What are the benefits of glutathione, glutamine, NAD+ (Nicotinamide adenine dinucleotide) and vitamin B12 injections?

Benefits of Glutathione, Glutamine, NAD+, and Vitamin B12 Injections

Based on current clinical guidelines and FDA-approved indications, only vitamin B12 injections have established clinical benefits for specific deficiency states, while glutathione, glutamine, and NAD+ injections lack sufficient evidence to recommend for general use outside of highly specific clinical scenarios.

Vitamin B12 Injections

Vitamin B12 (cyanocobalamin) injections are FDA-approved and clinically indicated for documented B12 deficiency states 1:

• Pernicious anemia (Addisonian anemia) - the primary indication where oral absorption is inadequate due to intrinsic factor deficiency 1
• Malabsorption conditions including gastrointestinal surgery (total or partial gastrectomy), gluten enteropathy/sprue, small bowel bacterial overgrowth, fish tapeworm infestation, and pancreatic or bowel malignancy 1
• Pharmacokinetics: Intramuscular B12 reaches peak plasma levels within 1 hour, with 50-98% excreted in urine within 48 hours after injection 1
• Clinical effects: Essential for growth, cell reproduction, hematopoiesis, nucleoprotein and myelin synthesis; prevents progression of neurologic damage (subacute combined degeneration of the spinal cord) when given promptly 1

Critical caveat: B12 injections are only necessary when oral absorption is compromised; oral supplementation is adequate for increased requirements due to pregnancy, thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, or hepatic/renal disease 1.

Glutamine Injections/Supplementation

Current ESPEN guidelines state there are insufficient consistent clinical data to recommend glutamine supplementation during conventional cancer therapy or for most clinical conditions 2, 3:

Limited Evidence for Specific Scenarios:

• Parenteral nutrition in acute pancreatitis: Glutamine supplementation (>0.30 g/kg Ala-Gln dipeptide) should be considered when parenteral nutrition is indicated, showing trends toward reduced complications and shorter hospital stays 2, 4
• Post-surgical trauma: One study showed intravenous glutamine (0.56 g/day/kg) attenuated glutathione depletion in skeletal muscle following surgery 5

Insufficient or Negative Evidence:

• Cancer patients: Heterogeneous data with some small studies showing benefits while larger controlled trials show no effect; concerns exist about potentially fueling cancer cell metabolism 2, 3
• Radiation-induced toxicity: Insufficient evidence to recommend for preventing radiation-induced enteritis, diarrhea, stomatitis, esophagitis, or skin toxicity 2
• Inflammatory bowel disease: No effect on disease course, intestinal permeability, or inflammatory markers 3, 6
• Hematopoietic stem cell transplantation: NOT recommended - one RCT showed more severe oral mucositis and higher relapse rates in the glutamine group 4

Major safety concern: High-dose glutamine is contraindicated in critically ill patients with organ dysfunction due to association with increased mortality 3.

Glutathione Injections

No clinical guidelines recommend glutathione injections for any specific indication:

• Theoretical rationale: Glutathione is the most important endogenous antioxidant system, essential for maintaining cellular thiols, protecting against oxidative damage, and interacting with various drugs 7
• Absorption problem: Oral or injected glutathione is not effectively utilized by cells; glutathione deficiency cannot be prevented or reversed by giving glutathione directly 7
• Cellular utilization pathway: Glutathione must be degraded extracellularly, products taken up by cells, then resynthesized intracellularly 7
• Potential alternative: Glutathione esters (not standard glutathione) can be transported into cells and hydrolyzed to form glutathione intracellularly, but these are not standard clinical formulations 7
• Protective interaction: Glutathione may protect vitamin B12 from depletion by xenobiotics through formation of glutathionylcobalamin complex 8

Clinical reality: Despite widespread marketing, there is no evidence-based indication for glutathione injections in clinical practice.

NAD+ Injections/Precursors

No clinical guidelines support NAD+ injections for general use:

• Metabolomic study findings: A 2023 human clinical trial showed that nicotinamide (Nam), nicotinamide mononucleotide (NMN), and nicotinamide riboside (NR) can boost NAD+ levels, but niacin (NA) caused flushing reactions with decreased phospholipids and increased bilirubin, which could be potentially risky 9
• Theoretical connection: NAD+ is required for glutathione synthesis and becomes essential during oxidative stress 10
• Sickle cell disease context: L-glutamine (which requires NAD for synthesis) at 0.6 g/kg/day showed reduction in painful episodes and hospitalizations in phase II/III trials, but was only tolerated in two-thirds of patients 10

Critical gap: While NAD+ precursors may boost NAD+ levels, there are no clinical outcome studies demonstrating benefits in morbidity, mortality, or quality of life that would justify routine use.

Clinical Bottom Line

Only vitamin B12 injections have established clinical utility for documented deficiency states with malabsorption 1. Glutamine supplementation has extremely limited indications (parenteral nutrition in acute pancreatitis) and significant safety concerns in critically ill patients 2, 3, 4. Glutathione and NAD+ injections lack evidence-based indications and should not be recommended in routine clinical practice.