The  Enzogenol® Story




 Benefits & Effects   





 Enzogenol® is a natural extract from the bark of Pinus radiata. The extraction process uses a patented water-only process with no waste streams. The extract is a well-balanced blend of antioxidants containing many flavonoids - including proanthocyanidins - and organic acids all of which may have therapeutic benefits.
Enzogenol® uses bark from both the inner and outer tree and so contains compounds from the living tissues as well as the cork layer. The bark is a rich source of natural antioxidants that protect tissues and cells from free radical damage. 

Enzogenol® is made from carefully selected bark using clean technology which preserves the nutritive and active properties of the compounds in the raw material. These compounds are selected at a molecular level according to their solubility and size. The process uses latest extraction, membrane separation and water purification technologies. It's a simple, clean, efficient process that produces no waste and leaves no chemical residues in the product.
Enzogenol® is manufactured in a sophisticated production plant run to highly defined standards. Each batch of Enzogenol® is monitored by several different techniques to ensure consistency and potency.
The bark is thoroughly screened and washed before production. Only bark of a certain age, from a particular portion of the tree, and free from contaminants is accepted. It is then ground before extensive washing (in pure water). Water used in this process has been de-ionised, filtered and cleared of all oxidants.

Bark & Traditional Medicine

Trees have provisioned man abundantly down through the ages. They have been a source of wood for shelter, transport, weapons of war and instruments of cultivation, not to mention fuel for cooking and heating. They also provide a lot of different foods: apples, pears, figs, citrus, coconuts, mangoes and dates to name a few of the most common.
Trees and especially the bark have provided traditional remedies for ailments in many of the world's cultures.

18th century Pacific explorer James Cook used a tea made up of rimu and manuka twigs to help his crew fight scurvy while in New Zealand. The Maori people of New Zealand used kahikatea bark for treating bruises. The inner bark of the pohutukawa was used externally to stop bleeding and promote healing.

Chinese herbalists carry a variety of barks. Cinnamon is used for fever control and to soothe indigestion and other ailments.

Certain trees and barks were considered by the Native Americans to hold supernatural medicinal powers. The Cherokee used pine bark for many remedies and in ceremonies.
Many treatments recognised by modern western culture originated from trees: quinine for 
Malaria for one; the active ingredient of aspirin was first isolated from the bark of the white willow tree. Today's medicine also turns to trees and bark to treat cancer: Taxol (trade name for paclitaxel), a compound found in the bark of the Pacific Yew, has shown positive results in the treatment of breast cancer. Many other trees contain cancer-fighting substances.

Bark is a rich source of flavonoids and has been used for many years in medicine. It is complex in its chemistry and physical structure, containing literally hundreds of compounds. All of these compounds work synergistically to protect the tree from insects, pests and fungal diseases.

We are just starting to understand the immense complexity and richness of the many compounds in tree bark.

Balanced Blend of Antioxidants in Enzogenol®

All plant extracts are made up of many compounds. The range is related to the biological evolution of the source material, and all materials are not equal in this regard.
Over time evolution has developed very complex compounds, which provide sophisticated defence mechanisms for plants. These compounds are important adjuncts to human health.
A well-balanced extract reflects the full spectrum of flavonoid compounds, especially proanthocyanidins, across all molecular weights. Pine bark extracts are important sources of the critical higher molecular weight proanthocyanidins. 
Enzogenol® is especially rich in these complex polymeric proanthocyanidins.

The Breakthrough Confirmed….

The Enzogenol® molecular selection process captures a mixture from many flavonoid groups. The bark from Pinus radiata undergoes a patented pure water and molecular selection process, which captures the whole range of naturally occurring compounds. 
Enzogenol®, then, is an unprecedented encapsulation of the natural defence mechanisms of many plants, but especially concentrated in the bark of Pinus radiata.
Unlike extraction processes that breakdown or diminish chemical structures, the technique used to make Enzogenol® allows them to remain in their natural state.
This unique blend was further confirmed in measurements of the antioxidant protection of a compound.
One of the most widely accepted scientific standard methods used to measure the antioxidant ability of different compounds is the Peroxyl Radical Scavenging Antioxidant assay. This assay is based on the procedure described by Pryor et al (1993)1 and measures the ability of a substance to inhibit the oxidation of a linoleic suspension by the free radical generating compound AAPH.

Comparison of Antioxidant Activity using the Peroxyl Radical Scavenging Assay

The results of this assay show that the breakthrough had been achieved and that the presence of the higher molecular weight proanthocyanidins explained these good results.

Flavonoids are antioxidant compounds found in plants. Animals do not produce flavonoids and so they get them from diet. Flavonoids not only protect plants they also protect animals - and therefore humans. Diets high in fruits and vegetables provide protection against cardiovascular disease, cancer and other diseases.
Flavonoids are diverse both in their characteristics and chemical structures. Over four thousand of them have been identified and some say there could be as many as twenty thousand in plants2.

Flavonoids including Proanthocyanidins
Flavonoids are divided into twelve main sub-groups by their structural class. Main groups of flavonoids are flavonols, flavanones, flavones, anthocyanidins and catechins. Simple flavonoids are able to join together to form other flavonoids. 
For example, the very simple group of monomeric flavonoids called catechins are able to join together to make bigger molecules. 
There are different types of catechins and they bond together in various ways to form different compounds with very different characteristics. 
Two catechins joined together are called a dimer and three catechins bonded together a trimer and so on up to oligomers and polymers. 
These new compounds are called proanthocyanidins, or condensed tannins. Catechins are the building blocks for proanthocyanidins and the number of the latter is almost endless.
Flavonoid research has really taken off over the past two decades. Acting as antioxidants, flavonoids and phenolic acids protect us against free radicals and other mechanisms that can contribute to disease. 
They have been shown to have an array of biological effects and can counter inflammatory, bacterial, carcinogenic and allergic disorders.

Flavonoids and Health
Flavonoids from many plants have been used all around the world as medical treatments.
Flavonoids first came into the spotlight back in the 1930s when  Szent-Györgyi and his colleagues extracted two flavonoids from citrus fruit. They investigated their effects and found they decreased capillary fragility and permeability in humans. 
This is why flavonoids were called "vitamin P" - for permeability. It was probably the first study on the effect of flavonoids on human health but the work could not be repeated so the claim that flavonoids were vitamins was dropped in the 1950s.
Since then a huge array of biological effects countering inflammatory, bacterial, viral, microbial, hormonal, carcinogenic, neoplastic and allergic disorders3 have been reported for flavonoids in both in vitro and in vivo systems. 
Flavonoids exert these antioxidant effects by neutralising all types of oxidising radicals4 - including the superoxide5 and hydroxyl radicals6 - and by chelation. A chelator binds to metal ions in our bodies to prevent them being available for oxidation. Flavonoids can also act as powerful chain-breaking antioxidants due to the hydrogen-donating capacity of their phenolic groups.

Flavonoids, Research, Coronary Heart Disease and Strokes
Coronary heart disease (CHD) is one of the biggest killers in the western world. 
Developments in cardiovascular disease research have shown that oxidative reactions and free radicals play a role in the myocardial injury and atherogenesis. Flavonoids reduce the oxidation of low-density lipoproteins and also prevent platelet aggregation by inhibiting the activity of the enzyme cyclooxygenase. Dietary flavonoids have been shown to have a positive impact on coronary heart disease. The epidemiological Zutphen Elderly Study7 investigated the relationship between dietary flavonoid intake and CHD.

 Graph 1 - Flavonoid intake level against relative risk of mortality from

 Coronary Heart Disease.
Relative Risk of Mortality from CHD 

 Flavonoid Intake

The Zutphen Elderly Study showed that fewer of those who ate larger amounts of flavonoids died of heart disease than those who consumed less. 

This result was still significant after adjustments were made for age, smoking, physical activity, coffee, vitamin C and E consumption.

Another looked at the intake of flavonoids and the incidence of stroke8. The results of these studies is shown below:

 Graph 2 - Flavonoid intake level against relative risk of stroke incidences.

Relative Risk of Stroke Incidence 

 Flavonoid Intake

Dietary intake of flavonoids was again inversely associated with stroke incidence after adjustment for age, systolic blood pressure, serum cholesterol, smoking, energy intake and consumption of fish and alcohol. Vitamins C and E were not associated with stroke risk. This indicates that the more flavonoids you consume the lower the risk of stroke.

1 Pryor, WA, Cornicelli, JA< Devall, LJ, Tait, B, Trivedi, BK, Witak, DT, Wu, M (1993) J.Org.Chem. 58 (13), 3521-3531
2 Colgan, M (1994) The New Nutrition. Medicine for the Millennium. CI Publications, San Diego.
3 Middleton, E (1996) Biological Properties of Plant Flavonoids: An Overview. International Journal of Pharmacognosy 34 (5)
4 Bors, W, Heller, W, Michel, C. (1998) The Chemistry of Flavonoids. From Flavonoids in Health and Disease, Edited by C A Rice-Evans and L Packer, Marcel Dekker, New York.
5 Robak, J, Gryglewski, R J. (1988) Flavonoids are Scavengers of Superoxide Anions. Biochemical Pharmacology, 37(5)
6 Husain, S R, Cillard, J, Cillard, P (1987) Hydroxyl Radical Scavenging Activity of Flavonoids.. Phytochemistry, 26 (9)
7 Hertog, MGL, Feskens EJM, Hollman PCH, Katan MB, Kromhout, D (1993) Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study Lancet 342 1007-1011
8 Keli, SO, Hertog MGL, Feskens EJM, Kromhout D (1996) Dietary Flavonoids, Antioxidant Vitamins, and Incidence of Stroke. Arch Intern Med 156, 637-642

Antioxidants and Health
Free Radicals: The villains of the piece

Free radicals are being generated in your body in there thousands every day. By curbing their activity, you can slow down the very processes in your body that cause disease and aging. Yes, you can feel better and live longer! 
The human body does not have a big reserve of antioxidant defence capacity and all the time it produces free radicals and other oxygen derived molecules (such as hydrogen peroxide). Today, people continuously subject themselves to many things that increase the level of free radicals in their bodies and so the body can easily become overpopulated with oxygen-derived species that upset cell biochemistry. This imbalance of free radicals in the body is called oxidative stress.

Oxidative Stress
Oxidative stress is caused by:
· Increases in free radicals meaning the body's antioxidant defence system can't cope.
· Antioxidants in the body decreasing with age.
· Increased Free Radical exposure.
An increase in the available transition metal ions, which causes more of the free radicals, produced in the body to be changed to more reactive peroxyl species.

What is a free radical? 

Just as oxidation takes place all around us, it also occurs in our bodies. There are millions of chemical reactions involving oxidation taking place in our bodies every second.
Free radicals are unstable molecules. They often contain oxygen. They are unstable because they have only one electron and they desperately want two to make them stable. To get another electron they rob one from anything they can. Healthy cells in our bodies are a good mark for them. They do this relentlessly and very quickly, and can cause a lot of damage. It is estimated that our DNA receives about 10,000 "hits" from free radicals every day1.
Cells can cope with small amounts of oxidative stress as they are quite ingenious and can repair minor free radical damage and other oxygen-derived species damage. However not all damage can be repaired and the un-repaired damage accumulates in the body.
Major oxidative stress can cause grave disturbances in cell metabolism and contribute to human disease. Tissue damage and injury can also lead to oxidative stress. Oxidative stress can cause DNA damage, lipid peroxidation, protein damage, and ischaemic (lack of oxygen) injury.

The sources of free radicals are many…

Metabolism by-products · Macrophages and neutrophils · UV radiation · Pollution · Fatty foods · Chemicals · Cigarette smoke · Exercise· Pesticides· Radiation· Solvents· Air Conditioners · Aerosol sprays, drycleaners· Car exhaust fumes· Physical stress or trauma· Emotional stress or trauma · Excessive alcohol intake· Illness and infection· Faulty protein digestion· Spoiled or tainted foods· Rancid and heated fats· Chemicals in food· Ozone· Ultra-violet rays

Associated diseases and conditions
Many conditions have been linked to free radical damage and oxidative stress:
· Allergies 
· Alzheimer's 
· Amyotrophic Lateral Sclerosis (ALS) 
· Cancer including bladder, breast, cervical, colorectal, lung melanoma, ovarian/ endometria, prostate, stomach, upper aerodigestive tract 
· Cardiovascular Disease 
· Cataracts 
· Cystic Fibrosis 
· Diabetes 
· Diabetic Neutrophy 
· Glaucoma 
· Huntington's Disease 
· Macular Degeneration 
· ME
· Multiple Sclerosis 
· Muscular Dystrophy 
· Pancreatitis 
· Parkinson's Disease 
· Rheumatoid arthritis and other inflammatory conditions 
· Schizophrenia 
· Stroke 
· Tardive Dyskinesia

The above list is a small selection as our continual understanding and enlightenment of diseases and oxidative stressed states continues to become known.

Antioxidants protect against oxidation. Antioxidants sacrifice themselves to the free radical and thereby protect our bodies' cells from free radical damage. Our body has two sources of antioxidants:
1. Our in-house antioxidants, such as superoxide dismutase, catalase and glutathione.
2. Dietary antioxidants, from sources such as fruit, vegetables, nuts and grains.
As we grow older our bodies in-house defense system loses its effectiveness. The body level of antioxidants diminishes as we age so not all the free radicals are neutralized and there is a slow build-up of damaged molecules in the body.
Many researchers claim that dietary changes designed to decrease the rate of free radical reactions in the body can increase the span of healthy life by at least five years.
Flavonoids like those found in Enzogenol® are antioxidant compounds in plants. They are natural dietary disease-preventing, health-promoting substances.

Living Longer
It is absolutely essential to establish the safety of a new product. We can't test on humans so laboratory mice were used for this study. By observing the animals we can determine any changes in health after dosage with Enzogenol®. The main aims of this study were to establish safety and determine the effects of Enzogenol® on acute and chronic toxicity, tumor incidence, longevity and behavior. 

Mice were randomly allocated within sex to cages. The mice were divided into three groups and fed ad libitum on normal mouse food (Archer's Mills Pellets) with additional Enzogenol® as outlined below:

Controls - No Enzogenol®

NHD - Normal Human Dose equivalents of Enzogenol® adjusted for the difference in body mass

100NHD - 100 times Normal Human Dose. If Enzogenol® were toxic half the mice would die in about three days.

What did we find?
No acute or chronic toxicity was evident in this trial. Enzogenol® was not toxic even in high doses. Mice fed Enzogenol® grew thicker, glossier fur; their eyes became brighter and noses & tails pinker - a sure sign of healthy mice! They appeared to be more social with fewer negative interactions (biting neighbors etc). When asked to pick the healthiest looking mice, independent observers all chose the 100 NHD group first, followed by the NHD group. The controls were invariably third and last.

What did we find?

Tumor Rates and Deaths


Percent with 1 or more tumors

 Percent dead due to tumors

 Percent dead due to old age

 Percent alive after 8 months
















From these results it can be seen that:

  • Longevity in this trial nearly doubled with Enzogenol® (from 40% without Enzogenol® to 73% with Enzogenol®).

  •  The rate of tumour incidence decreased in a dose-related manner with Enzogenol® (from 50% without Enzogenol® to 13% with Enzogenol®)

Statistical Significance

The statistical significance of these results was established by two approaches:
1. A standard Fisherian technique testing trends in linear proportions, (Snedecor and Cochran (1980) Statistical Methods, 7th Edition).
2. Modern re-sampling methods.
The linear trend analysis showed the results were highly significant (P < 0.0001). The details of the Fisherian statistical analyses are summarised in the following table.
Fisherian Analysis of Mouse Toxicity

Tumour Incidence Death Rate 

Z-score -1.982* 1.208 

Gradient -0.00338 -0.00211 

Standard Error -0.00170 0.00175 

The analysis in the above table shows that the death rate is not significantly related to dose and that the tumor rate is significantly related to dose rate.
Given that the sample sizes are small, a better means of analysis is to use the technique of resampling.

Resampling Results
Tumor Rate Longevity 

Mean p-value -0.001*** 0.021* 

Thus the decrease in tumor rate is highly significant, and the longevity increase is significant.

By how much?
The answer to this question is difficult to apply to human populations, but if the mouse results are reliable and they serve as a good model for humans, then a normal dose of Enzogenol® increases the number of people who survive to age X by 1.825 times. In other words old age survival to age X is nearly doubled. This effect is not strongly dose-dependent as indicated by the non-significant test for linear trends.
However, the tumor incidence rate is dose-dependent. For the 1x dose (NHD) the rate is reduced to 80% of the normal value and for the 100x NHD it is reduced to 26% of the normal value.
· There is no evidence of acute toxicity 
· There is no evidence of chronic toxicity 
· The incidence of tumors is strongly reduced by Enzogenol® in a dose-dependent manner 
The longevity is increased in a (perhaps) weakly dose-dependent manner.

The Benefits of Enzogenol®
Alpha (a) Effects
Alpha effects are the long-term effects of scavenging or neutralizing of free radicals. These effects do not change the way that people feel. There is no immediate health, psychological or emotional benefits. The antioxidant is taken in the expectation it will prevent disease, cancer, heart attacks etc. There is no obvious change - which could explain the longevity and reduced tumor incidence in the mice.
Beta (ß) Effects
Beta effects we see more quickly. These are the changes in health, psychological or emotional state that you do notice, or that others notice in you. In this case the antioxidant is affecting metabolic processes with consequent changes in physical, emotional or physiological state. When people comment on their increased alertness, improved skin condition, less flu and colds, faster recovery from soft tissue damage, improvement in joint movements or increased ability to cope with stress they are talking of beta effects. These may be the more compelling reason for taking a powerful antioxidant.

1 Ames, BN, Shigenaga, MK, Hagen, TM (1993) Oxidants, antioxidants, and the degenerative diseases of ageing. Proc. Natl. Acad. Sci. USA 90, 7915-7922


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