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Intravenous Anti-Aging Therapy with NAD⁺ and Glutathione: what does the scientific literature say?

  • 1 giorno fa
  • Tempo di lettura: 4 min

This contribution is the result of the research work of Dr. Silvia Bianchi, member of the Agorà Anti-Aging Medicine Focus Group, and represents one of the first concrete outcomes of the group's shared scientific activity. The dossier presents a systematic review of the recent literature (2019–2024) on intravenous anti-aging therapy with NAD⁺ and glutathione, with the aim of providing an evidence-based overview for aesthetic physicians, endocrinologists and specialists in regenerative medicine.


Cellular ageing is a multifactorial process driven by metabolic decline, chronic oxidative stress and loss of cellular homeostasis. In recent years, the scientific community has focused on two key endogenous molecules — NAD⁺ (Nicotinamide Adenine Dinucleotide) and reduced glutathione (GSH) — whose progressive depletion with age is now correlated with the main signs of cutaneous and systemic ageing.¹


NAD⁺: the anti-ageing metabolic powerhouse

NAD⁺ is an essential coenzyme involved in hundreds of redox reactions and a fundamental substrate for sirtuins and PARPs, pro-longevity enzymes that regulate DNA repair and mitochondrial function. With advancing age, cellular NAD⁺ levels decline significantly through three main mechanisms: reduced synthesis (decreased NAMPT), increased catabolism (CD38 hyperactivation under inflammaging conditions) and excessive consumption by DNA repair systems.¹·²

Intravenous administration of NAD⁺ — or its precursors such as NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) — aims to restore a more youthful biosynthetic and reparative capacity to ageing cells. The most robust clinical evidence to date concerns the improvement of muscular and metabolic parameters (strength, endurance, insulin sensitivity) and the modulation of chronic inflammation.³·⁴

A 2024 randomised trial comparing NAD⁺ IV with NR IV in healthy adults showed that both modalities increase the available NAD⁺ pool, with a favourable safety profile. Side effects reported during NAD⁺ infusion (nausea, headache, cramps) are transient and dose-dependent, manageable with an appropriately slow infusion rate.⁵


Glutathione: the master antioxidant

Reduced glutathione is the body's primary intracellular antioxidant, present at millimolar concentrations within cells. With age, GSH levels decrease by up to 50% compared to young subjects, contributing to increased oxidative stress and chronic low-grade inflammation (inflammaging).⁶

In the anti-ageing field, GSH IV acts on three main levels: direct neutralisation of free radicals and protection of dermal collagen, modulation of inflammation through NF-κB inhibition, and reduction of melanogenesis through tyrosinase inhibition — with clinically observable effects on skin tone and luminosity.⁷

The most robust clinical evidence concerns neuroprotection (improvement of motor symptoms in Parkinson's disease) and protection from chemotherapy-induced neuropathy. In the dermato-aesthetic field, cycles of GSH IV combined with vitamin C show results on skin tone and reduction of hyperpigmentation, albeit in the absence of formal dedicated RCTs.⁸·⁹


Protocols and outcome assessment

Currently used protocols for NAD⁺ IV involve doses of 250-500 mg per session, with slow infusions (2-6 hours) and weekly frequency for 4-8 weeks, followed by monthly maintenance. For GSH IV, the standard dose is 600-1200 mg per session, over 15-30 minutes, 1-2 times per week for 8-10 weeks, almost always in combination with intravenous vitamin C.

Objective outcome assessment relies on biochemical biomarkers (NAD⁺/NADH ratio, GSH/GSSG, oxidative stress markers), dermatological instrumentation (Mexameter for melanin, cutometer for elasticity, Visia for wrinkles and spots) and validated quality-of-life questionnaires (SF-36).


Conclusions

NAD⁺ and intravenous glutathione represent promising tools in the anti-ageing medicine toolkit, with a solid biological rationale and an overall favourable safety profile. Clinical evidence from the last 5 years shows positive signals — from improved muscular and metabolic performance with NAD⁺, to neuroprotection and cutaneous improvement with GSH — while still requiring confirmation from larger, controlled studies.

The approach must be rigorously medical: careful patient selection, protocol personalisation and monitoring with objective parameters, within the context of an integrated anti-ageing plan that includes lifestyle, nutrition and targeted therapies.¹²


References


  1. Radenkovic D, Verdin E. Clinical Evidence for Targeting NAD Therapeutically. Pharmaceuticals (Basel). 2020;13(9):247.

  2. Conlon NJ. The Role of NAD⁺ in Regenerative Medicine. Plast Reconstr Surg. 2022;150(10S):41S-48S.

  3. Hou Y, Lautrup S, Cordonnier S, et al. NAD⁺ supplementation normalizes key Alzheimer's features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Trends Cell Biol. 2019;29(9):549-564.

  4. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229.

  5. Spring B, Morin CM, Bhatt DL, et al. Niagen® IV versus NAD⁺ IV: pilot study in healthy adults. medRxiv. 2024. doi:10.1101/2024.06.06.24308565.

  6. Labarrere CA, Kassab GS. Glutathione: a life-sustaining small molecule against oxidative stress, ageing, and inflammation. Front Nutr. 2022;9:1007816.

  7. Alzahrani TF, Alshahrani MY, Alqahtani SM, et al. Glutathione supplementation for skin lightening: a narrative review. Cureus. 2025;17(1):e78045.

  8. Wang HL, Chou AH, Wu AS, et al. Potential use of glutathione as a treatment for Parkinson's disease. Exp Ther Med. 2020;20(6):art.125.

  9. Fu X, Liang Y, Zhao M, et al. Efficacy of interventions for chemotherapy-induced peripheral neuropathy: a network meta-analysis. Front Neurol. 2017;8:223.

  10. Weschawalit S, Thongthip S, Phutrakool P, Asawanonda P. Glutathione and its antiaging and antimelanogenic effects. Clin Cosmet Investig Dermatol. 2017;10:147-153.

  11. Labarrere CA, Kassab GS. Glutathione: a life-sustaining small molecule against oxidative stress, ageing, inflammation. Front Nutr. 2022;9:1007816.

  12. Gindri IM, Frizzo MEB, Bilibio D, et al. Safety and effectiveness of NAD in different clinical conditions: a systematic review. Am J Physiol Endocrinol Metab. 2024;326(4):E417-E427.












 
 
 
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