Other Factors

A number of environmental and biological factors may have an influence over an individual’s risk of developing fibrosis, and the chances of recovering from it. The body is a highly complex system of processes, with a large number of interactions and feedback effects between hormones and cells, and scientific advances in understanding are made regularly. Small alterations in one hormone can have powerful effects on many functions including stress, digestion, fertility and immune system function.

While the science behind the existence of these environmental and biological factors is sound, it’s not yet clear to what extent they impact on fibrotic processes.

Effect of the Seasons.

The processes and functions of the body, are governed by signalling factors the body makes called hormones. Hormones include growth factors and cytokines that signal cells in different parts of the body to start, stop, increase or decrease specific activities.

Recent research indicates that one of the main stress hormones, called cortisol, is significantly increased in winter in both men and women1, with the effect greater at higher latitudes.

This may have implications for those at risk of arthrofibrosis if they are planning surgery, since increased cortisol increases levels of proteins that make resistant scar tissue and adhesions. Cortisol also increases the risk of infection. This suggests that the seasonal timing of surgery may impact on recovery, with winter being the least-best season and autumn the best season.

Go Deeper: Effect of the Seasons.

Seasonal changes in hormones have been well studied in animals, and recent research indicates that humans also have significant seasonal alterations in their levels of a range of hormones. For example, the winter increase in the levels of cortisol increases the expression of lysyl oxidase (LOX), an enzyme (protein) that upregulates the production of scar tissue5 and cross-links collagen in scar tissue. Highly cross-linked collagen is a hallmark of fibrotic tissue6 and LOX is strongly implicated in fibrosis5.

LOX increases cell to collagen adhesion via focal adhesion kinase (FAK), thus increasing both scar tissue production, stiffness and adhesions. In addition, it upregulates IL-6, a pro-fibrotic and pro- inflammatory cytokine2.

Red Meat and Dairy Consumption.

Nutrition can dramatically affect health, and a range of inflammatory diseases are associated with the consumption of red meat and dairy products2,3. The exact cause of the increased inflammation is not well established, but we know that toxic products created during cooking (PAHs), and cancer-causing compounds are present in preserved meat2.

Recent research now suggests another causative link between the consumption of red meat and dairy products with disease. Animal products contain a type of sugar called sialic acid that humans are not able to make, and which triggers an inflammatory response3. Every time we consume these products there is more inflammation, and this inflammation can contribute to fibrosis.

We’re not suggesting that going vegetarian is the best approach; however, the science suggests that it is worth considering limiting the consumption of red meat to less than 3 times per week, and limiting dairy products.

Go Deeper: Red Meat and Dairy Consumption.

When we consume this foreign sialic acid (Neu5Gc) it’s taken in by our cells and presented on the surface them. This causes the body to make antibodies to it. Antibodies are proteins that the body makes that “tag” foreign objects like viruses so that the immune system will destroy them, and the cell that they are attached to.

Everybody has these antibodies to the sialic acids in red meat and dairy2, and the amount of antibodies depends on how much red meat and dairy we consume4. The antibodies see the sialic acid on the surface of our cells, sound the alarm, and activate the immune system. Evidence shows that this contributes to vascular inflammation, diabetes type 2 and cancer4, and very likely, fibrosis.

References

1. Tendler, A. et al. Hormone seasonality in medical records suggests circannual endocrine circuits. Proc Natl Acad Sci U S A 118, doi:10.1073/pnas.2003926118 (2021).

2  Bashir, S. et al. Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Sante study. BMC Med 18, 262, doi:10.1186/s12916-020-01721-8 (2020).

3. Papier, K. et al. Meat consumption and risk of 25 common conditions: outcome-wide analyses in 475,000 men and women in the UK Biobank study. BMC Med19, 53, doi:10.1186/s12916-021-01922-9 (2021).

 Pruimboom, L. SARS-CoV 2; Possible alternative virus receptors and pathophysiological determinants. Med Hypotheses 146, 110368, doi:10.1016/j.mehy.2020.110368 (2021).

5.  Nguyen, X.-X. M. et al. Lysyl Oxidase Directly Contributes to Extracellular Matrix Production and Fibrosis in Systemic Sclerosis. Am J Physiol Lung Cell Mol Physiol, doi:10.1152/ajplung.00173.2020 (2020).

6. Kalamajski, S., Bihan, D., Bonna, A., Rubin, K. & Farndale, R. W. Fibromodulin interacts with collagen cross-linking sites and activates lysyl oxidase. Journal of Biological Chemistry, doi:10.1074/jbc.M115.693408 (2016).