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Literature review & commentary.

5-Hydroxytryptophan Effective for Depression

Seventy patients (mean age, 37 years) who were experiencing their first episode of depression were randomly assigned to receive, in double-blind fashion, 5-hydroxytryptophan (5-HTP) or fluoxetine for 8 weeks. The dosage of 5-HTP was 50 mg 3 times per day for 2 weeks, then 100 mg 3 times per day for 2 weeks, then 400 mg per day in 3 divided doses per day. The dosage of fluoxetine was 20 mg per day for 2 weeks, then 30 mg per day for 2 weeks, then 40 mg per day. Beginning in week 2, both groups showed a significant reduction (improvement) in the mean score on the Hamilton Rating Scale for Depression. The improvement was slightly and nonsignificantly greater in the fluoxetine group than in the 5-HTP group. Adverse effects were slightly and nonsignificantly more common in the fluoxetine group than in the 5-HTP group. The most common adverse effects in both groups were nausea, anorexia, and headaches; insomnia was also a common side effect in the fluoxetine group.

Comment: The results of this study suggest that 5-HTP is as effective or nearly as effective as a commonly used selective serotonin-reuptake inhibitor (SSRI). Both 5-HTP and SSRIs work by increasing serotonin activity in the brain: 5-HTP by serving as a precursor for serotonin, and SSRIs by preventing the reuptake of serotonin at nerve synapses. Because 5-HTP and SSRIs both increase serotonin activity, they should not in most circumstances be used together, because combining them could increase the risk of developing serotonin toxicity (serotonin syndrome).

While 5-HTP appears to be an effective and relatively safe treatment for depression, it may be preferable to use L-tryptophan instead to treat depression. Unlike 5-HTP, L-tryptophan is a building block for

protein synthesis and is also metabolized to important compounds such as niacin and picolinic acid. Consequently, if a person is deficient in tryptophan, then supplementing with L-tryptophan would provide a broader spectrum of benefits than would treatment with 5-HTP. In addition, 5-HTP bypasses tryptophan hydroxylase (the rate-limiting enzyme involved in serotonin synthesis) and therefore bypasses a potential regulatory mechanism for preventing excessive serotonin production. In my experience, an effective dosage regimen for L-tryptophan is 1000 to 1500 mg twice a day, taken between meals or at bedtime. The addition of niacinamide (500 or 1000 mg with each L-tryptophan dose) appears to enhance the efficacy of L-tryptophan by inhibiting the enzyme tryptophan pyrrolase, which breaks down tryptophan in the liver.

About 25 years ago, L-tryptophan supplements were implicated as the cause of an epidemic of eosinophiliamyalgia syndrome, a serious and sometimes fatal condition. This epidemic was traced to a single manufacturer of L-tryptophan, which had changed its manufacturing process and introduced a contaminant into the product. The manufacturing error was identified and corrected relatively quickly, and there have been no reports of eosinophilia-myalgia syndrome resulting from the use of uncontaminated tryptophan.

Jangid Petal. Comparative study of efficacy of L-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian Psychiatr. 2013;6:29-34.

Green Tea Extract for Uterine Fibroids

Thirty-nine Egyptian women of reproductive age (mean age, 42 years) who had symptomatic uterine fibroids, with at least 1 fibroid lesion 2 [cm.sup.3] or larger (confirmed by transvaginal ultrasonography) were randomly assigned to receive, in double-blind fashion, 800 mg per day of green tea extract (containing 45% EGCG; n = 22) or placebo (n = 17) for 4 months. Thirty-three women completed the trial (22 in the active-treatment group and 11 in the placebo group). The mean total fibroid volume decreased in the EGCG group by 32.6% and increased in the placebo group by 24.3% (p < 0.001 for the difference in the change between groups). Compared with placebo, EGCG treatment resulted in a significant improvement in the mean symptom severity score (which measured symptoms such as heavy menstrual bleeding, tightness or pressure in the pelvic area, and feeling fatigued; p < 0.0001) and the mean Health-Related Quality of Life score (p < 0.02). No adverse effects, endometrial hyperplasia, or other endometrial pathology were observed.

Comment: Uterine fibroids (also called leiomyomas) are benign tumors of the smooth muscle tissue of the uterus (myometrium). They are a common problem among women of reproductive age. Fibroid growth is stimulated by estrogen and progesterone, which explains in part why fibroids occur mainly during the reproductive years. Various medications and surgical procedures are often used to control fibroids or their associated symptoms.

EGCG has been reported to inhibit the proliferation of, and to induce apoptosis in, human leiomyoma cells in experimental animals and in vitro. This effect is thought to be due to the inhibitory effect of EGCG on catechol-0-methyltransferase, an enzyme that appears to play a role in the pathogenesis of uterine fibroids. The results of the present study suggest that a green tea extract containing a high concentration of EGCG was effective in decreasing the size of uterine fibroids and improving their associated symptoms.

Roshdy E et al. Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study. Int 1 Womens Health. 2013;5:477-486.

Omega-3 Fatty Acids for Canker Sores

Fifty patients (mean age, 33 years) with recurrent aphthous ulcers were randomly assigned to receive, in double-blind fashion, a capsule containing 300 mg of eicosapentaenoic acid and 200 mg of docosahexaenoic acid 3 times per day or placebo for 6 months. The mean number of ulcers per month, the mean duration of ulcers, and the mean pain level of ulcers all improved progressively in the active-treatment group during the course of the study, whereas no significant changes were seen in the placebo group. In the active-treatment group, the mean number of ulcers per month decreased from 6.4 at baseline to 0.76 after 6 months (88% decrease; p < 0.001 for the difference between groups in the last month of the study). Active treatment was also significantly more effective than placebo with respect to duration of ulcers and pain level of ulcers (p < 0.001 for each comparison in the last month of the study). The beneficial effect of active treatment over placebo for each of the measured parameters reached statistical significance in the third month.

Comment: In this study, supplementation with moderate amounts of the omega-3 fatty acids present in fish oil decreased both the frequency and severity of recurrent aphthous ulcers. The dosages used are equivalent to about 1.7 g per day of fish oil. The study was conducted in Egypt, where fish consumption is similar to the world average. Other interventions that have been found to be beneficial for preventing recurrences of aphthous ulcers include identifying and avoiding allergenic foods; correcting deficiencies of nutrients such as iron, zinc, and B vitamins; and avoiding toothpastes that contain sodium lauryl sulfate.

El Khouli AM, EI-Gendy EA. Efficacy of omega-3 in treatment of recurrent aphthous stomatitis and improvement of quality of life: a randomized, double-blind, placebo-controlled study. Oral Surg Ora/ Med Oral Pathol Oral Radiol. 2014;117:191-196.

Vitamin C Prevents Myocardial Injury During Angioplasty

Five hundred thirty-two patients undergoing elective percutaneous coronary intervention were randomly assigned to receive, in double-blind fashion, 3 g of vitamin C intravenously in 250 ml of isotonic saline over 100 minutes, or isotonic saline alone (control group), 2 to 6 hours before the procedure. The primary end point was periprocedural myocardial injury defined as an increase of the troponin I level to more than 5 times the upper limit of normal. The secondary endpoint was periprocedural myocardial injury defined as an increase of the creatine kinase-MB (CK-MB) level to more than 5 times the upper limit of normal. The incidence of periprocedural myocardial injury was significantly lower in the vitamin C group than in the control group, as defined by each method of assessment: (troponin I, 10.9% vs. 18.4%; 41% reduction; p < 0.02; CK-MB, 4.2% vs. 8.6%; 51% reduction; p < 0.04).

Comment: Percutaneous coronary intervention (commonly known as angioplasty) is a procedure used to open narrowed coronary arteries. Myocardial injury, as demonstrated by elevated levels of troponin I or CK-MB, may occur as a complication of the procedure in up to 30% of cases, and such injury has been associated with an increased risk of later clinical outcomes such as death, myocardial infarction, and need for repeat revascularization procedures. The results of the present study indicate that intravenous administration of vitamin C can decrease the risk of myocardial injury during percutaneous coronary intervention. Vitamin C presumably works by decreasing free radical-induced cell damage.

Wang ZJ et al. The effect of intravenous vitamin C infusion on periprocedural myocardial injury for patients undergoing elective percutaneous coronary intervention. Can J Cardiol. 2014;30:96-101.

Melatonin for Endometriosis

Forty women (aged 18-45 years) with endometriosis were randomly assigned to receive, in double-blind fashion, 10 mg of melatonin or placebo once a day at bedtime for 8 weeks. Compared with placebo, melatonin significantly decreased (improved) mean scores for daily pain by 400%, dysmenorrhea by 38%, dysuria, and constipation (p < 0.01 for all comparisons). Melatonin also improved sleep quality (p < 0.02 compared with placebo).

Comment: Endometriosis is characterized by the presence of endometrial tissue at sites outside the uterus. Manifestations include pelvic pain, dysmenorrhea, painful intercourse, and infertility. The cause of endometriosis is unknown. Conventional therapy may include various medications (e.g., gonadotropin-releasing hormone agonists, progestins, or oral contraceptives) and surgical removal of affected tissue. The results of the present study suggest that melatonin is of value for this difficult-to-treat condition. The mechanism of action of melatonin may be related to its analgesic and anti-inflammatory properties.

Schwertner A et al. Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial. Pain. 2013;154:874-881.

Chewing Gum Improves Postoperative Recovery

One hundred forty-nine women (mean age, 54 years) undergoing abdominal surgical staging (including total abdominal hysterectomy with pelvic and paraaortic lymphadenectomy) for various gynecological cancers were randomly assigned to a gum-chewing group or a control group. The patients in the gum-chewing group chewed sugarless gum 3 times per day, starting on the first postoperative morning and continuing until the first passage of flatus. Each chewing session lasted 30 minutes. Mean time before passage of flatus (34.0 vs. 43.6 hours; p<0.001), mean time until a bowel movement occurred (41.5 vs. 50.1 hours; p = 0.001), mean time until the patients tolerated a diet (4.0 vs. 5.0 days; p < 0.001), and mean length of hospital stay (5.9 vs. 7.0 days; p < 0.001) were significantly shorter in the gum-chewing group than in the control group. Mild ileus symptoms were observed in 36% of patients in the control group and 14.9% of patients in the gum-chewing group (p = 0.004).

Comment: This study demonstrated that chewing gum following major abdominal surgery accelerated recovery of bowel function and decreased the length of hospital stay. Previous studies have shown similar results. Gum chewing works by stimulating bowel motility. Use of this simple and inexpensive intervention could decrease surgical complications and reduce the cost of health care.

Ertas IE et al. Influence of gum chewing on postoperative bowel activity after complete staging surgery for gynecological malignancies: a randomized controlled trial. Gynecol Oncol. 2013;131:118-122.

Chewing Gum May Cause Headaches in Children

Thirty children and teenagers (aged 6-19 years) with chronic headaches (mostly migrainelike) and excessive gum chewing were asked to stop chewing gum for 1 month, and then to resume the habit. During the period of no gum chewing, 26 of the 30 patients reported significant improvement, and headaches disappeared completely in 19. All 20 patients who resumed gum chewing experienced a return of headaches within days to 1 week. The number of daily hours of chewing had no influence on the response to the intervention.

Comment: These findings suggest that excessive gum chewing can cause headaches in some children and teenagers. The authors of the study hypothesized that overuse of the temporomandibular joint was the cause of the headaches. However, sensitivity to aspartame may have played a role in some cases, as has been reported previously.

Watemberg N et al. The influence of excessive chewing gum use on headache frequency and severity among adolescents. Pediatr Neurol. 2014;50:69-72.

N-Acetylcysteine for Gambling Addiction

Twenty-eight individuals with nicotine dependence and pathological gambling who were receiving behavioral therapy (imaginal desensitization) were randomly assigned to receive, in double-blind fashion, N-acetylcysteine (NAC) or placebo for 12 weeks. The initial dosage of NAC was 1200 mg per day; this was increased to a maximum of 3000 mg per day, based on clinical judgment. After 12 weeks, NAC and behavioral therapy were discontinued, and the subjects were reassessed 3 months later. During the 3-month follow-up period, compared with placebo, NAC significantly decreased the severity of problem gambling (p < 0.05), as measured by the mean score on the pathological gambling adaptation of the Yale-Brown Obsessive-Compulsive Scale.

Comment: Pathological gambling is an impulse control disorder characterized by persistent and recurrent maladaptive gambling behavior that disrupts relationships and daily activities. There is evidence that a subnormal concentration of glutamate in the nucleus accumbens region of the brain increases compulsive or addictive behaviors. Administration of NAC has been shown to increase glutamate concentrations in the nucleus accumbens. The results of the present study suggest that NAC can enhance the beneficial effects of behavioral therapy in nicotine-dependent pathological gamblers, and that the effect of NAC persists at least 3 months after treatment is discontinued.

Grant JE et al. A randomized, placebo-controlled trial of N-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers. J Clin Psychiatry. 2014;75:39-45.

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by Alan R. Gaby, MD
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Title Annotation:5-Hydroxytryptophan, green tea, and omega-3 fatty acids
Author:Gaby, Alan R.
Publication:Townsend Letter
Date:Jan 1, 2015
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