Sodium Bicarbonate Dietary Supplement

Abstract

Ingestible particles comprising sodium bicarbonate, the particles having a size in the range of greater than 1.0 mm and less than or equal to 5.0 mm, with at least one dimension having a thickness greater than 1.0 mm and less than or equal to 2.0 mm, and comprising greater than 50% (w / w) sodium bicarbonate, the ingestible particles being included in a dietary supplement composition that is a suspension comprising the ingestible particles dispersed in an aqueous liquid, preferably a viscous aqueous medium.

Description

[Technical field]

[0001] The present invention relates to the use of sodium bicarbonate as a dietary supplement for preventing, reducing or alleviating exercise-induced acidosis and for improving athletic performance. More specifically, the present invention relates to an improved dosage form of sodium bicarbonate useful as a dietary supplement for preventing, reducing or alleviating exercise-induced acidosis and for improving athletic performance. After ingestion, the dietary supplement releases bicarbonate into the bloodstream, where the bicarbonate acts as an extracellular buffer to improve athletic performance. The present invention further relates to an improved dosage form of sodium bicarbonate useful in a pharmaceutical composition for treating metabolic acidosis. [Background technology]

[0002] Various dietary supplements are known to be useful for athletes, see for example WO2019 / 185742A1 and EP2098124A1, which disclose hydrogels. WO2020 / 237340A1 discloses a high-energy dietary supplement based on inverted brown sugar.

[0003] Sodium bicarbonate (NaHCO3) is an established dietary supplement that enhances physical and mental functions. Sodium bicarbonate supplementation can improve high-intensity exercise performance by enhancing the body's extracellular buffering capacity through increased bicarbonate concentration, and various analyses have confirmed its effectiveness (Hadzic et al. The Impact of Sodium Bicarbonate on Performance in Response to Exercise Duration in Athletes: A Systematic Review. 2019. J Sports Sci Med 18: 271-281). Blood bicarbonate is part of the acid-base homeostasis bicarbonate buffer system, which is important in regulating blood pH concentration and supporting metabolic function. NaHCO3, an extracellular buffering agent, improves endogenous bicarbonate buffering capacity by inducing a large increase in extracellular bicarbonate. As a result, hydrogen cations (H + ) and delays muscle fatigue, positively influencing many performance variables such as power output and time to fatigue.

[0004] Sodium bicarbonate supplementation may help prevent, reduce and alleviate exercise-induced acidosis, an imbalance in the body's acid-base balance caused by exercise. Exercise-induced acidosis can lead to acidemia, defined as an arterial blood pH below 7.35. Sodium bicarbonate supplementation may also help prevent, reduce or alleviate exercise-induced acidemia.

[0005] Sodium bicarbonate supplementation may also help treat, including prevent, reduce or alleviate metabolic acidosis, a condition characterized by an imbalance in the body's acid-base balance. Metabolic acidosis is characterized by a plasma bicarbonate level below 22 mmol / l and a blood pH below 7.35 and may be acute and temporary, as when caused by high-intensity exercise, or chronic, as when caused by impaired kidney function (chronic kidney disease, KCD). Acute acidosis causes a temporary impairment of muscle function, whereas chronic acidosis is associated with increased mortality (Adamczak M et al.: Diagnosis and Treatment of Metabolic Acidosis in Patients with Chronic Kidney Disease - Position Statement of the Working Group of the Polish Society of Nephrology. Kidney Blood Press Res 2018;43:959-969. doi: 10.1159 / 000490475). Metabolic acidosis can lead to acidemia, defined as an arterial blood pH below 7.35. Sodium bicarbonate supplementation can also help treat, including prevent, reduce, or alleviate metabolic acidemia.

[0006] US2007 / 0218126A1 discloses a composition for reducing inflammation and pain associated with acidosis, comprising inter alia calcium carbonate. The bilayered particles have a size of about 3 μm.

[0007] Another benefit of sodium bicarbonate may be improved recovery from high-intensity exercise.

[0008] Substantial changes in blood sodium bicarbonate (~6 mmol / l) increase the likelihood of performance-enhancing effects (Heibel et al. Time to optimize supplementation: modifying factors influencing the individual responses to extracellular buffering agents. 2018. Front Nutr 5: 35). Therefore, large oral doses (0.2-0.3 g / kg body weight) are desirable to induce performance-enhancing increases in blood bicarbonate levels.

[0009] However, acute gastrointestinal (GI) disturbances are known side effects of ingesting large amounts of NaHCO3 (Burke & Pyne. 2007. Bicarbonate loading to enhance training and competitive performance. Int J Sports Physiol Perform 2: 93-97), especially when administered as an aqueous solution (Carr et al. 2011. Effect of sodium bicarbonate on [HCO3 - ], pH, and gastrointestinal symptoms. Int J Sport Nutr Exerc Metab 21: 189-194).

[0010] A recent study [Middlebrook et al. 2021. Capsule size alters the timing of metabolic alkalosis following sodium bicarbonate supplementation. Frontiers Nutr 8: 27] investigated the effects of NaHCO3 supplementation using large (5.6 mm or larger) capsules and reported that it had some effect on acid-base response, but no effect on GI symptoms or palatability.

[0011] Furthermore, GI disorders may deter individuals from using NaHCO3 regardless of its potential benefits to enhance physical and mental function (Heibel, supra).

[0012] In conclusion, gastrointestinal disorders such as nausea, vomiting and diarrhea pose major practical limitations to the use of NaHCO3 by athletes.

[0013] It has been suggested that gastro-resistant capsules may alleviate symptoms typical of NaHCO3 ingestion (de Oliveira et al. 2018. Is bypassing the stomach a means to optimize sodium bicarbonate supplementation? A case study with a postbariatric surgery individual. Int J Sport Nutr Exerc Metab 26: 1-4). This is supported to some extent by Hilton et al. 2019. A novel ingestion strategy for sodium bicarbonate supplementation in a delayed-release form: a randomised crossover study in trained males. Sports Med 5: 4, which showed that although the incidence of GI symptoms was low, blood [HCO3 - ] and an undesirable delay in the time to peak pH has been reported.

[0014] Additionally, enteric coating has been proposed as a means to reduce gastric symptoms [Hilton et al. 2020. Enteric-Coated Sodium Bicarbonate Attenuates Gastrointestinal Side-Effects. Int J Sport Nutr Exerc Metab 30: 6268]. Results showed a reduction in GI symptoms, but no significant increase in blood [HCO3 -] and could not demonstrate the desired increase in pH.

[0015] Furthermore, efficient gastroresistant coatings that have been widely studied and used in pharmaceuticals cannot be used in nutritional products, such as NaHCO3, because they use enteric polymers that are not considered natural ingredients by regulatory authorities or do not have GRAS (Generally Regarded as Safe) status (Barbosa et al. 2017. Going natural: using polymers from nature for gastroresistant applications. Br J Pharm 2: 14-30).

[0016] US2013 / 0236545A1 discloses an oral pharmaceutical formulation useful for the treatment of cystinurea when administered together with another formulation containing Krebs cycle precursor salts. The formulation is a bilayer mini-tablet consisting of a core containing at least bicarbonate and at least one sustained release matrix, and a coating containing at least one coating agent to ensure sustained release.

[0017] US 6,432,450 B1 and CN 109430669 A disclose effervescent compositions, i.e. compositions designed to release bicarbonate within seconds in water prior to ingestion, thereby generating carbon dioxide already prior to ingestion.

[0018] RU2550927C2 discloses a cough medicine containing sodium bicarbonate-containing granules for reducing the viscosity of sputum, which suggests that the sodium bicarbonate is pre-released in the oral cavity and released again within a few seconds in water.

[0019] Thus, there is a need for formulations and methods for nutritional intake of sodium bicarbonate NaHCO3 that have significantly reduced GI side effects following ingestion. Summary of the Invention

[0020] It is an object of the present invention to provide a formulation and method for nutritional intake of sodium bicarbonate, NaHCO3, with significantly reduced GI side effects following ingestion.

[0021] A further object is to provide a formulation and method for the nutritional intake of sodium bicarbonate with simultaneous high palatability and high gastrointestinal uptake.

[0022] A further object is to provide formulations and methods for nutritional intake of sodium bicarbonate that facilitate the intake of sufficient amounts of sodium bicarbonate to enhance high intensity exercise performance.

[0023] A further object is to provide formulations and methods for nutritional administration of sodium bicarbonate useful for exercise-induced acidosis or acidemia.

[0024] To these and other objects which will be apparent from the present disclosure, the present invention provides, according to a first aspect, a dietary supplement composition which is a suspension comprising ingestible particles dispersed in a viscous aqueous medium.

[0025] When ingestible particles are dispersed in a viscous aqueous medium, the viscosity of the aqueous medium prevents or delays settling of the ingestible particles until the dispersion is ingested.

[0026] The ingestible particles comprise sodium bicarbonate, the particles having a size in the range of greater than 1.0 mm and less than or equal to 5.0 mm, with at least one dimension having a thickness greater than 1.0 mm and less than or equal to 2.0 mm; the particles comprise greater than 50% (w / w) sodium bicarbonate.

[0027] The inventors have discovered and demonstrated an ingestible particle that achieves efficient uptake of sodium bicarbonate NaHCO3 but with a low incidence of GI side effects. The particle promotes uptake and incorporation of sodium bicarbonate salt in the range of 0.20-0.30 g / kg body weight or more required to achieve substantial changes in blood bicarbonate (4-6 mmol / l) that enhance the potential for performance enhancing effects.

[0028] The inventors have discovered and demonstrated that the ingestible particles achieve efficient uptake of sodium bicarbonate but with low incidence of GI side effects, especially when dispersed in a viscous medium such as a viscoelastic or viscous gel or liquid.

[0029] According to a second aspect, there is provided a kit for preparing a dietary supplement composition, the kit comprising: an ingestible particle as defined herein; and an aqueous medium as defined herein.

[0030] According to further aspects, dietary supplement compositions and kits comprising the ingestible particles are useful for improving high intensity athletic performance. The ingestible particles are useful in dietary supplement compositions for improving high intensity athletic performance.

[0031] According to a further aspect, a method is provided for improving high intensity exercise performance comprising ingesting a dietary supplement composition comprising ingestible particles.

[0032] According to a further embodiment, dietary supplement compositions and kits comprising the ingestible particles are useful for preventing, reducing or alleviating exercise-induced acidosis and / or acidemia. A method for preventing, reducing or alleviating exercise-induced acidosis and / or acidemia in a subject is provided, comprising ingesting a dietary supplement composition comprising the ingestible particles.

[0033] According to a further embodiment, the ingestible particles are useful in dietary supplement compositions for preventing, reducing or ameliorating exercise-induced acidosis and / or acidemia.

[0034] According to a further aspect, the composition and kit comprising the ingestible particles are further useful for treating metabolic acidosis and / or acidemia. This suggests that the composition of the present invention is a pharmaceutical composition. A method of treating metabolic acidosis and / or acidemia in a human subject in need thereof is provided, comprising ingesting a pharmacologic amount of a composition comprising the ingestible particles. The composition and kit of the present invention are useful in a method of treating metabolic acidosis and / or acidemia in a human subject in need thereof, comprising ingesting a pharmacologic amount of a composition comprising the ingestible particles.

[0035] According to a further embodiment, the ingestible particles are further useful for treating metabolic acidosis and / or acidemia. A method of treating metabolic acidosis and / or acidemia in a human subject in need thereof is provided, comprising ingesting a pharmacologic effective amount of the ingestible particles. The ingestible particles are useful in a method of treating metabolic acidosis and / or acidemia in a human subject in need thereof, comprising ingesting a pharmacologic effective amount of the ingestible particles.

[0036] Preferred embodiments and further aspects are defined in the appended claims, the enumerated embodiments and throughout the application. [Brief description of the drawings]

[0037] [Figure 1] FIG. 1 shows normalized plasma bicarbonate concentrations measured before and after ingestion of sodium bicarbonate particles. [Diagram 2] FIG. 2 shows normalized plasma bicarbonate concentrations measured before and after ingestion of sodium bicarbonate particles. [Diagram 3] FIG. 3 shows the uptake of bicarbonate from sodium bicarbonate particles in combination with either high or low viscosity media. [Figure 4] FIG. 4 shows plasma bicarbonate concentrations measured after ingestion of sodium bicarbonate particles. [Diagram 5] FIG. 5 shows a comparison of the dissolution progression of sodium bicarbonate in the form of 0.5-1.0 mm granules and sodium bicarbonate in the form of 1.5×3.0 mm mini-tablets. [Figure 6] FIG. 6 shows the release of NaHCO 3 over time from mini-tablets when dispersed in different media and under different conditions. [Figure 7] FIG. 7 shows a comparison of the viscosity and shear thinning properties of the two media. [Figure 8] FIG. 8 shows a vibration test of a viscoelastic medium. [Figure 9] FIG. 9 shows the effect of blood pH and plasma bicarbonate concentrations in athletes taking a dietary supplement composition of the present invention. Detailed Description of the Invention

[0038] The dietary supplement compositions provided herein are suspensions comprising ingestible particles dispersed in a viscous aqueous medium.

[0039] The ingestible particles comprise sodium bicarbonate and have a well-defined size.The ingestible particles are particles that are useful in themselves in dietary supplement compositions for improving high-intensity exercise performance.The ingestion of NaHCO3 particles according to the present invention can demonstrate a reduction in gastrointestinal side effects seen after the ingestion of the same amount of NaHCO3 in solution or capsule.

[0040] Of course, the ingestible particles are designed to release sodium bicarbonate in the body, and more specifically, to release sodium bicarbonate in the small intestine. The ingestible particles are designed to release sodium bicarbonate prior to the large intestine.

[0041] The ingestible particles comprise sodium bicarbonate salt, the particles having a size in the range of greater than 1.0 mm and less than or equal to 5.0 mm, such as less than or equal to 4.0 mm, and a thickness in at least one dimension of greater than 1.0 mm and less than or equal to 2.5 mm, such as less than or equal to 2.0 mm, such as less than or equal to 1.8 mm; and comprising more than 50% (w / w) sodium bicarbonate. The size of the ingestible particles is typically in the range of 1.2-5.0 mm, and a thickness in at least one dimension of 1.2-2.0 mm.

[0042] A particle size of less than 2.0 mm in at least one dimension is beneficial in providing good palatability while allowing the ingestible particles to pass freely through the pyloric sphincter, thereby shortening gastric transit time. This results in low levels of NaHCO3 dissolution within the gastric chamber, greatly reducing potential upper GI disturbances. The terms "dissolution" and "release" are used interchangeably in this document.

[0043] The ingestible particles do not disintegrate; instead, the sodium bicarbonate is continuously dissolved or eroded from the particle surface over time. This, first, reduces potential upper GI disturbances and, second, and just as important, reduces blood [HCO3 - ] and extend the period of desired elevation of pH.

[0044] The mechanism of sodium bicarbonate uptake in the intestine is Na + / H + This is done through the active uptake of sodium, including exchange. The protons secreted in the intestine thus neutralize the bicarbonate, which forms carbonic acid, and further forms water and CO2. The last emperor is catalyzed by carboanhydrase, located in the luminal wall of the small intestine. The dissolved CO2 diffuses easily through cell membranes and enters the bloodstream. There is no scientific evidence that the transport of bicarbonate ions themselves across cell membranes is important.

[0045] The net effect of these processes is an increase in both sodium and bicarbonate (cations and anions, respectively) and pH of the extracellular fluid (blood and interstitial fluid).

[0046] Over time, bicarbonate is further distributed to other compartments of the body. Most of the alkalizing effect of bicarbonate wears off within 24 to 36 hours as bicarbonate is eliminated by renal secretion.

[0047] Neutralization of bicarbonate in the stomach and small intestine is equivalent in terms of its alkalizing effect on the human body. Although excessive exposure to bicarbonate in the stomach should be avoided, it is believed that some exposure is possible while still maintaining high GI tolerance.

[0048] A partial but limited release of sodium bicarbonate occurs in the stomach. Some of the dissolved sodium bicarbonate reacts with gastric acid to produce carbonic acid / carbon dioxide, most of which is transported to the small intestine.

[0049] Preferably, substantially all of the sodium bicarbonate in the particles is completely dissolved and can be taken up into the blood before exiting the small intestine, thereby preventing release of sodium bicarbonate in the large intestine and reducing potential GI discomfort.

[0050] Thus, the ingestible particles could be used as a dietary supplement to enhance high-intensity exercise performance without the risk of severe GI upset observed with other types of NaHCO3 preparations.

[0051] It is preferred to contain more than 65% (w / w) sodium bicarbonate, such as more than 75% (w / w), for example 80% (w / w) or more sodium bicarbonate.

[0052] It is also preferred to contain less than 90% (w / w) sodium bicarbonate, for example 85% (w / w) or less sodium bicarbonate.

[0053] Preferably, each ingestible particle contains less than 80 mg of sodium bicarbonate, such as less than 50 mg, preferably less than 30 mg, more preferably less than 20 mg. More preferably, each ingestible particle contains more than 5 mg of sodium bicarbonate, such as more than 10 mg, preferably more than 15 mg. Typically, each tablet contains between 5 and 30 mg, such as between 10 and 20 mg, for example between 15 and 20 mg of sodium bicarbonate.

[0054] The ingestible particles have a thickness of 2.5 mm or less, for example 2.0 mm or less, in at least one dimension. It has been demonstrated herein that athletes find particles with a thickness of 2.0 mm or less, for example 1.5 mm, to be significantly easier to swallow than particles with a thickness of more than 2.0 mm, for example 2.3 mm. Palatability can be further improved by combining the particles with ingested viscous liquid. Furthermore, a thickness of 2.5 mm or less, for example 2.0 mm or less, is believed to allow the particles to pass through the pyloric sphincter and leave the stomach relatively freely, thus reducing the risk of GI disorders in the stomach.

[0055] Ingestable particles preferably have a thickness of 1.8 mm or less, for example 1.6 mm or less, preferably 1.5 mm or less in at least one dimension.These dimensions ensure good palatability and at the same time, the ingestible particles can freely pass through the pyloric sphincter, which is beneficial in shortening the gastric transit time.This reduces the dissolution level of NaHCO3 in the gastric chamber, which greatly reduces the possibility of GI disorders.

[0056] The ingestible particles may have a thickness of more than 1.0 mm, preferably 1.2 mm or more, for example 1.5 mm or more, in at least one dimension. It has been demonstrated that thin particles (0.5 mm or less) can lead to a faster dissolution time in the gastric chamber and cause GI disturbances. It has also been demonstrated herein that particles having a size of 0.5-1.0 mm are associated with moderate GI symptoms. The lower limit of thickness ensures that the degree of dissolution in the mouth is minimized and the release rate in the stomach is appropriately attenuated without the need for enteric coating. The ingestible particles, e.g. tablets or mini tablets, are preferably not layered. This means that the particles are essentially homogeneous and do not contain a coating. Thus, the particles are not multi-layered. Preferably, the ingestible particles are non-layered, non-coated tablets. This is beneficial for efficient release of sodium bicarbonate salt in the small intestine, so that the bicarbonate contained therein becomes incorporated into the blood. Typically, the sodium bicarbonate contained in the ingestible particles is completely dissolved within 3 hours after ingestion, preferably within 2 hours after ingestion. Slow dissolution, for example over 4 hours, can result in the release of sodium bicarbonate in the large intestine, causing undesirable lower GI symptoms such as diarrhea.

[0057] The ingestible particles preferably have a size of 4.0 mm or less, such as 3.5 mm or less, such as 3.0 mm or less, such as 2.0 mm or less, or even 1.8 mm or less, or 1.6 mm or less. Suitable particle sizes are, for example, 1.2 to 4.0 mm, such as 1.2 to 3.0 mm, such as 1.2 to 2.0 mm or 1.2 to 1.8 mm. These dimensions ensure good palatability with sufficient nutritional intake of bicarbonate. Large particle sizes of more than 5.0 mm, such as large capsules, are more difficult to consume, especially for performing athletes.

[0058] The ingestible particles are preferably spheroidal in shape. Typically, the ingestible particles may have a curvature such that the height of the side is less than the overall thickness. Preferred forms of the ingestible particles include pellets, beads, tablets and granules. Particularly preferred forms are tablets or mini-tablets.

[0059] In certain embodiments, the substantially spherical particles have a diameter / thickness ratio of 3:2 to 3:1, or 1:3 to 2:3.

[0060] In one embodiment, the ingestible particles are tablets or mini-tablets with a thickness of more than 1.0 mm and not more than 2.0 mm and a diameter of more than 1.0 mm and not more than 5.0 mm, for example, a thickness of 1.2-2.0 mm and a diameter of 1.2-5.0 mm. The tablets preferably have a thickness of 1.8 mm or less, for example 1.6 mm or less, preferably 1.5 mm or less. These dimensions ensure good palatability while at the same time allowing the tablet to pass freely through the pyloric sphincter, which is beneficial in shortening the gastric transit time. This results in a lower level of dissolution of NaHCO3 in the gastric chamber, which significantly reduces the possibility of GI disturbance. The thickness of the tablets is more than 1.0 mm, most preferably 1.2 mm or more. It has been demonstrated herein that thinner particles (0.5 mm or less) are associated with faster dissolution times in the gastric chamber, which may cause GI disturbance. It has also been demonstrated herein that particles with a size of 0.5-1.0 mm are associated with moderate GI symptoms. The tablets preferably have a diameter of 4.0 mm or less, such as 3.5 mm or less, such as 3.0 mm or less, such as 2.0 mm or less, or even 1.8 mm or less or 1.6 mm or less. Suitable tablet diameters are, for example, 1.2 to 4.0 mm, such as 1.2 to 3.0 mm, such as 1.2 to 2.0 mm or 1.2 to 1.8 mm. These dimensions ensure good palatability with sufficient nutritional intake of sodium bicarbonate. Large tablets over 5.0 mm are difficult to ingest, especially for performing athletes.

[0061] It is preferred that the particles, e.g. tablets or mini-tablets, are non-disintegrating. Because the ingestible particles do not disintegrate, the sodium bicarbonate will continually dissolve or erode from the particle surface over time. This reduces the potential for GI upset and reduces blood [HCO3 - ] and the desired increase in pH is sustained for an extended period of time.

[0062] The ingestible particles are less dissolved in the mouth and stomach. This reduces the possibility of GI disturbances. As the particles remain in the stomach for a significantly longer time, more sodium bicarbonate is released in the stomach than in the mouth. A suitable delay in the release of sodium bicarbonate from the ingestible particles can be advantageously achieved by incorporating the ingestible particles in a viscous medium, such as a gel or other viscoelastic medium.

[0063] The contained sodium bicarbonate dissolves completely before leaving the small intestine, which means that the contained sodium bicarbonate can be taken up into the blood. Typically, the sodium bicarbonate contained in the ingestible particles dissolves completely within 3 hours after ingestion, preferably within 2 hours after ingestion. As demonstrated in the examples, this is advantageous compared to, for example, larger capsules, since it ensures that the sodium bicarbonate can be taken up into the blood. Preferably, after ingestion of the ingestible particles, the time to reach 90% of the maximum plasma bicarbonate concentration (T90%max) is less than 3 hours after ingestion. Slow dissolution and the associated high T90%max, for example more than 4 hours, will result in the release of sodium bicarbonate in the large intestine, which will cause undesirable lower GI symptoms such as diarrhea. It is preferred that the ingestible particles do not have any enteric coating, as this will slow down the dissolution and the associated T90%max. Therefore, it is preferred that the ingestible particles are free of coating.

[0064] In addition to the sodium bicarbonate salt, the ingestible particles may include excipients that together with the sodium bicarbonate salt amount to up to 100% (w / w). Thus, the ingestible particles may further include at least one of a binder, a lubricant, and a glidant. The ingestible particles may include additional excipients.

[0065] In certain embodiments, the ingestible particles further comprise a binder, typically in an amount of 1-50% (w / w), such as 1-30% (w / w) or 1-15% (w / w). The binder component is selected to meet the requirements for sustained release of sodium bicarbonate by erosion of the particles, as described above. Preferred binders are selected from polyvinylpyrrolidone (PVP), calcium carbonate, calcium phosphate, hydroxypropylcellulose (HPC) and polysaccharides, and combinations thereof. Further preferred binders are microcrystalline cellulose and gelatin, which may be combined as described above. Preferred polysaccharide binders are selected from high molecular weight alginates, pectin, gum tragacanth and gum acacia, and combinations thereof, such as high molecular weight alginates, pectin and gum acacia, and combinations thereof. In certain embodiments, the binder is selected from calcium carbonate and gum acacia, and combinations thereof. In one preferred embodiment, the binder comprises HPC. HPC provides good mechanical stability to the particles. In certain preferred embodiments, the binder is HPC; for example, in an amount of 1-30% (w / w), 1-15% (w / w), or 5-15% (w / w) of the ingestible particle. In certain embodiments, the binder is selected from HPC and gum acacia, and combinations thereof.

[0066] In certain embodiments, the ingestible particles further comprise a lubricant, typically in an amount of 0.1-10% (w / w), for example 1-5% (w / w). Preferred lubricants are selected from stearic acid, magnesium stearate, sodium stearyl fumarate, and combinations thereof. In certain embodiments, the lubricant is magnesium stearate.

[0067] In certain embodiments, the ingestible particles further comprise a glidant, typically in an amount of 0.1-5% (w / w), for example 1-3% (w / w). A preferred glidant is fumed silica (anhydrous colloidal silica).

[0068] In certain embodiments, the ingestible particles further comprise a further excipient selected from sugars and complex carbohydrates, typically in an amount of 1-50% (w / w), such as 1-40% (w / w), for example 1-30% (w / w), such as 1-20% (w / w), for example 1-10% (w / w). Preferred sugars are selected from glucose, fructose, sucrose and isomaltulose, typically in an amount of 1-50% (w / w), such as 1-40% (w / w), for example 1-30% (w / w), such as 1-20% (w / w), for example 1-10% (w / w). Preferred complex carbohydrates are selected from maltodextrin, dried glucose syrup and dried fructose syrup, typically in an amount of 1-50% (w / w), such as 1-40% (w / w), for example 1-30% (w / w), such as 1-20% (w / w), for example 1-10% (w / w).

[0069] The ingestible particles preferably have one of the following compositions (totaling 100% by weight): (A) 75-85% by weight sodium bicarbonate; 5-10% by weight calcium carbonate; 5-10% by weight hydroxypropyl cellulose; 0.1-1.0% by weight maltodextrin; 1-3% by weight acacia gum; 1-3% by weight magnesium stearate; and 0.1-1.0% by weight anhydrous colloidal silica, (B) 82-92% by weight of sodium bicarbonate; 5-15% by weight of hydroxypropylcellulose; 1-3% by weight of magnesium stearate; and 0.1-1.0% by weight of anhydrous colloidal silica, (C) 80-90% by weight sodium bicarbonate; 5-15% by weight calcium phosphate; 1-5% by weight gum acacia; 1-3% by weight magnesium stearate; and 0.1-1.0% by weight anhydrous colloidal silica.

[0070] Preferably, the compositions of the present invention are formulated as mini-tablets with a diameter in the range of 1.2-5.0 mm and a thickness in the range of 1.2-2.0 mm.

[0071] The dietary supplement composition is a suspension that comprises ingestible particles dispersed in an aqueous medium.The ingestible particles are preferably suspended in an aqueous medium to facilitate ingestion and improve palatability.The aqueous medium may be, for example, a viscous solution or a colloidal suspension.

[0072] The ingestible particles are preferably freshly dispersed in an aqueous medium immediately prior to ingestion to prevent undesired dissolution of the sodium bicarbonate prior to ingestion. The resulting suspension is preferably ingested within 15 minutes of preparation. The amount of sodium bicarbonate released prior to ingestion should be as low as possible, preferably less than 20% of the total amount ingested, e.g., less than 15% of the total amount ingested.

[0073] To facilitate ingestion and improve palatability, the aqueous medium is preferably a viscous aqueous medium, e.g. a viscous aqueous liquid, e.g. a viscous aqueous solution. Preferably, the viscous aqueous medium is a viscoelastic medium. A preferred viscoelastic medium is a gel. The viscous aqueous medium may be a viscous liquid. Because sodium bicarbonate is dense, ingestible particles containing it in amounts up to 85% or more will also be dense. When these particles are dispersed in water, they will rapidly settle to the bottom of the container. The viscosity of the medium must be high enough to prevent the ingestible particles from settling when dispersed in the viscous medium until the dispersion is ingested. The settling velocity of a single ingestible particle in an unstirred viscous aqueous medium is preferably less than 70 mm / min, e.g. less than 20 mm / min, e.g. less than 10 mm / min. The settling velocity of mini-tablets in a medium of medium viscosity, such as in Example 2, is about 60 mm / min (see Example 8). Particularly preferably, the settling velocity of a single ingestible particle in an unstirred viscous aqueous medium is less than 5 mm / min, preferably less than 2 mm / min, more preferably less than 1 mm / min. As shown in Example 1, the settling velocity of a mini-tablet in a viscous medium is less than 0.5 mm / min (see Example 8). It is also demonstrated herein (Figure 3) that by using a high viscosity medium, a faster uptake of sodium bicarbonate is achieved during the first 90 minutes after ingestion, presumably due to faster emptying of the particles from the stomach. Furthermore, the viscous medium improves the palatability of the composition, allowing the particles to be easily ingested and not left behind in the container. An additional advantage of the viscous medium is that it slows down the mixing of the medium upon ingestion, thereby reducing the erosion rate of the tablets in the dietary supplement composition.

[0074] Without wishing to be limited to any particular theory, it is believed that the viscous medium prevents the particles from being directly exposed to the highly acidic environment of the stomach wall where hydrochloric acid is excreted, thereby protecting the integrity of the particles and preventing or reducing gastrointestinal problems that may otherwise occur.

[0075] The interactive combination of ingestible sodium bicarbonate particles and viscous aqueous medium in the dietary supplement composition of the present invention prevents acidosis, including exercise-induced acidosis, in a surprisingly efficient manner.The size of the ingestible particles allows both to facilitate ingestion and improve palatability, and to significantly reduce GI side effects.The viscous aqueous medium not only disperses the particles in the medium to facilitate the ingestion of sufficient amounts of sodium bicarbonate, but also delays the release of sodium bicarbonate from the particles both before ingestion and in the stomach.It is believed that the viscous aqueous medium delays the release of sodium bicarbonate from the ingested mini-tablets until the composition reaches the small intestine and is effectively absorbed.

[0076] In one advantageous embodiment of the dietary supplement composition, the viscous aqueous medium is a viscoelastic medium, preferably in the form of a gel. The mini-tablets are dispersed in the viscoelastic medium before the combined product is ingested. Preferably, the viscoelastic medium is a gel, such as an aqueous semi-solid gel with viscoelastic properties. The viscoelastic medium prevents settling and promotes the ingestion of the particles. An additional advantage of the viscoelastic medium is that it slows down the mixing of the medium, for example, upon ingestion, thereby reducing the erosion rate of the tablets in the dietary supplement composition. As shown in Example 7, the viscoelastic medium is believed to be useful for substantially delaying the release of NaHCO3 from the mini-tablets until the composition is ingested.

[0077] One of the properties of viscoelastic media is that they have shear thinning or pseudoplastic properties: compared to media that are viscous but not viscoelastic, viscoelastic media are viscous when at rest, but become less viscous when flowing at high velocity or when agitated, such as when swallowed.

[0078] Referring to Example 9 and FIG. 7, the viscosity can be measured, for example, at 20° C. using a shear rate controlled rheometer (Model 302, Anton Paar, Germany) using a parallel plate geometry (plate diameter 50 mm, gap 100 μm). With this setup, the viscosity of water ranges from 0 to 100 s -1For the avoidance of doubt, a viscous aqueous medium as defined herein is one that is significantly more viscous than water. A viscous aqueous medium as defined herein is typically one that is more viscous than water at shear rates between 0 and 100 s. -1 Shear rate between 40s -1 Preferably, the aqueous medium as defined herein has a viscosity of at least 50 mPa·s, for example at least 100 mPa·s. -1 Shear rate between 40s -1 In addition to the viscous properties, a viscoelastic medium as defined herein typically exhibits a viscosity of at least 300 mPa·s, such as at least 500 mPa·s, at 20°C. -1 Shear rate is 0 to 10 s -1 Viscoelastic media as defined herein typically exhibit a high viscosity at shear rates of 5s -1 At a shear rate of 40 s -1 The viscosity of the aqueous medium is at least twice the shear rate of the ingestible particles. The specific values ​​given above relate to this particular setup, but the skilled person can easily determine the corresponding values ​​of viscosity and viscoelasticity in other experimental setups by referring to Example 9. For the avoidance of doubt, the determined viscosity value refers to the viscous aqueous medium prior to combination with the ingestible particles, when this property can be determined by this experimental setup.

[0079] The viscoelastic medium (vehicle) is advantageous, for example, to slow down the mixing of the medium upon ingestion, thereby reducing the rate of tablet erosion in dietary supplement compositions. Upon contact with water, bicarbonate is released from the mini-tablets in a controlled manner. If the mini-tablets are surrounded by a viscoelastic medium, the release is slower than in low viscosity liquids due to the stagnation of water near the tablet. In the stomach, the viscoelastic medium also functions to some extent as a barrier against gastric juices.

[0080] Gels are generally described as colloids in which a dispersed phase combines with a dispersion medium to produce a semi-solid material with both viscous and elastic properties, with the elastic properties predominating. Viscoelastic properties are expressed as a function of strain (γ, dimensionless) and stress (τ, N / m 2) is measured. Between a phase shift of 45° and 90°, fluid properties dominate, whereas between a phase shift of 0° and 45°, elastic properties typical of gels dominate. The complex shear modulus is described as a vector G with normal components G' (storage of elastic energy, storage modulus) and G'' (energy loss by viscous dissipation, loss modulus). Gels are therefore characterized by G' being greater than G''. When G' (storage modulus related to the solid-like response part of the material) becomes higher than G'' (loss modulus related to the liquid-like response of the material), the system becomes gel-like at a certain frequency.

[0081] Gelled products are characterized by a relatively soft, chewy texture. Typical gelling products include gelatin-based products as well as products based on certain types of carrageenans, alginates, starches, agarose, β-glucans, gellan gum, pectin or cellulosics. In general, gels can be described as colloids in which the dispersed phase combines with the dispersion medium to produce a semi-solid material, e.g., a jelly.

[0082] In gels, despite their high density, the gel structure prevents settling / settling of the tablets. Gels also contribute to improving the perceived palatability of the dietary supplement composition. Thus, gels also facilitate the intake of mini-tablets.

[0083] For the avoidance of doubt, the sodium bicarbonate-containing ingestible particles do not constitute the dispersed phase of the gel system. The sodium bicarbonate-containing ingestible particles are themselves dispersed in the gel. The gel can be described as a colloid in which the dispersed phase (not the sodium bicarbonate-containing ingestible particles) combines with the dispersion medium to produce a semi-solid material.

[0084] In a particular embodiment, the viscous aqueous medium comprises one or more natural polymers dissolved in water as thickeners. Preferred natural polymers are selected from polysaccharides such as native and modified starches, xanthan gum, guar gum, carrageenan, alginates, pectins, and combinations thereof. Modified starches impart viscoelastic properties with good stability to the medium. A preferred modified starch is acetylated distarch adipate, preferably in an amount of more than 2% by weight, for example more than 3% by weight, of the viscous aqueous medium, to obtain very useful viscoelastic properties. To obtain high palatability, it is advantageous to combine starch with a small amount of a stronger thickener, such as xanthan gum. Preferred natural polymers are: (a) native or modified starch; and (b) Xanthan gum or guar gum The relative weight ratio of (a):(b) is 99:1 to 90:10.

[0085] In a preferred embodiment, the viscous aqueous medium contains starch or modified starch as the natural polymer, preferably modified starch, which is degraded by amylase, thereby weakening the gel and facilitating the release of sodium bicarbonate from the mini-tablets in the small intestine. The release of bicarbonate is accelerated and is expected to be complete before the mini-tablets reach the colon.

[0086] In some embodiments, the viscous aqueous medium comprises one or more sugars or complex carbohydrates dissolved in water.Preferred sugars are selected from glucose, fructose, sucrose and isomaltulose.Preferred complex carbohydrates are selected from starch, maltodextrin, glucose syrup and fructose syrup.

[0087] The viscous aqueous medium may preferably have one of the following compositions (100% by weight with water): (A) 4-12% by weight maltodextrin, 3-10% by weight fructose, 2-7% by weight acetylated distarch adipate, and 0.1-1.0% by weight xanthan gum; (B) 6-14% by weight maltodextrin, 2-5% by weight fructose, 1-3% by weight acetylated distarch adipate, and 0.1-1.0% by weight xanthan gum.

[0088] In some embodiments of the dietary supplement composition, the total amount of sodium bicarbonate salt in the ingestible particles in a single serving is greater than 10 g, preferably greater than 15 g. In some embodiments of the dietary supplement composition, the total amount of sodium bicarbonate salt in the ingestible particles in a single serving is less than 50 g, preferably less than 40 g, more preferably less than 30 g.

[0089] In one embodiment, the dietary supplement composition is a suspension comprising ingestible particles dispersed in an aqueous medium. The size of the particles ranges from 1.2 to 5.0 mm, with at least one dimension having a thickness of 1.2 to 2.0 mm. The particles comprise more than 65% (w / w) sodium bicarbonate salt. The ingestible particles are suspended in a viscous medium comprising, for example, maltodextrin dissolved in water and a sugar, such as fructose, to facilitate intake and improve palatability.

[0090] Also provided is a kit for preparing a dietary supplement composition. The kit comprises ingestible particles as defined herein; and an aqueous medium as defined herein. The kit is useful for preparing a dietary supplement composition as a suspension comprising ingestible particles dispersed in an aqueous medium. The resulting dietary supplement composition is useful for improving high-intensity athletic performance. In some embodiments, the total amount of sodium bicarbonate salt in the ingestible particles in one serving is greater than 10 g, preferably greater than 15 g. In some embodiments of the dietary supplement composition, the total amount of sodium bicarbonate salt in the ingestible particles in one serving is less than 50 g, preferably less than 40 g, more preferably less than 30 g.

[0091] According to a further aspect, the ingestible particles are useful in dietary supplement compositions for improving high intensity exercise performance. In particular, the ingestible particles are useful in dietary supplement compositions disclosed herein for improving high intensity exercise performance.

[0092] It is understood that dietary supplement compositions and kits that include ingestible particles are useful for preventing, reducing or alleviating exercise-induced acidosis and / or acidemia. The ingestible particles are themselves useful for preventing, reducing or alleviating exercise-induced acidosis and / or acidemia. Sodium bicarbonate supplementation can also help prevent, reduce or alleviate exercise-induced acidosis, i.e., an imbalance in the acid-base balance in the body caused by exercise. Exercise-induced acidosis can cause acidemia, which is defined as an arterial blood pH below 7.35. Sodium bicarbonate supplementation can also help prevent, reduce or alleviate exercise-induced acidemia.

[0093] According to a further aspect, there is provided a method for improving high-intensity exercise performance, comprising ingesting a dietary supplement composition comprising ingestible particles.Specifically, the dietary supplement composition is as defined herein.Preferably, the dietary supplement composition is freshly prepared by mixing ingestible particles with an aqueous medium immediately before ingestion, for example less than 5 minutes before ingestion.This ensures that the particles are essentially intact and do not dissolve when ingested.

[0094] Methods are provided for preventing, reducing or alleviating exercise-induced acidosis and / or acidemia in a subject, comprising ingesting a dietary supplement composition comprising ingestible particles.Typically, the ingestible particles comprise a total amount of 0.10-0.40 g bicarbonate per kg body weight; preferably 0.20-0.35 g bicarbonate per kg body weight; preferably 0.25-0.30 g bicarbonate per kg body weight.

[0095] In a preferred use or method as defined herein, ingestible particles are ingested comprising a total amount of 0.10-0.40 g sodium bicarbonate salt per kg body weight; preferably 0.20-0.35 g sodium bicarbonate salt per kg body weight; 0.25-0.30 g sodium bicarbonate salt per kg body weight. It is preferred that a sufficient amount of sodium bicarbonate is ingested to achieve an increase in blood sodium bicarbonate concentration of at least 5 mmol / l, such as at least 6 mmol / l. However, it has already been recognized that depending on the circumstances, it may be useful to increase blood bicarbonate concentration by 1 mmol / l, 2 mmol / l, 3 mmol / l or 4 mmol / l.

[0096] According to further aspects, the compositions and kits comprising the ingestible particles are further useful for treating metabolic acidosis and / or acidemia, i.e., conditions characterized by an imbalance in the acid-base balance in the body. This suggests that the compositions are pharmaceutical compositions. Metabolic acidosis can cause acidemia, which is defined as an arterial blood pH below 7.35. Clinically, metabolic acidosis can be caused by increased acid production, loss of bicarbonate, or a reduced ability of the kidneys to excrete excess acid.

[0097] Acute metabolic acidosis, lasting minutes to days, often occurs during critical illness or hospitalization and is generally caused by the body producing excess amounts of organic acids (ketoacids or lactic acid). A state of chronic metabolic acidosis, lasting weeks to years, may be the result of impaired kidney function (chronic kidney disease) or bicarbonate wasting. The adverse effects of acute and chronic metabolic acidosis also differ, with acute metabolic acidosis affecting the cardiovascular system in the hospital environment and chronic metabolic acidosis affecting muscle, bone, kidney, and cardiovascular health.

[0098] Methods of treating metabolic acidosis and / or acidemia in a human subject in need thereof are provided, comprising ingesting a pharma- ceutically effective amount of a composition comprising ingestible particles. Dietary supplement compositions and kits are useful in methods of treating metabolic acidosis and / or acidemia in a human subject in need thereof, comprising ingesting a pharma- ceutically effective amount of a composition comprising ingestible particles. Metabolic acidosis and / or acidemia may be caused by chronic kidney disease. Typically, ingestible particles are ingested comprising a total amount of 0.01-0.10 g of bicarbonate per kg body weight; preferably 0.02-0.07 g of bicarbonate per kg body weight; preferably 0.02-0.04 g of bicarbonate per kg body weight. In preferred embodiments, this corresponds to a daily dosage. In some embodiments, the daily amount of sodium bicarbonate salt in the ingestible particles is greater than 1 g, preferably greater than 2 g. In some embodiments of the composition, the daily amount of sodium bicarbonate salt in the ingestible particles is less than 5 g, preferably less than 4 g, more preferably less than 3 g, e.g., 2-5 g, 3-5 g, or 2-3 g per day. It may be desirable to take the entire daily dose at once, and the compositions disclosed herein reduce the associated risk of gastrointestinal disorders.

[0099] Additionally, the ingestible particles are themselves useful for treating metabolic acidosis and / or acidemia. Methods of treating metabolic acidosis and / or acidemia in a human subject in need thereof are provided, comprising ingesting a pharmacologic effective amount of the ingestible particles. The ingestible particles are useful in methods of treating metabolic acidosis and / or acidemia in a human subject in need thereof, comprising ingesting a pharmacologic effective amount of the ingestible particles. The metabolic acidosis and / or acidemia may be caused by chronic kidney disease. Typically, ingestible particles are ingested comprising a total amount of 0.01-0.10 g bicarbonate per kg body weight; preferably 0.02-0.07 g bicarbonate per kg body weight; preferably 0.02-0.04 g bicarbonate per kg body weight. In preferred embodiments, this corresponds to a daily dosage. In some embodiments, the daily amount of sodium bicarbonate salt in the ingestible particles is greater than 1 g, preferably greater than 2 g. In some embodiments of the composition, the daily amount of sodium bicarbonate salt in the ingestible particles is less than 5 g, preferably less than 4 g, more preferably less than 3 g, e.g., 2-5 g, 3-5 g, or 2-3 g per day. It may be desirable to take the entire daily dose at once, and the ingestible particles disclosed herein reduce the associated risk of gastrointestinal disorders. EXAMPLES

[0100] The invention will now be further illustrated by the following non-limiting examples.

[0101] Example 1 Minitablets with a diameter of 3.0 mm, height of 1.5 mm and average weight of 18 mg were prepared with the following composition: NaHCO3 85% by weight, calcium phosphate 10% by weight, gum acacia 2.5% by weight, magnesium stearate 2% by weight, and anhydrous colloidal silica 0.5% by weight. The ingredients were mixed in a Turbula mixer. Tablets were compressed using a Fette 52i rotary press equipped with a forced feeder.

[0102] Participants had breakfast at least 3 hours before ingesting the sodium bicarbonate mini-tablets and vehicle. A viscous vehicle was prepared by mixing 22 g maltodextrin, 16 g fructose, 12 g acetylated distarch adipate, and 0.4 g xanthan gum and mixing this mixture with 300 g water. The mixture was ready to use 10 minutes after mixing. A sodium bicarbonate mini-tablet equivalent to 0.3 g sodium bicarbonate per kg body weight was added to the mixture, and all was ingested within 5 minutes.

[0103] Arterialized capillary blood samples were collected before ingestion and at 30, 60 or 120 min intervals up to 8 h after ingestion. Blood samples were immediately analyzed on a blood gas analyzer.

[0104] Figure 1 shows the normalized plasma bicarbonate concentrations (mean + / - SD, n=4) measured before and after ingestion of the mini-tablets, corresponding to 0.30 g NaHCO3 / kg body weight ingested with 350 g of viscous drink.

[0105] At least 90% of peak bicarbonate concentration was reached at 120 min. The maximal increase from t=0 was approximately 7 mmol / l.

[0106] Example 2 The same mini-tablets as in Example 1 were used.

[0107] Participants had breakfast at least 3 hours before ingesting the sodium bicarbonate mini-tablets and vehicle. A viscous vehicle was prepared by mixing 33 g maltodextrin, 11 g fructose, 5.4 g acetylated distarch adipate, and 0.6 g xanthan gum and mixing this mixture with 300 g water (medium viscosity). A sodium bicarbonate mini-tablet equivalent to 0.3 g sodium bicarbonate per kg body weight was added to the mixture, and all was consumed within 5 min. A snack consisting of two rice cakes with almond butter and a drink of 26 g maltodextrin and 13 g fructose dissolved in 300 g water was consumed in 60 min.

[0108] On one of two experimental days (dashed lines in Figure 2), participants underwent three 20-min bouts of high-intensity interval training (HIIT) exercise, beginning approximately 3, 5, and 7 hours after sodium bicarbonate ingestion. Arterialized capillary blood samples were collected before and up to approximately 8.5 hours after ingestion.

[0109] FIG. 2 shows the normalized plasma bicarbonate concentrations measured before and after ingestion of a mini-tablet equivalent to 0.30 g NaHCO3 / kg body weight together with 350 g of a viscous drink (medium viscosity). Solid line: rest or low-intensity exercise (walking) condition. Dashed lines: rest and low intensity exercise interrupted by three 20 min high intensity interval training (HIIT) sessions, starting approximately 180, 300 and 420 min after blood draw, respectively.

[0110] Plasma bicarbonate was decreased by the HIIT session but recovered prior to the next HIIT session and at the end of the study compared to plasma short-chain bicarbonate levels during rest / low-intensity exercise conditions (Figure 2).

[0111] Example 3 Mini-tablets as in Examples 1 and 2 were used in combination with either a high viscosity vehicle as in Example 1, or a medium viscosity vehicle as in Example 2. The mixtures containing mini-tablets equivalent to 0.30 g sodium bicarbonate per kg body weight were ingested 2.5-3.5 hours after a standard breakfast. Standardized bicarbonate levels in arterialized capillary blood were monitored immediately before and after ingestion.

[0112] Figure 3 shows the bicarbonate uptake from mini-tablets combined with either a high viscosity medium (solid lines B and C) or an intermediate viscosity medium (dashed line A). For samples A and B, a snack was consumed after 60 minutes. For sample C, no snack was consumed.

[0113] As can be seen in Figure 3, normalized bicarbonate levels in arterialized capillary blood monitored immediately before and after ingestion showed that bicarbonate uptake was faster during the first 120 min after ingestion when using a high viscosity medium (B and C), presumably due to faster gastric emptying. A snack consumed 60 min later (consisting of two rice cakes with almond butter and a drink of 26 g maltodextrin and 13 g fructose in 300 g water) influenced bicarbonate uptake over the following 90–120 min (A and B).

[0114] Example 4 Different sodium bicarbonate formulations were each combined with vehicle and ingested 1-4 times by 2-6 subjects. Perceived palatability was recorded 6 hours after ingestion, as well as perceived upper and lower gastrointestinal symptoms. Standardized bicarbonate concentrations in capillary blood were monitored before ingestion and up to at least 210 minutes after ingestion. Results are summarized in Table 1. Examples of bicarbonate levels from a single experiment are shown in Figure 4.

[0115] FIG. 4 shows plasma bicarbonate levels measured in two different subjects after ingestion of: A: Sodium bicarbonate dissolved in 480 mL of water containing 33 g maltodextrin and 17 g sucrose; B: Sodium bicarbonate powder (<0.3 mm) mixed with vehicle as in Example 1 immediately before ingestion D1 and D2: Two identical experiments with sodium bicarbonate minitablets and a viscous medium as in example 1.

[0116] Table 1 Perceived palatability and GI symptoms following ingestion of various bicarbonate and vehicle formulations, and time to reach 90% of maximum plasma bicarbonate concentration (T90%max). A: Sodium bicarbonate dissolved in a low viscosity medium (33 g sucrose, 17 g maltodextrin, 480 ml water) B: Sodium bicarbonate powder added to a high viscosity medium immediately prior to ingestion C: Sodium bicarbonate granules D and E: Mini-tablets as in Examples 1 to 3, containing 85% sodium bicarbonate F: Placebo mini-tablets replacing sodium bicarbonate with calcium carbonate (50%) and maltodextrin (35%) G: Minitablets as in Examples 1 to 3, where calcium phosphate and gum acacia are replaced by 10% by weight of PVP. The sodium bicarbonate content is 87.5% by weight. H: Mini-tablets as in G with an enteric coating of Eudragit® L30D55 I: Hypromellose capsule size 00E filled with 1.2 g sodium bicarbonate powder (<0.3 mm). High viscosity medium as described in Example 1. The intermediate viscosity medium described in Example 2. Palatability: 1=very low, 5=very high. Upper and lower GI symptoms: 1=no symptoms, 4-5=severe symptoms.

[0117] [Table 1]

[0118] Example 5 Minitablets as in Example 1 containing 85% NaHCO3 were compared with sodium bicarbonate granules of particle size 0.5-1.0 mm (sample C in Table 1) for in vitro dissolution rate.

[0119] Mini-tablets or granules equivalent to 138 mg sodium bicarbonate were added to 30 ml of simulated intestinal fluid in a 50 ml screw-cap vessel. The vessel was gently shaken intermittently throughout the experiment and the pH was measured over time (see Figure 5).

[0120] The bicarbonate-induced increase in pH was significantly delayed in the minitablets compared to the small granules.

[0121] Example 6 (A) Mini-tablets having a diameter of 1.2 to 5.0 mm and a thickness of 1.2 to 2.0 mm were produced with the following composition: Sodium bicarbonate 80% by weight Calcium carbonate 8% by weight Hydroxypropyl cellulose 7% by weight Maltodextrin 0.5% by weight Acacia gum 2% by weight Magnesium stearate 2% by weight Anhydrous colloidal silica 0.5%

[0122] (B) Mini-tablets having a diameter of 1.2 to 5.0 mm and a thickness of 1.2 to 2.0 mm were produced with the following composition: Sodium bicarbonate 87.5% by weight Hydroxypropyl cellulose 10% by weight Magnesium stearate 2% by weight Anhydrous colloidal silica 0.5%

[0123] Example 7 Release of sodium bicarbonate from mini-tablets in three different experiments. (A) A dissolution apparatus similar to that of type 2 according to the European Pharmacopoeia (Ph.Eur.) 2.9.3 "Dissolution test for solid dosage forms" was used. As in Example 6B, eight mini-tablets, 1.5 x 3.0 mm in size and 144 mg total weight, containing 126 mg NaHCO3 and excipients, were placed on a stainless steel net 40 mm above the bottom of a 500 ml glass beaker and 25 mm above a rotating magnetic stirring bar. Demineralized water (500 ml) was kept at 37 + / - 2 °C and stirred at 150 rpm. The concentration of dissolved NaHCO3 was determined by electrical conductivity measurement. As a criterion for complete release, the conductivity was measured when no tablet remains could be observed and the conductivity did not increase further within 3 minutes. More than 75% of the NaHCO3 was released from the mini-tablets in demineralized water within 15 minutes, and more than 95% within 30 minutes.

[0124] (B) Six containers containing eight mini-tablets each, as in (A) above, were dispersed in 40 g of a viscoelastic medium, a semi-solid gel as described in Example 1, and tumbled at 12 rpm in an incubator maintained at 37°C. The containers were removed at different times, the mini-tablets were removed and gently washed with demineralized water, after which the gel and washings were mixed and diluted to a total weight of 200 g. The NaHCO3 concentration was measured by electrical conductance measurements. As a measure of complete release, eight mini-tablets were placed in 160 ml of demineralized water until completely disintegrated, then mixed with 40 g of gel. When the mini-tablets were left dispersed in the gently tumbling gel, approximately 25% of the NaHCO3 was released within 15 minutes, approximately 50% within 30 minutes, and approximately 75% within 60 minutes.

[0125] (C) Mini-tablets were dispersed and kept in the gel for 15 min at room temperature. The amount of NaCO3 released was determined as in (B). When the mini-tablets were left dispersed in the gel at room temperature without tumbling, approximately 10-15% of the NaCO3 was released within 15 min.

[0126] The results are shown in Figure 6, which shows the percentage of NaHCO3 released from the mini-tablets over time for experiments (A)-(C) detailed above.

[0127] From these experiments, it is concluded that the release of NaHCO3 from the mini-tablets is significantly slower when tumbling in a viscoelastic gel medium (B) than when stirred in an aqueous medium (A). In the context of the present invention, the viscoelastic medium is believed to be useful in delaying the release of NaHCO3 from the ingested mini-tablets until the composition reaches the small intestine. It is also concluded that the release of NaHCO3 from the mini-tablets is significantly slower when dispersed in a gel that does not tumble (C) than when tumbling (B). In the context of the present invention, the viscoelastic medium is believed to be useful in substantially delaying the release of NaHCO3 from the mini-tablets until the composition is ingested. In experiment (C), approximately 10-15% of NaCO3 is released within 15 minutes, and it is recommended to ingest the product within this time.

[0128] Example 8 The viscoelastic medium was tested for the sedimentation rate of bicarbonate minitablets as defined herein.

[0129] The tablets have a diameter of 3 mm, a height of 1.5 mm, a weight of 18 mg and a density of 2.6 mg / mm 3 Several tablets were placed below the surface of the medium and observed for up to 30 minutes or until they had settled at least 10 mm.

[0130] Medium A (A100%) contained 27 g maltodextrin, 20 g fructose, 15 g acetylated distarch adipate, 0.5 g xanthan gum, and 300 ml water. Dilutions of A with water were also prepared and designated A80% to A67%. Medium A67% corresponds to a 1.5-fold dilution of A100%. Medium E1 is of the same composition as in Example 1. Medium E2 is of the same composition as in Example 2.

[0131] The settling rates of the media tested are shown in Table 2. [Table 2]

[0132] Example 9 (A) Viscosity and shear thinning properties of two media A100% and A67% from Example 8 were measured using a shear rate controlled rheometer (Model 302, Anton Paar, Germany). A parallel plate geometry was used (plate diameter 50 mm, gap 100 μm). Viscosity was measured at 20° C. The viscosities of the media are shown in FIG. 7 (A-100 and A-67). The relative viscosity A-100 / A-67 is shown in FIG. 7.

[0133] As can be seen in Figure 7, the viscosity curves of the two hydrocolloid dispersions A-100 and A-67 show shear thinning properties. -1 Viscosity at shear rate: A-100 5900 mPa·s; A-67 560 mPa·s. Shear rate 40 s-1 Viscosity at: A-100 1540 mPa·s; A-67 220 mPa·s.

[0134] As shown in Figure 7, the viscosity of A-67 obtained by diluting the medium A-100 1.5 times resulted in a viscosity reduction of about 6 times or more depending on the shear rate.

[0135] (B) Oscillatory tests showing the elastic component G' (storage modulus) and viscous component G'' (loss modulus) of the complex shear vector G were performed on Media A of Example 8 (A 100%).

[0136] The measurements were carried out using a controlled shear rate rheometer (Model 302, Anton Paar, Germany) at 20° C. A parallel plate geometry was used (plate diameter 50 mm, gap 100 μm).

[0137] The storage modulus G' and loss modulus G'' of A100% are shown in Figure 8. The ratio G' / G'' is about 3, which means that the sample is a viscoelastic medium and has the properties of a gel.

[0138] Example 10 A well-trained male athlete weighing 80 kg performed high-intensity interval training on two consecutive days, following the same exercise protocol every day. Blood pH and plasma bicarbonate were measured before, during and after the high-intensity interval training. After a warm-up, the athlete performed 30 repetitions of a 45-second run from time 0 with a 15-second rest, with a 5-minute break in between. The exercise intensity exceeded the anaerobic threshold (plasma lactate exceeded 4 mmol / l). On the second day, the dietary supplement composition as defined herein was administered immediately after sampling, at approximately 90 minutes, before exercise. The dietary supplement composition included mini-tablets as described in Example 7, containing 22 g of NaHCO3, equivalent to 0.275 g / kg body weight, dispersed in a semi-solid medium as described in Example 1.

[0139] The results are shown in Figure 9. The top panel (A) shows blood pH and the bottom panel (B) shows plasma bicarbonate concentration. The grey bars indicate the intervals of high intensity interval training. Day 1: circle / dotted line; Day 2: square / solid line.

[0140] On the first day (control), exercise caused the pH to fall from pH 7.43 to pH 7.35 and the plasma bicarbonate concentration to fall from 24 mmol / l to 18 mmol / l, corresponding to mild acidosis. On the second day, the pH fall caused by exercise was countered by the pH rise caused by the continued intake of bicarbonate from the ingested dietary supplement composition. Blood pH remained above 7.40 and plasma bicarbonate concentration remained above 23 mmol / l. As can be seen in Figure 9, the changes in blood pH and plasma bicarbonate followed the same pattern.

[0141] Itemized List of Embodiments 1. A dietary supplement composition which is a suspension comprising ingestible particles comprising sodium bicarbonate dispersed in an aqueous medium; said particles being tablets having a thickness of 1.0-2.0 mm and a diameter of 1.0-5.0 mm; and said particles comprising greater than 50% (w / w) sodium bicarbonate; and said aqueous medium being a viscous aqueous medium. 2. The dietary supplement composition of claim 1, wherein the ingestible particles comprise more than 65% (w / w) sodium bicarbonate, such as more than 75% (w / w) sodium bicarbonate. 3. A dietary supplement composition according to any of the preceding paragraphs, wherein the ingestible particles comprise less than 90% (w / w) sodium bicarbonate, for example 85% (w / w) or less sodium bicarbonate. 4. The dietary supplement composition of any of the preceding claims, wherein the ingestible particles are adapted to release sodium bicarbonate in the small intestine. 5. The dietary supplement composition according to any of the preceding paragraphs, wherein the tablet has a thickness of 1.2 to 2.0 mm and a diameter of 1.2 to 5.0 mm. 6. A dietary supplement composition according to any of the preceding claims, wherein the tablet has a thickness of 1.8 mm or less, such as 1.5 mm or less. 7. A dietary supplement composition according to any of the preceding claims, wherein the tablet has a diameter of 4.0 mm or less, such as 3.0 mm or less. 8. A dietary supplement composition according to any of the preceding paragraphs, wherein the tablet has a diameter of 2.0 mm or less, such as 1.8 mm or less. 9. The dietary supplement composition of any of the preceding claims, wherein the ingestible particles are non-disintegrating. 10. A dietary supplement composition according to any of the preceding paragraphs, wherein the ingestible particles are free of any coating, for example free of any enteric coating. 11. The dietary supplement composition of any of the preceding claims, wherein the ingestible particles are non-lamellar particles. 12. The dietary supplement composition of any of the preceding paragraphs, wherein the ingestible particles further comprise a binder. 13. The dietary supplement composition of claim 12, wherein the binder is selected from polyvinylpyrrolidone (PVP), calcium carbonate, calcium phosphate, hydroxypropyl cellulose (HPC), microcrystalline cellulose, gelatin and polysaccharides, and combinations thereof. 14. The dietary supplement composition of claim 13, wherein the binder is selected from hydroxypropyl cellulose (HPC) and combinations thereof. 15. The dietary supplement composition of claim 13, wherein the polysaccharide is selected from high molecular weight alginates, pectins, gum tragacanth and gum acacia, and combinations thereof. 16. The dietary supplement composition of claim 12, wherein the binder is selected from calcium carbonate and gum acacia, and combinations thereof. 17. The dietary supplement composition of any of the preceding paragraphs, wherein the ingestible particles further comprise a lubricant. 18. The dietary supplement composition of item 17, wherein the lubricant is selected from stearic acid, magnesium stearate, sodium stearyl fumarate, and combinations thereof; preferably the lubricant is magnesium stearate. 19. The dietary supplement composition of any of the preceding paragraphs, wherein the ingestible particles further comprise a glidant. 20. The dietary supplement composition of claim 19, wherein the glidant is fumed silica. 21. The dietary supplement composition of any of the preceding paragraphs, wherein the ingestible particles comprise additional excipients selected from sugars and complex carbohydrates. 22. The dietary supplement composition according to claim 21, wherein the sugar is selected from glucose, fructose, sucrose and isomaltulose. 23. The dietary supplement composition according to claim 21, wherein the complex carbohydrate is selected from starch, maltodextrin, dried glucose syrup and dried fructose syrup. 24. The dietary supplement composition according to any one of items 1 and 4 to 11, wherein the ingestible particles have the following composition: Sodium bicarbonate 75-85% by weight; 5-10% by weight of calcium carbonate; 5-10% by weight of hydroxypropylcellulose; 0.1-1.0% by weight of maltodextrin; Acacia gum 1-3% by weight; 1-3% by weight of magnesium stearate; 0.1 to 1.0% by weight of anhydrous colloidal silica. 25. The dietary supplement composition according to any one of items 1 and 4 to 11, wherein the ingestible particles have the following composition: Sodium bicarbonate 82-92% by weight; 5-15% by weight of hydroxypropylcellulose; 1-3% by weight of magnesium stearate; Anhydrous colloidal silica 0.1-1.0%. 26. The dietary supplement composition according to any one of items 1 and 4 to 11, wherein the ingestible particles have the following composition: Sodium bicarbonate 80-90% by weight; calcium phosphate 5-15% by weight; Acacia gum 1-5% by weight; 1-3% by weight of magnesium stearate; 0.1 to 1.0% by weight of anhydrous colloidal silica. 27. A nutritional supplement composition according to any of the preceding paragraphs, wherein the settling velocity of a single ingestible particle in the unstirred viscous aqueous medium is less than 5 mm / min, preferably less than 2 mm / min, more preferably less than 1 mm / min. 28. A nutritional supplement composition according to any of the preceding claims, wherein the viscous aqueous medium is a viscoelastic medium. 29. A nutritional supplement composition according to any of the preceding claims, wherein the viscous aqueous medium is a liquid. 30. The nutritional supplement composition of claim 28, wherein the viscoelastic medium is a gel. 31. A nutritional supplement composition according to any of the preceding paragraphs, wherein the viscous aqueous medium comprises one or more natural polymers dissolved in water as thickening agents. 32. The dietary supplement composition according to claim 31, wherein the natural polymer is selected from polysaccharides such as natural and modified starches, xanthan gum, guar gum, carrageenan, alginates, pectins, and combinations thereof. 33. A natural polymer is (a) native or modified starch, and (b) Xanthan gum or guar gum Item 33. The dietary supplement composition according to Item 32, wherein the relative weight ratio (a):(b) of is 99:1 to 90:10. 34. The dietary supplement composition according to claim 32, wherein the natural polymer is selected from natural starch and modified starch. 35. The dietary supplement composition according to item 34, wherein the natural polymer is a modified starch. 36. A dietary supplement composition according to any of the preceding paragraphs, wherein the viscous aqueous medium comprises one or more sugars or complex carbohydrates dissolved in water. 37. The dietary supplement composition of claim 36, wherein the sugar is selected from glucose, fructose, sucrose and isomaltulose. 38. The dietary supplement composition of claim 36, wherein the complex carbohydrate is selected from starch, maltodextrin, glucose syrup and fructose syrup. 39. The dietary supplement composition according to any one of items 1 to 30, wherein the viscous aqueous medium has the following composition: maltodextrin 4-12% by weight; fructose 3-10% by weight; 2-7% by weight of acetylated distarch adipate; Xanthan gum 0.1-1.0% by weight; Make up to 100% by weight with water. 40. The dietary supplement composition according to any one of items 1 to 30, wherein the viscous aqueous medium has the following composition: 6 to 14% by weight of maltodextrin, 2 to 5% by weight of fructose, 1 to 3% by weight of acetylated distarch adipate, and 0.1 to 1.0% by weight of xanthan gum, Make up to 100% by weight with water. 41. A dietary supplement composition according to any of items 1 to 40, wherein the total amount of sodium bicarbonate in the ingestible particles in one serving is greater than 10 g, preferably greater than 15 g. 42. The dietary supplement composition according to item 41, wherein the total amount of sodium bicarbonate in the ingestible particles in one serving is less than 50 g, preferably less than 40 g, more preferably less than 30 g. 43. A kit for preparing a dietary supplement composition, comprising an ingestible particle according to any of the preceding paragraphs and an aqueous medium. 44. The kit of item 43, wherein the dietary supplement composition is a suspension comprising ingestible particles dispersed in an aqueous medium. 45. Use of a dietary supplement composition according to any one of items 1 to 42 or a kit according to any one of items 43 to 44 for improving high-intensity exercise performance. 46. ​​Use of a dietary supplement composition according to any one of items 1 to 42 or a kit according to any one of items 43 to 44 for preventing, reducing or alleviating exercise-induced acidosis and / or acidemia. 47. A method for improving high-intensity exercise performance, comprising the step of ingesting a dietary supplement composition comprising the ingestible particles according to any one of items 1 to 42. 48. The method according to item 47, wherein ingestible particles are ingested comprising a total amount of 0.10 to 0.40 g of bicarbonate per kg of body weight, preferably 0.20 to 0.35 g of bicarbonate per kg of body weight; preferably 0.25 to 0.30 g of bicarbonate per kg of body weight. 49. A method for preventing, alleviating or ameliorating exercise-induced acidosis and / or acidemia in a subject, comprising ingesting the dietary supplement composition according to any one of items 1 to 42. 50. A method for treating metabolic acidosis and / or acidemia in a human subject in need thereof, comprising ingesting a pharma- ceutical effective amount of a composition according to any one of items 1 to 42. 51. The method according to item 50, wherein the metabolic acidosis and / or acidemia is caused by chronic kidney disease. 52. The method according to any of items 50 to 51, wherein ingestible particles are ingested comprising a total amount of 0.01 to 0.10 g of bicarbonate per kg of body weight; preferably 0.02 to 0.07 g of bicarbonate per kg of body weight; preferably 0.02 to 0.04 g of bicarbonate per kg of body weight. 53. The composition according to any one of items 1 to 42 or the kit according to any one of items 43 to 44 for use as a medicament. 54. The composition according to any one of items 1 to 42 or the kit according to any one of items 43 to 44, for use in the method according to any one of items 50 to 52. 55. Use of the composition according to any of items 1 to 42 or the kit according to any of items 43 to 44 in the preparation of a medicament for the treatment of metabolic acidosis and / or acidemia. 56. An ingestible particle comprising sodium bicarbonate, said particle being a tablet having a thickness of 1.0-2.0 mm and a diameter of 1.0-5.0 mm; and said particle comprising more than 50% (w / w) sodium bicarbonate. 57. The ingestible particle according to item 56, comprising more than 65% (w / w) sodium bicarbonate, such as more than 75% (w / w) sodium bicarbonate. 58. The ingestible particle according to any of items 56 to 57, comprising less than 90% (w / w) sodium bicarbonate, such as 85% (w / w) or less sodium bicarbonate. 59. An ingestible particle according to any of items 56 to 58, wherein the particle is suitable for releasing sodium bicarbonate in the small intestine. 60. The ingestible particle according to any of items 56 to 59, wherein the tablet has a thickness of 1.2 to 2.0 mm and a diameter of 1.2 to 5.0 mm. 61. The ingestible particle according to any of items 56 to 60, wherein the tablet has a thickness of 1.8 mm or less, such as 1.5 mm or less. 62. The ingestible particle according to any of items 56 to 61, wherein the tablet has a diameter of 4.0 mm or less, such as 3.0 mm or less. 63. The ingestible particle according to item 62, wherein the tablet has a diameter of 2.0 mm or less, such as 1.8 mm or less. 64. The ingestible particle according to any one of items 56 to 63, wherein the particle is non-disintegrating. 65. The ingestible particle according to any of items 56 to 64, which is not provided with any coating, for example not provided with any enteric coating. 66. The ingestible particle according to any of items 56 to 65, wherein the ingestible particle is a non-lamellar particle. 67. The ingestible particle according to any one of items 56 to 66, further comprising a binder. 68. The ingestible particle according to item 67, wherein the binder is selected from polyvinylpyrrolidone (PVP), calcium carbonate, calcium phosphate, hydroxypropyl cellulose (HPC), microcrystalline cellulose, gelatin and polysaccharides, and combinations thereof. 69. The ingestible particle according to item 68, wherein the binder is selected from hydroxypropyl cellulose (HPC) and combinations thereof. 70. The ingestible particle according to item 68, wherein the polysaccharide is selected from high molecular weight alginates, pectins, gum tragacanth and gum acacia, and combinations thereof. 71. The ingestible particle according to item 67, wherein the binder is selected from calcium carbonate and gum acacia, and combinations thereof. 72. The ingestible particle according to any of items 56 to 71, further comprising a lubricant. 73. The ingestible particle according to item 72, wherein the lubricant is selected from stearic acid, magnesium stearate, sodium stearyl fumarate, and combinations thereof. 74. The ingestible particle according to item 73, wherein the lubricant is magnesium stearate. 75. The ingestible particle according to any one of items 56 to 74, further comprising a glidant. 76. The ingestible particle according to item 75, wherein the glidant is fumed silica. 77. The ingestible particle according to any of items 56 to 76, comprising a further excipient selected from sugars and complex carbohydrates. 78. The ingestible particle according to item 77, wherein the sugar is selected from glucose, fructose, sucrose and isomaltulose. 79. The ingestible particle according to item 77, wherein the complex carbohydrate is selected from starch, maltodextrin, dried glucose syrup and dried fructose syrup. 80. The ingestible particle according to any of items 56 and 59 to 67, wherein the ingestible particle has the following composition: Sodium bicarbonate 75-85% by weight; 5-10% by weight of calcium carbonate; 5-10% by weight of hydroxypropylcellulose; 0.1-1.0% by weight of maltodextrin; Acacia gum 1-3% by weight; 1-3% by weight of magnesium stearate; 0.1 to 1.0% by weight of anhydrous colloidal silica. 81. The ingestible particle according to any of items 56 and 59 to 67, wherein the ingestible particle has the following composition: Sodium bicarbonate 82-92% by weight; 5-15% by weight of hydroxypropylcellulose; 1-3% by weight of magnesium stearate; Anhydrous colloidal silica 0.1-1.0%. 82. The ingestible particle according to any of items 56 and 59 to 67, wherein the ingestible particle has the following composition: Sodium bicarbonate 80-90% by weight; calcium phosphate 5-15% by weight; Acacia gum 1-5% by weight; 1-3% by weight of magnesium stearate; 0.1 to 1.0% by weight of anhydrous colloidal silica. 83. Use of an ingestible particle according to any of items 56 to 82 in a dietary supplement composition for improving high-intensity exercise performance. 84. Use of an ingestible particle according to any of items 56 to 82 for improving high-intensity exercise performance. 85. Use of an ingestible particle according to any of items 56 to 82 in a dietary supplement composition for preventing, reducing or alleviating exercise-induced acidosis and / or acidemia. 86. Use of an ingestible particle according to any of items 56 to 82 for preventing, reducing or alleviating exercise-induced acidosis and / or acidemia. 87. A method for improving high intensity exercise performance, comprising a step of ingesting an ingestible particle according to any of items 56 to 82. 88. A method for preventing, reducing or alleviating exercise-induced acidosis and / or acidemia in a subject, comprising a step of ingesting an ingestible particle according to any one of items 56 to 82. 89. The method according to any of items 87 to 88, wherein ingestible particles are ingested comprising a total amount of 0.10 to 0.40 g of bicarbonate per kg of body weight; preferably 0.20 to 0.35 g of bicarbonate per kg of body weight; preferably 0.25 to 0.30 g of bicarbonate per kg of body weight. 90. A method for treating metabolic acidosis and / or acidemia in a human subject in need thereof, comprising the step of ingesting a pharma- tically effective amount of an ingestible particle according to any of items 56 to 82. 91. The method according to item 90, wherein the metabolic acidosis and / or acidemia is caused by chronic kidney disease. 92. The method according to any of items 90 to 91, wherein ingestible particles are ingested comprising a total amount of 0.01 to 0.10 g of bicarbonate per kg of body weight; preferably 0.02 to 0.07 g of bicarbonate per kg of body weight; preferably 0.02 to 0.04 g of bicarbonate per kg of body weight. 93. An ingestible particle according to any of items 56 to 82 for use as a medicament. 94. An ingestible particle according to any of items 56 to 82 for use in the method according to any of items 90 to 92. 95. Use of an ingestible particle according to any of items 56 to 82 in the preparation of a medicament for the treatment of metabolic acidosis and / or acidemia.

Claims

1. 1. A dietary supplement composition that is a suspension comprising ingestible particles comprising sodium bicarbonate dispersed in an aqueous medium; the particles being tablets having a thickness of 1.0-2.0 mm and a diameter of 1.0-5.0 mm; and the particles comprising greater than 50% (w / w) sodium bicarbonate; and the aqueous medium being a viscous aqueous medium.

2. 10. The dietary supplement composition of claim 1, wherein the ingestible particles comprise more than 65% (w / w) sodium bicarbonate, for example more than 75% (w / w) sodium bicarbonate.

3. 10. The dietary supplement composition of claim 1, wherein the ingestible particles are adapted to release sodium bicarbonate in the small intestine.

4. 10. The dietary supplement composition of claim 1, wherein the tablet has a thickness of 1.2 to 2.0 mm and a diameter of 1.2 to 5.0 mm.

5. 5. The dietary supplement composition of claim 4, wherein the tablet has a diameter of 2.0 mm or less, such as 1.8 mm or less.

6. 10. The dietary supplement composition of claim 1, wherein the ingestible particles do not have any coating, e.g., do not have any enteric coating.

7. 10. The nutritional supplement composition of claim 1, wherein the ingestible particles further comprise a binder.

8. 8. The dietary supplement composition of claim 7, wherein the binder is selected from hydroxypropyl cellulose (HPC) and combinations thereof.

9. The ingestible particles having a composition of: 82-92% by weight of sodium bicarbonate; 5 to 15% by weight of hydroxypropyl cellulose; 1-3% by weight of magnesium stearate; Anhydrous colloidal silica 0.1 to 1.0% 10. The dietary supplement composition of claim 1, having:

10. 10. The dietary supplement composition of claim 1, wherein the settling velocity of a single ingestible particle in an unstirred viscous aqueous medium is less than 5 mm / min, preferably less than 2 mm / min, more preferably less than 1 mm / min.

11. 10. The nutritional supplement composition of claim 1, wherein the viscous aqueous medium is a viscoelastic medium.

12. 12. The nutritional supplement composition of claim 11, wherein the viscoelastic medium is a gel.

13. 10. The dietary supplement composition of claim 1, wherein the viscous aqueous medium comprises one or more natural polymers dissolved in water as a thickening agent.

14. 14. The dietary supplement composition of claim 13, wherein the natural polymer is selected from polysaccharides such as native and modified starches, xanthan gum, guar gum, carrageenan, alginates, pectins, and combinations thereof.

15. The viscous aqueous medium has the following composition: 4-12% by weight of maltodextrin; 3-10% by weight of fructose; 2-7% by weight of acetylated distarch adipate; 0.1 to 1.0% by weight of xanthan gum; Water to 100% by weight 10. The dietary supplement composition of claim 1, having:

16. The viscous aqueous medium has the following composition: 6 to 14% by weight of maltodextrin, 2-5% by weight of fructose, 1 to 3% by weight of acetylated distarch adipate, 0.1 to 1.0% by weight of xanthan gum; Water to 100% by weight 10. The dietary supplement composition of claim 1, having:

17. 10. A kit for preparing a dietary supplement composition, comprising ingestible particles and the aqueous medium of claim 1.

18. 10. A method for improving high intensity exercise performance comprising ingesting the nutritional supplement composition of claim 1.

19. 10. A method of preventing, reducing or alleviating exercise-induced acidosis and / or acidemia in a subject, comprising ingesting the dietary supplement composition of claim 1.

20. 10. A method of treating metabolic acidosis and / or acidemia in a human subject in need thereof, comprising ingesting a pharmaceutically effective amount of the composition of claim 1.

21. 1. An ingestible particle comprising sodium bicarbonate, the particle being a tablet having a thickness of 1.0 to 2.0 mm and a diameter of 1.0 to 5.0 mm; the particle comprising more than 50% (w / w) sodium bicarbonate.

22. 18. Use of the nutritional supplement composition of claim 1 or the kit of claim 17 to improve high-intensity exercise performance.

23. 18. Use of the dietary supplement composition of claim 1 or the kit of claim 17 for preventing, reducing or alleviating exercise-induced acidosis and / or acidemia.

24. 18. The composition of claim 1 or the kit of claim 17 for use in a method for treating metabolic acidosis and / or acidemia in a human subject in need thereof, comprising ingesting a pharmaceutically effective amount of the composition of claim 1.

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