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Literature review & commentary.

Vitamins Don't Kill People

A meta-analysis was conducted on 21 randomized controlled primary or secondary prevention trials (including a total of 91,074 people, mean age, 62 years) that examined the effect on mortality of daily multivitamin-multimineral supplementation for at least 1 year. The mean duration of supplementation was 43 months. In the pooled analysis, compared with the control group, the multivitamin-multimineral group had a nonsignificant 2% decrease in all-cause mortality (relative risk [RR] = 0.98; 95% confidence interval [CI], 0.94-1.02). There was a trend toward a reduced risk of all-cause mortality in primary prevention trials (RR = 0.94; 95% CI, 0.89-1.00).

Comment: An observational study published in 2011, the results of which were widely disseminated by the media, raised concerns that taking multivitamins could increase mortality. In that study (Mursu J et al. Dietary supplements and mortality rate in older women: the Iowa Women's Health Study. Arch Intern Med. 2011;171:1625-1633), after adjustment for a large number of potential confounding variables, the mortality rate was significantly higher by 6% in multivitamin users than in nonusers. Observational studies cannot prove causality, and as I pointed out in a previous editorial in the Townsend Letter (January 2012), the study had several important weaknesses that may have invalidated its findings.

Randomized controlled trials are much more reliable than observational studies. The results of the new meta-analysis should therefore allay concerns that taking a multivitamin or multivitamin-multimineral supplement (these terms are often used interchangeably) might increase mortality. To the contrary, there was a nonsignificant trend toward lower mortality among subjects randomly assigned to take a multivitamin-multimineral.

Double-blind trials have shown that taking multivitamin or multivitamin-multimineral supplements can improve stress tolerance and overall well-being, and may relieve symptoms such as anxiety and fatigue. It is reassuring to know that obtaining these benefits does not come at the price of hastening one's demise.

Macpherson H et al. Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2013;97:437-444.

Vitamin D for Parkinson's Disease

One hundred fourteen patients (mean age, 72 years) with Parkinson's disease were randomly assigned to receive, in double-blind fashion, 1200 IU per day of vitamin D3 or placebo for 12 months. In the group receiving vitamin D, the mean serum 25-hydroxyvitamin D level increased from 22.5 ng/ml at baseline to 41.7 ng/ml after 12 months. Compared with placebo, vitamin D significantly decreased the mean amount of clinical deterioration as determined by the modified Hoehn and Yahr (HY) stage (p = 0.005), and nonsignificantly decreased the amount of deterioration as determined by the Unified Parkinson's Disease Rating Scale (UPDRS). Interaction analyses showed that vitamin D receptor (VDR) Fokl genotypes modified the effect of vitamin D on changes in the HY stage (p for interaction < 0.05), UPDRS total (p for interaction < 0.04), and UPDRS part II (p for interaction = 0.021). Compared with placebo, vitamin D significantly prevented deterioration of the HY stage in patients with Fokl TT (p < 0.01) or Fokl CT (p = 0.02), but not in those with Fokl CC. In the group with Fokl CC, there was a nonsignificant trend toward less deterioration in the placebo group than in the vitamin D group. Similar results were observed for UPDRS total and part II scores. Fourteen percent of the patients had Fokl TT, 51% had Fokl CT, and 35% had Fokl CC.

Comment: The results of the present study suggest that vitamin D supplementation may slow deterioration in patients with Parkinson's disease who have the VDR Fokl TT or CT genotypes (approximately two-thirds of the population studied). The Fokl C allele is considered to transduce the signal from the vitamin D receptor more efficiently than the Fokl T allele. What these findings suggest is that among patients with a mean baseline 25-hydroxyvitamin D concentration just above 20 ng/ml, those with a genetically efficient vitamin D receptor do not experience neurological benefit from vitamin D supplementation, whereas patients with a genetically less efficient vitamin D receptor do benefit from supplementation. Further research is needed to determine whether patients with higher baseline 25-hydroxyvitamin D levels would benefit from vitamin D supplementation, and whether vitamin D supplementation has a deleterious effect in those with the Fokl CC genotype (as suggested by the trend in this study).

Suzuki M et al. Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease. Am J Clin Nutr. 2013;97:1004-1013.

Vitamin D for Crohn's Disease

Eighteen patients (mean age, 38 years) with mild-to-moderate Crohn's disease (Crohn's disease activity index [CDAI] scores of 150-400) received vitamin D3 for 24 weeks. The initial dose was 1000 IU per day; this was increased every 2 weeks by 1000 IU per day until the serum 25-hydroxyvitamin D level reached 40 ng/ml or until the dose was 5000 IU per day. Fourteen of the 18 patients required the maximum vitamin D dose. The mean serum 25-hydroxyvitamin D concentration increased from 16 ng/ml at baseline to 45 ng/ml. The mean CDAI score improved from 230 at baseline to 118 (p < 0.0001), and quality-of-life scores improved significantly (p = 0.0004).

Comment: This study demonstrated that serum 25-hydroxyvitamin D levels were low in patients with Crohn's disease, and that supplementation with relatively large doses of vitamin D was associated with substantial clinical improvement. Low 25-hydroxyvitamin D levels in people with chronic inflammatory conditions do not necessarily indicate vitamin D deficiency, because 25-hydroxyvitamin D is an acute-phase reactant that falls in response to inflammation. Furthermore, because there was no control group in this study, one cannot rule out the possibility that the clinical improvement was due to a placebo effect or to factors related to participating in a study. Nevertheless, the potential value of vitamin D as a treatment for Crohn's disease is intriguing and warrants additional study.

Yang L et al. Therapeutic effect of vitamin D supplementation in a pilot study of Crohn's patients. Clin Transl Gastroenterol. 2013;4:e33.

Probiotic for Lactose Intolerance

Twenty-seven patients with lactose intolerance underwent 4 hydrogen breath tests after a dose of 20 g of lactose: baseline, after a single dose of lactase (9000 FCC units), after 4 weeks of probiotic supplementation (1 sachet 3 times per day), and 3 months after discontinuation of the probiotic. Each probiotic sachet contained Lactobacillus casei Shirota (2 x [10.sup.7] to [10.sup.9] colony-forming units) and Bifidobacterium breve Yakult (5 x [10.sup.7] to [10.sup.9] colony-forming units; Yakult S.S., Brazil). The probiotic combination significantly reduced symptom scores (p < 0.01) and breath hydrogen area under the curve (AUC; p = 0.04) compared with baseline. The probiotic was somewhat less effective than lactase, both for the hydrogen breath test and symptom reduction. Three months after the probiotic was discontinued, symptom scores and breath hydrogen AUC values remained similar to those at the end of probiotic treatment.

Comment: This study demonstrated that administration of a specific probiotic preparation improved symptoms and lactose digestion in lactose-intolerant patients, and that the effect persisted for at least 3 months after the treatment was discontinued. Further research is needed to determine whether other probiotic strains would have a similar effect.

Almeida CC et al. Beneficial effects of long-term consumption of a probiotic combination of Lactobacillus casei Shirota and Bifidobacterium breve Yakult may persist after suspension of therapy in lactose-intolerant patients. Nutr Clin Pract. 2012;27:247-251.

Selenium Increases Mercury Excretion

Because of a long history of extensive mercury mining and smelting activities, residents of Wanshan, China, are suffering from increased mercury exposure. One hundred three volunteers from Wanshan were randomly assigned to receive 100 pg per day of selenium (from high-selenium yeast) or placebo (low-selenium yeast) for 90 days. The mean urinary concentration of mercury did not change in the placebo group. In the selenium group, the mean urinary mercury concentration increased by 74% after 30 days (p < 0.01 compared with placebo) and increased by 175% after 90 days (p < 0.001 compared with placebo).

Comment: These results indicate that selenium supplementation can increase urinary mercury excretion (which would presumably decrease the body mercury burden) in chronically mercury-exposed individuals. Previous research has shown that selenium protects against mercury toxicity above and beyond any effect that it may have on mercury excretion. Selenium is thought to form a complex with mercury and to prevent mercury-induced free-radical formation. Thus, selenium appears to reduce the adverse effects of mercury by at least 2 different mechanisms.

Li YF et al. Organic selenium supplementation increases mercury excretion and decreases oxidative damage in long-term mercury-exposed residents from Wanshan, China. Environ Sci Technol. 2012;46:11313-11318.

Vitamin C for Idiopathic Sudden Sensorineural Hearing Loss

Seventy-two patients with idiopathic sudden sensorineural hearing loss were treated with systemic glucocorticoids for 15 days and were randomly assigned to receive or not to receive (control group) intravenous vitamin C for 10 days (200 mg/kg of body weight per day) followed by oral vitamin C (2000 mg per day for 30 days). Auditory evaluations were performed before and 1 month after treatment. The proportion of patients who demonstrated complete recovery (46.8% vs. 23.8%; p = 0.03) and the proportion of patients who demonstrated complete or partial recovery (65.5% vs. 42.0%; p = 0.035) was significantly higher in the vitamin C group than in the control group. The mean degree of improvement in hearing was significantly greater in the vitamin C group than in the control group (p = 0.03).

Comment: Idiopathic sudden sensorineural hearing loss is defined as sensorineural hearing loss of 30 dB or more in 3 contiguous frequencies over a period of 72 hours or less. The cause is unknown, although oxygen-derived free radicals are believed to be involved. Conventional treatment includes systemic glucocorticoids; vasodilators, diuretics, and antiviral agents have also been recommended. About one-third of patients recover normal hearing, another one-third are left with hearing loss of 40 to 60 dB, and the remainder progress to complete hearing loss. The results of the present study indicate that treatment with high-dose vitamin C, as an adjunct to glucocorticoids, can enhance recovery in patients with idiopathic sudden sensorineural hearing loss.

Kang HS et al. Effect of high dose intravenous vitamin C on idiopathic sudden sensorineural hearing loss: a prospective single-blind randomized controlled trial. Eur Arch Otorhinolaryngol. Epub 2012 Dec 4.

Weight Loss Relates to Timing of Food Intake

Four hundred twenty overweight or obese individuals (mean age, 42 years; mean body mass index, 31.4 kg/[m.sup.2]) who followed a 20-week weight-loss program were classified as early or late eaters, according to the timing of the main meal (lunch in this Mediterranean population). Fifty-one percent of the subjects were early eaters (lunch before 3 p.m.) and 49% were late eaters (lunch after 3 p.m.). Mean weight loss was significantly greater among the early eaters than among the late eaters (9.7 vs. 7.7 kg; p = 0.008), even though caloric intake and estimated energy expenditure were similar between groups.

Comment: Previous research has shown that food consumed earlier in the day is more satiating than food consumed later in the day. One study showed that people who consumed a larger percentage of their daily calories in the morning had lower total daily caloric intake, whereas people who ate a higher percentage of calories in the evening had higher total daily caloric intake. In the present study, overweight and obese people who ate an earlier lunch did not consume fewer calories or engage in more physical activity throughout the day, but they did lose more weight, compared with people who ate a later lunch. Those findings suggest that food consumed earlier in the day somehow results in an increase in resting metabolic rate.

Garaulet M et al. Timing of food intake predicts weight loss effectiveness. Int J Obes. 2013;37:604-611.

Whole Eggs Versus Egg Substitute

Forty men and women (aged 30-70 years) with metabolic syndrome were randomly assigned, in single-blind fashion, to consume daily 3 whole eggs or an equivalent amount of yolk-free egg substitute as part of a moderately carbohydrate-restricted diet (25%-30% of energy) for 12 weeks. Significant reductions in plasma triglyceride levels (p < 0.05) and significant increases in HDL-cholesterol levels (p < 0.05) were seen in both groups. These improvements tended to be greater with whole egg than with egg substitute. No significant changes were seen in LDL-cholesterol levels. Insulin resistance improved significantly with whole eggs and improved nonsignificantly with egg substitute.

Comment: Egg substitutes are popular because of the concern that eating the cholesterol in egg yolks would increase serum cholesterol levels. That concern has persisted despite multiple studies indicating that eating eggs has little effect on cholesterol levels. In the present study, a moderately carbohydrate-restricted diet that contained 3 whole eggs per day improved lipid metabolism and insulin resistance in individuals with metabolic syndrome. The effects tended to be greater than those achieved with an egg substitute. Egg yolks contain a number of beneficial nutrients, including lutein and choline, which have been largely removed from egg substitutes. The available evidence indicates that eggs can be included as part of healthful diet, and that whole egg is preferable to egg substitutes.

Blesso CN et al. Whole egg consumption improves lipoprotein profiles and insulin sensitivity to a greater extent than yolk-free egg substitute in individuals with metabolic syndrome. Metabolism. 2013;62:400-410.

by Alan R. Gaby, MD
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Author:Gaby, Alan R.
Publication:Townsend Letter
Geographic Code:1USA
Date:Nov 1, 2013
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