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From the Townsend Letter
April 2009


Literature Review & Commentary
by Alan R. Gaby, MD

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Case Report: D-Pinitol for Polycystic Ovary Syndrome
A 35-year-old woman had a nine-month history of amenorrhea, acne on the face and chest, and intermittent abdominal pains in the area of the ovaries. Her serum testosterone level was more than twice the upper limit of normal. She was given a presumptive diagnosis of polycystic ovary syndrome (PCOS) and was started on D-pinitol (Vital Nutrients) at a dosage of 600 mg twice a day. The D-pinitol product also provided daily 500 mcg of chromium and 1,200 IU of vitamin D. Within two weeks, the acne and abdominal pains had resolved, and menstruation returned shortly thereafter. After one month of treatment, the supplement was discontinued and the acne and abdominal pains returned rapidly. Resumption of treatment was again followed by a rapid resolution of symptoms. Menstruation has remained normal for several months, since shortly after D-pinitol treatment was started.

Comment:
D-Pinitol (3-O-methyl-D-chiro-inositol) is present in foods such as legumes and citrus fruits. It is structurally similar to and has biochemical actions similar to those of D-chiro-inositol, a compound found in small concentrations in the body. D-chiro-inositol is a component of an endogenous phosphoglycan that has been reported to mediate the action of insulin. There is evidence that the insulin resistance seen in women with PCOS is due in part to a deficiency of this D-chiro-inositol-containing phosphoglycan or to a defect in its tissue availability or utilization. In a double-blind trial, supplementation with 1,200 mg per day of D-chiro-inositol for eight weeks improved insulin resistance, decreased serum testosterone levels, and restored ovulation in women with PCOS. D-chiro-inositol is not commercially available, but the present case report and other anecdotal evidence suggest that D-pinitol is also useful for treating PCOS.

Nestler JE, Jakubowicz DJ, Reamer P, et al. Ovulatory and metabolic effects of d-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999;340:1314-1320.

Probiotic Treatment for Bacterial Vaginosis
One hundred-ninety women with bacterial vaginosis (Nugent scores between 7 and 10 on a scale of 0 to 10) received 300 mg of clindamycin twice a day for 7 days and were then randomly assigned to receive or not to receive (control group) vaginal capsules containing 109 colony-forming units of Lactobacillus casei rhamnosus (Lcr35) for seven days. Vaginal swabs for Nugent scoring were taken four weeks after the last probiotic dose. The proportion of women showing an improvement in the Nugent score of at least 5 points was significantly greater in the active-treatment group than in the placebo group (83% vs. 35%; p < 0.001). The median degree of improvement from baseline was 6.61 in the active-treatment group and 4.13 in the control group (p < 0.001).

Comment: Bacterial vaginosis, the most common form of vaginitis, is caused by an imbalance of the bacterial flora in the vagina. The condition can usually be treated successfully with antibiotics, but there is a high recurrence rate. Certain probiotic organisms can help restore normal vaginal flora and thereby prevent recurrences of bacterial vaginosis. In addition to the specific Lactobacillus strain investigated in this study, the combination of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (Fem-Dophilus; Jarrow Formulas) has been shown to enhance the effect of antibiotics in eradicating bacterial vaginosis, and may also help prevent recurrences of this condition. (FEMS Immunol Med Microbiol. 2003;35:131-134; Microbes Infect. 2006;8:1450-1454.)

Petricevic L, Witt A. The role of Lactobacillus casei rhamnosus Lcr35 in restoring the normal vaginal flora after antibiotic treatment of bacterial vaginosis. BJOG. 2008;115:1369-1374.

Healthful Pregnancy Diet for Healthy Children . . .
The association between maternal dietary patterns and fetal growth was investigated in a prospective cohort study of 44,612 women in Denmark. Compared with women who consumed large amounts of red and processed meat and high-fat dairy products, women who had a high intake of vegetables, fruits, poultry, and fish had 26% lower risk of having a small-for-gestational-age infant (birth weight below the 2.5th percentile for gestational age), even though the mean daily energy intake was 17% lower in the former than the latter. The analysis was adjusted for parity, maternal smoking, age, height, prepregnancy weight, and father's height.

Comment: The results of this study suggest that what a mother eats during pregnancy influences its outcome. Vegetables, fruits, poultry, and fish, which are considered helpful for preventing chronic diseases such as heart disease, hypertension, and cancer, now seem to be good for fetuses, too. In contrast, red and processed meat and high-fat dairy products, which are believed to promote the development of various chronic illnesses, may also make babies enter the world too short and too skinny. Many women avoid eating fish during pregnancy because of the fear that the mercury in fish might harm their babies. However, observational studies have shown that children of women who consume moderate amounts of fish during pregnancy (2 to 3 helpings per week) have better neurological development than children of women who avoid fish during pregnancy.

Knudsen VK, et al. Major dietary patterns in pregnancy and fetal growth. Eur J Clin Nutr. 2008;62:463-470.

Hepatitis from Red Yeast Rice?
A 62-year-old woman developed hepatitis after taking 1,200 mg per day of red yeast rice for four months. Clinical improvement was seen after the product was discontinued. The woman was also taking two prescription drugs, fluoxetine and montelukast sodium, both of which have been reported to cause hepatitis. These drugs were apparently not discontinued after hepatitis occurred.

Comment: Red yeast rice contains a group of compounds called monacolins, which have similar actions to those of statin drugs. In fact, some red yeast rice products contain substantial quantities of lovastatin, a statin drug sold under the brand name Mevacor. Hepatotoxicity is a known side effect of statins, but has not been reported previously with red yeast rice. While red yeast rice was not proven to be the cause of hepatitis, it cannot be ruled out as the causative factor. If red yeast does cause hepatitis, the incidence of this side effect is certainly rare. Concomitant use of two potentially hepatotoxic drugs may have increased this patient's susceptibility to liver damage. Based on this report, it would be prudent for individuals taking red yeast rice to discontinue it if they develop unexplained hepatitis or unexplained elevations of liver enzymes.

Roselle H et al. Symptomatic hepatitis associated with the use of herbal red yeast rice. Ann Intern Med. 2008;149:516-517.

Caffeine: A Cause of Panic Attacks
Twenty-five patients with panic disorder, 27 healthy first-degree relatives of these patients, and 22 healthy volunteers with no family history of panic disorder (controls) were randomly assigned to receive, in double-blind fashion, 480 mg of caffeine or placebo, and then the alternate treatment seven days later. After the caffeine challenge, 52% of the patients, 41% of their relatives, and none of the controls had a panic attack (p < 0.001 for patients vs. controls and for relatives vs. controls). The attacks usually began 30 to 40 minutes after caffeine ingestion. No panic attacks occurred after ingestion of placebo.

Comment: The results of this study indicate that ingestion of 480 mg of caffeine (equivalent to about 6 cups of coffee) can trigger a panic attack in people with a history of panic disorder, but not in healthy people. The fact that caffeine also triggered panic attacks in healthy relatives of patients with panic disorder suggests that caffeine sensitivity is genetically determined. Individual differences in susceptibility to caffeine-induced anxiety and caffeine-induced insomnia have also been observed. As part of a routine medical history, it might be useful to ask whether a patient has first-degree relatives who suffer from panic disorder. Patients who have such a family history might be more likely than others to benefit from avoiding caffeine.

Nardi AE et al. A caffeine challenge test in panic disorder patients, their healthy first-degree relatives, and healthy controls. Depress Anxiety. 2008;25:847-853.

Vitamin D Deficiency and Anticonvulsant Drugs
Of 38 children (mean age, 8 years) taking anticonvulsant drugs for epilepsy, 76% had vitamin D deficiency (serum 25-hydroxyvitamin D < 20 ng/ml) and an additional 21% had vitamin D insufficiency (serum 25-hydroxyvitamin D, 20-30 ng/ml). Markers of bone formation and resorption suggested that these patients had accelerated bone turnover. The mean serum 25-hydroxyvitamin D level was significantly lower in patients receiving more than one anticonvulsant than in those receiving a single drug (p < 0.04).

Comment: A number of anticonvulsant drugs induce liver enzymes that inactivate vitamin D. As a result, patients taking these drugs are at risk of developing vitamin D deficiency. Rickets, osteomalacia, and low bone mineral content have been observed in some drug-treated epileptic patients. The results of the present study indicate that vitamin D deficiency is extremely common in this patient population. Serum 25-hydroxyvitamamin D levels should be monitored in patients taking anticonvulsants, and vitamin D supplementation in doses sufficient to correct deficiencies should be recommended.

Nettekoven S et al. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy. Eur J Pediatr. 2008;167:1369-1377.

Panax Ginseng for Alzheimer's Disease
Fifty-eight patients (mean age, 66 years) with Alzheimer's disease were randomly assigned to receive 4.5 g per day of Panax ginseng (Asian ginseng) for 12 weeks or to serve as an untreated control group. Outcome was determined by the Alzheimer Disease Assessment Scale Cognitive Subscale (ADAS-cog) score. The mean ADAS-cog score improved by 15% in the active-treatment group and by 2% in the control group (p < 0.03 for the difference in the change between groups). The improvement reverted to the baseline value after the treatment was discontinued.

Comment: Ginseng has been reported to attenuate learning deficits in the damaged or aging brains of rodents and to increase the density of hippocampal synapses in mice. If this herb also increases synapse density in humans, then it might be capable of slowing or possibly even reversing the disease process in patients with Alzheimer's disease. Longer-term trials are needed to investigate that possibility. Panax ginseng is usually well tolerated, although it may cause overstimulation, increase blood pressure, or have estrogenic effects.

Lee ST et al. Panax ginseng enhances cognitive performance in Alzheimer disease. Alzheimer Dis Assoc Disord. 2008;22:222-226.

Probiotics Prevent Serious Complication of Prematurity
Four hundred thirty-four very-low-birth-weight infants (< 1500 g) who were being breast-fed or receiving mixed feedings (breast milk and formula) were randomly assigned to receive 109 colony-forming units each of Bifidobacterium bifidum and Lactobacillus acidophilus added to their feedings twice a day for 6 weeks or to receive the same feedings without the probiotics. The incidence of death or necrotizing enterocolitis stage 2 or greater was significantly lower in the active-treatment group than in the control group (1.8% vs. 9.2%; p = 0.002). The incidence of necrotizing enterocolitis stage 2 or greater was also significantly lower in the active-treatment group than in the control group (1.8% vs. 6.5%; p = 0.02). No adverse effects, such as sepsis, flatulence, or diarrhea, were seen.

Comment: Necrotizing enterocolitis is a serious gastrointestinal disease seen mainly in premature, very-low-birth-weight infants. It is characterized by necrosis of part of the intestine, which can lead to life-threatening complications. While the cause is unknown, it appears to be related to intestinal ischemia and to the presence of abnormal intestinal flora. The results of the present study indicate that the addition of probiotics to the feedings of very-low-birth-weight infants can reduce the incidence of necrotizing enterocolitis and decrease the death rate in these infants.

Lin HC, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial.
Pediatrics. 2008;122:693-700.



Alan R. Gaby, MD
drgaby@earthlink.net

 

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