Real Stories

• “.... A good friend told me about GLUCO-Z™. Reluctantly, having tried other products in the past that did nothing special, I decided to give the stuff a go. You would not think that something would work this quickly, but it has and am I thrilled....”Alan Braunstein, Seattle, WA
• “My husband Hector has type 2 and I am diagnosed pre-diabetic. Since starting GLUCO-Z™, our blood sugars have been much improved. Hector no longer gets the shakes and I am losing weight and am not getting hot flashes like I normally do. We are really happy with GLUCO-Z™. It really works in more ways than we had hoped!.”Raven Skye, Santa Barbara, CA

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Development of Gluco-Z

The chemical constituents, which are known to affect the intestinal zinc absorption mechanisms are numerous; e.g. prostaglandins, citric acid, picolinic acid, metallothionein metabolites, cystein-rich intestinal zinc-binding protein, L-histidine, arachidonic acid, and cyclo-hispro. These zinc absorption-stimulating agents are most richly packed into the prostate among all other organ tissues, and diabetic conditions of rats dramatically improved by the treatment with prostate extract supplemented with zinc. In collaboration with Dr. Mark J. Rosenthal, MD, MD, FACN, Professors of Medicine at UCLA Medical School, specialized in Aging, Diabetes, and Digestive disorders, Dr. M.K. Song demonstrated in 1998 that "Prostate powder supplemented with zinc, transport and other agents" (GLUCO-Z™) was effective in lowering blood sugar and metabolizing excess insulin . Prostate powder and zinc used in other tested compounds, however did not produce results. Formulation of the compound with transport, absorption, and accelerating agents generated the most efficacious results in managing glucose and insulin levels in patients studied.

 

Many of diabetic patients showed marked improvement of medical conditions such as oral glucose tolerance, hemoglobin A1c levels, and fasting blood glucose levels. These criteria are all indicatives of improving diabetic conditions of patients. Some patients were able to reduce or stop taking oral agents. GLUCO-Z™ also helped many patients with altered zinc metabolism. GLUCO-Z™ may not necessarily help every disease, however, some patients with certain diseases can have health improvements by oral intake of GLUCO-Z™. Zinc malabsorption syndromes occur in variety of disease states in such as diabetes mellitus, cancer skin disorders, acrodermatits enteropathica, sickle cells anemia arthritis etc. Enhancement of zinc metabolism is essential for prevention and healing of zinc malabsorption syndromes. Animal prostate contains highest amounts of zinc and zinc metabolism enhancing agents among all other organ tissues. Since all of the active ingredients in the
GLUCO-Z™ are natural origin, it is not possible that that GLUCO-Z™ expresses any adverse side effects on human health.

 

The highest amounts of active substances are present in animal prostate, more than in all other organ tissues. All of these constituents are involved in the regulation of intestinal zinc absorption. The beneficial effects of prostate substances on patients with diabetes and other zinc malabsorption syndromes are apparently due to their ability to stimulate intestinal zinc absorption. The active ingredients in the prostate are: zinc, cyclo (his-pro) (CHP), arachidonic acid (AA) and L-histidine. CHP is a thyrotrophin-releasing hormone (TRH) metabolite, which is synthesized in the cell. It is present in almost all of the body organ cells and in protein food sources such as milk, soybean protein etc. Its biological role is not clearly established, but no side effects when taken minute amounts (1-10 mg/day) of CHP are expected. Since it is an endogenous constituent and since CHP is an only dipeptide, it is not considered a toxic chemical even if taken in gram levels per day. Arachidonic acid and poly or monounsaturated fatty acids are already known food sources and the amounts provided to human subjects by GLUCO-Z™ are far less than toxic levels. Thus, prostate constituents are not at all harmful to humans when taken in amounts of 0.3 to 1.2g prostate powder per day. Zinc is known as an essential dietary food with an RDA of 15 mg/day. Chromium is also considered as essential trace element for maintaining health and managing blood sugar. Flax seed oil is a normal dietary food, which contains unsaturated fatty acids including arachidonic acid. Lecithin and inositol are biologically essential bio-chemicals. Thus, all the chemicals and active ingredients listed in the GLUCO-Z™ are food and food ingredients. The amounts of these constituents in the GLUCO-Z™ are again far less than toxic levels. Therefore, no known health hazardous constituents are included in the
GLUCO-Z™ gel capsule.

 

RESEARCH BACKGROUND AND DATA

• Importance of zinc in diabetes: Insulin resistance is a major characteristic of Type II diabetes (26), mainly due to a defective glucose transporter translocation (27). Insulin initiates glucose transport by binding to the -subunit of the insulin receptor, which in turn phosphorylates the receptor -subunit and activates its tyrosine kinase activity. This activated -subunit tyrosine kinase signals genes to translocate the insulin-sensitive glucose transporters from intracellular pools to plasma membranes or to express glucose transporter gene via several steps of signal transduction mechanism (28). Zinc has been reported to enhance tyrosine kinase activity of the insulin receptor and glucose transporter translocation in animal cells (29,30), and zinc deficiency decreased the insulin content in pancreas (31), physiological potency of insulin (32) and glucose tolerance (33,34), and increased the rate of insulin degradation (33). It has been reported that plasma zinc levels of diabetic animals and humans are low (35-38), partly due to decreased intestinal zinc absorption and hyperzincuria (18,39-44). Thus, inadequate zinc nutriture of organ cells may contribute to the clinical manifestations of diabetes.
  
  
• Mineral metabolism in diabetes: Numerous publications indicate that mineral absorption is decreased in diabetic animals and humans while the absorption of other nutrients such as amino acids and carbohydrates are either increased or not changed (44-46). Magnesium absorption is decreased in diabetic rats (45), and supplementation of magnesium improved diabetes manifestation (47). Chromium deficiency is also related to diabetes manifestation and supplementation improved glucose tolerance of diabetic patients (48). Thus, it appears that altered mineral metabolism is one of the major causes of clinical manifestations of diabetes. However, a defect in zinc metabolism most critically affects clinical manifestations of diabetes since zinc is involved in insulin stabilization (49), glucose transporter translocation from the cytosolic pool to cell membranes (29), and gene expression (50). Zinc is also an integral part of more than 50% of the total metallo-enzymes and biologically active proteins; including glycolysis involved metalloenzymes (51).
  
  
• Prostaglandin metabolism in diabetes: Prostaglandin (PG) s and arachidonic acid (AA) play an important role in the regulation of insulin release and participate in numerous glucose metabolic activities (52-54). PGE2 synthesis in kidneys is reduced in insulin dependent diabetic rats (55), and in rat embryos exposed to a high glucose in vitro or diabetes in vivo (56). PGI2 synthesis in vascular tissue of diabetic animals and humans was reduced (57-59). Insulin treatment normalized PGI2 release from the abdominal aorta (60). Our previous studies demonstrated that PGs are important intestinal zinc absorption regulators (6,7). PGs and essential fatty acids are capable of chelating zinc and regulate intestinal zinc absorption and secretion (6,7,13,61,62). The addition of arachidonic acid (AA) to the bathing media of intestinal segments did not enhance zinc transport from mucosa to serosa but increased zinc uptake capacity (from mucosa to intestinal cells) of the segments (39). Furthermore, dietary feeding AA plus zinc significantly lowered blood glucose levels and water consumption in diabetic rats (14, 18). Other studies (63) demonstrated that copper deficiency, which is often caused by excess zinc intake, and the addition of AA increased insulin secretion in isolated pancreatic islet cells. Thus, zinc and PG metabolism may synergistically affect clinical manifestations of diabetes (31-34,57-60).
  
  
• Cyclo (his-pro) and diabetes: CHP, which is structurally capable of chelating zinc and stimulates intestinal zinc absorption and zinc uptake by muscle tissues, is a metabolite of thyrotrophin releasing hormone (TRH). Plasma levels of TRH in both animal and human diabetics are significantly lower than those of control groups (64-66). Infusion of TRH increased insulin secretion (67), but TRH levels were not affected by hyperglycemia (68). Pancreatic TRH level decreased after streptozotocin injections (69). TRH stimulates pancreatic insulin secretion, but does not directly stimulate glucose utilization by muscle or adipocyte (70). In contrast to TRH, elevated blood glucose level increased peripheral CHP concentration (71), but oral glucose is more effective than intravenously infused glucose. Striatal CHP levels increased after the induction of hyperglycemia by streptozotocin injection, and reversed when insulin was given to lower glucose levels. CHP concentration in the brain of obese mice is also elevated compared to that in lean normal mice (12). These findings (21,64-71) are confusing, but they demonstrated that CHP metabolism is clearly related to diabetes. CHP concentration in the pancreatic islets is highest among all other tissues (22). It is present mainly in the pancreatic -cells and its secretion is similarly affected with glucagon (72). However, CHP infusion decreased both insulin and glucagon secretion by pancreatic islets (73), implying that both CHP and glucagon secretions are similarly regulated by a feedback regulatory mechanism. In contrast to this finding, Mizuma et al (74) suggested that CHP actually increases insulin excursion mediated by decreased hepatic insulin clearance. The fact that oral intake of CHP plus zinc greatly improved clinical manifestations of diabetic rats (14,18), clearly indicates that CHP may be involved in the regulation of insulin metabolism. Synthesis of TRH (75) as well as PGs (76) requires zinc, and CHP improved diabetes probably by stimulating intestinal zinc absorption and zinc uptake rate of muscle tissues.
  
  
• Optimal Concentrations of CHP and AA in controlling diabetes: Both body weight and water consumption rates of diabetic rats fed CHP plus zinc most favorably improved diabetes compared to other treatments. The rat group given all five chemicals showed the highest body growth rate for the entire period of 30 day experiment, but water consumption was the least in the rats given CHP (14), exhibiting the greatest improvement of diabetic symptom. The optimal concentration of CHP for the improvement of diabetes was 300 g/kg/day, and 11 mg/kg/day for AA. L-his (0.5 mg/kg) in the drinking water also improved clinical manifestations of diabetes.
  
  
• Prostate and diabetes: Prostaglandins (6,7), testosterone (20), Arachidonic acid (AA) (13), L-histidine (12,77), citric acid (8), picolinic acid (78), amino acids (9), metallothionein (10), cysteine rich intestinal zinc-binding protein (11) and CHP (14) have been suggested as intestinal zinc absorption stimulator(s). Although these constituents may participate in the regulation of intestinal zinc absorption mechanisms, none of these constituents have been identified as the key intestinal zinc absorption regulator. Testosterone levels in diabetic animals and humans are low (79,80). Castration, which eliminates testosterone, has been reported to worsen diabetic manifestation in mice (81) and humans (82). Citric acid chelates zinc and makes it available for intestinal absorption (8), and it is found in very high amounts chelated with zinc in the prostate (15). Low protein intake is associated with low zinc levels in the intestine and liver (9). Dietary feeding of CHP (a dipeptide) greatly reduced blood glucose levels, food intake and water consumption by streptozotocin-induced diabetic rats (18), and prostate is the tissue which contains very high amount of CHP (16). Subsequently we found that the optimal dosage of CHP for lowering blood glucose concentration of diabetic rats was 0.3 mg/kg/day and AA 11.0 mg/kg/day respectively (14). These facts (6-8,13,14,20) suggest that all of these chemicals, which are found in very high amounts in the prostate, may synergistically affect intestinal zinc absorption and improve clinical manifestations of diabetes; thus prostate contains the highest amount of zinc among all mammalian tissues (83). Therefore, we examined the effects of prostate extract (PE) on the intestinal zinc absorption and on the clinical manifestations of streptozotocin-induced diabetic rats (18). Oral intake of PE very significantly increased intestinal zinc absorption, and lowered blood glucose levels and water consumption in diabetic rats given PE plus zinc, CHP plus zinc or PE only compared to those given distilled water. Furthermore, dietary feeding of PE plus zinc for 3 weeks greatly reduced fasting blood glucose and insulin levels, and improved oral glucose tolerance (14). These results suggest that zinc, CHP and AA in the prostate may synergistically influence zinc and glucose metabolism, and insulin sensitivity.
  
  

In order to verify the effects of prostate constituents on the rats to those on the human subjects, we determined effects of prostate powder plus zinc on human diabetes (19, Table 1). Diabetic patients who took gel capsules containing 200 mg prostate powder (not PE) and 20 mg zinc with other agents (GLUCO-Z) two to four times a day for three months exhibited a significantly improved oral glucose tolerance and decreased HbA1c levels. Thus, it appears that prostate substance plus zinc and additional agents is effective for the improvement of clinical manifestation of diabetes in humans. The initial USA patent using prostate extract supplemented with zinc and other agents for the treatment of diabetic patients (patent # 5,411,748) was granted in May 1995 and the USA patent for the use of chemical combinations of zinc, arachidonic acid, CHP, L-Histidine and other agents for treating patients with diabetes in November 1998 (patent # 5,834,032). These patents were granted based on the facts that oral intake of these compounds greatly improved oral glucose tolerance, and lowered HbA1c and fasting blood glucose levels and other diabetic symptoms in both animal and human subjects (14,18,19, Table 1). Thus, experimental results with both rats and human subjects described in our previous publications (1,2) clearly demonstrate that GLUCO-Z intake is no doubt a beneficial treatment for human diabetes.

 

Mechanisms affecting Type 2 Diabetes by GLUCO-Z

GLUCO-Z is primarily prepared for the treatment and prevention of diabetes. GLUCO-Z™ contains prostaglandin precursor arachidoninc acid and gamma-linoleic acid. Prostaglandins activate peroxisome prolieferator Activated Receptor –gamma (86-88), which is a nuclear receptor stimulating gene expression for the synthesis of Glucose transporter -4 (GLUT-4), which is involved in enhancing muscle and fat cell glucose uptake. Thus prostaglandins E2, PGI2 and PGJ2 are beneficial for the treatment of diabetes (89-92), but TXB2 and PGF2 are harmful for the diabetes (89, 93) This activity is very similar to Glithazone products such as Avandia and Actos which are drugs available for the prevention and treatment of human diabetes. However, these drugs pose moderate to serious side effects including edema, cardiac hypertrophy, liver abnormalities, and nausea. GLUCO-Z does not pose any side effects but improved many of the blood chemistry abnormalities due to diabetes including lipid metabolism (19).

 

Table 1. Improved OGTT and Hemoglobin A1C levels in Type II Diabetic Patients Given GLUCO-Z™ Capsules for Three Months

Type of Medicine	Number of Patients		OGTT (mg G/dl/hr)	Hemoglobin A1C Values	Fasting Glucose Levels (mg/dl)
GLUCO-Z™	N=15	Pre-treatment	120.1 + 10.3	12.7 + 0.9	217.7 + 31.8
		Post-treatment	101.3 + 10.5	9.7 + 0.6	179.4 + 10.1
		Difference	18.8 + 6.3**	3.1 + 0.8**	38.3 + 31.2
Placebo	N=19	Pre-treatment	122.5 + 8.9	10.3 + 0.8	176.4 + 11.3
		Post-treatment	124.0 + 8.2	9.8 + 0.5	163.5 + 11.8
		Difference	-1.5 + 9.5	0.5 + 0.5	12.8 + 11.4

**P<0.01

Thirty-nine diabetic patients not treated with insulin were assigned randomly either A (Placebo) or B (GLUCO-Z™) labeled bottle. Five patients did not complete the study by not complying with the instruction. GLUCO-Z™ contains 20 mg Zinc, 200 mg prostate powder, 330 mg flax seed oils (PG precursors), 200 mg lecithin, 100 mg glycerin and other inactive ingredients that stabilize and maintain efficacy for prostate constituents such as PGs, and essential fatty acids. Placebo capsules contained 700-mg non-active ingredients.

 

SIGNIFICANCE

It is predicted that the number of diabetic and pre-diabetic patients will approach 80 million in the United States by the year 2006 (83). Diabetic patients are treated with several agents ranging from oral intake of sulfonylurea derivatives to insulin injection. Tremendous amounts of information on the insulin receptor functions and structure are now available (84), and yet the insulin receptor mediated signal transduction mechanisms are not thoroughly understood. We have demonstrated that PE, zinc, and other agents improved diabetic symptoms in both animal and human subjects (14,18,19, Table 1). More importantly, GLUCO-Z™ can be taken with other medications. Thus, GLUCO-Z™ could improve the quality of life of many diabetic patients.