Life Extension Magazine April 2008
Conversion ratio of tryptophan to niacin in Japanese women fed a purified diet conforming to the Japanese Dietary Reference Intakes.
In order to establish the human requirements of niacin, it is first important to know how much tryptophan is converted to niacin in the human body. In a general, 60 mg of tryptophan is equivalent to 1 mg of niacin, whereas the conversion ratio of tryptophan to niacin is yet to be confirmed. The aim of this study was to know the conversion ratio of tryptophan to niacin in Japanese females fed a purified diet, which followed the Japanese Dietary Reference Intakes. Ten young Japanese females were housed in the same facility and given the same daily living activity schedule for 7 d. The composition of their purified diet was conformed to the Dietary Reference Intakes in Japan. The diet was niacin free. In order to investigate the conversion ratio, daily urinary outputs were collected. Tryptophan-niacin metabolites in the urine were measured and the conversion ratio of tryptophan to niacin calculated. The conversion ratio was calculated by comparing the dietary intake of tryptophan and the sum of the niacin catabolites such as N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide, which were derived only from the dietary intake of tryptophan. The ratio was calculated as 1.5 +/- 0.1 (mean +/-SE for 10 women; in molar basis) on the last day of the experiment. It was calculated that if the excretory percentage of niacin metabolites in the urine were 60%, of the tryptophan ingested, the conversion factor would be a value of 67, meaning that is 67 mg of tryptophan is equal to 1 mg of niacin.
J Nutr Sci Vitaminol (Tokyo). 2004 Dec;50(6):385-91
Tryptophan depletion and its implications for psychiatry.
BACKGROUND: Over the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems. AIMS: To review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders. METHOD: Systematic review of preclinical and clinical studies. RESULTS: Tryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar. CONCLUSIONS: The findings that tryptophan depletion produces a relapse of symptoms in patients with depression and panic disorder who have responded to treatment with antidepressants suggests that enhanced 5-HT function is important in maintaining response in these conditions.
Br J Psychiatry. 2001 May;178:399-405
The tryptophan depletion test: impact on sleep in primary insomnia—a pilot study.
The application of the tryptophan depletion test is based on the assumption that the decrease of plasma or serum tryptophan concentration following the ingestion of a tryptophan-free amino acid drink reflects a central nervous effect on serotonin metabolism. In the present study the impact of tryptophan depletion on polysomnographically recorded sleep in patients with primary insomnia was studied. Fifteen patients with primary insomnia slept for four nights in the sleep laboratory. Prior to the fourth night the tryptophan depletion test was applied. Sleep EEG variables served as outcome parameters. Patients with primary insomnia, compared to baseline values showed a highly significant decrease of serum tryptophan concentrations after the amino acid drink. Concerning sleep parameters, stage 1 (% sleep period time=SPT) was increased, whereas stage 2 (% SPT) was decreased. Indices of phasic activity of rapid eye movement (REM) sleep (REM density) were increased after the tryptophan depletion compared to baseline. The results suggest a negative impact of tryptophan depletion on sleep continuity and a stimulating effect on phasic measures of REM sleep in patients with primary insomnia.
Psychiatry Res. 2002 Mar 15;109(2):129-35
Treatment of severe chronic insomnia with L-tryptophan: results of a double-blind cross-over study.
Thirty-nine subjects with chronic insomnia were treated with L-tryptophan (L-TRP) in a double-blind, cross-over study. Instead of a placebo, a very low dose of 0.04 g L-TRP was used. The subjects suffered from a sleeping disorder classified as “psychophysiological, persistent”. In the subgroup taking the full L-TRP (2 g) dose first, there was a significant difference between the treatment period with the full L-TRP dose and the ineffective dose (placebo). If the placebo was given first, however, there was no significant difference between the two treatment periods. It is suggested that psychological factors are responsible for the diverging results in the two subgroups of patients. On the basis of subjective ratings, it appears that L-TRP is effective in promoting sleep in cases of chronic insomnia.
Pharmacopsychiatry. 1987 Nov;20(6):242-4
Chronic insomnia: effects of tryptophan, flurazepam, secobarbital, and placebo.
This study compared the effects of l-tryptophan (1 g), secobarbital (100 mg), flurazepam (30 mg), and placebo on sleep in 96 serious insomniacs. Each treatment was given nightly for 7 nights in a separate-group design. Outcome measures were subjective estimates by subjects of a number of sleep parameters during the week of treatment and for 1 week after, and an overall evaluation made by subjects and investigators at the end of the 2 weeks. During the treatment week, flurazepam produced significant improvement on several sleep measures compared to placebo, while tryptophan and secobarbital did not. Flurazepam and secobarbital produced withdrawal symptoms during the post-treatment week, while tryptophan and placebo did not. Sleep latency was not significantly improved by tryptophan during the treatment week, but continued to improve during the post-treatment week, resulting in a significant difference between tryptophan and baseline in week 2.
Psychopharmacology (Berl). 1983;80(2):138-42
Meal-induced changes in tryptophan:LNAA ratio: effects on craving and binge eating.
This study investigated the effects of meals varying in macronutrient composition on plasma tryptophan/large neutral amino acid (tryp:LNAA) ratios and subsequent appetite and mood in women defined as “food cravers.” Nine women consumed one of each of a high protein, high carbohydrate and mixed meal on three separate days. Blood samples and appetite and mood ratings were taken before and at intervals up to 150 min after meal consumption. The first subsequent ad libitum food intake was recorded in diaries. The tryp:LNAA ratio increased significantly after the carbohydrate meal compared to protein and mixed meals. No significant correlations between change in tryp:LNAA ratio and mood or macronutrient intake at the ad libitum eating episode were observed. There was a negative correlation between tryp:LNAA ratio and desire to binge eat (p=0.03) and a trend towards a negative correlation between tryp:LNAA ratio and craving for carbohydrate-rich foods (p=0.07). Participants whose ad libitum eating episode was categorized as a binge had a trend (p=0.06) toward lower plasma tryp:LNAA ratio than those who did not binge. Regression analysis showed that the effects of change in tryp:LNAA ratio on desire to binge eat was independent of meal type and changes in insulin and glucose concentrations. These findings suggest that reducing plasma tryp:LNAA ratio, via consumption of a protein-rich meal, may mediate the desire to binge eat in susceptible women.
Eat Behav. 2000 Sep;1(1):53-62
Interval therapy with L-tryptophan in severe chronic insomniacs. A predictive laboratory study.
Interval therapy is the concept of intermittent applications with drug-free intervals, based on the observation that in many cases L-tryptophan has the best effects on disturbed sleep during the drug-free interval after-short-term application. This concept was formulated as an experimental hypothesis to be tested in the sleep laboratory in a predictive, double-blind design, comparing a 4-night placebo period following repetitive 3 X 2 g L-tryptophan application with baseline. All patients, severe chronic insomniacs, 5 males and 3 females (mean age 38.4 years) improved significantly at the predefined level of 0.05. Analyses of the polygraphic recordings proved highly significant sleep improvements in the parameters that are indicators of insomnia. No side effects were seen. It can be concluded that the interval therapy with L-tryptophan is a potent treatment for chronic primary insomnia.
Int Pharmacopsychiatry. 1981;16(3):162-73
Sleep induced by L-tryptophan. Effect of dosages within the normal dietary intake.
Previous results have demonstrated sleep-inducing effects of L-tryptophan in doses of 1 to 15 g at bedtime. The present laboratory study extends the dose-response curve downward, comparing doses of 1/4 g, 1/2 g, and 1 g of L-tryptophan with placebo, in 15 mild insomniacs (subjects who reported sleep latencies of over 30 minutes). One gram of L-tryptophan significantly reduced sleep latency: the lower doses produced a trend in the same direction. Stage IV sleep was significantly increased by 1/4 g of L-tryptophan. These results at low doses have interesting implications since the normal dietary intake of L-tryptophan is 1/2 g to 2 g per day.
J Nerv Ment Dis. 1979 Aug;167(8):497-9