Bioavailability Issues

Solving Poor Bioavailability with Liposomal Delivery

Targeted Delivery

Liposomal delivery offers a targeted and nearly complete absorption of active ingredients with a delayed‑release effect, unlike other nutrient delivery methods. This increased circulation time of specific nutrients in the bloodstream significantly increases bioavailability. The higher the bioavailability of an active compound, the greater effect it has on the body. (3)

The Liposome Advantage

Liposomes encapsulate active ingredients to protect them from stomach acid and enzymes so they can be delivered directly to the cells of our tissues, which are reached via the bloodstream. (1)

Liposomes stabilize therapeutic compounds—overcoming obstacles to cellular and tissue uptake—and improve the biodistribution of compounds to target sites.

Solving the Bioavailability Problem

The aim of taking any supplement is to ensure it’s transport into the bloodstream via the mucosal membrane and intestinal epithelial cells.

However, due to the low absorption and bioavailability rates of traditional oral dietary capsules, active ingredients lose most of their potency while passing through the gastrointestinal tract or are simply not absorbed in the small intestine at all. The majority is excreted unused via the intestines or kidneys. (2)

Liposomes are vesicles comprised of phospholipids—the primary building blocks of cell membranes. Because they are made of the same material our cell membranes are made of, as they bond to these membranes, they facilitate the delivery of nutrients that are difficult for your body to absorb.

Understanding Liposomes

Advanced Absorption

Liposomes are absorbed through the oral mucosal lining and through lymphatic mechanisms in the gut, skipping first-pass metabolism and breakdown in the liver. This ensures retention of intact liposomes to enter into circulation. Synthesis takes place inside cells which allows vitamins, minerals, or micronutrients to be utilized more easily. This higher absorption means greater efficacy and smaller doses needed to achieve better results. (4)

Biocompatibility

Phospholipids, which are found throughout the body in the membranes of cells are so naturally-occurring that the body recognizes these as body-compatible and does not treat them as ‘toxic’ or ‘foreign’—and therefore does not mount an immune attack on the liposome. (5)

Masking

Liposomes shield nutrients from detection by the body’s immune system, mimicking biological membranes and giving the active ingredients more time to reach their intended destination.Phospholipids mask the active ingredients so that larger amounts can be absorbed and escape the selective function of the small intestine. Osmotic (hydrophilic) side effects of some high-dose vitamins and minerals can thus be reduced. (6)

Crosses the Blood-Brain Barrier

Liposomes have demonstrated the ability to cross this barrier, giving the liposomes the ability to deposit the active ingredients directly into the cells and enhance the circulation of nutrients by your lymphatic system. (7)

Nanoscale Power

This profound effect of liposome size on complement recognition can also affect liver uptake. Generally, large unmodified liposomes are eliminated more rapidly than small liposomes, which is why our Fluidizing Liposomes™ are very small—less than 100 nm to prevent their uptake by macrophages of the liver and the spleen. (8)

What are Liposomes made of?

The word liposome comes from the Greek words ‘lipo’ for fat and ‘soma’ for body. Liposomes are spherical ‘sacs’ consisting of a double ring of fatty-acid molecules—phosphatidylcholine molecules (phospholipid attached to a choline particle).

The liposomal spherical ‘sac’ can be used to enclose and deliver contents of the ‘sac’ directly into the cells and body tissues. The phospholipid molecule consists of a hydrophilic phosphate head and two hydrophobic fatty acid tails. This enables liposomes to be carriers of both hydrophobic and hydrophilic compounds. Liposomes are lipid vesicles made of phospholipids strung together, which form a double membrane, just like almost all cell membranes of our body.

The encapsulation of hydrophilic or hydrophobic nutrients within liposomes, such as NMN, allows the active ingredient to bypass the destructive elements of the gastric system, improving its oral bioavailability and increasing peak plasma concentration. (9)

What does phosphatidylcholine do?

Phosphatidylcholine (PC) is required for many vital functions in the cardiovascular, reproductive, immune, and nervous systems.

PC and its components are needed for the synthesis of important messenger molecules called prostaglandins which, among other functions, regulate the contraction and relaxation of muscles. Choline is required for the synthesis of intracellular messenger molecules including the neurotransmitters that allow nerve cells to communicate with muscles and each other, and are essential for proper heart and brain function. At birth, up to 90% of cellular membranes are made up of PC. As you age, the percentage of PC in your cellular membranes can decrease to about 10%. This fact leads many to recommend consistent supplementation with this essential phospholipid. (10)

How do Liposomes work?

Liposomes release bioactive nutrients by membrane fusion. They delay the clearance and increase the intravascular circulation time of encapsulated nutrients and prolong retention time.

At the first stage of liposome-cell interaction, liposomes adhere to the cell surface. Following such binding, the liposome is internalized into the cell by the mechanism of endocytosis (or phagocytosis). This is followed by the enzymatic digestion of the liposome in the intracellular compartment, accompanied by the intracellular distribution.

The active nutrient encapsulated in the liposome is protected from metabolism and the molecule becomes active only after released from the liposome.

These encapsulating phospholipids bond with cell membranes to facilitate intracellular delivery. They are successful in this because they are able to bypass the digestive processes that normally degrade foreign substances. Liposomes ensure the safe delivery of encapsulated cargo nutrients and retain them in tissues and cells.

Liposomes Demonstration

Why Liposomes?

Biovailability Issues

Key Advantages of Liposomal Delivery

Protects against the harsh environment of the GI tract and increases transmucosal (oral) uptake and absorption.

Optimizes bioavailability of both hydrophilic and hydrophobic, unstable compounds.

Timing of the dose intake does not require accompaniment or exclusion of food as liposomal absorption avoids the digestive processes.

Bioavailability Issues with NAD+ Precursors

When taken as oral supplements, NAD+ and its precursors are almost entirely degraded to Nicotinamide (NAM) in the stomach, intestines, and liver, greatly diminishing the effectiveness. (11, 12, 13, 14)

Delivery methods that avoid digestion and deliver the product intact to cells throughout the body are needed to realize the potential of NAD+ Boosters.

Provides a larger nutrient payload per particle.

Offers higher bioavailability and absorption compared to conventional capsules.

Increases peak plasma concentration of encapsulated nutrients.

DIGESTED, METABOLIZED & DEGRADED

“Oral NR dosing increased circulating NAM ~40-fold while NMN remained unchanged and NR was detected only at trace levels in the blood.”

“Thus, the majority of the orally administered NR that reaches the muscle appears to enter in the form of liberated NAM or as NMN.” (15)

Digested by bacteria in stomach – NAD+ and precursors are mostly digested in the stomach, with research pointing to bacteria as voracious consumers.

(The chart above shows huge increase in NMN after antibiotics.)

Study Results

NR quickly degraded in bloodstream – NR has an even bigger bio-availabilty problem than NMN and NAD+. It is very unstable in the bloodstream, so it is never found at more than trace levels. (16)
Even supplementation of 1,000 mg a day of NR in humans does not increase NR levels in the blood. (click to learn more)
Digested by enzymes in intestines – “Dietary NAD was hydrolyzed primarily in the small intestine…to NMN… was rapidly hydrolized to NR… and NR more slowly to NAM.” (17)
Metabolized to NAM in Liver – Any that makes it past the gauntlet of the GI tract to the liver get mostly metabolized to the less effective Nicotinamide (NAM) before being excreted to the bloodstream. (18)

Quotes From Research

“Unlike in cell culture where NR and NMN are readily incorporated into NAD, oral administration fails to deliver NR or NMN to tissues.”

“Interestingly, we found that neither compound was able to enter the circulation intact in substantial quantities when delivered orally.”

“Orally delivered NR and NMN are converted into NAM before reaching the systemic circulation.” (19)