Patent Application
20160114002
This application claims its priority to French patent application FR 14 60157 filed on Oct. 22, 2014, the entire disclosure of which is incorporated herein by reference.
The present invention relates to compositions with plant proteins and their use to prevent cardiometabolic risk.
Cardiometabolic risk groups together several risk factors that may lead, over a longer or shorter term, to metabolic pathologies such as type 2 diabetes and/or cardiovascular disease. These risk factors are, in particular, increased glycaemia dyslipidemia, high blood pressure, excess abdominal fat.
A patient with cardiometabolic risk must have at least three of these factors, some combinations being more dangerous than others. It has in particular been recognized that in combinations where hyperglycemia is present, a risk is doubled with respect to other factors. It is also known that the consequences are different depending on the factors involved:
Clinically, the major factors in terms of morbidity/mortality are hyperglycemia, significant waist girth involving a significant visceral body fat mass, hypertension, low HDL cholesterol level and high triglyceride level.
In terms of the physiopathology of the cardiometabolism, the main cause is the presence of excessive visceral fat due to oxidative stress, which causes inflammation (in particular measured using the PAI-1 level, prothrombotic marker, and secondarily by more general markers such as TNα, IL6 or CRP us) and insulin resistance (determined by abnormal insulinemia and/or an abnormal evaluation of the HOMA IR, HOMA B and/or HOMA S homeostatic model).
Until recently, the existing solutions to avoid cardiometabolic risk were limited.
None of the many diets proposed since the appearance of cardiometabolic risk in the 1980s, whether balanced, hyperproteinated, hyperglucidic, hyperlipidic, very restrictive or unbalanced, have resolved the specific deficiency problems and pathological particularities of this syndrome.
Furthermore, the proposed drugs work on only one of the consequences of the metabolic syndrome, such as hyperglycemia or hypertension or hypertriglyceridemia or hypercholesterolemia, but not the entire metabolic syndrome. The pollypill proposed as prevention for cardiometabolic risk was rejected by all of the Drug Agencies.
More recently, effective solutions have been proposed, in particular the composition described in application FR2981544. In clinical trials, this composition proved to be particularly suitable for people with high waist girth and a high triglyceride level.
There is therefore a need for a composition more suited to people with a metabolic syndrome whose essential risk factor is hyperglycemia.
The aim of the present invention is to meet this need and propose a composition able to prevent cardiometabolic risk, and therefore metabolic and/or cardiovascular pathologies resulting therefrom, by acting simultaneously on:
The present invention provides a composition suitable for oral administration and comprising at least one plant protein chosen from among pea proteins, rice proteins or mixture of pea protein(s) and rice protein(s), and:
Advantageously, such a composition may be used as a healthcare product, in particular as a medical nutrition product, to prevent cardiometabolic risk, in particular to prevent metabolic and/or cardiovascular pathologies associated with cardiometabolic risk. The composition according to the invention may in particular be used to act on vectors of the visceral fat physiopathology and clinical risk factors for cardiometabolic risk. The invention is particularly suitable for cardiometabolic risk for patients whose main risk factor is hyperglycemia.
The invention will now be described in detail.
The invention therefore relates to a particular composition suitable for oral administration in humans comprising at least one plant protein chosen from among pea proteins, rice proteins or mixture of pea protein(s) and rice protein(s), and:
Preferably, the composition according to the invention does not comprise other components except excipients.
The composition therefore comprises at least plant proteins and one or more elements belonging to one of the four following groups:
The composition therefore comprises at least one plant protein chosen from among pea proteins and rice proteins, or several pea proteins, or several rice proteins, or mixture of one or more pea proteins and one or more rice proteins.
The plant proteins may be in native form (isolate or concentrate or isolate and concentrate mixture) or in hydrolyzed form (hydrolysate).
Preferably, the plant protein(s) are in the form of an isolate or concentrate.
If the plant protein is in hydrolyzed form, the hydrolysis level varies from 10 to 35%.
Still more preferably, the pea proteins(s) are present in isolate form with a high viscosity level to obtain good solubility, and that isolate must make it possible to obtain at least an 85% level of pure proteins. The rice protein(s) are preferably in rice protein isolate form with a level of at least 85% pure proteins.
The plant proteins used in the composition according to the invention have the advantage of acting on the microbiota, the intestinal barrier of the adipose tissue and the adipocyte, and they have a clinical impact on glycaemia and insulin resistance, the lipolysis, and lastly the dyslipidemia and the antithrombotic effect.
The composition may also comprise at least one animal protein chosen from among calcium caseinate and lactoserum proteins, or a mixture of at least two of those animal proteins.
The animal proteins may be in native form (isolate or concentrate or mixture of isolate and concentrate) or in hydrolyzed form (hydrolysate).
Preferably, the composition comprises at least one calcium caseinate.
If the composition comprises lactoserum proteins, it preferably comprises lactoserum in isolate, concentrate and/or hydrolysate form, or α-lactalbumin.
If the animal protein is in hydrolyzed form, the hydrolysis level preferably varies from 10 to 35%.
The animal protein(s) of the composition according to the invention act on the AMPK and PPAR energy cycle, the adipose tissue with lipolysis, the differentiation of pre-adipocytes and above all the inflammation cycle by infiltrated macrophages.
The total quantity of whole proteins (without taking any free amino acids added in the composition into account) present in a daily ration of the composition according to the invention for oral administration to humans is preferably comprised between 15 and 50 g, preferably distributed in two doses.
The proteins present in the composition according to the invention are made up of amino acids participating in the efficacy of the composition on the prevention of cardiometabolic risk, in particular:
Preferably, the protein(s) of the composition according to the invention comprise at least the following amino acids: leucine, isoleucine, valine, glutamine, tryptophan, lysine, alanine, tyrosine, phenylalanine, threonine. Still more preferably:
Thus, the proteins present in the composition according to the invention preferably act on the energy, ketogenesis and muscle proteolysis cycles.
The composition according to the invention may also comprise free amino acids. These amino acids reinforce the action of whole proteins in the energy cycle, ketogenesis, muscle proteolysis and anti-inflammatory action.
In particular, the composition according to the invention may comprise a free amino acid chosen from among leucine, threonine, glutamine, isoleucine, valine, tryptophan or plant 5HTP, lysine, arginine and taurine, or a mixture of at least two of those amino acids. According to one preferred embodiment, the composition comprises the following free amino acids: leucine, tryptophan or plant 5HTP, threonine, taurine and arginine.
The total daily leucine intake for person with abdominal obesity should be between 3 and 5 g, branched amino acids between 6.5 and 10.5 g, tryptophan between 0.4 and 0.8 g, neutral amino acids between 10 and 16 g and threonine between 1 and 2.5 g; to preserve a low body weight and maintain the energy cycle, the group of tryptophan, leucine and lysine amino acids must be between 5 and 10 g. The aim of the present invention is to cover, by the whole proteins and free amino acids, between 50 and 100% of the average quantity necessary for all of those amino acids or amino acid groups, knowing that these people have a deficiency and that a greater intake for a period limited to 12 to 24 weeks is sometimes necessary to regulate the different cycles, including the energy cycle.
The composition according to the invention may also comprise at least one micronutrient chosen from among vitamin D, vitamin B6, vitamin B9, vitamin E, milk calcium, marine magnesium, zinc and chromium, or a mixture of at least two of those micronutrients. Preferably, it comprises all of those micronutrients.
These micronutrients make it possible to offset deficiencies in people with cardiometabolic risk, generally with abdominal obesity.
Lastly, the composition also comprises at least one anti-inflammatory and/or antioxidant compound of plant origin chosen from among ALA omega-3 fatty acid, purified EPA, protectin in PD1 or PDX form, and curcumin, or a mixture of at least two of these anti-inflammatory compounds of plant origin. Preferably, it comprises ALA and curcumin.
ALA is the plant form of the omega-3 precursor for EPA, whose essential action is anti-inflammatory, in particular on the endothelial barrier. The composition may also contain purified EPA. This molecule allows better protection at the intestinal barrier to prevent LPS from passing that barrier.
Curcumin has a local anti-inflammatory effect on the intestinal barrier as well, which is combined with that of the glutamine present in the composition.
The composition according to the invention may be obtained using a method as described below:
This obtains a powder that can be transformed into a tablet or liquid, or used in its powder form in sachets, sticks, cans or gelcaps, for example.
The composition according to the invention may assume any form suitable for oral administration. It may in particular assume the form of powder or granules, ready-to-use beverages or bars or an extruded form, the composition being supplemented by excipients and traditional fillers known by those skilled in the art.
Preferably, it assumes the form of powder or granules packaged in a sachet to be diluted in water.
Advantageously, the various components of the composition act synergistically to affect risk factors for cardiometabolic risk.
The composition according to the invention can therefore be used as a healthcare product, in particular a medical nutrition product, to prevent cardiometabolic risk, in particular to prevent metabolic and/or cardiovascular pathologies resulting from cardiometabolic risk.
Within the meaning of the present invention, “medical nutrition product” refers to a particular healthcare product, namely a food or food supplement for therapeutic use, alone or combined with other therapies.
The composition according to the invention, when administered orally in a sufficient quantity, makes it possible to act directly on different risk factors for cardiometabolic risk, in particular:
It is particularly suitable for people with risk factors for cardiometabolic risk, with increased prediabetic glycaemia. This combination is, however, recognized as the most dangerous combination of risk factors for cardiometabolic risk.
It also has surprising efficacy on hyperlipidemia risk factors.
Furthermore, it acts very powerfully on the regulation of intestinal microbiota, in particular by increasing bacteriodetes and decreasing firmicutes. It is also able to decrease inflammation of the intestinal barrier to decrease the passage of LPS.
It also makes it possible to increase lipolysis of the adipocytes, stop differentiation of pre-adipocytes, and reduce the size of adipocytes, as well as modulate the inflammatory expression of macrophages in the tissue.
The invention therefore targets the composition as previously described for its use as an oral medical nutrition product to prevent cardiometabolic risk in human beings, in particular to prevent metabolic and/or cardiovascular pathologies associated with cardiometabolic risk, in particular type 2 diabetes and cardiovascular diseases.
It is particularly effective to prevent cardiometabolic risk with the risk of hyperglycemia as the main factor.
The composition according to the invention may be used as an oral medical nutrition product to prevent and/or combat prediabetes.
The invention also specifically relates to the use of the composition to prevent and/or combat at least one of the risk factors for cardiometabolic risk, in particular to decrease glycaemia, but also to decrease waist circumference, normalize blood pressure, increase HDL cholesterol, decrease LDL cholesterol, decrease total cholesterol, decrease triglycerides, decrease visceral body fat mass, decrease inflammation (particularly decrease PAI 1, pro-thrombotic adipocytokine) and decrease insulin resistance (in particular to regulate insulinemia, HOMA IR, HOMA B and/or HOMA S).
Lastly, the invention may also be used to regulate intestinal microbiota, in particular by increasing bacteriodetes and decreasing firmicutes.
The daily dose of the composition according to the invention (dose of mixture of active ingredient without excipients) is preferably comprised between 60 and 120 g, preferably in two doses of 30 to 60 g taken one in the morning with breakfast or at 11 a.m. with a snack, and one with a snack in the afternoon.
The composition according to the invention should preferably be accompanied by a calorie restriction comprised between 500 and 800 kcal for a resting energy expenditure (REE) of about 1,800 kcal.
The invention is illustrated through examples and trial results demonstrating the efficacy of the composition according to the invention.
The composition of example 1 is made up of:
Furthermore, the amino acids present in the composition (amino acids making up proteins and free amino acids) are the following:
The composition of example 2 is made up of:
Furthermore, the amino acids present in the composition (amino acids making up proteins and free amino acids) are the following:
The composition of example 3 is made up of:
Furthermore, the amino acids present in the composition (amino acids making up proteins and free amino acids) are the following:
The composition of example 4 is made up of:
Furthermore, the amino acids present in the composition (amino acids making up proteins and free amino acids) are the following:
The composition of example 5 is made up of:
Furthermore, the amino acids present in the composition (amino acids making up proteins and free amino acids) are the following:
The composition of example 6 is made up of:
Furthermore, the amino acids present in the composition (amino acids making up proteins and free amino acids) are the following:
The composition of example 7 assumes the form of a powder containing 43 g of active molecules and excipients.
The active molecules are the following:
Furthermore, the amino acids present in the composition (amino acids making up proteins) are the following:
The composition according to the invention underwent a 12-week random, double-blind clinical trial in comparison to the product described in application FR2981544.
The study was carried out on patients:
Patients followed a diet appropriate for their food habits, balanced (50% carbohydrates, 35% lipids, 15% proteins; carbohydrates with glycemic load below 10), hypocaloric (restriction of 600 kcal on calculated Resting Energy Expenditure [REE]) and including two doses per day of the composition according to the invention (that of the example 7) providing 380 kcal taken into account in the daily ration. A physical activity of at least 5000 steps (measured using a pedometer) was prescribed. This intensive phase was to be stopped after 12 weeks.
This intensive phase should be followed by a 4-week stabilization phase including a balanced diet with no calorie restriction and taking the composition according to the invention (that of example 7) per day.
When the results were analyzed, it was revealed that there was indeed a difference resulting in 2 distinct groups consisting of patients with more fat (greater visceral body fat mass, total fat mass and hypertriglyceridemia) and patients who had more of a hyperglycemic tendency; the former responded better to the composition of invention FR2981544, and the latter to the composition according to the invention.
A sub-group of 27 hyperglycemic subjects therefore yielded better results on all of the parameters.
The obtained results, given in the intent to treat population (i.e., 53 people for the entire group and 27 for the hyperglycemia subgroup) are provided in the table below:
It will in particular be noted that the composition according to the invention acts significantly (p<0.0001) on visceral fat with a loss of 8.4% for the entire population and 9.3% for the sub-group of hyperglycemic subjects. The total fat loss (p<0.0001) is 6.6% for the total population and 7.7% for the sub-group accompanied by a modest lean body mass loss of 1.1%, respectively.
It also acts on the risk factors and the fundamental factors of cardiometabolic risk:
It should be noted that the Per Protocol results, with 4 people deducted for noncompliance with the protocol, are even better.
The composition according to the invention therefore provides concrete and probative results on subjects with cardiometabolic risk, in particular those in the most dangerous position with the presence of hypertriglyceremia, which may be defined as a prediabetes situation with cardiovascular risk.
| Number | Date | Country | Kind |
|---|---|---|---|
| 14 60157 | Oct 2014 | FR | national |
