The methods for our study and any claims are based on our randomized, placebo-controlled, double-blind trial and not generalized claims made from published literature
GENERAL EVALUATION OF SAFETY AND EFFICACY
LathMize™ Oral NAD+ with Significant Intracellular Impact
(Institute of Systems Biology)
REVIEW OF TRIAL METHODOLOGY, DATA, AND RESULTS
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What is NAD+?
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme central to cellular energy metabolism and a variety of biological processes, including DNA repair, oxidative stress response, and cell signaling. In clinical settings, NAD+ has gained significant attention due to its potential therapeutic applications, particularly in combating age-related conditions and metabolic disorders.
As NAD+ levels naturally decline with age, replenishing these levels through supplementation has been explored as a strategy to improve cellular function and overall health.
What is LathMize™ NAD+?
NAD+ is a highly unstable molecule, which in its natural form begins to break down after five days if not kept refrigerated. “LathMizing” is a unique, patented process in manufacturing, ensuring that the NAD+ dose is stable on the shelf (two years documented shelf life), within the gut, and in the bloodstream.
Where has NAD+ been studied for use? *
Neurodegenerative Conditions
NAD+ supplementation has been linked to improved mitochondrial function, reduced neuroinflammation, and enhanced neuronal survival, which are critical factors in mitigating the progression of these disorders.
Cardiovascular Health
NAD+ plays a crucial role in cardiovascular health by maintaining mitochondrial function, regulating oxidative stress, and supporting healthy vascular function; declining NAD+ levels are being linked to various cardiovascular diseases like heart failure, atherosclerosis, and hypertension.
Metabolic Conditions
NAD+ has been shown to enhance insulin sensitivity and reduce inflammation.
Ovarian Function
Recent research highlights the role of enzymes such as CD38 in regulating ovarian aging and fertility via NAD+ pathways. This finding suggests that NAD+ boosters could potentially mitigate age-related fertility decline and support reproductive health.
Autoimmune Conditions
By modulating immune cell function and reducing inflammatory cytokines, NAD+ could help manage conditions such as rheumatoid arthritis or systemic lupus erythematosus.
These supplements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent disease.
*These study examples are generalized studies across many formulations of NAD+ and not NADEssence specifically.
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In a double-blind, placebo-controlled, NADEssence was studied in 60 healthy adults who were assessed through a 7-day baseline period followed by a 5-day treatment protocol with patients taking 500mg NAD+ four times per day.
The data revealed a statistically significant elevation in intracellular NAD levels in those administered NADEssence, with an average increase of 52%, in stark contrast to the 4.5% decrease in the placebo group (p=4.13x10^-13). Few studies measure intracellular NAD levels; measuring intracellular changes is a more accurate assessment when taking oral NAD+. Additionally, the study observed 3,000 proteins, 1,500 metabolites, and 49 clinical labs per patient, collecting a total of over 5,000 data points per patient. NAD+ favorably impacted 87 biomarkers and 67 biological pathways. Furthermore, NADEssence administration was associated with enhanced levels of various NAD metabolites and increased activity of Sirtuin 1 (“SIRT1”).
SIRT1 is an NAD-dependent enzyme that typically increases in plasma when levels of NAD are increased. SIRT1 regulates reward-related behaviors (Ferguson, et al., 2013) and is actively involved in the regulation of energy sensing and homeostasis, oxidative stress response, and anti-inflammatory cascades.
Every individual in the treatment group showed an increase in intracellular NAD (icNAD), averaging a 52% increase from baseline during the 5-day intervention.
These supplements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent disease.
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NADEssence administration also led to a statistically significant increase in plasma abundance of two key NAD metabolites, supporting the bioavailability of NADEssence.
Specifically, we saw increases in 1- methyl-nicotinamide (MeNAM; B=0.47, SE=0.065, p=7.59x10-11) and N1-methyl-2-pyridone-5- carboxamide (2PY; B=0.47, SE=0.055, p=1.03x10-13), compared to placebo.
We also observed a significant differential increase in SIRT1 plasma abundance in the treatment group relative to placebo (B=0.14, SE=0.09, t=1.76, p=0.041), again suggesting the bioavailability of NADEssence.
These supplements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent disease.
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Safety Profile Results
Although analyses across 52 predefined clinical laboratory tests did not reveal any statistically significant unfavorable changes across tested analytes (all p’s > 0.05). As mentioned previously, we did see unexpected improvement in several key areas:
Liver and kidney function: We observed evidence supporting an association between NAD+ supplementation and improved liver functioning. Compared to the placebo group, the NADEssence group showed significant decreases in total bilirubin (p=0.0005), ALP (p=0.0326), serum albumin (p=0.0378) and GGT (p=0.0404). Changes in total bilirubin survived statistical corrections for multiple testing and suggest improved heme catabolism and bile acid oxidation and clearance. Follow-up analyses indicated that the effect on GGT was likely driven by participants in the NADEssence group who were taking acetaminophen, a common hepatotoxic agent, as adjusting for acetaminophen use resulted in no significant group difference in GGT. ALT, AST, BUN and creatinine did not change significantly in either group.
Oxidative stress: As noted above, NADEssence administration was associated with a preferential decrease in serum GGT relative to placebo. In addition to being a sensitive marker of liver function, GGT is also a marker of oxidative stress. Its biological significance is largely mediated by its ability to transfer gamma-glutamyl groups to amino acids and hydrolyze glutathione (GSH), a key cellular antioxidant.
Inflammation: No changes were observed for circulating inflammatory biomarkers as assayed using clinical laboratory tests, i.e., cardiac CRP and hsCRP, TNF, IL-6, or white blood cell counts (all p’s >0.05).
Lipid metabolism: Although no statistical differences were obtained for triglycerides, LDL, or HDL, NADEssence administration led to a significant differential decrease in LDL/HDL ratio (p=0.0312), compared to placebo.
Serum glucose: We observed no significant changes in serum glucose in either group.
Self-reported symptoms: Throughout the 5-day treatment period, a Review of Systems questionnaire targeting 14 organ and functional systems was administered daily (baseline and post-treatment data were also obtained). The study did not observe differences in incidence of adverse symptoms in the NADEssence vs. the placebo group (overall incidence for self-reported symptoms on-protocol was estimated at 2.89% in the NADEssence group vs. 2.30% in the placebo group). One participant in the active treatment group withdrew due to nausea – the symptom resolved after discontinuing NADEssence. Another participant withdrew when they were diagnosed with COVID-19.
Vital signs and body composition: No differential changes in the NADEssence vs. placebo group were detected in vital signs or body composition (SBP, DBP, MAP, Body Mass Index, Waist 11 Circumference; all p’s >0.05) in response to NADEssence administration. Analyses of wearable data revealed that NADEssence administration is associated with a differential reduction in resting heart rate (p=0.033) and number of minutes it took the participants to fall asleep as estimated by the Fitbit (p=0.001), relative to placebo. No other changes were observed for levels of activity or sleep measures (all p’s>0.05).
These supplements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent disease.
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Why you can rely on our measured results:
We paired a clinical-grade intracellular NAD+ assay with state-of-the-art multiomics profiling to capture both the direct cellular impact of NAD+ supplementation and the resulting cascade of systemic changes.
Intracellular NAD+ Measurement
The study utilized a validated colorimetric cycling assay performed on whole venous blood draws (not finger-prick dried blood spot cards) to precisely quantify intracellular NAD+ concentrations. The assay quantifies the total intracellular pool of NAD+ and NADH (total NAD(H)), reported as icNAD in μM units.
Comprehensive Biomarker Profiling
Since NAD+ functions as a fundamental cellular co-enzyme and signaling molecule, we implemented advanced platforms to track system-wide effects using biobanked frozen plasma samples. This includes Metabolon's untargeted global discovery platform for biochemical pathways activated or attenuated following NAD+ repletion, and Olink's explore platform for high-resolution Proteomics.
Together, this state-of-the-art biomarker measurement approach allowed us to track the direct intracellular impact, its propagation through metabolic pathways, and the resulting protein changes that translate increased NAD+ availability into measurable improvements in cardio-metabolic, neuroendocrine, and immune function.