Diabetic angiopathy

Magnesium treatment of narcotic addiction

Eighteen patients on a methadone-maintenance program who were continuing to use illicit opiates and cocaine (as determined by urine testing) were randomly assigned to receive oral magnesium (Mg; 732 mg/day, as Mg L-aspartate hydrochloride) or placebo for 12 weeks. Patients also received a 30-minute counseling session once a week. In intent-to-treat analysis, the percentage of urine screens testing positive for opiates was 22.6% in the Mg group, compared with 46.4% in the placebo group (51% reduction; p =0.04). The difference was even greater among those who demonstrated at least 50% compliance with the treatment (16.3% vs. 47.9%; 66% reduction; p = 0.02). Although cocaine craving was lower in the Mg compared than in the placebo group, there was no difference between groups in the amount of cocaine used.

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Comment: This study demonstrates that supplementation with Mg L-aspartate hydrochloride can decrease illicit opiate use among individuals in a methadone-maintenance program. The results are consistent with those of animal studies, in which Mg delayed the development of morphine tolerance. An animal study also showed that Mg can decrease cocaine self-administration; however, the dose of Mg used in that study was greater (on a body-weight basis) than that used in the present study.

I once worked with a patient who was experiencing the typical symptoms of morphine withdrawal. I gave him an intravenous injection of 1 g of magnesium chloride, plus calcium gluconate, B vitamins, and 1.3 g of vitamin C (the Myers' cocktail). Within 2 minutes of the start of the injection, all of his withdrawal symptoms had disappeared, and this improvement lasted approximately 36 hours. When the benefit wore off, he was given a second injection, which again produced the same rapid improvement. In all, he received three treatments, which allowed him to remain essentially symptom-free during his five-day withdrawal period.

Margolin A, et al. A preliminary, controlled investigation of magnesium L-aspartate hydrochloride for illicit cocaine and opiate use in methadone-maintained patients. J Addict Dis 2003;22:49-61.

Preventing diabetic nephropathy

One hundred ninety-one patients with type 2 diabetes who had been referred to a nephrology clinic for various degrees of renal failure and proteinuria were randomly assigned to consume either 1) a carbohydrate-restricted (35% of energy), low-iron-available, polyphenol-enriched (CR-LIPE) diet or 2) a standard low-protein diet (control). A reduction in iron availability was accomplished by substituting red meats with poultry and fish, and by consuming foods that inhibit iron absorption (dairy products, eggs, tea, and soy). All beverages other than tea, water, and red wine (maximum, 150 ml with lunch and 150 ml with dinner) were eliminated, except for milk, which was recommended at breakfast. Tea, which is rich in polyphenols, was highly recommended. Outside mealtimes, water was the only beverage permitted. Polyphenol-rich extra-virgin olive oil was used for dressing and frying. In the CR-LIPE group, during a mean follow-up period of 3.9 years, the mean serum ferritin concentration decreased from 301 to 36 mcg/l (p < 0.001), but was unchanged in the control group. During the follow-up period, the serum creatinine concentration doubled in 21% of patients on CR-LIPE and in 39% of controls (p < 0.01). Renal replacement therapy (dialysis or transplantation) or death occurred in 20% of patients on CR-LIPE and in 39% of controls (p < 0.01).

Comment: The results of this study indicate that this specific dietary approach was considerably more effective than a standard low-protein diet for preventing the progression of renal failure in type 2 diabetics with renal failure and proteinuria. Previous studies have shown that iron can adversely affect glycemic control, by promoting insulin resistance. Depleting body-iron stores, even in patients without iron overload, can improve insulin sensitivity. In addition, because of its role as an oxidizing agent, excess iron presumably can increase free-radical damage to tissues. Polyphenols, on the other hand, function as antioxidants, and may protect tissues from oxidative damage. The importance of decreasing dietary carbohydrates is not clear, although such a dietary change has been shown in some studies to improve blood-glucose regulation.

Facchini FS, et al. A low-iron-available, polyphenol-enriched, carbohydrate-restricted diet to slow progression of diabetic nephropathy. Diabetes 2003;52:1204-1209.

Don't cook your goose

Eleven type 1 or type 2 diabetics consumed each of two different diets for two weeks, with a washout period of one-to-two weeks between diets. Thirteen other diabetics participated in a six-week randomized trial of the same diets. The two diets had a similar content of protein, carbohydrate, and fat, but differed by approximately 5-fold in the content of advanced glycation end products (AGEs), which was accomplished by varying the cooking time and temperature. After two weeks on the high-AGE diet, serum AGEs increased by 64.5% from baseline (p = 0.02); on the low-AGE diet serum AGEs decreased by 30% from baseline (p = 0.02). The values at six weeks were +28.2% (p = 0.06) and -40% (p = 0.02), respectively. After six weeks, the mean C-reactive protein concentration increased by 35% relative to baseline on the high-AGE diet and decreased by 20% relative to baseline on the low-AGE diet (p = 0.014). Other inflammatory mediators also increased on the high- and decreased on the low-AGE diet.

Comment: AGEs are created during the heating of common foods. They result from reactions between reducing sugars and proteins or lipids. In contrast to AGEs that form slowly in vivo, dietary AGEs form in the presence of heat much more rapidly and in far greater concentrations. Approximately 10% of ingested AGEs are absorbed; of that 10%, two-thirds is retained in tissues in reactive forms. The infusion of AGEs into rabbits results in the formation of atheroma-like lesions. Other research suggests that AGEs, whether formed in vivo or ingested as part of the diet, play a key role in the aging process and in the development of end-organ damage in diabetes.

Recently, C-reactive protein (CRP), an inflammatory mediator, has emerged as a potentially important risk factor for cardiovascular disease. It is believed that one of the main reasons statin drugs are so successful at preventing heart disease is that they reduce CRP levels. The fact that heavily cooked food can increase CRP, whereas lightly cooked or uncooked food decreases CRP levels, has important implications for the prevention of heart disease. The results of the present study suggest that the degree to which we cook our food can have a profound influence on our health. I always request that my steak be cooked midway between E. coli and heterocyclic amines.

Vlassara H, et al. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci 2002;99:15596-15601.

Vitamin D prevents falls

One hundred twenty-two elderly women (mean age, 85.3 years) in a long-stay geriatric care facility were randomly assigned to receive daily, in double-blind fashion, either 1) 1,200 mg of calcium plus 800 IU of vitamin D, or 2) 1,200 mg of calcium alone for 12 weeks. Before treatment, the mean number of falls per person per week was approximately 0.06 in each group. After adjustment for potential confounding variables, calcium-plus-vitamin D treatment resulted in a 49% reduction in the incidence of falls, compared with calcium alone (p < 0.01). Musculoskeletal function (as determined by a summed score of knee flexor and extensor strength, grip strength, and the timed up-and-go test) improved significantly in the calcium-plus-vitamin D group, compared with the calcium-alone group (p < 0.01).

Comment: Specific receptors for vitamin D have been identified in human muscle tissue. Previous studies have shown that vitamin D deficiency results in muscle weakness and impaired balance, factors that could increase the risk of falling down. The results of the present study demonstrate that vitamin D supplementation improved musculoskeletal function and reduced the risk of falling by 49%. Recurrent fallers seemed to benefit most. Thus, maintaining adequate vitamin D levels should prevent fractures by two different mechanisms: improving bone health and preventing falls. Vitamin D deficiency is common among the elderly; it results from a combination of inadequate dietary intake, reduced absorption capacity, and lack of sunlight. Vitamin D supplementation should be considered as part of the routine management of most elderly individuals.

Bischoff HA, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 2003;18:343-351.

Berberine for congestive heart failure

One hundred fifty-six patients with congestive heart failure (CHF) secondary to coronary artery disease (n = 94) or idiopathic dilated cardiomyopathy (n = 62) and greater than 90 ventricular premature complexes (VPCs) and/or nonsustained ventricular tachycardia on 24-hour Holter monitoring were randomly assigned to receive, in double-blind fashion, berberine or placebo for 8 weeks. The initial dose of berberine was 300 mg 4 times per day; the dose was adjusted to maintain a plasma level greater than 0.1 mg/L, with a maximum dose of 500 mg 4 times per day. All patients received conventional therapy, which included angiotensin-converting-enzyme inhibitors, digoxin, diuretics, and nitrates. Compared with placebo, berberine treatment resulted in a significant increase in left ventricular ejection fraction (22 vs. 32% with berberine; 22 vs. 27% with placebo; p < 0.02), improvements in exercise capacity and in the dyspnea-fatigue index, and a decrease in the of frequency and complexity of VPCs. There was a significant 47% decrease in mortality in the berberine group compared with the placebo group during a mean follow-up period of 24 months (8.9% vs. 16.9%; p < 0.02). No side effects were seen.

Comment: Berberine is used in Asia to treat CHF. It is reported to have antihypertensive activity, an inotropic effect, and class III antiarrhythmic properties. The results of the present study indicate that berberine improved cardiac function, decreased the number of ventricular premature complexes, and reduced mortality in patients with CHF, without causing any adverse effects. Additional research is needed to determine how best to combined berberine with conventional therapy and with natural treatments such as coenzyme Q10 and hawthorn.

Zeng XH. Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 2003;92:173-176.

Perennial rhinitis due to food additives

Letter: The writer reports three cases of perennial rhinitis that was traced in two cases to monosodium glutamate (MSG) and in one case to sodium benzoate. In each case, the offending additive induced severe rhinitis 4-6 hours after ingestion; symptoms lasted for two days in the two MSG-intolerant patients and for one week in the sodium-benzoate-intolerant patient. Each reaction was confirmed by double-blind, placebo-controlled challenges. Avoidance of the offending agent resulted in disappearance of nasal symptoms in each case.

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Comment: While many cases of perennial rhinitis can be traced to food or inhalant allergy, in other cases a specific cause cannot be identified. This report suggests that intolerance to common food additives may be an overlooked cause of rhinitis. As these reactions are probably not true allergic reactions, standard allergy testing may not identify the causal agent. A comprehensive elimination diet that excludes common allergenic foods, as well as all food additives, followed by individual food and food-additive challenges, will often be useful for determining what dietary components are contributing to the problem.

Asero R. Food additives intolerance: a possible cause of perennial rhinitis. J Allergy Clin Immunol 2002;110:937-938.

Apparent cure of ulcerative colitis

Six patients (aged 25-53 years) with ulcerative colitis, with severe and recurrent symptoms, received fecal flora from healthy donors who had been extensively screened for parasites and bacterial pathogens. The patients were prepared with antibiotics and oral polyethylene glycol lavage. Fecal suspensions were administered as retention enemas within 10 minutes of preparation and the process was repeated daily for 5 days. Improvement in symptoms was seen within one week after the end of the treatment period. Complete reversal of symptoms was achieved in all patients within four months, by which time all medications for ulcerative colitis had been discontinued. At follow-up 1-13 years after the treatment, there was no clinical, colonoscopic, or histologic evidence of ulcerative colitis in any patient, and no patient was taking medication for ulcerative colitis.

Comment: The rationale for administering normal fecal flora is that ulcerative colitis may be caused, at least in part, by the presence of abnormal intestinal microorganisms. Although the study was small and there was no control group, the results are so dramatic that this approach may be considered a potential cure for selected patients with ulcerative colitis. Clearly, additional research is warranted.

Borody TJ, et al. Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol 2003;37:42-47.

Ginkgo biloba for vitiligo

Fifty-two patients (mean age, 29 years) with slowly spreading vitiligo were randomly assigned to receive, in double-blind fashion, Ginkgo biloba extract (standardized to contain 24% ginkgoflavonglycosides), 40 mg 3 times per day, or placebo. Treatment was continued for as long as the response was considered adequate (i.e., arrest of disease progression and some repigmentation of existing lesions), or up to 6 months. Forty-seven patients completed the trial. Arrest of disease progression was seen in 80% of patients in the ginkgo group, compared with 36% of those in the placebo group (p = 0.006). Marked-to-complete repigmentation was seen in 40% of patients in the ginkgo group and in 9% of those in the placebo group (statistical significance not stated). Side effects of ginkgo were limited to mild nausea in two patients.

Comment: This study suggests that Ginkgo biloba extract is a simple, safe, and fairly effective treatment for arresting the progression of vitiligo and for inducing repigmentation. While the mechanism of action of ginkgo is not known, oxidative stress has been shown to play a role in the pathogenesis of vitiligo, and ginkgo has antioxidant activity. Because currently available treatments for vitiligo are often of limited benefit, treatment with ginkgo is worth considering.

Parsad D, et al. Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo. Clin Exp Dermatol 2003;28:285-287.

by Alan R. Gaby, MD

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