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From The March 2001 Issue of Nutrition Science News
At the Counter with Dan Lukaczer, N.D.
Melatonin Helps Break Valium Dependence
Q: Are there natural ways to wean patients from benzodiazepines?
A: Benzodiazepines, which include Ativan, diazepam, Librium, Valium and Xanax, are a group of tranquilizer drugs used short-term for stress and anxiety. The drugs are frequently prescribed but can be problematic because of potential abuse and dependence. Furthermore, patients often have difficulty discontinuing these therapies because of the resulting insomnia.
The hormone melatonin is known to affect sleep and sleep cycles; studies show melatonin secretion is frequently disturbed in those with chronic sleep problems.1
Recently, an Israeli research group postulated that if melatonin indeed promotes sleep, it might be helpful in individuals who are trying to discontinue benzodiazapine therapy. In a randomized, crossover trial, the team enrolled 34 subjects on benzodiazepines and gave 18 of them 2 mg melatonin in a controlled-release formulation and 16 placebo nightly for six weeks. Participants were encouraged to reduce their benzodiazepine dosage 50 percent during week two, 75 percent during weeks three and four, and to discontinue completely during weeks five and six.
Results showed that 14 out of 18 subjects (78 percent) who received melatonin therapy—but only 4 out of 16 (25 percent) in the placebo group—were able to discontinue benzodiazepine therapy altogether. Sleep-quality scores were significantly higher in the melatonin group as well.2
The researchers then had all subjects try melatonin (blinded) for six additional weeks. Six more subjects in the original placebo group discontinued benzodiazepine therapy. The six-month, unblinded follow-up assessments revealed that of the 24 patients who discontinued benzodiazepines and received melatonin, 19 (79 percent) maintained good sleep quality. It appears melatonin may be a useful adjunct in weaning patients off these potentially addictive drugs.
Take NAC Orally
Q: What is the difference between N-acetylcysteine and glutathione, and which one should I suggest to customers?
A: N-acetylcysteine (NAC) is an amino acid precursor, or building block, to the tripeptide glutathione (GSH). In conventional medicine, NAC has been used to break up mucus in respiratory illnesses and as an antidote for hepatotoxicity caused by acetaminophen (Tylenol) overdose.3 In animal and human studies oral NAC enhances the synthesis of GSH.4,5 GSH, an antioxidant, promotes liver detoxification. For the most part, oral glutathione appears to be cleaved by digestive enzymes and broken down into its component amino acids. Although glutathione taken orally may have some benefit in the gut, it is unlikely that it has any systemic effect by itself because it is not absorbed intact. Most of the literature regarding glutathione's benefits have concentrated on either oral NAC or intravenous glutathione.
Niacin Good for Diabetics
Q: I have a customer who is a diabetic with high cholesterol. Niacin is said to help lower cholesterol but is contraindicated in diabetes. Why is this so?
A: Some older studies have suggested that while niacin is an effective agent to lower cholesterol and triglyceride levels for many diabetics, it has a tendency to increase blood-sugar levels.6 However, a recent large study casts doubt on that long-held belief.
In a prospective, randomized, placebo-controlled clinical trial conducted in six U.S. centers, researchers studied 468 participants, including 125 diabetics.7 Participants were randomly assigned to receive either 3,000 mg/day niacin as crystalline nicotinic acid or the maximum tolerated dosage (n = 64 with diabetes; n = 173 without diabetes), or placebo (n = 61 with diabetes; n = 170 without diabetes) for up to 60 weeks. The study had an unusual design in that all participants were on niacin first for 12 weeks, before being randomized. Niacin use significantly increased high-density lipoproteins (HDL) by 29 percent in both groups, decreased triglycerides by 23 and 28 percent, and decreased low-density lipoprotein cholesterol (LDL) by 8 and 9 percent.
These results were not unexpected. What was surprising was that niacin only modestly increased glucose levels (8.7 and 6.3 mg/dL) in participants with and without diabetes, respectively. Levels of hemoglobin A(1c) were unchanged from baseline to follow-up in diabetics treated with niacin. This is important because diabetics with unregulated blood-glucose levels tend to have increased hemoglobin A(1c) levels. The authors concluded that lipid-modifying dosages of niacin can be used safely by diabetics and that niacin therapy may an alternative to statin drugs or fibrates. Based on this study, it seems reasonable to suggest niacin supplementation to your diabetic customers but having them monitor their blood-sugar levels carefully.
Dan Lukaczer, N.D., is director of clinical research at the Functional Medicine Research Center, a division of Metagenics Inc., in Gig Harbor, Wash.
References
1. Rodenbeck A, et al. Nocturnal melatonin secretion and its modification by treatment in patients with sleep disorders. Adv Exp Med Biol 1999;467:89-93.
2. Garfinkel D, et al. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med 1999;159(20):2456-60.
3. Jones AL. Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: a critical review. J Toxicol Clin Toxicol 1998;36(4):277-85.
4. Pocernich CB, et al. In-vivo glutathione elevation protects against hydroxyl free radical-induced protein oxidation in rat brain. Neurochem Int 2000 Mar;36(3):185-91.
5. De Rosa SC, et al. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest 2000 Oct;30(10):915-29.
6. Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA 1990;264(6):723-6.
7. Elam MB, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. Arterial Disease Multiple Intervention Trial. JAMA 2000 Sep 13;284(10):1263-70.
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