A Finnish study showed that low hemoglobin levels are associated with a lower body mass index and better metabolic health

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Hemoglobin is a protein found in the blood and a key oxygen transporter in the body. High hemoglobin levels have generally been considered desirable for a person’s health.

However, the latest research evidence appears to point in the opposite direction: high hemoglobin levels are linked to metabolic morbidity and mortality, while low hemoglobin levels are an indication of better metabolic health.

Earlier this year, a research team led by Professor Peppi Karppinen from the University of Oulu, Finland, published a study which showed low hemoglobin levels to be associated with a lower body mass index and better metabolic health.

The researchers now wanted to investigate the effect of hemoglobin levels on metabolic morbidity and mortality in the elderly population.

The study subjects were members of the OPERA cohort study (Oulu Project Elucidating Risk of Atherosclerosis). Nearly a thousand middle-aged individuals were included in the study, and their health was monitored until old age.

The study examined hemoglobin values within the normal range, in other words, 117–155 grams/liter for Finnish women and 134–167 grams/liter for Finnish men.

During 20 years of follow-up, higher hemoglobin levels were linked to common metabolic disorders, such as diabetes and hepatic steatosis, and also associated with higher cardiovascular morbidity and total mortality.

“In our previous study, we demonstrated that low hemoglobin levels induce a hypoxic response in the body. The activation of this response leads to changes in energy metabolism and the inflammatory response which provide individuals with lower hemoglobin level protection against metabolic disturbances.

The current results regarding the connection between higher hemoglobin levels and metabolic disorders and mortality are in line with our previous findings, supporting the idea that the body’s hypoxic response plays a key role in the regulation of energy metabolism in humans,” states principal investigator MD Joona Tapio.

Blood hemoglobin is one of the least expensive and most commonly tested laboratory parameters in the primary health care setting. According to Tapio, hemoglobin measurements could potentially be helpful in the early diagnosis of metabolic disorders.

The results could also help develop drug therapies for metabolic disorders. The hypoxic response is regulated by the HIF molecule which tries to ensure optimal oxygen uptake and energy metabolism in tissues under conditions of reduced oxygen availability.

According to the researchers, drugs that act as inhibitors of HIF enzymes, which regulate a hypoxic response, could potentially be used as anti-obesity and metabolism drugs in humans. These medicinal agents are currently being used in the treatment of anemia caused by kidney disease.

Metabolic syndrome is a cluster of concurrent disorders involving high blood glucose, adverse blood lipids and high blood pressure. Over the last few decades, this syndrome has become a global epidemic, and the conditions associated with it, such as diabetes, are major public health problems in Finland.

Over a billion people around the world have metabolic syndrome, and it has been estimated that about one out of four adult Finns suffers from it.


Metabolic syndrome (MetS) is a global epidemic which coincides with the increasing prevalence of obesity. MetS is defined as a group of metabolic disorders which increases the risk for type 2 diabetes (T2DM), cardiovascular diseases (CVD) and total mortality. The major components of MetS are visceral obesity, dyslipidemia and hypertension1,2.

Non-alcoholic fatty liver disease (NAFLD) is also considered a co-morbidity of MetS3. The average prevalence of MetS was 31% in 20174. Individuals with MetS have a 46% increased risk of mortality compared to individuals without the syndrome5.

Hb is the main carrier of oxygen in the cardiovascular system. Hb levels are regulated genetically and environmentally and they vary by sex, race, age and living altitude6,7. However, individual Hb levels during adult life are relatively stable although Hb levels successively decrease with ageing in men and postmenopausal women6.

In general, high-end Hb levels within the normal range are considered beneficial for health6. However, Hb levels can be elevated by factors such as smoking, a well-known risk factor for metabolic diseases and higher Hb levels are also observed in obesity, which likewise is a well-known risk factor for cardiometabolic diseases1,2.

Previous studies with selected cohorts, cross-sectional setting and often including only one sex have shown associations of higher Hb levels with individual components of MetS including insulin resistance, NAFLD, dyslipidemia and hypertension8,9,10,11,12,13,14,15.

However, higher Hb levels have also been associated with lower glycated hemoglobin (HbA1c) levels16. Regarding obesity-related peptide hormones, Hb levels have previously been both positively and negatively associated with serum leptin levels and negatively associated with serum adiponectin levels17,18,19.

Studies have also reported lower Hb levels (especially anemic) and very high Hb levels as predictors of total and CVD-related mortality20,21,22,23. The underlying mechanisms of the reported associations between higher Hb levels and metabolic markers have been poorly understood.

Hyperviscosity or changes in plasma volume10,11,12,22,24, endothelial cell dysfunction 10 or higher iron/ferritin levels 13,15 have been suggested as mediators of these associations. However, we have recently shown that lower Hb levels associate with an overall healthier metabolic profile in males and females in two middle-aged Finnish sea level birth cohorts studied in a longitudinal setting until age of 46 years, and that these alterations are mediated by hypoxia25. All in all, the role of Hb levels as a risk factor of MetS and its comorbidities requires further studies.

The aims of this study were

(1) to assess cross-sectionally the associations between Hb levels and some 20 key metabolic parameters, obesity-related peptides and ambulatory blood pressure (ABP) measurements in middle-age (average age 51 years) and senescence (average age 72 years),

(2) evaluate in a cross-sectional design Hb levels as a risk factor for fatty liver disease, and in a longitudinal design evaluate the role of Hb levels

(3) in prediction of the development of impaired glucose metabolism and

(4) as a risk factor for CVD events and -related mortality and total mortality. Long-term studies considering the risk profile of the highly prevalent metabolic disorders are needed and this study offers a follow-up period of ~ 20 years, to our knowledge the longest in the literature. Increased information about the risk profile of MetS would eventually lead to decreased morbidity and mortality through improved primary prevention.

reference link :https://www.nature.com/articles/s41598-021-99217-9


More information: Joona Tapio et al, Higher hemoglobin levels are an independent risk factor for adverse metabolism and higher mortality in a 20-year follow-up, Scientific Reports (2021). DOI: 10.1038/s41598-021-99217-9

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