Literature Review and Commentary

by Alan R. Gaby, MD

Ginkgo Effective for Alzheimer’s Disease

Four hundred-ten patients (mean age, 65 years) with mild to moderate dementia (Alzheimer’s disease with or without cerebrovascular disease or vascular dementia) were randomly assigned to receive, in double-blind fashion, 240 mg of Ginkgo biloba extract EGb 761 (ginkgo) once a day or placebo for 24 weeks. The mean composite score on the Neuropsychiatric Inventory improved by 19.6% in the ginkgo group and did not change in the placebo group (p < 0.001 for the difference in the change between groups). Ginkgo was significantly superior to placebo for the symptoms apathy/indifference, sleep/nighttime behavior, irritability/lability, depression/dysphoria, and aberrant motor behavior. Caregivers’ distress evaluation also indicated a beneficial effect of ginkgo.

Comment

: Numerous studies have investigated the effect of ginkgo in patients with mild to moderate dementia. Although the results have been conflicting, the bulk of the evidence (including the present study) indicates that ginkgo has a modest beneficial effect and is well tolerated. In the present study, ginkgo not only improved behavioral and neuropsychiatric symptoms of the patients, it also improved the well-being of their caregivers. Ginkgo has been found in previous studies to be ineffective for preventing dementia in elderly people with normal cognitive function. That fact that has been emphasized by skeptics to support their erroneous conclusion that ginkgo is worthless as a treatment for mild to moderate dementia.

Bachinskaya N et al. Alleviating neuropsychiatric symptoms in dementia: the effects of Ginkgo biloba extract EGb 761. Findings from a randomized controlled trial. Neuropsychiatr Dis Treat. 2011;7:209–215.

Folic Acid and Vitamin B12 Prevent Cognitive Decline

Nine hundred men and women (aged 60–74 years) with elevated psychological distress (Kessler Distress 10-Scale; scores > 15) were randomly assigned to receive, in double-blind fashion, 400 µg per day of folic acid plus 100 µg per day of vitamin B12 or placebo for 2 years. Cognitive function improved in both groups (presumably due at least in part to practice effects), but the improvement at 24 months was significantly greater in the vitamin group than in the placebo group for scores that measured total cognitive functioning (Telephone Interview for Cognitive Status-Modified [TICS-M]; p = 0.032; effect size = 0.17), immediate recall, (p < 0.05; effect size = 0.15), and delayed recall (p = 0.013; effect size = 0.18).

Comment

: Several studies have shown that supplementation with various B vitamins can slow the rate of cognitive decline in elderly individuals. In the present study, the combination of folic acid and vitamin B12 improved immediate and delayed memory performance relative to placebo in a group of older volunteers. Nutritional status tends to decline and nutrient requirements tend to increase with advancing age. As a result, many seniors may not be consuming the amounts of micronutrients needed for optimal brain health. Supplementation with B vitamins and possibly other micronutrients appears to be a simple, low-cost method of preserving cognitive function in elderly people.

Walker JG et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms – the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr. 2012;95:194–203.

Magnesium Prevents Bleeding During Surgery

Forty patients (aged 18–65 years; mean, 49 years) undergoing single-level microscopic lumbar discectomy under general anesthesia were randomly assigned to receive, in double-blind fashion, intravenous magnesium sulfate (50 mg per kg of body weight in 100 ml of normal saline over 10 minutes, followed by a continuous infusion of 20 mg per kg per hour) or placebo (saline alone). Mean estimated blood loss was significantly lower in the magnesium group than in the placebo group (190 vs. 362 ml). The median Fromme’s scale score (a measure of the extent to which bleeding interfered with the surgical procedure) was significantly better in the magnesium group than in the placebo group. Bleeding time, hemoglobin, platelet count, prothrombin time, international normalized ratio and fibrinogen levels were similar in the two groups. After the bolus of magnesium, mean heart rate was higher and mean arterial pressure was lower in the magnesium group than in the placebo group.

Comment

: This study demonstrated that intravenous administration of magnesium sulfate decreased blood loss and provided better surgical conditions, without having marked hemodynamic effects, in patients undergoing lumbar discectomy. Magnesium deficiency is common in surgical patients; this may be due in part to a loss of intracellular magnesium secondary to the physiological stresses associated with surgery. In addition to reducing blood loss, perioperative magnesium supplementation may reduce the risk of postoperative confusion and delirium, and possibly postoperative atrial fibrillation.

Goral N et al. Effect of magnesium sulphate on bleeding during lumbar discectomy. Anaesthesia. 2011;66:1140–1145.

Bisphenol a from Soup Cans

Seventy-five healthy volunteers (median age, 27 years) were randomly assigned to consume 12 ounces per day of fresh soup (prepared without canned ingredients) or 12 ounces per day of canned soup for 5 days. After a 2-day washout period, each person consumed the other soup for 5 days. Bisphenol A (BPA) was detected in 77% of urine samples after consumption of fresh soup and in 100% of samples after consumption of canned soup. Specific gravity-adjusted mean urinary bisphenol A concentration was 1221% higher after canned than after fresh soup (p < 0.001).

Comment

: BPA is widely used to produce plastic polymers, including those that coat the inner surfaces of food and beverage cans. BPA has estrogenic activity, and is also an endocrine disrupter, in that it alters the synthesis, metabolism, and levels of various hormones in the body. In experimental animals, subcutaneous administration of BPA (100 µg per kg of body weight per day for 4 days) resulted in hyperinsulinemia and impaired glucose tolerance. In addition, observational studies suggest that BPA exposure may increase the risk of developing cardiovascular disease, diabetes, and liver disease. The food and beverage industry should stop exposing people to this toxic compound and, until they do, we should do our best not to buy products that contain it.

Carwile JL et al. Canned soup consumption and urinary bisphenol A: a randomized crossover trial. JAMA. 2011;306:2218–2220.

Micronutrient Supplement Enhances Fertility

Fifty-eight subfertile women (mean age, 32 years) undergoing ovulation induction with clomiphene citrate or gonadotropins were randomly assigned to receive a multiple micronutrient supplement (MMN) or folic acid alone (dose not specified). The MMN provided daily thiamine (8 mg), riboflavin (5 mg), niacin (20 mg), pantothenic acid (6 mg), vitamin B6 (10 mg), folic acid (400 µg), vitamin B12 (20 µg), biotin (150 µg), vitamin C (90 mg), beta-carotene (3 mg), vitamin D (600 IU), magnesium (60 mg), iron (14 mg), zinc (15 mg), copper (1 mg), selenium (50 µg), iodine (140 µg), vitamin E (30 mg), L-arginine (100 mg), inositol (50 mg), and N-acetylcysteine (50 mg). Ovulation induction was attempted 4 weeks after the supplements were started, and the supplements were continued throughout 3 cycles of ovulation induction. In intent-to-treat analysis, the cumulative conception rate after 3 cycles was significantly higher in the MMN group than in the folic acid group (66.7% vs. 39.3%; p = 0.013). In addition, women receiving MMN required significantly fewer attempts to achieve pregnancy compared with women receiving folic acid alone (p < 0.001).

Comment

: Many different nutrients play an essential role in conception and reproduction. The results of the present study indicate that administration of a multiple micronutrient can increase the pregnancy rate in women undergoing ovulation induction.

Agrawal R et al. Prospective randomized trial of multiple micronutrients in subfertile women undergoing ovulation induction: a pilot study. Reprod Biomed Online. 2012;24:54–60.

Low-FODMAPs Diet for Irritable Bowel Syndrome

Eighty-two patients (mean age, 38 years) with irritable bowel syndrome (IBS) were studied. Prior to June 2009, 39 patients were given standard dietary advice (control group), which included regular meal pattern; limiting insoluble fiber intake for diarrhea and increasing it for constipation; reducing alcohol and caffeine intake; limiting fruit to 3 portions a day; avoiding resistant starch (e.g., pulses, sweet corn, green bananas); limiting sorbitol intake; and, in selected cases, avoiding lactose, doing an elimination diet, and/or using probiotics. From June 2009 onward, 43 patients were given a diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols). This diet restricted foods high in fructans (e.g., wheat, onion, garlic), galactooligosaccharides (e.g., chickpeas, lentils), and sorbitol and other polyols; and, in patients with lactose or fructose malabsorption, restricted foods high in lactose and fructose, respectively. After an unspecified period of time, significantly more patients in the low-FODMAPs group than in the control group reported satisfaction with their symptom response (76% vs. 54%; p < 0.04) and improvements in bloating (82% vs. 49%; p = 0.002), abdominal pain (85% vs. 61%; p = 0.023), and flatulence (87% vs. 50%; p = 0.001). Among 10 patients who were asked, mean and median times to improvement were 3.5 and 2 weeks, respectively (range, 2–8 weeks).

Comment

: Numerous studies have shown that food allergy and intolerance to specific food components (such as lactose, fructose, and sorbitol) can provoke gastrointestinal symptoms in people with IBS. The results of the present study indicate that other food components can also contribute to the symptomatology. Information on how to follow a low-FODMAPs diet is available at www.myfoodmyhealth.com/FODMAP/index.php.

Staudacher HM et al. Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. J Hum Nutr Diet. 2011;24:487–495.

Omega-3 Fatty Acids As Adjunctive Therapy for Depression

Forty-two patients (mean age, 40.5 years) with major depressive disorder, whose diet contained no more than 3 g per day of total omega-3 fatty acids, received 20 mg per day of citalopram (a selective serotonin-reuptake inhibitor) and were randomly assigned to receive omega-3 fatty acids (1.8 g per day of eicosapentaenoic acid and 0.4 g per day of docosahexaenoic acid, in 2 divided doses per day) or placebo (olive oil) for 8 weeks. After the first 4 weeks, the dosage of citalopram could be increased to 40 mg per day if clinically appropriate. The proportion of patients who achieved full remission (Hamilton Depression Rating Scale score < 7) was greater in the active-treatment group than in the placebo group (44% vs. 18%). The proportion of patients who did not improve was lower in the active-treatment group than in the placebo group (11% vs. 50%) (p < 0.02 for the overall treatment effect, active vs. placebo). A significant difference between treatments was evident after 4 weeks, but not after 2 weeks. At 4 weeks, nonsignificantly more patients in the active treatment group than in the placebo group increased the dosage of citalopram (61% vs. 50%; p = 0.5).

Comment

: Some studies have shown that omega-3 fatty acids are beneficial in the treatment of depression, but other trials have shown little or no effect. The results of the present study indicate the combination of citalopram and omega-3 fatty acids is significantly more effective than citalopram alone in the treatment of major depressive disorder.

Gertsik L et al. Omega-3 fatty acid augmentation of citalopram treatment for patients with major depressive disorder. J Clin Psychopharmacol. Epub 2011 Dec 22.

N-Acetylcysteine for Polycystic Ovary Syndrome

One hundred women with polycystic ovary syndrome (mean age, 23 years; mean body mass index [BMI], 23.5 kg/m², who had hirsutism and irregular menses, were randomly assigned to receive conventional treatment with metformin (500 mg 3 times per day) or N-acetylcysteine (NAC; 600 mg 3 times per day) for 24 weeks. In both groups there was a small but statistically significant decrease in BMI. Significant improvements were seen in both groups in hirsutism score, insulin resistance (as determined by homeostasis model assessment), and serum testosterone (a decrease). The proportion of patients with regular menses increased in the metformin group from 17% at baseline to 47%, and increased in the NAC group from 29% at baseline to 53%. Both treatments had similar efficacy for all of these parameters. NAC significantly decreased both total-cholesterol and LDL-cholesterol levels, whereas metformin significantly decreased only total cholesterol.

Comment

: This study suggests that that metformin and NAC have comparable effects on hyperandrogenism, insulin resistance, and menstrual irregularity in women with polycystic ovary syndrome. The mechanism of action of NAC is not known.

Oner G, Muderris II. Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2011;159:127–131.