Lower haemoglobin may prevent obesity, metabolic syndrome

New research led by Finland’s University of Oulu refutes the belief that high haemoglobin levels are always desirable for health, indicating that lower haemoglobin levels may protect against both obesity and metabolic syndrome. The phenomenon may be related to the body’s response to low-oxygen conditions and is used, for example, by endurance athletes in high-altitude training.

Haemoglobin is a protein in the blood that is responsible for transporting oxygen to the tissues of the body. Haemoglobin levels vary from one individual to another, with normal levels in the Finnish population ranging from 117 to 155 g/L in females and 134 to 167 g/L in males. The recent study, published in the journal Science Advances, showed that individual differences in haemoglobin levels are strongly associated with metabolic health in adulthood.

In the study of more than 12,000 Finnish residents, whose health and wellbeing have been regularly monitored since birth, haemoglobin levels were associated with body mass index, glucose metabolism, blood lipids and blood pressure, with subjects having lower haemoglobin levels being healthier in terms of metabolic measures. The study examined haemoglobin values within the normal range.

“We found a clear association between haemoglobin levels and key cardiovascular traits, and the associations became more pronounced as the subjects aged,” said principal investigators Professor Juha Auvinen, Joona Tapio and Ville Karhunen.

The effect of lower haemoglobin observed in the study is related to a mild oxygen deficiency in the body and the corresponding response (so-called HIF response) which is activated as a result. The finding reinforces the understanding of the central role that the HIF response has in regulating the body’s energy metabolism.

“Haemoglobin levels are a good measure of the body’s ability to carry oxygen,” said Professor Peppi Karppinen, who led the study. “A mild lack of oxygen activates the HIF response, which makes the body’s energy metabolism less economical and thus may protect against obesity and unfavourable metabolism.”

Prof Karppinen’s team has already shown that activation of the hypoxia response protects mice from obesity, metabolic syndrome, fatty liver and atherosclerosis (hardening of the arteries). The new study is believed to be the first in which the link between oxygen deficiency and a wide range of metabolic health markers is demonstrated in humans as well.

“Although this study uses multiple methods to establish links between lower body oxygen levels and metabolic health, it is very challenging to establish causality for the observed associations in human data,” said study co-leader Professor Marjo-Riitta Järvelin, from Imperial College London and the University of Oulu. “However, combining evidence from different components of the study, the results support that hypoxia response may also play an important role in people’s metabolic health.”

“We also already know that in people living high above sea level, low oxygen levels in the habitat cause long-term activation of the HIF response,” added Prof Karppinen. “These people are slimmer, and they have better sugar tolerance and a lower risk of cardiovascular death.”

A key question in the future is how to reduce the body’s oxidation levels if needed, so as to achieve a permanent low-level activation of the HIF response and thus protection against obesity. According to Prof Karppinen, the HIF enzymes that cause a hypoxic response could potentially be used as targets of obesity and metabolism drugs in humans.

Image credit: ©stock.adobe.com/au/Happyphotons

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