Literature Review and Commentary

by Alan R. Gaby, MD

Keep Sodium Intake Low for Heart Failure Patients …

Sodium intake was estimated from 3-day food records in 123 patients (mean age, 60 years) with stable systolic heart failure, and the patients were then followed for a median of 3 years. Mean sodium intakes in the lower, middle, and upper tertiles were 1.4, 2.4, and 3.8 g per day, respectively. The cumulative number of episodes of acute decompensated heart failure (ADHF) after 3 years were 12%, 15%, and 46% in the lower, middle, and upper tertiles of sodium intake, respectively (p = 0.001), and the upper tertile was associated with an adjusted hazard ratio of 2.55 (p < 0.001). In addition, the upper tertile was associated with an adjusted hazard ratio of 1.39 (p < 0.02) for all-cause hospitalization and 3.54 (p = 0.005) for mortality.

Comment

: Most experts recommend that patients with symptomatic heart failure limit sodium intake to 2 to 3 g per day. However, current guidelines of the American College of Cardiology/American Heart Association suggest that as much as 4 g per day may be appropriate for a similar patient group. The results of the present study support more stringent guidelines for sodium intake than those currently recommended for heart failure patients. However, because this was an observational study, it does not prove causality. The better outcomes in patients who consumed less sodium may have been due in part to compliance bias. It is well known that patients who comply with doctors’ recommendation tend to have better outcomes than patients who do not comply, regardless of what the recommendations are.

Arcand J et al. A high-sodium diet is associated with acute decompensated heart failure in ambulatory heart failure patients: a prospective follow-up study. Am J Clin Nutr. 2011;93:332–337.

…

but Severe Sodium Restriction Can Increase Insulin Resistance

One hundred fifty-two healthy men and women (mean age, 39 year) consumed a low-salt diet (urinary sodium < 0.46 g per day) and a high-salt diet (urinary sodium > 3.45 g per day) for 7 days each, in random order. Compared with the high-salt diet, the low-salt diet resulted in a significant increase in insulin resistance, as determined by the homeostasis model assessment index (mean, 2.8 vs. 2.4; p < 0.01). Low salt intake was associated with insulin resistance independently of age, gender, blood pressure, and body mass index.

Comment

: A low-salt diet activates the renin-angiotensin-aldosterone and sympathetic nervous systems, both of which can increase insulin resistance. Several other studies have also shown that severe sodium restriction can worsen insulin resistance and impair blood glucose control. Thus, both excessive sodium intake and sodium deficiency can have deleterious consequences. For many people, a moderate level of sodium intake (about 2.3 g per day of sodium, equivalent to 5.8 g per day of salt) appears to be preferable to higher or lower levels of intake. Moderate sodium intake can be achieved by avoiding high-sodium foods and by not adding salt to food during cooking or at the table. People who do not use table salt should monitor their dietary iodine intake and take a low-dose iodine supplement (e.g., 150 mcg per day) if necessary.

Garg R et al. Low-salt diet increases insulin resistance in healthy subjects. Metabolism. 2011;60:965–968.

Green Tea Lowers Serum Cholesterol

A meta-analysis was conducted on 14 randomized controlled trials (with a total of 1,136 subjects) that examined the effect of green tea beverages and extracts on lipid profiles in adults. Compared with controls, green tea significantly lowered mean total cholesterol by 7.2 mg/dl (p < 0.001) and LDL cholesterol by 2.19 mg/dl (p < 0.001). Green tea had no effect on HDL cholesterol. The effect of green tea was not influenced by the dose of green tea catechins, study duration, or individual health status.

Comment

: Green tea is widely regarded as a health-promoting beverage. Previous studies have shown that consumption of green tea or green tea extracts may help prevent influenza, dental caries, and certain types of cancer. The results of the present study indicate that green tea also has a modest cholesterol-lowering effect, and therefore may reduce the risk of developing cardiovascular disease.

Zheng XX et al. Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials. Am J Clin Nutr. 2011;94:601–610.

L-Carnitine for Autism Spectrum Disorders

Thirty children (aged 3–10 years) with autism spectrum disorders were randomly assigned to receive, in double-blind fashion, L-carnitine (50 mg per kg of body weight per day) in liquid form or placebo for 3 months. The treatment was administered in 2 divided doses per day, morning and evening. In the L-carnitine group, compared with baseline, the mean score on the Childhood Autism Rating Scale improved by 5.3%, whereas no change was seen in the placebo group (p = 0.02 for the difference in the change between groups). In the L-carnitine group, compared with baseline, the mean score on the Modified Clinical Global Impression improved by 25%, whereas no change was seen in the placebo group (p = 0.03 for the difference in the change between groups). L-Carnitine was generally well tolerated.

Comment

: Carnitine facilitates the transport of fatty acids into mitochondria, where they are metabolized to produce ATP, the body’s main storage form of energy. The present study demonstrated that L-carnitine has a modest beneficial effect in children with autism spectrum disorders. While the mechanism of action is not known, L-carnitine might exert a nonspecific beneficial effect on brain function by enhancing mitochondrial energy production.

Geier DA et al. A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders. Med Sci Monit. 2011;17:PI15–PI23.

Flavonoid from Oranges Lowers Blood Pressure

Twenty-four overweight men (aged 50–65 years) were randomly assigned to consume 250 ml of orange juice twice a day (providing 292 mg per day of hesperidin); a control drink with sugar composition similar to that of orange juice, plus 146 mg twice a day of hesperidin in capsule form; or the control drink plus 1 capsule twice a day of placebo (control group). Each participant received each of the 3 treatments during 3 separate 4-week periods. Compared with the control period, mean diastolic blood pressure was significantly lower by 3.2 mm Hg with the control drink plus hesperidin, and by 5.5 mm Hg with orange juice. Systolic blood pressure did not differ between treatment periods.

Comment

: The results of this study indicate that supplementation with approximately 300 mg per day of hesperidin (an amount present in 500 ml of orange juice) significantly decreased diastolic blood pressure in overweight males. The greater effect of orange juice, as compared with quercetin, suggests that other substances present in orange juice (such as potassium) also have an antihypertensive effect. The concentration of hesperidin in oranges is greatest in the pith (the white portion of the peel).

Morand C et al. Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers. Am J Clin Nutr. 2011;93:73–80.

Ginkgo Biloba Does Not Increase the Risk of Bleeding

A meta-analysis was conducted on 18 randomized controlled trials with a total of 1,985 adults that examined the effect of Ginkgo biloba extract (ginkgo) or placebo in patients with dementia, peripheral artery disease, or diabetes mellitus (13% were healthy volunteers). In the pooled analysis, ginkgo significantly reduced blood viscosity, but had no significant effect on ADP-induced platelet aggregation, fibrinogen concentration, prothrombin time, or activated partial thromboplastin time. Subgroup analyses revealed a significant reduction in activated partial thromboplastin time for subgroups receiving high-dose ginkgo (240 mg per day or more) and for studies including only patients, not healthy volunteers; however, both findings were not considered clinically relevant.

Comment

: Because ginkgo has been reported to inhibit platelet-activating factor, concerns have been raised that this herb could increase the risk of bleeding. There have been several case reports in which spontaneous or excessive bleeding (including one case of subdural hematoma) occurred in individuals taking ginkgo. However, a cause-effect relationship was not proven in any of these cases. In a study of 309 demented patients randomly assigned to receive 120 mg per day of ginkgo or placebo for 12 months, one subdural hematoma occurred in the placebo group and none in the ginkgo group. The results of the present study suggest that ginkgo is unlikely to increase the risk of bleeding.

Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy. 2011;31:490–502.

Magnesium for Menopausal Hot Flashes

Twenty-nine women (mean age, 53.5 years) who were experiencing hot flashes after treatment for breast cancer (at least 14 hot flashes per week for at least 1 month) received 250 mg per day of magnesium (as magnesium oxide) for 2 weeks. If adequate symptom relief was obtained (i.e., a reduction of at least 50% in the frequency or severity of symptoms), then the same dose was continued for a total of 4 weeks. If adequate symptom relief was not obtained, then the dose was increased to 250 mg twice a day for the second 2 weeks. Twenty-five patients completed the trial, of which 17 increased the magnesium dose. The mean frequency of hot flashes per week fell by 47% (p < 0.01), from 52.2 at baseline to 27.7. The mean hot flash score (the product of the hot flash frequency and the average severity) improved by 56% (p = 0.02).

Comment

: Some of the chemotherapy drugs and hormones used to treat breast cancer can induce a state of menopause. The present study suggests that magnesium is effective for women experiencing hot flashes after treatment for breast cancer. Anecdotal information suggests that magnesium is also beneficial for menopausal symptoms in women who have not had breast cancer. While placebo-controlled trials are needed to confirm these reports, considering its safety and low cost, magnesium supplementation should be considered for all women suffering from menopausal hot flashes.

Park H et al. A pilot phase II trial of magnesium supplements to reduce menopausal hot flashes in breast cancer patients. Support Care Cancer. 2011;19:859–863.

Probiotics Enhance Bowel Prep for Colonoscopy

One hundred-four patients with constipation and 107 patients without constipation who were scheduled for colonoscopy were randomly assigned to receive, in double-blind fashion, a probiotic preparation (Bacillus subtilis [10⁹ colony-forming units], and Streptococcus faecium [9 x 10⁹ colony-forming units]) or placebo 3 times per day for 2 weeks prior to the colonoscopy. All patients received oral sodium phosphate for bowel cleansing prior to the procedure. In the group with constipation, the proportion of patients who had a satisfactory bowel preparation was significantly higher in the probiotics group than in the placebo group (54.9% vs. 20.8%; p < 0.001). Preparation quality was significantly better in patients without constipation than in those with constipation, and was not affected by probiotics treatment. Among constipation patients, preparation-related adverse events and post-colonoscopy symptoms were less frequent and less severe in the probiotics group than in the placebo group.

Comment

: This study demonstrates that, in patients with constipation, pretreatment with a specific probiotic preparation for 2 weeks as part of bowel preparation significantly improved colonic mucosa visualization during colonoscopy and reduced preparation-related and post-colonoscopy gastrointestinal symptoms. Previous research has demonstrated that a wide range of other probiotic strains are beneficial for chronic constipation. It is therefore likely that other strains would also be useful for bowel preparation in constipated patients scheduled for colonoscopy.

Lee H et al. A feasibility study of probiotics pretreatment as a bowel preparation for colonoscopy in constipated patients. Dig Dis Sci. 2010;55:2344–2351.