A healthy circulatory system is necessary for the correct function of every organ in your body. As the heart pumps blood around your body, it ensures that all the tissues receive oxygen and nutrients. A serious defect in the circulatory system can lead to multiple organ failure, of course, but you might not be aware of your cardiovascular system not working at peak efficiency. In that case the consequences are less serious, they will probably not result in serious illness, at least in the short term, however your brain and muscles will not be working at optimal efficiency. You might feel sluggish and suffer from ‘brain fog’, because your central nervous system is not receiving quite as much oxygen and glucose as it needs. Looking after your circulation will result in improvements to your overall health and performance in all areas of life.

One little known addition to your health regimen that can improve your circulatory system by working on several different levels is a nucleotide supplement. Nucleotides are famous as the building blocks of the nucleic acids, DNA and RNA, which carry all the genetic information in our cells. Nucleotide supplements have mostly been studied for their effects at boosting the immune system. However, nucleotides are so fundamental to life that they have many other functions; improving circulation is one of them.

There are three different areas in which nucleotides influence the circulatory system ensuring that it can adopt efficiently to circumstances. A well functioning cardiovascular system depends on a healthy heart, the organ responsible for pumping blood around your body. It also requires blood vessels that can constrict or dilate according to need, relaxed blood vessels allow a lot more blood to pass through them. The final factor in ensuring that enough oxygen gets to all the tissues of the body is a sufficient level of haemoglobin, the oxygen-transporting molecule in red blood cells. Dietary nucleotides can play a role in ensuring all these systems work well.

Nucleotides as Signaling Molecules

There are five different nucleotides in the body, adenosine-, guanine-, thymidine-, cytosine-,uracil-triphosphate. They differ by the nucleic base that However, it is thought that most of the functions of nucleotides, other than building the nucleic acids DNA and RNA depend mostly on just one, adenosine triphosphate or ATP. This is because ATP can give rise to cyclic AMP (cAMP), another form of the nucleotide, which plays a crucial role in signaling by various hormones and neurotransmitters. Hormones and other signaling molecules are for the most part outside the cell. They bind to their receptors on the cell membrane, but cannot enter the cell. Somehow their message must be transferred to the inside of the cell, and often to the nucleus. It is precisely this function that is performed by cAMP, which acts as a second messenger.

There are two enzymes involved in the synthesis of cyclic AMP form ATP and vice versa, adenylyl cyclase and phosphodiesterases (PDEs). The first enzyme synthesizes cAMP from ATP, and PDEs recycle the molecule back to ATP. Hormones interact with the system by activating the enzyme adenylyl cyclase, therefore increasing the levels of cAMP. In cells the enzyme is found inside the cells, but closely associated with the plasma membrane. When hormones or other signaling molecules bind their receptors, which span the plasma membrane, they activate the enzyme leading to cAMP being produced from ATP. The second messenger then goes on to activate protein kinases, which phosphorylate various proteins activating them and causing a signaling cascade. One of the proteins activated is cAMP Response Element Binding Protein (CREB), which translocates to the nucleus, binds to specific DNA sequences known as cAMP response elements, and regulates the expression of target genes.

The Adenosine Nucleotide Regulates Blood Vessel Constriction

It is thought that constriction and relaxation of blood vessels is controlled in part through purinergic receptors, which are activated by ATP, ADP and cAMP. The nucleotide ATP is released from red blood cells, and is then converted into ADP and AMP. The nucleotides act on purinergic receptors on the surface of capillary cells and cause vasodilation. The effect of the ATP nucleotide was demonstrated in animal experiments in which added ATP was seen to increase coronary blood flow. Similarly infants that were fed a nucleotide supplemented formula showed increased blood flow to the gut after feeding compared to infants that were fed a formula without nucleotides.

Nucleotides Improve Cardio-Vascular Health

Another factor that plays a crucial role in effective blood circulation is a healthy cardio vascular system. The heart is a big muscle that pumps blood around the body all through your life without stopping. The heart itself is dependent on a healthy arterial system, any blockage in the blood vessels that lead to it will result in heart cells nor receiving sufficient oxygen and dying off. One of the most common diseases affecting the heart nowadays is atherosclerosis the hardening of the arteries. Atherosclerosis starts with a combination of high levels of cholesterol in the blood, and oxidative stress. To understand it properly you first have to understand that cholesterol isn’t found in the plasma in isolation. The molecule is hydrophobic, and is not soluble in blood. To transport it in the blood stream it has to be combined with special molecules called lipoproteins. These have a hydrophobic site, which can contact the cholesterol, and a hydrophilic, water soluble side, which can face out, in contact with the plasma. The lipoprotein molecules surround the cholesterol molecule and allow it to stay in solution in blood, despite the fact that it is not water-soluble.

There are different types of lipoproteins classified according to their density. The two principle types that are involved in cholesterol transport are low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL-cholesterol particles generally go from the liver to the all the other tissues, where they bind to their receptors on cells and release the cholesterol. HDL-cholesterol particles, on the other hand, take cholesterol back to the liver for excretion. LDL-cholesterol is generally considered to be ‘bad’, while HDL-cholesterol is ‘good’. However, in reality, cholesterol is absolutely necessary for life. The problem occurs when there is too much cholesterol in the body. The LDL receptors in cells become saturated, and the level of LDL-cholesterol in the blood rises.

The problems for the heart occur when the LDL particles are oxidized. This causes them to be engulfed by macrophages, which then settle on the walls of arteries, and form a net, which traps other macrophages and triglycerides resulting in the formation of plaques. These harden the artery walls so they can no longer dilate when necessary. The plaques can also grow in height filling up the lumen of arteries and impeding the passing of blood. This leads to heart disease and circulatory problems; it is harder for the heart to pump blood through the constricted vessels, and tissues don’t receive the oxygen they require for optimal function.

A yet unpublished study done by the team of Lars McNaughton at Hull University showed that sixty days of supplementation with nucleotides caused a 15% increase in the level of the ‘good’ HDL cholesterol compared to volunteers taking a placebo. At the same time supplementary nucleotides caused a drop in LDL-cholesterol. In this way nucleotides can protect heart health and ensure a free circulation of blood without blockages.

Nucleotides for Healthy Red Blood Cells

The central role of circulation is to bring oxygen to all the tissues of the body for respiration. Oxygen is carried bound to haemoglobin, an iron containing molecule, which is packed into red blood cells. Red blood cells are specialized for the sole function of carrying oxygen, they lose their nuclei as they mature, to provide more space for haemoglobin, and their biconcave disc shape allows them to squeeze into narrow capillaries.

The system depends on sufficient levels of iron in the body, which has to be absorbed from the intestine. Anaemia caused by iron deficiency is a common disorder, especially among women. Now scientists think that the nucleotide inosine, and its metabolites, hypoxanthine and uric acid, can aid the absorption of iron from the small intestine. Inosine, in turn, is a metabolite from adenosine, a commone nucleotide found in the diet.

Nucleotide supplements therefore ensure an adequate level of ATP, which is an important signaling molecule acting as itself, or after conversion to cyclic AMP, on purinergic receptors to dilate blood vessels allowing optimal circulation and profusion of tissues. Nucleotides also act to increase the levels of good HDL cholesterol while decreasing the levels of LDL cholesterol in the plasma. This ensures a healthy cardio vascular system, preventing the formation of plaques which block arteries. Finally adenosine, and its derivative inosine, is important for the efficient absorption of iron in the intestine. Iron is essential for the synthesis of haemoglobin, which transports oxygen in red blood cells to oxygenate all the cells in the body.

Further Reading:

ATP controls coronary blood flow during exercise:


Dietary nucleotides improve intestinal blood flow in infants:


Inosine, a derivative of adenosine, improves the absorption of iron from the small intestine: