Diabetes Protocol

Biotin--aids in metabolism of macronutrients and glucose utilization and is beneficial in diabetic neuropathy
Biotin, a member of the vitamin B-complex family, assists in the metabolism of fats, proteins, and particularly carbohydrates. Enhanced metabolism is important to the diabetic, who often presents with allergies and food sensitivities, compounding absorption problems.

Biotin directly influences blood glucose levels by working synergistically with insulin to increase the activity of glucokinase, an enzyme responsible for the first step in glucose utilization (Murray 1996). Glucokinase is found concentrated in the liver, but the enzyme is usually very low in diabetic patients. If biotin supplementation is high enough (16,000 mcg/day), the activity of glucokinase is upgraded and a significant improvement in blood glucose control typically occurs (Coggeshall et al. 1985).

Although biotin supplementation plays a pivotal role in blood glucose control, a deficiency is rare. In fact, researchers have found that diabetics have higher levels of biotin (produced by bacteria in the intestines) than nondiabetics. Supplementing with high doses is apparently not correcting a deficiency but rather overcoming a defect in biotin metabolism.

Animal studies indicate that biotin reduces postprandial blood glucose levels and improves insulin's responsiveness (Zhang et al. 1997). Human studies reached similar conclusions, showing that 9 mg (9000 mcg) of biotin a day countered a glucose rise following meals (Maebashi et al. 1993). Diabetic neuropathy, a significant problem among diabetics, also responds well to high dose biotin supplementation (Koutsikos et al. 1990).

A suggested dosage is 8000-16,000 mcg/day for blood glucose management. Biotin is a water-soluble vitamin, meaning it does not accumulate in the body. Toxicity has not been reported, but pregnant and lactating women should avoid high doses.

Biotin food sources, enhancers, and antagonists.
Cooked egg yolk, most fish (especially sardines), liver, poultry, dairy products, beans, and brewer's yeast are good sources of biotin. Enhancers are vitamins B12, folic acid, and B5, along with vitamin C, zinc, magnesium, and high-quality protein. Antagonists to biotin are raw egg whites, sulfa drugs, antibiotics, alcohol, coffee, and the antiseizure medications carbamazepine and primidone.

L-Carnitine--improves blood glucose and HbA1c levels, increases insulin sensitivity and glucose storage, and optimizes fat and carbohydrate metabolism; deficiencies appear allied to cardiomyopathy and diabetic neuropathy
Carnitine is a popular dietary supplement because it has been shown to produce many health benefits. The following list illustrates its multidirectional value in the treatment of diabetes:

Carnitine improves insulin sensitivity, increases glucose storage, and optimizes carbohydrate metabolism (Crayhon 1999). A significant effect on whole body insulin-mediated glucose uptake was also observed in normal subjects (Mingrone et al. 1999).
L-carnitine (200 mg daily), together with chromium (400-600 mcg daily) and moderate caloric restriction, typically results in impressive fat losses (Challem 2000).
Carnitine appears to protect against diabetic neuropathy. One of the mechanisms of neuropathy is the accumulation of polyols (alcohol) in nerve cells. In animal studies, acetyl-L-carnitine increased nerve carnitine levels and decreased the accumulation of sorbitol (a polyol) in nerves. This finding suggests a close relationship between increased polyol activity and a carnitine deficiency in the development of diabetic neuropathy (Nakamura 1998). Note: Diabetic neuropathy is a noninflammatory process characterized by sensory and/or motor disturbances in the peripheral nervous system. Symptoms (in those even mildly hyperglycemic) can include pain and loss of reflexes in the legs.
Carnitine deficiency is associated with cataract formation in diabetic patients. A significant loss of carnitine from the lens is observed in diabetic test animals, often foretelling the appearance of a cataract (Pessotto 1997). Because of the increased risk of cardiovascular disease and reduced kidney and liver function in diabetic patients, supplementation with L-carnitine appears warranted (Murray 1996).
A carnitine deficiency is linked to cardiomyopathy, a condition common among diabetics. In animal studies (6 months after developing diabetes), the myocardial ultrastructure often reveals abnormal-appearing mitochondria, consistent with a carnitine deficiency (Malone 1999). Note: Cardiomyopathy is the partial replacement of heart tissue with a nonfunctional fibrous material that lacks the ability to move blood efficiently.
Many animal and human studies have used acetyl-L-carnitine (the better absorbed and more active form of carnitine) in diabetic trials. Robert Crayhon, a carnitine expert, suggests avoiding carnitine supplements after 3 p.m. to preserve a restful night's sleep. Because increased energy production, a hallmark of carnitine, fosters a greater generation of free radicals, carnitine should always be used with an antioxidant program. A suggested acetyl-L-carnitine dosage is 500-1000 mg twice daily.

Carnosine and a Glycation Review
Glycation, a reaction occurring between proteins and glucose, is recognized as a major contributor to aging and perhaps cancer, as well as the complications arising from diabetes. Glucose provides the fuel for glycation, the insidious protein-glucose combination that (following several steps including the oxidation process) results in the formation of an advanced glycated end product or AGEs. Once AGEs are formed, they interact with neighboring proteins to produce pathological crosslinks that toughen tissues. It has been speculated that no other molecule has the potential toxic effects on proteins as AGEs.

Diabetic individuals form excessive amounts of AGEs earlier in life than nondiabetics, a process that disrupts the normality of organs that depend on flexibility for function. AGEs impair proteins, DNA, and lipids as well as triggering a cascade of destructive events as AGEs cling to cellular binding sites. One of the consequences of AGEs is a 50-fold increase in free-radical formation. Because diabetes (a condition of accelerated aging) spawns a harvest of AGEs, the kidneys are under specific attack.

By opposing glycation, glomerular damage and the resulting inflammation and renal degeneration are reduced. Diabetic rats that were not treated with glycation inhibitors showed a twofold increase in glomerular staining for AGEs compared with a similar group of diabetic rats receiving treatment (Forbes et al. 2001). In addition, glycation inhibitors (protecting against protein damage) are likely to inhibit cataract formation, a complication common to diabetics.

If ever approved by the FDA, glycation inhibitors such as aminoguanidine will enable humans to prevent many of the adversities that accompany aging. In the interim, carnosine (an amino acid peptide) has demonstrated in several studies to be a safe and effective antiglycating agent. Because carnosine structurally resembles the sites that glycating agents attack, it appears to sacrifice itself to spare the target (Hipkiss et al. 2000). Carnosine also bolsters proteolytic pathways, a function that enhances the disposal of damaged and potentially destructive proteins. A suggested carnosine dosage is 1000 mg/day.

Chromium--modulates blood glucose levels, fights insulin resistance, lowers HbA1c levels, aids weight loss, and inhibits glycation
Anecdotal but confirmed reports of brewer's yeast (a source of chromium) normalizing blood glucose levels hints of chromium's remarkable contribution to diabetic care. Researchers validated the anecdotal stories when the results of a study involving 78 Type II diabetics were published (Bahijiri et al. 2000). One-half of the enrollees received an inorganic chromium (200 mcg a day); the other half received brewer's yeast (supplying 23.3 mcg of chromium per day). Both groups realized a significant decrease in glucose in urine and fasting blood glucose levels as well as after a 2-hour, 75-gram glucose load. In fact, some trial participants were able to decrease antidiabetic drugs, and others no longer required insulin. Interestingly, a higher percentage responded positively to brewer's yeast, presumably because of better absorption; that is, the body retained more of the trace mineral.

The literature teems with similar reports regarding chromium's ability to modulate errant blood glucose levels. In fact, chromium is so important it is considered essential nearly every time you eat. Unfortunately, about 90% of adults are chromium deficient, according to the U.S. Department of Agriculture. (The highest tissue levels of chromium are found in newborns, with the tissue levels dwindling over a lifetime.) The conundrum surrounding chromium is that as chromium becomes deficient, more insulin is required, and as insulin production becomes excessive, a chromium deficiency occurs. In addition, chromium levels are seriously depleted when eating a diet high in refined sugar and white flour products.

It was known by the 1950s that chromium was required by animals to control blood sugar, but it was not until the 1970s that chromium's essential role in humans was clearly proven. The following chance finding established chromium's validity in reducing diabetic symptoms: patients receiving Total Parenteral Nutrition (TPN), a specially prepared feeding solution delivered through the patient's veins, developed high blood sugar in the absence of diabetes. Insulin therapy was begun but without satisfying results. It was determined that the TPN was deficient in amounts of chromium adequate to stave off diabetes-like symptoms. When 50 mcg of chromium were added to their IV feedings, the patients no longer required insulin and their blood glucose levels returned to normal (Mennen 1996).

Several mechanisms render chromium valuable in blood glucose management:

Chromium is essential in glucose metabolism. Note: It is estimated only about 3% of ingested chromium is absorbed into body tissues. The mineral is stored primarily in the spleen, skin, kidneys, and testes (Whiting 1989).
Chromium assists in overcoming insulin resistance (McCarty 2000).
Chromium appears to be involved in the insulin-induced movement of glucose into cells, probably by encouraging the binding of insulin to the receptor site or participating in reactions that occur immediately after the binding process, called postreceptor events.
The results of a 4-month study, presented at the 57th Annual Scientific Session of the American Diabetes Association Meeting in 1997, demonstrated that daily supplementation with 1000 mcg of chromium (supplied as chromium picolinate) significantly enhanced the action of insulin. The trial participants (29 overweight individuals with a family history of diabetes) completed the randomized, double-blind, placebo-controlled clinical trial showing that chromium reduced insulin resistance by 40% over the placebo group. (The study was conducted by William Cefalu, M.D., director of the Diabetes Comprehensive Care and Research Program at the Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC.)

High blood glucose damages proteins, a process called glycation. When blood sugar is high, glucose becomes attached to various proteins, including hemoglobin (the oxygen-carrying protein in red blood cells). A protein with glucose attached is said to be glycosylated, and in the case of hemoglobin is measured as HbA1c. Glycation is responsible for many of the complications of diabetes, a process that chromium inhibits.

To assess the effects of chromium on glycosylated hemoglobin levels, 180 Type II diabetes patients were divided into three groups and supplemented daily with 200 mcg of chromium, 1000 mcg of chromium, or a placebo (Baker 1996). After 4 months, there was improvement in both chromium-treated groups. Glycosylated hemoglobin (a measurement of average blood glucose) over a 2- to 3-month period was (on an average) 6.6% in the high dose group, 7.5% in the low-dose group, and 8.5% in the placebo group. For a nondiabetic, HbA1c is normal at 4-6%; for a diabetic, the goal is to maintain HbA1c at less than 7%.

To fully understand the previous study, HbA1c (expressed in percentages) and the blood sugar equivalents (mg/dL) follow:

4.0% = an average of 60 mg/dL of glucose
5.0% = an average of 90 mg/dL of glucose
6.0% = an average of 120 mg/dL of glucose
6.6% = an average of 138 mg/dL of glucose
7.0% = an average of 150 mg/dL of glucose
7.5% = an average of 165 mg/dL of glucose
8.5% = an average of 195 mg/dL of glucose

The data presented show how the HbA1c blood test measures average glucose levels over an extended period of time. When interpreting HbA1c, keep in mind that the results differ depending upon the test method used. Some laboratories measure hemoglobin A1, which is different from A1c. Also, the results may reflect the averaging of a period of high glucose with a period of low glucose as opposed to the consistent readings required for diabetes control.

Unfortunately, chromium supplementation is not as popular as it should be. One of the major problems hindering chromium usage is the fact that deficiencies are not easily gauged. Supplementation, followed by the laboratory assessment of blood glucose levels, appears the best appraisal of chromium's worth.

A chromium dosage of 50-100 mcg daily is high enough to correct a deficiency but not sufficient to improve blood sugar control. Dr. Richard Anderson (a biochemist and nutritionist with the Department of Agriculture) recommends that persons with diabetes and impaired glucose tolerance take 400-600 mcg of chromium daily. (Some practitioners report superior results in treating diabetes with the polynicotinate form of chromium, citing greater absorptive powers as the biological advantage.) Because significant changes in insulin requirements can occur with chromium therapy, physician monitoring is advisable.

Note: In the mid-1990s, chromium picolinate came under fire when it was linked with chromosome damage. Extensive toxicological testing proved that this indictment was invalid. Multiple trials have shown it is extremely difficult to harm laboratory animals with oral chromium supplementation. The public can be grateful for this because chromium is the chief nutritional barrier between healthy blood glucose levels and diabetes..
Chromium food sources, enhancers, and antagonists.
Brewer's yeast, whole grains, liver, cheese, meat, and potatoes are good sources of chromium. Enhancers are essential amino acids, selenium, and vitamin E. Hemochromatosis (excesses of iron) antagonizes chromium absorption.

Coenzyme Q10--has antioxidant value and may enhance beta cell function and glycemic control
Some researchers credit CoQ10, a lipid soluble antioxidant, with being able to counter much of the oxidative stress imposed by diabetes. However, the results of a study conducted at Indiana University School of Medicine (Bloomington) leaves the question unsettled (Rauscher et al. 2001).

According to one member of the research team, a group of rats with streptozotocin-induced diabetes was treated with CoQ10 (700-mg human equivalent per day) 30 days following inducement and continued for 14 days. Before beginning CoQ10 supplementation, all of the animals were extremely ill, with tissues showing increased oxidative stress and disturbances in oxidative defenses compared to normal controls. Treatment with CoQ10 ameliorated some of the diabetes-induced changes caused by oxidative stress but caused others. For example, treatment with CoQ10 reversed diabetic effects on liver glutathione peroxidase activity, renal superoxide dismutase activity, cardiac lipid peroxidation, and oxidized glutathione concentrations in the brain. However, treatment exacerbated the increase in cardiac catalase activity (which was already elevated in diabetes), further decreased hepatic glutathione reductase activity, augmented the increase in hepatic lipid peroxidation, and further increased glutathione peroxidase activity in the brain and heart. The tradeoff continued on several important parameters.

The Indiana researcher commented that other laboratories administering CoQ10 earlier in the trial had more gratifying results. He also mentioned the brevity of the CoQ10 administration (only 2 weeks) as another mitigating factor. Currently, the Indiana team is using the same model, but adding quercetin (a bioflavonoid) to the CoQ10. It is hoped that the synergistic value of cooperating nutrients will deliver greater therapeutic value.

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These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease