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Dietary Fat and Inflammation: New revealing evidence that is truly eye-opening

James Meschino DC, MS, ROHP

Introduction

Chronic Inflammation plays a key role in the exacerbation of cardiovascular disease, diabetes, Alzheimer’s disease, other neurological diseases and cancer. A large body of evidence suggests that various dietary factors can enhance or diminish inflammation; an important dietary factor being dietary fats.

High Fat Intake Increases Absorption of Inflammation-inducing Endotoxins

Studies show that simply eating a high fat diet increases the absorption into the bloodstream of endotoxins produced by gut bacteria, which in turn, promote the secretion of inflammatory cytokines from immune and other cells. Other studies have shown that the consumption of meats, cheese and dairy products also increase the endotoxin load in the body’s circulation, which in turn, also trigger the release of inflammatory cytokines and biomarkers (such as CRP).

Conservative estimates suggest that there are over 100 trillion commensal (normal) microorganisms in the gut, known as the gut microbiome or gut microflora. Collectively they contain over 1 gm of lipopolysaccharide (LPS or endotoxin), which are part of the cell wall of all gram-negative bacteria. LPS can have toxic effects in most mammals and is a very potent stimulus in the immune inflammatory response. There is great diversity in the LPS structure among the gram-negative bacteria species. As such, the gut microbiome from one person to another may be more or less pro-inflammatory depending upon the composition of gram-negative bacteria strains that reside in the gut.

It appears that the absorption of bacterial endotoxins into the bloodstream is facilitated by fat, and together they areincorporated into chylomicrons. Chylomicrons distribute endotoxins throughout the body and also transfer them to HDL-cholesterol lipoproteins, which further distribute these endotoxins to bodily tissues.

Different Fats Exert Different Inflammatory Effects: Good Fats-Bad Fats

Other studies show that the types of fat we eat can influence the types of bacteria within the gut microflora, and thus, can increase or decrease the endotoxin load by affecting the microflora bacterial composition. Rodent studies show that milk fat, in particular, promotes the growth of undesirable gut bacteria rich in inflammatory endotoxin content.

In addition to increasing the production and absorption of endotoxins, dietary fats can also influence inflammation by directly affecting signaling pathways within immune cells, such as macrophages. More specifically, it is known that saturated fatty acids are an integral part of the endotoxin structure that promotes inflammation, and that substitution with monounsaturated fats (i.e. olive oil – oleic acid) or polyunsaturated fat (i.e. corn oil – linoleic acid) eliminates the pro-inflammatory activity of the LPS (endotoxin). Macrophages, and other cells of the innate immune system, possess toll-like receptors (i.e. TLR4) on their surface that recognize LPS. LPS-mediated signalling through TLR4 leads to activation of pro-inflammatory Nuclear factor-kappa beta (NF-kb), a transcription factor that subsequently turns on the expression of numerous pro-inflammatory cytokines, such as Tumor Necrosis Factor- alpha (TNF-alpha), IL-1, IL-6, and IL-8. More than a dozen toll-like receptors have been found on cells throughout the body and are critical for host defence against invading pathogens.

In 2006 it was first shown that saturated fatty acids (SFAs) were able to directly stimulate inflammatory gene expression by way of TLR4 signaling in vitro, with lauric acid (meat) showing the greatest inflammatory activity, and myristic acid (dairy) and stearic acid showing much less inflammatory effects. In contrast to SFAs, monounsaturated fats and polyunsaturated fats failed to activate TLR4 signaling, and pre-treatment (3 hours in advance) with oleic acid (olive oil) and polyunsaturated fats significantly reduced the subsequent inflammatory effect of lauric acid treatment.

Researchers showed that monounsaturated fats and polyunsaturated fats blocked the inflammatory response by LPS or lauric acid via their effects on TLR4 signaling. Inhibition of TLR4 activation also appears to decrease the activity of cyclooxygenase enzyme, which in turn, reduces the synthesis of inflammatory eicosanoids. With respect to EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) from fish and fish oil, experimental evidence shows a wide range of anti-inflammatory effects, including diminishing microbial agonist-mediated signaling of a wide variety of TRLs.

Is Linoleic Acid Inflammatory?

It has been believed for sometime that high ingestion of linoleic acid (found in many vegetable and seed oils) increases inflammation via the conversion to arachidonic acid, which is the immediate precursor to numerous inflammatory eicosanoids (i.e. PG-2, LTB-4, HETE etc.). However, a review of all pertinent human clinical trials show the opposite effect in that higher intakes of linoleic acid appear to reduce inflammatory cytokine and biomarkers. This was again seen in a 2011 study reported by Rett and Whelan, which showed that extra saturated fat consumption from butter resulted in elevations in plasma biomarkers of inflammation in obese subjects, whereas increasing linoleic acid consumption from 4% to 13% of calories improved (diminished) biomarkers of inflammation in obese subjects (1). Keep in mind that many experimental animal studies demonstrate that high intake of linoleic acid and/or arachidonic acid promote cancer development, although conclusions from human epidemiological studies, case-controlled studies and prospective studies suggest only a small increase in cancer risk. (2)  Nevertheless, many experts suggest that it is wise to use monounsaturated fat and omega-3 fats as the predominant fats in the human diet, and to exercise caution with more moderate consumption of foods high in linoleic acid (3).

Omega-3 Fats Show Impressive Anti-inflammatory Effects

Experimental and murine (mice) studies using DHA and EPA have demonstrated various pathways through which these specific omega-3 fats decrease the inflammatory process. In concert with this, human studies suggest that a daily intake of over 2 grams (2000 mg) of EPA plus DHA is required to elicit anti-inflammatory actions. This amount exceeds that which can be ingested from food alone and implies that dietary supplements containing EPA and DHA are needed to obtain the anti-inflammatory effects available from EPA and DHA.

Conclusion

Several recent studies have shown that a high saturated fat diet increases risk of breast, prostate and possibly other cancers. One mechanism is via the stimulation of Insulin-like growth factor (IGF-1) receptors on cell membranes, which triggers signal transduction pathways that ultimately increase the rate of cell division. Faster cell division rates lead to increased genetic mutations and shorter telomeres, which increase cancer risk (4,5).  High intake of saturated fat has been linked to estrogen-receptor positive and progesterone-receptor positive breast cancer and the over expression of the Her2 receptor; a well known biomarker for increased breast cancer risk (4). The review paper by KL Fritsche, addressing fatty acids and inflammation, suggest that a high fat diet, as well as saturated fat itself, play a significant role in up-regulating inflammatory pathways via several mechanisms. We have long had an understanding of the mechanisms through whichspecific polyunsaturated fats affect the inflammatory cascade, which primarily involves their conversion to various inflammatory and anti-inflammatory eicosanoids. The review paper by KL Fritsche brings into focus the inflammatory modulating effect of saturated fat, particular saturated fats from animal products (meat, cheese, dairy). As the inflammatory process is contributing factor todiabetes, cardiovascular disease, arthritis, autoimmune disease, Alzheimer’s disease, other neurological disease and cancer, dietary modification of total fat intake and saturated fat intake appear to be prudent steps to take in the prevention and complementary lifestyle management of these common health conditions.

References

  1. Fritsche KL. The science of fatty acids and inflammation. Advances in Nutrition Journal, 2015, vol 6:2935-3015.
  2. https://www.ncbi.nlm.nih.gov/pubmed/9665108
  3. 3. http://healthyeating.sfgate.com/risks-polyunsaturated-fats-human-body-8863.html
  4. S. Sieri, P. Chiodini, C. Agnoli, V. Pala, F. Berrino, A. Trichopoulou, V. Benetou, E. Vasilopoulou, M.-J. Sanchez, M.-D. Chirlaque, P. Amiano, J. R. Quiros, E. Ardanaz, G. Buckland, G. Masala, S. Panico, S. Grioni, C. Sacerdote, R. Tumino, M.-C. Boutron-Ruault, F. Clavel-Chapelon, G. Fagherazzi, P. H. M. Peeters, C. H. van Gils, H. B. Bueno-de-Mesquita, H. J. van Kranen, T. J. Key, R. C. Travis, K. T. Khaw, N. J. Wareham, R. Kaaks, A. Lukanova, H. Boeing, M. Schutze, E. Sonestedt, E. Wirfalt, M. Sund, A. Andersson, V. Chajes, S. Rinaldi, I. Romieu, E. Weiderpass, G. Skeie, E. Dagrun, A. Tjonneland, J. Halkjaer, K. Overvard, M. A. Merritt, D. Cox, E. Riboli, V. Krogh. Dietary fat intake and development of specific breast cancer types. JNCI Journal of the National Cancer Institute, 2014. Vol 106, issue 5. http://jnci.oxfordjournals.org/content/106/5/dju068
  5. Di Sebastiano KM and Mourtzakis M. The role of dietary fat throughout the prostate trajectory. Nutrients, 2014. Vol 6:6095-6109.
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