Luxury Regeneration

NAD+ and REJUVIO

  1. Salin

    Treats dehydration.

  2. Zinc

    Helps your immune system and metabolism function.

  3. Glutathione

    Aids in liver detoxification, blood sugar regulation and enhances skin appearance.

  4. Vitamin B12

    Helps keep your body's blood and nerve cells healthy and helps make DNA.

  5. Vitamin B-Complex

    Aids in brain and nervous system function, metabolism, and circulatory function.

  6. Vitamin C

    Necessary for the growth, development and repair of all body tissues.

  7. Nicotinamide Adenine Dinucleotide (500mg)

    Promotes mitochondrial and metabolic health.

Nicotinamide Adenine Dinucleotide (NAD+)

Nicotinamide Adenine Dinucleotide (NAD+) is a universal cellular electron transporter, coenzyme, and signaling molecule present in all cells of the body and is essential for cell function and viability. Along with NAD+, its reduced (NADH) and phosphorylated forms (NADP+ and NADPH) are also important. NAD+ and its redox partner NADH are vital for energy (ATP) production in all parts of cellular respiration: glycolysis in the cytoplasm and the Krebs cycle and electron transport chain in the mitochondria.

 

NADP+ and NADPH tend to be used in anabolic reactions, including biosynthesis of cholesterol and nucleic acids, elongation of fatty acids, and regeneration of glutathione, a key antioxidant in the body. In other cellular processes, NAD+ and its other forms are used as substrates by NAD+-dependent/-consuming enzymes to make post-translational modifications to proteins. NAD+ also serves as a precursor for the secondary messenger molecule cyclic ADP ribose, which is important for calcium signaling.

 

NAD+ is naturally synthesized de novo in the body from the amino acid tryptophan or vitamin precursors, nicotinic acid and nicotinamide, collectively known as vitamin B3 or niacin; it can also be synthesized from biosynthetic intermediates, including nicotinamide mononucleotide and nicotinamide riboside. Within salvage pathways, NAD+ is continuously recycled within cells being interconverted to and from its other forms. Cell culture studies also suggest that mammalian cells can take up extracellular NAD+.

 

NAD+ levels are highest in newborns and steadily decline with increasing chronological age.6 After age 50, they are approximately half of the levels seen in younger adults. The question of why NAD+ levels decline with age has been investigated in model organisms. During redox reactions NAD+ and NADH are not consumed but continuously recycled; however, during other metabolic processes, NAD+ is consumed by NAD+-dependent enzymes and thus could become depleted over time, contributing to increased DNA damage, age-related conditions and diseases, and mitochondrial dysfunction. Age-related decline in mitochondrial health and function is prominent in theories of aging and senescence, and studies of NAD+ depletion and subsequent oxidative damage and stress support these ideas.

 

A 2016 study in mice, which present age-related declines in NAD+ levels similar to those observed in humans, revealed that the age-related decline in NAD+ levels is driven by increasing levels of CD38, a membrane-bound NADase that breaks down both NAD+ and its precursor nicotinamide mononucleotide. The study also confirmed elevated CD38 gene expression in human adipose tissue from older adults (mean age, 61 years) relative to younger adults (mean age, 34 years). However, other studies in mice have demonstrated that inflammation and oxidative stress caused by aging reduce NAD+ biosynthesis. Thus, it is likely that a combination of mechanisms contribute to age-related decline of NAD+ in humans.

 

The clinical importance of maintaining NAD+ levels was established in the early 1900s, when it was discovered that the disease pellagra, which is characterized by diarrhea, dermatitis, dementia, and death, could be cured with foods containing NAD+ precursors, in particular vitamin B3. Notably, in contrast to vitamin B3 (niacin) supplementation, which causes the skin to flush, this side effect has not been observed with NAD+ injection. In recent years, low NAD+ levels have been linked to a number of age-related conditions and illnesses associated with increased oxidative/free radical damage, including diabetes, heart disease, vascular dysfunction, ischemic brain injury, Alzheimer’s disease, and vision loss.

 

IV infusion of NAD+ has been used extensively for the treatment of addiction, stemming from a study a 1961 report by Paul O’Hollaren, MD, of Shadel Hospital in Seattle, Washington. Dr. O’Hollaren described the successful use of IV-infused NAD+ for the prevention, alleviation, or treatment of acute and chronic symptoms of addiction to a variety of substances, including alcohol, heroin, opium extract, morphine, dihydromorphine, meperidine, codeine, cocaine, amphetamines, barbiturates, and tranquilizers, in over 100 cases. However, no clinical trials to date have evaluated the safety and efficacy of NAD+ treatment in addiction.

 

NAD+-replacement therapy may promote mitochondrial health and homeostasis, genome stability, neuroprotection, healthy aging, and longevity and may aid in treating addiction. Clinical trials evaluating these effects in humans treated with NAD+ injection have not yet been published; however, numerous clinical trials evaluating the efficacy and safety of NAD+-replacement therapy or augmentation in the context of human disease and aging have recently been completed, and many others are ongoing.

Zinc

With zinc playing a prominent role in many major processes within the human body, its mechanism of action varies depending on the organ system as well as the relevant process involved.

Immune System and Anti-Inflammation

In the immune system, zinc functions as a second messenger for immune cells; intracellular zinc participates in signaling events in immunity. It is involved in the development of monocytes and macrophages and regulates macrophagic functions such as phagocytosis and the production of proinflammatory cytokines. Zinc also inhibits phosphodiesterase, resulting in increased levels of guanosine-3' 5'- cyclic monophosphate which leads to the suppression of Tumor Necrosis Factor alpha (TNF-a), interleukin-1 beta (IL-1B), as well as other inflammatory cytokines. Additionally, zinc increases the expression of peroxisome proliferator-activated receptor- alpha; this results in the downregulation of inflammatory cytokines and adhesion molecules. Due to these and several other actions in the immune system, zinc is considered to be a key anti-inflammatory agent in the human body.

Zincs Effect on Skin

In the skin, zinc exerts its effects through several means in the development and maintenance of the skin cells. Zinc is most concentrated in the stratum spinosum layer of the skin compared to the other three layers namely basal layer, stratum granulosum, and stratum corneum. Studies have shown that zinc facilitates the proliferation as well as the survival of keratinocytes in the stratum spinosum; it also suppressed the activation of interferon-gamma and tumor necrosis factor-alpha by these keratinocytes. Additionally, zinc plays an active role in the development of Langerhans cells, a type of antigen-presenting cells, within the skin. Furthermore, the expression of melanocytes in the human skin is facilitated by zinc through mechanisms that are not yet fully understood.

Central Nervous System

In the central nervous system, zinc is essential in the formation and development of the growth factors, hormones, enzymes, and proteins during neurodevelopment; mild zinc deficiency during pregnancy has been shown to result in learning and memory abnormalities. Zinc helps in the development of the neural tube, the first brain structure that develops during pregnancy, the neural crest, and the process of stem cell proliferation during neurogenesis. Furthermore, free zinc is found in synaptic vesicles where it acts to modulate a variety of postsynaptic receptors; in the synaptic cleft it reduces the inhibitory actions of GABA receptors. Free zinc also exerts inhibitory actions on the release of glutamate, an excitatory neurotransmitter.

Glutathione

Glutathione is an essential molecule required for detoxification. Glutathione acts by assisting the body’s machinery in the removal of harmful destructive oxygen containing molecules.

 

During the body’s normal functioning an excess of oxygen containing molecules are produced, these molecules are typically very reactive with other molecules they come in contact with. In modern biochemistry these are referred to as reactive O2 species.

 

Reactive O2 species molecules include peroxide (H2O2) and superoxide anions (O2 with unpaired electron) these molecules are very toxic to the cell. The toxicity can be explained by the tendency of these molecules to bind or destroy important biomolecules.

 

The body has a natural system to remove these reactive O2 species. These systems metabolize and scavenge for reactive oxygen species, in a controlled and precise fashion.

 

The system that removes these toxic reactive oxygen species includes a host of enzymes:

 

  • Glutathione peroxidase (GPX): GPX detoxifies peroxides with glutathione acting as an electron donor in the reduction reaction, producing glutathione disulfide as an end product. GPX is a 80 kDa protein that is composed of four identical subunits. It is expressed throughout the entire body, individual isoforms are present in specific tissues. When the body is in a state of excess oxidative stress the expression of this enzyme is induced. Abnormal expression has been associated with a wide variety of pathologies, including hepatitis, HIV, and a wide variety of cancers, including skin, kidney, bowel, and breast. Glutathione reductase (GR)- catalyzes reduction of glutathione disulfide is by requires NADPH producing two glutathione molecules as an end product. GR is a member of the flavoprotein disulfide oxidoreductase family and exists as a dimer. Expression of GR is upregulated during periods of increased oxidative stress, to prepare for reactive oxygen species removal. The level at which regulation takes place is at the transcriptional level as well as at the post-translational level. Down regulation of GR production and activity are thought to be associated with cancer and aging.

 

  • Catalase: is involved in detoxification of reactive oxygen species.

 

  • Superoxide dismutase (SOD): is involved in the removal of superoxide species.

Immune Function: Glutathione plays a significant role in immune function. It encourages the T-cell function that’s essential for a healthy immune system and protects from environmental toxins.

 

Additionally, glutathione is essential in a broad range of metabolic processes:

  • Glutathione acts to neutralize a toxic metabolic byproduct: Methylglyoxal
  • Glutathione is involved in the protein disulfide bond rearrangement that is necessary for the synthesis of one third of the body’s proteins
  • It protects the body from the oxidative damage caused by glutathione peroxidase by acting as a helper molecule for certain enzymes
  • The liver uses Glutathione to help detoxify fats before the gallbladder emits bile, supporting healthy digestion

Detoxification: Glutathione may also be crucial in the removal and detoxification of carcinogens, and according to recent studies alterations in this metabolic pathway, can influence cell survival profoundly. Glutathione may be responsible for several vital roles within a cell besides antioxidation: 

  • Maintenance of the redox state (chemical reactions in which the oxidation state of atoms are modified)
  • Modulation of the immune response
  • Detoxification of foreign bacteria and viruses

Chronic Disease: Research has demonstrated that glutathione deficiency may be a factor in many chronic conditions; HIV/AIDS, Alzheimer’s, Parkinson’s disease, asthma, different cancers, cataracts, macular degeneration, open angle glaucoma, diabetes, and many diseases of the liver, kidneys, lungs, and digestive system.

 

Depletion Due to Aging and Alcohol Consumption: Glutathione plays a major role in the detoxification of ethanol (consumed as alcoholic beverages) and people who routinely drink will experience Glutathione depletion.20 Aging is another factor; as the body ages glutathione levels may drop below the level necessary to maintain healthy immune function (among other processes).

 

Depletion may also Caused by Other Factors: Besides alcohol consumption and the aging process, there are other factors that can deplete levels of Glutathione:

  • Acetaminophen
  • Aspartame
  • Benzopyrenes (tobacco smoke, fuel exhaust, etc.)
  • Many household chemicals (detergents, fabric softeners, air fresheners, mothballs, cleaners, bleach, etc.)

Fertility: In a study of eleven infertile men, suffering from dyspermia associated with various andrological pathologies - Glutathione was observed to exert a significant effect on sperm motility. Glutathione appeared to have an observable therapeutic effect on certain andrological pathologies that cause male infertility.

 

Artherosclerosis: In one study, ten patients with artherosclerosis were administered glutathione which resulted in a significant increase in blood filtration, in addition to a significant decrease in blood viscosity and platelet aggregation. Consequently, Glutathione infusion was determined to be an effective method of decreasing blood viscosity while increasing blood filtration.

 

Dermatological Properties: In a three-month study of female subjects, the women taking Glutathione showed significantly improved skin elasticity and amelioration of wrinkles compared to test subjects who received a placebo.

Vitamin B12 (Methylcobalamin)

Methylcobalamin, or vitamin B12, is a B-vitamin. It is found in a variety of foods such as fish, shellfish, meats, and dairy products. Although methylcobalamin and vitamin B12 are terms used interchangeably, vitamin B12 is also available as hydroxocobalamin, a less commonly prescribed drug product (see Hydroxocobalamin monograph), and methylcobalamin. Methylcobalamin is used to treat pernicious anemia and vitamin B12 deficiency, as well as to determine vitamin B12 absorption in the Schilling test. Vitamin B12 is an essential vitamin found in the foods such as meat, eggs, and dairy products. Deficiency in healthy individuals is rare; the elderly, strict vegetarians (i.e., vegan), and patients with malabsorption problems are more likely to become deficient. If vitamin B12 deficiency is not treated with a vitamin B12 supplement, then anemia, intestinal problems, and irreversible nerve damage may occur.

 

The most chemically complex of all the vitamins, methylcobalamin is a water-soluble, organometallic compound with a trivalent cobalt ion bound inside a corrin ring which, although similar to the porphyrin ring found in heme, chlorophyll, and cytochrome, has two of the pyrrole rings directly bonded. The central metal ion is Co (cobalt). Methylcobalamin cannot be made by plants or by animals; the only type of organisms that have the enzymes required for the synthesis of methylcobalamin are bacteria and archaea. Higher plants do not concentrate methylcobalamin from the soil, making them a poor source of the substance as compared with animal tissues.

Vitamin C (Ascorbic Acid)

Ascorbic acid is necessary for collagen formation (e.g., connective tissue, cartilage, tooth dentin, skin, and bone matrix) and tissue repair. It is reversibly oxidized to dehydroascorbic acid. Both forms are involved in oxidation-reduction reactions. Vitamin C is involved in the metabolism of tyrosine, carbohydrates, norepinephrine, histamine, and phenylalanine. Other processes that require ascorbic acid include biosynthesis of corticosteroids and aldosterone, proteins, neuropeptides, and carnitine; hydroxylation of serotonin; conversion of cholesterol to bile acids; maintenance of blood vessel integrity; and cellular respiration.

 

Vitamin C may promote resistance to infection by the activation of leukocytes, production of interferon, and regulation of the inflammatory process. It reduces iron from the ferric to the ferrous state in the intestine to allow absorption, is involved in the transfer of iron from plasma transferrin to liver ferritin, and regulates iron distribution and storage by preventing the oxidation of tetrahydrofolate. Ascorbic acid enhances the chelating action of deferoxamine during treatment of chronic iron toxicity (see Interactions). Vitamin C may have a role in the regeneration of other biological antioxidants such as glutathione and α-tocopherol to their active state.

 

Ascorbate deficiency lowers the activity of microsomal drug-metabolizing enzymes and cytochrome P-450 electron transport. In the absence of vitamin C, impaired collagen formation occurs due to a deficiency in the hydroxylation of procollagen and collagen. Non-hydroxylated collagen is unstable, and the normal processes of tissue repair cannot occur. This results in the various features of scurvy including capillary fragility manifested as hemorrhagic processes, delayed wound healing, and bony abnormalities.

Currently, the use and dosage regimen of vitamin C in the prevention and treatment of diseases, other than scurvy, is unclear.

 

Although further study is needed to recommend vitamin C therapy for the following ailments, recent data indicate a positive role for vitamin C for: overall increased mortality; the prevention of coronary heart disease (especially in women); management of diabetes mellitus; reducing the risk of stroke; management of atherosclerosis in combination with other antioxidants;789 osteoporosis prevention;10 reducing the risk of Alzheimer disease in combination with vitamin E; and the prevention of cataracts. In humans, an exogenous source of ascorbic acid is required for collagen formation and tissue repair.

References (for NAD+)

  • 1. Cantó C, Menzies KJ, Auwerx J. NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22(1):31-53. doi:10.1016/j.cmet.2015.05.023
  • 2. Johnson S, Imai SI. NAD+ biosynthesis, aging, and disease. F1000Research. 2018;7. doi:10.12688/f1000research.12120.1
  • 3. Belenky P, Bogan KL, Brenner C. NAD+ metabolism in health and disease. Trends Biochem Sci. 2007;32(1):12-19. doi:10.1016/j.tibs.2006.11.006
  • 4. Guse AH. The Ca2+-Mobilizing Second Messenger Cyclic ADP-Ribose. In: Calcium: The Molecular Basis of Calcium Action in Biology and Medicine. Springer Netherlands; 2000:109-128. doi:10.1007/978-94-010-0688-0_7
  • 5. Billington RA, Travelli C, Ercolano E, et al. Characterization of NAD uptake in mammalian cells. J Biol Chem. 2008;283(10):6367-6374. doi:10.1074/jbc.M706204200
  • 6. Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue. Polymenis M, ed. PLoS One. 2012;7(7):e42357. doi:10.1371/journal.pone.0042357
  • 7. Camacho-Pereira J, Tarragó MG, Chini CCS, et al. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 2016;23(6):1127-1139. doi:10.1016/j.cmet.2016.05.006
  • 8. Yoshino J, Mills KF, Yoon MJ, Imai SI. Nicotinamide mononucleotide, a key NAD + intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536. doi:10.1016/j.cmet.2011.08.014
  • 9. Goldberger J. Public Health Reports, June 26, 1914. The etiology of pellagra. The significance of certain epidemiological observations with respect thereto. Public Health Rep. 1975;90(4):373-375. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1437745/. Accessed October 11, 2020.
  • 10. Grant R, Berg J, Mestayer R, et al. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+. Front Aging Neurosci. 2019;11. doi:10.3389/fnagi.2019.00257
  • 11. Wu J, Jin Z, Zheng H, Yan LJ. Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications. Diabetes, Metab Syndr Obes Targets Ther. 2016;9:145-153. doi:10.2147/DMSO.S106087
  • 12. Pillai JB, Isbatan A, Imai SI, Gupta MP. Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2α deacetylase activity. J Biol Chem. 2005;280(52):43121-43130. doi:10.1074/jbc.M506162200
  • 13. Csiszar A, Tarantini S, Yabluchanskiy A, et al. Role of endothelial NAD+ deficiency in age-related vascular dysfunction. Am J Physiol - Hear Circ Physiol. 2019;316(6):H1253-H1266. doi:10.1152/ajpheart.00039.2019
  • 14. Ying W, Xiong Z-G. Oxidative Stress and NAD+ in Ischemic Brain Injury: Current Advances and Future Perspectives. Curr Med Chem. 2010;17(20):2152-2158. doi:10.2174/092986710791299911
  • 15. Zhu X, Su B, Wang X, Smith MA, Perry G. Causes of oxidative stress in Alzheimer disease. Cell Mol Life Sci. 2007;64(17):2202-2210. doi:10.1007/s00018-007-7218-4
  • 16. Abeti R, Duchen MR. Activation of PARP by oxidative stress induced by β-amyloid: Implications for Alzheimer’s disease. Neurochem Res. 2012;37(11):2589-2596. doi:10.1007/s11064-012-0895-x
  • 17. Lin JB, Apte RS. NAD + and sirtuins in retinal degenerative diseases: A look at future therapies. Prog Retin Eye Res. 2018;67:118-129. doi:10.1016/j.preteyeres.2018.06.002
  • 18. O’Hollaren P. Diphosphopyridine nucleotide in the prevention, diagnosis and treatment of drug addiction. West J Surg Obstet Gynecol. May 1961.
  • 19. Mestayer PN. Addiction: The Dark Night of the Soul/ Nad+: The Light of Hope - Paula Norris Mestayer - Google Books. Balboa Press; 2019. https://books.google.com/books?id=t7qEDwAAQBAJ&lr=&source=gbs_navlinks_s. Accessed October 11, 2020.
  • 20. Braidy N, Villalva MD, van Eeden S. Sobriety and satiety: Is NAD+ the answer? Antioxidants. 2020;9(5). doi:10.3390/antiox9050425
  • 21. Gerdts J, Brace EJ, Sasaki Y, DiAntonio A, Milbrandt J. SARM1 activation triggers axon degeneration locally via NAD+ destruction. Science (80- ). 2015;348(6233):453-457. doi:10.1126/science.1258366
  • 22. Essuman K, Summers DW, Sasaki Y, Mao X, DiAntonio A, Milbrandt J. The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD+ Cleavage Activity that Promotes Pathological Axonal Degeneration. Neuron. 2017;93(6):1334-1343.e5. doi:10.1016/j.neuron.2017.02.022
  • 23. Oshima J, Sidorova JM, Jr. Monnat RJ. Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions. Ageing Res Rev. 2017;33:105-114.
  • 24. Yu CE, Oshima J, Fu YH, et al. Positional cloning of the Werner’s syndrome gene. Science (80- ). 1996;272(5259):258-262. doi:10.1126/science.272.5259.258
  • 25. Fang EF, Hou Y, Lautrup S, et al. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun. 2019;10(1):1-18. doi:10.1038/s41467-019-13172-

References

Zinc: https://www.empowerpharmacy.com/drugs/zinc-sulfate-injection

 

Glutathione: https://www.empowerpharmacy.com/drugs/glutathione-injection

 

Methylcobalamin: https://www.empowerpharmacy.com/drugs/methylcobalamin-vitamin-b12-injection

 

Vitamin B-Complex: https://www.empowerpharmacy.com/drugs/b-complex-injection

 

Ascorbic Acid: https://www.empowerpharmacy.com/drugs/ascorbic-acid-injection

Contact us

Feel free to contact us

    Our offices

    Zurich

    Our Contact

    Email

    Phone

    Subscribe and receive latest insights & news.