COMPOSITIONS COMPRISING ORGANIC MINERAL CHELATES, NIACINAMIDE, AND HEMP OIL AND USES THEREOF FOR NEUROPROTECTION, CARDIOPROTECTION, DETOXIFICATION, IMMUNE SUPPORT, AND ANTI-AGING

Abstract

The compositions of this disclosure provide broad-spectrum nutrient supplementation to support the health of multiple organ and tissue systems in which mitochondrial function plays a fundamental role. In particular, the formulations promote neuroprotective, cardioprotective, immunosupportive, and anti-aging benefits. Also provided herein are novel, neuroprotective preparations containing a combination of broad- or full-spectrum hemp oil extract combined with niacinamide, a non-flushing form of vitamin B3, and methods of use are described allowing for safe, effective, and convenient use of a neuroprotective, antioxidant preparation for general and clinical use.

Claims

1. A composition comprising 100-5,000 milligrams glycine, 100-2,000 milligrams taurine, 100-2,000 milligrams malic acid, and 10-400 milligrams magnesium.

2. The composition of claim 1, wherein the composition comprises a broad-spectrum hemp oil extract, magnesium, and a base of synergistic (e.g., antioxidant, neuroprotective, cardioprotective, immunosupportive) vitamins, minerals, and other nutrients or nutraceuticals.

3. The composition of claim 1, wherein the composition comprises a full spectrum of naturally occurring cannabinoids and phytochemicals obtained from hemp oil extract, magnesium, and a base of synergistic (e.g., antioxidant, neuroprotective, cardioprotective, immunosupportive) vitamins, minerals, and other nutrients or nutraceuticals.

4. The composition of claim 1, wherein said magnesium is either inorganic or organic magnesium.

5. The composition of claim 4, wherein the magnesium compound or chelate comprises a counterion or chelating compound selected from the group consisting of oxide, sulfate, carbonate, chloride, succinic acid, ascorbic acid, aspartic acid, citric acid, gluconic acid, threonic acid, lysinic acid, glycine, malic acid, or taurine.

6. The composition of claim 5, wherein the magnesium chelate comprises a chelating compound selected from the group of glycine, malic acid, or taurine.

7. The composition of claim 4, wherein the magnesium is elemental magnesium.

8. The composition of claim 5, wherein the magnesium is provided as malate, glycinate, taurinate, or threonate for maximum therapeutic efficacy.

9. The composition of claim 1, with the base of synergistic vitamins, minerals, and other nutrients including more specifically (per serving): vitamin A as retinol, retinyl palmitate, retinyl acetate, or beta-carotene, 250-10,000 iu; vitamin B1, 0.25-100 mg; vitamin B2, 0.25-100 mg; vitamin B3, 5-250 mg; vitamin B5, 5-1,000 mg; vitamin B6, 0.25-100 mg; vitamin B12, 5-5,000 mcg; biotin, 5-1,000 mcg; PABA, 0.50-100 mg; vitamin C, 50-5,000 mg; vitamin D2 or D3, 400-10,000 IU; natural vitamin E (tocopherols and/or tocotrienols), 5-1,000 iu; vitamin K2 (Mk-7), 5-500 mcg; boron (glycinate), 0.1-10 mg; copper (glycinate), 0.1-5 mg; zinc (glycinate), 2-50 mg; manganese (glycinate), 0.1-10 mg; selenium (glycinate), 5-400 mcg; molybdenum (glycinate), 5-400 mcg; chromium (nicotinate glycinate or polynicotinate), 5-1,000 mcg; and kelp (as a source of natural iodine), 5-200 mg.

10. The composition of claim 9, with the addition of one or more of the following synergistic nutraceuticals or phytochemicals (per serving): coenzyme Q10 as ubiquinone or ubiquinol, 2.0-1,000 mg; alpha lipoic acid, 2.0-1,000 mg; Extramel French melon extract, 0.5-20 mg, AuroraBlue Alaskan Blueberry Concentrate or Extract, 5-5,000 mg; hemp oil extract, 1-1,000 mg supplying 0.5-100 mg of cannabidiol (CBD) and other cannabinoids, terpenes, and phenolics.

11. The composition of claim 10, comprising iodine as potassium iodide, 50-500 mcg; vitamin A as retinol or retinyl palmitate or acetate or beta-carotene, 500-5,000 iu; vitamin B1, 0.5-100 mg; vitamin B2, 0.5-100 mg; vitamin B6, 0.5-100 mg; Vitamin B3, 0.5-250 mg; vitamin B5, 5-200 mg; Vitamin B12, 3-5,000 mcg as cyanocobalamin or methylcobalamin or hydroxocobalamin or adenosylcobalamin; folic acid or methyl-folate or folinic acid, 10-1,000 mcg; 25-1,000 mcg; vitamin C, 25-1,000 mg; vitamin D2 or D3, 500-10,000 IU; vitamin E as d-alpha tocopherol or dl-alpha tocopheryl and/or mixed tocopherols and/or tocotrienols, 5-400 iu for alpha-tocopherol and 5-500 mg for mixed tocopherols including gamma-tocopherol or the family of tocotrienols; vitamin K2 (Mk-7), 5-500 mcg; boron as glycinate (as well as other organic or inorganic forms of the mineral), 0.1-10 mg; copper as bisglycinate (as well as other organic or inorganic forms of the mineral), 0.1-5 mg; zinc as bisglycinate (as well as other organic or inorganic forms of the mineral), 2-50 mg; manganese as bisglycinate (as well as other organic or inorganic forms of the mineral), 0.1-10 mg; selenium as glycinate (as well as other organic or inorganic forms of the mineral), 5-200 mcg; molybdenum as glycinate (as well as other organic or inorganic forms of the mineral), 5-400 mcg; and chromium as nicotinate glycinate or polynicotinate (as well as other organic or inorganic forms of the mineral), 5-1,000 mcg.

12. The composition of claim 1, comprising vitamin A as retinol or retinyl palmitate or acetate or beta-carotene, 500-5,000 iu; vitamin B1, 0.5-25 mg; vitamin B2, 0.5-25 mg; vitamin B3, 0.5-50 mg; vitamin B5, 10-100 mg; vitamin B6, 0.5-25 mg; vitamin B12, 10-1,000 mcg as methylcobalamin or hydroxocobalamin or adenosylcobalamin; folic acid or methyl-folate or folinic acid, 100-400 mcg; vitamin C, 25-1,000 mg; vitamin D2 or D3, 500-2,000 IU; vitamin E as d-alpha tocopheryl succinate and/or mixed tocopherols and/or tocotrienols, 30-100 iu for alpha-tocopherol and 5-500 mg for mixed tocopherols including gamma-tocopherol or the family of tocotrienols; vitamin K2 (Mk-7), 45-200 mcg; boron as glycinate (as well as other organic or inorganic forms of the mineral), 0.25-5 mg; copper as bisglycinate (as well as other organic or inorganic forms of the mineral), 0.25-2 mg; zinc as bisglycinate (as well as other organic or inorganic forms of the mineral), 5-20 mg; manganese as bisglycinate (as well as other organic or inorganic forms of the mineral), 0.5-5 mg; selenium as glycinate (as well as other organic or inorganic forms of the mineral), 25-200 mcg; molybdenum as glycinate (as well as other organic or inorganic forms of the mineral), 25-200 mcg; and chromium as nicotinate glycinate (as well as other organic or inorganic forms of the mineral), 25-200 mcg; and kelp (as a source of natural iodine), 5-200 mg.

13. The composition of claim 1, further comprising a soft chew, gummy, or tableting agent and an excipient that facilitates oral bioavailability through mucosal absorption from within the oral cavity.

14. The composition of claim 13, wherein said excipient that facilitates oral bioavailability through mucosal absorption from within the oral cavity comprises one or more of tapioca syrup, isomalto-oligosaccharide (IMO) syrup, powdered isomalto-oligosaccharide (IMO), honey, powdered honey, yacon syrup, agave syrup, corn syrup, glucose syrup, coconut sugar syrup, coconut sugar, date syrup, molasses, rice syrup, sugar cane syrup, raw cane sugar, cane sugar syrup, turbinado syrup, allulose syrup, maltitol syrup, polyglycitol syrup, sugar beet syrup, inulin syrup, powdered inulin, fibrosol, maltodextrin, dextrin, gum arabic, dextrose anhydrous, dextrose monohydrate, dried glucose syrup, sorghum syrup, tagatose syrup, and the following sugar alcohols: erythritol syrup, mannitol syrup, sorbitol syrup, or xylitol syrup, ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, and inositol combined with any combination of the following: palm oil, coconut oil, citric acid, malic acid, fumaric acid, tartaric acid, soy and/or sunflower lecithin, silicon dioxide, cellulose, stevia (leaf) extract, monk fruit extract, natural or artificial flavors, saccharin, acesulfame, aspartame, neotame, sucralose.

15. A composition comprising hemp oil extract containing of about between 0.5 and 500 mg, and a cannabidiol content of about between 0.25 and 100.0 milligrams, and niacinamide in an amount of about between 1.0 and 250 milligrams per serving.

16. The composition of claim 15, comprising hemp oil extract of about between 12.5 and 500 mg, and a cannabidiol content of about between 1.25 and 50 milligrams, and niacinamide in an amount of about between 5 and 100 milligrams per serving.

17. The composition of claim 15, comprising hemp oil extract of about between 25 and 250 mg, and a cannabidiol content of about between 2.5 and 50 milligrams, and niacinamide in an amount of about between 10 and 100 milligrams per serving.

18. The composition of claim 15, comprising hemp oil extract of about between 0.5 and 500 milligrams, and niacinamide of about between 2 and 250 milligrams, and/or nicotinamide riboside of about between 0.5 and 500 mg per serving.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0078] FIG. 1 is a picture and the supplement facts of Vitafusion MultiVites—2 gummies per serving which completely lacks vitamin B1 (thiamine), B2 (riboflavin), magnesium, zinc, copper, manganese, and selenium;

[0079] FIG. 2 is a picture and the supplement facts of Vitafusion Men's Gummy Vitamins, Multivitamin—2 gummies per serving which completely lacks vitamin B1 (thiamine), B2 (riboflavin), B3 (niacin), magnesium, copper, manganese, and selenium;

[0080] FIG. 3 is a picture and the supplement facts of Vitafusion Women's Gummy Vitamins, Multivitamin—2 gummies per serving which contains less than 25% of the RDA for zinc, and completely lacks vitamin B1 (thiamine), B2 (riboflavin), B3 (niacin), magnesium, copper, manganese, and selenium; and

[0081] FIG. 4 is a picture and the supplement facts of Smarty Pants Adult Formula, Daily Gummy Multivitamin—6 gummies per serving which contains less than 25% of the RDA for vitamin B1 (thiamine), B2 (riboflavin), and completely lacks vitamin B3 (niacin), magnesium, copper, manganese, and selenium.

[0082] FIG. 5 is a picture and the supplement facts of Olly The Perfect Men's Multi, Gummy Multivitamin—2 gummies per serving which contains less 25% of the RDA for vitamin B1 (thiamine) and B2 (riboflavin), 50% of the RDA for vitamin B3 (niacin), and 250% of the RDA for vitamin B6. Contains no magnesium, copper, manganese, and only 33% of the RDA for zinc.

DETAILED DESCRIPTIONS OF THE INVENTION

[0083] The drawings are for the purpose of describing selected versions of the present invention and are not intended to limit the scope of the present invention.

[0084] The embodiments herein relate to novel, multi-nutrient, antioxidant preparations containing organic mineral chelates (e.g., glycinates, malates, taurinates) for optimizing neurological, cardiovascular, and immune system function for broad-spectrum mitochondrial support, and multisystem protective effects. The novel, multi-nutrient preparations presented herein possess broad-spectrum antioxidant, anti-inflammatory activity, which may confer superior neuroprotective, cardioprotective, immunoprotective, and anti-aging benefits. This formulation represents the culmination of over 30 years of research and clinical study of nutritional biochemistry, orthomolecular nutrition, general nutrition, nutrient therapeutics, and functional medicine.

[0085] An optimal, therapeutic intervention to prevent and/or treat unabated oxidative stress and associated mitochondrial injury (damage) would ideally create a microenvironment wherein oxidative stress is minimized or reduced. Additionally, the therapeutic must be convenient for use in humans and animals—and easy to take—making a “soft-chew”, “gummy”, lozenge, chewable tablet, water soluble powder in packet form, “food-form,” partially orally-absorbable preparation greatly advantageous. Tablet and capsule forms of the preparation (formulation) will also be provided and will provide similar benefits with a slower onset of therapeutic effects.

[0086] The embodiments contained herein relate to preparations containing a full-spectrum of antioxidant nutrients (e.g., glycine, taurine, magnesium, selenium) and/or nutraceuticals (e.g., coenzyme Q10, alpha lipoic acid) and/or plant-based antioxidants (e.g., terpenes, polyphenolics) working in perfect biological synergy at optimal therapeutic doses for exceptional mitochondrial protection, function, and repair.

[0087] The average American diet coupled with the exposure to a wide range of nutrient-depleting antagonists and toxins (e.g., stress, heavy metals, medications) does not afford an optimal degree of nutrition or antioxidant support to prevent mitochondrial, neurological, cardiovascular, and immunological deficits leading to disease. In addition, the majority of multivitamins on the market are subpar at best, especially food-form supplements (e.g., soft chew, gummy). They are often poorly balanced, deficient, or completely lacking in specific neuroprotective, cardioprotective, immune supportive, mitochondrial nutrients (FIGS. 1-5). Embodiments of the present disclosure consist of efficacious, mitochondrial supportive, cellular rejuvenating, anti-aging, broad-spectrum nutrient preparations that address and correct these deficits for consumer benefit.

[0088] In addition, the embodiments herein also relate to antioxidant, mitochondrial supportive preparations of hemp oil containing a full-spectrum of beneficial, nontoxic, phytochemicals in combination with highly-bioavailable, lipophilic, mineral chelates (e.g., glycinates) of magnesium and other essential minerals—in a blend for highly-efficient, oral (e.g., gingival, buccal absorption) and topical delivery, and methods of use in humans and animals.

[0089] An optimal, therapeutic neuroprotective, cardioprotective, immunoprotective (immunosupportive) intervention to prevent and/or treat unabated oxidative stress and associated mitochondrial injury would ideally create a microenvironment wherein oxidative stress and mitochondrial function and integrity is improved and preserved. Additionally, preventative therapy must be convenient for use and easy to take. A soft chew, gummy, chewable tablet, lozenge, quick-dissolve tablet, “chewing gum”, liquid spray, liquid beverage, liquid “shot”, tincture, “food-form,” or topical application formulations are advantageous.

[0090] The, multi-nutrient, antioxidant preparation, in some embodiments, is a commercially available blend of vitamins, minerals, and other antioxidant nutrients (e.g., glycine, taurine, nutraceuticals, phytochemicals) combined to improve mitochondrial function, reduce oxidative stress, and promote healthy neurological, cardiovascular and immunological function with optimal anti-aging support. In some embodiments, the preparation comprises (per serving; chewable tablet, soft chew, gummy, lozenge, tablet, capsule, or packet): glycine, 100-5,000 mg; taurine, 100-2,000 mg; malic acid, 100-2,000 mg; vitamin A as retinol, retinyl palmitate, retinyl acetate, or beta-carotene, 250-10,000 iu; vitamin B1, 0.25-100 mg; vitamin B2, 0.25-100 mg; vitamin B3, 5-250 mg; vitamin B5, 5-1,000 mg; vitamin B6, 0.25-100 mg; vitamin B12, 5-5,000 mcg; biotin, 5-1,000 mcg; PABA, 0.50-100 mg; vitamin C, 50-5,000 mg; vitamin D2 or D3, 400-10,000 IU; natural vitamin E (tocopherols and/or tocotrienols), 5-1,000 iu; boron (glycinate), 0.1-10 mg; copper (glycinate), 0.1-5 mg; zinc (glycinate), 2-50 mg; manganese (glycinate), 0.5-5 mg; selenium (e.g., glycinate), 10-400 mcg; molybdenum (glycinate), 10-400 mcg; and chromium (nicotinate glycinate or polynicotinate), 10-1,000 mcg.

[0091] The foregoing base formulation is by way of example only; other formulations of the, multi-nutrient, antioxidant, mitochondrial supportive preparation are contemplated by the present disclosure. In some cases, the formulation comprises one or more additional components such as, for example, coenzyme Q10 as ubiquinone or ubiquinol, 2.5-1,000 mg; alpha lipoic acid, 2.5-1,000 mg; kelp, 5-200 mg; Extramel French melon extract, 0.5-10 mg, AuroraBlue Alaskan Blueberry Concentrate or Extract, 10-2,000 mg; hemp oil extract, 1-1,000 mg supplying 0.5-100 mg of cannabidiol (CBD) and other cannabinoids, terpenes, and phenolics. Additionally, it is anticipated that as scientific investigation generates additional data regarding the role of the various compounds comprising the preparation are generated, the composition of the preparation will change accordingly.

[0092] The form of nutrient delivery in some embodiments is a highly specialized mucoadhesive delivery system, which facilitates oral bioavailability through mucosal absorption from within the oral cavity. Some non-limiting examples of such excipient compounds include xylitol, erythritol, allulose, cellulose, palm oil, coconut oil, silicon dioxide, citric acid, malic acid, organic stevia (leaf) extract, monk fruit extract, and natural flavors. Other such compounds as are known in the art of oral nutrient and/or drug absorption and delivery systems may be used. In these and some other embodiments, the mitochondrial preparation is taken as a tablet, capsule, powder packet, liquid, soft chew, gummy, chewable wafer, quick-dissolve tablet, or lozenge placed in the mouth. In some embodiments, the lozenge is held under the tongue or placed in a buccal recess and allowed to dissolve. In some embodiments, the soft chew is chewed, allowing exposure of the vitamins, minerals, and other nutrients to the microvascular tissue (e.g., gingival, buccal) of the oral cavity for efficient absorption of the nutrients, and swallowed.

[0093] Topical creams, lotions, salves, balms, “patches”, and other external methods of application could also be employed to deliver the antioxidant, mitochondrial preparation consisting of synergistic, antioxidants nutrients (e.g., vitamins, minerals, nutraceuticals) to the skin. Hence, in some embodiments, the novel, antioxidant mitochondrial supportive preparations, as described herein, could also be employed for a wide range of skin conditions (e.g., acne, eczema, dermatitis, psoriasis) known to have excess oxidative stress and chronic inflammation, as a common, underlying component. Cannabinoids and the essential mineral magnesium are known to have antioxidant and anti-inflammatory properties both independent of, and dependent on NMDA receptor inhibition, respectively. Cannabinoids exert their beneficial effects through their innate free-radical scavenging (antioxidant) activity, cannabinoid receptor activation, and epigenetic modulation whereas magnesium exerts its influence through NMDA receptor inhibition, and multi-modal, synergistic interactions with a wide-variety of vitamins (e.g., vitamin D, B-complex), minerals (e.g., lithium, zinc), and the upregulation of endogenous, antioxidant enzyme systems.

[0094] In view of the above, some embodiments relate to mitochondrial supportive (nourishing) and protective, antioxidant, anti-inflammatory preparations containing hemp oil with a broad-spectrum of beneficial, antioxidant phytochemicals and highly bioavailable, magnesium coupled with selected, synergistic vitamins, trace elements, and/or nutraceuticals. Other embodiments relate to hemp oil—containing a broad-spectrum of beneficial terpenes, phenolics, and cannabinoids—in combination with highly bioavailable magnesium enhanced with additional synergistic antioxidant nutrients and/or nutraceuticals for neuroprotective, cardioprotective, and immunoprotection for a wide-variety of health-related and skin benefits.

[0095] In some embodiments, the mitochondrial supportive preparation further comprises a hemp extract (i.e., hemp oil) containing a full spectrum of naturally occurring phytochemicals (e.g., terpenes, phenolics, cannabinoids) obtained from the hemp plant. In some embodiments, the hemp oil is derived from organically grown hemp. In some embodiments, the hemp oil is derived from conventionally grown hemp.

[0096] In some embodiments, the mitochondrial support preparation further comprises an inorganic counter-ion carrying a variety of essential minerals, such as carbonate, chloride, oxide, or sulfate. In some embodiments, the counter-ion is an organic chelating compound chosen from the group consisting of acetic acid, succinic acid, ascorbic acid, aspartic acid, threonic acid, lysinic acid, malic acid, tauric acid, citric acid, and gluconic acid. In some embodiments, the chelating compound is a salt of orotic acid. In some embodiments, the chelate is a salt of glycine.

[0097] In some embodiments, the amount of glycine is between about 100 and 5,000 milligrams per serving.

[0098] In some embodiments, the amount of taurine is between about 100 and 2,000 milligrams per serving.

[0099] In some embodiments, the amount of malic acid is between about 100 and 2,000 milligrams per serving.

[0100] In some embodiments, the amount of cannabidiol (CBD) is between about 0.50 and 100 milligrams per serving.

[0101] In some embodiments, the amount of elemental magnesium is between about 5 and 400 milligrams per serving.

[0102] In some embodiments, the amount of elemental copper is between about 0.1 and 5 milligrams per serving.

[0103] In some embodiments, the amount of elemental zinc is between about 2.0 and 50 milligrams per serving.

[0104] In some embodiments, the amount of elemental selenium is between about 5 and 400 micrograms per serving.

[0105] In some embodiments, the amount of elemental boron is between about 0.10 and 10 milligrams per serving.

[0106] In some embodiments, the amount of elemental chromium is between about 5 mcg and 1,000 micrograms per serving.

[0107] In some embodiments, the amount of iodine is between about 50 mcg and 500 mcg per serving.

[0108] In some embodiments, the amount of kelp is between about 5 mg and 200 mg per serving.

[0109] In some embodiments, the amount of elemental manganese is between about 0.10 and 10 milligrams per serving.

[0110] In some embodiments, the amount of elemental molybdenum is between about 5 mcg and 400 micrograms per serving.

[0111] In some embodiments, the amount of thiamine is between about 0.25 mg and 100 milligrams per serving.

[0112] In some embodiments, the amount of riboflavin is between about 0.25 mg and 100 milligrams per serving.

[0113] In some embodiments, the amount of niacin is between about 5 mg and 250 milligrams per serving.

[0114] In some embodiments, the amount of pantothenate is between about 5 mg and 200 milligrams per serving.

[0115] In some embodiments, the amount of pyridoxine is between about 0.25 mg and 100 milligrams per serving.

[0116] In some embodiments, the amount of cobalamin is between about 3 mcg and 5,000 micrograms per serving.

[0117] In some embodiments, the amount of PABA is between about 0.1 mg and 100 milligrams per serving.

[0118] In some embodiments, the amount of vitamin A is between about 250 iu and 10,000 iu per serving.

[0119] In some embodiments, the amount of vitamin C is between about 10 mg and 2,000 milligrams per serving.

[0120] In some embodiments, the amount of vitamin D is between about 50 iu and 5,000 iu per serving.

[0121] In some embodiments, the amount of vitamin E is between about 5 iu and 1,000 iu per serving.

[0122] In some embodiments, the amount of vitamin K2 (Mk-7) is between about 5 iu and 500 mcg per serving.

[0123] In some embodiments, the amount of coenzyme Q10 is between about 2.0 mg and 1,000 milligrams per serving.

[0124] In some embodiments, the amount of alpha lipoic acid is between about 2.0 mg and 1,000 milligrams per serving.

[0125] In some embodiments, the amount of AuroraBlue Alaskan Blueberry Concentrate is between about 5 and 5,000 milligrams per serving.

[0126] In some embodiments, the amount of Extramel French Melon Extract is between about 0.5 and 20 milligrams per serving.

[0127] As discussed above, the disclosed invention relates to preparations of hemp oil containing a full-spectrum of naturally-occurring phytochemicals (e.g., terpenes, phenolics, cannabinoids) obtained from the hemp plant in combination with niacinamide for oral, topical, and portable electronic vaporization delivery as a general antioxidant, anti-inflammatory, central nervous system neuroprotectant and neurotrophic, and methods of use.

[0128] A wide range of primary central neurological diseases and secondary conditions manifest cognitive, memory, motor, and sensory impairment as primary and debilitating symptoms. A few non-limiting examples of such diseases and conditions are listed herein above and include amyotrophic lateral sclerosis (“ALD”), Parkinson's Disease (“PD”), Alzheimer's Disease (“AD”), post-traumatic stress disorder (“PTSD”), attention deficit hyperactivity disorder (“ADHD”), depression/anxiety, and tinnitus. Examples of secondary conditions include traumatic brain injury (“TBI”), chronic post-traumatic or post-surgical neuropathic pain, acute or chronic exposure to certain toxins, for example mercury, lead, cadmium, arsenic, polychlorinated biphenyls, and ethanol; and cerebral ischemia.

[0129] Phytochemicals from hemp oil (e.g., cannabinoids, terpenes, phenolics) and niacinamide exert a myriad of antioxidant, anti-inflammatory benefits on a number of body systems including the brain and nervous system, liver, kidneys, and skin—promoting improved mood and cognitive function, stress reduction, decreased pain, and a wide-variety of health benefits.

[0130] The cannabinoids, terpenes, and phenolics in hemp oil exert a portion of their neuroprotective, antioxidant, anti-inflammatory effects through inhibition of the N-methyl-D-aspartate receptor (“NMDA”). NMDA receptors are ubiquitous throughout the brain and play a role in regulation of the excitatory state of post-synaptic neurons. NMDA receptors act as a cationic membrane “pore,” primarily for calcium ions although other cations such as sodium, zinc, and protons may pass into the cell.

[0131] Several physiologic mechanisms resist a partially depolarized state in the post-synaptic cell membrane, keeping the pore closed to the influx of calcium an enhancing appropriate NMDA receptor function. One of these potentiating mechanisms is tyrosine-mediated phosphorylation of the NMDA receptor subunits, tending to “close” the receptor pore by causing an amphoteric shift in one or more protein subunits. Tyrosine phosphatase-mediated NR2B subunit phosphorylation potentiated by the lithium cation has been shown to cause depression of NMDA receptor currents.

[0132] In addition to its use in a preventative capacity, the hemp oil/niacinamide therapeutic possesses a number of immediate benefits to the consumer including: decreased inflammation, decreased pain and tension, a calming/relaxing effect on the brain and body, and improved energy, mood, and cognitive function (e.g., memory, focus, concentration). By reducing neural and general inflammation in the body, the therapeutic helps to relieve tension, and promote restful, restorative sleep.

[0133] Niacin (also known as vitamin B3) includes two biologically active forms, nicotinic acid and nicotinamide (niacinamide), which give rise to the coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP are coenzymes required for oxidative reactions important in energy production and non-redox signaling pathways regulating biological functions such as gene expression, cell cycle progression, DNA repair and cell death. The ratio of NAD and NADP play different metabolic roles in the cytosol: the NADH/NAD+ratio is small (˜8×10.sup.−4), thus favoring oxidative catabolism, whereas the NADPH/NADP+ratio is higher (˜75), thus providing a strongly reducing environment for biosynthetic reactions. NAD+ is an essential cofactor of enzymes involved in various signaling pathways that are important in cellular functions such as cellular energy metabolism, differentiation, and stress resistance. Niacinamide is considered to be the main NAD precursor in mammals and is involved in the coordination and regulation of a diversity of cellular responses, including proliferation, differentiation, and apoptosis, through the regulation of a wide range of enzymatic activities. As a precursor of NAD+, NADH, NADP+, and NADPH, niacinamide plays an integral role in cellular metabolism, cellular proliferation and the repair of damaged cells.

[0134] In the brain and nervous system, vitamin B3 (e.g., niacinamide) serves a vital role in neuroprotection, neurogenesis, neuronal development, and neuron survival (see Table 1). Like other neurotrophic vitamins and minerals (e.g., ascorbic acid, zinc) whose intake is often suboptimal or deficient due to a wide variety of factors (e.g., nutrient poor diets, excess refined sugar, increased requirements due to stress, medication induced deficiencies)—niacinamide in sufficient or optimal amounts promotes the formation of new neurons (i.e. neurogenesis) by promoting stem cell proliferation, stem cell survival, and increasing the rate of differentiation of embryonic stem cells or neural progenitors into post-mitotic neurons. Due to its importance in energy metabolism, and biosynthetic reactions essential for healthy brain function, niacinamide has been demonstrated to move freely in and out of the brain.

TABLE-US-00001 TABLE 1 Main findings on the role of niacin in neurodegeneration Effector Main Findings Alzheimer's Niacin Inverse association between AD and dietary disease niacin intakes. NAD.sup.+ High brain levels restore mitochondrial function and antagonize cognitive decline. Nam/Nam Protect against Aβ-induced neurotoxicity via mono- reduction of App and PSEN-1 expression and nucleotide ROS levels. Nam Reduces DNA damage, neuroinflammation riboside and cell death of hippocampal neurons. SIRT1 Supports the non-amyloidogenic pathway of AD. Lessens AD neuroinflammation, oxidative stress and mitochondrial dysfunction. NMNAT1-3 Protects against axon degeneration via reduction of nicotinamide mononucleotide levels and SIRT1 activation. NMNAT2 Activity downregulated prior to neurodegeneration; restoration of activity is neuroprotective against tauopathy. Low gene expression in AD patients. Parkinson's Niacin Increased intake enhances striatal dopamine disease synthesis and restores optimal NAD.sup.+/NADH ratio. High levels sequester transition metal ions. Low doses impact macrophage polarization from M1 (pro-inflammatory) to M2 (anti- inflammatory) profile. NAD.sup.+ Decreased levels in PD patients. NADPH Inhibits MPTP.sup.+-induced oxidative stress and glia-mediated neuroinflammation. NNMT High levels in the cerebrospinal fluid and midbrain dopamine neurons of PD patients. High activity associated with low activity of mitochondrial complex 1; it counteracts the MPP.sup.+-dependent toxicity on mitochondrial complex 1 and activates neuronal autophagy. Induces neurite branching, synaptophysin expression and dopamine release. Huntington's NAD Low levels correlate with disease progression disease in DrosophilaHD model. Nam Protects against the toxicity of polyQ proteins in DrosophilaHD models. Restores BDNF protein levels, increases acetylated PGC-1α, improves motor deficits. Prevents motor abnormality via PARP-1- dependent inhibition of neuronal death and oxidative stress. SIRT1 Rescues neurons from mutant huntingtin toxicity. Ameliorates pathological mechanisms underlying disease onset.

[0135] Cannabinoids and vitamin B3 (e.g., nicotinic acid, nicotinamide, niacinamide) are known to have antioxidant and anti-inflammatory properties both independent of, and dependent on NMDA receptor inhibition, respectively. By definition, antioxidants possess anti-inflammatory properties. Cannabinoids exert their beneficial physiological effects through a myriad of activities including antioxidation, CB1 and CB2 receptor interaction, and epigenetic modulation whereas niacinamide (vitamin B3) exerts its influence through its innate antioxidant activity, regeneration of endogenous antioxidants such as glutathione, and the support of numerous biochemical pathways involved in energy production, biosynthetic processes, and cellular repair. Evidence from both in vitro and in vivo studies demonstrate that niacinamide possesses potent antioxidant properties, and niacinamide deficiency contributes to increased oxidative stress and inflammation.

[0136] Preventative therapy or treatment must be convenient for use making a vaporization delivery method such as provided by a portable electronic vaporization device (e.g., vape pen) greatly advantageous. Given the similar boiling point temperatures for hemp oil and niacinamide, and their lack of harmful degradation byproducts, makes this combination especially well-suited for vaporization delivery. For example when heated to vaporization, the cannabinoids in hemp oil undergo a beneficial “activation process”, chemically referred to as decarboxylation (loss of a carboxyl group), and niacinamide like its chemical cousin nicotine with their pyridine rings, remain largely intact when exposed to temperatures that approach or exceed vaporization. A study published in the journal Chemical Research in Toxicology found that nicotine vaporized using e-cigarette delivery produced no detectable levels of pyridine (a nicotine breakdown product) in the aerosolized vapor. Of the 150 analytes measured in the e-cigarette aerosol, 104 were not detected, and 9 out of the 25 aerosol analytes detected were too low to be quantified. The authors concluded, “thus, the aerosol from the e-cigarette is compositionally less complex than cigarette smoke and contains significantly lower levels of toxicants. These data demonstrate that e-cigarettes can be developed that offer the potential for substantially reduced exposure to cigarette toxicants.”

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[0137] Vaporization of Niacinamide, Nicotinic Acid, Nicotine, and Cannabinoids

[0138] Niacinamide (nicotinamide) undergoes vaporization from a solid to a vapor at a relatively low 150-160° C., whereas nicotinic acid undergoes sublimation from a solid to a vapor at 236° C. In comparison, nicotine vaporizes at 247° C. and cannabinoids at a much lower, 157-220° C. The vaporization temperature of cannabidiol is between 160° C.-180° C.

[0139] Other convenient and effective delivery forms include liquid spray, liquid beverage, liquid “shot”, tincture, gummy or “chewing gum”, chewable, “food-form,” and partially orally-absorbable (e.g., gingival, buccal) soft chew or gummy preparations utilizing mucoadhesive technologies. Topical creams, lotions, salves, balms, “patches”, and other external methods of application could also be employed to deliver the neuroprotective, antioxidant, anti-inflammatory preparation consisting of a broad- or full spectrum of cannabinoids, niacinamide, and/or a blend of synergistic nutrients (e.g., vitamins, minerals) to the skin for dermatological issues related to chronic inflammation such as acne, eczema, dermatitis, psoriasis and other inflammatory skin conditions.

[0140] The neurosupportive blend, in some embodiments, is a commercially available blend of organic or conventionally grown hemp oil extract with vitamin B3 (niacinamide) and/or nicotinamide riboside. In some embodiments, the neurosupportive blend comprises: hemp oil extract, 0.5-500 mg; niacinamide, 0.5-250 mg. In some embodiments, the neurosupportive blend comprises: hemp oil extract, 5-500 mg; niacinamide, 5-250 mg. In other embodiments, the neurosupportive blend comprises: hemp oil extract, 0.5-500 mg; nicotinamide riboside, 0.5-500 mg.

[0141] The delivery system in some embodiments is a highly specialized combination of the most bioavailable nutrients along with non-GMO tableting agents and excipients which facilitate oral bioavailability through mucosal absorption from within the oral cavity. Some non-limiting examples of such excipient compounds include tapioca syrup, isomalto-oligosaccharide (IMO) syrup, powdered isomalto-oligosaccharide (IMO), honey, powdered honey, yacon syrup, agave syrup, corn syrup, glucose syrup, coconut sugar syrup, coconut sugar, date syrup, molasses, rice syrup, sugar cane syrup, raw cane sugar, cane sugar syrup, turbinado syrup, allulose syrup, maltitol syrup, polyglycitol syrup, sugar beet syrup, inulin syrup, powdered inulin, fibrosol, maltodextrin, dextrin, gum arabic, dextrose anhydrous, dextrose monohydrate, dried glucose syrup, sorghum syrup, tagatose syrup, and the following sugar alcohols: erythritol syrup, mannitol syrup, sorbitol syrup, or xylitol syrup, ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, and inositol combined with any combination of the following: palm oil, coconut oil, citric acid, malic acid, fumaric acid, tartaric acid, soy and/or sunflower lecithin, silicon dioxide, cellulose, stevia (leaf) extract, monk fruit extract, natural or artificial flavors, saccharin, acesulfame, aspartame, neotame, sucralose.

[0142] Other such compounds as are known in the art of oral drug absorption and delivery systems may be used. In these and some other embodiments, the neuroprotective preparation is taken as a tablet, soft chew, gummy, chewable wafer, quick-dissolve tablet, or lozenge placed in the mouth. In some embodiments, the lozenge is held under the tongue or placed in a buccal recess and allowed to dissolve. In some embodiments, the soft chew is chewed, allowing exposure of the phytochemicals (e.g., terpenes, phenolics, cannabinoids), bioavailable magnesium, and other nutrients to the microvascular tissue (e.g., sublingual, lingual, and buccal surfaces) of the oral cavity for efficient absorption of the nutrients, and swallowed.

[0143] A neuroprotective, antioxidant, anti-inflammatory preparation and method of use has been described. Based upon known mechanisms for unabated oxidative stress (e.g., nutrient deficiencies, suboptimal dietary antioxidant consumption), chronic inflammation, and neuronal cell death secondary to excitotoxicity—the neuroprotective preparation acts to decrease oxidative stress through the innate antioxidant activity of a full-spectrum of terpenes, phenolics, and cannabinoids (from hemp oil), the upregulation of endogenous antioxidant enzyme systems (e.g., superoxide dismutase, SOD; glutathione peroxidase, GPx; catalase), and to militate against development of increased post-synaptic neuronal intracellular calcium levels by acting upon (via modulation and inhibition) NMDA receptors in the post-synaptic cell membrane. The synergistic effects of a broad-spectrum cannabinoid (hemp) extract (i.e. hemp oil) and niacinamide are effectively coupled to create an optimal therapeutic effect while reducing undesirable, adverse effects (i.e. side-effects).

[0144] The embodiments and examples set forth herein were presented in order to best explain the present invention and its practical application and to thereby enable those of ordinary skill in the art to make and use the invention. However, those of ordinary skill in the art will recognize that the foregoing description and examples have been presented for the purposes of illustration and example only. The description as set forth is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of the teachings above.

[0145] Nutritional deficiencies are extremely prevalent today due to a variety of factors. Nutrient-depleted soils, unbalanced diets, increased requirements due to stress, injury, excess refined sugar, caffeine, alcohol consumption, individual idiosyncrasies, poor appetite, dieting to promote weight loss, and pharmaceutical medications can inhibit nutrient absorption and/or increase excretion leading to nutrient deficiencies.

[0146] Vitamins and minerals serve as important cofactors and catalysts for thousands of enzymatic reactions and chemical processes in the human body. They are indispensable to life, and in health maintenance and disease prevention, but are often deficient due to a variety of factors.

[0147] As briefly discussed, there are many circumstances in which the level of one or more vitamins or minerals may be insufficient leading to compromised biological processes and signs of deficiency. Symptoms indicative of suboptimal nutrient intake (e.g., copper and/or zinc) include, fatigue, poor stamina, cognitive impairment, cardiovascular dysfunction, skin problems, weakened immune system, and susceptibility to infections. Other common signs of vitamin and/or mineral deficiency (e.g., magnesium, B-vitamins) include digestive disturbances, hair loss, impaired wound healing, and sleep disturbances. Malabsorption of vitamins and minerals is also seen in a variety of conditions. Examples are irritable bowel syndrome, prolonged diarrhea, pernicious anemia, disorders of the liver and digestive system, prolonged diarrhea, and hyperthyroidism. In addition, since a number of vitamins (e.g., biotin, vitamin K2) are provided by the gastrointestinal microbiome, use of antibiotics that destroy beneficial bacterial flora may inevitably lead to decreased intestinal vitamin production.

[0148] The wide-ranging effects of nutrient deficiencies on multiple health outcomes has been extensively studied and described in hundreds of international studies. It has been well-documented that several key, neuroprotective, cardioprotective, immune strengthening nutrients are commonly deficient due to mineral-depleted soils and the Standard American Diet (SAD), and are further depleted by chronic stress, physical work, exercise, pregnancy, excess refined sugar, alcohol, caffeine, nicotine, glyphosate (e.g., divalent (2+) ions: magnesium, zinc, iron, copper, manganese, selenium), and various medications that inhibit vitamin absorption (e.g., proton pump inhibitors, antacids, metformin; vitamin B12), and promote the excretion of protective elements (e.g., spironolactone, copper).

[0149] Vitamin B3 (e.g., niacinamide) functions as a potent antioxidant in biological systems. As a potent antioxidant, on par or greater than ascorbate and alpha-tocopherol, niacinamide also possesses powerful anti-inflammatory properties. Niacinamide showed significant inhibition of oxidative damage induced by reactive oxygen species (ROS) generated by ascorbate-Fe.sup.2+ and photosensitization systems in brain mitochondria, and at millimolar concentrations, niacinamide protected against both protein oxidation and lipid peroxidation. However, its effect on the inhibition of protein oxidation was greater than that for lipids. The protective effect was observed at biologically relevant concentrations, with an effect greater than that of the endogenous antioxidants, ascorbic acid and alpha-tocopherol. The results from a 1999 study by Kamat and Devasagayam demonstrate that niacinamide can be viewed as a potent antioxidant capable of protecting cell membranes in the brain against oxidative stress causes by free radical assault.

[0150] In addition to its neuroprotective effects on the brain and nervous system, as a powerful antioxidant, topical application of niacinamide has been shown to exhibit anti-inflammatory properties, and improve the tone and texture of the skin, as well as reduce fine lines, wrinkles, and hyperpigmentation.

[0151] This invention relates to cognitive-enhancing, stress-reducing, pain-relieving, antioxidant, anti-inflammatory preparations containing niacinamide and broad or full spectrum hemp oil extract.

[0152] This invention relates to hemp oil extracts containing a broad or full spectrum of cannabinoids in combination with niacinamide—as the 2-component core—potentially enhanced with selected, synergistic nutrients in a next-generation, antioxidant, anti-inflammatory neuroprotective preparation.

[0153] Niacin Deficiency

[0154] A suboptimal intake of niacin (vitamin B3) can result in the following symptoms of deficiency: fatigue, apathy, depression, headache, and disorientation. Further symptoms of deficiency include dermatitis, swollen mouth and bright red tongue, alopecia, muscle weakness, twitching, burning in the extremities, altered gait, diarrhea, depression, anxiety, progressing to vertigo, memory loss, paranoia, psychotic symptoms, and aggression.

[0155] Niacin (vitamin B3) is a water-soluble vitamin whose derivatives such as NAD, NADH, NAD+, and NADP play essential roles in energy metabolism in the living cell and DNA repair. The designation vitamin B3 includes the acid (carboxy) form, nicotinic acid, and the basic (amide) form, nicotinamide or niacinamide. A severe lack of niacin causes the deficiency disease pellagra characterized by dermatitis and dementia, whereas a mild deficiency can present with a wide variety of symptoms such as fatigue, depression, headache, and muscle weakness. The recommended daily allowance of niacin is 2-12 mg a day for children, 14 mg a day for women, 16 mg a day for men, and 18 mg a day for pregnant or breast-feeding women. The liver can synthesize niacin from the essential amino acid tryptophan, but the synthesis is extremely slow and requires vitamin B6; 60 mg of tryptophan are required to make one milligram of niacin. Bacteria in the gut may also perform the conversion but are inefficient. Although nicotinic acid and nicotinamide (niacinamide) are identical in their vitamin activity, nicotinamide does not have the same lipid-modifying effects as nicotinic acid. When niacin takes on the -amide group, it does not reduce cholesterol or cause flushing.

[0156] The central redox coenzyme in cellular metabolism, NAD+ functions as a hydride (H.sup.−) acceptor, forming NADH with simultaneous oxidation of carbohydrate, fat, and protein metabolites. Thus, proper carbohydrate, fat, and protein metabolism requires NAD+ as a hydride acceptor, whereas oxidative phosphorylation, gluconeogenesis, ketogenesis, lipogenesis, and detoxification of reactive oxygen species (ROS) require the reduced co-factors, NADH and NADPH, as hydride donors.

[0157] Cannabinoids (from hemp extract) and magnesium exert a myriad of antioxidant, anti-inflammatory benefits on the brain and nervous system, cardiovascular system, skin, bones, and possess wide-ranging, general health benefits.

[0158] A neuroprotective, antioxidant, anti-inflammatory preparation and method of use has been described. Based upon known mechanisms for unabated oxidative stress (e.g., nutrient deficiencies, suboptimal dietary antioxidant consumption), chronic inflammation, and neuronal cell death secondary to excitotoxicity—the neuroprotective preparation acts to decrease oxidative stress through the innate antioxidant activity of a full-spectrum of cannabinoids (from hemp extract), upregulation of endogenous antioxidant enzyme systems (e.g., superoxide dismutase, SOD; glutathione peroxidase, GPx; catalase), and to militate against development of increased post-synaptic neuronal intracellular calcium levels by acting upon NMDA receptors in the post-synaptic cell membrane. The synergistic effects of a broad-spectrum cannabinoid (hemp) extract and niacinamide are effectively coupled to create an optimal therapeutic effect while reducing undesirable, adverse effects (i.e. side-effects).

[0159] In this disclosure, “about” means within +/−10% of a stated value.

[0160] The embodiments and examples set forth herein were presented in order to best explain the present invention and its practical application and to thereby enable those of ordinary skill in the art to make and use the invention. However, those of ordinary skill in the art will recognize that the foregoing description and examples have been presented for the purposes of illustration and example only. The description as set forth is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of the teachings above.

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[0190] Although the invention has been explained several embodiments, it is to be understood that many other possible modifications and variations can be made without departing from the spirit and scope of the invention.