NUTRITIONAL COMPOSITIONS FOR PROMOTING GERIATRIC HEALTH

MAINTENANCE

Field of Invention

The present invention relates to liquid compositions providing complete and balanced nutrition, helping with muscle tissue building and cardiovascular health maintenance in geriatric patients.

The background of the invention

Many people do not take in sufficient nutrients fora nutritionally complete diet. In order to assist these people, nutritional supplements have been developed. Nutritional supplements are usually not intended to provide all the nutrients necessary for a nutritionally complete diet; instead they are generally intended to supplement the diet such that it becomes more nutritionally complete. However, in some instances they may provide complete nutrition.

High protein nutritional supplements and drinks have been used for years by individuals with increased needs, such as athletes, pregnant women, patients recovering from illness or surgery and the elderly. A hallmark of aging is a progressive loss of muscle mass. Loss of muscle in aging individuals may lead to reduced muscle strength, increased incidence of falls and fractures and, consequently, hospitalization, impaired functioning of the immune system and reduced overall physical performance. Together with inactivity, which is also frequently observed in elderly individuals, this results in a downward spiral of functional and cognitive decline and loss of independence. It has been established that loss of muscle mass is less severe in elderly having or maintaining a high level of physical activity. However, even active elderly individuals experience muscle loss. This muscle loss occurs independent from health status, meaning that otherwise healthy elderly suffers from loss of muscle mass and function. Progressive muscle loss with aging is therefore not only a concern in e.g. ill, hospitalized or frail elderly, but also in otherwise healthy elderly individuals in order to stay physically active and improve quality of life.

In addition to physical activity, good nutrition is important to counteract loss of muscle mass in elderly individuals. It has been shown that they need more protein to support good health and maintain physical functionality. However, aging seniors rarely consume enough proteins. Dietary habits, nutrient intake, lifestyle and the aging process are interrelated. For example, with decreasing activity during the applied life style, and the age-associated decline in basal metabolic rate, neuro-endocrine function, immune function and taste and smell perception, older people tend to consume less food, and consequently fewer nutrients, which may lead to a nutritional status, which does not the specific requirements of the elderly of the frail individuals. Involuntary weight loss during aging above 65 years is strongly associated with impaired mood and low stamina. Consequently, several high protein liquid or semi-liquid products have been described or are available on the market. However, they are usually provided in a large volume necessary to achieve a high protein content of at least 20 g protein. As a result, compliance among, in particular, the elderly generally has difficulties consuming food in large volumes. Further, it is well known that a high protein content in liquid or semi liquid products results in an unpleasant taste and texture.

Besides a decreased protein intake, many elderlies also have inadequate vitamin and supplement intake. Supplement deficiencies have been correlated with disorders that are frequent among the elderly, such as cardiovascular disorders, type-2 diabetes, Alzheimer's disease and several types of cancer such as breast, prostate and colon cancer.

Aging is a well-recognized risk factor in the development of cardiovascular disease, which is the primary cause of death and disability in the elderly population. The normal process of aging is associated with progressive deterioration in structure and function of the heart and vasculature. These age-related changes likely act as both a catalyst and accelerator in the development of cardiovascular disease.

The effects of most dietary supplements on cardiovascular health have been studied for a long time. However, despite several studies explored the association of the various supplements to the cardiovascular risk, there is still a lack of consensus. Multivitamin supplementation has been advocated to reduce cardiovascular events; Vitamin D levels have been associated with the occurrence of coronary artery disease, heart failure, and atrial fibrillation; CoQ 10 deficiency has been associated with myocardial dysfunction and with statin myopathy; probiotics has been suggested to lower both blood pressure and circulating lipids. However, the study of the effects of dietary supplementations is not straightforward, since people assuming dietary supplements generally have a healthier diet and lifestyle, and randomized studies are rarely performed.

In the patent literature also, there are nutritional compositions which are specifically formulated for different age ranges and for different objectives. They can be supplementary to a malnourishment or they can provide a complete nutrition for patients with disabilities. For example, in patent document numbered US2010143543A1, macular degeneration related vision loss and functional blindness among the elderly are taken for technical problem. It reveals nutritional formulations comprising zinc, copper and other relevant metal ions, and antioxidants and to fortified foods containing such formulations in amounts believed to be effective in reducing the severity or slowing development of macular degeneration and preventing other age-related deficiencies. It is emphasized that the compositions subjected to the invention comprise supplements specifically focused on promoting visual functions such as lutein and zeaxanthin.

Similarly, patent document numbered US2017189446A1 emphasizes eye health in elderly; accordingly, zeaxanthin and lutein are included in the formulation.

Another patent document numbered WO2010/002257 discloses the use of a nutritional preparation comprising whey protein (preferably 22 to 32 %), at least 12 g leucine per 100 g proteinaceous matter and a lipid fraction which comprises at least one of EPA, (DPA, DHA and ETA for improving muscle function in a mammal. This improvement was claimed to occur when the mammal suffered from specific diseases or during aging and was claimed to result in improving daily activity, physical performance and quality of life. The composition as disclosed comprises preferably the components as mentioned and in addition specific indigestible oligosaccharides, glutamine, cysteine, oligosaccharides, carnitine and taurine.

However, the state of art does not include any mention or motivation to combine specific components serving to improve both muscle tissue and cardiovascular health which are the leading problems in geriatric patients.

Another challenge with the nutritional compositions is to reduce both the oxidation depending on the fat content and the sedimentation due to the dry matter content as much as possible to extend the shelf life. In the state of art, the high protein and fat contents used to prevent age- related dysfunctions, while providing a technical solution, on the other hand create such technical problems.

Considering the state of art, there is still a need for nutritional compositions customized for geriatric patients, providing complete and balanced nutrition, helping with muscle tissue recovering and cardiovascular health maintenance while enhancing stability by reducing sedimentation and oxidation at the same time. Objects and Brief Description of the Invention

The main object of the present invention is to obtain liquid nutritional compositions for providing complete and balanced nutrition, helping with muscle tissue building and cardiovascular health maintenance in geriatric patients.

Another object of the present invention is to obtain nutritional compositions enhancing stability by reducing sedimentation and oxidation at the same time.

Another object of the present invention is to obtain nutritional compositions having reduced osmolarity and osmolality, and accordingly enhanced patient compliance.

Another object of the present invention is to obtain nutritional compositions having balanced carbohydrate content which is free of glucose, ensuring patient’s daily energy need.

Another object of the present invention is to obtain nutritional compositions biocompatible components with no redundancy or competitive absorption.

Another object of the present invention is to obtain nutritional compositions essentially comprising water, at least one source of protein, at least one source of carbohydrate, at least one source of fat, at least one source of fiber, vitamins and minerals.

Another object of the present invention is to obtain nutritional compositions comprising beta- hydroxy-beta-methylbutyrate in combination with lutein and zeaxanthin to ensure both muscle tissue maintenance, cardiovascular health and eye health.

Another object of the present invention is to obtain nutritional compositions comprising beta- hydroxy-beta-methylbutyrate in combination with lutein and zeaxanthin to ensure both muscle tissue maintenance, cardiovascular health and eye health.

Another object of the present invention is to obtain nutritional compositions further comprising homotaurine to support muscle tissue maintenance and cardiovascular health and also to enhance nervous system.

Another object of the present invention is to obtain nutritional compositions free of lactose to protect gastrointestinal system in elderly patients with sensitive stomach and gut. Another object of the present invention is to obtain nutritional compositions with enhanced fiber range to support gastrointestinal system.

Another object of the present invention is to obtain nutritional compositions comprising caseinates in specific ranges as protein sources to provide reduced osmolarity and sedimentation.

Another object of the present invention is to obtain nutritional compositions comprising docosahexaenoic acid and eicosapentaenoic acid in encapsulated form to reduce oxidation and provide deodorization.

Another object of the present invention is to develop a process for preparing such compositions to enhance homogenization and reduce oxidation.

Detailed description of the invention

In accordance with the objects outlined above, detailed features of the present invention are given herein.

The present invention relates to liquid composition useful for providing complete and balanced nutrition and helping with muscle tissue building and cardiovascular health maintenance in geriatric patients, comprising;

- water

- at least one source of protein,

- at least one source of carbohydrate,

- at least one source of fat,

- at least one source of fiber,

- vitamins,

- minerals, wherein the composition further comprises at least one source of beta- hydroxy- beta- methyl butyrate in combination with lutein and zeaxanthin.

Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the amino acid leucine. This metabolite has received attention due to its anti-catabolic properties, through inhibition of muscle proteolysis and enhancement of protein synthesis. The aims of HMB supplementation are to counteract catabolic conditions, as well to enhance skeletal muscle mass and strength. Moreover, HMB has been shown to produce an important effect in reducing muscle damage induced by mechanical stimuli of skeletal muscle. HMB acts as precursor to the rate-limiting enzyme HMG-coenzyme, a reductase in cholesterol synthesis, which can enhance sarcolemmal integrity. For these reasons, HMB supplementation has a critical importance for elderly individuals and patients with diseases associated with muscle-wasting syndromes.

Besides, HMB is also a proven metabolite in terms of cardiovascular health. In literature researches, compared with the placebo, HMB supplementation resulted in a net decrease in total cholesterol (5.8%, P < 0.03), a decrease in LDL cholesterol (7.3%, P < 0.01) and a decrease in systolic blood pressure (4.4 mm Hg, P < 0.05). These effects of HMB on surrogate markers of cardiovascular health could result in a decrease in the risk of heart attack and stroke.

On the other hand, lutein has several beneficial effects, especially on eye health. In particular, lutein is known to improve or even prevent age-related macular disease which is the leading cause of blindness and vision impairment. Furthermore, many studies have reported that lutein may also have positive effects in different clinical conditions, thus ameliorating cognitive function, decreasing the risk of cancer, and improving measures of cardiovascular health.

Similarly, zeaxanthin intake is positively correlated with increased macular pigment density. Like lutein, zeaxanthin is an oxygenated non-pro-vitamin A carotenoid that consists of a 40- carbon hydroxylated compound. Zeaxanthin is not only implied in the health of the eye but also in cardiovascular aspects, such as beta-carotene; zeaxanthin, which resulted inversely correlated with right common carotid artery stiffness, pulse wave velocity and elastic modulus. Earlier studies showed that higher levels of plasma zeaxanthin may be protective against early atherosclerosis. These results indicated that zeaxanthin might be beneficial to arterial health.

In the light of these information, beta-hydroxy-beta-methylbutyrate is combined specifically with lutein and zeaxanthin to provide an enhanced effect on arterial and cardiovascular health. They are all biocompatible components with no redundancy or competitive absorption. On the contrary, it has been observed that this ternary combination has been observed to increase absorption for each component in the combination. Accordingly, increase in the effectiveness of the components is also expected.

According to the preferred embodiment, the amount of the source of beta-hydroxy-beta- methyl butyrate is sufficient to provide at least 0.5 g/100mL beta-hydroxy-beta-methylbutyrate. In the most preferred embodiment, the composition comprises calcium beta-hydroxy-beta- methyl butyrate in an amount of 0.6 - 1 g/100mL. According to the preferred embodiment, the weight ratio of beta-hydroxy-beta-methylbutyrate to lutein is in the range of 1:0.0001 to 1:0.002, preferably 1 :0.0005 to 1:0.0015, most preferably 1 :0.0007 to 1:0.001.

According to an embodiment, the composition further comprises homotaurine.

Homotaurine is a natural amino acid found in seaweed. It is analogous to taurine, but with an extra carbon in its chain. It has GABAergic activity, apparently by mimicking GABA, which it resembles. In 1965, Abbott Laboratories first patented this analog and marketed it as tramiprosate. As a promising drug, homotaurine (Alzhemed™) is also known for treating Alzheimer's disease. Recent studies demonstrated also its potential protective role against multiple sclerosis. It prevents amyloid formation and deposition and preserves Ab in a nonfibrillar form though preferentially binding to soluble Ab peptide. In addition, homotaurine action is dependent on changes in cortical GABA transmission, displaying a potential role in attenuating cholinergic transmission by modulating inhibitory cortical action. Homotaurine treatment reduced volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex of patients, which demonstrated its role in improving short-term memory performance. Therefore, homotaurine supplementation in individuals with mild cognitive impairment has a beneficial effect on hippocampus atrophy and episodic memory loss.

Homotaurine has also shown reduction in skeletal muscle tonus and hypothermic activity. For this invention, the combination of homotaurine and HMB has been shown to provide a surprising enhancement in muscle tissue recovering and muscle strength by slowing muscle protein breakdown and speeding protein synthesis, and also by preserving the structural integrity of your muscle cells. Accordingly, it has been seen that this combination has also remarkably significant effects on preventing muscle loss and reducing frailty in elderly patients.

According to the preferred embodiment, the weight ratio of beta-hydroxy-beta-methylbutyrate to homotaurine is in the range of 1 :0.01 to 1:0.1 preferably 1 :0.02 to 1:0.08. These ratios of combination have shown the most effective results for the enhancement of muscle tissue building. Most preferably, said ratio is in the range of 1 :0.03 to 1 :0.06. According to one embodiment, said source of carbohydrate is selected from the group comprising sucrose, maltodextrin, fructose, hydrolyzed corn starch, corn syrup solids, high fructose corn syrup or mixtures thereof.

Preferably, the composition is free of glucose to reduce insulin resistance insulin resistance, especially in elderly who have prediabetes and who are likely to develop type 2 diabetes since they are not physically active. Prediabetes usually occurs in people who already have some insulin resistance or whose beta cells in the pancreas aren’t making enough insulin to keep blood glucose in the normal range. Glucose intake significantly increases this risk since it is absorbed directly across the lining of the small intestine into your bloodstream, which delivers it to your cells and it raises blood sugar more quickly than other sugars, which stimulates the release of insulin.

Additionally, in a preferred embodiment, the composition is also free of lactose to increase patient compliance; since studies demonstrate that the prevalence of lactose malabsorption increases significantly after the age of 70-75 years.

In the preferred embodiment; the composition comprises maltodextrin and sucrose. The weight ratio of maltodextrin to sucrose is in the range of 1 :0.1 to 1 :1.5, preferably 1 :0.5 to 1:1. It has been surprisingly seen that osmolality of the composition can be reduced by using specifically these ranges.

Accordingly, osmolality of the composition is in the range of 100-1000 mOsm/kg water, preferably 200-800 mOsm/kg water. Besides, osmolarity of the composition is in the range of 100-800 mOsm/L, preferably 200-600 mOsm/L.

According to one embodiment, said source of protein is selected from the group comprising casein, soy, rice, pea, carob, oat, whey, caseino-glyco-macropeptides or mixtures thereof.

Preferably, the composition is free of whey to provide a balanced solid content and to achieve good heat stability and flowability on a tubular plant production.

According to the preferred embodiment, the composition comprises sodium caseinate and calcium caseinate as protein sources. The weight ratio of sodium caseinate to calcium caseinate is in the range of 1 :0.1 to 1:10, preferably 1:1 to 1:5. Specifically these ratios provide enhanced stability by reducing sedimentation over time and increase shelf-life accordingly. It has been also observed that the use of sodium caseinate and calcium caseinate as protein sources supports the reduction of osmolality. Most preferably, said ratio is 1 :3.

According to one embodiment, said source of fat is selected from the group comprising fish oil, medium chain triglycerides, rapeseed oil, sunflower oil, high oleic sunflower oil, safflower oil, rapeseed oil, soy oil, olive oil, canola oil, corn oil, peanut oil, rice bran oil, butter fat, hazelnut oil, structured lipids or mixtures thereof.

According to the preferred embodiment, said source of fat is selected from the fish oil, medium chain triglycerides, rapeseed oil, sunflower oil, high oleic sunflower oil or mixtures thereof. This selection of fat source has been shown to reduce oxidation and prolong shelf life of the composition.

According the preferred embodiment, the composition further comprises docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Most preferably, DHA and EPA are included in the composition in encapsulated form to assure deodorization of the fishy flavor and odor. Additionally, encapsulation reduces oxidation during the production process and the shelf-life.

Specific ranges of DHA, which have been surprisingly found during the trials, are used to reinforce the reduction of oxidation. According to one embodiment, the weight ratio of total fat to docosahexaenoic acid is in the range of 1:0.005 to 1:0.05, preferably 1:0.01 to 1:0.02.

According the one embodiment, said source of fiber is selected from the group comprising fructooligosaccharides, inulin, guar gum, xanthan gum, xylo-oligosaccharides, gum arabic, pectin, acacia gum, resistant starch, dextrans or mixtures thereof.

According the preferred embodiment, the composition comprises fructooligosaccharides and inulin. Preferably, the total amount of fructooligosaccharides and inulin is 0.5-2 g/100ml_, most preferably 0.75-1 g/100ml_. It is aimed to improve the bowel functions of elderly patients by the specific selection of these water-soluble fibers and their amounts which are relatively high considering the prior art.

According the one embodiment, said vitamins are selected from the group comprising palmitate, beta carotene, vitamin D3, vitamin E, vitamin K1, vitamin C, folic acid, vitamin B1 , vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B12 or mixtures thereof. According the one embodiment, said minerals are selected from the group comprising sodium, potassium, chloride, calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, selenium, chromium, molybdenum or mixtures thereof.

According the preferred embodiment, the composition further comprises at least one component selected from carnitine, choline, omega 9.

According the one embodiment, the energy value of the composition is in the range of 140- 170 kcal/100 mL to ensure daily energy need of elderly patients.

According to one embodiment, the composition comprises;

- 8-12 g/100ml_ protein

- 5-8 g/100ml_ carbohydrate

- 3-6 g/100ml_ fat

- 15-300 mg/100m L docosahexaenoic acid

- 5-30 mg/100m L eicosapentaenoic acid

- 0.5-1 g/100m L fiber

- 0.5-0.6 g/100ml_ beta-hydroxy-beta-methylbutyrate

- 5-60 mg/100m L homotaurine

- 0.05-1.2 mg/100ml_ lutein

- 0.05-0.2 mg/100ml_ zeaxanthin

According to one preferred embodiment, the composition further comprises;

- 2-50 mg/100m L carnitine

- 50-100 mg/100ml_ choline

- 50-100 mcg/100ml_ palmitate

- 50-100 mcg/100ml_ beta-carotene

- 2-5 mcg/100ml_ vitamin D3

- 1-5 mcg/100ml_ vitamin E

- 10-30 mcg/100ml_ vitamin K1

- 10-30 mg/100ml_ vitamin C

- 20-70 mcg/100ml_ folic acid

- 0.1-0.5 mg/100ml_ vitamin B1

- 0.1-0.5 mg/100ml_ vitamin B2

- 0.1-0.5 mg/100ml_ vitamin B6

- 0.3-1 mcg/100m L vitamin B12

- 2-5 mg/100ml_ vitamin B3 - 0.5-5 mg/100ml_ vitamin B5

- 3-10 mcg/100ml_ vitamin B7

- 100-300 mg/100ml_ sodium

- 200-500 mg/100ml_ potassium

- 50-100 mg/100m L chloride

- 100-500 mg/100ml_ calcium

- 50-200 mg/100m L phosphorus

- 10-50 mg/100ml_ magnesium

- 1-5 mg/100ml_ iron

- 1-5 mg/100ml_ zinc

- 0.1-1 mg/100ml_ manganese

- 100-500 mcg/100ml_ copper

- 10-50 mcg/100ml_ iodine

- 5-20 mcg/100ml_ selenium

- 5-20 mcg/100mL chromium

- 10-30 mcg/100ml_ molybdenum

These analytically selected ratios ensure the required effective doses for the complete nutrition, toxic safety and patient compliance. Furthermore, they enhance the stability and prolonged shelf-life.

According to all these embodiments, the below given formulations can be used in the liquid composition subjected to the invention.

Example 1 : Liquid composition providing complete and balanced nutrition for geriatric patients Example 2: Liquid composition providing complete and balanced nutrition for geriatric patients

The preparation method of the above-mentioned liquid compositions given in examples 1 and 2 is prepared by following these steps: a. Blending water soluble components in water b. Pasteurizing the mixture c. Adding fat sources to the mixture d. UHT processing the total mixture