NMN and NR Formulations Exert Similar Metabolic Health Effects: Latest International Study  

Of five different NAD+ precursors, NMN and NR similarly reduce blood fat levels and boost NAD+ levels when combined with an antioxidant and fat-burning blend, called the combined metabolic activator (CMA), in healthy adults.

By Daniel R. Miranda, Ph.D.

Key Points: 

  • Nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), nicotinamide (Nam), nicotinic acid (NA), and flush-free NA (FFN) were each tested for their metabolic effects when combined with L-serine, N-acetyl cysteine (NAC) and L-carnitine tartrate (LCAT) — the combined metabolic activator (CMA). 
  • The CMA with NMN, NR, or Nam similarly reduced blood fat (triglyceride) levels in healthy adults. 
  • In order of speed, Nam, NA, NMN, and NR raised NAD+ breakdown products — a measure of NAD+ levels.

The original CMA was designed to restore NAD+ levels, promote fat metabolism, reduce inflammation, and increase glutathione — our most powerful natural antioxidant. Initially including NR, the CMA was previously shown to help treat non-alcoholic fatty liver disease and Alzheimer’s disease patients. Now, researchers based in the United States, Sweden, China, Turkey, Denmark, and England have tested the effects of other NAD+ precursors in this antioxidant and fat-metabolizing blend. 

As reported in Free Radical Biology and Medicine, Li and colleagues find that switching NR with NMN in the CMA formulation leads to similar effects after one day of administration. They show that NMN, NR, and Nam similarly reduce blood fat levels. Furthermore, each precursor (except for FFN) raises NAD+ byproducts, albeit to different degrees. Additionally, NMN and NR perturb fat metabolism the least, while NAM and NA reduce important fats. 

This study examined the effects of different precursor combinations on blood fats, NAD+ levels, lipid metabolism, and plasma bilirubin in seventy adults. The participants were divided into three groups: placebo, CMA without a precursor (F), and CMA with one of five precursors (F-NR, F-NMN, F-Nam, F-NA, or F-FFN). Blood samples were collected at six time points (T1-T6). Only the F-NA combination caused side effects, specifically flushing. The study analyzed the impact of each group on plasma triglycerides, plasma nicotinamide (NAD+ boosting), lipid metabolism, and plasma bilirubin. The image also shows the three NAD+ synthesis pathways: Salvage, De novo, and Preiss-Handler.
(Li et al., 2023 | Free Radic. Biol. Med.) Study Summary. Seventy adults were given either a placebo, the CMA without a precursor (F), or the CMA with one of the five precursors (F-NR, F-NMN, F-Nam, F-NA, or F-FFN). Blood samples were taken at six different time points (T1-T6). F-NA was the only mix to cause side effects, namely flushing. The effect of each group on blood fats (plasma triglycerides), NAD+ boosting (plasma nicotinamide), fat (lipid) metabolism, and plasma bilirubin are summarized. The top right shows the three NAD+ synthesis pathways (Salvage, De novo, and Preiss-Handler).

To begin, 70 healthy subjects (18 to 47 years old) were divided into groups of 10 and randomly assigned to receive a placebo or one of the six CMAs. The CMA formulation without an NAD+ precursor (F) contains 12.35 g L-serine, 3.73 g LCAT, and 2.55 g NAC. Serine is a source of glycine which together with cysteine drives the synthesis of glutathione. Carnitine (LCAT) is required for transporting fatty acids into mitochondria for energy production. One gram of one of the five different NAD+ precursors were added to the CMA (F-NR, F-NMN, F-Nam, F-NA, and F-FFN. 

After having identical breakfasts at 8:00 am, blood samples were collected from the participants at 9:00 am (T1) followed by oral intake of their CMA or placebo. Blood samples were again taken at 10:00 am (T2), 11:00 am (T3), 12:00 pm (T4), 3:00 pm (T5), and 4:30 pm (T6). Flushing was observed in all 10 subjects from the F-NA group, encompassing skin redness, burning, and itching. Otherwise, each formulation was considered safe and without side effects. 

The blood samples were used to make all measurements, including blood fat levels. It was found that the F, F-NR, F-NMN, and F-Nam groups had lower blood fat levels at T6 compared to T1. Of note, the F-NR group also showed reduced blood glucose levels. Nonetheless, blood glucose and fat levels remained within the average range. These findings suggest that CMA, even without an NAD+ precursor can elevate fat metabolism, perhaps due to carnitine. 

Comparison of blood fat (triglyceride) levels before and after administration of different CMA formulations. Measurements were taken at two time points: T1 (blue) before administration and T6 (red) approximately 7.5 hours after administration. The CMA alone (F), the CMA with NR (F-NR), the CMA with NMN (F-NMN), and the CMA with Nam (F-Nam) all showed reductions in blood fat levels.
(Li et al., 2023 | Free Radic. Biol. Med.) The CMA alone and with NR, NMN, and Nam Reduce Blood Fat Levels. Measurements were taken before administration of a CMA formulation (T1, blue) and compared to measurements taken about 7.5 hours after administration (T6, red). The CMA alone (F), the CMA with NR (F-NR), the CMA with NMN (F-NMN), and the CMA with Nam (F-Nam) reduced blood fat (Triglyceride) levels.

To examine NAD+ levels, Li and colleagues measured metabolites associated with the three NAD+ synthesis pathways (shown in the study summary figure). The F-Nam and F-NA groups showed the fastest and highest increase in NAD+ breakdown products, including Nam. Furthermore, the F-NMN group showed a faster increase in nicotinamide (at T4) compared to F-NR (at T6), suggesting that NMN is metabolized to NAD+ faster than NR. This could be because NMN is directly converted to NAD+, whereas NR takes an extra step to be converted.

The other NAD+ precursors tested either depleted or had no effect on NAD+ byproducts. With the F group, there was a depletion of nicotinamide and no effect on the other byproducts, suggesting that an NAD+ precursor is needed in the CMA formulation to maintain NAD+ levels. With the F-FFN group, there was no effect on any byproducts, suggesting that FFN does not acutely boost NAD+ levels. This is likely because FFN is designed for slow release as to prevent flushing.

Comparison of NMN and NR metabolism and their effects on NAD+ levels. The metabolic pathway shows the breakdown of NAD+ into nicotinamide, which is further metabolized into MNA and then 2-PY. These metabolites are expected to correlate with NAD+ levels. The data indicates that compared to placebo, F (CMA without a precursor) depletes NAD+ levels, while F-FFN has no effect on NAD+. On the other hand, F-Nam and F-NA show the highest increase in NAD+ levels. The graph on the left shows the effect of F-NMN, which raises NAD+ levels faster than F-NR (T4 for NMN compared to T6 for NR).
(Li et al., 2023 | Free Radic. Biol. Med.) NMN is Metabolized Faster than NR. NAD+ is broken down into nicotinamide, which is then broken down to MNA, then 2-PY. These metabolites should correlate with NAD+ levels. Based on this data and compared to placebo, F depletes NAD+, while F-FFN does not affect NAD+. F-Nam and F-NA increase NAD+ the most. Looking at the Nam graph (left), F-NMN raises NAD+ faster than F-NR (T4 for NMN vs T6 for NR).

To further examine the effect of different NAD+ precursors in the CMA, Li and colleagues compared which metabolites were either increased or decreased between groups. It was found that the F and F-NA groups had the highest number of perturbations in metabolites. From these findings, it can be assumed that, with more differences in metabolites, there is a higher likelihood of potential imbalances.

Analysis of metabolic perturbations with different treatments. The number of differential metabolites (DM) was assessed by comparing all measured metabolites across different time points for each group. The group treated with CMA alone (F) and CMA with NA (F-NA) exhibited the highest number of differential metabolites, indicating significant metabolic changes. In contrast, the group treated with CMA with F-FN (F-FFN) had the fewest differential metabolites, suggesting minimal metabolic perturbations.
(Li et al., 2023 | Free Radic. Biol. Med.) Metabolic Perturbations are the Highest with CMA alone and with NA. Differential metabolites (DM), which are differences in all measured metabolites combined from all time points were measured from each group. The F and F-NA group had highest number of DMs, while the F-FFN group had the least.

To investigate the potential consequences of the above metabolite differences, Li and colleagues mapped each metabolite to its cellular pathway. From this, the researchers observed reduced phospholipid-related metabolites in the F, F-Nam, and F-NA groups. Phospholipids are the primary component of cellular membranes. Therefore, a reduction in these important fat molecules could compromise cellular function and potentially lead to disease. That being said, in the NA group, there was an increase in bilirubin metabolites, which are markers of liver disease. 

Overall, the findings of Li and colleagues suggest that both NMN and NR have similar acute effects on select metabolic measurements when combined the CMA in healthy adults. Whether these similarities remain after one day is unknown and requires further testing. Importantly, blood NAD+ levels were not directly measured, but it can be deduced that NMN and NR raise NAD+ levels similarly. Further studies are needed to compare the effects of these NAD+ precursors with the CMA on organ NAD+ levels. 


NMN and NR are the two most popular and well-studied NAD+ precursors. Both have been shown to raise NAD+ levels and ameliorate features of aging and disease in animal models and humans. However, it is difficult to determine which is better without comparing the two directly under the same experimental conditions, like in this study. 

Animal studies have also directly compared NMN to NR under the same conditions. One study showed that Nam, NR, and NMN similarly improve skin regrowth. Another study showed NMN and NR similarly inhibit the release of inflammatory molecules from immune cells. Both NMN and NR also similarly restore age-related lubricant-secreting eye gland atrophy. Therefore, based on these studies, it would seem that both NMN and NR have similar effects on multiple conditions. 

Participants and Dosage

Participants: Healthy adults (18 to 47 years old)

Dosage: 1 g of an NAD+ precursor, 12.35 g of L-serine, 3.73 g of L-carnitine tartrate, and 2.55 g of N-acetyl cysteine


Li, X., Yang, H., Jin, H., Turkez, H., Ozturk, G., Doganay, H. L., Zhang, C., Nielsen, J., Uhlén, M., Borén, J., & Mardinoglu, A. (2023). The acute effect of different NAD+ precursors included in the combined metabolic activators. Free Radical Biology and Medicine.

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