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, cod liver oil.
Thereafter blood samples were drawn from each pig at baseline, and at hours 1,2,3, & 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 from an increase in bacterial metabolic activity in the intestines. Rather it is due to an increase in transport of endotoxin from the intestines 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 absorbed 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, 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 delivered to the liver, where upon arrival, they are rapidly oxidized to generate energy in the mitochondria.
Over time–on the order of weeks–membrane lipids in certain cells, including the intestinal cells, will reflect the types of fat 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 body (Lallès, 2010) is enhanced when it operates in the environment of higher membrane saturation indices (Dudley et al., 1994; Vázquez, Zanetti, Santa-María, & Ruíz-Gutiérrez, 2000; Wahnon, Cogan, & Mokady, 1992).
For that matter vitamins K1 and K2 enhance the activity of the intestinal alkaline phosphatase as well (Haraikawa, Sogabe, Tanabe, Hosoi, & Goseki-Sone, 2011).
Longer-term studies have borne out the protective effects of saturated fats against the toxic effects of endotoxin on tissues–many of which are similar to the damages caused by alcohol (Mencin, Kluwe, & Schwabe, 2009).
Take for example this one by Nanji & 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 (Nanji et al., 1997).
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 can take the results of the Mani study to the bank, and saturated fats in fact increase endotoxin absorption more than unsaturated fats do, the damages executed at the tissue level are protected against by saturated fats, but intensified by unsaturated fats.
A non-essential amino acid, glycine, is, like saturated fats, protective against the damages caused by endotoxin (Senthilkumar, Viswanathan, & Nalini, 2004).
Other studies (like this one Kirpich et al., 2012) have shown–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 comparison to unsaturated fats by increasing the expression of tight junction proteins, and this in turn is associated with a significant reduction in the damages sustained by the liver on the exposure to ethanol.
When the results are officially made available, we will have ample opportunity to judge what exactly happened in the Mani study. (Though, 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 & K2
- Glycine
- Raw, fibrous vegetables that are resistant to breakdown by microbial & our own intestinal enzymes (e.g., carrots)
- MCT oil
References
Dudley, M. A., Wang, H., Hachey, D. L., Shulman, R. J., Perkinson, J. S., Rosenberger, J., & Mersmann, H. J. (1994). Jejunal brush border hydrolase activity is higher in tallow-fed pigs than in corn oil-fed pigs. The Journal of nutrition, 124(10), 1996–2005. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7931709
Haraikawa, M., Sogabe, N., Tanabe, R., Hosoi, T., & Goseki-Sone, M. (2011). Vitamin K1 (phylloquinone) or vitamin K2 (menaquinone-4) induces intestinal alkaline phosphatase gene expression. Journal of nutritional science and vitaminology, 57(4), 274–9. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22041909
Kirpich, I. a, Feng, W., Wang, Y., Liu, Y., Barker, D. F., Barve, S. S., & McClain, C. J. (2012). 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(5), 835–46. doi:10.1111/j.1530-0277.2011.01673.x
Lallès, J.-P. (2010). Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. Nutrition reviews, 68(6), 323–32. doi:10.1111/j.1753-4887.2010.00292.x
Mani, V., Hollis, J. H., & Gabler, N. K. (2013). Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia. Nutrition & metabolism, 10(1), 6. doi:10.1186/1743-7075-10-6
Mencin, A., Kluwe, J., & Schwabe, R. F. (2009). Toll-like receptors as targets in chronic liver diseases. Gut, 58(5), 704–20. doi:10.1136/gut.2008.156307
Nanji, A. A., Zakim, D., Rahemtulla, A., Daly, T., Miao, L., Zhao, S., Khwaja, S., et al. (1997). 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(6), 1538–45. doi:10.1002/hep.510260622
Senthilkumar, R., Viswanathan, P., & Nalini, N. (2004). Effect of glycine on oxidative stress in rats with alcohol induced liver injury. Die Pharmazie, 59(1), 55–60. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/14964423
Vázquez, C. M., Zanetti, R., Santa-María, C., & Ruíz-Gutiérrez, V. (2000). Effects of two highly monounsaturated oils on lipid composition and enzyme activities in rat jejunum. Bioscience reports, 20(5), 355–68. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11332598
Wahnon, R., Cogan, U., & Mokady, S. (1992). Dietary fish oil modulates the alkaline phosphatase activity and not the fluidity of rat intestinal microvillus membrane. The Journal of nutrition, 122(5), 1077–84. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1564560