Further investigation is warranted when seeing increased ferritin with low transferrin saturation. Such a pattern may be associated with inflammation, oxidative stress, and increased risk of type 2 diabetes and CVD.
Ordinarily, increased ferritin due to iron overload would be associated with increased transferrin saturation versus decreased saturation as mentioned in the cases mentioned here. Therefore, other causes for elevated ferritin must be investigated, including inflammation and oxidative stress (Rambod 2008, DePalma 2021).
Elevated ferritin may also be a sign of cardiometabolic dysfunction. A review of NHANES data suggests that elevated ferritin with a low transferrin saturation may be associated with an increased risk for pre-diabetes (Cheung 2013). This pattern was substantiated in the prospective randomized Iron and Atherosclerosis Study (FeAST). The study observed an increased risk of type 2 diabetes and CVD with ferritin above 100 ng/mL and decreasing transferrin saturation. The study noted that ferritin above 127 ng/mL was associated with an increased risk of cancer. Increasing ferritin was also associated with increased biomarkers of inflammation and oxidative stress (DePalma 2021).
Further evaluation of cardiometabolic health and glucose regulation is warranted when observing this pattern.
References
Cheung, Ching-Lung et al. “High ferritin and low transferrin saturation are associated with pre-diabetes among a national representative sample of U.S. adults.” Clinical nutrition (Edinburgh, Scotland) vol. 32,6 (2013): 1055-60. doi:10.1016/j.clnu.2012.11.024
DePalma, Ralph G et al. “Optimal serum ferritin level range: iron status measure and inflammatory biomarker.” Metallomics : integrated biometal science vol. 13,6 (2021): mfab030. doi:10.1093/mtomcs/mfab030
Rambod, Mehdi et al. “Combined high serum ferritin and low iron saturation in hemodialysis patients: the role of inflammation.” Clinical journal of the American Society of Nephrology : CJASN vol. 3,6 (2008): 1691-701. doi:10.2215/CJN.01070308