~ Nutritional Interventions for the Prevention and Treatment of Syndrome X and Type II Diabetes, Part II

Continued from Part I

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.

The Indiana University study is representative of the inclusive results that can manifest when one supplement is examined by itself. Antioxidants (as CoQ10) should be taken with other antioxidants, rather than emphasizing a single factor. Many commercial CoQ10 products are complexed with other antioxidants to balance the effects of CoQ10 at the cellular level.

On the other hand, Japanese researchers gave a favorable nod to CoQ10, citing (among CoQ10's virtues) its ability to enhance beta cell function and improve glycemic control (McCarty 1999). Recall that the Helicon Foundation (San Diego, CA) selected CoQ10 as one of four nutrients (the others are biotin, chromium, and conjugated linoleic acid) as a part of a wholly nutritional therapy against Type II diabetes. A suggested CoQ10 dosage is 100 mg/day. Take higher doses if you have neurological or cardiac impairment.

Conjugated Linoleic Acid (CLA)--aids in weight management, improves insulin sensitivity, and reduces blood glucose levels

According to information released at the national meeting of the American Chemical Society (ACS) in August 2000, the long-awaited first results of human studies evaluating conjugated linoleic acid (CLA), a naturally occurring fatty acid, indicate that the supplement may help overweight adults lose weight and maintain the loss.

Animal studies have for the past 10 years affirmed CLA's importance in weight management, but human studies were lacking. More recently, human studies (conducted in Norway and the United States) substantiated animal studies, confirming that overweight individuals experienced a statistically significant reduction in body fat while supplementing with CLA. The trial participants did not alter eating habits, and no adverse side effects accompanied supplementation.

It is also speculated that CLA may reduce body fat by increasing energy expenditure. Researchers at the Pennington Biomedical Research Center (Baton Rouge, LA) observed that CLA-fed mice (after only 1 week of dosing) experienced increased energy output, a perk that was sustained 6-weeks postsupplementation (DeLany et al. 2001).

The University of Wisconsin (Madison) released results of a 6-month study involving 89 overweight people. Michael Pariza, Ph.D., one of the researchers, determined that exercise and food restriction initially caused a weight loss but noted that the loss was difficult to maintain. Typically, individuals regained their lost weight at a ratio of 75% fat to 25% lean. Individuals supplementing with CLA were better able to maintain goal weight, with less fat regained and more muscle mass retained (ACS 2000; Pariza 2000).

A team from Purdue University and Pennsylvania State University announced that CLA appears to reduce blood glucose levels and prevent diabetes, at least for the short-term. Animal studies demonstrated that CLA worked as well as a new class of diabetes-fighting drugs, the thiazolidinediones (TZDs).

Karen Houseknecht (assistant professor of animal studies) at Purdue says that CLA may have advantages over current drug therapies considering overall health benefits. When Zucker Diabetic Fatty rats (those specially bred to become obese and develop glucose intolerance) are given TZD, they become fatter. Conversely, when laboratory animals are given CLA, they become leaner. (During the course of the CLA study, obese animals lost 10% of body fat and lean animals lost 25%.) After 2 weeks, the CLA-supplemented rats were diabetes free; all of the unsupplemented rats had developed diabetes (Houseknecht et al. 1998).

Among 22 individuals enrolled in an 8-week CLA/diabetes study, 64% experienced improved insulin sensitivity (the premier focus in reversing Type II diabetes) while taking 6.0 grams a day of CLA (ACS 2000). Maureen Charron (diabetes researcher and associate professor of biochemistry at the Albert Einstein College of Medicine at Yeshiva University in New York), although excited about CLA as an antidiabetic agent, is tempering her enthusiasm until more studies are completed. In the interim, the Purdue team is considering feeding CLA to hogs to see if the CLA content of pork can be increased. The researchers jest that the ramifications of a pork chop that fights both cancer and diabetes is "emotionally overwhelming" (Houseknecht et al. 1998). A suggested CLA daily dose is 3000-4000 mg, usually four to five 1000-mg (76%) capsules.

Food sources of CLA The polyunsaturated fat is found in meats and cheeses and in lesser amounts in milk, yogurt, poultry, eggs, and cooking oil. (According to Purdue researchers, CLA looks like corn oil, just a little clearer. Note that the CLA content of dairy products and meat is lower than what it used to be because cows primarily eat in feedlots as opposed to eating grass. As a result, CLA supplements have become a popular adjunct weight-loss approach.)

DHEA (Dehydroepiandrosterone)--is beneficial to diabetic and obese individuals, reduces IL-6 levels, and eventually converts to testosterone in some individuals

Although not universally accepted, some studies suggest that high serum insulin predisposes one to low levels of DHEA (Yamaguchi et al. 1998). A fall in serum levels of DHEA is associated with a higher incidence of atherosclerosis and obesity. An association has now been made with diabetes. These observations suggest that DHEA may play a protective role in diseases that gain a stronghold when DHEA levels become low (Lukaczer 1999).

A lack of DHEA appears to be a primary cause of insulin resistance (likely because a DHEA shortage interferes with insulin's ability to regulate blood glucose). Since insulin is one of the hormones that affect fatty acid metabolism, insulin resistance is often observed when fatty acid metabolism is abnormal. Illustrative of this, rats fed a diet containing 0.3% DHEA (ages 5-25 months) had about 25% less body fat than animals not supplemented. Concurrently, the rate of glucose disposal was 30% higher in the DHEA-treated group due to greater insulin responsiveness (Han et al. 1998).

More recently, the dangers of C-reactive protein (CRP), a newer risk factor associated with heart disease, have expanded to include diabetes, with researchers referring to it as a predictive factor for the disease (Pradhan et al. 2001). Since individuals who are obese and insulin resistant often present with higher levels of CRP, addressing CRP levels has become even more relevant for diabetic patients. In addition, elevations in interleukin-6 (IL-6), an inflammatory cytokine, has emerged as another prognostic evaluation for diabetes. Israeli researchers showed that DHEA, an intrinsic neurosteroid, inhibited IL-6 by 95% (Kipper-Galperin et al. 1999).

The kidneys are of significant concern in nonresponsive hyperglycemia. DHEA, a major secretory product of the human adrenal gland, has been shown to possess multitargeted antioxidant activity, including effectiveness against glucose-induced lipid peroxidation. This adaptation protects the kidneys against oxidative damage and impairment of cell growth, suggesting effectiveness in overcoming chronic renal complications associated with diabetes (Brignardello et al. 2000).

Suggested DHEA dosage and caveats. A suggested dosage is 15-75 mg, taken early in the day (50 mg represents a typical daily dose.) Blood tests are valuable 3-6 weeks into therapy to assist in assigning appropriate dosages. Optimal DHEA levels for men are between 400-560 mcg/dL; for women, the range is considered ideal at 350-430 mcg/dL.

Because DHEA invigorates hormonal systems, it is not recommended for men with prostate cancer or for women with estrogen-dependent cancer, without physician approval. (DHEA can be converted into testosterone and estrogen.) Before starting DHEA therapy, men should know their serum PSA (prostate specific antigen) level and have passed a digital rectal examination (DRE). DHEA does not cause prostate cancer, but because DHEA can cause an increase in testosterone levels, the presence of an undetected cancer should be ruled out before initiating the therapy.

For a comprehensive review of the natural products capable of reducing proinflammatory cytokines, please consult the Inflammation: Chronic protocol. The Cardiovascular Disease protocol contains valuable information regarding the risks imposed by elevated CRP and natural measures to counter it.

Essential Fatty Acids--promote release of prostacyclin, help maintain cell membrane insulin responsiveness, are beneficial to dieters, and lower CRP

Omega-3 fatty acids (alpha-linolenic acid), the parent of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), help maintain healthy cell membranes. This means that the membranes are flexible and contain larger numbers of insulin receptors that are more receptive and responsive to insulin (Lukaczer 1999). Researchers have shown that eating a diet that emphasizes omega-3 fatty acids (herring, mackerel, sea bass, salmon, cod, sardines, fresh tuna, whitefish, coldwater halibut, anchovy, and walnuts) along with monounsaturated fats (olives, almonds, pecans, cashews, filberts, and macadamias) is effective medicine against membrane alterations.

Japanese researchers recently showed that EPA reduced plasma lipids and abdominal fat deposits and increased glucose disposal. Results indicate that long-term feeding of EPA appears effective in preventing insulin resistance in diabetic-prone laboratory animals (in part) by improving blood lipid levels (Minami et al. 2002).

Depressed levels of prostacyclin, a major vasoprotective molecule, are central to the pathogenesis of diabetic neuropathy. Because of inadequate amounts of prostacyclin among diabetics, red blood cells (responsible for oxygen carriage) become brittle and rigid. This prevents oxygen from freely entering the cells, a process that most damages small capillaries and the tissues they serve. Gamma-linolenic acid (GLA), an omega-6 fatty acid, promotes the release of prostacyclin. This function (in turn) adds flexibility to blood cells, regenerates capillaries, and stabilizes nerves (Guivernau et al. 1994; Angilley 2001). Using evening primrose oil (EPO), a good source of GLA, resulted in a 22% increase in endoneural (nerve sheath) capillary density (Cameron 1990). Persons beginning EPO therapy should allow 8-10 weeks to realize a significant effect (Fang 1997; Angilley 2001).

Studies have shown that genetically obese people also profit from essential fatty acid supplementation. The weight loss in these individuals is gradual but reliable, even among those considered intractably obese.

GLA appears to stimulate brown fat cells by producing prostaglandin E1 (PGE1). Brown fat is of particular advantage in maintaining a desirable weight because it uses extra calories to provide heat, preventing the deposit of unsightly white fat. Brown fat's energy-use capacity accounts for major differences between brown fat and white fat. Mitochondria are abundantly dispersed throughout brown fat cells (Braly 1985).

Type II diabetics should supplement with at least 900 mg of GLA a day from borage oil, along with 500 mg of EPA and 1300 mg of DHA from fish oil. Research suggests the DHA fraction of fish oil is particularly effective in reducing CRP (Madsen et al. 2001; Pradhan et al. 2001). This quantity of fatty acids GLA, EPA, and DHA can be obtained in 8 capsules by using highly concentrated borage and fish oil supplements.

Fiber--lowers blood glucose levels

It is difficult to overstate the benefits garnered from fiber in regard to blood glucose control. Eating a diet rich in high fiber foods has spared countless individuals the risks imposed by chronically elevated blood glucose and the rigors of aggressive antidiabetic therapy.

A high fiber diet offers many health benefits, some of which accrue whether the appropriate fiber is selected or not (Hayes 2001). However, therapeutically speaking, fibers are not equal; they have different metabolic dispositions.

The two types of fiber are insoluble (does not disperse in water) and soluble (does dissolve in water). Insoluble fibers are identified as cellulose and many hemicelluloses and lignins; soluble fibers include pectin, gums, mucilages, and some hemicelluloses.

Fibers target different metabolic disturbances. For example, the benefits gleaned from insoluble fibers usually involve the gastrointestinal (GI) tract, promoting bowel regularity, while slowing the breakdown of starch and delaying glucose absorption into the blood. Soluble fibers (the type popularized since the 1980s) slow gastric emptying and the transit of chyme (the semifluid material produced by gastric digestion of food) through the intestines. This function forestalls the quick entry of glucose into the bloodstream. Soluble fibers appear to improve insulin sensitivity and reduce hyperinsulinemia as well. Many of the conditions surrounding Syndrome X, including poor lipid levels and disrupted coagulation factors, are favorably impacted by fiber.

Some people associate fiber with bran products, but dietary fiber also includes the nondigestible portion of plant foods found in whole grains, fruits, vegetables, and dried beans and peas, as well as nuts and seeds. Although fiber cannot be digested and does not supply calories or nutrients, it is far from a purposeless food factor. In addition to direct impact upon various forms of ill health, soluble fibers provide short-chain fatty acids. Bacteria in the human digestive tract ferment fiber, that is, they digest fibers in the absence of oxygen. This process generates water and short-chain fatty acids. The short-chain fatty acids are absorbed in the colon and yield energy when metabolized (depending upon the extent to which they are broken down and absorbed) (Murray 1996). The short-chain fatty acids produced by GI bacteria are primarily acetic acid, propionic acid, and butyric acid (Whitney 1998).

The American Diabetes Association (ADA) recommends that individuals with diabetes consume the same amount of fiber (both soluble and insoluble) as that recommended for the general population: 20-35 grams a day. This recommendation may not be sufficient to stabilize blood glucose levels. The ADA's guidelines for fiber consumption were based on the rationale that 20-35 grams of fiber were a reasonable amount to expect individuals to obtain from dietary sources. (Considering the amount of fast and convenience foods consumed, it is estimated many people consume only 5-17 grams of fiber a day.)

A study reported in the New England Journal of Medicine involved diabetic patients consuming a diet supplying 25 grams of soluble fiber and 25 grams of insoluble. (This amount is about double the amount that is currently recommended by the ADA.) The fiber was derived from foodstuffs, with no emphasis placed on special or unusual fiber-fortified foods or fiber supplements. After 6 weeks, tests revealed that the high fiber diet had reduced blood glucose levels by an average of 10%; equally important, levels of circulating insulin were also reduced (Chandalia et al. 2000).

Fiber is also valuable to persons on diets because it produces a feeling of satiety, negating the desire to overeat. Apart from getting an early sense of fullness, fibrous foods require more chewing; by extending mealtime, the person on a diet is satisfied both physically and emotionally. Because high-fiber foods are digested more slowly, hunger pangs are forestalled. For the most part, fibrous foods represent healthy food (nutrient-dense and low-fat), additional perks for weight watchers.

Fiber should be added slowly, gradually substituting low-fiber foods with high-fiber alternatives. This is necessary for the following reasons: (1) insulin and prescription drugs may have to be adjusted to accommodate lower blood glucose levels, and (2) without a gradual introduction of the new material, gastric distress could occur.

Some individuals prefer to bolster fiber volume by adding supplemental pectin, gums, and mucilages to each meal. Calculate the amount of fiber gained from foodstuffs and supplement with enough to compensate for shortfalls. Recall that successful trials used soluble and insoluble fibers (a total of 50 grams a day). Monitor blood glucose levels closely to assess gains and to adjust oral or injectable hypoglycemic agents.

High-fiber foods follow (those emphasized in the study in the New England Journal of Medicine), with soluble fiber identified by (S) and insoluble identified by (I) and expressed in grams per serving (Chandalia et al. 2000). (Fiber content of foods was collected from sources apart from the published study.)


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