Soy isoflavones for menopausal symptoms
Seventy-nine postmeno-pausal women (mean age, 54 years) were randomly assigned to receive, in double-blind fashion, 120 mg/day of soy isoflavones in two divided doses or 0.625 mg/day of conjugated equine estrogens (CEE) for six months. There was a significant improvement in menopausal symptoms (as determined by the Kupperman Menopausal index) in both groups, and the amount of improvement did not differ significantly between groups. There was a significant decrease in vaginal pH and an increase in superficial vaginal cells and endometrial proliferation after three and six months in the group receiving CEE, but these parameters did not change in the isoflavone group.

Comment: The results of this study suggest that supplementation with 120 mg/day of soy isoflavones had a similar effect as CEE on certain menopausal symptoms. In contrast to CEE, however, soy isoflavones had no effect on endometrial tissue or vaginal mucosa. Thus, soy isoflavones may be less effective than CEE for relieving symptoms related to vaginal thinning, but safer than CEE with respect to the risk of causing endometrial cancer. Not all studies using soy isoflavones to treat menopausal symptoms have demonstrated a beneficial effect. Nevertheless, because of its better safety profile, isoflavones may be considered for first-line treatment of mild-to-moderate menopausal symptoms. Some, but not all, studies have shown that soy isoflavones can also prevent bone loss in postmenopausal women.

Kaari C, et al. Randomized clinical trial comparing conjugated equine estrogens and isoflavones in postmenopausal women: A pilot study. Maturitas. 2006;53:49-58.

Intravaginal vitamin C for non-specific vaginitis
One hundred women (mean age, 35 years) with non-specific vaginitis (NSV; bacterial vaginosis) were randomly assigned to receive, in double-blind fashion, vitamin C vaginal tablets (250 mg) or placebo once a day at bedtime for 16 days. The vitamin C product was specially formulated to release the vitamin over a period of hours, in order to enhance its action and to prevent irritation of the vaginal epithelium. It was not specified whether ascorbic acid or buffered vitamin C was used. In intent-to-treat analysis, one week after the end of treatment, NSV was still present in more women in the placebo group than in the vitamin C group (35.7% vs. 14.0%; p = 0.02). Two weeks after the end of treatment, NSV was present in 34.1% and 21.7% of patients, respectively (p = 0.06). Clue cells disappeared in 79% of patients treated with vitamin C and in 53% of patients on placebo; bacteria disappeared in 77% and 54%, respectively; and lactobacilli reappeared in 79.1 and 53.3%, respectively; all of these differences were statistically significant. Adverse events occurred in four patients: two on placebo (pruritus, cystitis) and two on vitamin C (candidiasis).

Comment: NSV is a common and often difficult-to-treat gynecological condition. The results of the present study suggest that intravaginal administration of vitamin C is a safe and moderately effective treatment for this problem. A slow-release preparation, as used in this study, may be preferable to a regular vitamin C tablet or capsule, both for increasing tolerability and enhancing efficacy.

Another promising treatment for NSV is a combination of two specific strains of lactobacilli. That treatment is discussed in my editorial, elsewhere in this issue.

Petersen EE, Magnani P. Efficacy and safety of vitamin C vaginal tablets in the treatment of non-specific vaginitis. A randomised, double blind, placebo-controlled study. Eur J Obstet Gynecol Reprod Biol. 2004;117:70-75.

Response of ovarian cancer to fermented soy beverage
A 56-year-old woman with rapidly progressive, platinum-resistant ovarian cancer began self-treatment with four ounces per day of Haelan951, a commercially available fermented soy beverage. The disease stabilized during a nine-month follow-up period, including improvement in the serum tumor marker CA-125.

Comment: Women with ovarian cancer who experience disease progression during or within six months of first-line treatment with platinum-based anticancer drugs are considered to have platinum-resistant tumors and have a poor prognosis. Fermented soy products contain high concentrations of genistein (an isoflavone) and other compounds that exhibit anticancer activity in animal studies or in vitro. The amount of isoflavones in Haelan951 is said to be two-to-four times higher than that present in other soy products such as tofu and soy milk.

Klein A, et al. Prolonged stabilization of platinum-resistant ovarian cancer in a single patient consuming a fermented soy therapy. Gynecol Oncol. 2006;100:205-209.

Potassium prevents heart disease
Some 1,981 men (mean age, 75 years) living in a retirement home in Taiwan were randomly assigned to receive food prepared with regular salt (control group) or with potassium-enriched salt (49% potassium chloride, 49% sodium chloride, two percent other additives) for approximately 31 months. Patients with impaired renal function were excluded. Age-adjusted cardiovascular mortality was significantly lower by 41% in the group receiving potassium-enriched salt than in the control group. Persons in the potassium group spent significantly less ($426 per year) on inpatient care for cardiovascular disease than did the control group, after adjustment for age and previous hospitalization expenditures.

Comment: The results of this study indicate that switching from regular salt to potassium-enriched salt decreased cardiovascular disease mortality and health care costs among elderly men. The beneficial effect was probably due mainly to the increase in potassium intake, although the decrease in sodium intake may have contributed as well. Previous studies have shown that increasing potassium intake reduces blood pressure in people with hypertension. Furthermore, observational studies in humans and experimental studies in animals have shown that potassium supplementation reduces the incidence of stroke, independently of any effect on blood pressure. Mechanisms by which potassium may improve cardiovascular disease include inhibition of platelet aggregation, enhancement of myocardial metabolism, and regulation of blood pressure (prevention of both hypertension and hypotension). The high potassium content of fruits and vegetables may explain in part why ingestion of these foods is associated with a reduced risk of developing cardiovascular disease.

Chang HY, et al. Effect of potassium-enriched salt on cardiovascular mortality and medical expenses of elderly men. Am J Clin Nutr. 2006;83:1289-1296.

N-acetylcysteine for obsessive-compulsive disorder
A 58-year-old woman with a history of obsessive-compulsive disorder since childhood had a stable but partial response to fluvoxamine (Luvox; a selective serotonin-reuptake inhibitor), which she had been taking for 12 years. N-acetylcysteine (NAC) was added at a dose of 600 mg/day, which was increased progressively over six weeks to 3 g/day for an additional seven weeks. A clear improvement in compulsive hand-washing was seen, and this improvement persisted for a further two months with continued NAC treatment.

Comment: Hyperactivity of glutamatergic neuro-transmission has been implicated in the pathophysiology of obsessive-compulsive disorder. NAC was tried in this case, because it is believed to reduce synaptic glutamatergic activity. Obsessive-compulsive disorder frequently fails to respond adequately to medications and psychotherapy, so additional studies of NAC are warranted. While NAC is generally well tolerated, long-term use has the potential to deplete zinc and copper, so supplementation with these minerals is probably a good idea for people taking NAC.

Lafleur DL, et al. N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder. Psychopharmacology. 2006;184:254-256.

Antioxidants for chronic pancreatitis
Thirty-six patients with chronic pancreatitis, many of whom had problems with alcohol or drug dependence, were randomly assigned to receive, in double-blind fashion, an antioxidant tablet or placebo four times a day for ten weeks, and then the alternate treatment for an additional ten weeks. The antioxidant tablets provided daily 300 mcg of selenium, 12 mg of beta-carotene, 282 IU of vitamin E, 600 mg of ascorbic acid, and 1,600 mg of methionine. Nineteen patients completed the trial. Improvements were seen during the active-treatment period (as compared with baseline) in physical function, social function, pain, and health perception. These parameters worsened during placebo treatment, and each of the improvements during active treatment was significant when compared with the change during placebo treatment (p < 0.05). Two patients complained of nausea, and one complained of an unpleasant taste from the antioxidant preparation; this was probably due to the presence of methionine.

Comment: Patients with chronic pancreatitis typically suffer from intractable abdominal pain that is resistant to most analgesics. There is evidence that the pain may be due in part to oxygen free radical-induced pancreatic damage. The results of the present study suggest that supplementation with an antioxidant preparation containing selenium, beta-carotene, vitamin C, vitamin E, and methionine can reduce pain and improve quality of life in patients with chronic pancreatitis.

Kirk GR, et al. Combined antioxidant therapy reduces pain and improves quality of life in chronic pancreatitis. J Gastrointest Surg. 2006;10:499-503.

Eating cherries reduces inflammation
Eighteen healthy men and women consumed 280 grams (about ten ounces) of Bing sweet cherries per day for 28 days. The mean serum C-reactive protein (CRP) concentration decreased compared with baseline by eight percent (p = 0.11) after 14 days and by 25% (p < 0.05) after 28 days. Four weeks after cherry consumption was discontinued, the mean CRP level was ten percent higher (p = 0.11) than at the end of the period of cherry consumption. These results suggest that cherry consumption exerts an anti-inflammatory effect.

Comment: In a pilot study published in 1950 (Tex Rep Biol Med. 1950;8:309-311), consumption of one-half pound of fresh or canned cherries per day (or an equivalent amount of cherry juice) prevented recurrences of gout attacks in patients with a history of gout. While that study has never been followed up, ingestion of cherries or cherry juice has become a popular folk remedy for the treatment of acute gout attacks and for the prevention of recurrences.

The results of the present study suggest that cherries contain one or more substances that have anti-inflammatory activity and provide a potential mechanism whereby eating cherries might be helpful for patients with gout. Because there was no control group in the new study, the possibility of a placebo effect cannot be ruled out. However, the time has come for a controlled trial to determine whether eating cherries is an effective treatment or prophylaxis for gout.

Kelley DS. Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women. J Nutr. 2006;136:981-986.

Eating overcooked food may impair protein utilization
Eighteen healthy adolescent males (aged 11-14 years) were randomly assigned to consume a diet that was either low (white diet) or high (brown diet) in Maillard reaction products for two weeks. After a six-week washout period, each person consumed the alternate diet for an additional two weeks. The foods included in the two diets were basically the same, but were processed differently when possible; e.g., fried vs. boiled chicken and fried vs. boiled potatoes. Compared with consumption of the white diet, consumption of the brown diet resulted in 47% higher fecal nitrogen excretion (p = 0.002), 12% lower apparent nitrogen absorption (p < 0.001), and six percent lower nitrogen digestibility (p = 0.001).

Comment: The Maillard reaction (also known as “glycation” or the “browning reaction”) occurs when protein is heated in the presence of a reducing sugar such as fructose, glucose, or lactose. A similar type of reaction (called lipoxidation) also occurs when proteins are heated in the presence of certain lipids. Previous studies have shown that ingestion of the molecules that form during these chemical reactions (i.e., advanced glycation end-products and advanced lipoxidation end-products) can evoke an inflammatory response and probably contribute to the pathogenesis of cardiovascular disease, diabetic end-organ damage, and chronic renal failure.

The results of the present study indicate that eating heavily cooked food also impairs protein digestion and absorption. While that effect would probably not be clinically significant for people consuming a high-protein diet, it could be important for those whose diets are marginal or low in protein.

The best approach would be to eat as many raw foods as possible and to use the least harsh cooking techniques when eating cooked foods. Thus, boiling and poaching are preferable to frying and grilling; medium-rare would be better than well-done; and protein-containing foods that are baked in the presence of lactose (i.e., milk) or high-fructose corn syrup (e.g., pastries, pies, doughnuts) should be avoided.

Seiquer I, et al. Diets rich in Maillard reaction products affect protein digestibility in adolescent males aged 11-14 y. Am J Clin Nutr. 2006;83:1082-1088.

Alan R. Gaby MD
drgaby@earthlink.net