The NAD⁺ liposome problem: supplement science vs marketing claims

Key findings: A March 2025 analytical report by supplement company Niagen Bioscience on 21 top-selling NAD⁺ supplements on Amazon revealed significant discrepancies between product claims and actual content¹:

• Only 24% met claims: Only 5 hard capsules contained NAD⁺ levels matching their labeled amounts.

• Significant discrepancies: 12 products (57%) contained less than 1% of the advertised NAD⁺, with 11 of these showing no detectable NAD⁺ at all.

• Liposome claims questioned: Among 11 products labeled as "liposomal," 8 softgels contained no detectable NAD⁺. The remaining 3 contained NAD⁺, but robust evidence supporting claims of enhanced absorption via liposome technology was absent.

Figure 1: Results from quantitative analysis of twenty-one commercial NAD⁺ products¹

These findings highlight significant quality control issues within the NAD⁺ supplement market and raise broader questions about the implementation and verification of liposome products in dietary supplements.

I. Liposomes 101: valid science with technical hurdles

Liposomes represent a scientifically valid delivery approach. These microscopic vesicles, composed of phospholipid bilayers, mimic cell membrane structures. When properly engineered, they offer potential advantages for supplement delivery²:

• Protection of sensitive ingredients from degradation in the digestive tract.

• Enhanced solubility and absorption for poorly absorbed compounds.

• Potential for sustained release, leading to more stable blood concentrations.

However, effective liposome formulation is technically demanding. It requires more than basic mixing; successful liposomal delivery depends on three critical factors³⁻⁵:

1. Precise formulation: Requires optimization of phospholipid types, cholesterol (essential for membrane stability), and the active ingredient ratio. The drug-to-lipid (D/L) ratio typically falls between 1:5 and 1:20 for effective encapsulation. This translates to an active ingredient content typically between 5% and 17% of the total lipid mass. Deviations often compromise encapsulation or stability.

2. Advanced manufacturing: Production involves multiple critical steps (vesicle formation, active ingredient loading, size control) requiring stringent process control to ensure batch consistency and quality.

3. Comprehensive characterization: Validating liposome quality necessitates rigorous data beyond imagery:

   • Encapsulation efficiency (EE): This critical metric measures the percentage of the active ingredient successfully encapsulated within the liposome structure. High EE (>70%) is fundamental for delivery efficacy, indicating most of the active is protected. Specialized analytical methods are required for accurate EE measurement.

   • Zeta potential: This measures the electrical charge on the particle surface and is a key indicator of colloidal stability. An absolute value >|30| mV is generally required to prevent particle aggregation or sedimentation during storage.

   • Particle size: Optimal size ranges between 100–200 nanometres (nm). Larger particles (>200 nm) may be rapidly cleared by the liver’s system. Smaller particles (<50 nm) often exhibit reduced drug loading capacity and instability. Notably, particles below 100 nm lack FDA approval for oral use due to insufficient safety data. Concerns exist regarding potential direct passage into the bloodstream via gut tight junctions, bypassing normal digestive processes.

   • Particle size distribution: The polydispersity index (PDI) measures the uniformity of particle sizes. A PDI <0.3 (measured by dynamic light scattering – DLS) indicates a narrow size distribution, reflecting a controlled manufacturing process.

   • Structural verification (TEM): Transmission electron microscopy should confirm the presence of intact, closed vesicle structures displaying the characteristic "dark-light-dark" trilamellar membrane profile. Amorphous shapes or simple spheres are insufficient proof.

II. NAD⁺ liposomes: discrepancies and verification gaps

Analysis of the 11 "liposomal" NAD⁺ products in the Niagen report identified several recurring issues:

1. Lack of EE transparency: EE data is rarely disclosed by liposome suppliers. Products lacking detectable NAD⁺ strongly suggest extremely low EE or an absence of functional liposomes. Independent testing of some commercial "NAD⁺ liposome" ingredients reported EE values as low as 3–7%.

2. Formulation concerns: NAD⁺ is a large, hydrophilic molecule requiring specific phospholipids and precise formulation for effective encapsulation. While achieving 20% active content in functional liposomes is challenging, claims of "40%+ NAD liposomes" are inconsistent with established formulation principles.

3. Dosage form incompatibility: Popular "liposomal NAD⁺" softgels utilize an oily internal phase designed for lipid-soluble compounds. NAD⁺ (and related molecules like NMN and vitamin C) are water-soluble, making this dosage form fundamentally incompatible with effective encapsulation within an aqueous core.

4. Poor manufacturing: Many materials marketed as "liposome ingredients" appear to be simple phospholipid blends—expensive mixtures that don’t form functional liposomes.

5. Absence of stability data: Critical stability parameters, particularly zeta potential and long-term storage stability data, are generally not provided, raising questions about product shelf-life and consistency.

6. Unsubstantiated efficacy claims: Products containing NAD⁺ frequently lack robust pharmacokinetic studies or human bioavailability data demonstrating superior absorption attributed to the liposomal form. Claims often rely on technological association rather than product-specific evidence.

III. Beyond NAD⁺: liposomal misrepresentation across ingredients

Similar concerns regarding liposome technology verification extend to other popular supplement ingredients like vitamin C, silymarin (milk thistle), curcumin, and glutathione:

• "Nano" particle ambiguity: Marketing emphasizing "nano" or "ultra-micro" size often overlooks the technical challenges: particles below 100 nm typically exhibit reduced drug loading, instability, rapid clearance, and lack established safety profiles for oral consumption.

• Questionable high-content claims: Products like a top-selling "liposomal vitamin C" with a vitamin C-to-phospholipid ratio of 29:1 (far exceeding the typical functional range) and lacking cholesterol contradict fundamental liposome formulation requirements. Claims such as "50% liposomal VC" or "75% liposomal glutathione" exceed plausible encapsulation limits.

• Scientific challenges with liposomal powders: Liposomes are water-based vesicles dependent on hydration for stability, with hydrophilic ingredients encapsulated in their internal aqueous phase. When turned to powder via spray drying or freeze-drying, they reconstitute in gastrointestinal fluids—but this process causes significant leakage of the encapsulated active ingredient, fully disabling liposome functionality. The scientific basis for "liposomal powders" of hydrophilic compounds remains unproven.

• Insufficient structural and quality data: Manufacturer-provided TEM images often lack resolution to confirm closed vesicle structures with the defining trilamellar membrane. Essential quality metrics (EE, zeta potential, stability data) are frequently absent.

• Lack of human bioavailability evidence: Dramatic absorption claims (e.g. glutathione "12.9x to 64x better absorption") are typically unsupported by publicly available, methodologically sound human studies. References often involve unrelated molecules or non-predictive in vitro models. Liposome effectiveness is molecule-specific; results are not universally transferable.

IV. How to evaluate "liposomal" supplements: practical tips

To avoid misleading products, use these science-backed, actionable steps:

1. Question the need for liposomes: Not all ingredients benefit from liposomal delivery. For example, oral NAD⁺ has limited evidence of effectiveness—adding "liposomal" may not improve it. Ask: does the ingredient have poor absorption issues that liposomes would realistically solve?

2. Check the ingredient list: Does the ingredient list include specific phospholipids and stabilising agents like cholesterol? Their absence suggests an incomplete formulation.

3. Spot unrealistic ratios: If the label lists both active ingredient and phospholipid amounts, do a quick check, calculate the D/L ratio. Ratios significantly outside the 1:5 to 1:20 range indicate potential formulation issues. Beware products that hide phospholipid amounts.

4. Require core data verification (essential): Reputable manufacturers should provide accessible evidence including: EE report and methodology, particle size and PDI report, zeta potential report, stability studies, human bioavailability data, and clinical efficacy data.

5. Stay vigilant against data fraud: When suppliers claim liposome metrics, downstream companies without R&D expertise may struggle to verify authenticity. Prevention measures include: requiring data reports signed by multiple responsible personnel at the supplier; requesting third-party lab reports and verifying batch consistency; obtaining supplier commitments to provide raw data and spectra; and legally safeguarding rights with evidence.

Conclusion:
Liposome technology is scientifically sound, but its misuse in supplements creates confusion and erodes trust. Advancing the field requires greater transparency in quality metrics, robust scientific validation of product-specific claims, and enhanced regulatory oversight to ensure consumer trust and product integrity. The focus must remain on translating genuine scientific potential into reliably effective products.

About Bonerge
Bonerge Lifescience is an innovative manufacturer that offers comprehensive turnkey solutions in the nutraceutical and cosmeceutical ingredients industries. Committed to scientific rigor and quality assurance, Bonerge is at the forefront of healthspan optimization, pioneering promising longevity ingredients such as Fisetin, Urolithin A, S-equol, Dihydroberberine, Pyrroloquinoline Quinone (PQQ), and L-Ergothionine. Through groundbreaking research and next-generation solutions, Bonerge is shaping the future of healthy aging.

Contact us at  kim.c@bonerge.com  to explore how we can collaborate.

References:
[1] Niagen Bioscience, Inc. Quantitative Analysis Report on Consumer Products Containing Nicotinamide Adenine Dinucleotide (NAD+). March 2025.
[2] Sercombe, L., et al. Advances and Challenges of Liposome Assisted Drug Delivery. Front. Pharmacol. 6, 286 (2015).
[3] Laouini, A., et al. Preparation, Characterization and Applications of Liposomes: State of the Art. J. Colloid Sci. Biotechnol. 1, 147–168 (2012).
[4] Fan, Y., Marioli, M., & Zhang, K. Analytical characterization of liposomes and other lipid nanoparticles for drug delivery. J. Pharm. Biomed. Anal. 192, 114210 (2021).
[5] Chountoulesi, M., et al. The significance of drug-to-lipid ratio to the development of optimized liposomal formulation. J. Liposome Res. 28, 249–258 (2018).