A new study from the University of Oulu in Finland refutes the assumption that high hemoglobin levels are always desirable for health. A study based on two large human cohorts, as well as experimental work, confirmed that lower hemoglobin levels can protect against both obesity and metabolic syndrome. The phenomenon can be related to the body’s reaction to low-oxygen conditions and is used, for example, by endurance athletes for high-altitude training.
Hemoglobin is a protein in the blood that is responsible for transporting oxygen to the tissues of the body. Hemoglobin levels vary from person to person, with normal levels in the Finnish population being between 117 and 155 grams per liter for women and 134 to 167 grams per liter for men.
A study recently published in the prestigious journal Science Advances showed that individual differences in hemoglobin levels are strongly linked to metabolic health in adulthood. Hemoglobin levels were linked to body mass index, glucose metabolism, blood lipid levels, and blood pressure, with subjects with lower hemoglobin levels being healthier in terms of metabolic measurements. The study examined hemoglobin levels in the normal range.
“We found a clear connection between the hemoglobin level and the most important cardiovascular characteristics, which became stronger with the age of the test subjects,” say the main researchers Professor Juha Auvinen, PhD student Joona Tapio and postdoctoral researcher Ville Karhunen.
The effect of the lower hemoglobin observed in the study is related to a slight lack of oxygen in the body and the corresponding reaction (so-called HIF reaction) that is activated as a result. Professor Peppi Karppinen’s research team is internationally known for its studies on this phenomenon. The finding enhances understanding of the central role the HIF response plays in regulating the body’s energy metabolism.
“The hemoglobin level is a good measure of the body’s ability to carry oxygen. A slight lack of oxygen activates the HIF reaction, which makes the body’s energy metabolism less economical and can thus protect against obesity and an unfavorable metabolism, ”explains Karppinen, head of study.
At the Faculty of Biochemistry and Molecular Medicine and at the Oulu Biozentrum, Karppinen’s team has already shown in previous research that activating the hypoxia response protects mice from obesity, metabolic syndrome, fatty liver and atherosclerosis (hardening of the arteries). The study that has now been published is the first to demonstrate the connection between oxygen deficiency and a wide range of metabolic markers in humans as well.
“Although this study uses several methods to make links between lower body oxygen levels and metabolic health, it is very difficult to establish causality for the associations observed in human data. However, by combining evidence from different components of the study, the results support that the response to hypoxia can also play an important role in people’s metabolic health, ”said Professor Marjo-Riitta Järvelin, co-lead study at Imperial College London , UK and University of Oulu, Finland.
We also already know that in people living high above sea level, low oxygen levels in their habitat cause long-term activation of the HIF response. These people are leaner, have better sugar tolerance and a lower risk of cardiovascular death. “
Professor Peppi Karppinen
A central question of the future is therefore: How can the body’s own oxidation levels be reduced if necessary in order to achieve permanent low-level activation of the HIF reaction and thus protection against obesity? Karppinen said the HIF enzymes that cause a hypoxic reaction could potentially be used as targets for obesity and metabolic drugs in humans. They are currently used in Asia to treat renal anemia.
The study was based on a large cohort of people born in Northern Finland in 1966. The study monitored the health and wellbeing of more than 12,000 people on a regular basis since birth. The results were also replicated in the cohort material of the Cardiovascular Risk Study in Young Finns, a five multicenter study in Finland that included more than 1,800 people in the present study. In particular, this work was carried out in collaboration between researchers from the Universities of Turku and Tampere in Finland and Imperial College London, UK.
Obesity and the metabolic syndrome are major health problems worldwide, associated with numerous comorbidities and premature mortality. Half of Finnish adults are overweight and a quarter have metabolic syndrome. Child obesity is also increasing, and the same phenomenon can be seen around the world. New ways to prevent and treat obesity are urgently needed.
Auvinen, J., et al. (2021) The systematic assessment of the association between hemoglobin levels and metabolic profile implies positive effects of hypoxia. Scientific advances. doi.org/10.1126/sciadv.abi4822.