Australian scientists have confirmed a link between the role of regular fish oil to break down the ability of 'superbugs' to become resistant to antibiotics. The discovery, led by Flinders University and just published in international journal mBio, found that the antimicrobia

scitechdaily.com

This might work, but in the long run it will lead to lots of fat storage, poor body comp, and maybe more glycation.

Most people on the SAD do this and are very overweight as a result. Their fat cells become too insulin sensitive, and their fat stores are essentially 'trapped' in place for the organism's own safety...

 

[rockarolla]

Beneficial effect of long-chain n-3 polyunsaturated fatty acid supplementation on tuberculosis in mice,Prostaglandins, Leukotrienes and Essential Fatty Acids - X-MOL

Intakes of the omega-3 essential fatty acids (n-3 EFAs) are low in the general adult population, with high n-6/n-3 polyunsaturated fatty acid (PUFA) ratios and the accompanying suboptimal n-3 PUFA status. Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) have antibacterial and...

www.x-mol.com

Intakes of the omega-3 essential fatty acids (n-3 EFAs) are low in the general adult population, with high n-6/n-3 polyunsaturated fatty acid (PUFA) ratios and the accompanying suboptimal n-3 PUFA status. Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) have antibacterial and inflammation-resolving effects in tuberculosis (TB). However, whether switching to a diet with optimum n-3 EFA intake after the infection has comparable benefits has not been investigated. We aimed to compare the effects of a diet with sufficient n-3 EFA content in an acceptable n-6/n-3 PUFA ratio for rodents ((n-3)eFAS group) with those on the same diet supplemented with EPA and DHA (EPA/DHA group) in Mycobacterium tuberculosis (Mtb)-infected C3HeB/FeJ mice with a low n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient diet with a high n-6/n-3 PUFA ratio for 6 weeks before Mtb infection and randomized to either (n-3)eFAS or EPA/DHA diets 1 week post-infection for 3 weeks. At endpoint, EPA and DHA compositions were higher and arachidonic acid, osbond acid, and total n-6 LCPUFAs lower in all lipid pools measured in the EPA/DHA group (all P < 0.001). Percentage body weight gain was higher (P = 0.017) and lung bacterial load lower (P < 0.001) in the EPA/DHA group. Additionally, the EPA/DHA group had a more pro-resolving lung lipid mediator profile and lower lung in IL-1α and IL-1β concentrations (P = 0.023, P = 0.049). Inverse correlations were found between the lung and peripheral blood mononuclear cell EPA and DHA and selected pro-inflammatory cytokines. These are the first findings that indicate that EPA/DHA supplementation provides benefits superior to a diet with sufficient n-3 EFAs concerning bacterial killing, weight gain and lung inflammation resolution in Mtb-infected mice with a low n-3 PUFA status. Therefore, EPA and DHA may be worth considering as adjunct TB treatment.