Delivery methods to maximize bioavailability and reach tissues throughout the body are the first consideration.
Research shows that if not protected from digestion, NAD, NMN, and NR all suffer from very poor bioavailability.
LIPOSOMES protect a far greater percentage of active ingredients from digestion, slowly releasing the payload in the bloodstream (1).
We believe Liposomes are the most effective at reaching cells throughout the body.
SUBLINGUAL delivery is faster than liposomal delivery and provides the strongest response that most users can feel immediately.
TRANSDERMAL delivery avoids the gastrointestinal tract to reach systemic circulation
INTRANASAL is ideally suited for delivery of NAD+ to the brain.
LIPOSOMES DELIVER THE HIGHEST PERCENTAGE OF ACTIVE INGREDIENTS
Liposomes are specialized delivery vehicles composed of phospholipid molecules—the same molecules that comprise our cell membranes. This prevents them from being digested in the gastrointestinal tract or attacked as a foreign body in the bloodstream, so they can protect and deliver nutrients directly into cells throughout the body.
Our liposomal formulations are made from the highest-grade phospholipids and are small enough to pass between cells (nano-sized) to enter the bloodstream. They are stabilized to prolong the blood circulation time of active nutrients, allowing optimal absorption.
We use liquid liposomes in our LSG products, and powdered liposomes in LIPO NR and NAD+ Complex Capsules.
SUBLINGUAL PROVIDES THE FASTEST DELIVERY DIRECTLY TO THE BLOODSTREAM Research suggests 20-30% of the product may be absorbed directly to the bloodstream, with the remainder being swallowed and subject to digestion in the gastro-intestinal tract. Everyone is different, but many users describe a stimulating effect similar to a strong cup of coffee, so enjoy taking it in the morning and before exercise.
TRANSDERMAL DELIVERY AVOIDS THE GI TRACT TO REACHCIRCULATION
Liposomes are an advanced delivery vehicle, offering superior stability of active ingredients, higher absorption and greater efficacy, while treating the target area. Transdermal liposomal serums and lotions deliver active ingredients deep into the skin and systemic circulation.
INTRANASAL IS IDEALLY SUITED FOR DELIVERY OF NAD+ TO THE BRAIN
Studies in mice show that intranasally-administered NAD+ increase hippocampal NAD+ levels and reduce TBI-induced neuronal death in the hippocampus.(4) In mice replenishment of NAD+ levels have also shown neuroprotective effects in prion diseases.(5)
STABILITY IN BLOODSTREAM MOST IMPORTANT
NR has shown benefits for Fatty Liver Disease (14) in humans and may be more effective than other options for Liver function. However, NR is very unstable in the bloodstream (12) and is never found at more than trace levels (13).
To reach beyond the liver, delivering NR in liposomes that protect it from degradation in the bloodstream is the solution.
NMN is more stable than NR and remains available in the bloodstream for many hours (17, 18) but not as stable as NAD+. NMN research in mice have shown very impressive benefits for endurance and new blood vessel growth. (19)
NAD+ is very stable in the bloodstream. Some studies in mice show it is able to cross the blood brain barrier, while NMN and NR cannot (20), and may have more benefit on neurological issues.
ENTRY TO CELLS – NOT AN ISSUE
Although NMN and NAD+ must be converted to NR to cross the membrane on some cell types, the CD73 enzyme present on the membrane does this efficiently and is increased when needed to bring more NMN and NAD+ into the cells. (8)
When added to the serum outside of cells, all NAD+ metabolites were equally effective at restoring the NAD+ levels INSIDE the cells (9, 10,11).
Very large dosages injected by IV in humans are well tolerated and is so quickly metabolized by cells there is no increase in extracellular NAD+ levels in plasma for 2 hours. After 2 hours, an increase of 4x and 5x was found in plasma NAD+ and NMN. (5,).
Some studies show NAD+ may be more effective at reaching the brain as it crosses the blood brain barrier, while NMN and NR do not.(6)
In mice, replenishment of NAD+ levels have shown neuroprotective effects in prion diseases, as well as frontotemporal dementia (7).
NAD+ may have more effect on the brain than NMN and NR.
Our NMN powder provides the most mg NMN per dollar of any NMN product on the market, and provides an immediate boost that most users notice. However, the 70% or more that is not absorbed sublingually is subject to digestion.
We learned in 2020 that when swallowed, NMN is almost totally digested by bacteria in the stomach (2),
Hence the need for Liposomal delivery that can protect 100% of NMN, NR and NAD+ through the digestive system. Our LSG NMN shown here is one such product.
Top quality Nanosized Liposomal NMN is expensive to produce, so does cost quite a bit more than other products. However, published research on other Liposomal products and our internal testing indicate our LSG NMN delivers around 3x more NMN to the bloodstream than our Sublingual products, making them a much better value.
In addition, it is unstable in the bloodstream and only found briefly and at trace levels after supplementation (19). When given to human at 1,000 mg per day for 3 weeks, NR levels in the blood were not increased at all and still barely detectable (20).
The solution is LIPO NR, the only truly bioavailable Nicotinamide Riboside.
LIPO NR encapsulates nanosized NR particles in Liposomes, which are then freeze-dried to remove the moisture.
The creates a very stable powder that “re-inflates” the liposomes in the body to protect the NR through the stomach, liver, and in the bloodstream where it is able to reach tissues throughout the body without being degraded by enzymes.
NMN, NR, and NAD+ all have similar effects in many situations, but also have some differences in stability, uptake, and affinity for different tissues. Unfortunately, there have been few direct comparisons in research.
There is some research that shows NAD+ may cross the blood brain barrier, while NMN and NR do not (1). There is also research showing impressive results for endurance and blood vessel growth in muscle with NMN which have not yet been duplicated for NR or NAD (2).
While it is possible researchers will find one is “better” than the others overall, it is most likely that all are beneficial in different situations. As a result, we have developed a product that contains all three. Our NAD+ COMPLEX Capsules contain NMN, NR, and NAD+ in liposomes freeze-dried to a very stable powder. This protects the ingredients through the digestive system and in the bloodstream.
Read more about NAD+ Complex Capsules
250 to 2,000 mg a day, depending on your age, health, and the delivery method.
But, don’t waste your money taking HUGE doses of inefficient NAD+ Boosters.
For example, when taken as capsules, NR is mostly degraded to NAM as noted by the authors of this study
Oral NR dosing increased circulating NAM 40-fold while NMN remained unchanged and NR was detected only at trace levels in the blood.
Research has not found a benefit from taking 1,000 mg of NR capsules per day vs 300-500 mg per day. Large dosages result in massive increases of NAM which must be methylated so it can be excreted, which may lead to problems from shortage of methyl donors.
With sublingual delivery, you can take somewhat larger dosages before you max out, so we recommend up to 1,000 mg a day.
Liposomal delivery is best as it provides a sustained release of payload in the bloodstream which is far more efficient at lower dosages, without the problem of excessive NAM production at higher dosages.
Regardless of how efficient the delivery method is, we believe providing NAD+ and precursors through multiple pathways is best to avoid bottlenecks and feedback loops.
We recommend 2,000 mg per day only if you use multiple delivery methods, or liposomal delivery spread out over multiple dosages during the day.
Below are links to articles we have written about research on NAD+ metabolism over the last few years that help us decide what products are likely to be the most effective.
NAD⁺ Injection Restores NAD⁺ Levels in Brain and Cognition in Mice
NAD+ IV increases NAD+ levels in blood plasma 400% in humans
Exogenous NAD+ Increases Metabolism
NAD+ Supplements Regulate Energy Metabolism via the Hypothalamus
Bacteria in Gastrointestional Tract Metabolize NMN and Impact NAD+ Metabolome
NAD+ is the Transport Molecule Used by the Body, Not Nicotinamide Riboside
CD73 utilization shows importance of NMN to restore NAD+