Compositions comprising magnesium oxide

Abstract

The disclosed invention relates to a composition comprising from 30 to 70 wt.% of magnesium oxide; from 20 to 60 wt.% of modified starch; and from 0.05 to 5 wt.% of lecithin. The composition useful for the prevention or treatment of a condition or disease related to magnesium deficiency. The invention also contemplates pharmaceutical products, food supplements and food products thereof.

Description

4843-01.1.COMPOSITIONS COMPRISING MAGNESIUM OXIDE FIELD OF THE INVENTION

[0001] The invention relates to the field of nutraceuticals and pharmaceuticals. In particular, the present invention relates to magnesium oxide compositions that are particularly suitable for the prevention or treatment of a condition or disease related to magnesium deficiency.BACKGROUND OF THE INVENTION

[0002] Magnesium (Mg) is a vital mineral and an essential element in the biochemistry of living organisms. It plays a crucial role as a cofactor in over 600 enzymatic reactions, including those involved in energy production, DNA synthesis and protein synthesis [Jana L Kröse, Jeroen H F de Baaij, Magnesium biology, Nephrology Dialysis Transplantation, 2024],

[0003] In humans, Mg is particularly important for maintaining normal muscle and nerve function, regulating blood glucose levels, inflammation, response to cancer and infectious diseases and supporting a healthy immune system. It also contributes to the structural development of bones and is required for the synthesis of the antioxidant glutathione [Ashique, S.; Kumar, S.; Hussain, A.; Mishra, N.; Garg. A.; Gowda, B. H. J.; Farid, A.; Gupta, G.; Dua, K.; Taghizadeh-Hesary, F. Correction: A Narrative Review on the Role of Magnesium in Immune Regulation, Inflammation, Infectious Diseases, and Cancer. J. Health Popul. Nutr. 2023, 42 (1), 117], A deficiency in Mg may lead to mild to severe physiological problems, such as muscle cramps, fatigue, cardiac arrhythmias, biochemical abnormalities of hypokalemia and hypocalcemia, hypertension, atherosclerotic vascular disease, altered glucose homeostasis, and metabolic bone disease [Abbott, L. G.; Rude, R. K. Clinical Manifestations of Magnesium Deficiency. Miner. Electrolyte Metab. 1993, 19 (4-5), 314-322],

[0004] Therefore, maintaining adequate levels of Mg is critical for overall health and well-being. Magnesium supplements are commonly used to prevent or treat magnesium deficiency and to support various bodily functions. They are available in several forms, including Mg oxide (MgO), Mg citrate (Mg-C), Mg bisglycinate (Mg-BG), and Mg chloride, each with different absorption rates and potential effects on the body. These supplements are often recommended for individuals who have difficulty getting enough magnesium through their diet, such as those with gastrointestinal disorders, certain chronic conditions, or increased physiological needs like pregnancy or intense physical activity.4843-01-2-

[0005] However one of the problems of magnesium supplements is that magnesium absorption is low. When administered orally, magnesium is primarily absorbed in the small intestine in the ileum and jejunum and non-absorbed magnesium can cause a number of side effects, including diarrhea, heartburn, nausea and upset stomach.

[0006] Different efforts have been made to improve bioavailability of magnesium and reduce its side effects. However, there is still the need in the art for magnesium compositions that improve magnesium bioavailability while reducing side effects.

[0007] The present invention sets out to meet some or all of the above-identified needs and to solve some or all of the above-identified problems.SUMMARY OF THE INVENTION

[0008] The problem solved by the present invention is the provision of a magnesium oxide composition with improved effect. In particular, it has been found that the magnesium oxide composition of the invention enhances the bioavailability of magnesium and leads to a fast increase in the Mg levels (e.g. as soon as 1 hour after the oral intake). Remarkably, the impact of higher plasma levels persists over an extended duration (i.e. there is a sustained effect). In addition, the magnesium oxide composition of the invention reduces the side effects caused by magnesium intake such as, for example, gastric or intestinal side effects.

[0009] Thus, in a first aspect the invention provides a composition comprising: a) from 30 to 70 wt.% of magnesium oxide;b) from 20 to 60 wt.% of modified starch; andc) from 0.05 to 5 wt.% of lecithin;wherein the sum of the components does not exceed 100 wt.%.

[0010] In another aspect, the invention relates to a composition according to the first aspect, for the prevention or treatment of a condition or disease related to magnesium deficiency.

[0011] In another aspect, the invention provides a pharmaceutical product comprising an effective amount of the composition of the first aspect, together with acceptable excipients.

[0012] In another aspect, the invention provides a food supplement comprising an effective amount of the composition of the first aspect, together with acceptable excipients.

[0013] In another aspect, the invention provides a food product or edible product comprising an effective amount of a compositions according to the first aspect.4843-01-3-

[0014] A method for preventing or reducing the risk of a condition or disease caused by a deficiency of magnesium comprising the administration to a subject in need thereof of a composition, a pharmaceutical, a food supplement, food product or edible product is also contemplated herein.BRIEF DESCRIPTION OF THE DRAWING

[0015] Figure 1. Graphical representation of Mg levels in plasma (normalized to basal time; 0 h) in all volunteers in the assessed time points for each product. Data are represented as mean ± S. E. M. A, magnesium citrate; B, magnesium oxide; C, magnesium bisglycinate; D, magnesium oxide composition of the invention.

[0016] Figure 2. Bar graph representation of the increase of Mg levels in plasma in in mg / L after 6 h of the oral intake compared to the basal levels for each product. Data are represented as mean ± S. E. M. A, magnesium bisglycinate; B magnesium oxide composition of the invention; C, magnesium citrate; D, magnesium oxide.DETAILED DESCRIPTION OF THE INVENTION

[0017] Various preferred features and embodiments will be described below by way of non-limiting illustration.

[0018] The articles "a” and "an" are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article unless the context clearly indicates otherwise. By way of example, "an element" means one element or more than one element.

[0019] Except in the Examples, or where otherwise explicitly indicated, all numerical quantities in this description specifying amounts of materials, reaction conditions, molecular weights, number of carbon atoms, and the like, are to be understood as modified by the word "about". The term “about" as used herein, e.g. when referring to a measurable value (such as an amount or weight of a particular component or temperature), refers to variations of ±20%, ±10%, ±5%, ±1%, ±0.5%, or. particularly, ±0.1% of the specified amount. Except where otherwise indicated, all numerical quantities in the description specifying amounts or ratios of materials are on a weight basis.

[0020] While overlapping weight ranges for the various components and ingredients that can be contained in the disclosed compositions have been expressed for selected embodiments the disclosed technology, the amount of each component in the disclosed compositions is selected from its disclosed range such that the sum of all components or ingredients in the composition will total 100 weight percent. The amounts employed4843-01-4-will vary with the purpose and character of the desired product and can be readily determined by one skilled in the art.

[0021] As used herein, the term “comprising", which is inclusive or open-ended and does not exclude additional unrecited elements or method steps, is intended to encompass as alternative embodiments, the phrases “consisting essentially of’ and “consisting of’ where “consisting of’ excludes any element or step not specified and “consisting essentially of’ permits the inclusion of additional unrecited elements or steps that do not materially affect the essential or basic and novel characteristics of the composition or method under consideration.

[0022] The terms “subject”, “patient” and “individual” and variants thereof are used interchangeably herein and refer to any animal subject, particularly mammalian, or human. Thus, it includes, without limitation not only humans but also domestic animals (e.g., dogs, cats and the like), farm animals (e.g., cows, sheep, pigs, horses and the like), and laboratory animals (e.g., monkey, rats, mice, rabbits, guinea pigs and the like) for whom diagnosis, treatment, or therapy is desired. The compositions described herein are applicable to both human therapy and veterinary applications. “Subject in need thereof” as used herein includes subjects that would benefit from administration of the compositions of the disclosure.

[0023] The terms “treatment” and “therapy” and derivatives thereof refer to, e.g., the reduction in severity of disease or condition disclosed herein; the mitigation / amelioration or elimination of one or more symptoms, complication, or sequelae associated with a disease disclosed herein (e.g., weakness, fatigue, tremors, muscle disfunction or aches, etc.); the provision of beneficial effects to a subject with a condition / disease disclosed herein, without necessarily curing the disease or condition. The term also includes prophylaxis or prevention of a disease or condition or symptoms, complications, or sequelae thereof. Therefore, the expression “treating” as used herein, encompasses treating, preventing or ameliorating a disease, or symptoms, complications and / or sequela thereof. The term refers to a clinical or nutritional intervention to prevent the disease or condition; cure the disease or condition; delay onset of the disease or condition; delay onset of a symptom, complication or sequela; reduce the seriousness of the disease or condition; reduce the seriousness of a symptom, complication, or sequela; improve one or more symptoms; improve one or more complications; improve one or more sequelae; prevent one or more symptoms; prevent one or more complications; prevent one or more sequelae; delay one or more symptoms; delay one or more symptoms; delay one or more complications; delay one or more sequalae; mitigate / ameliorate one or more symptoms; mitigate / ameliorate one or more4843-01-5-complications; mitigate / ameliorate one or more sequelae; shorten the duration one or more symptoms; shorten the duration one or more complications; shorten the duration of one or more sequelae; reduce the frequency of one or more symptoms; reduce the frequency of one or more complications; reduce the frequency of one or more sequelae; reduce the severity of one or more symptoms; reduce the severity of one or more complications; reduce the severity of one or more sequelae; improve the quality of life; increase survival; prevent a recurrence of the disease or condition; delay a recurrence of the disease or condition; or any combination thereof, e.g., with respect to what is expected in the absence of the treatment with the composition of the present disclosure.

[0024] The terms “prevention”, “preventing”, “prophylaxis” and variants thereof as used herein, refer, e.g. (i) partially or completely delaying onset of a disease, disorder and / or condition disclosed herein; (ii) partially or completely hindering or delaying onset of one or more symptoms, features, or clinical manifestations, complications, or sequelae of a particular disease, disorder, and / or condition disclosed herein; (iii) partially or completely delaying onset of one or more symptoms, features, or manifestations, complications, or sequelae of a particular disease, disorder, and / or condition disclosed herein; (iv) partially or completely delaying progression from a particular disease, disorder and / or condition disclosed herein; and / or (v) decreasing the risk of developing pathology associated with the disease, disorder, and / or condition disclosed herein.

[0025] The term condition "condition” is used herein in its broad sense and refers to a specific state of health that affects an individual. The term condition encompasses a wide range of health disorders, including without limitations mild, acute and chronic health disorders.

[0026] The term "disease" as used herein refers to a specific abnormal condition or disorder that affects the body or mind, resulting in impaired functioning or discomfort. They can manifest with a wide range of symptoms and can affect different organs or systems in the body. Diseases can be acute (short-term) or chronic (long-lasting), and they may require medical intervention for diagnosis, treatment, and management.

[0027] The term “symptom’’ as used herein refers to subjective or physical sign, indication, or evidence of disease or condition observed by the subject. Symptoms are felt or noticed by the individual experiencing the symptom but may not easily be noticed by others. A symptom can be a mild symptom, a moderate symptom, or severe symptom. As used herein, the term “mild symptom” refers to a symptom that is not life threatening and does not require, e.g., intensive care treatment. As used herein, the term “moderate symptom” refers to a symptom that requires monitoring because it may become life threatening and may require, e g., hospitalization. As used herein, the term “severe4843-01-6-symptom” refers to a symptom that is life threatening and requires, e.g., intensive care treatment.

[0028] The terms “bioavailability" and “bioavailable", as used herein, refer to the extent to which a nutrient or micronutrient can be absorbed and utilized by the body. Magnesium oxide compositions

[0029] The present invention provides a composition comprising:a) from 30 to 70 wt.% of magnesium oxide;b) from 20 to 60 wt.% of modified starch;c) from 0.05 to 5 wt.% of lecithin; andwherein the sum of the components does not exceed 100 wt.%

[0030] In particular, the magnesium oxide is in a concentration of from 40 to 60 wt.%. More particularly, the concentration of magnesium oxide can be from 50 to 60 wt.%.

[0031] The term “modified starch”, as used herein, refers to a starch that has been chemically or physically altered to change its properties. Common methods of modifying starch include physical treatments such as heat, pressure, and mechanical shear, as well as chemical treatments such as acid hydrolysis, cross-linking, oxidation, esterification and enzymatic modification.

[0032] In some embodiments, the modified starch can be selected from the group consisting of thermally treated, starch, mechanically treated starch, oxidatively degraded, starch, hydrolytically degraded starch, enzymatically degraded starch

[0033] The starch can be obtained from different natural sources such as, for example, potato starch, corn starch, wheat starch, rice starch, tapioca starch, maize, pea starch, sorghum starch, and mixtures thereof. In particular, the starch can be a maize starch.

[0034] In particular, the modified starch can be in a concentration from 30 to 50 wt.%. More particularly, from 40 to 45 wt.%.

[0035] The lecithin can be obtained from different sources. Non-limiting examples of sources of lecithin include soybean, eggs, sunflower seeds, rapeseed, milk, wheat germ, peanuts and corn. In particular, the lecithin can be sunflower lecithin.

[0036] In particular, the lecithin can be in a concentration of from 0.1 to 2 wt.%. More particularly, the concentration of lecithin can be from 0.1 to 1 wt.%.

[0037] Some exemplary compositions of the invention include:I. A nutraceutical or pharmaceutical composition comprising:a) from 40 to 60 wt.% of magnesium oxide;b) from 30 to 50 wt.% of modified starch; and4843-01-7- c) from 0.1 to 2 wt.% of lecithin;wherein the sum of the components does not exceed 100 wt.%II. A nutraceutical or pharmaceutical composition comprising:a) from 50 to 60 wt.% of magnesium oxide;b) from 40 to 45 wt.% of modified starch; andc) from 0.1 to 1 wt.% of lecithin;wherein the sum of the components does not exceed 100 wt.%

[0038] Advantageously, the composition can be in the form of microcapsules.

[0039] The term “microcapsules” as used herein is understood in its broader meaning and refers to minute container that is commonly spherical and includes, without limitation, microspheres, core / shell microcapsules and polynuclear microcapsules.

[0040] In particular, the microcapsule can comprise an internal phase (i.e. core) comprising magnesium oxide and an outer layer (i.e. a shell) comprising modified starch and lecithin.

[0041] The microcapsules can be obtained by different methods well known in the art of microencapsulation. Useful examples in the context of the present invention include, but are not limited to, spray drying, fluid bed coating, extrusion (e.g. coextrusion), freeze drying, prilling, powder catch, agglomeration, coacervation, lyposomes and lipidic particles, electrospraying, solvent evaporation, in situ polymerization, complexation, phase separation, layer-by-layer assembly, nucleate, spray congealing (or spray chilling) and the like. Exemplary microencapsulation method are also disclosed in “Microencapsulation: Methods and Industrial Applications” (Drugs and The Pharmaceutical Sciences, Volume 158, Edited by Simon Benita, 2006) and Jyothi et al. “Microencapsulation techniques, factors influencing encapsulation efficiency” (J Microencapsul. 2010 May;27(3): 187-97), incorporated herein by reference.Uses and applications

[0042] Given the improved effects increasing magnesium absorption, sustained effect and low side effects, the composition of the invention is particularly useful for preventing, treating, ameliorating or reducing the risk of conditions or diseases related to magnesium deficiency.

[0043] Thus, one aspect relates to a composition as disclosed herein for the prevention or treatment of a condition or disease related to magnesium deficiency.

[0044] This aspect can be alternatively formulated as the use of a composition as disclosed herein for the manufacture of a pharmaceutical product, a medical food, a food supplement or a food product for the prevention or treatment of a condition or disease related to magnesium deficiency. This may be alternatively formulated as a method for4843-01-8-preventing or reducing the risk of a condition or disease caused by a deficiency of magnesium comprising the administration to a subject in need thereof of a composition as disclosed herein.

[0045] In one embodiment, the condition or disease is selected from the group consisting of weakness, fatigue, tremors, muscle disfunction or aches, arrhythmia, metabolic syndrome and pregnancy. In particular, the prevention or treatment can comprise improving muscular function.

[0046] The composition of the present invention for use in the prevention or treatment of a condition or disease related to magnesium deficiency can prevent the side effects associated with magnesium consumption. In particular, the side effects can be diarrhea, bloating stomach and / or gut discomfort.

[0047] The administration of the composition of the invention can be determined by the ordinary person skilled in medicine or nutrition. The composition can be administered in a single dose or repeated dose at specific time intervals, e.g., can be administered daily for a specific number of days or according to a specific dosing schedule. The composition can be administered, for example from at least 1 week or at least 10 days or at least 1 month. In some embodiments, the composition can administered for from 10 days to 180 days, particularly from 10 to 90 days. More particularly, it is administered for from 10 days to 60 days or from 15 to 45 days.

[0048] In some embodiments, the composition is administered from once every three days to thrice a day, particularly, once a day.

[0049] Of particular interest as a route of administration in the context of the present invention is oral administration.

[0050] In some embodiments, the administration of the composition results in at least one outcome selected from the group consisting of: increasing magnesium absorption; maintaining the duration of magnesium absorption on time; reducing intestinal sensitivity or improving intestinal tolerability; reducing diarrhoea; reducing bloating stomach and / or reducing gut discomfort.Pharmaceutical products and forms

[0051] In one aspect the invention provides a pharmaceutical or veterinary product comprising an effective amount of the composition disclosed herein.

[0052] The term “effective amount” as used herein refers to amount the composition of the present invention that is high enough to significantly modify the condition to be prevented and / or treated in a positive way but low enough to avoid serious side effects (at a reasonable benefit / risk ratio), within the scope of sound medical judgment.4843-01-9-

[0053] The term “pharmaceutical product” or “pharmaceutical form” or “medicament” are used herein interchangeably and is understood in its widely meaning in this description, including any composition that comprises an active ingredient — in this case, the composition of the invention with pharmaceutically acceptable excipients. The term “pharmaceutically acceptable” as used herein pertains to compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of a subject (e.g. human) without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. Each carrier, excipient, etc. must also be “acceptable” in the sense of being compatible with the other ingredients of the formulation. Suitable carriers, excipients, etc. can be found in standard pharmaceutical texts. Selection of the excipients and the most appropriate methods for formulation in view of the particular purpose of the composition is within the scope of ordinary persons skilled in the art of pharmaceutical technology.

[0054] The pharmaceutical product can adopt different forms or names depending on the product approval route and also depending on the country. For instance, a medicament is a particular pharmaceutical product. However, the term “pharmaceutical product" is not limited to refer to products for human administration but includes products for human as well as animal administration (“veterinary products”). In particular, the pharmaceutical products can be a product for administration to mammal subject, more particularly a human subject.

[0055] A medical food is considered in this description as another particular pharmaceutical product. The terms “medical food” or “food for special medical purposes” are used in some countries to refer to a food specially formulated and intended for the dietary management of a disease that has distinctive nutritional needs that cannot be met by normal diet alone. They are defined in regulations such as the Food and Drug Administration's 1988 Orphan Drug Act Amendments in the United States, and the Commission Directive 1999 / 21 / EC in Europe. Medical foods are distinct from the broader category of food supplements and from traditional foods that bear a health claim. Thus, in a particular embodiment, the composition of the invention is a medical food.

[0056] In each case, the presentation of the pharmaceutical product can be adapted to the type of administration used by means known by the person skilled in the art. Thus, the pharmaceutical product may be presented in the form of solutions or any other form of clinically permissible administration and in a therapeutically effective amount. The composition can be thus formulated into solid, semisolid or liquid preparations, such as tablets, capsules, powders (such as those derived from lyophilization (freeze-drying) or4843-01-10-air-drying), granules, powders, solutions, suppositories, gels or microspheres. In a particular embodiment, the composition is formulated for administration in liquid form or in solid form. In one embodiment, the product is formulated in solid form.Food supplements and products

[0057] The invention also provides a food supplement comprising an effective amount of the composition of the present invention, together with acceptable excipients.

[0058] A “food supplement”, also known as dietary supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients or beneficial ingredients that are not usually ingested in the normal diet or may not be consumed in sufficient quantities. Mostly, food supplements are considered as food products, but sometimes they are defined as drugs, natural health products, or nutraceutical products. In the sense of the present invention, food supplements also include nutraceuticals. Food supplements are usually sold “over the counter”, i.e. without prescription. If the food supplement adopts the form of a pill or a capsule, it comprises excipients which are the same as the used in medicaments. The food supplement typically also includes pharmaceutically acceptable ingredients.

[0059] If the composition according to the invention is used as a food supplement, it can be administered as such, can be mixed with a suitable drinkable liquid, such as water, yoghurt, milk or fruit juice, or can be mixed with solid or liquid food. In this context the food supplements can be in the form of tablets, pills, capsules, granules, powders, suspensions, sachets, pastilles, sweets, bars, syrups and corresponding administration forms, usually in the form of a unit dose. Particularly, the composition of the invention can be administered in the form of tablets, capsules or powders, manufactured in conventional processes of preparing pharmaceutical products.

[0060] The composition of the invention can also be included in a variety of food products or edible products. The terms “food product”, “edible product” and “nutritional product” are used herein in its broadest meaning, including any type of product, in any form of presentation, which can be ingested by an animal, i.e., a product that is organoleptically acceptable. The term “food product” is understood as an edible product which also provides a nutritional support for the body. Non-limiting examples of food products include meat products, dairy products, milks from animal or vegetable origin, chocolate spreads, fillings and frostings, chocolate, confectionery, baked goods, sauces and soups, fruit juices, coffee, fermented foods, infant formulas, baby foods, food fortifiers, and the like.

[0061] The present invention will be better understood by reference to the following examples, which serve to illustrate the invention, but not to limit the same.4843-01-11-EXAMPLES EXAMPLE 1

[0062] A clinical trial was conducted to compare the efficacy of various magnesium food supplements:- Mg oxide (MgO)- Mg citrate (Mg-C),- Mg bisglycinate (Mg-BG)- Magnesium oxide microcapsules comprising: 56.6 wt.% magnesium oxide; 42.9 wt.% modified maize starch; 0.5 wt.% sunflower lecithin (Composition of the invention, Mg-Inv).Study population:

[0063] A total of 40 healthy volunteers between 20 and 55 years old, men and women of all races / ethnicities, with a body mass index of 18-35 kg / m2were enrolled in this clinical study. The exclusion criteria for the selection of volunteers were: (i) individuals with gastrointestinal diseases (diabetes, gastritis, Crohn’s disease, celiac disease, ulcers, intolerances, etc.); (ii) individuals with cardiorespiratory diseases (chronic bronchitis, chronic obstructive pulmonary disease, pulmonary emphysema, asthma and bronchiectasis, thrombi, heart disease, heart disorders, arrhythmias, insufficiencies, etc.); (iii) pregnant or lactating women or who plan to become pregnant during the study; (iv) individuals under medical treatment in the weeks prior to the study that could interfere with the evaluations of the present study (according to the investigator’s criteria); (v) individuals who are within a dietary period outside their usual habit; (vi) individuals who are within a dietary period where cannot follow the diet restrictions needed to run this study; (vii) individuals who demonstrate manifest incapacity to understand or follow the protocol or the informed consent; (viii) individuals with allergy or reactivity to any of the components; (ix) individuals surgically operated for a heart condition; (x) individuals with forecast of changing routine or relevant way of life, during the period of the study; (xi) individuals that participated in a clinical study of this type, at least 15 days before the start of this study. Additionally, volunteers were asked to avoid consumption of food supplements, nutricosmetics or specific food containing high levels of Mg during the week before the start of each treatment and during the study. One of the volunteers did not complete the study due to adverse effects upon the oral intake of Mg-BG, and 2 volunteers did not complete the study due to personal reasons;4843-01-12-all these 3 volunteers were replaced, and the data of the replaced volunteers were not considered for the analysis.Study design

[0064] The study was a randomized, double-blind trial to compare the increase of Mg in plasma after the oral intake of the different Mg products. 40 healthy volunteers, women and men, between 20-55 years old were on a low-Mg diet for 7 days, excluding Mg-rich food. The study was divided in 4 stages, each of them corresponding to a specific product (1 week per product). For each product / stage, volunteers were on the low Mg diet for 1 week; then, after an 8-hour (h) fasting, a blood sample was taken from a digital puncture before (0 h) and 1 h, 4 h and 6 h after the oral intake of the product. This 1-week procedure was repeated for all 4 tested products. Blood samples were taken by digital puncture (non-invasive fingerstick procedure, by using VeriFine safety lancets 21 G) for each one of the 40 volunteers. Blood samples were collected in EDTA-containing tubes (Minicollect tube K3E EDTA), centrifuged at 1000 rpm, 5 minutes at 4°C, and plasma (supernatant) was collected and stored at -20°C. During the day of the experiment, volunteers followed a standardized low-Mg diet, consisting of a ham and cheese sandwich after the 1 h time point, and low-mineralization water ad libitum. Magnesium quantification in plasma

[0065] The quantification of the Mg levels in plasma was performed by ICP-MS (Mass Spectrometry with Inductively coupled plasma) with the instrument Agilent ICPMS7900, and expressed as mg L-1. ICP-MS is a type of mass spectrometry that uses an inductively coupled plasma to ionize the sample. It atomizes the sample and creates atomic and small polyatomic ions, which are then detected. It is known and used for its ability to detect metals and several non-metals in liquid samples at very low concentrations. The ICP-MS has been successfully implemented for Mg quantification [Yan, Y. et al. Measurement of Serum Sodium and Magnesium by Inductively Coupled Plasma Mass Spectrometry with Aluminum as Internal Standard. Clin. Lab. 2016, 62 (4), 719-725; Inductively-Coupled Plasma Mass Spectrometry-Novel Insights From an Old Technology Into Stressed Red Blood Cell Physiology. Front. Physiol. 2022, 13, 828087], Self-assessment questionnaire

[0066] Different parameters associated with the products were subjectively evaluated by the volunteers with self-assessment questionnaires (Supplemental information 1). These questionnaires were completed by all volunteers for all the products, gathering information right after the oral intake, and at the end of the day.4843-01-13- Bioavailability of Mg upon oral intake

[0067] Figure 1 shows the Mg levels in plasma for each product at each time point normalized to the baseline (Time Oh, before oral intake), expressed as mg L-1. Figure 1 shows that oral supplementation with Mg-C increased Mg levels in plasma after 4 h by 7.5%, while Mg levels increased at 1 h by 7.1% upon oral intake of MgO. On the other hand, the increase in plasma Mg after oral intake of Mg-BG was not significant at any of the time points evaluated. Most importantly, when volunteers ingested Mg-lnv, the levels of Mg in plasma increased at all tested time-points; specifically, Mg levels increased by 7.9%, 7.5% and 8.8% after 1 h, 4 h and 6 h of the oral intake, respectively. These results show that Mg-lnv outperforms Mg-BG, one of the gold standards in the Mg-based supplement field, in terms of increasing the bioavailability of Mg levels in plasma upon oral intake.

[0068] Most importantly, the dynamics of the levels of Mg in plasma after the oral intake of Mg-lnv was different, since it increased Mg levels at short term (1 h after the ingestion) and kept them significantly higher than the basal time at least up to 6 h. These findings indicate that, compared to the non-encapsulated MgO, Mg-lnv improves the dynamics of Mg release by leading to a sustained increase in Mg bioavailability up to, at least, 6 hours.

[0069] In order to directly compare the efficacy of the tested supplements, the increase on the amount of Mg in plasma after 6 h of the oral intake of each product was compared to their corresponding basal (time 0 h) levels. This increase was calculated in mg L-1and in percentage (%). As we observe in Figure 2 the increase of Mg absorption after 6 h of the oral intake induced by Mg-lnv was higher than that observed for other products, especially compared to MgO.Subjective evaluation of the tested products

[0070] The perception and efficacy of the different tested products were subjectively evaluated using a test (self-assessment questionnaire) right after the oral intake of each product and at the end of the day in which volunteers ingested the products, to evaluate their effects after several hours of the oral intake. In this self-assessment questionnaire, different parameters were evaluated by a subjective category, which is indicated for each specific question. The results at the end of the day of the oral intake are presented in Tables 1 to 3.4843-01-14- Table 1Question: Have you noticed any digestive change?Magnesium Magnesium Magnesium Composition of the Bisglycinate Citrate Oxide invention (Mg-lnv) None 60 65 50 65Some 32.5 27.5 42.5 27.5Many 7.5 7.5 7.5 7.5Table 2Question: Does the supplement increase gastrointestinal transit?Magnesium Magnesium Magnesium Composition of the Bisglycinate Citrate Oxide invention (Mg-lnv)60 47.5 50 60None30 37.5 37.5 27.5Some10 15 12.5 12.5ManyTable 3Question: Have you noticed any side effect directly related with the supplement intake?Magnesium Magnesium Magnesium Composition of the Bisglycinate Citrate Oxide invention (Mg-lnv) None 77.5 75 80 67.5Some 15.5 22.5 20 30Many 52.5

[0071] Of note, Mg-lnv exhibits fewer adverse side effects than other sources of Mg, in terms of increase intestinal flow or full stomach after oral intake. Specifically, volunteers reported increased intestinal flow with MgO and Mg-C, and stomach heaviness with Mg-BG and MgO. 67.5% of the volunteers manifested that they are satisfied with their state of health after consumption of Mg-lnv, a percentage higher than the other Mg products.

[0072] Altogether, the results indicate that Mg-lnv presents fewer side effects compared to the other Mg sources in terms of increased intestinal flow and stomach heaviness, demonstrating that the tested microencapsulation technology decreases the adverse effects usually associated to the ingestion of Mg-based supplements.4843-01-15-

[0073] The invention has been explained in relation to its preferred embodiments, it is to be understood that various modifications thereof will become apparent to those skilled in the art upon reading the specification. Therefore, it is to be understood that the invention disclosed herein is intended to cover such modifications as fall within the scope of the appended claims.

Claims

4843-01-16- CLAIMS:

1. A composition comprising:a) from 30 to 70 wt.% of magnesium oxide;b) from 20 to 60 wt.% of modified starch; andc) from 0.05 to 5 wt.% of lecithin;wherein the sum of the components does not exceed 100 wt.%.

2. The composition of claim 1, wherein the modified starch is selected from the group consisting of thermally treated starch, mechanically treated starch, oxidatively degraded, starch, hydrolytically degraded starch, enzymatically degraded starch.

3. The composition of claim 1 or claim 2, wherein the starch comprises modified maize starch.

4. The composition of any one of the previous claims, wherein the lecithin comprises a sunflower lecithin.

5. The composition of any one of the previous claims, wherein the magnesium oxide is in a concentration of from 40 to 60 wt.%, preferably from 50 to 60 wt.%6. The composition of any one of the previous claims, wherein the modified starch is in a concentration of from 30 to 50 wt.%, preferably from 40 to 45 wt.%.

7. The composition of any one of the previous claims, wherein the lecithin is in a concentration of from 0.1 to 2 wt.%, preferably from 0.1 to 1 wt.%.

8. The composition of any one of the previous claims, wherein the composition is in the form of microcapsules.

9. The composition of claim 8, wherein the microcapsules comprise an internal phase comprising magnesium oxide and an outer layer comprising modified starch and lecithin.

10. A composition according to anyone of the previous claims, for the prevention or treatment or a condition or disease related to magnesium deficiency.

11. The composition for use according to claim 10, wherein the condition or disease is selected from the group consisting of weakness, fatigue, tremors, muscle disfunction or aches, arrhythmia, metabolic syndrome and pregnancy.

12. The composition for use according to claim 10 or 11, wherein the prevention or treatment improves muscular function.

13. The composition for use according to any one of claims 10 to 12, which prevents side effects associated with magnesium consumption.

14. The composition for use according to claim 13, where the side effects include diarrhea, bloating stomach and / or gut discomfort.4843-01-17- 15. A pharmaceutical product comprising an effective amount of a composition according to any one of claims 1 to 9, together with acceptable excipients.

16. A food supplement comprising an effective amount of a composition according to any one of claims 1 to 9, together with acceptable excipients.

17. A food product or edible product comprising an effective amount of a composition according to any one of claims 1 to 9.

18. A method for preventing or reducing the risk of a condition or disease caused by a deficiency of magnesium comprising the administration to a subject in need thereof of a composition according to any one of claims 1 to 9, a pharmaceutical product according to claim 15, a food supplement according to claim 16 or a food product or edible product according to claim 17.

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