NAD+ Precursor Formulations for Supporting Healthy Aging.
Patent Information
- Application Number
- NL2039020
- Authority / Receiving Office
- NL · NL
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-11-07
- Publication Date
- 2026-06-08
- Estimated Expiration
- 2044-11-06
Abstract
Description
l P 138312NL00 NAD+ Precursor Formulations for Supporting Healthy Aging. The invention relates to an instant beverage composition comprising anNAD+ precursor, which composition can be reconstituted in water to provide a beverage. The invention further relates to various uses of the instant beverage composition or beverage, which uses are in particular related to longevity. Nicotinamide adenine dinucleotide (NAD) is a key co-enzyme in life. It is essential for proper functioning of cells, amongst others in the production ofcellular energy. Moreover, NAD plays an essential role in DNA repair, epigenetic alteration, proper protein regulation, mitochondrial dysfunction, cellular senescence, and deregulated nutrient sensing, which are all well-known hallmarks of aging. It has been reported that properNAD levels contribute, amongst others, to increased energy, better sleep, improved physical performance, reduction in muscle and joint pains, enhancedimmunity against infections, reducedinammation, reduction in insulin resistance, clearer mental clarity, andimproved liver function. It is known thatNAD levels tend to decline with age. Loss of function and vitality, and an increased risk of developingmany age-related diseases may be associated with reducedNAD levels. Many options for raising one'sNAD levels have been considered in the art. These fall into four different categories. One way to raise intracellularNAD is through supplementation withNAD precursors, the building blocks that cells use to make theNAD molecule. Nicotinamide mononucleotide (NMN) is a one-step precursor to makeNAD and nicotinamide riboside (NR) is a two-stepNAD precursor. Nicotinamide (NAM) and nicotinic acid (NA) can also be converted into NAD. Other ways that have been explored to raiseNAD levels include theNAD molecule, inhibition ofthe enzymes that degrade NAD, and increasing the enzymes that make NAD. One commonly used approach to elevateNAD levels has been intravenous infusion oftheNAD molecule. However, treatment by in vitro infusion is not straightforward, as it requires intervention by a medical professional. NAD precursors such asNMN andNR have recently been used as supplements to increaseNAD levels. In clinical trials both precursors were shown to be able to increaseNAD levels. As discussed in US2024 / 17334, there is a need for formulations that can: 1) efciently elevateNAD levels, and 2) provide benefits in improving biochemical, physical, physiological, sexual, and / or mental health. US2024 / 17334 proposes compositions comprising anNAD precursor and / or theNAD molecule (NAD+ and / or NADH). For compositions withNAD precursor, a content of30-70 %NAD precursor is described. The compositions can take any form. In the clinical examples a powder containing 50 wt.%NMN is used. The need for alternative formulations remains. For instance, the level of effectivity ofone treatment or the other can be dependent on the person. Absorption rates ofNR andNMN vary between individuals. Transport mechanisms across cell membranes may vary between individuals. Such variations can be age-related, have a genetic component (associated withNAD+ metabolism) or be gender-related. Further, it is a well-known phenomenon in the elds ofhealth supplements and pharmaceuticals that consumer compliance can be a challenge. Some people may have difculty with timing of doses. Current formulations may require specic timing with meals. Multiple daily doses may be needed for optimal effects. It is therefore important to develop novel products useful to elevateNAD levels with high efciency and in as many people as possible. It is an object ofthe present invention to provide such a novel product, in particular a product with an advantageous effect, as described herein below. The inventors realised that it is possible to provide an effective product addressing such need, by choosing a specic administration form and combining specifically a relatively low content ofNAD+ precursor, thereby allowing the inclusion of other active ingredients in relatively high concentrations. Accordingly, the present invention relates to an instant beverage composition - in particular a granular composition, e.g. a powder - comprising (i) at least one nicotinamide component the total content of said nicotinamide components being 1-25 wt.% ofthe instant beverage composition; (ii) two or more further components selectedfrom the group consisting of creatine, glycine, alpha-ketoglutarate, glucosamine, betaine, Lions Mane, green-tea extract, malate, taurate, quercetin (preferably quercetin phytosome), coenzyme Q10 (preferably Ubiquinol), astaxanthin, ashwagandha, malate, rhodiola rosea, trans-resveratrol, vitamin C, citrulline-malate, ginger, inositol. aspartate, luteol, pterostilbene, hyaluronic acid, setin, L-glutathione, L-lysine, L-theanine, L-threonate, Apigenin, Carnosine, Sulforaphane, N-Acetyl-Cysteine, curcumin, zinc and magnesium, the total content of said further components being at least 25 wt.% ofthe instant beverage composition. The invention further relates to a non-alcoholic beverage comprising water and a solids fraction, wherein the solids fraction has a composition as given for the instant beverage composition according to the invention. The nicotinamide component is a component containing a nicotinamide moiety; The nicotinamide component in an instant beverage composition respectively beverage ofthe invention typically is selectedfrom the group consisting ofnicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), including combinations thereof. It is also possible to replace part or all oftheNMN, NR, or both with one or more other nicotinamide compounds selected from NAD+, NADH, Nicotinamide / niacinamide (NAM) and Nicotinic Acid. Ifany ofthese are present, the total content ofNR, NMN, NAD+,NADH Nicotinamide / niacinamide (NAM) and Nicotinic Acid is generally in the range of 1-25 wt. % ofthe instant beverage composition respectively the dry weight ofthe beverage ofthe invention; the total content ofNR+NMN (ofwhich one may be absent), is typically at least 1 wt.% of total weight ofthe composition respectively dry weight ofthe beverage. It is also possible that ribose is included (D or L); ifincluded ribose is generally present in such an amount that the total ofsaid nicotinamide component or components plus the ribose is in the range of 1- 25 wt. % ofthe instant beverage composition respectively the dry weight of the beverage ofthe invention; herein typically total content ofNR+NMN (of which one may be absent), is at least 1 wt.% oftotal weight ofthe composition respectively dry weight ofthe beverage; thus, the total content ofthe other nicotinamide components plus ribose is typically 0-24 wt.% of the instant beverage composition respectively the dry weight ofthe beverage. Herein below quantitative information will generally be provided referring to NR,NMN or both. The skilled person will be able to adapt such information for compositions and beverages in accordance with the invention in case one or more other nicotinamide components or ribose is included. The beverage according to the invention respectively the instant beverage composition is usually acidic, preferably having apH (at 20 degrees C) in the range of about 4 to about 6. This is advantageous for stability / effectivity ofthe NR / NMN. Accordingly, the instant beverage composition. ThepH ofthe beverage is the value as measured with a calibratedpH electrode inserted in the beverage. ThepH ofthe instant beverage composition is determinedby preparing a beverage ofthe instant beverage compositions (such as by reconstituting about 10 g in 250 ml water) and measuring thepH ofthe beverage with thepH electrode. The invention further relates to a non-medical use according to claim 9. The invention further relates to an instant beverage composition or beverage according to claim 12. The invention provides in particular an instant beverage product, which can simply be dissolved or suspended in water, to provide a beverage that can easily be administered orally into the gastrointestinal tract. The dosage form is found to be advantageous for a good consumer compliance. Factors that contribute to a good compliance include acceptable organoleptic properties, ease ofadministration / dosage regime, effectivity. Despite the relatively low amount ofthe nicotinamide component, a satisfactory effectivity is reached. Without beingboundby theory, the inventors consider that this is achievedby having a relatively high content ofother active ingredients with one or more specific benefits, in particular in support of longevity, on their own resulting in a synergetic effect with NR,NMN or both, at least in a number ofembodiments. In addition, in at least a number ofembodiments, an additional active ingredientmay contribute to an improved absorption rate ofNR / HMN into the blood stream or improved transport across cell membranes. Furthermore, in at least some embodiments a reduced risk of side-effects can be achieved, due to the relatively low content oftheNR / HMN in the product ofthe invention. It is further an advantage ofthe present instant beverage composition that it can be stored at ambient conditions, whilst remaining satisfactory activity for a relatively long time. It is further an advantage that the instant composition respectively beverage can be formulated conveniently whilst being essentially free of allergens. Unless defined otherwise, terms as used herein are as generally used in the art, e.g. in the prior art cited herein. The terms comprise(s), include(s), having, has, can, contain(s), and variants thereof, as used herein, are intended to be open- ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures The term or is used to mean "and / or", unless the context clearly indicates otherwise. The terms or respectively and / or include any and all combinations ofone or more ofthe associated listed items. It will be understood that the terms "comprises" and / or "comprising" specify the presence ofstated features but do not preclude the presence or addition of one or more other features. Any text or reference signs placed between parentheses shall not be construed as limiting, unless the context clearly indicates otherwise. It will be understood that when a particular step of a method is referred to as subsequent to another step, it can directly follow said other step or one or more intermediate steps may be carried out before carrying out the particular step, unless specied otherwise. As is used herein, the term wt. %, or weight percentage, or percentage by weight, generally refers to the mass fraction of a substance in a composition dividedby the total mass of said composition, unless specied otherwise. When referring to a dry weight, this is the weight ofingredients other than water. The term (at least) substantial(ly) is generally used herein to indicate that it has the general character or function ofthat which is specied. When referring to a quantiable feature, this term is in particular used to indicate that it is at least 50 %, more in particular more than 75 %, even more in particular more than 90 % ofthe maximum ofthat feature. The term (at least) essential(ly) is generally used herein to indicate that it has the general character or function ofthat which is specied. When referring to a quantiable feature, it generally includes a deviation of 15 % or less from the given value, in particular a deviation of 10% or less, more in particular a deviation of5% or less. In the context ofthis application, the term "about" includes generally a deviation of 15 % or less from the given value, in particular a deviation of 10% or less, more in particular a deviation of5% or less. When referring to a physical state ofa product, such as uid, liquid, or solid this generally means uid respectively liquid respectively solid at 20 °C unless specied otherwise or unless iffollows otherwise from the context. When referred herein to a base (e.g. citrate, alpha-ketoglutarate, taurate, malate) or an acid (e.g. citric acid, alpha-ketoglutaric acid, taurine) these terms are meant to include its conjugated base respectively conjugated acid, as well as salts thereof. When referring herein to an amino acid, this term is meant to include the amino acid in which the amino group(s) and carboxylate group(s) are in their neutral form or chargedform as well as salts thereof. When mentioning weight amounts (e.g. weight %) of a compound, the amount ofthe compound as such is meant and not the amount of, e.g., the salt or hydrate in which itmay be commercially available. In particular when referring to an amount ofnicotinamide riboside, the amount ofthe cation is meant and for nicotinamide mononucleotide the zwitterionic form, unless specied otherwise. Nicotinamide riboside (beta-form): o NH2 0 N / 93 Nicotinamide mononucleotide: o 5NH2 _ o fi \ Ho OH For the purpose of clarity and a concise description, features are described herein as part ofthe same or separate aspects and preferred embodiments thereof, however, it will be appreciated that the scope ofthe inventionmay include embodiments having combinations of all or some of the features described. The instant beverage composition respectively the beverage ofthe invention has a total content ofnicotinamide riboside plus nicotinamide mononucleotide (ofwhich one or both are present) of 1-25 wt.%, preferably of 20-15 wt.%, more preferably of22-12 wt.%. In a specific embodiment, said content is at least about 2.5 wt.% at least about 4.0 wt.% or at least about 5.0 wt % ofthe instant beverage composition respectively ofthe dry weight ofthe beverage ofthe invention. In a specific embodiment, said total content ofNR+NMN is up to about 10 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage ofthe invention Good results have been achieved with such a composition which is free ofnicotinamide mononucleotide. In a further advantageous embodiment, both nicotinamide riboside and nicotinamide mononucleotide are present. Ifboth are present the weight to weight ratio nicotinamide riboside to nicotinamide mononucleotide is usually 1:9 to 9:1, in particular 2:9 to 1:1. Good results are in particular achieved with an instant beverage composition respectively a beverage having a nicotinamide riboside content in the range of 15-15 wt.%, more preferably of2.0-10 wt.%, in particular of 2.0-5 wt.%. Usually, the nicotinamide riboside is included in the instant beverage composition respectively beverage ofthe invention as nicotinamide riboside. Alternatively, or in addition another nicotinamide riboside salt may be included, such as nicotinamide riboside hydrogen malate. Ifthe instant beverage composition respectively beverage ofthe invention contains nicotinamide mononucleotide, the content thereof usually is 30-25 wt.%, in particular of40-15 wt.%, more in particular 5.0- 10 wt.% ofthe weight ofthe instant beverage composition respectively the dry weight ofthe beverage. The instant beverage composition respectively beverage composition usually comprises at least six further components, preferably at least eight further component, more preferably ten or more further components selected from the group consisting ofcreatine, glycine, alpha- ketoglutarate, glucosamine, betaine, Lions Mane, green-tea extract, malate, taurate, quercetin phytosome, coenzyme Q10 (as Ubiquinol), astaxanthin, ashwagandha, malate, rhodiola rosea, trans-resveratrol, vitamin C, citrulline-malate, ginger, inositol, aspartate, luteol, pterostilbene, hyaluronic acid, setin, L-glutathione, L-lysine, L-theanine, L-threonate, zinc, Apigenin, Carnosine, Sulforaphane, N-Acetyl-Cysteine, curcumin and magnesium. In a particularly preferred embodiment, the instant beverage composition respectively beverage ofthe invention at least includes creatine, more preferably at least creatine, alpha-ketoglutarate and glucosamine. Astaxanthin, glycine or both astaxanthin and glycine are also particularly preferred in combination with creatine, more in particular in combination with at least creatine, alpha-ketoglutarate and glucosamine. The total content ofsaid further components is at least 25 wt.%, preferably at least 50 wt.%, more preferably at least 70 wt.%, in particular at least about 75 wt.% ofthe instant beverage composition respectively the dry weight ofthe beverage. The total content of said components, including any counterions and hydrated water if any, is up to 99 wt.%, preferably up to about 95 wt.%, in particular up to 80 wt.%, more in particular up to 85 wt.% ofthe instant beverage composition respectively ofthe dry weight of the beverage ofthe invention. The balance is usually formed ofone or more ingredients typical for (instant) beverages, such as avour / aroma components, acidity regulators (e.g. citric acid / citrate) and the like; and optionally one or more further active ingredients. Creatine, such as in the form ofcreatine monohydrate, is preferably included. Ifpresent, the creatine content (calculated as creatine monohydrate) is usually 5-40 wt.%, preferably 15-35 wt.%, more preferably 20-30 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage. Creatine is advantageously included to support cellular energy production in tissues with high energy demands, such as muscle and brain cells, andmay have mild anti-inammatory effects . In combination with NR,NMN or both creatine is in particular advantageous because creatine can complement cellular energy production, whereby in combination withNR / NMN itmay contribute to an enhanced overall energy metabolism,. Supplementing with creatine can be included to reduce the need forNAD+ in these tissues. This can increase the potential ofNMN,NR or both to be more effectively utilised elsewhere in the body. Glycine is preferably included. Ifpresent, the glycine content is usually 3-30 wt.%, preferably 10-25 wt.%, more preferably 15-20 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage. Glycine acts as both an inhibitory neurotransmitter in the spinal cord and brainstem and as a co-agonist forNMDA (N-methyl-D-aspartate) receptors in the brain, which play a key role in synaptic plasticity andmemory formation. OptimalNMDA receptor activation is important for cognitive health, but dysfunction can contribute to neurodegenerative diseases. Glycine supports cognitive function andmay have a role in memory processes through its action as a neurotransmitter.. By supporting cellular health through its anti-inammatory and repair-promoting effects, glycine may complement the role ofNMN andNR in maintaining proper cellular function Alpha-Ketoglutarate (AKG) is preferably present. It is usually included as its calcium salt, although another form may be included, e.g. magnesium AKG. Ifpresent, theAKG content (calculated as calcium AKG) is usually 1-15 wt.%, preferably 3-10 wt.%, more preferably 5-10 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage. AKG supports cellular metabolism and energy production andmay complementNMN andNR in energy pathways. . Glucosamine is preferably included, for instance as a sulphate salt. Ifpresent, the glucosamine content (calculated as glucosamine sulphate) is usually 1-15 wt.%, preferably 3-10 wt.%, more preferably 5-10 wt.% ofthe instant beverage composition respectively ofthe dry weight of the beverage. Glucosamine can be used as a protectant against oxidative stress, to support metabolism or to improve mitochondrial function. Known for its anti-inammatory properties, the inventors realised that glucosamine may be used to support cellular health by reducing inammation. By reducing inammation, glucosamine can support cellular health, which may indirectly allow for more efcient NAD+ utilization, thereby complementing the role ofNMN andNR in cellular processes. Betaine (trimethylglycine) is preferably included. Ifpresent, the betaine content is usually 1-15 wt.%, preferably 3-10 wt.%, more preferably 5-10 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage. Betaine is a known methyl donor. It may be used to support liver function or detoxication processes. The combination withNMN, NR or both is in particular preferred for support ofmethylation processes, which can be important whenNMN, NR or both, as they can increase methylation demand in the body. Lions Mane is preferably included. Ifpresent, the Lions mane content is usually 05-10 wt.%, preferably 1-8 wt.%, more preferably 2-6 wt.% ofthe instant beverage composition respectively ofthe dry weight of the beverage. Lions Mane, known for its neuroprotective and cognitive- enhancing properties, supports nerve health andmay aid neuromuscular function by promoting optimal nerve signaling. Additionally, its antioxidant properties can help reduce oxidative stress, supporting overall cellular health Itmay be used to contribute to better muscular function, e.g. by improving neuromuscular signalling, or to support energy production. In accordance with the invention is advantageously is included to support overall cellular health, thereby indirectly benefittingNMN / NR by reducing oxidative and metabolic stress in nerve cells. This can help preserveNAD+ levels and enhance the effectiveness ofNMN / NR in supporting brain health. Green-tea extract is preferably included. Ifpresent, the green tea extract content is usually 0.5-10 wt.%, preferably 1-8 wt.%, more preferably 2-6 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage. Green-tea extract is a preferred source ofcatechins like, epigallocatechin gallate (EGCG). Catechins are known for their antioxidant properties. Green-tea extract (providing EGCG), can be included to support mitochondrial function. By protecting mitochondria from oxidative damage, catechins in green tea extract, such as EGCG, can help to maintain cellular help, to allowNMN andNR to be more effective in sustainingNAD+ levels for other cellular functions and to maximize the effectiveness ofNMN and NR in supportingNAD+ production and cellular energy. Malate is preferably included, in particular as a magnesium salt. Ifpresent, the malate content (calculated as magnesium malate) is usually 05-10 wt.%, preferably 1-8 wt.%, more preferably 1.5-6 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage. The magnesium salt shows good bioavailability. Malate can be included to support liver function, energy, muscle health, cardiovascular health, neurological health or skin health. Taurate, in particular magnesium taurate, is preferably included. Ifpresent, the taurate content (calculated as magnesium taurate) is usually 05-10 wt.%, preferably 1-8 wt.%, more preferably 1.5-6 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage. Taurate, preferably in combination with magnesium, is advantageously include to support cardiovascular health, cellular hydration, electrolyte balance. It can be used in particular to support cellular energy production, to improve hearth health, to reduce oxidative stress or to support overall cellular health. Indirectly cellular energy maintenance can benet from the inclusion oftaurate. Quercetin is preferably included, in particular quercetin phytosome. Quercetin is a avonoid with antioxidant properties, often used to support immune and cellular health. Quercetin phytosome has improved bioavailability, due its binding to phospholipids. Ifpresent, the quercetin content, preferably the quercetin liposome content is usually 05-10 wt.%, preferably 1-8 wt.%, more preferably 1.5-6 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage. It can in particular be included to reduce oxidative stress, may inhibit enzymes that degrade NAD+, thus supportingNAD+ levels. This can synergise withNMN andNR by extending the duration and availability ofNAD+. By reducing oxidative stress and potentially inhibiting NAD+-degrading enzymes like CD38, quercetinmay help maintainNAD+ levels, complementing the effects ofNMN andNR in sustaining cellular energy and health Coenzyme Q10 is preferably included, typically as Ubiquinol. If present, the coenzyme Q10 content (calculated as ubiquinol) is usually 0.1-5 wt.%, preferably 0.8-8 wt.%, more preferably 0.5-2 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage. Coenzyme Q10, typically included as ubiquinol for better bioavailability, plays a key role in cellular energy (ATP) production, particularly in muscle and brain cells. It supports muscle health andmay help mitigate age-related muscle decline. As part ofthe mitochondrial electron transport chain (following the Krebs cycle), Coenzyme Q10 works alongside NAD+-boosting compounds likeNMN andNR to potentially enhance cellular health and metabolic efciency. Astaxanthin is preferably included. Astaxanthin is a powerful antioxidant carotenoidfound in certain algae and seafood (like salmon, shrimp, and krill). Ifpresent the astaxanthin content is usually 0.001-1 wt.%, preferably 0.01-0.4 wt.%, more preferably 0.05-0.1 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage. Known for supporting skin and eye health, it also has anti-inammatory properties. By reducing oxidative stress, astaxanthin supports mitochondrial health, whichmay complement the effects ofNMN andNR in cellular energy and NAD+ utilisation. Thus, astaxanthin can support the effectiveness ofNMN andNR. Zinc is preferably included in an instant beverage composition or beverage according to the invention. Ifpresent, the zinc content is usually less than 1 wt.%, preferably up to about 0.5 wt.% ofthe total instant beverage composition respectively the dry weight ofthe beverage. Ifpresent, the zinc content preferably is at least about 0.05 wt.%, more preferably at least 0.1 wt.% ofthe total instant beverage composition respectively the dry weight ofthe beverage. Zinc acts as a cofactor for various enzymes, including those involved in synthesizingNAD+ from precursors like tryptophan and nicotinamide. Thus, the inclusion ofzinc in an instant composition respectively beverage according to the invention is considered to have a positive effect in combination withNR / NMN. Magnesium is usually included in an instant beverage composition or beverage ofthe invention. Generally, magnesium is present usually in a content of0.05-4 wt.%, preferably 0.4-3 wt.% or 0.5-2 wt.% of the instant beverage composition respectively beverage ofthe invention. Generally, it sufces to include magnesium as part ofone or more ofthe other active compounds ofwhich a magnesium salt form exists, such as magnesium taurate, magnesium malate, magnesium threonate. It may also be included as part of a further salt, such as magnesium citrate. Magnesium is essential forATP production and various enzymatic processes, including those involved inNAD+ synthesis. Itmay in particular supportNMN / NR by enhancing cellular energy, enhancing metabolic processes, or both. In an advantageous embodiment each ofcreatine (in particular monohydrate), glycine, alpha-ketoglutarate (in particular calcium AKG), glucosamine (in particular glucosamine sulphate), betaine, Lion's Mane, green-tea extract, magnesium malate, magnesium taurate, quercetin phytosome, Coenzyme Q10 and astaxanthin are included in the instant beverage composition respectively beverage ofthe invention, typically in a total content of at least 25 wt.% ofthe instant beverage composition respectively ofthe dry weight ofthe beverage, preferably each ofthe components being present in an amount in a range as given elsewhere herein for said compositions. In an advantageous embodiment hyaluronic acid is included, if present generally in a content of0.4 - 4 wt.%, preferably of 1 3 wt.% ofthe instant beverage composition respectively beverage ofthe invention. While primarilyknown for skin hydration, hyaluronic acid can support cellular health by reducing inammation. Healthier cells are more efficient inNAD+ usage. The inventors realised that thereby hyaluronic acidmay be used to enhance the effectiveness ofNMN, NR or both. In an advantageous embodiment L-theanine is included, if present generally in a content of 0.5 - 4 wt.%, preferably of 1-3wt.% ofthe instant beverage composition respectively beverage ofthe invention. L- theonine promotes relaxation and (indirectly) supports mitochondrial health. Its potential in an advantageous effect in combination with NMN / NR in maintaining cellularNAD+ levels in particular is thought to reside in L-theonines contribution to reduce oxidative stress in cells. Pterostilbene is included in an advantageous embodiment; if present usually in a content of 0.2-2 wt.%, preferably of 0.5-1.5 wt.% ofthe instant beverage composition respectively beverage ofthe invention. Structurally similar to resveratrol, pterostilbene has antioxidant and anti- inammatory properties that support mitochondrial health. It can enhance sirtuin activation, apathway through whichNMN andNR also exert their effects, which supports its potential to amplifyNAD+ benets, when used in combination withNR orNMN. Fisetin is advantageously included; ifpresent generally in a content of 0.2-5 wt.%, preferably of 0.5-3 wt.% ofthe instant beverage composition respectively beverage ofthe invention. Fisetin is a avonoid known for its antioxidant and anti-inammatory effects, as well as potential senolytic properties (removing senescent cells). By reducing cellular senescence and inammation, setin can help maintainNAD+ levels and enhance cellular environments, creating favourable conditions forNMN, NR or both to boostNAD+ more effectively. Advantageously, glutathione is included; ifpresent generally in a content of 1-10 wt.%, preferably of2-10 wt.% ofthe instant beverage composition respectively beverage ofthe invention. L-Glutathione is a key antioxidant that protects cells from oxidative damage. By supporting cellular detoxication and reducing oxidative stress, it can decreaseNAD+ depletion. This allowsNMN / NR to sustain higherNAD+ levels, optimising cellular energy production and repair processes. Advantageously, L-threonate is included, in particular magnesium L-threonate, ifpresent generally in a content (calculated as magnesium threonate) of 5-20 wt.%, preferably of 10-17 wt.% ofthe instant beverage composition respectively beverage ofthe invention. It is known for enhancing cognitive function and supporting synaptic plasticity. Preferably, L-lysine is included. Ifpresent the L-lysine content is usually 2-23 wt.%, preferably 5-15 wt.% ofthe instant composition respectively the dry weight ofthe beverage. Lysine may in particular be used to complement an effect ofNR / NMN. Lysine is an essential amino acid. It is involved in cellular metabolism, and there are signs that it has a role together withNAD+ for their potential impact on health, particularly in areas like energy production,DNA repair, and cellular aging. Other preferred active ingredients ofwhich one or more are advantageously present include (wt.% are total weight ofthe instant beverage composition respectively dry weight ofthe beverage): ashwagandha, ifpresent preferably 1-20 wt.%, in particular 2-10 wt.%; rhodiola rosea ifpresent preferably 1-9 wt.%, in particular 2-7 wt.%; trans- resveratrol, ifpresent preferably 0.5-9 wt.%, in particular 1-4 wt.%; vitamin C, ifpresent preferably 2-23 wt.%, in particular 4-15 wt.%; citrulline-malate, ifpresent preferably 9-44 wt.%, in particular 15-25 wt.%; ginger, ifpresent preferably 2-17 wt.%, in particular 5-12 wt.%; inositol, ifpresent preferably 5-29 wt.%, in particular 10-20 wt.%; aspartate, ifpresent preferably 5-17 wt.%, in particular 8-12 wt.%; luteol, ifpresent preferably 0.1-2 wt.%, in particular 0.5-1.5 wt.% , Apigenin, ifpresent preferably 0.1-2 wt.%, in particular 0.2-1 wt.%; Carnosine, ifpresent preferably 2-18 wt.%, in particular 3-10 wt.%; Sulforaphane, ifpresent preferably 0.1-4 wt.%, in particular 0.5-3 wt.%; N-Acetyl-Cysteine, ifpresent preferably 5-19 wt.%, in particular 6-10 wt.%; and curcumin, ifpresent preferably 2-17 wt.%, in particular 5-14 wt.%. These may be included for a known health benefit, such as for its antioxidant function, its positive effect onimmune function etc. The instant beverage composition or beverage ofthe invention may further comprise one or more additional bioactive agents, such as one or more (further) vitamins, (further) antioxidants etc, anti-inammatory components. In principle, the instant beverage composition or beverage can contain macronutrients, such as fats, digestible carbohydrates (such as sugars, starch) and protein. However, good results are in particular achieved with an instant beverage composition respectively beverage that is essentially free of digestible carbohydrates, or at least essentially free of mono-hexoses and di-hexoses; with an instant beverage composition or beverage that is essentially free ofadded fats (other than potentially fats providing polyunsaturated fatty acid); and with an instant beverage composition respectively beverage that is essentially free ofprotein (i.e. polypeptidic proteinaceous matter). In addition, the instant beverage composition or beverage ofthe invention usually contains one or more avour / aroma components. E.g. a sweetener, such as stevia, may be included. Further, a fruit avour may be included, e.g. a citrus avour. A citrus avour may not only enhance compliance, but citrus avours may also contribute to a longevity related effect. Without beingboundby theory it is believed that the presence of terpenes or terpenoids can be a reason for this. The instant beverage composition is usually in a solid form, such as a granulate or powder, or a table or other solid shape that disintegrates in water. In a specific embodiment, the instant beverage composition is a liquid concentrate. The beverage ofthe invention can be produced by dissolving or suspending an instant beverage composition in a suitable amount ofwater. The amount ofwater can be chosen as desired, taking organoleptic preferences, such as taste into account. Usually, about 10 to about 100 ml water is used per gram of instant beverage composition (total weight for a solid form, dry weight for liquid concentrate). Preferably about 25 to about 50 ml water is used per gram ofproduct (total weight for a solid form, dry weight for liquid concentrate). The instant beverage composition or beverage according to the invention can be used for a variety ofpurposes, in particular one or more used that contribute to longevity. As follows from the above, the effect ofthe composition or beverage can underly a variety ofmechanism, e.g. also depending on the active components that are combined with the NR,NMN or both. Generally, there is believed to be at least an effect due to an action on theNAD metabolism. E.g. an enhancedDNA repair, a reduced damage to cells, epigenetic alteration, loss ofproteostasis, mitochondrial dysfunction, cellular senescence, deregulated nutrient sensing, reduction in muscle and joint pains, enhancedimmunity against infections, reducedinammation, reduction in insulin resistance, improved liver functionmay be achieved in accordance with the invention. The instant beverage composition or the beverage ofthe invention is generally for administration to a human, preferably ahuman aged 18 years or more, in particular a middle-aged (50 years ofage or older) or an elderlyhuman (65 yeast or older). The instant beverage composition or the beverage ofthe invention can be used for a non-medical purpose or for a medical purpose. The skilled person will be able will be able to distinguish between the two. In particular, the non-medical use may have a cosmetic purpose, be aimed at sports enhancement, or enhancing quality of life in aspects not related to a medical disorder. More in particular, a non-medical use may be a use wherein a purpose is achieved that goes beyondwhatmay be generally expectedfrom an averagehuman ofthe same age and gender. In a preferred embodiment, the use is selectedfrom the group of supporting longevity to a human, supporting healthy aging ofa human, increasing health span, making ahuman more energetic, improving sleep of a human, increasing physical performance ofa human, improving mental clarity ofa human, improving sexual function ofa human, improving cognitive functioning of a human, improving muscle strength, supporting athletic endurance, maintaining physical stamina, supporting joint mobility, supporting physical resilience, reducing fatigue ofa human, supporting focus and concentration, supportingmemory function, supporting mental performance, maintaining mental vitality, supporting stress resilience, supporting mental alertness, supporting wellbeing, supporting quality of life, and supporting activity of daily life. Any ofsuch use may advantageously be directed to a non-medical application. In a further advantageous embodiment, the instant beverage composition or the beverage according to the invention is for use in the treatment ofa medical disorder. Such treatmentmay be a prophylactic treatment.A prophylactic treatment in particular involves reducing the risk that an individual develops the medical disorder. Effectivity in a prophylactic treatment can e.g. be assessed by a cohort study wherein a first group receives the beverage ofthe invention and a second group receives a placebo. The beverage is effective ifthe incidence of developing the medical disorder is reduced (see also US2024 / 17334).A medical treatment may also be a treatment ofahuman having the disorder. Such therapeutic treatment can, but does not have to be curative. In an embodiment the therapeutic treatment reduces a discomfort due to the medical disorder, e.g. a symptom such as pain, partially restores damage associated with the disorder (e.g. a catabolic effect, e.g. a loss ofmuscle mass) or at least halts or reduces progression ofthe medical disorder. The invention may in particular be used in the treatment of a medical disorder associated with lowNAD levels. The invention may in particular be used to reduce a likelihood of developing an age-related medical disorder. In an advantageous embodiment, the medical disorder is selected from the group of addictions, neurological diseases (such as dementia), infectious diseases, lipid disorders, diabetes, cardiovascular diseases, kidney disease, chronic fatigue syndrome, lung diseases, autoimmune diseases, obesity, mental disorders, sexual dysfunction. When using the instant beverage composition or the beverage of the invention for physical performance, one may in particular use it for at least one ofthe following: supporting muscle recovery after exercise, promoting muscle strength, supporting athletic endurance, maintaining physical stamina, supporting joint mobility, supporting physical resilience. When using the instant beverage composition or the beverage of the invention for a mental or cognitive purpose, one may in particular use it for at least one ofthe following: supporting focus, supporting concentration, supportingmemory function, supporting mental performance, maintaining mental vitality, supporting stress resilience, supporting mental alertness. When using the instant beverage composition or the beverage of the invention for a general wellbeing purpose, one may in particular use it for at least one ofthe following: supporting cellular health, supporting mitochondrial function, supporting metabolic health, supporting healthy NAD+ levels, supporting cellular energy production, supporting healthy aging processes, supporting antioxidant functions. In an advantageous embodiment, the instant beverage composition or the beverage ofthe invention, is used for one or the following purposes, supporting cardiovascular health, supportingimmune system function, supporting healthy blood sugar levels, supporting healthy inammatory response, supporting skin health, supporting healthyDNA repair processes, supporting healthy cellular aging, supporting Quality of Life (QOL), supporting daily vitality, supporting healthy stress response, supporting work-private life balance. The instant beverage composition or the beverage ofthe invention is recommended to be used for a period for at least 1 month, preferably for at least 4 months, in particular for at least a year. It is recommended that the instant beverage composition is ingested at least 2 times a week, preferably at least 4 times a week, more preferably (on average) at least about once a day. The instant beverage composition or beverage is generally to be ingested in a dosage of 100-2000mg nicotinamide component(s), i.e. NR, NMN or the total ofthe two), per dosage and / or per day, preferably of200- 1500 mg per dosage and / or per day, more preferably of250-1000 mg per dosage and / or per day. In particular good results are achieved with an amount of200-500 mg nicotinamide riboside per dosage and / or per day, preferably dosed as nicotinamide riboside chloride, also in the absence ofNMN. In a specically preferred embodiment, the dosage, preferably the daily dosage is about 300 mg nicotinamide riboside chloride (providing about 258 mg NR). In a specic embodiment, the instant beverage composition or the beverage is dosed to provide 500-1500 mgNMN per dose or per day. This may be dosed in a composition further comprising NR, e.g. about 300mg nicotinamide riboside chloride and about 1000 mgNMN. The invention will now be illustrated by the following examples. EXAMPLE 1 Instant Beverage composition (powder) Table 1 mg per (daily) Nicotinamide Mononucleotide _-- _ __ ___ 1preferably as 800 mgRN chloride, The composition is reconstituted in water, preferably in 150-500 ml ofthe total amount ofcomponents in the Table (ca 11 g). In a further example,NMN is also included, preferably in an amount ofabout 1000mg per (daily) dosage, whilst the dosages ofother ingredient are essentially the same. EXAMPLE 2 People are taking a beverage according to the invention containingNR (or (i) a reference product containing the same ingredients except NR, or (ii) a reference product containing onlyNR as active ingredient or (iii) a placebo) daily for a test period of up to 180 days. The beverage is made from an instant beverage composition (powder) according to the invention, reconstituted in water. During the test period the following information is gatheredfrom the participants: 1. Baseline Information (Day 0 Only) . Demographics: Age, gender, weight, height, lifestyle (e.g., smoking, alcohol consumption), exercise frequency, and dietary habits. . Medical History: Any current health conditions, medications, allergies, and supplement usage. . Primary Health Concerns: What are the main reasons for taking this supplement? (e.g., energy, longevity, cognitive function, joint health, etc.) 2. General Health and Wellbeing (Day 0, 30, 90, 180) . On a scale of 1 to 10, how would you rate your overall energy levels? . How would you describe your sleep quality over the past week? (Poor, Fair, Good, Very Good, Excellent) . On a scale of 1 to 10, how would you rate your mental clarity and focus? . On a scale of 1 to 10, how would you rate your mood and emotional wellbeing? . Have you noticed any changes in your skin, hair, or nails? 3. Cognitive and Physical Performance (Day 0, 30, 90, 180) . Cognitive Performance: o On a scale of 1 to 10, how would you rate your memory over the past month? o On a scale of 1 to 10, how would you rate your concentration and focus? . Physical Performance: 0 On a scale of 1 to 10, how would you rate your stamina and physical endurance? o Have you noticed any changes in your muscle strength or recovery after physical activity? 4. Specic Symptom Tracking (Day 0, 30, 90, 180) . Have you noticed any changes in joint comfort or exibility? . Have you experienced any digestive issues or changes (e.g., bloating, discomfort)? . Do you feel that youve had fewer instances ofillness (e.g., colds, infections) since starting the supplement? 5. Biomarker Perception (IfApplicable, Day 0, 30, 90, 180) . Do you feel that your supplement has impacted any health markers that you track (e.g., blood pressure, cholesterol, blood glucose)? Ifyes, please specify. 6. Subjective Longevity Perception (Day 0, 30, 90, 180) . Do you feel that the supplement has contributed to a feeling of increased vitality or longevity? (Yes, No, Unsure) . On a scale of 1 to 10, how condent are you that this supplement is positively impacting your long-term health? 7. Supplement Tolerance and Side Effects (Day 0, 30, 90, 180) . Have you experienced any adverse effects since starting this supplement? If yes, please specify. . On a scale of 1 to 10, how easy has it been to integrate this supplement into your daily routine? . How likely are you to continue using this supplement? 8. Overall Satisfaction and Perceived Effectiveness (Day 30, 90, 180) . On a scale of 1 to 10, how satised are you with the results ofthis supplement so far? . Would you recommend this supplement to others? (Yes, No, Unsure) In addition to this information providedby the participants, lytical biomarker tests may be carried out, such as blood tests (on day 0 d at at least one point later in the test period, preferably at least after ut 90 days) forNAD+ and optionally other longevity biomarkers.
Claims
1. Instant drink composition - in particular a granular composition, for example a powder - which contains: (i) at least one nicotinamide component selected from nicotinamide riboside, nicotinamide mononucleotide and a combination of nicotinamide riboside and nicotinamide mononucleotide, where the total content of the said nicotinamide components 1-25 weight percent of the instant beverage composition amounts to; (ii) two or more other components selected from the group consisting of creatine, glycine, alpha-ketoglutarate, glucosamine, betaine, Lions Mane, green tea extract, malate, taurate, quercetin (preferably quercetin- phytosome), coenzyme Q10 (preferably ubiquinol), astaxanthin, ashwagandha, malate, rhodiola rosea, trans-resveratrol, vitamin C, citrulline malate, ginger, inositol, aspartate, luteole, pterostilbene, hyaluronic acid, setin, L-glutathione, L-lysine, L-theanine, L- threonate, apigenin, carnosine, sulforaphane, N-acetylcysteine, curcumin, zinc and magnesium, where the total content of said other components at least 25 weight percent of the amounts to the instant drink composition.
2. Instant beverage composition within the meaning of claim 1, where the nicotinamide riboside is included in the composition as nicotinamide riboside chloride.
3. Instant beverage composition within the meaning of claim 1 or 2, where the composition has a nicotinamide riboside content of 1.5-15 weight percent, preferably 2.0-10 weight percent, more at preference of 2.0-5 weight percent.
4. Instant beverage composition according to one of claims 1-3, where the composition has a nicotinamide mononucleotide content has of 3.0-25 weight percent, in particular of 4.0-15 weight percent, more specifically 5.0-10 weight percent.
5. Instant drink composition according to one of the preceding conclusions, regarding the composition creatine, alpha-ketoglutarate and contains glucosamine, and preferably furthermore at least one of glycine and astaxanthin.
6. Instant beverage composition according to claim 5, which 15-30 weight percent creatine (calculated as creatine monohydrate), 10-20 weight percent glycine, 5-10 weight percent alpha-ketoglutarate (calculated as calcium ketoglutarate), 5-10 weight percent glucosamine (calculated as glucosamine sulfate), 5-10 weight percent betaine, 2-6 weight percent Lion's Mane, 2-6 weight percent green tea extract, 0.5-5 weight percent malate, 0.5-5 weight percent taurate (calculated as magnesium taurate), 0.5-5 weight percent quercetin phytosome, 0.3-3 weight percent coenzyme Q10 (as ubiquinol) and contains 0.03-0.2 weight percent astaxanthin.
7. Instant beverage composition within the meaning of claim 5 or 6, which creatine monohydrate, glycine, calcium alpha-ketoglutarate, glucosamine sulfate, betaine, Lion's Mane, green tea extract, magnesium malate, magnesium taurate, quercetin phytosome, co- contains enzyme Q10 and astaxanthin.
8. Non-alcoholic beverage, comprising water and a solid fraction, where the standing group has a composition as given for the instant beverage composition according to one of the conclusions 1-7 .
9. Non-medical use of an instant drink composition according to one of claims 1-7 or a drink within the meaning of claim 8, where the use is selected from the group of non-medical: supporting the lifespan of a human, supporting healthy aging of a human, increasing the a person's health span, giving a person more energy, improving a person's sleep, increasing physical human performance, improving the mental clarity of a human, improving the sexual function of a human, improving a person's cognitive functioning, improving of muscle strength, supporting athletic endurance, maintaining physical endurance, supporting joint mobility, supporting physical resilience, reducing a person's fatigue, supporting focus and concentration, supporting memory, support of mental performance, maintaining mental vitality, supporting stress resistance, supporting mental alertness, supporting well-being, supporting quality of living and supporting daily activities.
10. Non-medical use within the meaning of claim 9, where the instant beverage composition or drink is administered to an average daily dosage of 250-1500 mg nicotinamide component or - to supply components.
11. Non-medical use within the meaning of claim 9 or 10, where the instant beverage composition or drink is administered to an average to deliver a daily dosage of 250-500 mg nicotinamide riboside.
12. Instant beverage composition according to one of claims 1-7 or a drink within the meaning of claim 8, for use in the treatment of a medical condition.
13. Instant beverage composition for use in accordance with claim 12, where the medical condition is selected from the group of medical conditions associated with low NAD levels.
14. Instant beverage composition for use in accordance with claim 12 or 13, where the use involves reducing the chance of developing an age-related medical condition.
15. Instant drink composition for use according to one of the conclusions 12-14, where the medical condition is chosen from the group of addictions, neurological diseases (such as dementia), infectious diseases, lipid disorders, diabetes, cardiovascular diseases, kidney disease, chronic fatigue syndrome, lung diseases, auto- immune diseases, obesity, mental disorders, sexual dysfunction.
16. Instant drink composition for use according to one of the conclusions 12-15, where the instant beverage composition or drink is administered for an average daily dosage of 200- to supply 1500 mg nicotinamide component or components.
17. Instant drink composition for use according to one of the conclusions 12-16, where the instant beverage composition or drink is administered for an average daily dose of 200-500 to deliver mg nicotinamide riboside. PORT CONCERNING RESEARCH INTO THE STATE OF THE ART Patent application 2039020 1 1 classification of the subject : Investigated areas of technology : L2 / 52; A61K31 / 7084; A61P43 / 00; A23L; A61K; A61P K9 / 00; A61K31 / 194; A61K31 / 205; K36 / 82; A61K36 / 06; A61K31 / 122; K31 / 215; A61K31 / 198; A61K31 / 185; K47 / 18; A61K31 / 352; A23L33 / 10 PC files: Scope of the investigation: -PATENTS; AbS-NPL Fully um of the investigated conclusions: Uninvestigated conclusions: November 2024 - Relevant literature 2 Citation of literature with indication, where necessary, of relevance to gory conclusion(s) of text passages or figures of particular importance X US 2018 / 0071273 A1 (SPECCIALTY NUTRITION GROUP INC) 1-17 March 15, 2018 * paragraphs [0007]-[0009], [0014]-[0018], [0023]-[0029], [0039], [0040], [0085], [0098]-[0106]; conclusions 1, 2, 4-12, 15-23, 31, 32 * – – – X EP 3756668 A1 (SCANDIBIO THERAPEUTICS AB) December 30 1-17 2020 * paragraph [0035]; conclusions 1-4, 15 * – – – X WO 2024 / 125113 A1 (HOBOOMLIFE BIO TECH SHENZHEN CO 1-17 LTD) June 20, 2024 * machine translation paragraphs [0007], [0031]-[0036], [0049], [0051]; conclusions 2, 3, 9, 10 * – – – X US 2021015788 A1 (NUCHIDO LTD) January 21, 2021 1-17 * paragraphs [0009], [0033], [0034], [0036], [0037], [0053], [0054], [0082], [0088], [0089], [0094], [0095], [0108], [0118], [0166]; conclusions 1, 13, 16, 25 * – – – X US 2019060336 A1 (HUIZENGA JOEL) February 28, 2019 1-17 * paragraphs [0101], [0103], [0128]-[0132], [0141], [0182], [0186], [0211], [0248]; conclusions 1, 2, 19, 23, 26 * – – – See explanation on the next page. 2 Citation of literature with indication, where necessary, of relevance to gory conclusion(s) of text passages or figures of particular importance X GB 2596849 A (ROMY JARDINE) January 12, 2022 1-17 * paragraphs [0006], [0007], [0012], [0013], [0015]-[0017], [0019], [0034]-[0058], [0060]-[0063], [0066] * – – – – – Date on which the investigation was completed: The competent official: June 2025 Dr. A. Breukink Netherlands Patent Office part of the Netherlands Enterprise Agency direction: welding areas of engineering: defined according to International Patent Classification (IPC). Generosity of the cited literature: p state of T being of particular importance in itself: literature on theory or not published in time the technical principle underlying the invention in conjunction with other cited literature E: patent literature published on or after the filing a state of the art of particular importance date of the present application and of which the submission date or the priority date is before the something of importance belonging to category X or Y submission date of the present application being state of the art D: mentioned in the application referring to an unrecorded state of affairs e technique L: literature mentioned for other reasons literature published between priority and &: member of the same patent family; corresponding literature submission date APPENDIX Accompanying the Report on the State of the Art Survey Patent application 2039020 The appendix contains a list of patent applications or patents published elsewhere (so-called and of the same patent family), which correspond to patent specifications mentioned in the report. The statement has been compiled based on data from the computer file of the European insurance agency as of June 30, 2025. The accuracy and completeness of this statement are neither guaranteed by the European Patent Office, nor guaranteed by the Netherlands Patent Office; the data are Provided for informational purposes. In the report mentioned Date of Corresponding Date of patent specification publication of patent specifications publication US 2018071273 A1 15-03-2018 WO 2016149277 A1 22-09-2016 EP 3756668 A1 30-12-2020 AU 2017378616 A1 27-06-2019 AU 2017378616 B2 14-12-2023 CA 3046457 A1 28-06-2018 CN 110381944 A 25-10-2019 CN 110381944 B 21-02-2023 EP 3558313 A1 30-10-2019 EP 3558313 A4 17-06-2020 EP 3558313 B1 04-08-2021 EP 3808347 A1 21-04-2021 JP 2020502254 A 23-01-2020 JP 7065856 B2 12-05-2022 JP 2022088435 A 14-06-2022 KR 20190110544 A 30-09-2019 KR 102558494 B1 24-07-2023 SE 1651735 A1 23-06-2018 SE 540582 C2 02-10-2018 WO 2018117954 A1 28-06-2018 US 2020113859 A1 16-04-2020 US 11141396 B2 12-10-2021 US 2021401787 A1 30-12-2021 US 11813236 B2 14-11-2023 WO 2024125113 A1 20-06-2024 CN 116236499 A 09-06-2023 CN 116236499 B 22-03-2024 US 2021015788 A1 21-01-2021 AU 2019233807 A1 22-10-2020 AU 2019233807 B2 20-02-2025 CA 3093598 A1 19-09-2019 CN 111918670 A 10-11-2020 EP 3765086 A1 20-01-2021 EP 3765086 B1 08-01-2025 EP 3765086 C0 08-01-2025 ES 3008907 T3 25-03-2025 WO 2019175587 A1 19-09-2019 GB 2586745 A 03-03-2021 GB 2586745 B 05-04-2023