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Ecklonia Cava Extract - Superior Polyphenol Antioxidant
Many Times Stronger Than Green Tea Extract

Ecklonia Cava Extract: Polyphenol / Phlorotannin Derived from Brown Algae

Ecklonia Cava Extract (ECE) is a standardized natural complex of unique marine molecules that originate from a specific species of brown algae (Ecklonia cava). Polyphenols are a group of chemical substances found in plants, characterized by the presence of more than one phenol group per molecule. ECE represents a unique category of polyphenols often called phlorotannins. Their unique polyphenolic structure endows them with biological activities that are not found in land-based plants. Various physiological activities have been evaluated in both the individual compounds found in ECE and in the more complex forms through in vitro, in vivo and clinical studies.

Millions on Research

Dr. Haengwoo Lee and his team of M.D.’s and Ph.D.’s have spent over thirty million dollars on research, from in vitro to animal and human studies. Much of the work was done in Korea, and some at the University of Washington. ECE has been found to be an impressive therapeutic agent for a wide variety of health conditions.

SUPER ANTIOXIDANT

The power of an antioxidant is often determined by its molecular structure, which is made up of rings. These rings provide the antioxidant function. Most flavonoids generally have three interconnected rings. ECE has up to eight interconnected rings, making its free-radical scavenging ability 10-100 times more powerful than other polyphenols. It is substantially more powerful than green tea catechins, which only have four rings.

Multiple Antioxidant Profiles of ECE

ECE’s antioxidant activities against various free radicals have been confirmed to be highly potent. ECE itself and its individual compounds have demonstrated potent reducing power and scavenging activities against free radicals such as oxidized LDL ("bad" cholesterol) and peroxynitrite (a powerful free radical that appears to play a major role in many disease processes).

Much Longer Half-Life

ECE is a unique polyphenol in that it has a very long half-life (remains in the body longer). This is because ECE is a marine-based polyphenol which is 40% fat-soluble. Virtually all other polyphenols are derived from land-based plants and are water-soluble. The half-life of ECE is up to 12 hours, compared to 30 minutes for water-soluble, land-based polyphenols. Because it is fat-soluble, ECE also has the ability to cross the blood-brain barrier.

The Research of Martin Pall, Ph.D.

Peroxynitrite is the most notorious of the free radicals incriminated by Martin Pall, Ph.D.'s groundbreaking research on multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, post traumatic stress disorder, Gulf War syndrome, and fourteen other conditions. Peroxynitrite plays a main role in Dr. Pall’s mechanism, along with NF-kappaB (an important inflammatory mediator). ECE has been found to reduce NF-kappaB as well.

FIBROMYALGIA

ECE: Phase I Clinical Trial Results (Preliminary)

In an 8-week, double-blinded, placebo-controlled study of established fibromyalgia patients, ECE was used as an adjunct therapy to the patients’ current standard of physician care. The results established the general safety of ECE. ECE cut the time it took the participants to fall asleep by 47 minutes; it increased total nighttime sleep by 1.6 hours; it improved soundness of sleep by 80%; it boosted their energy levels by 71%; it gave them 2 1/4 more good days per week; it helped reduce their pain by 31%; and their general condition improved by 39%. Interestingly, these improvements were achieved at all doses. Patients given the placebo had no improvement during the study.

ECE & FIBROMYALGIA

BRAIN FUNCTION: MEMORY, RELAXATION, ALERTNESS

Acetylcholine & Memory

Memory is related to the neurotransmitter acetylcholine (ACh). In an animal study, ECE increased rodent ACh by 140% in the brain regions responsible for learning and memory in just seven days. Memory enhancement increased by 100-200% at an oral dose as low as 0.2-1mg/kg.

With regard to mechanism, it is thought that ECE works by mildly inhibiting an enzyme that breaks down acetylcholine called acetylcholinesterase. By inhibiting this enzyme, the availability and utilization of acetylcholine in the body would be enhanced.

Increased Blood Flow

Because ECE is fat-soluble, it has the ability to cross the blood-brain barrier and significantly improves blood flow to the brain. This is likely another way ECE improves memory. More specifically, Dr. Lee’s group found that ECE increases the velocity of blood flow in the carotid artery (the main artery to the brain) from an average of 36.68 cm/ sec. to 40.09 cm/sec., while the placebo showed no improvement.

Relaxation & Alpha-Waves

An EEG study on brain waves of healthy middle age volunteers found that ECE compounds increase alpha-waves. Alpha-waves are an indicator of relaxation.

Alertness

Yet another study found that ECE compounds prevented sleepiness in bus drivers and in high school students during daytime activities. This is also likely due to increased blood flow and oxygen delivery to the brain.

Neuroprotective Effects

ECE has demonstrated powerful neuroprotective effects owing to several features of its components. ECE compounds are both powerful antioxidants and anti-inflammatory agents capable of scavenging free radicals and suppressing excessive inflammatory reactions. Fucoidan, an ECE compound, has recently been found to protect neuronal cells from ischemia-induced (reduced blood flow) inflammatory reactions which often occur in the aged and highly stressed brain. ECE compounds also neutralize the powerful neurotoxic free-radical peroxynitrite.

Enhancement of Acetylcholine Levels in Mice

After 7 days oral administration of two ECE compounds (DE 10 mg/kg and PFF 2 mg/kg), mice under ethanol-induced cognitive impairment showed substantial enhancement of acetylcholine levels in three brain regions related to memory formation, as compared with non-treated mice. Acetylcholine was enhanced by 140% in the frontal cortex, the part of the brain crucial for long-term memory and associative thinking.

Resistance of Stress-Induced Learning Deficit in Mice

In a 5-day study, ECE treated mice showed significant resistance to electric shock treatment-induced learning deficiency, as compared to non-treated mice whose learning process was significantly retarded during the test period.

Memory Enhancement in Mice

The beneficial effects of ECE compounds on memory enhancement were further demonstrated by measuring the latency time avoiding the previously experienced electric shock treatment in mice as passive-avoidance memory testing. After 7 days oral administration of two ECE compounds DE and PFF (as low as 1 and 0.2 mg/kg), mice under ethanol-induced cognitive impairment showed 130-140% improvement, especially in the PFF group.

Beta-Amyloid Deposition Inhibition in Rats

Researchers at the National Institute of Health’s aging research labs in Baltimore studied ECE in rats, and found it to inhibit beta-amyloid deposition in the brain. Beta-amyloid is the substance that accumulates in Alzheimer’s disease. The rats also learned maze challenges faster, which demonstrated improvement in short-term memory.

ARTHRITIS, INFLAMMATION, NEURALGIA

Dr. Lee and colleagues found ECE to naturally suppress inflammatory responses and neutralize inflammatory damage caused by free radicals. The optimal combination of ECE’s natural anti-inflammatory and tissue-protective properties appears to enable dramatic improvement in both arthritis and neuralgia. In a human trial, ECE significantly reduced pain in a group of knee arthritis patients compared with placebo.

Comparable to Celebrex®

ECE’s ability to treat arthritis was found to be comparable to Celebrex®, the prescription drug that reduces inflammatory enzymes known as "COX" enzymes.

In the study, the influence of ECE on the generation of inflammatory prostaglandins known as PGE2 was studied. ECE, celecoxib (Celebrex®) and aspirin all showed significant inhibition of PGE2 generation in the concentration range tested. More specifically, ECE showed inhibition of 61%, 85%, 92% and 99% at concentrations of 10, 30, 60 and 100 µg/mL respectively, showing similar activity to celecoxib which showed 65%, 79%, 85% and 96%.

Cartilage Protecting Activities

As demonstrated above, ECE compared almost identically to celecoxib in the ability to reduce PGE2 by slowing down the lipoxygenase (LOX) system (a key inflammatory enzyme system). ECE compounds have more than double the ability of resveratrol (a powerful antioxidant polyphenol found in red grapes) to inhibit LOX. These results were demonstrated in a study on rabbit cartilage cells. Those cells treated with ECE had up to an 80% reduction in degeneration.

Neuropathy: 4-Week Clinical Trial

Researchers recently studied ECE on 40 patients with neuropathy. ECE reduced nerve pain by 40% in four weeks. Overall, 80% of the patients responded favorably.

Speculation about Neuropathy Mechanism

The strong lipid and cholesterol reducing potential of ECE supports reduced vascular inflammation. Increasingly, the scientific literature supports the notion that many forms of nerve pain or neuropathy are caused by nerve pressure, as exerted by swollen, inflamed blood vessels adjacent to the nerves.

ALLERGIES / ASTHMA

Overall, ECE appears to significantly relieve allergic reactions without drowsiness, dizziness and other side effects of anti-histamine drugs.

Allergic Inflammation: Mouse Study

Dr. Lee and his team found that ECE significantly reduced allergic inflammation in mice. Specifically, ECE reduced the migration of eosinophils (inflammatory white blood cells) to the lungs by 75%. Eosinophils and resulting cytokines were reduced by 50%. Mucus plugs in the airways were reduced by 75%. Airway epithelial hyperplasia reduced by 75%. Collagen-causing fibrosis in lung interstitium (fibrosis, airway remodeling) and smooth muscle cell thickness was reduced by 20% and 32%. These latter findings suggest that ECE compounds may prevent or reverse the progression of chronic lung disease such as asthma and Chronic Obstructive Pulmonary Disease (COPD).

5-Lipoxygenase (5-LOX)

Because the 5-LOX system plays such a major role in inflammatory and allergic responses, inhibition of 5-LOX has become a medicinal target for the treatment of inflammatory diseases. One of the ECE compounds (8,8-BE) significantly inhibits 5-LOX compared with other well-known natural medicinal compounds such as resveratrol and EGCG.

University of Washington Asthma Mouse Study

The efficacy of ECE for asthma was demonstrated in an allergen-induced murine asthma mouse study by Dr.
Emil Chi, Chairman, Department of Histopathology, University of Washington.

The researchers tested an ECE product (KLS) in a mouse study of allergen-induced chronic lung inflammation and fibrosis. The antigen-treated mice developed an extensive cellular inflammatory response, overproduction of mucus and airway mucus plugging.

KLS was found to be effective in reducing allergic reaction in inflammation. KLS reduced airway mucus plugging, and sub-epithelial fibrosis in the antigen-sensitized / challenged mice. KLS was shown to be effective in improving the asthmatic lung structures. No pathological alterations in the liver, kidney, spleen, or small intestine were found.

CARDIOVASCULAR BENEFITS

Coronary Artery Disease

ECE has been shown to improve coronary artery disease (CAD). Researchers found that ECE is even more potent at inhibiting the oxidation of LDL cholesterol ("bad" cholesterol) than green tea catechins, and appears to scrub the plaque off the endothelial lining. ECE also reduces vascular inflammation by preventing oxidation, which also directly effects the body's inflammatory response.

Coronary Artery Disease: 6-Week Clinical Trial

A clinical trial using ECE was conducted confirming its capacity to regenerate the vascular endothelium (the cells critical to the inner lining of the blood vessels) and recover plasticity of blood vessels after 6 weeks of treatment. The results indicate ECE's remarkable ability to induce recovery of endothelial cells and improve vascular plasticity. These findings demonstrate ECE’s ability to support restoration of vascular integrity by reversing atherosclerosis.

Cholesterol: 6-Week Clinical Trial

Researchers gave 39 adults (average age 55.6) low dose (100 mg) ECE compounds for six weeks. Their average cholesterol dropped from 228 to 224. LDL dropped from 141 to 135. HDL rose from 46.5 to 50.7 (highly significant). Triglycerides fell from 215 to 195, and the atherogenic index dropped 12.5%.

Some of the parameters from the above study show very moderate changes, which in themselves, may not be statistically significant. However, all parameters went in a health-positive direction, so taken together, the changes in LDL, HDL, triglycerides, blood pressure, and antioxidant protection are very significant. Also, endothelial cells were protected against oxidative damage, and were able to produce significantly more nitric oxide, which dilates blood vessels. Dramatic increases in blood flow were also found at this low dose.

High Blood Pressure: 4-Week Animal Study

The remarkable effect of ECE on vasodilation was clearly demonstrated in a study of rats with induced high blood pressure. Upon oral administration of ECE phlorotannin (50 mg/kg) or enalapril (a commercial drug for high blood pressure 10 mg/kg), blood pressure dropped to as low as 160 and 140 mm Hg. Upon cessation of treatment, blood pressure increased again in both cases. Although ECE showed a similar pattern to the drug, it also showed a slower rebounding of blood pressure during the no treatment period, which indicates its potential as a vascular protector with prolonged oral administration.

ACE Inhibition

ACE (angiotensin-converting enzyme) is the enzyme that converts angiotensin I to angiotensin II in the body. Angiotensins are vasoppresive substances that lead to constriction of the smooth muscles and arteries, which reduces blood flow and leads to high blood pressure. Angiotensin I is the inactive form and angiotensin II is the powerful active form. Since ACE converts angiotensin I to angiotensin II, inhibiting ACE is very desirable. Angiotensin II is also involved in cellular proliferation, inflammation, and endothelial function, and plays a key role in the development of atherosclerosis and its complications. Aging or various vascular risk factors tend to increase ACE levels resulting in excessive vasoconstriction and hypertension. Current hypotensive drugs block the action of ACE or its by-product angiotensin II.

ECE tannins have been found to be potent natural ACE inhibitors, demonstrating more than 15 times the power to inhibit ACE as the most powerful land-based polyphenols, including the natural hypotensive substance catechin found in green tea.

In addition, one of the compounds found in ECE (THP-BE) is comparable to bradykinin, an important hormone produced by the body that helps keep blood vessels dilated and open, thus encouraging healthy blood flow and blood pressure.

Antiplasmin Inhibition

Plasmin (an important fibrinolytic enzyme that breaks down blood clots) is rapidly blocked by a protein called antiplasmin. ECE compounds are natural potent inhibitors of anti-plasmin, capable of efficient promotion of plasmin that performs fibrinolysis. ECE compounds have shown remarkable activity which is 40-200 times greater than the anti-plasmin inhibiting drugs Flufenamate and Chloramine T.

ERECTILE FUNCTION ECE V. VIAGRA®

Nitric Oxide

As previously discussed, ECE can regenerate the vascular endothelium. They generate the chemical nitric oxide (NO), which keeps the arterial walls relaxed and dilated. After a six-week study of ECE, flow mediated dilation and NO mediated dilation increased by 60% and 50%. In another study, coronary artery disease patients were given ECE for six weeks. Blood flow controlled by NO increased 50-60%. These results confirm that ECE can rejuvenate damaged endothelial cells to produce NO. This effect was further confirmed in a study on erectile dysfunction (see below). Interestingly, Viagra® works by increasing NO in the penile artery.

ECE v.Viagra®: 8-Week Clinical Trial

Scientists studied 31 men with erectile dysfunction (ED) for over six months. For eight weeks they compared ECE to Viagra®. They looked at orgasmic function, intercourse satisfaction, erectile function, and overall satisfaction. No side effects were reported with ECE.

Over the course of eight weeks ECE & Viagra® scored as follows:

ECE scored:
• Orgasmic Function: 87%
• Intercourse Satisfaction: 74%,
• Erectile Function: 66%
• Overall Satisfaction: 62%

Viagra® scored:
• Orgasmic Function: 27%
• Intercourse Satisfaction: 44%,
• Erectile Function: 66%
• Overall Satisfaction: 39%

In addition, scores on key questions (frequency of penetration and frequency of maintaining an erection after penetration), which directly indicate the ability to achieve and maintain an erection sufficient for sexual activity, were improved 74% and 77%.

These results strongly indicate that the long-term oral administration of ECE significantly contributes to the normalization of the general vascular conditions around the sexual organ. The mechanism of which is most likely due to neutralization of oxidative risk factors, thereby improving peripheral blood circulation around muscles and nerves involved in sexual function as well as the penile artery.

Long-Term Improvement Possible

When taking all of ECE's benefits into consideration, long-term oral administration of ECE may contribute to long-term improvement in vascular health, including the penile artery.

WEIGHT LOSS

DGAT Inhibition

Diacylglycerol acetyl transferase (DGAT) is an important enzyme involved in triglyceride synthesis. Triglycerides are circulating fat molecules that ultimately wind up in the fat cells, and are almost always elevated in diabetes. They also have emerged as a major risk factor for vascular diseases.

Dr. Lee found that ECE compounds inhibited DGAT more than 50%. In genetically caused obese laboratory rats, ECE reduced body fat and increased physical activity. In another study, ECE caused leanness and fat-resistance in animals given a high fat diet.

ECE Beverage: 2-Week Clinical Trial

In a human study, 141 young adults were given a beverage containing ECE at 200 mg daily. In two weeks their average weight dropped nearly 2.5 pounds, muscle mass increased by nearly 2.5 pounds, and body fat dropped by 4 pounds, or 7.48%. ECE stimulates the body to burn fat by increasing muscle mass.

OBESITY

Extra Cardiovascular Protection

Obviously, ECE's many health benefits provide additional cardiovascular protection for obese patients, who are more prone to cardiovascular and coronary heart disease. As discussed, ECE lowers LDL cholesterol, suppresses triglyceride production, promotes healthy blood flow, lowers blood pressure, and scavenges free radicals, to name a few.

DGAT Inhibition & Obesity

DGAT (diacylglycerol acyltransferase) is a key enzyme involved in intestinal fat absorption, triglyceride levels, fat storage, and energy metabolism in muscles. DGAT inhibition has recently been recognized as a novel and safe target for the treatment of obesity. In a mouse study in which DGAT was inhibited, mice demonstrated obesity resistance with a high-fat diet. ECE compounds are found to inhibit  DGAT.

DIABETES

Aldose Reductase Inhibition

When blood sugar levels become elevated, the enzyme aldose reductase converts excess glucose into the sugar alcohol sorbitol. Sorbitol can build up in critical cells and cause damage. Recent research found that animals deficient in aldose reductase were protected from the retinal complications of diabetes. ECE compounds have been found to be potent aldose reductase inhibitors, which may be of benefit for patients with metabolic syndrome, syndrome X, or diabetes.

Reduced Fat in Liver & Pancreas

A mouse study showed that ECE reversed fat deposition in liver and pancreas cells. Furthermore, this same study showed that ECE served to markedly inhibit inflammation in the pancreas. A recent Harvard (Joslin School of Diabetes) mouse study directly implicates excessive fat deposition in the mouse pancreas for turning on the inflammation pathway, resulting in full-blown type II diabetes and insulin insensitivity in the mice.

SAFETY

ECE is manufactured from edible algae through food-compatible processes. Tens of thousands of people throughout the world have experienced ECE in various forms without side effects. To date, Dr. Lee’s team has not found any toxicity at any level. Several toxicity tests have been performed, and no adverse effects have been found at the effective human dose level of 1-10 mg/kg.

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