Tuesday, January 15, 2013

Saturated fats, unsaturated fats, endotoxin, and implications of the Mani study



Recently, a study by Mani et al., was brought to my attention (Mani, Hollis, & Gabler, 2013).  Although I could only get my hands on the study’s abstract (the full paper is not available yet), in it, similar to the protocol followed by the studies referenced on this blog by Ghanim et al., pigs were fed 5 different oils, each given in porridge: coconut oil, olive oil, vegetable oil, fish oil, and cod liver oil.

Thereafter, blood samples were drawn from each pig at baseline, and at hours 1,2,3, and 5.  Surprisingly, changes in blood endotoxin concentrations were lowest in the pigs who received fish oil, and highest in those who received coconut oil; in fact, as much as 2-fold more, and in every sample analyzed.

As opposed to starch, any increase in blood endotoxin levels seen on the ingestion of fat is not likely due to an increase in bacterial proliferation and metabolic activities in the intestines.  Rather, it is more likely due to an increase in the transport of endotoxin from the intestines and into the body.  This is why results of the Mani study were surprising: For one, long-chain unsaturated fats stimulate chylomicron formation in the intestines, and this is one means by which endotoxin is taken into the body.  And two, unsaturated fats weaken the intestinal barrier, enhancing the incidental passage of substances like endotoxin into the body. 

Saturated fats, on the other hand, tend to fortify the intestinal barrier, and medium-chain saturated fats, in addition to fortifying the intestinal barrier, bypass absorption via the chylomicron system.  Instead, medium chain fats are passively slide, from the intestines, into the liver, where upon arrival they are rapidly oxidized to generate energy in the mitochondria.

Over time–on the order of weeks–the lipids in cellular membranes, including the ones of the intestinal cells, will reflect the types of fats consumed near perfectly.  A consequence of these changes concerns the enzymes that function in their proximity.

The activity of the intestinal enzyme, alkaline phosphatase, for instance, which regulates the passage of harmful substances like endotoxin into the body1 is enhanced when it operates within higher membrane saturation indices.2–4

For that matter, vitamins K1 and K2 enhance the activity of the intestinal alkaline phosphatase as well.5

Longer-term studies have borne out the protective effects of saturated fats against the toxic effects of endotoxin, specifically in the tissues, and these toxic effects are similar to the damages caused by alcohol.6

Take for example this study by Nanji and his colleagues, where rats were first challenged with ethanol for 6 weeks, and then were given fish oil, fish oil + ethanol, palm oil, or MCT oil for 2 additional weeks.7 Supplementation with the MCT oil and palm oil apparently reversed the damages caused by ethanol, attendant to a decrease in inflammation, expression of COX-2 & TNF-α, lipid peroxidation, and endotoxin levels. 

So, even if we could, in fact, take the results of the Mani study to the bank, and saturated fats, in fact, increase the absorption of endotoxin more than unsaturated fats do, the potential damages to the tissues are protected against by saturated fats, but intensified by unsaturated fats.

Providing additional protection, the non-essential amino acid, glycine, is, like saturated fats, protective against the damages caused by endotoxin.8  

Other studies, like this one by Kirpich et al., have show, in contrast to the permeability studies conducted on isolated strips of intestines in the second part of the Mani study, that saturated fats, over time, fortify the intestinal barrier to endotoxin, in contrast to unsaturated fats, by increasing the expression of tight junction proteins.9

When the results are officially made available, we will have ample opportunity to judge what exactly happened in the Mani study. (Though, in my opinion, saturated fat eaters still don’t have much to worry about.)  In the meantime we can take a few precautionary measures to protect ourselves from the potentially adverse consequences of eating rather big doses of fat, saturated or unsaturated.

   Vitamins K1 and K2
   Glycine
   MCT oil, coconut oil, and butter


References

1.       Lallès, J.-P. Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. Nutrition reviews 68, 323–32 (2010).
2.       Dudley, M. A. et al. Jejunal brush border hydrolase activity is higher in tallow-fed pigs than in corn oil-fed pigs. The Journal of nutrition 124, 1996–2005 (1994).
3.       Vázquez, C. M., Zanetti, R., Santa-María, C. & Ruíz-Gutiérrez, V. Effects of two highly monounsaturated oils on lipid composition and enzyme activities in rat jejunum. Bioscience reports 20, 355–68 (2000).
4.       Wahnon, R., Cogan, U. & Mokady, S. Dietary fish oil modulates the alkaline phosphatase activity and not the fluidity of rat intestinal microvillus membrane. The Journal of nutrition 122, 1077–84 (1992).
5.       Haraikawa, M., Sogabe, N., Tanabe, R., Hosoi, T. & Goseki-Sone, M. Vitamin K1 (phylloquinone) or vitamin K2 (menaquinone-4) induces intestinal alkaline phosphatase gene expression. Journal of nutritional science and vitaminology 57, 274–9 (2011).
6.       Mencin, A., Kluwe, J. & Schwabe, R. F. Toll-like receptors as targets in chronic liver diseases. Gut 58, 704–20 (2009).
7.       Nanji, A. A. et al. Dietary saturated fatty acids down-regulate cyclooxygenase-2 and tumor necrosis factor alfa and reverse fibrosis in alcohol-induced liver disease in the rat. Hepatology (Baltimore, Md.) 26, 1538–45 (1997).
8.       Senthilkumar, R., Viswanathan, P. & Nalini, N. Effect of glycine on oxidative stress in rats with alcohol induced liver injury. Die Pharmazie 59, 55–60 (2004).
9.       Kirpich, I. a et al. The type of dietary fat modulates intestinal tight junction integrity, gut permeability, and hepatic toll-like receptor expression in a mouse model of alcoholic liver disease. Alcoholism, clinical and experimental research 36, 835–46 (2012).