Ecklonia Cava Extract – Super Antioxidant & Beyond
Ecklonia Cava Extract: Polyphenol / Phlorotannin Derived from Brown Algae
Disclaimer: For educational purposes only This information has not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease
Ecklonia Cava Extract (ECE) is a standardized natural complex of unique marine molecules that originate from a specific species of brown algae (Ecklonia cava). 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.
ECE naturally occurs as high-molecular weight tannin (Mw> 2,000 Dalton) and low-molecular weight tannin (Mw=400-1000 Dalton). ECE can be classified into four types depending on the ratio of high molecular weight and low molecular weight tannins. Various physiological activities of ECE have been evaluated in vitro, in vivo and clinically as individual compounds (ECE1-ECE14) and complex forms (ECE, Type I-IV).
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 in a wide array of clinical applications.
The power of an antioxidant is determined by its structure, which is made up of rings. These rings capture stray electrons from free radicals. 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 reactive oxygen species have been confirmed to be highly potent in physiologically relevant concentrations. The effective dose of ECE for free radical scavenging is in the 10-20 µg/mL range which belongs to most potent families of natural antioxidants. ECE itself and its individual compounds have demonstrated potent reducing power and radical scavenging activities against DPPH radical, oxidized LDL and peroxynitrite.*
Much Longer Half-Life
ECE is a unique polyphenol in that it has a very long half-life in the body. 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. ECE 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 and other inflammatory mediators. ECE also reduces tissue specific NF-kappaB.
*Peroxynitrate is a central reactive oxidant, which appears to play a major role in many disease processes.
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 dependent on the neurotransmitter acetylcholine (ACh). In an animal study, ECE increased rodent ACh by 140% in brain regions responsible for learning and memory in 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 the mild acetylcholinesterase inhibitory activity of two phlorotannin compounds found in ECE, dieckol (DE) and phlorofurofucoeckol (PFF), may be involved in the up-regulation of acetylcholine.
Increased Blood Flow
ECE crosses the blood-brain barrier and significantly improves blood flow, which is likely another way ECE improves memory. More specifically, Dr. Lee’s group found that ECE can increase the velocity of blood flow in the carotid artery 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.
Yet another study found that ECE compounds prevented sleepiness in bus drivers and in high school students during daytime activities. This is likely due to increased blood flow and oxygen delivery.
ECE 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 in ECE has recently been found to protect neuronal cells from ischemia-induced inflammatory reactions which often occur in the aged and highly stressed brain. ECE compounds also neutralize the neurotoxic free-radical peroxynitrite.
Enhancement of Acetylcholine Levels in Mice
After 7 days oral administration of two ECE compounds (DE 10mg/kg and PFF 2mg/kg), mice under ethanol-induced cognitive impairment showed substantial enhancement of acetylcholine in three brain regions related to memory formation, as compared with non-treated mice. Especially, 140% enhancement was observed in the frontal cortex that is crucial in 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 0.2mg/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 same 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 reactive oxygen species. 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 cox enzymes.
The influence of ECE in lipopolysaccharide (LPS)-induced generation of prostaglandin E2 (PGE2) using RAW 246.7 cells was studied. While PGE2 was barely detectable in non-stimulated cells, more than one hundred times the amount of PGE2 was detected in the stimulated cells. ECE, celecoxib (Celebrex®) and aspirin all showed significant inhibition of PGE2 generation in the concentration range tested. ECE showed inhibition of 61%, 85%, 92% and 99% at concentrations of 10, 30, 60 and 100 µg/mL, 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. ECE compounds have more than double the ability of resveratrol 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.
In an animal study, rabbit articular cartilage explant culture was treated with recombinant human interleukin 1 (rhIL-1) to induce proteoglycan degradation. The amount of glycosaminoglycan released into the medium was measured as an index of proteoglycan degradation. When the rabbit cartilage explants were treated with rhIL-1 for 60 hours, the amount of released glycosaminoglycan into the culture medium increased significantly compared to the vehicle group (1.44 ± 0.06µg/mg vs. 0.30 ± 0.01µg/mg). Diclofenac, which is known as a selective COX-2 inhibitor was used as a positive control at a dose of 10µM (3.2µg/mL). ECE significantly interfered with the rhIL-1-mediated degradation of proteoglycan in all concentrations tested (p <0.001). It showed 53%, 79%, 81% and 70% of inhibition at 1, 3, 10 and 30 µg/mL concentration.
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 Model
Dr. Lee and his team found that ECE significantly reduced allergic inflammation in mice. Specifically, ECE reduced the migration of eosinophils to the lungs by 75%. Inflammatory white blood cells (CD4+4 T Cells, resultant cytokines Il-4, 5, 13) 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 can prevent or reverse the progression of chronic lung disease such as asthma and Chronic Obstructive Pulmonary Disease (COPD).
5-Lipoxygenase (5-LOX) catalyzes the first step in the oxygenation of arachidonic acid, thus leading to the production of biologically active compounds such as leukotrienes and 5-hydroxyeicosatetraenoic acid. The peptidoleukotrienes (leukotriene C4, leukotriene D4 and leukotriene E4) are powerful spasmogens, which have been implicated in inflammatory and allergic responses. Therefore, inhibition of 5-LOX is 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 Model
The efficacy of ECE for asthma was demonstrated in an allergen-induced murine asthma mouse model by Dr. Emil Chi, Chairman, Department of Histopathology, University of Washington.
The researchers tested an ECE product (KLS) in a mouse model of allergen-induced chronic lung inflammation and fibrosis. BALB/c mice, after intraperitoneal antigen sensitization on day 0 and day 14, were given weekly intranasal inhalations of antigen from day 14-60. The antigen-treated and challenged mice developed an extensive eosinophil and mononuclear cell inflammatory response, mucus cell hyperplasia and mucus occlusion of the airway.
KLS was found to be effective in reducing allergic reaction in inflammation. By feeding at a concentration of 5.4 mg/ml in the drinking water for 12 days, KLS reduced the airway mucus plugging, and sub-epithelial fibrosis in the antigen-sensitized / challenged mice. The reduced BAL fluid eosinophil indicated that KLS is effective in improving the asthmatic lung structures. No pathological alterations in the liver, kidney, spleen, or small intestine were found.
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 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 inflammatory mediators such as inflammatory prostaglandins, etc.
Coronary Artery Disease: 6-Week Clinical Trial
A clinical trial using ECE was conducted confirming its capacity to regenerate vascular endothelium and recover plasticity of blood vessels after 6 weeks of treatment by measuring flow-mediated dilation (FMD) & nitroglycerin-mediated dilation (NMD) of normal and CAD patients with narrowed coronary arteries by 50+%. FMD indicates nitric oxide (NO) releasing ability of endothelial cells to expand blood vessels by detecting shear stress caused by incoming blood flow (low FMD value can indicate endothelium damage).
After 6 weeks of treatment with ECE, clinical data showed that FMD, the endothelium-dependent dilation, was greatly enhanced in the CAD group, indicating its remarkable activity of inducing recovery of endothelial cells. NMD, the endothelium-independent dilation, which represents the vascular plasticity, also showed remarkable improvement in the CAD group, again supporting ECE’s ability to support restoration of vascular integrity by reversing atherosclerosis.
Cholesterol: 6-Week ClinicalTrial
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 mild 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 NO, which dilates blood vessels. Dramatic increases in blood flow were also found at this low dose.
Hypertension: 4-Week Animal Study
The remarkable effect of ECE on vasodilation was clearly demonstrated in renovascular clipping induced hypertensive rats. Renovascular clipping surgery is known to increase ACE activity via the renin-angiotensin-aldosterone system, which increased systolic blood pressure (SBP) from 140 to over 200 mm Hg after 4 weeks. Upon oral administration of phlorotannin (99.4%, 50 mg/kg) or enalapril (commercial hypotensive drug, 10 mg/kg) SBP dropped to as low as 160 and 140 mm Hg. Upon cessation of treatment, SBP increased again in both cases. Although ECE showed a similar pattern to the drugs, 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.
Angiotensin-converting enzyme (ACE), is responsible for conversion of angiotensin I to angiotensin II and degradation of bradykinin, and is a key component in the renin-angiotensin-aldosterone system. Angiotensin II regulates cellular proliferation, inflammation, and endothelial function, and is therefore important in the pathogenesis 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. One of the compounds found in ECE, THP-BE is comparable to the physiological vasodilative hormone bradykinin.
Plasmin (a 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 synthetic compounds Flufenamate and Chloramine T. One study on ECE compounds found a small but significant rise in prothrombin time and a fall in fibrinogen levels.
ERECTILE FUNCTION – ECE V. VIAGRA®
ECE can regenerate the vascular endothelium, the cells critical to the inner lining of the blood vessels. 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. They compared eight weeks of ECE use to Viagra®. They looked at orgasmic function (OF), intercourse satisfaction (IS), overall satisfaction (OS), and erectile function (EF). Over those eight weeks, ECE scored 87%, 74%, 62%, and 66%. Viagra® scored 27%, 44%, 39%, and 66%. No side effects were reported with ECE:
Population with 25+% Improvement in IIEF (International Index of Erectile Function) score was as high as 81%. Total IIEF score significantly increased from 29.1 ± 13.1 to 47.0 ± 14.5 with 62% of improvement. When the IIEF scores were grouped into five separate domains, mean IIEF scores at the 8th week were significantly greater than those at week 0 for all domains (all p<0.01). The degree of improvement was significant in the following order: OF (87%), IS (74%), EF (66%), and OS (62%). Scores on key questions (asking frequency of penetration and asking frequency of maintaining an erection after penetration), which directly indicate the ability to achieve and maintain an erection sufficient for sexual activity, were improved up to 74% and 77%, respectively (p<0.01).
It is very important to note that despite the marginal improvement in sexual desire (20%) that is of psychological nature, great improvements were reported in the domains directly related with erection that is of physical nature and dependent on normal vascular function of the penile artery.
Also noteworthy, was a significant increase in the orgasmic function score (87%), intercourse satisfaction (74%) and overall satisfaction (62%) as well as erectile function (66%) in comparison with the results for sildenafil reported by Marks, et al. (Marks, et al., 1999) (27%, 44%, 39% and 66%, respectively), which indicates that ECE significantly contributed to the normalization of the general vascular conditions around the sexual organ.
These results strongly indicate that the long-term administration of ECE significantly contributes to the neutralization of oxidative risk factors, thereby improving peripheral blood circulation around muscles and nerves involved in sexual function as well as the penile artery. No side effects were reported.
Vasodilation & Erectile Function
It has been reported that vasculogenic ED patients have elevated levels of angiotensin II for the duration of the erection process. The demonstrated action of ECE on ACE and resulting vasodilation is thought to play an important role in inducing successful erectile function.
Long-Term Improvement Via Vascular Protection
As discussed, ECE phlorotanins have potent antioxidant and anti-inflammatory effects. Together with ECE’s ACE inhibitory activity, which is also beneficial to vascular homeostasis, these activities, upon long-term oral administration, may all contribute to supporting a healthy vascular system, including the penile artery.
Diacylglycerol acetyl transferase (DGAT) is the enzyme involved in the final step of triglyceride synthesis. Triglycerides are circulating fat bodies that ultimately wind up in the fat cells, and are almost always elevated in diabetes. They also have emerged as a major risk factor in vascular disease.
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 & Cardiovascular Disease
As discussed, ECE contains an optimal combination of natural compounds capable of suppressing triglyceride synthesis, while promoting cholesterol removal and cardiovascular protection. ECE provides additional cardiovascular protection for obese patients prone to CVD and CHD through lowering LDL cholesterol and scavenging free radicals.
DGAT Inhibition & Obesity
DGAT inhibition has recently been recognized as a novel and safe target for the treatment of obesity. DGAT is involved in intestinal fat absorption, lipoprotein assembly, regulation of plasma TG concentration, fat storage in adipocytes, and energy metabolism in muscle. DGAT knockout mice have been shown to have obesity resistance with a high-fat diet, the mechanism of which was confirmed to be through energy expenditure.
Aldose Reductase Inhibition
When blood sugar levels become elevated, aldose reductase is the enzyme that 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 NF-kappaB inflammation in the pancreas. A recent Harvard (Joslin School of Diabetes) mouse study directly implicates excessive fat deposition in the mouse pancreas as turning on the NF-kappaB inflammation pathway, resulting in full-blown type II diabetes and insulin insensitivity in the mice.
ECE is manufactured from edible algae through food-compatible processes. Tens of thousands of people throughout the world have experienced ECE in various forms of product 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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- Ruehl ML, Orozco JA, Stoker MB, Mcdonagh PF, Coull BM, Ritter LS. Protective Effects Of Inhibiting Both Blood And Vascular Selectins After Stroke And Reperfusion. Neurol Res. 2002 Apr;24(3):226-32.
- Sheehan, D.C., B.B. Hrapchak. 1980. Connective Tissue/Muscle Fiber Stains. In Theory And Practice Of Histotechnology. Battelle Press, Columbus, OH. 180-201.
- Shibata, T., Fujimoto, K., Nagayama, K., Yamaguchi, K., Nakamura, T. Inhibitory Activity Of Brown Algal Phlorotannins Against Hyaluronidase. Int. J. Food Sci. Tech. 37: 703-709 (2002)
- Shibata, T., Nagayama, K., Tanaka, R., Yamaguchi, K., Nakamura, T. Inhibitory Effects Of Brown Algal Phlorotannins On Secretory Phospholipase A2S, Lipoxygenases And Cycloxygenases. J. Appl. Phycol. 15: 61-66 (2003)
- Shin HC, Hwang HJ, Kang KJ, Lee BH. An antioxidative and antiinflammatory agent for potential treatment of osteoarthritis from Ecklonia cava. Arch Pharm Res. 2006 Feb;29(2):165-71.
- Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese RV Jr. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet. 2000 May;25(1):87-90.
- Temann UA, Prasad B, Gallup MW, Basbaum C, Ho SB, Flavell RA, Rankin JA. A novel role for murine IL-4 in vivo: induction of MUC5AC gene expression and mucin hypersecretion. Am J Respir Cell Mol Biol. 1997 Apr;16(4):471-8.
- Tsukada H, Nishiyama S, Fukumoto D, Ohba H, Sato K, Kakiuchi T. Effects of acute acetylcholinesterase inhibition on the cerebral cholinergic neuronal system and cognitive function: Functional imaging of the conscious monkey brain using animal PET in combination with microdialysis. Synapse. 2004 Apr;52(1):1-10.
- Uhm CS, Kim KB, Lim JH, Pee DH, Kim YH, Kim H, Eun BL, Tockgo YC. Effective treatment with fucoidin for perinatal hypoxic-ischemic encephalopathy in rats. Neurosci Lett. 2003 Dec 15;353(1):21-4.
- Virag R, Floresco J, Richard C. Impairment Of Shear-Stress-Mediated Vasodilation Of Cavernous Arteries In Erectile Dysfunction. Int J Impot Res. 2004 Jan;16(1):39-42
- Wills-Karp, M., J. Luyimbazi, X. Xu, B. Schofield, T.Y. Neben, C.L. Karp, D.D. Donaldson. 1998. Interleukin-13: Central Mediator Of Allergic Asthma. Science 282:2258-2261.
- Zhu, Z., R.J. Homer, Z. Wang, Q. Chen, G.P. Geba, J. Wang, Y. Zhang, J.A. Elias. 1999. Pulmonary Expression Of Interleukin-13 Causes Inflammation, Mucus Hypersecretion, Subepithelial Fibrosis, Physiologic Abnormalities, And Eotaxin Production. J. Clin. Invest.
Testing for Optimal Wellness
Four Tests Lay the Foundation for An Effective Supplement Regimen
Individuals who want to make a stronger commitment to enhancing their health in 2008 as well as newcomers to the healthy aging supplement field, can dramatically improve the success of their regimen by first taking a series of tests. Beginning a supplement regimen without taking the tests mentioned below is a little like trying to navigate the streets of an unfamiliar city without a road map. I always tell my patients “Tests Don’t Guess.”
In this article, I will explain the different testing options available and how individuals can use the results to either build a new supplement program or refine an existing supplement regimen to enhance overall health.
Organic Acid Testing
One of the most underutilized tests, organic acid testing is a crucial step in determining exactly which vitamins and minerals a person’s body needs. Perhaps the reason why this test has been underutilized is simply because its relevance to personal health is not understood. Yet, it is one of the easiest ways to determine which supplements are right for each individual. It truly takes the guesswork out of creating the foundation for a personal customized supplement program. I tell my patients it provides a glimpse of their “own biochemical thumbprint.” Anyone who asks the questions “Where do I begin?” or “Now that I’m taking the basic supplements, what other nutrients do I need to improve my overall health?” will find the answers they’re looking for in the results of the organic acid testing.
We are all unique biochemical creatures. Therefore, each of us has different supplement needs. Some individuals may be deficient in vitamin E while others need extra coenzyme Q10, regardless of apparent cardiac issues or concerns. Everyone has inherent strengths and weaknesses within their personal biochemistry that determines how much of a particular nutrient—or even if that particular nutrient—will be of benefit to their bodies. Organic acid testing can help pinpoint the vitamin, mineral, and amino acid deficiencies present in each patient. The lack of proper nutritional sufficiency relative to your own “biochemical individuality” will play a pivotal role when it comes to expressing genetic strengths or weaknesses.
Organic acid tests are important for both those seeking to fine tune or increase a supplement program’s effectiveness and anyone beginning a supplement regimen. The clinical benefits seen when the body’s unique needs are addressed can be the difference between modest clinical results versus a significant metamorphosis.
Organic acids are key compounds of many biochemical pathways. Organic acid testing provides critical insights into the functioning of the Krebs cycle in the mitochondria. The Krebs cycle is comprised of nine organic acids and eight enzymes and is the main way that all dietary fuel sources—including carbohydrates, proteins, and fats—are metabolized (Figure 1). Because the Krebs cycle provides the energy required for the body to function, any disruption in its flow can be disastrous to health.
Abnormal organic acid metabolism, therefore, can indicate that an individual is deficient in a number of nutrients or is simply not using those nutrients effectively.
Supplementation of specific vitamins and nutrients can help balance altered and imbalanced metabolic pathways, but it’s impossible to know which nutrients to give which patients unless an organic acid test is completed
Organic acid tests can now be done in the convenience of your home. Easily collected urine samples are sent to an internationally recognized and nationally certified laboratory. By taking this test, you can have a better understanding of your own unique health needs.1-5
Salivary Hormone Testing
Another important way to get serious about building a supplement regimen tailored to an individual’s own needs is salivary hormone testing.
There are several ways to test hormones (saliva, serum and urine), but the state-of-the-art testing is through saliva. This is because it measures only the active portions of hormones and it is these portions that determine how a patient feels.
The five hormones monitored through saliva testing are testosterone, progesterone, estrogen (estradiol), cortisol and DHEA. As we age, levels of these hormones often become imbalanced. Using a saliva test as a blueprint for proper supplementation with these hormones can make a dramatic difference in patients’ health.
Testosterone is important for both men and women. In males, the decline in testosterone commonly referred to as andropause often begins in the early 30s and eventually hits a crescendo when symptoms are unmistakable in the 50s and 60s. A progressive decline in testosterone in men starting at age 30 is well documented with a free testosterone decline of 1 percent per year. After age 60, 25 percent of men are clinically overtly hypogonadal (low in testosterone). Overt testosterone deficiency occurs in about 24 percent of men aged 50-60 years and 40 percent in men aged 60-80.6 Yet, subclinically, low testosterone levels are likely prevalent in nearly double these very conservative estimates. Furthermore, SHBG (sex hormone binding globulin) increases with age, binding up more free testosterone.
Low testosterone levels in men are linked to low energy, decreased libido, decreased concentration, insomnia, night sweats, depression, infertility and, surprisingly, even hot flashes.
Balanced testosterone levels are important in females as well, with lower than normal levels associated with a reduced sex drive.7 Testosterone is considered the “desire hormone” due to its ability to enhance libido. Women, however, often tend to have an excess of prolactin, the “anti-desire” hormone.8 In addition, with age, and especially after menopause, testosterone levels in women decline.7
Salivary hormone tests also are used to measure levels of estradiol, one of the main forms of estrogen found in the female body. Levels of this hormone drop dramatically during perimenopause and menopause and its deficiency is associated with vaginal dryness, hot flashes, and the many other symptoms of menopause. It is also thought that when estrogen levels plummet during menopause, it increases the risk of cardiovascular disease and high cholesterol. Excessively high estrogen levels, on the other hand, have been associated with an increased risk of breast cancer.
In males, estrogen levels are important to monitor since testosterone often can be converted into excess amounts of estrogen. Estrogen also tends to decrease testosterone production, creating a vicious circle.
Progesterone is another important hormone to have tested. During premenopause and menopause, the drop in progesterone levels is associated with estrogen dominance. Even before premenopause a progesterone deficiency can cause PMS, breast tenderness, and a host of other symptoms. Furthermore, groundbreaking work by Dr. John Lee noted that prostate problems in men can be associated with low progesterone levels.9
Cortisol and DHEA are important because of their role in adrenal health. Cortisol levels that are too low or too high can be a sign that a patient is suffering from adrenal exhaustion, a common cause of fatigue, weight gain and many other health problems. Imbalanced DHEA levels also can be a sign of exhausted adrenals. Like many other hormones, DHEA, which is associated with skin elasticity, well being, and cardiovascular health, drops dramatically with age. In some cases, however, individuals with impaired adrenals can produce excessive amounts.
Salivary testing can help a patient determine which hormonal supplements are needed to counteract any detected imbalances. Progesterone cream can be used in both females and males who test low for this important hormone. BioDIM® and Extension Resveratrol can be used in males who are converting testosterone into excess estrogen. Adaptogens and special cortisol-lowering herbs known as Relora® and Sensoril™ can be used in individuals with adrenal dysfunction while DHEA supplementation can be used to replenish the body’s low supplies of this hormone. Women who have lower than normal testosterone levels can use DHEA to raise testosterone levels, since women very efficiently convert DHEA to testosterone. Many males with low testosterone find it helpful to either increase their levels pharmaceutically or use a combination of the botanicals Eurycoma longifolia jack extract, stinging nettle, and Luteolin. Finally, women with low estrogen levels can seek out bio-identical hormone replacement (BHRT).
Retesting after initiating a hormonal support regimen ensures that individuals have achieved the proper hormonal balance and that excess estrogen levels are not created as a result of therapy.
Food Allergy Testing
Clinically, one of the most important tools I use to unearth hidden factors affecting patients’ health is Food Allergy Testing. This approach ensures that individuals can understand how their daily diet may be harming their health.
Food allergens can be broken down into two categories: immediate and delayed. It is the delayed or hidden food allergens that silently erode away ones health, frequently going undetected since the response is not immediate but rather delayed up to 72 hours, long after the offending food(s) were ingested. Thus, identifying and controlling food sensitivities is essential.
Hippocrates “The Father of Western Medicine” stated in 400 BC, “May Food be your Medicine and Medicine be your Food.” The problem that I discover with my patients is that even supposedly healthy foods such as garlic, broccoli, grapes, and fish can be sources of extremely detrimental health signs and symptoms.
ELISA immunoassay testing for delayed food allergies helps identify delayed IgG immunoglobulin allergens. This technology is used worldwide and has now been applied to home test kits that can identify 96 different food reactions ranging from dairy, wheat, corn, fish, vegetables, fruits, sugar cane, numerous nuts, eggs and other commonly consumed foods. A simple fingerstick done at home, much like that done by diabetics, makes gaining insight into ones own personal delayed food allergies both affordable and convenient. Once collected, the sample is sent from the home to a CLIA (nationally licensed) laboratory. Within a couple of weeks, results are sent back directly to the patient’s home. These results indicate low, moderate or high reactions to different foods.
The food allergy test will help individuals avoid the foods they are allergic to and will produce dramatic results in improving overall health. After understanding ones food sensitivities, Digestive Enzymes, a good probiotic supplement that includes Lactobacillus GG and Lectin Lock™ can be added to a supplement regimen to compensate for those times when people are exposed to their most common food allergens.
Anyone who is on immunosuppressant drugs, such as corticosteroids, should be aware that these drugs can alter the results of food allergy testing.
Iodine Sufficiency Test
Thyroid disorders are becoming almost epidemic in this country. Hypothyroidism is one of the most common disorders I see in my patients, who often don’t realize that their weight gain, moodiness, thinning hair and other symptoms are caused by hypothyroidism.
Noted iodine expert Dr. Guy Abraham has established a link between iodine deficiency and both hypothyroidism and hyperthyroidism. Because so many dietary components—such as the bromide found in bread and baked goods and fluoride in drinking water—compete with iodine absorption, iodine deficiency has become all too common.10
A user-friendly, oral loading test can detect iodine deficiencies. Testing involves collecting urine immediately upon arising in the morning to use in what’s called a spot test. Then, 50 mg. of potassium iodide and iodine (included in the test kit) is ingested. Urine is collected throughout the day until the first urine of the next morning. The samples, including the baseline spot test, are shipped to the lab.
If the body has sufficient iodine, at least 90 percent will be excreted in the urine. In iodine deficiency, however, the body will hold on to some of the iodine to compensate for the deficiency. The more iodine that remains in the body, the more a person is iodine deficient and needs to begin supplementation.
If the tests indicate an iodine deficiency, patients often begin supplementing with iodine, such as found in Iodoral®, a combination of iodide and iodine. Testing should be repeated every three to four months to monitor proper iodine doses. Working closely with your personal healthcare provider is always an important part of refining your health program.
Organic acid, salivary hormone, food allergy, and iodine sufficiency testing are the best way to build a supplement program that is specific for an individual’s needs. In my practice, I have noted dramatic improvement in the overall quality of my patients’ health after they have begun a supplement regimen based on these tests. Not using this important tool is like stumbling around in the dark when all one needs to do is turn on the flashlight that’s already in his or her hand. For individuals who want to get serious about overall wellness in 2008, taking each of these tests is a crucial step toward good health.
1. Fu X, Iga M, Kimura M, Yamaguchi S. Simplified screening for organic academia using GC/MS and dried urine filter paper: a study on neonatal mass screening. Early Human Development. 2000;58:41-55.
2. Fu X, Kimura A, Iga M, Yamaguchi S. Gas chromatographicmass spectrometric screening for organic acidemias using dried filter paper: determination of alpha-ketoacids. J Chromatography B Biomed Science Applications. 2001;758:87-94.
3. Greter J, Jacobson C. Urinary organic acids: isolation and quantification for routine metabolic screening. Clin. Chem. 1987;33:473-480.
4. Sweetman L. Organic acid analysis. Techniques in diagnostic human biochemical genetics. A laboratory manual. Wiley- Liss, New York, 1991.
5. Tanaka K, et al. Gas chromatographic method of analysis for urinary organic acids. I. retention indices of 155 metabolically important compounds. Clin. Chem. 1980;26:1839-1846.
6. Morgentaler A, Bruning CO 3rd, DeWolf WC. Occult prostate cancer in men with low serum testosterone levels. JAMA. 1996 Dec 18;276(23):1904-1906.
7. Kingsberg S, Shifren J, Wekselman K, Rodenberg C, Koochaki P, Derogatis L. Evaluation of the clinical relevance of benefits associated with transdermal testosterone treatment in postmenopausal women with hypoactive sexual desire disorder. J Sex Med. 2007 Jul;4(4 Pt 1):1001-8.
8. Hirch E. [Libido disorders] [Article in French]. Rev Med Brux. 2007 Sep;28(4):368-73.
9. Lee, J. Prostate disease and hormones. The John R. Lee, M.D. Medical Letter Feb. 2002.
10. Abraham G. Iodine: The Universal Nutrient. Vitamin Research News. October 2005.
Selective immunodeficiency, exposure to broad-spectrum antibiotics, and consumption of sugars, individually or in combination, can stimulate an overgrowth of intestinal yeast or bacteria, normally present in much lower quantities. Once any abnormalities are detected there are a variety of treatment options. Improvements that have been reported to us during and after treatment include better eye contact, improved language, less self-abusive behavior, less hyperactivity, better sleeping habits and less stimming. These organisms and their metabolites can produce or exacerbate symptoms in many conditions.
The organic acid test evaluates all of the well-defined inborn errors of metabolism that can be detected with this technology (called GC/MS) such as PKU, maple-syrup urine disease, and many others. In addition, we check for many other abnormalities such as vitamin deficiencies and abnormal metabolism of catecholamines, dopamine, and serotonin. We currently quantitate 65 substances, but also evaluate other substances that are not quantitated. Some of the other biochemical abnormalities common in autism include elevated uracil and elevated glutaric acid.
- Yeast metabolites
- Bacteria metabolites
- Nutritional deficiencies
- Antioxidant deficiencies
- Inborn errors of metabolism
- Amino acid abnormalities
- Fatty acid abnormalities
- Exposure to solvent toxins
- Deficiencies of B vitamins or vitamin C
- Indications of diabetic conditions
- Krebs cycle metabolites
- Clostridia overgrowth
- 65 important compounds
In which conditions is the test useful?
|AD(H)D||Chronic Fatigue Syndrome||Endometriosis|
The test kit is free; please see our price list for current processing charges including courier charges (for US residents) and a full report, along with professional consultation concerning test results.
Depending on test results, suggestions can include:
- Diet modification
- Diet supplementation, primarily with nutrients which increase the quantity of beneficial bacteria (e.g. lactobaccilli) in the GI tract
- Oral antifungal or antibacterial (anaerobic) medications
- Vitamins and Antioxidants
- Reduction of exposure to toxic chemicals
- Measures 65 important compounds for overall health
- Focuses on detecting yeast and bacteria byproducts that have been implicated in many disorders
- Requires a first morning urine sample only
- Consultation on results is included with each test from The Great Plains Laboratory
- Test with the experts – The Great Plains Laboratory holds one patent (*) on this test and two others pending.
* Certain uses of the compounds arabinose, citramalic, tartaric, 3-oxoglutaric, carboxycitric, 3,4-dihydroxyphenylpropionic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropionic acid in their application to autism in the organic acid test and microbial organic acid test are protected by USA patent 5,686,311 granted November 11, 1997.
What is the organic acid test for, and how can it help?
In Dr. Shaw’s work, he noticed that people with autism and other conditions (such as attention deficit disorder and fibromyalgia) frequently had overgrowths of yeast and bacteria in the gastrointestinal tract, due to a high-sugar diet and antibiotic overuse. This led Dr. Shaw, now Director of The Great Plains laboratory, to devise a urine test to detect such disorders–an organic acid test which measures nearly 70 different biochemical compounds.
Both children and adults who have taken the test and sought appropriate treatments have enjoyed marked improvements in condition as a result.
Do I have to obtain a physician’s approval to get the urine sample tested?
Yes. A medical practitioner who is licensed to order urine testing in your state must approve the test order. Regulations vary from state to state so an approved medical practitioner could be a medical doctor (MD), osteopath (DO), nurse practitioner, chiropractor (DC) or naturopath (ND).
Why should I get the organic acid test? Why don’t I just start the antifungal treatment?
Some children with autism don’t have the yeast problem, but have an overgrowth of the Clostridia. Treating these children with an antifungal could make the bacteria problem even worse. Also, if your child has the yeast problem, it will likely require major changes in diet (for the child and the family) along with drug therapy for six months or longer. It will be very difficult to make this type of commitment if you are nor even sure if your child has the yeast problem.
Also, your child could have a yeast overgrowth with a drug-resistant yeast and if you don’t do the testing beforehand, it would be difficult to know what was happening. If the problem is severe, the yeast die-off reaction may be more severe and you may want to take additional steps to control the yeast before using antifungals. Additionally, it may be very difficult to get your doctor’s cooperation for the prescriptions and insurance reimbursement if there is no evidence that the yeast problem even exists.
How often should I get my child retested?
As a general rule, every three months is satisfactory. However, retesting should be done sooner if the child does not respond favorably by the end of one month of antifungal therapy, since the yeast or bacteria might be resistant to the drugs used for treatment.
My child is currently taking antibiotics now. Should I wait until after antibiotics treatment until I get tested?
An assumption is frequently made that if the child has a significant yeast overgrowth of the intestine while on antibiotics, the yeast overgrowth will disappear when the antibiotics are stopped.
However, this is not necessarily the case and the yeast overgrowth may even become worse–especially if the person is on a high-sugar, high carbohydrate diet. There is no evidence that the yeast overgrowth will spontaneously disappear. Furthermore, the yeast overgrowth may be suppressing the immune system, preventing your child from recovering from the infection.
The sooner the yeast problem is controlled, the sooner the vicious cycle of antibiotics and frequent infections will be broken.
Will drugs or nutritional supplements interfere in the organic acid test?
No, there is no interference from any known drug or supplement. However, if antifungal supplements or drugs are taken before the test, you will probably get a lower value for the yeast byproducts. We advise you to get the test first so that you will know what the starting point is.
I already had the urine organic acid test done earlier by another lab. Can’t I get the information from the earlier test?
No. No other laboratory routinely analyzes the same compounds as this laboratory. Most test for the inborn errors of metabolism and nothing more.
I have an HMO and they have to send the test to a certain lab. Is that OK?
No. No other laboratory routinely analyzes the same compounds as this laboratory (including Labcorp, SmithKline, or Mayo Medical laboratories).
If you do not specify our laboratory, your child’s urine will be sent to one of the large reference labs which cannot accurately evaluate your child’s condition. Most test for the inborn errors of metabolism and that’s all.
Are there any other reasons that I should choose the Great Plains Lab to do the organic acid testing?
Dr. William Shaw, Director of the Great Plains Laboratory, is a recognized expert in the identification of practical, biomedical treatments for autism (as well as many other disorders). His work and the testing procedure that he developed have helped many children and adults with autism and other conditions see dramatic improvements and experience an enhanced quality of life–all based on seeking appropriate therapies using the information gained from the test.
Dr. Shaw has also authored many books and provided other materials to help you better understand the medical treatments and how to use this information to help people with autism and other conditions.