Liposomal NMN is the Best Form of NMN to Take, According to Latest Study from Japan

Highlights

• Liposomal NMN increases NAD+ levels more than non-liposomal NMN in middle-aged men. 
• Liposomal NMN may increase NAD+ more than non-liposomal NMN by bypassing normal transport. 
• Whether the increase in NAD+ provided by liposomes is more beneficial in mitigating aging is not clear. 

Our lifestyle can drastically alter how fast or slow we age, affecting how easily we move, how fast we think, and how well our body fights infections. Depending on what we eat, how often we exercise, and the level of toxic substances we consume (e.g., cigarettes and alcohol), our cells can either decline or maintain relative stability. However, the passage of time eventually catches up, disturbing the intricate processes that keep our cells alive.  

Of the cellular symptoms of aging, low NAD+ levels are among the most detrimental. Raising NAD+ levels with NAD+ precursors like NMN can counteract this symptom, potentially delaying cellular decline. Nevertheless, scientists are still actively researching which form of NMN raises NAD+ levels most efficiently. In doing so, Kawakami and colleagues have found that liposomal NMN increases NAD+ levels more than non-liposomal NMN. 

Liposomal NMN Increases NAD+ More than Non-Liposomal NMN

To determine which form of NMN increases NAD+ levels the most, Kawakami and colleagues enrolled 15 male subjects over the age of 40 into an 8-week study. The subjects were divided into three groups of five. One group took a placebo, another group took liposomal NMN, and the other group took non-liposomal NMN for 4 weeks, consuming the supplement before breakfast. NAD+ levels were then measured from blood cells after 4 and 8 weeks.

The results showed that after 4 weeks, NAD+ levels were significantly higher in the liposomal NMN group compared to the placebo group and non-liposomal NMN group. However, only the liposomal NMN group showed an increase in NAD+ when comparing baseline levels (before the study) to the 8-week mark, suggesting that NAD+ levels remain slightly higher after stopping supplementation for 4 weeks. 

How Might Liposomal NMN Enhance NAD+ Level Increases? 

Liposomes are fatty structures with a similar composition to cell membranes, allowing them to enter cells without a transport protein. NMN can thus be transported within liposomes across cellular membranes, bypassing other transport systems. When this occurs, NMN enters a cell and is immediately converted to NAD+ by an enzyme called NMNAT. To convert NMN into NAD+, NMNAT requires one molecule of ATP (adenosine triphosphate), which is the form of energy the biochemical reactions within our cells utilize. 

Without a liposome, NMN needs to be converted to NR (nicotinamide riboside) before entering cells by an enzyme called CD73, which requires a molecule of ATP. Once in the cell, NR is converted back to NMN by an enzyme called NRK1, requiring another molecule of ATP. Finally, NMN is converted to NAD+ by NMNAT, consuming a third ATP. Thus, two more ATP-consuming enzymatic steps are needed to transport NMN into cells if NMN is not housed within a liposome. This could explain why NAD+ levels are increased more by liposomal NMN than non-liposomal NMN.

While a protein called Slc12a8 that transports NMN into cells in animal models has been discovered, this transporter has not been observed in humans. For this reason, it is more widely accepted that NMN is transported into cells after being converted to NMN in humans. Still, liposomal NMN bypasses all protein transporter mechanisms, so in this case, whether Slc12a8 exists in humans is moot. 

Is Raising NAD+ Above Normal Levels Beneficial?

Many studies suggest that restoring NAD+ to normal levels counteracts aging and age-related disease. However, whether raising NAD+ levels above normal levels reaps the same benefits as NAD+ will require more research. Based on measurements from blood samples, human NAD+ levels vary widely but average about 35 µM (µmol/L) in young men. By the time men reach the age of 40, their NAD+ levels drop slightly to about 34 µM. 

Kawakami and colleagues showed that after 4 weeks of supplementation, liposomal NMN increased NAD+ levels to about 50 µM, whereas in the non-liposomal NMN group, NAD+ levels increased to about 42 µM. Both of these values are above normal, so it is unclear whether liposomal NMN is more beneficial than non-liposomal NMN, at least in terms of mitigating aging and age-related diseases. Studies measuring functional outcomes, such as memory and/or physical performance, in response to liposomal vs non-liposomal NMN supplementation would help to make this clearer.