EP4731018A1 - Compositions and methods using a nettle concentrate for cellular energy - Google Patents

Abstract

Compositions comprising a nettle concentrate are provided. The compositions can be administered to an individual in need thereof for (i) improving a physiological state linked to metabolic fatigue in one or more cells, and/or (ii) increasing mitochondrial energy and mitochondrial calcium uptake in one or more cells, and/or (iii) enhancing mitochondrial function, and/or (iv) treating or preventing a calcium deficiency / depletion disorder in an individual. Additionally or alternatively, the compositions can be administered for treating or preventing a mitochondria-related disease or a condition associated with altered mitochondrial function in an individual in need thereof or at risk thereof.

Description

COMPOSITIONS AND METHODS USING A NETTLE CONCENTRATE FOR CELLULAR ENERGY TECHNICAL FIELD The present invention relates generally to compositions and methods that use a nettle concentrate to manage energy at a cellular level. The compositions and methods can boost mitochondrial function and increase bioenergetics through activation of the mitochondrial calcium uniporter to thereby promote cellular activation, in some embodiments in an older adult, an elderly or a patient in ICU. BACKGROUND OF THE INVENTION Population aging has been a remarkable demographic event. As the growth of the older population has outpaced the total population due to increased longevity, the proportion of older persons relative to the rest of the population has increased considerably due to decreased fertility rates. For example, one in every twelve individuals was at least 60 years of age in 1950, and one in every ten was aged 60 years or older by the end of 2000. By the end of 2050, the number of persons worldwide that is 60 years or over is projected to be one in every five. Aged or aging individuals frequently suffer some degree of physical decline and/or cognitive impairment, including decline in cognitive function, that progresses with age, and age-related changes in brain morphology and cerebrovascular function are commonly observed. Cognitive decline has been consistently reported with aging across a range of cognitive domains including processing speed, attention, episodic memory, spatial ability and executive function. Brain imaging studies have revealed that these normal age-related cognitive declines are associated with decreases in both grey and white matter volume in the brain, with the fronto-striatal system most heavily compromised with aging. These decreases in cortical volume can be attributed to a number of detrimental cellular processes involved with normal aging, such as accumulation of damage by free radicals over time leading to oxidative damage, chronic low-grade inflammation, homocysteine accumulation (which when elevated are a risk factor for cognitive impairment and dementia), and decreased mitochondrial efficiency. In addition to direct cellular damage, the brain is also indirectly impaired by insults to micro-vascular structures. It is evident that the pathology of aging and also dementia involves a complexity of these interacting factors which are linked together. For example, mitochondrial dysfunction leads to increased oxidative stress, and oxidative stress can trigger inflammation and vascular insults. Mitochondria are the primary source of aerobic energy production in mammalian cells and also maintain a large Ca2+ gradient across their inner membrane, providing a signaling potential for this molecule. Furthermore, mitochondrial Ca2+ plays a role in the mitochondria in the regulation of ATP generation and potentially contributes to the orchestration of cellular metabolic homeostasis. (Glancy, B. et al. (2012). "Role of mitochondrial Ca2+ in the regulation of cellular energetics." Biochemistry 51(14): 2959-2973). Alterations in mitochondrial Ca2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases (Arduino et al. Journal Physiol.2018 Jul; 596(14):2717- 2733). Nutrition, education, physical exercise and cognitive exercise have been recently demonstrated as possible intervention to prevent physical and cognitive decline with aging. An abundance of clinical, epidemiological, and individual evidence is in favor of individual nutritional factors that reduce dementia risk and age-related neurodegeneration. However, formal trial testing of nutritional interventions has yielded mixed results (Schmitt et al., Nutrition Reviews 68: S2–S5 (2010). Also, efforts have been taken to harness mitochondrial Ca2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca2+ homeostasis are currently lacking. It would therefore be desirable to provide compounds that direct and selectively modulate mitochondrial Ca2+ homeostasis. It would be also desirable that such compounds are natural. It would be also desirable that such compounds can be suitable for vegetarian or vegan diet. Any reference to prior art documents in this specification is not to be considered an admission that such prior art is widely known or forms part of the common general knowledge in the field. SUMMARY OF THE INVENTION The object of the present invention is to improve the state of the art, and in particular to provide compositions, unit dosage form and methods that overcome the problems of the prior art and addresses the needs described above, or at least to provide a useful alternative. The inventors were surprised to see that the object of the present invention could be achieved by the subject matter of the independent claims. The dependent claims further develop the idea of the present invention. Especially, in view of the experimental data disclosed later herein, it is believed that a nettle concentrate as disclosed herein enhances the efficiency of mitochondria to produce energy. Accordingly, an embodiment of the invention proposes a composition comprising a nettle concentrate, in an effective amount for use in (i) improving a physiological state linked to metabolic fatigue in one or more cells, and/or (ii) increasing mitochondrial energy and mitochondrial calcium uptake in one or more cells, and/or (iii) enhancing mitochondrial function, and/or (iv) treating or preventing a calcium deficiency / depletion disorder in an individual, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. In a particular embodiment, at least a portion of the one or more cells are part of at least one body part selected from the group consisting of a liver, a kidney, a brain, and a skeletal muscle. In a further particular embodiment, the physiological state linked to metabolic fatigue comprises muscle fatigue, muscle weakness, lack of vitality, weakness or lack of energy, in particular lack of physical energy. In a further particular embodiment, the effective amount of nettle concentrate is orally administered daily for at least one week. In an additional particular embodiment, the composition further comprises at least one compound selected from the group consisting of antioxidants, anti-inflammatory compounds, glycosaminoglycans, prebiotics, fibres, probiotics, fatty acids, enzymes, minerals, trace elements and/or vitamins. In a further particular embodiment, the composition is selected from the group consisting of food compositions, dietary supplements, nutritional compositions, complete nutritional compositions, pharmaceuticals, oral nutritional supplement, medical food, nutraceuticals, beverages, powdered nutritional products to be reconstituted in water or milk before consumption, food additives, food for special medical purpose (FSMP), medicaments, petfood, and combinations thereof. In a further particular embodiment, the composition is in a form of a solid powder, a powdered stick, a capsule or a solution. In a further particular embodiment, the effective amount of nettle concentrate is administered in a food product or beverage further comprising a component selected from the group consisting of protein, carbohydrate, fat and mixtures thereof. Another embodiment of the invention proposes a composition comprising a nettle concentrate for use in an effective amount for treating, reducing an incidence of, and/or reducing a severity of a mitochondria-related disease or a condition associated with altered mitochondrial function in an individual in need thereof or at risk thereof, the method comprising orally administering an effective amount of the nettle concentrate to the individual in need thereof or at risk thereof, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. In a particular embodiment, the mitochondria-related disease or condition is selected from the group consisting of stress, physiological ageing, obesity, reduced metabolic rate, metabolic syndrome, diabetes mellitus, complications from diabetes, hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder, anxiety disorder, age-related neuronal death or dysfunction, musculoskeletal disorder, frailty, pre-frailty, chronic kidney disease, kidney failure, trauma, infection, cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof and combinations thereof. Another embodiment of the invention proposes a composition comprising a nettle concentrate for use in an effective amount for delaying off-set of metabolic decline, maintaining muscle mass and/or muscle function, maintaining immune function and/or maintaining cognitive function in a healthy older adult, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. Another embodiment of the invention proposes a composition comprising a nettle concentrate for use in an effective amount for enhancing at least one of mental performance or muscle performance in an individual, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. Another embodiment of the invention proposes a composition comprising a nettle concentrate for use in an effective amount for improving or maintaining cognitive function, in an individual, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. In a particular embodiment, wherein the cognitive function is selected from the group consisting of perception, memory, attention, speech comprehension, speech generation, reading comprehension, creation of imagery, learning, reasoning, and combinations thereof. In a particular embodiment of all the preceding embodiments, the effective amount of nettle concentrate may be administered in a composition further comprising calcium. In a particular embodiment of all the preceding embodiments, the individual is an older adult, an elderly or a patient in ICU. Another embodiment of the invention proposes a unit dosage form comprising a nettle concentrate for use in an effective amount for at least one of (i) treating, reducing an incidence of, or reducing a severity of a mitochondria-related disease or condition associated with altered mitochondrial function, and/or (ii) improving in a physiological state linked to metabolic fatigue in one or more cells, and/or (iii) increasing mitochondrial energy and mitochondrial calcium uptake in one or more cells, and/or (iv) treating or preventing a calcium deficiency / depletion disorder, and/or (v) increasing metabolic rate, and/or (vi) improving or maintaining cognitive function, and/or (vii) increasing or maintaining mitochondrial function, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. In a particular embodiment, the physiological state linked to metabolic fatigue comprises muscle fatigue, muscle weakness, lack of vitality, weakness or lack of energy, in particular lack of physical energy. These and other aspects, features and advantages of the invention will become more apparent to those skilled in the art from the detailed description of embodiments of the invention, in connection with the attached drawings. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows iron content (mg/kg) based on dry weight (DW) in nettle material and corresponding nettle concentrate obtained from said nettle material according to the method of example 1. The values represent the average between triplicate independent samples and error bars represent the standard deviation. By “nettle material” in figure 1, it is understood the together of leaves and stems of the dry nettle material that were ground into powder before being further processed into the concentration process of example 1. Figure 2 shows the molar ratio (M/M) between iron and oxalic acid molar concentrations in nettle material and corresponding nettle concentrate obtained from said nettle material according to the method of example 1. The values represent the average between duplicate measurements. By “nettle material” in figure 2, it is understood the together of leaves and stems of the dry nettle material that were ground into powder before being further processed into the concentration process of example 1. Figure 3 shows the molar ratio (M/M) between iron and phytic acid molar concentrations in nettle material and corresponding nettle concentrate obtained from said nettle material according to the method of example 1. The values represent the average between duplicate independent samples and error bars represent the standard deviation. By “nettle material” in figure 3, it is understood the together of leaves and stems of the dry nettle material that were ground into powder before being further processed into the concentration process of example 1. Figure 4 shows the iron bioaccessibility of nettle concentrate prepared with water (according to the method of example 1) and nettle concentrates prepared with water in presence of respectively citric acid or hydrochloric acid (according to the method of example 2). The values represent the average between duplicate independent samples and error bars represent the standard deviation. Figure 5 shows the absolute amount of bioaccessible iron contained in nettle material and corresponding nettle concentrates prepared with water according to the concentration process of example 1 or with water in presence of respectively citric acid or hydrochloric acid, according to the concentration process of example 2. The absolute amount of bioaccessible iron was calculated multiplying the iron content in the sample by the bioaccessibility value. The values represent the average between duplicate independent samples and error bars represent the standard deviation. By “nettle material” in figure 5, it is understood the together of leaves and stems of the dry nettle material that were ground into powder before being further processed into the concentration process of example 1 or example 2. Figure 6 is a graph showing the total mitochondrial Ca2+ uptake in C2C12-derived myotube (expressed in relative luminescence units (RLU)) over time in absence of nettle concentrate (no stim) or in presence of different concentration (dilution from 1/10 to 1/80) of the nettle concentrate prepared according to the method of example 1. The moment of the addition of the nettle concentrate at different concentrations (dilution from 1/10 to 1/80) or standard Aequorin buffer alone (no stim) is illustrated by an arrow. The results are representative of 8 biological experiments. Figure 7 is a bar graph showing the total mitochondrial Ca2+ uptake in C2C12-derived myotube without stimulation, i.e. only addition of aequorin buffer alone (no stim) or after stimulation with different concentrations of nettle concentrate prepared according to the method of example 1 (dilution from 1/10 to 1/80) in C2C12-derived myotubes. Results are expressed as mean +/- SEM, from n = 8 biological replicates. * indicates statistically significant difference between the conditions, at P < 0.05 (One-way ANOVA). DETAILED DESCRIPTION OF THE INVENTION As used herein, the words “comprise”, “comprising” and the like are to be construed in an inclusive sense, that is to say, in the sense of “including, but not limited to”, as opposed to an exclusive or exhaustive sense. Likewise, the terms “include,” “including” and “or” should all be construed to be inclusive, unless such a construction is clearly prohibited from the context. Nevertheless, the compositions disclosed herein may lack any element that is not specifically disclosed herein. Thus, a disclosure of an embodiment using the term “comprising” includes a disclosure of embodiments “consisting essentially of” and “consisting of” the components identified. As used herein, a “composition consisting essentially of a nettle concentrate” and a “composition consisting essentially of calcium a nettle concentrate” do not include any additional compound that affects mitochondrial calcium import other than the nettle concentrate as disclosed herein and the optional calcium. In a particular non-limiting embodiment, the composition consists of an excipient, the nettle concentrate as disclosed herein, and optionally calcium. All numerical ranges should be understood to include each integer, whole or fractions, within the range. Moreover, these numerical ranges should be construed as providing support for a claim directed to any number or subset of numbers in that range. For example, a disclosure of from 1 to 10 should be construed as supporting a range of from 1 to 8, from 3 to 7, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, and so forth. All percentages expressed herein are by weight of the total weight of the composition unless expressed otherwise. As used herein, “about,” “approximately” and “substantially” are understood to refer to numbers in a range of numerals, for example the range of -10% to +10% of the referenced number, preferably -5% to +5% of the referenced number, more preferably -1% to +1% of the referenced number, most preferably -0.1% to +0.1% of the referenced number. As used herein, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a bioactive compound” or “the bioactive compound” includes one bioactive compound but also two or more bioactive compounds. Unless noted otherwise, all percentages in the specification refer to weight percent, where applicable. Unless defined otherwise, all technical and scientific terms have and should be given the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. As used herein, the term “and/or” used in the context of “X and/or Y” should be interpreted as “X,” or “Y,” or “X and Y.”. Similarly, “at least one of X or Y” should be interpreted as “X,” or “Y,” or “both X and Y.”. For example, “at least one of mental performance or muscle performance” means “mental performance,” or “muscle performance,” or “both mental performance and muscle performance.”. As used herein, the terms “example” and “such as,” particularly when followed by a listing of terms, are merely exemplary and illustrative and should not be deemed to be exclusive or comprehensive. But, a disclosure of an embodiment using the term “example” and “such as” includes a disclosure of embodiments where the terms are exclusive and/or comprehensive. As used herein, “associated with” and “linked with” mean occurring concurrently, preferably means caused by the same underlying condition, and most preferably means that one of the identified conditions is caused by the other identified condition. As used herein, the terms “food,” “food product” and “food composition” mean a product or composition that is intended for ingestion by an individual such as a human and provides at least one nutrient to the individual. The compositions of the present disclosure, including the many embodiments described herein, can comprise, consist of, or consist essentially of the elements disclosed herein, as well as any additional or optional ingredients, components, or elements described herein or otherwise useful in a diet. As used herein, the terms “beverage” and “drink” refers to a “food”, “food product” or “food composition” which is generally consumed by drinking. In particular, the terms “beverage” and “drink” are used interchangeably. As used herein, the terms “treat” and "treatment" mean to administer a composition as disclosed herein to a subject having a condition in order to lessen, reduce or improve at least one symptom associated with the condition and/or to slow down, reduce or block the progression of the condition. The terms “treatment” and “treat” include both prophylactic or preventive treatment (that prevent and/or slow the development or progression of a targeted pathologic condition or disorder) and curative, therapeutic or disease-modifying treatment, including therapeutic measures that cure, slow down, lessen symptoms of, and/or halt progression of a diagnosed pathologic condition or disorder; and treatment of patients at risk of contracting a disease or suspected to have contracted a disease, as well as patients who are ill or have been diagnosed as suffering from a disease or medical condition. The terms “treatment” and “treat” do not necessarily imply that a subject is treated until total recovery. The terms “treatment” and “treat” also refer to the maintenance and/or promotion of health in an individual not suffering from a disease but who may be susceptible to the development of an unhealthy condition. The terms “treatment” and “treat” are also intended to include the potentiation or otherwise enhancement of one or more primary prophylactic or therapeutic measures. As non-limiting examples, a treatment can be performed by a patient, a caregiver, a doctor, a nurse, or another healthcare professional. Both human and veterinary treatments are within the scope of the present disclosure. Preferably the nettle concentrate as disclosed herein is administered in a serving or unit dosage form that provides a therapeutically effective or prophylactically effective amount. As used herein, the terms "prevent and “prevention” mean to administer a composition as disclosed herein to a subject is not showing any symptoms of the condition to reduce or prevent development of at least one symptom associated with the condition. Furthermore, “prevention” includes reduction of risk, incidence and/or severity of a condition or disorder. As used herein, an “effective amount” is an amount that treats or prevents a deficiency, treats or prevents a disease or medical condition in an individual, or, more generally, reduces symptoms, manages progression of the disease, or provides a nutritional, physiological, or medical benefit to the individual. As used herein, the relative terms “improved,” “improve”, “increased,”, “increase” “enhanced”, “enhance” and the like refer to the effects of the composition disclosed herein, namely a composition comprising a nettle concentrate as disclosed herein, relative to administration over the same time period of a composition lacking/devoid of a nettle concentrate as disclosed herein but otherwise identical. As used herein, “administering” includes another individual providing a referenced composition to an individual so that the individual can consume the composition and also includes merely the act of the individual themselves consuming a referenced composition. As used herein, the term “animal” includes, but is not limited to, mammals, which includes but is not limited to rodents; aquatic mammals; domestic animals such as dogs, cats and other pets; farm animals such as sheep, pigs, cows and horses; and humans. Where “animal,” “mammal” or a plural thereof is used, these terms also apply to any animal that is capable of the effect exhibited or intended to be exhibited by the context of the passage, e.g., an animal benefitting from improved mitochondrial calcium import. While the term “individual” or “subject” is often used herein to refer to a human, the present disclosure is not so limited. Accordingly, the term “individual” or “subject” refers to any animal, mammal or human that can benefit from the methods and compositions disclosed herein. As used herein, a "subject" or “individual” is a mammal, preferably a human. The term “elderly” in the context of a human means an age from birth of at least 60 years, preferably above 63 years, more preferably above 65 years, and most preferably above 70 years. The term “older adult” in the context of a human means an age from birth of at least 45 years, preferably above 50 years, more preferably above 55 years, and includes elderly individuals. The term “older adult” in the context of a human means an age from birth of at least 45 years, preferably above 50 years, more preferably above 55 years, and includes elderly individuals. As used herein, “frailty” is defined as a clinically recognizable state of increased vulnerability resulting from aging-associated decline in reserve and function across multiple physiologic systems such that the ability to cope with everyday or acute stressors is compromised. A pre-frail stage, in which one or two of these criteria are present, identifies a high risk of progressing to frailty. As used herein, the terms “serving” or "unit dosage form," are interchangeable and refer to physically discrete units suitable as unitary dosages for human and animal subjects, each unit containing a predetermined quantity of the composition comprising a nettle concentrate, as disclosed herein, in an amount sufficient to produce the desired effect, preferably in association with a pharmaceutically acceptable diluent, carrier or vehicle. The specifications for the unit dosage form depend on the particular compounds employed, the effect to be achieved, and the pharmacodynamics associated with each compound in the host. In an embodiment, the unit dosage form can be a predetermined amount of liquid housed within a container such as a bottle. As used herein, an “oral nutrition supplement” or “ONS” is a composition comprising at least one macronutrient and/or at least one micronutrient, for example in a form of sterile liquids, semi-solids or powders, and intended to supplement other nutritional intake such as that from food. Non-limiting examples of commercially available ONS products include MERITENE®, BOOST®, NUTREN® and SUSTAGEN®. In some embodiments, an ONS can be a beverage in liquid form that can be consumed without further addition of liquid, for example an amount of the liquid that is one serving of the composition. As used herein, “incomplete nutrition” refers to preferably nutritional products that do not contain sufficient levels of macronutrients (protein, fats and carbohydrates) or micronutrients to be sufficient to be a sole source of nutrition for the animal to which the nutritional product is being administered. The term "complete nutrition" refers to a product which is capable of being the sole source of nutrition for the subject. An individual can receive 100% of their nutritional requirements from a complete nutrition composition. As used herein, “metabolic fatigue” means reduced mitochondrial function in one or more cells (e.g., one or more of liver, kidney, brain, skeletal muscle) due to a shortage of substrates within the one or more cells and/or an accumulation of metabolites within the muscle fiber which interfere either with the release of calcium or with the ability of calcium to stimulate mitochondrial function. Physiological states linked to metabolic fatigue may comprise muscle fatigue, muscle weakness, lack of vitality, weakness or lack of energy, in particular lack of physical energy. As used herein, the term “added organic solvent” refers to an organic solvent which is exogenous to the nettle material and that is added in addition to the nettle material for the preparation of the nettle material concentrate. The term “added organic solvent” excludes organic solvent that are inherently present in the nettle material of the nettle material concentrate. As used herein, the term “vegan” refers to an edible composition which is entirely devoid of animal products, or animal derived products. As used herein, the term “vegetarian” refers to an edible composition which is devoid of meat, including fish. As used herein, the term “bioaccessibility” refers to the fraction of the total amount of a substance that is theoretically available for absorption. As used herein, the term “blend” and “mix” are used interchangeably. Process for obtaining the nettle concentrate The nettle concentrate provided herein is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending mixing the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. In an embodiment, the ratio of nettle material to aqueous liquid within the nettle material suspension is of 1:3 to 1:20, preferably of 1:5 to 1:20, more preferably 1:10 to 1:20, most preferably 1:12 to 1:18. The nettle material comprises nettle plant cells. Likewise, the nettle material suspension comprises nettle plant cells, including intact nettle plant cells. The nettle plant cells of the nettle material suspension come from the nettle material. The nettle material suspension is the resulting product of step a). The nettle material slurry is the resulting product of step b). The nettle material suspension and nettle material slurry are different. In particular, in the nettle material slurry, the nettle plant cells are disrupted, and the intracellular material of the nettle plant cells is released while in the nettle material suspension, the nettle plant cells are not disrupted such that the intracellular material of the nettle plant cells is not released. The aqueous liquid and so the nettle material suspension are free from added organic solvent. For example, the aqueous liquid and so the nettle material suspension are free from any added organic solvent selected from the list consisting of acetic acid, acetone, acetonitrile, benzene, 1-butanol, 2-butanol, 3-butanone, t-butyl alcohol, carbon tetrachloride, chlorobenzene, chloroform, cyclohexane, diethylene glycol, diethyl ether, diethylene glycol dimethyl ether, 1,2-dimethoxy-ethane (glyme, DME), dimethyl-formamide (DMF), dimethyl sulfoxide (DMSO), 1,4 dioxane, 1,2-dicholoroethane, ethanol, ethyl acetate, ethylene glycol, glycerin, heptane, hexamethylphosphoramide (HMPA), hexane, methanol, methylene chloride, N-methyl-2-pyrrolidinone (NMP), nitromethane, naphthalene, pentane, 1-propanol, 2-propanol, pyridine, toluene, triethyl amine, tricine, tris, tetrahydrofuran, o-xylene, m- xylene, p-xylene and combination thereof. In a preferred embodiment, the aqueous liquid of step a) comprises at least 80wt.% water, more preferably 90wt.% water, even more preferably at least 95wt.% water. Most preferably, the aqueous liquid of step a) is water. In an embodiment, osmotic agent may be further added to the nettle material suspension before step b). The osmotic agent may be selected from the list consisting of glucose, glycerol, sucrose, sorbitol, sodium chloride, potassium chloride or a combination thereof. Preferably, the osmotic agent is sucrose. The quantity of the osmotic agent to be added to the nettle material suspension may be defined easily by a person having ordinary skills in the art depending on the type of the osmotic agent and the osmolarity of the suspension. The osmotic agent may be used to modulate the osmotic pressure. Without wishing to be bound by theory, this may contribute to keep some plant structures that store bioactive compounds and/or micronutrients intact and avoid their lysis upon osmolar pressure. Without wishing to be bound by theory, this may allow to further improve bioactive compounds and/or micronutrient stability. In a preferred embodiment, an acid may be further added to the nettle material suspension before step b). In an embodiment, the acid is added to the nettle material suspension before step b) until reaching a pH of 2 to 5.5, preferably 2.5 to 4.5, most preferably 3 to 4. The acid may be selected from the group consisting of hydrochloric acid, citric acid, malic acid, ascorbic acid, acetic acid, lactic acid, propionic acid, fumaric acid, tartaric acid, phosphoric acid, adipic acid, succinic acid, gluconic acid or a mixture thereof. Preferably, the acid is selected from the group consisting of malic acid, citric acid, hydrochloric acid or a mixture thereof. In an even more preferred embodiment, the acid is selected from the group consisting of citric acid, hydrochloric acid or a mixture thereof. In a most preferred embodiment, the acid is hydrochloric acid. In another most preferred embodiment, the acid is citric acid. The acid may be provided as pure acid solution, as diluted acid solution or as acid- containing food ingredient. Examples of acid-containing food ingredient include citrus juice such as lemon juice, lime juice, orange juice, tangerine juice and the like. The nettle material suspension may comprise 0.01wt% to 5wt% of acid. When the acid is citric acid, the nettle material suspension may comprise 0.01 to 3wt% citric acid, preferably 0.5 to 2.3wt% citric acid. When the acid is hydrochloric acid, the nettle material suspension may comprise 0.01 % to 0.5 wt% hydrochloric acid, preferably 0.02 to 0.54wt% hydrochloric acid. When the acid is malic acid, the nettle material suspension may comprise 0.01 % to 3 wt% malic acid, preferably 0.5 to 2.5 wt% malic acid. The use of acid has a dual effect. In particular, the acid decreases the pH and chelates micronutrient, in particular iron. The decrease in pH and chelation contributes to improve micronutrient solubility, in particular iron solubility and so contributes to improve micronutrient, in particular iron bioaccessibility in the nettle concentrate. In some embodiment, nettle refers to any plants from the genus Urtica, preferably any edible plants from the genus Urtica. Preferably, nettle refers to Urtica dioica. The nettle material may comprise any part of the nettle plant such as leaves, stems, flowers, buds, roots. In an embodiment, the nettle material comprises leaves and/or stems from nettle. Preferably, the nettle material comprises a substantial quantity of leaves. The nettle material comprises at least 80wt.% leaves from nettle, more preferably at least 90wt.% leaves from nettle, even more preferably at least 95wt.% leaves from nettle, even more preferably at least 98wt.% leaves from nettle. The remainder of the nettle material may be any parts of the nettle plant different from leaves from nettle as disclosed herein. In an embodiment, the remainder of the green plant material consists only stems from nettle. In a most preferred embodiment, the nettle material consists only of leaves from nettle. The leaves are preferred because they generally contain a high fraction of bioactive compounds and/or micronutrients while being edible. Hence, the leaves are a good edible starting materials to concentrate substantial amount of bioactive compounds and/or micronutrients from nettle. In an embodiment, the nettle material is dried nettle material and/or fresh nettle material. For example, the nettle material is dried leaves and/or fresh leaves from nettle. Advantageously, the nettle material is dried nettle material. Dried nettle materials are more convenient to handle on an industrial scale as they have a longer shelf-life than fresh nettle materials. In an embodiment, when the nettle material comprises or is dried nettle plant material, the dried nettle material may be ground to a powder before step a). The dried nettle material may be ground via dry milling. Dry milling may be obtained using any machine providing shear or containing a cutting device. For example, the dry milling may be performed by means of hammer mill, stone mill, roller mill, ball mill, jet mill, colloidal mill, stirred media mill, bead mill, pin mill, roller grinder, roller refiner, impact mill, cryogenic milling, rod mill, vibratory mill, cutting mill, disc mill, perforated disc mill, microcut mill or extrusion apparatus. In an embodiment, the blending step c) may be performed by means of any kind of shearing or mixing device. Examples of mixing devices are: mixer, kitchen mixer, tumbler blender, paddle mixer, agitator, flow impeller, planetary mixer, multi shaft mixer, Scanima mixer or Stephan mixer. In an embodiment, the blending may be performed in step b) for at least 8 seconds, preferably for 8 seconds to 5 minutes, more preferably for 1 minute to 3 minutes. In an embodiment, the blending may be performed in step b) at a temperature of 4 to 80°C, preferably at a temperature of 4 to 25°C, more preferably at a temperature of 10 to 25°C. The preferred temperature range of 4 to 25°C is advantageous as it limits oxidation/chemical degradation of plant organelles that can occur at high temperature, e.g. 60°C to 100°C. For example, the blending may be performed at room temperature. This step allows to disrupt the plant cells and release their intracellular material, including bioactive compounds and/or micronutrients. This contributes to improve the bioaccessibility of the bioactive compounds and/or micronutrients in the final concentrate when ingested by humans. In an embodiment, the step c) is performed through filtration and/or centrifugation and/or decantation and/or heat treatment. In an embodiment, the filtration of step c) may be performed with the same conditions or features of the filtration step c₁) provided below in section “Step c₁) of filtration”. In an embodiment, the heat treatment of step c) may be performed with the same conditions or features of the heat treatment step c₂) provided below in section “Step c₂) of heat treatment”. In an embodiment, the decantation or centrifugation of step c) may be performed with the same conditions or features of the decantation or centrifugation step c₃) provided below in section “Step c₃) of decantation or centrifugation”. In an embodiment, the step c) of applying a physical mean is performed through the steps of: c₁) filtering the nettle material slurry to obtain a permeate, c2) optionally, heat-treating the permeate, c3) centrifugating or decanting the permeate to obtain a nettle concentrate. Step c1) of filtration As mentioned above, in an embodiment, the process may comprise a step c1) of filtering the nettle material slurry of step b) to obtain a permeate. After the step c1) of filtration, a retentate and a permeate are obtained. Material that passes through a filter is called “permeate”; material that does not pass through a filter and is recirculated is called “retentate”. The retentate is removed after step c1) and the permeate is recovered and further processed after step c1). In a preferred embodiment, the step c1) of filtration is performed with a filter having a mesh of 25 µm to 1000µm, preferably of 25 µm to 500µm, more preferably of 100 µm to 200µm. This mesh size contributes to separate, concentrate and so increase the purity in compounds of interests from nettle, such as bioactive compounds and/or micronutrients while discarding/decreasing undesired compounds such as insoluble nettle compounds. The mesh size also decreases the particle size of the nettle concentrate to a level such that the concentrate is less incline to sedimentation, in particular when use in liquid form. The step c1) of filtration may be performed in one or several steps. In an embodiment, the step c₁) of filtration may be performed in one to ten steps, preferably one to five steps. When the step c1) of filtration is performed in several steps, i.e. in two to ten steps, preferably two to five steps, the size of the mesh of the filter decreases at each consecutive filtration step. In other words, the size of the mesh of the filter used in a predetermined step of filtration (e.g. first step of filtration) is higher than the size of the mesh of the filter used in the consecutive and downstream step of filtration (e.g. second step of filtration) and so on. In a more preferred embodiment, the step c₁) of filtration is performed in two steps, in particular the nettle material slurry is first filtered with a filter having a mesh of 400 to 500 microns, preferably of 500 microns and then filtered with a filter having a mesh of 50 to 200 microns, preferably of 180 microns. The performance of the filtration step in several steps, in particular two steps, decreases the propensity of the filter to clog. In an embodiment, the sequence of steps a), b) and c₁) is repeated at least two times, preferably 2 to 5 times before step c2) and as of the second sequence of steps a), b) and c1), the nettle material of step a) is replaced by the retentate obtained in the step c₁) of the preceding sequence of steps a), b) and c1). For sake of clarity, as of the second sequence of steps a), b) and c1), the retentate of the preceding sequence of steps a), b) and c1) is suspended in an aqueous liquid in step a) of the consecutive sequence of steps a), b) and c₁) instead of the nettle material. Hence, as of the second sequence of steps a), b) and c1), the suspension of step a) and b) is not a nettle material suspension but a retentate suspension and the slurry of step b) and c1) is not a nettle material slurry but a retentate slurry. In addition, as of the second sequence of steps a), b) and c1), a permeate is still obtained in step c1). Moreover, as of the second sequence of steps a), b) and c1), a retentate is also still obtained in step c1). The obtained retentate may be further processed in the consecutive sequence of steps a), b) and c1) and so on. Step c2) of heat treatment As mentioned above, in an embodiment, the process may comprise a step c2) of optionally heat-treating the permeate obtained in step c1). This heat treatment step allows to extend the shelf-life of the final nettle concentrate. In an embodiment, this step c2) is not optional. In an embodiment, the step c2) of heat treatment is performed at a temperature of at least 60°C for at least 2 seconds. Preferably, the step c2) of heat treatment is performed at a temperature of 60-125°C for 2 seconds to 30 minutes. More preferably, the step c2) of heat treatment is performed at a temperature of 70-85°C for 1 minute to 3 minutes. Step c₃) of decantation or centrifugation As mentioned above, in an embodiment, the process may comprise a step c3) of centrifugating or decanting the permeate to obtain a nettle concentrate. Preferably, the step c₃) is a step of centrifugating the permeate. In an embodiment, the step c3) of centrifugation is performed at 500 to 10000g, preferably at 1000g to 5000g, more preferably 1000g to 3000g. In an embodiment, the step c₃) of centrifugation is performed for 2 to 30 minutes, preferably 2 to 20 minutes, more preferably 5 to 15 minutes. After centrifugation or decantation, a supernatant and a precipitate are obtained. The precipitate corresponds to the material, which is generally solid or semi-solid (in particular, paste), that forms deposits at the bottom of the centrifugation/decantation container while the supernatant corresponds to the material, which is generally liquid, that floats or lies above the precipitate. The supernatant is discarded. The precipitate is recovered. The precipitate obtained after step c3) corresponds to the nettle concentrate. In an embodiment, the step c3) of centrifugation or decantation is performed one time. In other words, the precipitate obtained in step c3) is not further centrifuged or decanted. After step d) of drying, the nettle concentrate is not in the form of a semi-solid (in particular, form of a paste) but is in the form of a powder. For example, the step of drying may be performed by spray drying, roller drying, air drying or freeze drying. In an embodiment, the step d) of drying is not optional. As an alternative to the drying of the nettle concentrate into powder, the water activity of the nettle concentrate may be decreased to improve its microbiological stability over time. Hence, in an alternative embodiment, the process may comprise after step c) of application of physical mean or step c3) of centrifugation or decantation, a step d’) of decreasing the water activity of the iron nettle concentrate. After step d’) of decreasing the water activity, the nettle concentrate has a water activity below 0.85, preferably of 0.5 to 0.85. After this step d’) of water activity decrease, the nettle concentrate is not in powder form. Indeed, the nettle concentrate obtained after step d’) is in the same form as the nettle concentrate obtained after step c) or step c3), i.e. in semi-solid form (in particular, paste form). But, the nettle concentrate obtained after step d’) has a water activity which is lower than the water activity of the nettle concentrate obtained just after step c) or step c3). This step d’) of decreasing the water activity may be performed by evaporating the nettle concentrate, by drying nettle concentrate or by adding a humectant to the nettle concentrate. Preferably, the humectant is sucrose. The quantity of the humectant to be added to the nettle concentrate may be defined easily by a person having ordinary skills in the art depending on the type of the humectant and the targeted water activity. The drying may be performed by freeze drying, spray drying, air drying or roller drying. The evaporation step may be performed with an evaporator. In some embodiment, the step d’) of decreasing the water activity of the nettle concentrate and the step d) of drying the nettle concentrate may be performed sequentially. In this embodiment, the step d’) of decreasing the water activity of the nettle concentrate is before the step d) of drying the nettle concentrate. In some embodiment, in particular when a step d) of drying is applied, the process does not comprise evaporation or drying before step d) of drying. In some embodiment, in particular when a step d) of drying is applied, the process does not comprise any step of evaporation or drying. In some embodiment, when a step d) of drying is not applied, the process does not comprise any step of evaporation or drying. In some embodiment, the step c) is not performed by evaporation or does not comprise any use of evaporation machine, such as rotavapor. Likewise, step c1, c2, c3 and c4 are not performed by evaporation or do not comprise any evaporation, any use of evaporation machine, such as rotavapor. It has been observed that the iron concentration in ppm in the final concentrate is significantly increased in the process of the invention compared to processes that apply drying or evaporation as a concentration method, directly on the permeate without additional physical separation, in particular without centrifugation step. In some embodiment, the process may comprise a step d”) of heat-treating nettle concentrate after step c) or step c3). This step d”) of heat treatment may be before or after step d’). This step d”) of heat treatment may be before or after step d). This step d”) of heat treatment may be performed at a temperature of at least 60°C for at least 2 seconds. Preferably, the step d”) of heat treatment is performed at a temperature of 60-125°C for 2 seconds to 30 minutes. The process allows the effective concentration of the bioactive compounds and/or micronutrients, including bioactive compounds and/or micronutrients that direct and selectively modulate mitochondrial Ca2+ homeostasis. The obtained concentrate has substantial amount of the bioactive compounds and/or micronutrients, including iron. The concentrate through its bioactive compounds and/or micronutrients composition directs and selectively modulates mitochondrial Ca2+ homeostasis. The concentrate is coming from plant materials. Hence, it is from a natural source and is suitable for vegetarian/vegan diet. In addition, the concentrate has good sensory properties and does not impart or impart very limited sensory defects, in particular limited metallic off taste, when use in products to be delivered/consumed orally (e.g. beverage, food product etc…). In addition, the concentrate is a significant source of iron and the iron of the concentrate has satisfactory bioaccessibility properties. Without wishing to be bound by theory, the significant amount of iron in the nettle concentrate may impart immune benefits, in particular may contribute to maintain immune function. The process is substantially natural. It does not involve the use of added organic solvent but still allow effective concentration of bioactive compounds and/or micronutrients, including iron. In a preferred embodiment, the process does not involve the use of any added organic solvent. For example, the process does not involve the use of any added organic solvent selected from the list consisting of acetic acid, acetone, acetonitrile, benzene, 1-butanol, 2- butanol, 3-butanone, t-butyl alcohol, carbon tetrachloride, chlorobenzene, chloroform, cyclohexane, diethylene glycol, diethyl ether, diethylene glycol dimethyl ether, 1,2- dimethoxy-ethane (glyme, DME), dimethyl-formamide (DMF), dimethyl sulfoxide (DMSO), 1,4 dioxane, 1,2-dicholoroethane, ethanol, ethyl acetate, ethylene glycol, glycerin, heptane, hexamethylphosphoramide (HMPA), hexane, methanol, methylene chloride, N-methyl-2- pyrrolidinone (NMP), nitromethane, naphthalene, pentane, 1-propanol, 2-propanol, pyridine, toluene, triethyl amine, tricine, tris, tetrahydrofuran, o-xylene, m-xylene, p-xylene and combination thereof. The process allows to effectively concentrate micronutrients, such as iron of the nettle material. Advantageously, the iron concentration by weight percent is at least 2 times higher, preferably 2 to 10 times higher in the nettle concentrate obtained in step c) or c3) than in the nettle material of step a). For example, the concentration of iron in the nettle concentrate and the nettle material may be measured according to the method provided in the examples. The process allows to effectively decrease the ratio of undesirable antinutritional factors compared to micronutrients, such as iron, in particular antinutritional factors that may decrease or prevent absorption of micronutrients, such as iron in body. In particular, the molar ratio of iron to oxalic acid (M/M) is significantly increased through the process. It is advantageous to increase the molar ratio of iron to oxalic acid to decrease the impact of oxalic acid on iron. Indeed, oxalic acid may decrease or prevent absorption of iron in body. Advantageously, the molar ratio of iron to oxalic acid is at least 2 times higher, preferably 2 to 10 times higher in the nettle concentrate obtained in step c) or c3) than in the nettle material of step a). The molar ratio of iron to oxalic acid of nettle concentrate is expressed by dry weight of the nettle concentrate. The molar ratio of iron to oxalic acid of the nettle material is expressed by dry weight of the nettle material. For example, the molar ratio of iron to oxalic acid in the nettle concentrate and the nettle material may be measured according to the method provided in the examples. In some embodiment, the molar ratio of iron to phytic acid (M/M) is significantly increased through the process of the invention. It is advantageous to increase the molar ratio of iron to phytic acid to decrease the impact of phytic acid on iron. Indeed, phytic acid may decrease or prevent absorption of iron in body. Advantageously, the molar ratio of iron to phytic acid is at least 2 times higher, preferably at least 3 times higher, more preferably 3 to 10 times higher in the nettle concentrate obtained in step c) or c3) than in the nettle material of step a). The molar ratio of iron to phytic acid of the nettle concentrate is expressed by dry weight of the nettle concentrate. The molar ratio of iron to phytic acid of the nettle material is expressed by dry weight of the nettle material. For example, the molar ratio of iron to phytic acid in the nettle concentrate and the nettle material may be measured according to the method provided in the examples. In some embodiment, the process does not comprise any steps of addition of enzymes. For example, the process does not comprise any steps of addition of protein-degrading enzymes, carbohydrate-degrading enzymes, fibre-degrading enzymes, oxalic acid-degrading enzymes, phytic acid-degrading enzymes and/or phenolic compound-degrading enzymes. Nettle concentrate In an embodiment, the nettle concentrate as disclosed herein comprises at least 500 ppm iron by dry weight of the nettle concentrate. In a preferred embodiment, the nettle concentrate comprises at least 1000 ppm iron, more preferably at least 1500 ppm iron by dry weight of nettle concentrate. In an embodiment, the nettle concentrate comprises at most 15000ppm iron, preferably at most 4000 ppm, more preferably at most 2000 ppm by dry weight of nettle concentrate. For example, the concentration of iron of the nettle concentrate may be measured according to the method provided in the examples. In an embodiment, the nettle concentrate is coming from nettle material. In particular, the nettle concentrate comprises a nettle material. The nettle material may be a nettle material as provided above in the section “Process for obtaining the nettle concentrate”. In some embodiment, the nettle concentrate as disclosed herein has an iron bioaccessibility of at least 3%, preferably at least 5%, more preferably of at least 7%, even more preferably of at least 8%. In some further embodiment, the nettle concentrate as disclosed herein has an iron bioaccessibility of at most 50%, preferably at most 35%, more preferably at most 25%, most preferably at most 9%. The iron bioaccessibility of the nettle concentrate may be measured as provided in the examples. In an embodiment, the nettle concentrate as disclosed herein has an absolute amount of bioaccessible iron of at least 35 ppm, preferably of at least 50 ppm, more preferably of at least 100 ppm, even more preferably of at least 120 ppm. In some further embodiment, the nettle concentrate has an absolute amount of bioaccessible iron of at most 1500 ppm, preferably of at most 1000 ppm, more preferably at most 500 ppm, even more preferably of at most 200 ppm, even more preferably of at most 150 ppm, even more preferably of at most 50 ppm. For example, the absolute amount of bioaccessible iron of the nettle concentrate may be measured according to the method provided in the examples. In an embodiment, the nettle concentrate as disclosed herein has a molar ratio of iron to oxalic acid (M/M) of at least 0.3, preferably 0.3 to 3, more preferably 0.4 to 3, even more preferably 0.4 to 1.5, most preferably 0.4 to 1.2. The molar ratio of iron to oxalic acid is expressed by dry weight of the nettle concentrate. For example, the molar ratio of iron to oxalic acid of the nettle concentrate may be measured according to the method provided in the examples. In some embodiment, the nettle concentrate as disclosed herein comprises less than 15000 ppm, preferably less than 10000 ppm, more preferably less than 5000 ppm, most preferably less than 3000ppm oxalic acid by dry weight of nettle concentrate. For example, the concentration of oxalic acid in the nettle concentrate may be measured according to the method provided in the examples. In some embodiment, the nettle concentrate as disclosed herein has a molar ratio of iron to phytic acid (M/M) of at least 2, preferably at least 5, more preferably 5 to 80, even more preferably 5 to 50, even more preferably 5 to 20, most preferably 7 to 15. The molar ratio of iron to phytic acid is expressed by dry weight of the nettle concentrate. For example, the molar ratio of iron to phytic acid of the nettle concentrate may be measured according to the method provided in the examples. In some embodiment, the nettle concentrate as disclosed herein comprises less than 3000 ppm, preferably less than 2500 ppm, more preferably less than 2200ppm phytic acid by dry weight of nettle concentrate. For example, the concentration of phytic acid in the nettle concentrate may be measured according to the method provided in the examples. In an embodiment, the nettle concentrate as disclosed herein is free from added organic solvent, in particular is free from any added organic solvent listed above in the section “Process for obtaining the nettle concentrate”. In an embodiment, the nettle concentrate as disclosed herein has a pH of 3 to 8. In an embodiment, the nettle concentrate as disclosed herein comprises 0.01% to 5% wt% of acid. The acid may be an acid as provided above in the section “Process for obtaining the nettle concentrate”. Preferably, the acid is selected from the group consisting of ascorbic acid, malic acid, citric acid, hydrochloric acid or a mixture thereof. In a more preferred embodiment, the acid is selected from the group consisting of malic acid, citric acid, hydrochloric acid or a mixture thereof. In an even more preferred embodiment, the acid is selected from the group consisting of citric acid, hydrochloric acid or a mixture thereof. In a most preferred embodiment, the acid is hydrochloric acid. In another most preferred embodiment, the acid is citric acid. The acid may be provided as pure acid solution, as diluted acid solution or as acid- containing food ingredient. Examples of acid-containing food ingredients include citrus juice such as lemon juice, lime juice, orange juice, tangerine juice and the like. When the acid is citric acid, the nettle concentrate as disclosed herein may comprise 0.01 to 3wt%, preferably 0.5 to 2.3wt% citric acid. When the acid is hydrochloric acid, the nettle concentrate as disclosed herein may comprise 0.01 % to 0.5wt% hydrochloric acid, preferably 0.05 to 0.5wt% hydrochloric acid. When the acid is malic acid, the nettle concentrate as disclosed herein may comprise 0.01 % to 3wt% malic acid, preferably 0.5 to 2.5wt% malic acid. In an embodiment, the nettle concentrate as disclosed herein may comprise an osmotic agent. The osmotic agent may be an osmotic agent as provided above in the section “Process for obtaining the nettle concentrate”. In an embodiment, the nettle concentrate as disclosed herein may comprise a humectant. The humectant may be a humectant as provided above in the section “Process for obtaining the nettle concentrate”. In an embodiment, the nettle concentrate as disclosed herein may comprise a total sucrose content of 1 to 50 wt.%, preferably 5 to 20 wt.%. The sucrose in the nettle concentrate may be used as humectant and/or osmotic agent. The total sucrose content range provided herein applies regardless sucrose is used as humectant and/or osmotic agent. The nettle concentrate as disclosed herein has substantial amount of bioactive compounds and/or micronutrients, including iron. The nettle concentrate through its bioactive compounds and/or micronutrients composition directs and selectively modulates mitochondrial Ca2+ homeostasis. The nettle concentrate is coming from plant materials. Hence, it is from a natural source and is suitable for vegetarian/vegan diet. In addition, the nettle concentrate has good sensory properties and does not impart or impart very limited sensory defects, in particular very limited metallic off taste, when use in products to be delivered/consumed orally. In addition, the nettle concentrate is a significant source of iron and the iron of the concentrate has satisfactory bioaccessibility properties. Without wishing to be bound by theory, the significant amount of iron in the nettle concentrate may impart immune benefits, in particular may contribute to maintain immune function. Composition The composition may also further comprise one or more additional bioactive compounds. In particular, the composition may further comprise at least one compound selected from the group consisting of antioxidants, anti-inflammatory compounds, glycosaminoglycans, prebiotics, fibers, probiotics, fatty acids, enzymes, minerals, trace elements and/or vitamins. The compound(s) may be from a natural source. Thus, the compound(s) may be from extracts of plants, animals, fish, fungi, algae, or microbial fermentation. Preferably, the compound(s) are from plants, fungi or algae. Minerals are considered to be from a natural source. In a preferred embodiment, enzymes may be proteases such as trypsin, or enzyme extracts such as bromelain, for example. The effective amount of nettle concentrate varies with the particular composition, the age and condition of the recipient, and the particular disorder or disease being treated. Nevertheless, in a general embodiment, 0.20 mg to 20 g can be administered to the individual per day, preferably from 1 mg to 20 g per day, more preferably from 1 mg to 10 mg per day, more preferably from 1 g to 10 g per day. The composition can comprise an effective amount of the nettle concentrate. For example, a single serving or dose of the composition can comprise the effective amount, and a package can contain one or more of the servings or doses. Optionally, the composition can further comprise calcium. In a particular embodiment, the nettle concentrate, in particular the effective amount of nettle concentrate may be administered in a composition further comprising calcium. The composition can comprise a food additive selected from the group consisting of acidulants, thickeners, buffers or agents for pH adjustment, chelating agents, colorants, emulsifiers, excipients, flavor agents, minerals, osmotic agents, a pharmaceutically acceptable carrier, preservatives, stabilizers, sugars, sweeteners, texturizers, vitamins, minerals and combinations thereof. The nettle concentrate, in particular the effective amount of nettle concentrate can be administered in any composition that is suitable for human and/or animal consumption. In a preferred embodiment, it is administered to the individual orally or enterally (e.g. tube feeding). For example, it can be administered to the individual in a beverage, a food product, a capsule, a tablet, a powder or a suspension. Non-limiting examples of suitable compositions include food compositions, dietary supplements (e.g., liquid ONS), nutritional compositions, complete nutritional compositions, beverages, pharmaceuticals, oral nutritional supplement, medical food, nutraceuticals, food for special medical purpose (FSMP), powdered nutritional products to be reconstituted in water or milk before consumption, food additives, medicaments, petfood, and combinations thereof. Food products according to the present invention may include dairy products, such as fermented milk products, e.g., yoghurts, buttermilk, etc; ice creams; concentrated milk; milk; dairy creams; flavoured milk beverages; whey based beverages; toppings; coffee creamers; plant-based dairy product analogues, chocolate; cheese based products; soups; sauces; purees; dressings; puddings; custards; baby foods; nutritional formulas, such as those for complete nutrition, for example for infants, children, teenagers, adults, the elderly or the critically ill; cereals and cereal bars, for example. Beverages (or drinks) may include for example milk- or yoghurt-based beverages, fermented milk, protein beverages, coffee, tea, energy drinks, soy beverages, water-based beverage, dairy beverage analogue, fruit and/or vegetable beverages, fruit and/or vegetable juices. The nettle concentrate, in particular the effective amount of nettle concentrate can be administered in a food product or beverage further comprising a component selected from the group consisting of protein, carbohydrate, fat and mixtures thereof. In an embodiment, the source of protein is preferably purified protein (i.e., isolated from the native food ingredient in which it was created). The protein content of the composition is preferably 20-99 wt.% of the composition, for example 20-90 wt.% of the composition, for example, 30-80 wt.% of the composition, for example 40-80 wt.% of the composition, for example 50-80 wt.%, for example 40-70 wt.% of the composition. Non-limiting examples of suitable protein or sources thereof for use in the compositions include hydrolyzed, partially hydrolyzed or non-hydrolyzed proteins or protein sources. They may be derived from any known or otherwise suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, corn) or vegetable (e.g., soy, pea) sources. Combinations of sources or types of proteins may be used. Non-limiting examples of proteins or sources thereof include intact pea protein, intact pea protein isolates, intact pea protein concentrates, milk protein isolates, milk protein concentrates, casein protein isolates, casein protein concentrates, whey protein concentrates, whey protein isolates, sodium or calcium casemates, whole cow's milk, partially or completely defatted milk, yoghurt, soy protein isolates and soy protein concentrates, and combinations thereof. Combinations of sources or types of proteins may be used. Preferred proteins include pea protein, oat protein, faba protein, whey protein, soy protein and casein. Casein proteins may, for example, comprise sodium caseinate and calcium caseinate. The source of protein may be provided by individual amino acids, polypeptides comprising amino acids, or mixtures thereof. For many muscle growth, muscle maintenance and/or muscle enhancement treatments, particular amino acids beneficial, for example L- arginine, L-glutamine, lysine and the branched-chain amino acids (i.e. leucine, isoleucine, and valine; in particular leucine and isoleucine). These particular amino acids may be provided as the source of protein, or they may be additional to a main source of protein. Thus, the source of protein in the composition may include one or more branched-chain amino acids (leucine, isoleucine, and valine); one or both of L-arginine and L-glutamine; and lysine. In a preferred embodiment, the composition comprises whey protein and/or casein protein together with one or more individual amino acids, for example one or more of (or all of) leucine, isoleucine and L-arginine. In an embodiment, the composition further comprises a medium-chain triglyceride, for example one or more of caproic acid, caprylic acid, capric acid and lauric acid. In an embodiment, the composition further comprises a phospholipid, for example phosphatidylcholine. The composition may also contain a carbohydrate and/or a source of fat. Non-limiting examples of suitable fats include canola oil, corn oil and high-oleic acid sunflower oil. Non- limiting examples of suitable carbohydrates include sucrose, lactose, glucose, fructose, corn syrup solids, maltodextrins, and mixtures thereof. Additionally or alternatively, a dietary fiber may be added. Dietary fiber passes through the small intestine undigested by enzymes and functions as a natural bulking agent and laxative. Dietary fiber may be soluble or insoluble and generally a blend of the two types is preferred. Non-limiting examples of suitable dietary fibers include soy, pea, oat, pectin, guar gum, partially hydrolyzed guar gum, gum Arabic, fructo-oligosaccharides, acidic oligosaccharides, galacto-oligosaccharides, sialyl-lactose and oligosaccharides derived from animal milks. A preferred fiber blend is a mixture of inulin with shorter chain fructo-oligosaccharides. In an embodiment, the fiber content is between 2 and 40 g/L of the composition, for example between 4 and 10 g/L. One or more other minerals additional to any calcium can be used in the composition. Non-limiting examples of suitable minerals include boron, chromium, copper, iodine, iron, magnesium, manganese, molybdenum, nickel, phosphorus, potassium, selenium, silicon, tin, vanadium, zinc, and combinations thereof. One or more other vitamins can be used in the composition. Non-limiting examples of suitable vitamins include vitamin A, Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (niacin or niacinamide), Vitamin B5 (pantothenic acid), Vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine, or pyridoxine hydrochloride), Vitamin B7 (biotin), Vitamin B9 (folic acid), and Vitamin B12 (various cobalamins; commonly cyanocobalamin in vitamin supplements), Vitamin C, Vitamin D, Vitamin E, Vitamin K, folic acid and biotin), and combinations thereof. “Vitamin” includes such compounds obtained naturally from plant and animal foods or synthetically made, pro-vitamins, derivatives thereof, and analogs thereof. One or more food grade emulsifiers may be incorporated into the composition, such as diacetyl tartaric acid esters of mono- and di-glycerides, lecithin, and/or mono- and di- glycerides. Suitable salts and stabilizers may be included. The compositions disclosed herein can use any of a variety of formulations for therapeutic administration. More particularly, pharmaceutical compositions can comprise appropriate pharmaceutically acceptable carriers or diluents and may be formulated into preparations in solid, semi-solid, liquid or gaseous forms, such as tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalants, gels, microspheres, and aerosols. As such, administration of the composition can be achieved in various ways, including oral, buccal, rectal, parenteral, intraperitoneal, intradermal, transdermal, and intratracheal administration. The active agent may be systemic after administration or may be localized by the use of regional administration, intramural administration, or use of an implant that acts to retain the active dose at the site of implantation. In pharmaceutical dosage forms, the nettle concentrate may also be used in appropriate association with other pharmaceutically active compounds. The following methods and excipients are merely exemplary and are in no way limiting. For oral preparations, the nettle concentrate can be used alone or in combination with appropriate additives to make tablets, powders, granules or capsules, for example, with conventional additives, such as lactose, mannitol, corn starch or potato starch; with binders, such as crystalline cellulose, cellulose functional derivatives, acacia, corn starch or gelatins; with disintegrators, such as corn starch, potato starch or sodium carboxymethylcellulose; with lubricants, such as talc or magnesium stearate; and if desired, with diluents, buffering agents, moistening agents, preservatives and flavoring agents. In some embodiment, the composition is in a form of a solid powder, a powdered stick, a capsule or a solution. The composition, in particular the nettle concentrate, more particularly the effective amount of nettle concentrate can be administered at least one day per week, preferably at least two days per week, more preferably at least three or four days per week (e.g., every other day), most preferably at least five days per week, six days per week, or seven days per week. The time period of administration can be at least one week, preferably at least one month, more preferably at least two months, most preferably at least three months, for example at least four months. In an embodiment, dosing is at least daily; for example, a subject may receive one or more doses daily. In some embodiments, the administration continues for the remaining life of the individual. In other embodiments, the administration occurs until no detectable symptoms of the medical condition remain. In specific embodiments, the administration occurs until a detectable improvement of at least one symptom occurs and, in further cases, continues to remain ameliorated. In some embodiment, the composition, in particular the nettle concentrate, more particularly the effective amount of nettle concentrate is orally administered daily for at least one week. In an embodiment, the compositions is free from milk and/or soy. In an embodiment, the composition is vegetarian. In another embodiment, the composition is vegan. Methods of treatment An aspect of the present disclosure is a composition comprising a nettle concentrate, in an effective amount for use in (i) improving a physiological state linked to metabolic fatigue in one or more cells, and/or (ii) increasing mitochondrial energy and mitochondrial calcium uptake in one or more cells, and/or (iii) enhancing mitochondrial function, and/or (iv) treating or preventing a calcium deficiency / depletion disorder in an individual. The nettle concentrate is a nettle concentrate as disclosed herein and the nettle concentrate is obtainable or obtained by a process as disclosed herein. In an embodiment, at least a portion of the one or more cells are part of at least one body part selected from the group consisting of liver, kidney, brain and skeletal muscle. In a preferred embodiment, the cells are cells from skeletal muscle. Non-limiting examples of cells from skeletal muscle include myoblasts, myotubes, and combination thereof. In a more preferred embodiment, the cells are myotubes. In another embodiment, the physiological state linked to metabolic fatigue comprises muscle fatigue, muscle weakness, lack of vitality, weakness or lack of energy, in particular lack of physical energy. In some embodiments, the methods comprise identifying the individual as having the condition or being at risk of the condition before the administration. Another aspect of the present disclosure is a composition comprising a nettle concentrate, for use in an effective amount for treating or preventing (e.g., reducing incidence and/or severity of) a mitochondria-related disease or a condition associated with altered mitochondrial function in an individual in need thereof or at risk thereof. The method comprises orally administering an effective amount of the nettle concentrate to the individual in need thereof or at risk thereof. The nettle concentrate is a nettle concentrate as disclosed herein and the nettle concentrate is obtainable or obtained by a process as disclosed herein. Without being bound by theory, it is believed that various types of stress result in stress injury to mitochondria, thereby reducing their ability to perform numerous functions essential to overall cell function. The methods disclosed herein can be useful for treating conditions involving stress injury to mitochondria, which injury may be manifest in any of a number of ways including, but not limited to, mitochondrial disease. Mitochondrial diseases are the result of either inherited or spontaneous mutations in mitochondrial DNA or nuclear DNA which lead to altered functions of the proteins or RNA molecules that normally reside in mitochondria. Problems with mitochondrial function, however, may only affect certain tissues as a result of factors occurring during development and growth that are not yet fully understood. Even when tissue-specific isoforms of mitochondrial proteins are considered, it is difficult to explain the variable patterns of affected organ systems in the mitochondrial disease syndromes seen clinically. Mitochondrial diseases result from failures of the mitochondria, specialized compartments present in every cell of the body except red blood cells. Mitochondria are responsible for creating more than 90% of the energy needed by the body to sustain life and support growth. When they fail, less and less energy is generated within the cell. Cell injury and even cell death follow. If this process is repeated throughout the body, whole systems begin to fail, and the life of the person in whom this is happening is severely compromised. Mitochondrial diseases primarily affect children, but adult onset is becoming more recognized. Diseases of the mitochondria appear to cause the most damage to cells of the brain, heart, liver, skeletal muscles, kidney, and the endocrine and respiratory systems. Many symptoms in mitochondrial disorders are non-specific. The symptoms may also show an episodic course, with periodic exacerbations. The episodic condition of migraine, as well as myalgia, gastrointestinal symptoms, tinnitus, depression, chronic fatigue, and diabetes, have been mentioned among the various manifestations of mitochondrial disorders in review papers on mitochondrial medicine. In patients with mitochondrial disorders, clinical symptomatology typically occurs at times of higher energy demand associated with physiological stressors, such as illness, fasting, over-exercise, and environmental temperature extremes. Furthermore, psychological stressors also frequently trigger symptomatology, presumably due to higher brain energy demands for which the patient is unable to match with sufficient ATP production. Depending on which cells are affected, symptoms may include loss of motor control, muscle weakness and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes developmental, respiratory complications, seizures, visual/hearing problems, lactic acidosis, delays and susceptibility to infection. Mitochondrial diseases include, without limitation, Alper's disease; Barth syndrome; beta-oxidation defects; carnitine deficiency; carnitine-acyl-carnitine deficiency; chronic progressive external ophthalmoplegia syndrome; co-enzyme Q10 deficiency; Complex I deficiency; Complex II deficiency; Complex III deficiency; Complex IV deficiency; Complex V deficiency; CPT I deficiency; CPT II deficiency; creatine deficiency syndrome; cytochrome c oxidase deficiency; glutaric aciduria type II; Kearns-Sayre syndrome; lactic acidosis; LCHAD (long-chain acyl-CoA dehydrogenase deficiency); Leber's hereditary optic neuropathy; Leigh disease; lethal infantile cardiomyopathy; Luft disease; MAD (medium-chain acyl-CoA dehydrogenase deficiency); mitochondrial cytopathy; mitochondrial DNA depletion; mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms; mitochondrial encephalopathy; mitochondrial myopathy; mitochondrial recessive ataxia syndrome; muscular dystrophies, myoclonic epilepsy and ragged-red fiber disease; myoneurogenic gastrointestinal encephalopathy; neuropathy, ataxia, retinitis pigmentosa, and ptosis; Pearson syndrome; POLG mutations; pyruvate carboxylase deficiency; pyruvate dehydrogenase deficiency; SCHAD (short-chain acyl-CoA dehydrogenase deficiency); and very long-chain acyl-CoA dehydrogenase deficiency. In an embodiment, the mitochondria-related disease or condition is selected from the group consisting of stress (e.g., early-life stress and/or effects therefrom), physiological ageing, obesity, reduced metabolic rate, metabolic syndrome, diabetes mellitus, complications from diabetes, hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder (e.g., stress-induced or stress-related mood disorder), anxiety disorder (e.g., stress-induced or stress-related anxiety disorder), age-related neuronal death or dysfunction (e.g., age-related neuronal death or dysfunction not attributable to a specific neurodegenerative disease), musculoskeletal disorder, frailty, pre-frailty, chronic kidney disease, kidney failure, trauma, infection (e.g. in ICU), cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof. Accordingly, an aspect of the present disclosure is a unit dosage form comprising a nettle concentrate for use in an effective amount for treatment or prevention of at least condition selected from the group consisting of stress (e.g., early-life stress and/or effects therefrom), physiological ageing, obesity, reduced metabolic rate, metabolic syndrome, diabetes mellitus, complications from diabetes, hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder (e.g., stress-induced or stress-related mood disorder), anxiety disorder (e.g., stress-induced or stress-related anxiety disorder), age-related neuronal death or dysfunction (e.g., age-related neuronal death or dysfunction not attributable to a specific neurodegenerative disease), musculoskeletal disorder, frailty, pre-frailty, chronic kidney disease, kidney failure, trauma, infection (e.g. in ICU), cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof. The nettle concentrate is a nettle concentrate as disclosed herein and the nettle concentrate is obtainable or obtained by a process as disclosed herein. Another aspect of the present disclosure is a method of treating at least one condition selected from the group consisting of stress, obesity, reduced metabolic rate, metabolic syndrome, diabetes mellitus, cardiovascular disease, hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder (e.g., stress-induced or stress-related mood disorder), anxiety disorder (e.g., stress- induced or stress-related anxiety disorder) and age-related neuronal death or dysfunction (e.g., age-related neuronal death or dysfunction not attributable to a specific neurodegenerative disease), trauma, infection (e.g. in ICU) or cancer in an individual having the at least one condition, said method comprising the administering of a composition comprising a nettle concentrate in an effective amount to said individual having the at least one condition. In an embodiment, the hyperlipidemia that is treated or prevented comprises hypertriglyceridemia. In an embodiment, the hyperlipidemia that is treated or prevented comprises elevated free fatty acids. In an embodiment, the age-related neuronal death or dysfunction that is treated or prevented is by administration of the composition to an older adult, such as an elderly individual. The stress that is treated or prevented can be early-life stress, i.e., stress experienced while under the age of five years from birth. Early-life stress has been reported to have a significant detrimental effect on cognitive performance, including psychological parameters such as increased rates of or susceptibility to depression, anxiety, and abnormal risk-taking behavior. Increased rates of attention-deficit/hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), and major depression have been reported in individuals having experienced early-life stress. Another aspect of the present disclosure is a method of delaying off-set of metabolic decline, maintaining muscle mass, decreasing oxidative stress, maintaining immune function and/or maintaining cognitive function in a healthy older adult, said method comprising the administering of a composition comprising a nettle concentrate in an effective amount to said healthy older adult. The nettle concentrate is a nettle concentrate as disclosed herein and the nettle concentrate is obtainable or obtained by a process as disclosed herein. Another aspect of the present disclosure is a composition comprising a nettle concentrate for use in an effective amount for delaying off-set of metabolic decline, and/or maintaining muscle mass and/or maintaining immune function and/or maintaining cognitive function in a healthy older adult. The nettle concentrate is a nettle concentrate as disclosed herein and the nettle concentrate is obtainable or obtained by a process as disclosed herein. Another aspect of the present disclosure is a method for enhancing at least one of mental performance or muscle performance in an individual, said method comprising the administering of a composition comprising a nettle concentrate in an effective amount to said individual. The nettle concentrate is a nettle concentrate as disclosed herein and the nettle concentrate is obtainable or obtained by a process as disclosed herein. Another aspect of the present disclosure is a composition comprising a nettle concentrate for use in an effective amount for enhancing at least one of mental performance or muscle performance in an individual. The nettle concentrate is a nettle concentrate as disclosed herein and the nettle concentrate is obtainable or obtained by a process as disclosed herein. Another aspect of the present disclosure is a method for improving or maintaining cognitive function, in an individual, said method comprising the administering of a composition comprising a nettle concentrate in an effective amount to said individual. The nettle concentrate is a nettle concentrate as disclosed herein and the nettle concentrate is obtainable or obtained by a process as disclosed herein. In an embodiment, the cognitive function is selected from the group consisting of perception, memory, attention, speech comprehension, speech generation, reading comprehension, creation of imagery, learning, reasoning, and combinations thereof. Another aspect of the present disclosure is a composition comprising a nettle concentrate for use in an effective amount for improving or maintaining cognitive function, in an individual. The nettle concentrate is a nettle concentrate as disclosed herein and the nettle concentrate is obtainable or obtained by a process as disclosed herein. In an embodiment, the cognitive function is selected from the group consisting of perception, memory, attention, speech comprehension, speech generation, reading comprehension, creation of imagery, learning, reasoning, and combinations thereof. The compositions disclosed herein can also be used in the treatment of any of a variety of additional diseases and conditions in which defective or diminished mitochondrial activity participates in the pathophysiology of the disease or condition, or in which increased mitochondrial function will yield a desired beneficial effect. Non-limiting examples of such conditions include male infertility associated with diminished sperm motility, macular degeneration and other age-related and inherited eye disorders, and hearing loss (e.g., age- related hearing loss). Yet another aspect of the present disclosure is a unit dosage form comprising a nettle concentrate in an amount effective for at least one of (i) treating, reducing an incidence of, or reducing severity of a mitochondria-related disease or condition associated with altered mitochondrial function, and/or (ii) improving in a physiological state linked to metabolic fatigue in one or more cells, and/or (iii) increasing mitochondrial energy and mitochondrial calcium uptake in one or more cells, and (iv) treating or preventing a calcium deficiency / depletion disorder, and/or (v) increasing metabolic rate, and/or (vi) improving or maintaining cognitive function, and/or (vii) increasing or maintaining mitochondrial function. The nettle concentrate is a nettle concentrate as disclosed herein and the nettle concentrate is obtainable or obtained by a process as disclosed herein. In an embodiment, the physiological state linked to metabolic fatigue comprises muscle fatigue, muscle weakness, lack of vitality, weakness or lack of energy, in particular lack of physical energy. In an embodiment, the mitochondria-related disease or condition is selected from the group consisting of stress (e.g., early-life stress and/or effects therefrom), physiological ageing, obesity, reduced metabolic rate, metabolic syndrome, diabetes mellitus, complications from diabetes, hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder (e.g., stress-induced or stress-related mood disorder), anxiety disorder (e.g., stress-induced or stress-related anxiety disorder), age-related neuronal death or dysfunction (e.g., age-related neuronal death or dysfunction not attributable to a specific neurodegenerative disease), musculoskeletal disorder, frailty, pre-frailty, chronic kidney disease, kidney failure, trauma, infection (e.g. in ICU), cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof. In an embodiment, the cognitive function is selected from the group consisting of perception, memory, attention, speech comprehension, speech generation, reading comprehension, creation of imagery, learning, reasoning, and combinations thereof. In a further embodiment, the unit dosage form consists essentially of the nettle concentrate. In some embodiment of the different aspects of the present disclosure, the individual may be an older adult, an elderly or a patient in ICU. The above examples of administration do not require continuous daily administration with no interruptions. Instead, there may be some short breaks in the administration, such as a break of two to four days during the period of administration. The ideal duration of the administration of the composition can be determined by those of skill in the art. In a preferred embodiment of any of the above aspects, the above benefits/effects (e.g. enhancing at least one of mental performance or muscle performance improving or maintaining cognitive function etc.) are obtained by enhancing mitochondrial calcium uptake in cells, preferably skeletal muscle cells. In a preferred embodiment of any of the above aspects, any effects/benefits on the mitochondria functioning (e.g. mitochondrial energy increase, mitochondrial calcium uptake increase mitochondrial function enhancement etc.) are preferably effects/benefits on mitochondria of skeletal muscle cells. Those skilled in the art will understand that they can freely combine all features of the present invention disclosed herein. In particular, features described for the products/compositions of the present invention may be combined with the treatment method of the present invention and vice versa. Further, features described for different embodiments or aspects of the present invention/disclosure may be combined. Furthermore, where known equivalents exist to specific features, such equivalents are incorporated as if specifically referred in this specification. Further advantages and features of the present invention are apparent from the figures and non-limiting examples. EXAMPLES In all the following examples, the nettle material is Urtica dioica material and the nettle concentrate is a concentrate obtained by processing Urtica dioica through the processes described in the examples. Example 1 – Nettle concentration process of the invention from dry herbs without acids Dry nettle (Urtica dioica) material, comprising leaves and stems was ground to a powder. The powder was mixed with water in a ratio 1:15 (w:v) and the powder was let to hydrate for 5 min to form a suspension. The suspension was then blended for 1 min to obtain a slurry. The obtained slurry was filtered through a 500 µm mesh size filter. The permeate was recovered and subsequentially filtered through a 180 µm mesh size filter. The permeate was recovered again and the obtained permeate was heat-treated to reach a temperature of 71 °C for 2 min. After cooling to 4 °C, the permeate was centrifuged at 2500g for 10 min. The precipitate was recovered and formed the nettle concentrate. Optionally, the concentrate can be dried. Example 2- Nettle concentration process of the invention from dry herbs in presence of acids Dry nettle (Urtica dioica) material, comprising leaves and stems was ground to a powder. The powder (50 g) was mixed with water (700 mL) in a ratio 1:15 (w:v) to prepare a suspension, and pure citric acid (15,8 g anhydrous citric acid) or hydrochloric acid (15 mL 6 M HCl solution) was added in the suspension to reach a pH of 3.5. After acid addition, the suspension was let for 2 minutes to ensure appropriate hydration of the powder in the suspension. The suspension was then blended for 2 min to obtain a slurry. The obtained slurry was filtered through a 500 µm mesh size filter. The permeate was recovered and subsequentially filtered through a 180 µm mesh size filter. The permeate was recovered again and the obtained permeate was heat-treated to reach a temperature of 71 °C for 2 min. After cooling to 4 °C, the permeate was centrifuged at 2500g for 10 min. The precipitate was recovered and formed the nettle acid concentrate. Optionally, the concentrate can be dried. Example 3 – Iron quantification Materials and Methods Iron contents of the nettle material (i.e. dry nettle powder obtained after grinding) and nettle concentrate obtained in either example 1 or 2 were determined by atomic emission spectrometry, using a Microwave plasma atomic emission spectroscopy (MP-AES) 4200 (Agilent, Switzerland). For MP-AES analysis, samples (approx.100–400 mg) were mineralized in duplicate in a Microwave Digestion System (Mars 6, CEM, USA) using Xpress microwave bombs with 4 mL of 70% HNO₃ supra pure quality (Sigma-Aldrich, St. Louis, MO, USA 1 mL of 30% H₂O₂ (Merck KGaA, (Darmstadt, Germany). Mineral solutions were then transferred to 50 mL Falcon tubes and the volume was adjusted to 20 mL with Milli-Q water. Iron content was measured using external calibration with multi element standards at the wavelength 371 nm. Accuracy of the analysis was checked by analyzing the standard reference materials (SRM 3233, Typical Diet; NIST, MD, USA). Results Figure 1 shows the iron concentration (based on DW) of nettle material (i.e. dry nettle powder obtained after grinding of dy nettle material) and nettle concentrate obtained according to the method of example 1. The concentration process of the invention resulted in a significant increase in iron concentration from 288 ppm in nettle material to 1355 ppm in nettle concentrate. Example 4 – Quantification of antinutritional factors Materials and Methods: Oxalic acid was extracted from the sample with water under mechanical agitation. Oxalic acid was determined by ion chromatography (Dionex ICS-5000, with column Dionex Ion PAC AS16 REFIC Analytical (250 x 2 mm)) coupled to mass spectrometry (SCIEX Triple Quad 5500 with Selexion). The phytic acid was measured according to the “phytic acid (phytate) / Total phosphorus” Megazyme kit. This kit enables quantification of free and total phosphorus in the sample by means of colorimetric detection. Total phosphorus is defined as the phosphorus that is derived from phytic acid as well as other sources and is measured after treating sample first with phytase followed by alkaline phosphatase. Free phosphorus, on the other hand, is defined as phosphorus derived from non-phytic acid sources within the sample and is measured without enzymatic treatment from the kit. In short, 1 g of sample was mixed with 20 mL HCl acid (0.66 M) and stirred vigorously for 3 h. The extract (1 mL), was centrifuged at 13000 rpm for 10 min and 0,5 mL of the resulting supernatant was neutralised with 0.5 mL NaOH solution (0.75 M). The neutralised sample extract (0.05 mL) was mixed with distilled water (0.60 mL), the provided buffer I (0.20 mL) and a phytase suspension (0.02 mL) for the quantification of total phosphorus. A control sample was prepared by mixing the sample extract (0.05 mL) with distilled water (0.62 mL) and the provided buffer I (0.20 mL) to quantify free phosphorus. Both samples were vortexed and incubated at 40 °C for 10 min. Distilled water (0.02 mL) and provided buffer 3 (0.2 mL) were added to the control, while buffer 3 (0.20 mL) and suspension 4 (ADP, 0.02 mL) were added to the sample for total phosphorus. Samples were vortexed and incubated at 40 °C for 15 min. The reaction was stopped by adding 0.30 mL of trichloroacetic acid (50% w/v). Samples were centrifuged at 13000 rpm for 10 min. The supernatant (1 mL) was used for the colorimetric determination of phosphorus. The samples was mixed with 0.5 mL of color reagent. The color reagent was prepared by mixing 1 part of ammonium molybdate solution (5% w/v) with 5 parts of ascorbic acid (10 % w/v)/sulphuric acid (1 M) solution. After mixing the sample with the color reagent, it was incubated at 40 °C for 1 h and afterwards the absorbance read at 655 nm. Measured absorbance was used to calculate concentration of phosphorus, which was in turn used to calculate concentration of PA. Formula (1) was used to calculate concentration of phosphorus in free phosphorus as well as total phosphorus reactions. mean M × vHCl × F × ΔA c = _^^^^^^ ^_^^^^^^^^^ w × v × 10000 c_phosphorus = concentration of phosphorus in the sample [g/100g] mean M = mean value of phosphorus standards [μg/ΔA_standard], where M = μg of phosphorus in the standard solution (i.e., 0.5 – 7.5) divided by ΔA_standard (i.e., A_{standard X} - A_{standard 0}) vHCl = original sample extract volume [mL] F = dilution factor (in this work, F = 1) ΔA_sample = absorbance difference of the sample (i.e., A_{sample tot} – A_{sample free}) w= weight of original sample material [g] v = sample volume used in the colourimetric determination step [mL] (= 1 mL) 10000 = conversion from μg/g to g/100 g Equation (2) is used to convert calculated concentration of bound phosphorus into PA concentration. It assumes that the amount of bound phosphorus measured is exclusively of PA-origin. c c = _{^^^^^^^^^^ ^^} (2) 0.282 c_{PA =} concentration of PA in the sample [g/100g] cphosphorus = concentration of bound phosphorus in the sample [g/100g] 0.282 = mass fraction of phosphorus in PA The molar ratio between iron and phytic acid was then calculated. Results: Table 1 shows the amount of oxalic acid and phytic acid based on dry weight of nettle concentrate obtained according to the method of example 1. Oxalic acid and phytic contents (ppm) based on dry weight of nettle concentrate Oxalic acid (ppm) Phytic acid (ppm) Nettle concentrate 2229 1575 ± 461 Table 1 Figure 2 shows the molar ratio between iron and oxalic acid molar concentrations in nettle material (i.e. dry nettle powder obtained after grinding of dry nettle material) and nettle concentrate obtained according to the method of example 1. The concentration process of the invention resulted in an increase in the iron to oxalic acid ratio from 0.23 to 1.11, indicating a lower concentration of iron potentially chelated by oxalic acid in the nettle concentrate than in the nettle material, and therefore potentially more iron available for absorption. Figure 3 shows the molar ratio between iron and phytic acid molar concentrations in nettle material (i.e. dry nettle powder obtained after grinding of dry nettle material) and nettle concentrate obtained from them according to the method of example 1. The concentration process of the invention resulted in an increase in the iron to phytic acid ratio from 1.3 in nettle material to 8.9 in nettle concentrate. These results indicate a lower concentration of iron potentially chelated by phytic acid in the nettle concentrate than in the nettle material, and therefore potentially more available for absorption. Example 5 – in vitro digestion to quantify iron bioaccessibility Materials and Methods: Briefly, 1 g of nettle material (i.e. dry nettle powder obtained after grinding) and nettle concentrates prepared according to the concentration processes of example 1 and 2 were mixed with 10 mL of KCl 5mmol + NaCl 140 mmol pH 2. After adjusting the pH to 2, 0.5 mL of pepsin solution (prepared by dissolving 200 mg pepsin in 10 mL 0,1 M HCl) was added and the samples were incubated at 37 °C for 1 h. After 1 h, the pH was adjusted to 5.5 with 1 M NaHCO3. The volume of the samples was adjusted to 15 mL by adding 6.7 KCl 5 mmol + NaCl 140 mmol. Pancreatin solution (2.5 mL, prepared by adding 87.5 mg pancreatin and 525 mg bile extract to 44 mL 0.1 M NaHCO3) was added, and the samples were incubated at 37 °C for 2 h. An aliquot of the full digesta (2.5 g) was analysed for iron content by MPAES. The rest of the sample was centrifuged at 10000g for 30 min at 4 °C, and 2.5 g of supernatant was analysed for iron content by MPAES. Iron bioaccessibility was defined as: Iron bioaccessibility refers to the fraction of the total amount of iron that is theoretically available for absorption. Results: Figure 4 shows the iron bioaccessibility of nettle concentrates prepared with water (according to example 1) or water in presence of respectively citric acid, and hydrochloric acid (according to example 2). Citric acid and hydrochloric acid positively impacted the iron bioaccessibility of the nettle concentrates. Figure 5 shows the absolute amount of bioaccessible iron contained in nettle material, and nettle concentrates prepared with water according to the concentration method of example 1 or water in presence of respectively citric acid and hydrochloric acid according to the method of example 2. The absolute amount of bioaccessible iron was calculated multiplying the iron content in the sample by the bioaccessibility value. The nettle concentrates prepared with either water, citric or hydrochloric acid have clear advantages compared to nettle material as they contain greater amounts of bioaccessible iron (39, 114, 147 ppm in nettle concentrate prepared with water, citric acid, hydrochloric acid, respectively, compared to 28 ppm in dry nettle). Example 6 - Nettle concentrate increases mitochondrial activity via Mitochondrial calcium rise. Materials and Methods: To test the effect of the nettle concentrate prepared according to example 1 on mitochondrial activation in living cells, the inventors measured mitochondrial calcium elevation in myotubes differentiated from C2C12 cells. C2C12 cells were purchased from ATCC. C2C12 cells were seeded in 384-well plates at a density of 4500 cells per well in DMEM high glucose (Gibco) + 10% fetal calf serum. Myotubes were differentiated from C2C12 cells by growing the cells in DMEM containing 2% horse serum, for 7 days. Mitochondrial calcium measurements were carried out using myotubes infected with the adenovirus (from Sirion biotech) expressing the luminescent mitochondrially-targeted calcium sensor mitochondrial mutated aequorin (Montero et al., 2004). For aequorin reconstitution, 48 hours after infection, cells or myotubes were incubated for 2 h at room temperature (22 ±°C) in standard Aequorin buffer (145 mM NaCl, 5 mM KCl, 1 mM MgCl2, 1 mM CaCl2, 10 mM glucose and 10 mM Hepes, pH 7.4) with 1 μM wild-type coelenterazine. Cells were washed with Aequorin buffer before stimulation. For sample preparation, the different concentrations/dilutions of nettle concentrate were prepared by dilution of the nettle concentrate in the above mentioned standard Aequorin buffer. For treatment, nettle concentrate (at different concentration/dilution, as indicated in figure 6 or 7) were directly injected during measurement to the myotubes cultures. For control (no stim), only standard Aequorin buffer alone was directly injected during measurement to the myotubes cultures. The total mitochondrial calcium uptake (=mitochondrial calcium rise) during stimulation was calculated as the area under the curve (AUC). Luminescence was measured at the FLIPR cell imaging reader (Molecular devices). Calibration of the luminescence data into Calcium concentration was carried out using an algorithm as described previously (Alvarez & Montero, 2002). Custom module analysis based on Excel (Microsoft) and GraphPad Prism 7.02 (GraphPad) software was used for quantification. Results: The results are shown in Figures 6 and 7. As shown in Figures 6 and 7, the nettle concentrate (at different concentration) activates mitochondria, via mitochondrial Ca2+ rise, in C2C12-derived myotubes. In particular, Figure 6 is a graphical representation of the effect of the nettle concentrate on mitochondrial Ca2+ uptake in C2C12-derived myotubes over time. Figure 6 showed a dose dependent boosting effect of nettle concentrate according to the invention on mitochondrial activation (dilution from 10 to 80 of the nettle concentrate). No mitochondrial activation is observed when aequorin buffer only is injected (no stim). Figure 7 confirms the dose dependent boosting effect of the nettle concentrate according to the invention on the total mitochondrial calcium uptake in C2C12-derived myotubes.

Claims

19229-EP-EPA CLAIMS 1. A composition comprising a nettle concentrate, in an effective amount for use in (i) improving a physiological state linked to metabolic fatigue in one or more cells, and/or (ii) increasing mitochondrial energy and mitochondrial calcium uptake in one or more cells, and/or (iii) enhancing mitochondrial function, and/or (iv) treating or preventing a calcium deficiency / depletion disorder in an individual, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. 2. The composition for use according to claim 1, wherein at least a portion of the one or more cells are part of at least one body part selected from the group consisting of a liver, a kidney, a brain, and a skeletal muscle. 3. The composition for use according to any one of the preceding claims, wherein the physiological state linked to metabolic fatigue comprises muscle fatigue, muscle weakness, lack of vitality, weakness or lack of energy, in particular lack of physical energy. 4. The composition for use according to any one of preceding claims, wherein the effective amount of nettle concentrate is orally administered daily for at least one week. 5. The composition for use according to any one of preceding claims, wherein the composition further comprises at least one compound selected from the group consisting of antioxidants, anti-inflammatory compounds, glycosaminoglycans, prebiotics, fibres, probiotics, fatty acids, enzymes, minerals, trace elements and/or vitamins. 6. The composition for use according to any one of preceding claims, wherein the composition is selected from the group consisting of food compositions, dietary supplements, 19229-EP-EPA nutritional compositions, complete nutritional compositions, pharmaceuticals, oral nutritional supplement, medical food, nutraceuticals, beverages, powdered nutritional products to be reconstituted in water or milk before consumption, food additives, food for special medical purpose (FSMP), medicaments, petfood, and combinations thereof. 7. The composition for use according to any one of preceding claims, wherein the composition is in a form of a solid powder, a powdered stick, a capsule or a solution. 8. The composition for use according to any one of preceding claims, wherein the effective amount of nettle concentrate is administered in a food product or beverage further comprising a component selected from the group consisting of protein, carbohydrate, fat and mixtures thereof. 9. A composition comprising a nettle concentrate for use in an effective amount for treating, reducing an incidence of, and/or reducing a severity of a mitochondria-related disease or a condition associated with altered mitochondrial function in an individual in need thereof or at risk thereof, the method comprising orally administering an effective amount of the nettle concentrate to the individual in need thereof or at risk thereof, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. 10. The composition for use according to claim 9, wherein the mitochondria-related disease or condition is selected from the group consisting of stress, physiological ageing, obesity, reduced metabolic rate, metabolic syndrome, diabetes mellitus, complications from diabetes, hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress- related cognitive dysfunction, mood disorder, anxiety disorder, age-related neuronal death or dysfunction, musculoskeletal disorder, frailty, pre-frailty, chronic kidney disease, kidney 19229-EP-EPA failure, trauma, infection, cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof and combinations thereof. 11. A composition comprising a nettle concentrate for use in an effective amount for delaying off-set of metabolic decline, maintaining muscle mass and/or muscle function, maintaining immune function and/or maintaining cognitive function in a healthy older adult, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. 12. A composition comprising a nettle concentrate for use in an effective amount for enhancing at least one of mental performance or muscle performance in an individual, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. 13. A composition comprising a nettle concentrate for use in an effective amount for improving or maintaining cognitive function, in an individual, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, 19229-EP-EPA c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. 14. The composition for use according to claim 13, wherein the cognitive function is selected from the group consisting of perception, memory, attention, speech comprehension, speech generation, reading comprehension, creation of imagery, learning, reasoning, and combinations thereof. 15. The composition for use according to according to any preceding claims, wherein the effective amount of nettle concentrate is administered in a composition further comprising calcium. 16. The composition for use according to any preceding claims, wherein the individual is an older adult, an elderly or a patient in ICU. 17. A unit dosage form comprising a nettle concentrate for use in an effective amount for at least one of (i) treating, reducing an incidence of, or reducing a severity of a mitochondria- related disease or condition associated with altered mitochondrial function, and/or (ii) improving in a physiological state linked to metabolic fatigue in one or more cells, and/or (iii) increasing mitochondrial energy and mitochondrial calcium uptake in one or more cells, and/or (iv) treating or preventing a calcium deficiency / depletion disorder, and/or (v) increasing metabolic rate, and/or (vi) improving or maintaining cognitive function, and/or (vii) increasing or maintaining mitochondrial function, wherein the nettle concentrate is obtainable or obtained by the process comprising the steps of: a) suspending a nettle material in an aqueous liquid to form a nettle material suspension, b) blending the nettle material suspension to obtain a nettle material slurry, c) applying a physical mean on the nettle material slurry to separate and obtain a nettle concentrate, d) optionally, drying the nettle concentrate. 19229-EP-EPA 18. The unit dosage form of claim 17, wherein the physiological state linked to metabolic fatigue comprises muscle fatigue, muscle weakness, lack of vitality, weakness or lack of energy, in particular lack of physical energy.