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From the Townsend Letter
October 2008

Literature Review & Commentary
by Alan R. Gaby, MD

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Topical vitamin A prevents wrinkles
Thirty-six elderly subjects (mean age, 87 years) were randomly assigned to apply, in double-blind fashion, topical 0.4% vitamin A (retinol) lotion to one arm and placebo (vehicle) to the other arm three times per week for 24 weeks. The mean improvement in the score for fine wrinkling (as determined from biopsy samples) was significantly greater in the active-treatment group than in the placebo group (-1.64 vs. -0.08 on a 9-point scale, with 0 being no wrinkles and 9 being severe wrinkles; p < 0.01 for the difference in the change between groups). Application of vitamin A significantly increased the production of glycosaminoglycans, which are known to retain water, and of collagen, which may increase skin integrity.

Comment: Tretinoin (Retin-A), a vitamin A analogue, has been known for many years to be effective for the prevention and treatment of age-related skin wrinkling. The results of the present study indicate that vitamin A itself is also effective for this indication. Topical vitamin A may be better tolerated than tretinoin, which can cause skin irritation, redness, peeling, blistering, photosensitivity, allergic reactions, and other adverse effects.

Kafi R, et al. Improvement of naturally aged skin with vitamin A (retinol).
Arch Dermatol. 2007;143:606-612.

Zinc effective for hidradenitis suppurativa
Twenty-two patients with hidradenitis suppurativa, mainly of grade I or II in Hurley's classification (with I being the least severe and III being the most severe) who had failed to respond to conventional medical or surgical treatment were treated with 90 mg per day of zinc (as zinc gluconate). The mean follow-up period was two years. All patients improved, and eight patients (36.4%) had a complete resolution of the skin condition. The duration of treatment before improvement occurred was not specified. When the maximum improvement was maintained for four months, the dosage of zinc was decreased by 15 mg per day every two months, depending on the clinical response. The zinc dosage needed to maintain the initial improvement was usually 30-60 mg per day. Patients with more severe disease required higher doses of zinc to maintain their improvement than did those with less severe disease. Three patients experienced gastrointestinal side effects from zinc.

Comment: Hidradenitis suppurativa is a chronic, frequently painful, suppurative dermatosis involving apocrine glands. It affects 0.3-0.4% of people in industrialized societies. Results of conventional therapy, which may include antibiotics, local antiseptics, isotretinoin, or surgery, are frequently disappointing. Although controlled trials are needed, the results of the present study suggest that zinc is an effective treatment for mild-to-moderate hidradenitis suppurativa.

Brocard A, et al. Hidradenitis suppurativa and zinc: A new therapeutic approach. A pilot study. Dermatology. 2007;214:325-327.

Prebiotic oligosaccharides prevent eczema in infants
Two hundred fifty-nine bottle-fed infants who were at risk of developing atopy were randomly assigned to receive, in double-blind fashion, a hydrolyzed protein formula supplemented with a prebiotic mixture consisting of 90% short chain galacto-oligosaccharides and 10% long chain fructo-oligosaccharides (0.8 g per 100 ml) or the same formula supplemented with placebo (maltodextrin). The incidence of atopic dermatitis in the first six months of life was 9.8% in the prebiotic group and 23.1% in the placebo group (58% reduction with active treatment; p = 0.014). Active treatment was associated with a significantly higher number of fecal bifidobacteria compared with placebo.

Comment: Oligosaccharides are a component of human milk. They promote the development of an intestinal flora dominated by bifidobacteria and lactobacilli. The prebiotic mixture used in the present study was designed to mimic the oligosaccharide content of human milk. In a previous study, supplementation with this oligosaccharide preparation was found to produce intestinal flora similar to that of breast-fed infants. While breast-feeding is preferable to formula-feeding for many reasons, infants at risk for atopy who cannot be breast-fed may benefit from a formula that contains oligosaccharides.

Moro G, et al. A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child. 2006;91:814-819.

N-acetylcysteine for obsessive-compulsive "grooming disorders"
Of five patients with various combinations of trichotillomania (pathological hair-pulling), pathological nail biting, and pathological skin picking, three experienced a resolution of these disorders after treatment with N-acetylcysteine (NAC). The initial dose was 600 mg per day, which was increased to 1,200 mg per day. Improvements were noted in each case after the dose was increased to 1,200 mg per day. Further improvement occurred when the dose was increased again. At a final dose of 1,800 mg per day (n = 2) or 2,400 mg per day (n = 1), the patients remained free of these compulsive behaviors during follow-up periods of three-to-five months.

Comment: Hyperactivity of glutamatergic neurotransmission has been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). NAC is believed to reduce synaptic glutamatergic activity. In a previous case report, administration of NAC resulted in improvement of chronic OCD in a middle-aged woman. The results of the present study suggest that NAC may also be useful in the treatment of compulsive grooming disorders that share certain characteristics with OCD.

Odlaug BL, Grant JE. N-acetyl cysteine in the treatment of grooming disorders. J Clin Psychopharmacol. 2007;27:227-229.

Trans-forming a big belly
Male monkeys were assigned to diets containing approximately eight percent of energy either as cis-monounsaturated fatty acids (control) or as the trans-isomers for six years. The diets provided maintenance energy requirements and were intended not to promote weight gain. Mean change in body weight (7.2% vs. 1.78%; p < 0.05), mean ratio of intra-abdominal fat volume to subcutaneous fat volume (1.67 vs. 1.36; p < 0.02), and mean postprandial serum insulin concentration (18 µIU/ml vs. 4.5 µIU/ml; p < 0.05) were significantly greater in animals fed trans-fatty acids than in controls.

Comment: The results of this study indicate that long-term consumption of trans-fatty acids by monkeys increases body weight and intra-abdominal fat deposition and promotes the development of insulin resistance, even in the absence of excessive caloric intake. These findings raise the possibility that trans-fatty acid consumption is one of the factors contributing to the epidemic of obesity in Western societies. The mechanism by which eating these industrially produced fatty acids might cause weight gain is not clear, although trans-fatty acids probably interfere with multiple aspects of intermediary metabolism and cell membrane function. This study adds to the growing list of adverse effects of partially hydrogenated oils.

Kavanagh K, et al. Trans fat diet induces abdominal obesity and changes in insulin sensitivity in monkeys. Obesity. 2007;15:1675-1684.

Does vitamin D prevent heart disease?
Of 69 patients with type 2 diabetes, 34 (49%) had a serum 25-hydroxyvitamin D level less than 50 nmol/L (mean, 38.3 nmol/L). Those 34 patients were randomly assigned to receive, in double-blind fashion, a single dose of 100,000 IU of vitamin D2 or placebo during the winter. Compared with placebo, vitamin D significantly improved flow-mediated vasodilatation (FMD) of the brachial artery (a measure of arterial health). The improvement in FMD remained significant after adjusting for changes in blood pressure. The mean systolic blood pressure (BP) decreased by 7.3 mm Hg in the vitamin D group and increased by 6.6 mm Hg in the placebo group (difference between groups, 13.9 mm Hg; p = 0.001). The mean diastolic BP decreased by 2.2 mm Hg in the vitamin D group and increased by 2.3 mm Hg in the placebo group (difference between groups, 4.5 mm Hg; p = 0.08).

Comment: For many years, doctors were concerned about the possibility that excessive vitamin D intake could cause cardiovascular disease. Those concerns were based on animal studies, in which feeding large doses of vitamin D3 or vitamin D2 caused arterial calcifications and other changes that resembled human atherosclerosis. While very large amounts of vitamin D were administered in most of these studies, feeding as little as 2,000 IU of vitamin D3 per kg of diet to swine was sufficient to cause intimal lesions and calcification of coronary arteries in one study. Because of these concerns, many multivitamin products limited their vitamin D content to 100-200 IU per day.

In contrast, a recent observational study found that the prevalence of cardiovascular disease decreased with increasing serum 25-hydroxyvitamin D levels. Those findings, when combined with the results of the new study, should alleviate concerns that taking moderate doses of vitamin D (up to 2,000 IU per day) might increase the risk of developing heart disease. Whether vitamin D supplementation actually prevents heart disease remains to be determined.

Sugden JA, et al. Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med. 2008;25:320-325.

Melatonin enhances preoperative anesthesia
Thirty-three patients (mean age, 44 years) undergoing abdominal hysterectomy were randomly assigned to receive, in double-blind fashion, 5 mg of oral melatonin or placebo the night before and one hour before surgery. The severity of postoperative pain and the amount of postoperative morphine use were significantly less in the melatonin group than in the placebo group. Of the patients who had moderate or intense pain during the first 24 hours after surgery, the incidence of high anxiety was 30% in the melatonin group and 77% in the placebo group. Of the patients who had no pain or mild pain, the incidence of high anxiety was 20% in the melatonin group and 33% in the placebo group. The number of patients that needed to be treated to prevent one additional patient reporting high postoperative anxiety and moderate-to-intense pain in the first 24 hours after surgery was 2.53 (95% CI, 1.41-12.22) and 2.20 (95% CI, 1.26-8.58), respectively.

Comment: Melatonin has sedative and analgesic effects. The results of the present study indicate that preoperative administration of melatonin can produce clinically relevant anti-anxiety and analgesic effects in the first 24 hours after surgery.

Caumo W, et al. The clinical impact of preoperative melatonin on postoperative outcomes in patients undergoing abdominal hysterectomy. Anesth Analg. 2007;105:1263-1271.

Is the RDA for vitamin B6 too low?
Plasma concentrations of pyridoxal 5'-phosphate (PLP; the biologically active form of vitamin B6) were measured in 6,000 people participating in the National Health and Nutrition Examination Survey (2003-2004). The proportion of subjects whose dietary vitamin B6 intake was less than the Recommended Dietary Allowance (RDA) of 2 mg per day ranged from 35% in men aged 13-54 years to 65% in menstruating women. The proportion of subjects who had a low plasma PLP level while consuming 2.0-2.9 mg/day of vitamin B6 was 19% for boys and girls younger than 13 years, 10% for males aged 13-54, 20% for menstruating females, 14% for men and women aged 65 or older, 12% for white males aged 13 or older, and 9% for male nonsmokers aged 13 or older. The prevalence of low plasma PLP level while consuming 3.0-4.9 mg per day of vitamin B6 was 3-7% in the different groups. The prevalence of low plasma PLP level while consuming more than 5.0 mg per day of vitamin B6 was 1-6% in the different groups, with three of the five groups studied having a prevalence of 4-6%.

Comment: This study demonstrates that laboratory evidence of vitamin B6 deficiency is relatively common, even among people whose diets exceed the RDA for this vitamin. In 1984, I wrote a book called The Doctor's Guide to Vitamin B6, in which I pointed out that a number of different environmental pollutants may be interfering with the way our body utilizes this important vitamin. Certain diseases that respond to high doses of vitamin B6 have increased in prevalence over the past several decades (such as asthma and ADHD) or were unknown 50 years ago (such as carpal tunnel syndrome). The results of the new study support that possibility that many people need more vitamin B6 than was previously thought. A copy of my book can be obtained by sending $23 to Nutrition Seminars, 12 Spaulding Street, Concord, New Hampshire 03301 (free shipping in the US, add $10 for shipping to Canada).

Morris MS, et al. Plasma pyridoxal 5'-phosphate in the US population: The National Health and Nutrition Examination Survey, 2003-2004.
Am J Clin Nutr. 2008;87:1446-1454.

Alan R. Gaby, MD


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