New Link Found in Nitrate-Heart Disease Mechanism

17 Mar 2015 --- In three recent studies, a collaboration of scientists from MRC HNR – Dr Jules Griffin and Dr Lee Roberts – and the Universities of Cambridge and Southampton have identified how nitrate, found in leafy green vegetables, may improve cardiovascular and metabolic health.

Hypoxia – oxygen starvation – affects many intensive care patients and is a very common symptom of cardiovascular diseases such as heart failure and chronic obstructive pulmonary disease. Hypoxia causes thickening of the blood, which increases the risk of dangerous clots forming and the risk of stroke and heart attacks.

In the first study published by the collaboration in FASEB journal, the researchers showed that consuming a moderate dose of nitrate reduced the production of a hormone called erythropoietin, which controls red blood cell production. Lower levels of erythropoietin reduced the production of red blood cells and decreased blood viscosity in a rat model.

Professor Martin Feelisch, from the University of Southampton, who also led the study said: “These findings suggest simple dietary changes may offer treatments for people suffering from heart and blood vessel diseases that cause too many red blood cells to be produced. It is also exciting as it may have broader implications in sport science, and could aid recovery of patients in intensive care by helping us understand how oxygen can be delivered to our cells more efficiently.”

The scientists also studied hypoxia using the low oxygen conditions at high altitude on the on the Xtreme Everest expedition.

In these conditions, the body produces more red blood cells in an attempt to get more oxygen into the blood stream, but this can cause the blood to become very thick. Thick blood may carry more oxygen, but is less able to pass through small blood vessels and therefore prevents tissues and organs from being supplied with the oxygen they need to function.

The researchers have filmed this using a special camera, capturing blood flowing through capillaries at sea level and at 6400 meters above sea level.

“Lowering the blood’s thickness without compromising oxygen delivery may also help prevent blood clots, reducing the risk of a stroke or heart attack,” said Dr Andrew Murray from the University of Cambridge, who co-led the study.

Hypoxia also impairs the function of the heart and alters the function of the cells’ powerhouses, called mitochondria.

The scientists demonstrated that dietary nitrate supplementation in a rat model prevented hypoxia-induced changes in cardiac mitochondrial function and energetics and may improve tissue oxygenation, according to research published in the Journal of Physiology.

In a third study – led by Dr Roberts and Dr Griffin from HNR and published in Diabetes - the researchers identified nitrate’s ability to stimulate conversion of white fat cells, which store fat, into beige fat cells, which burn fat, in a process called browning.

“This study demonstrates how nitrate may be an effective means of inducing the browning response in adipose tissue to treat the metabolic syndrome,” said Dr Roberts, lead author on the study and scientist in the LPS group at HNR. “These data suggest simple changes in the diet could increase our ability to burn fat, reducing the risk of obesity and Type-2 diabetes.”

This work was part funded by the Biotechnology and Biological Sciences Research Council, The WYNG Foundation, EU framework 7 inheritance project, Wellcome Trust, British Heart Foundation (BHF) and Medical Research Council.

Professor Jeremy Pearson, Associate Medical Director at the BHF, said: “It has long been thought that nitrate-rich vegetables have cardiovascular benefits. This research suggests that a previously unsuspected mechanism by which nitrate controls red blood cell production is important. These findings add to the evidence that dietary nitrate promotes cardiovascular health.”