Literature Review and Commentary

by Alan R. Gaby, MD

Fruit and Vegetable Powder Prevents Colds

Five hundred forty-three health-care professionals (mean age, 40 years) residing in Berlin, Germany, were randomly assigned to receive, in double-blind fashion, 4 capsules per day of Juice Plus (a proprietary product that contains dried fruit and vegetable powders) or placebo for 6 months. The mean number of days with moderate or severe cold symptoms during the study was significantly lower by 20% in the active-treatment group than in the placebo group (7.6 vs. 9.5; p = 0.023). The mean number of days with any cold symptoms did not differ between groups.

Comment

: The results of this study indicate that regular use of Juice Plus produced a modest decrease in the severity of cold symptoms among healthy volunteers. Dehydrated fruit and vegetable concentrates should not be considered a substitute for regular consumption of fruits and vegetables. However, for people who are unable to consume adequate amounts of these healthful foods, such a supplement may be worthwhile.

Roll S et al. Reduction of common cold symptoms by encapsulated juice powder concentrate of fruits and vegetables: a randomised, double-blind, placebo-controlled trial. Br J Nutr. Epub 2010;Aug 23:1–5.

Nutrition Guidelines: Foods Versus Nutrients

This editorial points out that classifying foods as healthful or unhealthful on the basis of their content of a small number of specific nutrients (such as fat, cholesterol, or certain vitamins) may lead to dietary practices that defy common sense. For example, some low-fat processed foods are high in refined sugar. School nutrition guidelines specify a minimum number of total calories but a maximum proportion of fat calories, and foods like gelatin desserts and sugar-sweetened low-fat milk have been used to achieve these guidelines. Based primarily on the content of a few nutrients, a national obesity-prevention program categorizes whole-milk and cheese with doughnuts and french fries as foods to eat occasionally. Sautéed vegetables and canned tuna packed in vegetable oil are categorized with processed cheese spread and pretzels as foods to eat sometimes, and fresh fruits and vegetables are categorized with trimmed beef and fat-free mayonnaise as foods to eat almost anytime. The food industry adds a few selected micronutrients to highly processed foods such as refined cereals and sugar-sweetened beverages, and claims that these foods are nutritious. Greater emphasis on food-based guidelines (as opposed to nutrient-based guidelines) could help correct widespread misunderstandings about what constitutes a healthful diet and would reduce the possibility for industry manipulation.

Comment

: It is refreshing to see such a common-sense editorial in the Journal of the American Medical Association. Promoting healthful eating patterns could have a major positive impact on the prevalence of obesity, cardiovascular disease, diabetes, nonalcoholic fatty liver disease, and other chronic diseases.

Mozaffarian D, Ludwig DS. Dietary guidelines in the 21st century – a time for food. JAMA. 2010;304:681–682.

S-Adenosylmethionine as Adjunctive Treatment for Depression

Seventy-three patients with major depressive disorder who had failed to respond to serotonin-reuptake inhibitors (SRIs) were randomly assigned to receive, in double-blind fashion, 800 mg of S-adenosylmethionine (SAMe) twice a day or placebo for 6 weeks, while continuing SRIs. A response was defined as at least a 50% decrease in the Hamilton Depression Rating Scale (HAM-D) score or a final score of 7 or less. The proportion of patients who responded was significantly higher in the SAMe group than in the placebo group (46% vs. 18%; p = 0.01). The remission rate was also significantly higher in the SAMe group than in the placebo group (36%. vs. 12%; p = 0.02). The proportion of patients who discontinued treatment because of adverse events was lower in the SAMe group than in the placebo group (5.1% vs. 8.8%).

Comment

: The results of this study indicate that the addition of SAMe was safe and beneficial for SRI nonresponders with major depressive disorder. In previous studies, SAMe has demonstrated an antidepressant effect when administered by itself. Therefore, it is not clear in the present study whether SAMe exerted a direct antidepressant effect or whether it augmented the effect of SRIs. Nevertheless, the combination of SAMe and an SRI is worth considering for patients with refractory depression.

Papakostas GI et al. S-Adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry. 2010;167:942–948.

Vitamin C Improves Mood in Hospitalized Patients

Fifty-five mentally competent patients admitted to a non-ICU medical or surgical ward of a university teaching hospital in Canada were randomly assigned to receive, in double-blind fashion, 500 mg of vitamin C twice a day or 1000 IU of vitamin D twice a day for up to 10 days. Patients who were already receiving supplemental vitamin D on admission were assigned to the vitamin C group. Prior to treatment, 56% of the patients had a moderately low plasma vitamin C concentration and 9% had a very low level. Thirty-two patients completed the study (i.e., they received treatment for at least 5 days). Among those 32 patients, there was a mean improvement of 34% (p = 0.013) in the score on the Profile of Mood States (a questionnaire that measures mood). No improvement of mood was seen in the vitamin D group.

Comment

: Acutely and chronically ill patients often have suboptimal or deficient levels of vitamin C. Poor vitamin C status can result in decreased resistance against infection, impaired wound healing, and other abnormalities that would delay recovery in the hospital. The present study demonstrates that vitamin C supplementation improves mood in hospitalized patients, which may enhance recovery or at least make hospitalization more tolerable. A case can be made that most patients should receive supplemental vitamin C upon admission to the hospital.

Zhang M et al. Vitamin C provision improves mood in acutely hospitalized patients. Nutrition. Epub Aug 4, 2010.

Selenium Supplementation for Early Prostate Cancer

One hundred forty men with localized nonmetastatic prostate cancer, who had elected to forgo active treatment, and instead to be followed by active surveillance, were randomly assigned to receive, in double-blind fashion, selenium (200 or 800 mcg per day as high-selenium yeast) or placebo for up to 5 years. Prostate-specific antigen (PSA) velocity was used as a marker of cancer progression. The median PSA doubling time was 6.24 years in the placebo group, 6.98 years in the group receiving 200 mcg per day of selenium, and 8.45 years in the group receiving 800 mcg per day of selenium (differences not statistically significant). In secondary subgroup analysis, among men in the highest quartile of baseline plasma selenium, mean PSA velocity was significantly higher in those receiving 800 mcg per day of selenium than in those receiving placebo (p = 0.018). The authors concluded that selenium supplementation did not slow the rise in PSA levels in men with localized prostate cancer, and that high-dose selenium was associated with increased PSA velocity in men with high baseline plasma selenium concentrations.

Comment

: Selenium has demonstrated anticancer activity in animals, and there is some evidence (though conflicting) that it can help prevent some types of cancer in humans. In addition, selenium supplementation has been reported to decrease the adverse effects of certain chemotherapy regimens. In the present study, there was a nonsignificant trend toward slower progression of early prostate cancer in men given selenium supplements. However, high-dose selenium treatment may have had an adverse effect in men with high baseline plasma selenium levels. This latter effect must be interpreted with caution, since it was derived from a secondary subgroup analysis, which can be prone to error. At present, there is no strong evidence for or against the use of selenium in men with early prostate cancer, although high-dose selenium should probably not be given to men with initially high serum selenium levels.

Stratton MS et al. Oral selenium supplementation has no effect on prostate-specific antigen velocity in men undergoing active surveillance for localized prostate cancer. Cancer Prev Res. 2010;3:1035–1043.

Diabetes Drug Bites the Dust

In late September, the US Food and Drug Administration greatly restricted the availability of rosiglitazone (Avandia; a drug used to treat type 2 diabetes), and the European Medicines Agency banned the drug completely. These actions were taken because of accumulating evidence that rosiglitazone increases the incidence of cardiovascular events when compared with other antidiabetes drugs, even though it is very effective at lowering blood glucose levels. At its peak several years ago, annual sales of rosiglitazone totaled $3 billion. However, its use declined over the past few years because of mounting safety concerns. There have been more than 13,000 lawsuits against GlaxoSmithKline (the manufacturers of Avandia), and in July the company agreed to pay $460 million to settle 10,000 such suits. Plaintiffs have alleged that GlaxoSmithKline failed to warn users about the serious side effects of the drug.

Comment

: Although improving hyperglycemia is known to reduce the risk of cardiovascular disease, rosiglitazone apparently has other adverse effects that outweigh the beneficial effect of blood glucose-lowering. I have previously pointed out in the Townsend Letter that statin drugs (which are used to prevent cardiovascular disease) increase the risk of developing diabetes. Now we find that a drug used to treat diabetes increases the risk of developing cardiovascular disease. No wonder so many people are becoming interested in natural alternatives.

Mandated Preventive Care: The Expensive ‘Free Lunch’

Beginning on September 23, medical insurance companies will be required to pay for a wide range of preventive care services with no out-of-pocket costs to the patient (i.e., no deductible and no copay). These mandates apply to all new or revised insurance plans. Covered services include mammograms, colonoscopies, smoking cessation programs, and weight loss and alcoholism treatment programs. According to some estimates, these new mandates will increase the cost of health insurance by 20% to 50% (depending on the type of policy), because insurance companies will need to recoup their payouts for these “free” services that policy holders will be lining up to receive.

Comment

: Some of the mandated benefits (such as mammograms and colonoscopies) may eventually save money, because of a lower incidence of breast and prostate cancer. However, treatments for tobacco, alcohol, and food addiction can be very expensive, have a high rate of failure or recidivism, and may not be cost-effective. Irrespective of their cost-effectiveness, these mandates raise philosophical and constitutional questions regarding whether the government has the right to force us to purchase specific medical services that are deemed to be “good for us.” Moreover, some of these mandates may not be in society’s best interest, since they remove financial disincentives against unhealthful behaviors, while diluting the reduction in health-insurance premiums currently enjoyed by nonobese, nonsmoking, nonalcoholic policy holders.

Iron Deficiency and Congestive Heart Failure

Iron status was examined in 546 patients (mean age, 55 years) with stable systolic congestive heart failure (CHF). Iron deficiency was defined as a serum ferritin level < 100 mcg/L or a serum ferritin level of 100–300 mcg/L with transferrin saturation < 20%. Thirty-seven percent of the patients had iron deficiency. During a mean follow-up period of 2 years, 28% of the patients died and 6% had a heart transplant. In multivariate analysis, iron deficiency (but not anemia) was associated with a 58% increase in the incidence of death or heart transplant. The authors concluded that iron deficiency is common in patients with systolic CHF, and is a strong and independent predictor of an unfavorable outcome.

Comment

: In addition to playing a role in oxygen transport (as a component of hemoglobin), iron is involved in mitochondrial energy production and muscle contraction. Thus, iron deficiency could adversely influence heart function, even if the deficiency is not severe enough to cause anemia. The definition of iron deficiency in the present study was extremely liberal, and some of the patients considered to be deficient may have had normal iron status. According to one report, iron deficiency is extremely unlikely in elderly people whose serum ferritin level is greater than 75 mcg/L. Clinical trials are needed to determine whether iron supplementation would improve outcomes in CHF patients who are iron-deficient according to the criteria outlined in the present study.

Jankowska EA et al. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J. 2010;31:1872–1880.