ACTIVATOR – Senolytic – Liposomal Quercetin, Fisetin, Spermidine Capsules
$59.95
- Liposomal Quercetin – 77 mg per capsule
- Liposomal Fisetin – 35 mg per capsule
- Liposomal Spermidine – 3 mg per capsule
- 60 capsules per bottle
Activator is specially formulated with the most powerful senolytics to eliminate senescent cells that increase inflammation and consume NAD+, along with AMPK activators to increase NAD+ production inside cells and throughout the body.
About Activator
Activator has been specially formulated with Lipo Quercetin, Lipo Fisetin, and Lipo Spermidine to be a powerful combination senolytic and AMPK activator. As we age, we accumulate more and more senescent cells.
Senescent cells are cells that refuse to die, creating toxins that cause inflammation and play a causal role in aging. Supplements in Activator have been shown to eliminate a significant number of senescent cells, which in turn reduce the inflammation and aging these cells cause.
Activator also includes AMPK activators that increase NAD+ and promote mitochondrial biogenesis, which create new mitochondria that burn excess glucose and fats. This allows them to be used for energy instead of storing them in the stomach and elsewhere in the body.
About Liposomal Delivery
Our Lipo products are part of a sustained-released liposomal delivery system that provides superior absorption in easy-to-swallow capsules. Our process encapsulates and delivers our products intracellularly in its complete form where it can be absorbed and utilized rather than being destroyed in the stomach.
Lipo Quercetin
As a plant pigment, quercetin belongs to a group of plant compounds called flavonoids. Flavonoids are compounds commonly found in: vegetables, fruits, grains, tea, and wine. Flavonoids are associated with a wide variety of health benefits.
There is some research that indicates Quercetin is a senolytic, especially when paired with Dasatanib, but evidence is mixed. Many researchers now believe the strong anti-inflammation properties noted with Quercetin are due to its effect on lowering CD38 enzyme which consumes NAD+.
Research has shown that CD38 is inhibited by flavonoids, including quercetin and apigenin. David Sinclair takes quercetin for its senolytic properties every day.
“Treatment of cells with apigenin or quercetin inhibits CD38 and promotes an increase in intracellular NAD+ levels” (1)
“researchers at the Buck Institute have identified chronic inflammation as a driver of NAD+ decline… via the activation of CD38” (2)
“It’s in a class of polyphenols from stressed plants (eg resveratrol) with broad health benefits in mice. I take 500 mg quercetin, a suspected senolytic and a SIRT1 activator.” – David Sinclair
Lipo Fisetin
Like quercetin, fisetin is yet another flavonoid that is a natural polyphenol and antioxidant. Found in strawberries, apples, onions, and other plants that are particularly good at getting rid of senescent or “Zombie cells”, fisetin has been called “The King of Senolytics”.
In human trials at the prestigious Mayo Clinic, fisetin was shown to significantly reduce the number of senescent cells in adipose tissue, thereby reducing systemic inflammation and increasing strength and joint mobility in elderly test subjects.
The ability of fisetin to destroy senescent cells clears a path for NAD+ boosters to be much more effective by ridding the body of the toxins that create inflammation in the body, one of the main drivers of age-related diseases.
Increased inflammation leads to more CD38 that consumes NAD+, which leads to more age-related diseases. Removing senescent cells lowers inflammation and spares NAD+ from being consumed.
Fisetin has also been shown to increase NAD+ levels through the activation of AMPK, a key modulator of energy levels and the production of ATP, needed by mitochondria.
“We found that the AMPK/mTOR signaling pathway was enhanced after fisetin treatment” (3)
“Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity.” (6)
Lipo Spermidine
Spermidine is a naturally occurring molecule that is vital to cell function and survival. It’s part of a group of molecules called polyamines. Declining polyamine levels are associated with inflammation-driven aging.
“Changes in polyamine levels have been associated with aging and diseases. Their levels decline continuously with age and polyamine (spermidine or high-polyamine diet) supplementation increases life span in model organisms.” (4)
Spermidine Induces Autophagy and Reduces Inflammation
Spermidine’s main mechanism of action is its ability to induce autophagy, a self-preservation process which clears out toxic, damaged and dysfunctional cells, resulting in lower levels of inflammation in the body.
Normally, the process of autophagy is induced by an extended period of fasting. However, it can also be induced by compounds like Spermidine, which mimic the anti-aging benefits of caloric restriction.
“A defective autophagy mechanism and a lack of spermidine are highly correlated with reduced life spans, chronic stress, and acute inflammation.” (5)
Spermidine Induces Autophagy and Reduces Inflammation
Spermidine’s main mechanism of action is its ability to induce autophagy, a self-preservation process which clears out toxic, damaged and dysfunctional cells, resulting in lower levels of inflammation in the body.
Normally, the process of autophagy is induced by an extended period of fasting. However, it can also be induced by compounds like Spermidine, which mimic the anti-aging benefits of caloric restriction.
“A defective autophagy mechanism and a lack of spermidine are highly correlated with reduced life spans, chronic stress, and acute inflammation.” (5)
Inflammation Is A Major Consumer of NAD+
Chronic inflammation is a risk factor for a wide range of age-related diseases and it’s a major consumer of NAD+. In order to restore your NAD+ pool, minimizing inflammation is vital.
Spermidine’s Potential Impact On Aging
According to Dr. David Sinclair, professor of genetics at Harvard and one of the leading longevity scientists, Spermidine can reduce disease and lower bioage by 5.7 years.
“Spermidine, a tiny molecule from wheat germ, protects the heart and extends the lifespan of mice, even when given mid-life. In people, increased consumption is associated with fewer diseases & a 5.7-year age reduction.” – David A. Sinclair
References:
1 – Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38
2 – Chronic inflammation causes a reduction in NAD+
4 – Polyamines in aging and disease
5 – Induction of autophagy by spermidine promotes longevity
6 – Fisetin is a senotherapeutic that extends health and lifespan
RENUE BY SCIENCE introduces LIPO Caps™ the Gold Standard in supplement delivery systems that provides maximum nutrient absorption throughout the body and is clinically proven to enhance the bioavailability up to 6x more than liquid liposome formulations(1)
ABOUT LIPOSOMES
Liposomes encapsulate active ingredients in a phospholipid "bubble" to protect and deliver them directly to the cells of our tissues, which are reached via the bloodstream.
They are specialized delivery vehicles serving multiple roles in enhancing the capabilities of active ingredients.
Liposomes stabilize therapeutic compounds—overcoming obstacles to cellular and tissue uptake—and improve the biodistribution of compounds to target sites.
- Protects ingredients from digestion in stomach and intestines
- Greatly increased circulation time in the bloodstream (not filtered out by liver)
BENEFITS OF LIPOSOMAL DELIVERY
The increased bioavailability of Liposomal Delivery make it:
MORE ECONOMICAL - MORE BANG FOR THE BUCK
Manufacturing liposomes does add cost to the finished product, which is why their usage has been more limited for vitamins and supplement as opposed to expensive pharmaceutical drugs. However, a 2x increase in cost is vastly outweight by the 5-20x or greater increase in effectiveness of liposomal delivery.
Many people realize liposomal delivery provides more "bang for the buck", but it is clear they also enable much greater effectiveness and safety, and should be used for all products with known bioavailability problems.
MORE EFFECTIVE - HIGHER LEVELS OF SATURATION IN TARGET TISSUES
Many popular supplements such as Curcumin, Resveratrol, Berberine, Apigenin, Quercetin and others are well documented to have extremely poor bioavailability. When you're taking a supplement that has 5% or less bioavailability, it is not possible to achieve high blood saturation levels safely. Liposomes deliver much higher quantities of the target molecules to the bloodstream.
SAFETY - MINIMIZES LIVER TOXICITY FROM EXCESSIVE DOSAGES
Many nutraceutical supplements have been shown to cause problems in the liver at higher dosages. The risk of liver damage greatly limits the dosage that can safely be used, which diminishes the effectiveness. The liver does not filter out molecules delivered by liposomes, so the risk from toxicity is greatly diminished.
POWDERED LIPOSOME NAD+ PRODUCTS
Our LIPO CAPS tm powdered liposomes technology encapsulates nanosized particles in liposomes, which are then freeze-dried to remove the aqueous phase. It's a bit like grapes that are dehydrated to raisins, except that liposomes re-inflate in the body.
This ensures maximum bioavailability and stability, protecting the bio-active ingredients against degradation.
This encapsulation technology is clinically proven through safety, absorption and blood glucose studies to maximize nutrient bioavailability. (2)
A peak particle size of less than 50 nm (nanometers) ensures the maximum bioavailability and stability.
The advanced liposomes retain the core structure of the liposomal bilayer in its powder form, which stabilizes the active ingredient and ensures maximum bioefficiency, potency and absorption.
We use natural non-hydrogenated sunflower phosphatidylcholine in our manufacturing process, derived from non-GMO certified sunflower oil from Europe. It undergoes a multi-step, purification and filtration process during liposome manufacturing to ensure the utmost purity.
Testing
About Liposomes
Liposomes protect ingredients through the GI tract, merging their contents into cells to improve the biodistribution of compounds.
https://www.youtube.com/watch?v=fNI8voyTSuQ
Liposomes Demonstration
Why Liposomes
Bioavailability Issues
Solves the Bioavailibility Problem
Targeted Delivery
Liposomal delivery offers a targeted and complete absorption of active ingredients with a delayed‑release effect, unlike all other nutrient delivery methods. This increased circulation time of key nutrients in the bloodstream significantly bioavailability. The higher the bioavailability of an active substance, the more effect it has on the body. 3
Advanced Absorption
Liposomes are absorbed through the oral mucosal lining and through lymphatic mechanisms in the gut, bypassing first pass metabolism and breakdown in the liver ensuring the retention of liposome integrity. A synthesis takes place which allows vitamins, minerals or micronutrients to be transported more easily. This higher absorption, means greater efficacy and with smaller doses needed to achieve better results. 4Biocompatibility
Phospholipids, which are found throughout the body in the membranes of body cells, are so naturally-occurring, that the body recognizes these as body-compatible and does not treat them as ‘toxic’ or ‘foreign’—and, so, does not mount an immune attack on the liposome. 5Masking
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. 6Crosses the Blood Brain Barrier
Liposomes have demonstrated the ability to cross this barrier, giving the liposomes the ability to deposit the supplement directly into the cells and enhance circulation of nutrients by your lymphatic system. 7Nanoscale 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. 8What are Liposomes made of?
What does phosphatidylcholine do?
Phosphatidylcholine 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 prolonging 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 release from 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 safe delivery of encapsulated cargo retain it in tissues and cells.References
1. Potential of Liposomes for Enhancement of Oral Drug Absorption 2. Nanocarriers for oral drug delivery 3. Composition design and medical application of liposomes 4. Liposomal Delivery Systems: Design Optimization and Current Applications 5. Oral Bioavailability: Issues and Solutions via Nanoformulations 6. Spontaneous In Situ Formation of Liposomes from Inert Porous Microparticles for Oral Drug Delivery 7. Stabilization of liposomes during drying 8. Powdered lipid nano and microparticles: production and applications. Lipid nanoparticles as vehicles for macromolecules: nucleic acids and peptides 9. Scalable solvent-free production of liposomes 10. Membrane lipids: where they are and how they behave
Key Advantages of Liposomal Delivery:
- Protects against the harsh environment of the GI tract and increases transmucosal (oral) uptake and absorption.
- Optimizes both hydrophilic and hydrophobic, unstable compounds.
- Timing of the dose does not require accompaniment or exclusion of food as the absorption via the liposome avoids the digestive processes.
- Provides a larger nutrient payload per particle.
- Offers higher bioavailability and absorption compared to conventional capsules.
- Increases increase peak plasma concentration.
Liposome Research
RESEARCH ON LIPOSOMES FOR INCREASED BIOAVAILABILITY
Liposomes, vesicles enclosed by phospholipid bilayers, can solubilize water-insoluble drugs into the lipid domain of the liposomal membrane. In addition to their solubilizing capacity and biocompatibility, the structural and compositional similarity of liposomes with bio-membranes has also encouraged their application for non-invasive oral delivery of poorly-permeable nutrients. 2
Liposomes are non-toxic, biocompatible, biodegradable, and have the following advantages as carriers in drug delivery: first, liposomes can reduce toxicity; second, hydrophilic and lipophilic agents can be incorporated into liposomes; third, liposomes control the drug release; and fourth, the liposome delivery system increases bioavailability. 3
WATER SOLUBILITY
Molecules with very poor water solubility usually have the worst bioavailability and can benefit the most from liposomal delivery. Fisetin is one example shown below up to 27x more bioavailable.
Liposomal Fisetin 1.6 to 27x More Bioavailable
This study in mice found a 2.7-fold increase (in Cmax) with Liposomal Fisetin, with a dose 10 times lower than that of the free fisetin when given by IP.
With IV, the Cmax of liposomal fisetin was 10, vs 6 for free fisetin.
Liposomal Vitamin B-12 Formulas 3-5x More Bioavailable Than Tablet.
This study compared five formulations for bioavailabilty in humans over 6 hours.A standard table (iii) was compared against an emulsion (ii), a chewabletablet (iv), an oral spray comprised of larger liposomes (v) and an oral spray comprised of very small (20 nanometer) liposomes.
- (i) Nanocelle 1000ug -28% - A nano liposomal formulation of B12sublingual spray with an average particle size of about 20 nm
(ii) Emulsion 1000ug - 10% -An emulsion formulation of B12 sublingual
(iii) Tablet 1000ug - 5% - A standard tablet formulation of B12 that is absorbed through the gastrointestinal tract.
(iv) Chewable 5000ug - 27% - A dissolvabletablet of B12 that is absorbed through the sublingual mucosa
(v) Liposome 1000ug - 14% - A liposome oral spray of B12 with particle sizes of approximately 100 nm.
The chewable showed similar increase as nano liposomal, but a 5x higher dosage was used.
The standard liposomal product was 3x more bioavailable than tablet.
The nano liposomal spray exhibited sustained release with more than 5x increased bioavailability over standard tablets.
Read moreLiposomal Berberine Increases Circulation Time 23-46x
Preparation, Pharmacokinetics and Tumour-Suppressive Activity of Berberine Liposomes (Zheng, 2017)
Administration of standard Liposomal Berberine increased retention time in circulation from .42 to 10 hours. Use of PEG modified Liposomes further increased retention to to 14 hours.
Administration of Berberine solution injection is hindered by unsatisfactory pharmacokinetics and, more importantly, the risk of lethal cardiovascular adverse reactions due to rapid uptake into heart and lung. This study validated common and long-circulating liposomes as safe and effective method for sustained release of Berberine.
Read moreLiposomal Curcumin & Resveratrol Capsules 10-20x More Bioavailable in Circulation and Prostate Tissue vs Standard Capsules
Liposome capsules of resveratrol and curcumin may inhibit prostate problems by increasing their bioavailability synergistically.
In this study, we determined the bioavailability of liposome encapsulated curcumin and resveratrol, individually and in combination and evaluated the inhibitory effects of these agents against prostate growth and progression.
Serum and prostate tissue samples harvested at different time points of 30 min to12 hr with plain liposome (0.1%), curcumin (50 mg/kg/bw), lipo-curcumin (50 mg/kg/bw),lipo-resveratrol (50 mg/kg/bw) and lipo-curcumin administered with lipo-resveratrol (25 mg/kg/bw for each).
figure a - Levels of curcumin and resveratrol recorded in the serum.
figure b - Levels of curcumin and resveratrol recorded in the prostate.
figure d - Quantification of tumor growth inhibition. Total number of adenocarcinomas observed under 10 high-power fields of control vs. treatment groups.
Read more
Liposomal Glutathione More Effective
Clinical research aiming to improve glutathione concentration requires sufficient glutathione absorption and delivery.Researchers turn to liposomal glutathione to achieve sustained bioavailability.
Results from two recent studies showed that liposomal nanoformulation absorption is more effective for raising blood glutathione levels in humans than non-liposomal glutathione. 1
Both studies report a very rapid decline in bioavailability of non-liposome-encapsulated glutathione compared to liposomal glutathione.
Liposome Encapsulated Glutathione Elevates Body Stores
The results of a recent study demonstrated increased body stores of Glutathione (GSH) after oral administration of Liposomal GSH humans. 2
Since GSH is subject to destruction in the acid environment of the stomach, researchers tested that oral liposomal GSH might be an effective means of GSH delivery in vivo.
Finally, liposomal GSH was highly tolerated and its administration was not associated with any signs of adverse effects. 3
The results from this study provide support for the potential use of oral liposomal Glutathione as an intervention strategy for enhancing tissue Glutathione levels for use in disease therapy or prevention.
Liposomal Glutathione effects were often greater that previously observed for non-liposomal Glutathione . 4
Read More
Enhanced Efficacy of Apigenin Liposomes
A recent study focusing on establishing apigenin as a potential chemotherapeutic agent for alleviating colorectal cancer reports the development of a stable liposomal nanocarrier with high encapsulation of the hydrophobic flavone apigenin for enhanced chemotherapeutic effects.
"Apigenin liposomes bypass the hurdles posed by apigenin as a chemotherapeutic due to its high hydrophobicity. The enhanced pharmacological activity of apigenin has been assigned to its ability to interact and subsequently influence membrane properties which also resulted in optimal yield of a stable, rigidified, non-leaky nano-carrier with ideal release kinetics."
Liposomal Quercetin:Prolonged Circulation Time in Vivo
New research using Quercetin liposomes demonstrates higher quercetin concentrations in plasma than non-encapsulated quercetin and prolonged circulations time in the blood.
"The effect of quercetin liposomes was stronger than quercetin alone. This formulation provides characteristics such as high drug encapsulation ratio, low in vitro release rate and slow drug clearance and prolonged circulation time in vivo. This provides an alternative solubilization vehicle for administration of quercetin."
Liposomal Nanoparticles Improve the Solubility and Bioavailability of Quercetin in Liver
Liposomal nanoparticles may improve the solubility and bioavailability of quercetin in liver. A 2020 study on the protective and therapeutic effects of nanoliposomal quercetin found liposomal quercetin could effectively protect rats against acute liver injury and may be a new hepatoprotective and therapeutic agent for patients with liver diseases.
Fig. 1:Effect of nanoliposomal quercetin on histopathological changes in rat liver tissues. (Scale bar: 50 μm; HE staining). a Normal control; b-d hepatic-injured rats with b saline treatment; c quercetin treatment; and d nanoliposomal quercetin treatment.
"Interestingly, nanoliposomal quercetin was more effective on decreasing liver index and interstitial inflammatory infiltration of hepatic-injured rats than pure quercetin, which indicated that the protective effect of nanoliposomal quercetin in the injured liver was stronger than that of pure quercetin."
