The present invention refers to a glycerol ester composition comprising glyceryl

monobutyrate for balancing cholesterol levels.

The high fat diets of the western world has become a growing problem since several decades. It is part of human nature to eat while food is available and also to prefer food with high energy content. This is a genetically inherited disposition that has served humanity well since before civilization during times when food supply was seasonal and sometimes scarce. In modern time, with all types of food being available out of season and in abundance in the so called developed part of the world, our genetic disposition will become a burden. A majority of us will still select food with high energy value as if we were expecting times of starvation.

Besides known consequences such as obesity and all the health problems that follows with this also clogging of blood vessels known as atherosclerosis is a growing health issue. The latter is a known effect of heightened levels of cholesterol in the blood stream. There is a desire to be able to lower the cholesterol levels in a simple way. Cholesterol is a collective phrase for describing several types of lipoproteins. In the present invention Low- Density Lipoprotein (LDL) and High-Density Lipoprotein (HDL) are of particular interest. LDL, also known as "bad cholesterol" has a particle size of about 220 - 275 Angstrom.

LDL particles pose a risk for cardiovascular disease when they invade the endothelium and become oxidized, since the oxidized forms are more easily retained by proteoglycans. A set of biochemical reactions regulates the oxidation of LDL particles, primarily stimulated by the presence of necrotic cell debris and free radicals in the endothelium. Increased concentrations of LDL particles are strongly associated with accumulation of atherosclerosis within the walls of arteries over time. This will eventually result in sudden plaque ruptures. Even though it may take decades, this can trigger clots within the artery, narrowing or even closing of the arteries, i.e. cardiovascular disease, stroke, and other vascular disease complications.

LDL particles are often referred to as "bad cholesterol" because they can transport their content of lipid molecules into artery walls, attract macrophages, and thus drive atherosclerosis. In contrast, HDL particles are often called "good cholesterol" because they can remove lipids from macrophages in the wall of arteries. In healthy individuals, about 30% of cholesterol carried in the blood stream, along with other fats, is carried by HDL. This is often contrasted with the amount of cholesterol estimated to be carried within low-density lipoprotein particles, LDL.

HDL particles remove fats and cholesterol from cells, including cholesterol within artery wall atheroma, and transport it back to the liver for excretion or re-utilization. This is the reason why cholesterol carried within HDL particles is sometimes called "good cholesterol" despite the fact that it is basically the same as the cholesterol in the LDL particles. Those with higher levels of HDL tend to have fewer problems with cardiovascular diseases, while those with low HDL levels have increased rates for heart disease. Higher HDL levels are correlated with better cardiovascular health. It does, however not appear that further increasing one's HDL levels improves cardiovascular outcomes. The ratio between LDL and HDL cholesterol as well as the total levels of lipoproteins in the blood stream seem to be equally critical factors for avoiding cardiovascular disease and maintaining a good cardiovascular health.

Accordingly the present invention relates to a glycerol ester composition comprising glyceryl monobutyrate, for use in treating systemic low-grade inflammation. Long term sequelae metabolic diseases comprising coronary heart diseases and atheroscleorosis is hereby alleviated. This is achieved through the treatment which decreases the ratio between low density lipoprotein (LDL) and high density lipoprotein (HDL) in the blood stream of a monogastric animal (including human).

The glyceryl monobutyrate is preferably administered in the range 0.3 - 0.8 % by weight of the daily food ration for decreasing the LDL/HDL ratio in the blood stream of a monogastric animal (including human).

The LDL/HDL ratio in the blood stream is decreased by at least 10%.

As discussed above both LDL and HDL will always be present in the blood stream. LDL, "the bad cholesterol", will always be present in higher levels than HDL, "the good cholesterol". Even though there does not seem to be established an ideal best health ratio between LDL and HDL in the blood stream it is known that too low levels of HDL and too high levels of LDL is a driving factor behind atherosclerosis. A decrease in the ratio between LDL and HDL is accordingly positive.

High fat diets are known to cause dysbiosis, i.e. an imbalance of the microbiota composition in colon and therefore also in the gut metabolites formed, such as short-chain fatty acids (SCFA). SCFA are important substrates for the colon mucosa, especially butyrate. At a low formation of colonic butyrate the mucosal permeability may increase, with an increased influx of toxic substances that can cause systemic low-grade inflammation and in the long term metabolic diseases as coronary heart diseases and atheroscleorosis. By supplying a surplus of butyric acid in colon the mucosal permeability may decrease and as a consequence low-grade inflammation and metabolic risk factors connected to this inflammation, (such as decreased cholesterol levels).

The invention also relates to a glycerol ester composition comprising glyceryl monobutyrate, for use in treating systemic low-grade inflammation. Long term sequelae metabolic diseases comprising coronary heart diseases and atheroscleorosis is hereby alleviated. This is achieved through the treatment which decreases total cholesterol levels in the blood stream of a monogastric animal (including human).

The glyceryl monobutyrate is preferably administered in the range 0.3 - 0.8 % by weight of the daily food ration for decreasing total cholesterol levels in the blood stream of a monogastric animal (including human).

The total cholesterol levels in the blood stream is decreased by at least 30%.

According to one embodiment of the invention said glycerol ester composition comprises the reaction product obtained from reacting butyric acid and glycerol at a molar ratio of between 1 : 0.8 and 1 : 1.2.

Said glycerol ester composition preferably comprises at least 30% by weight of glyceryl monobutyrate, below 20% by weight of glyceryl dibutyrate and below 5% by weight of glyceryl tributyrate.

According to an even more preferred embodiment of the invention said glycerol ester composition comprises at least 40% by weight of glyceryl monobutyrate, below 15% by weight of glyceryl dibutyrate and below 2% by weight of glyceryl tributyrate. The amount of free butyric acid in said glycerol ester composition is suitably below 0.5 % by weight.

According to one embodiment of the invention said glycerol ester composition is adsorbed on a carrier, such as a silica carrier, thereby allowing said glycerol ester composition to be distributed as a dry product.

The claimed invention is particularly suited for treatment of animals (including human) consuming diets with high fat content.

A study was performed on rat fed a high fat diet.

A group of male Wistar rats were randomly divided into two subgroups, group A and group B. Group A and group B were allowed a three day period of acclimatization and were then given the test diet. Group A (control) were given free access to the test diet of table 1 column A while Group B (tested group) were given free access to the test diet of table 1 column B.

Table 1.

As said above, both test groups where allowed free access to their respective diet above for a period of 21 days. In addition the test groups also had free access to water. The temperature during the test was 21 °C and a 12 hour day / 12 hour night cycle was applied.

After the test period the rats were anaesthetised for tissue harvesting. From blood samples of the test subjects the levels of cholesterols were analysed and compared between the two test groups. See diagram A (total cholesterol) and diagram B (LDL/HDL ratio). Diagram A

It is shown that the administered composition in accordance with the invention radically lowered the total cholesterol levels in the blood stream of the animal.

Diagram B

It is shown that the administered composition in accordance with the invention significantly decreased the LDL/HDL ratio in the blood stream of the animal.

The collected effect of both lowering the total cholesterol levels and also changing the LDL/HDL ratio in favour of HDL is regarded as very positive results. A follow up study was performed to ascertain the effect of different dosage levels. The same diet as disclosed in table 1 was used but with glycerol monobutyrate added at 0.25, 075 and 1.5 % dwb. Even though the results of this dosage study was not considered statistically significant between the different levels there was a clear indication that peak efficiency was 0.75% of glycerol monobutyrate dwb dosing. The dose levels 0.25% and 1.5% was slightly less effective considering the lowering of total cholesterol levels in the blood stream. The same were found for HDL levels as well as LDL/HDL ratio in the blood stream where the 0.75% was found to be slightly more efficient in lowering levels and ratio than the 0.25% and 1.5% dosing.