While other studies have established that nitrate, a nitric oxide metabolite, is beneficial for endurance during exercise – nitrate supplements are used by athletes to boost performance – the role played by the liver and kidneys was previously unknown - and natural regulation of EPO (erythropoietin) is part of the finding.
Andrew Murray from the University of Cambridge, who led the research team, spoke to NutraIngredients: “While we need more [red blood cells] during exercise, we don’t want too many or the blood gets too thick and it’s harder to reach tissue. It’s about finding that spot where our bodies produce enough red blood cells for exercise but not too many.
“Scientists have known for a number of years that nitrate supplements improve how efficiently our bodies use oxygen in exercise. Here we have found that the liver and kidneys also act as a sensor ensuring that fewer red blood cells are needed to get this oxygen.”
Nitrate sources include leafy green vegetables such as beetroot, spinach or lettuce.
The scientists monitored the haemoglobin (red blood cell) levels in four groups of rats who were housed in either normoxic (normal oxygen) or hypoxic (low oxygen) conditions and were supplemented with 7 mg per kilo body weight of sodium nitrate via drinking water each day or sodium chloride – salt – as a control.
Nitrate acted by causing the liver to reduce its production of EPO, a glycoprotein hormone which controls red blood cell production. This decreased the thickness of the blood allowing oxygen to reach tissue more quickly.
The researchers found that higher doses of nitrate further reduced haemoglobin levels by the liver, kicking into action a brake mechanism: The kidneys then began to produce more erythropoietin in order to avoid too low a drop in red blood cells.
“The predominant effect of nitrate would appear to be a suppression of liver erythropoietin (EPO) production, and although this is thought to represent a relatively small proportion (approximately 10% of total EPO production), this proportion might increase to approximately 33% during prolonged/severe hypoxia,” said the study.
“Hepatic [liver] and renal [kidney] mechanisms appear to work in concert to optimize tissue oxygen delivery.”
Synthetic EPO is a banned blood booster that has nonetheless been used for decades to boost endurance in sports like cycling and athletics.
Applying the findings
People who transition from low to high altitude begin to produce more red blood cells to counter the lack of oxygen in the atmosphere, and moderate doses of nitrate supplementation may suppress this effect.
According to Murray: “Studies at altitude provide an interesting model for research into diseases where patients have a low red blood count, such as heart or lung failure or patients in intensive care. Would nitrate supplementation help by making their bodies more efficient?
“Sherpas in the Himalayas have fewer red blood cells and higher nitrate levels...This is interesting because the nitrate is naturally occurring and not acquired through diet – but we don’t know where it comes from.”
Murray called for more research on human subjects, but said that trials on how nitrate improves blood efficiency have already been successfully carried out in humans.
Source: The FASEB Journal
November 24, 2014, DOI: 10.1096/fj.14-263004
“Suppression of erythropoiesis by dietary nitrate”
Authors: A Murray, T Ashmore et al.