Changes in plasma amino acid and subjective sleepiness ratings in humans after consumingL-tryptophan/maltodextrin mixes.

In animals, there is some evidence that increasing brain tryptophan (TRP) levels can increase brain serotonin (5-HT) synthesis and facilitate sleep onset. The plasma ratio of TRP to the other large neutral amino acids (TRP/LNAA ratio) must at least triple before detectable increases in brain 5-HT occur. In young men, consumption of 500 mg TRP combined with a carbohydrate (CHO) load will triple this ratio. In a study on 72 volunteers with mild insomnia, using subjective ratings of sleep onset and quality, this combination significantly decreased sleep latency. We noticed, however, that young women seemed to be particularly responsive to the sleepiness-inducing effects of TRP/CHO mixes. The present study was designed to examine more closely the effects of TRP/CHO mixes on subjectively rated sedation in young women and to check if their plasma amino acid response differs from that of men. On three evenings, nine healthy young women consumed 0, 500, or 1000 mg TRP combined with 30 g of maltodextrin. Blood samples were collected at 0, 30, 60, 90 and 120 minutes. Sleepiness was rated during the evening. The study was carried out double-blind, and each woman received all 3 treatments balanced across days. Plasma TRP/LNAA ratios tripled after 500 mg and quadrupled after 1000 mg of TRP. All women reported a marked increase in sleepiness with TRP. We conclude that young women do seem to be more sensitive than men to the sedating effect of TRP/CHO mixes but their plasma amino acid responses are similar.

Effect of an oral tryptophan/carbohydrate load on tryptophan, large neutral amino acid, and serotonin and 5-hydroxyindoleacetic acid levels in monkey brain.

Plasma and brain levels of tryptophan and other large neutral amino acids, and brain levels of serotonin and 5-hydroxyindoleacetic acid (5 HIAA) were measured in groups of adult cynomolgus monkeys 1 hr after they ingested one of four doses of a tryptophan-carbohydrate mixture. The doses had been administered once daily for 13 weeks. Dose-related increments occurred in plasma tryptophan, the plasma ratio of tryptophan to the sum of other large neutral amino acids, and in brain tryptophan levels. In contrast, the plasma ratios and brain levels of the other neutral amino acids each declined. Serotonin and 5 HIAA levels increased significantly, and in a dose-related manner in the brainstem and striatum, but not in cortex or hypothalamus. The results suggest that while tryptophan administration can stimulate serotonin production in primate brain, the effect may be restricted to certain brain regions. They also suggest that the transport of the large neutral amino acids into brain occurs via a competitive mechanism similar to that for other mammals.

Some evidence for short-term caloric compensation in normal weight human subjects: the effects of high- and low-energy meals on hunger, food preference and food intake.

This study compared the effects of high- and low-energy lunches upon subjective motivation to eat and food intake. Subjects ate four cooked lunch-time meals on separate days, two of which were high-energy (1820 kJ or 435 kcal) and two low-energy (1090 kJ or 260 kcal). The meals were of similar bulk, contained similar amounts of protein and carbohydrate but different fat contents, the low-energy meals containing very little. Motivational ratings and food preference assessments were completed before, and at hourly intervals for 3 h after the meals during which time subjects were not allowed to eat. Food intake diary records were kept for the rest of the day. Immediately after consumption of the meals none of the ratings differentiated between the high- and low-energy meals. At 1 h rated hunger was significantly higher after the low-energy meal and by 3h high- and low-energy meals were significantly differentiated by almost all measures. When subjects were allowed to eat freely, food intake records showed that energy intake was higher following the low-energy meal during the first 2 h but was lower thereafter. At the end of the assessment period (i.e. 8h after lunch) subjects had made a statistically non-significant 43 per cent compensation for the energy 'lost' at lunch. These findings are of theoretical importance since they provide evidence of short-term monitoring of energy. This study is of practical significance since it discloses certain consequences of using reduced energy foods which may form part of a weight control programme.

Evidence for diminished brain 5-hydroxytryptamine biosynthesis in obese diabetic and non-diabetic humans.

Obese persons are often reported to have marked cravings for simple carbohydrate-rich foods. Because of the proposed relationships between protein/carbohydrate selection, plasma tryptophan (TRP) to large neutral amino acids (LNAA) ratios, and brain 5-hydroxytryptamine (5-HT) neurotransmission, we examined the plasma TRP/LNAA ratios in four categories of obese subjects, before and 120 min after oral glucose tolerance test (GTT). Plasma TRP/LNAA ratios were reduced in obese, non-diabetics by 18%, the same extent as for older (approximately 52 yr old) nonobese subjects. In more advanced obesity, ie obesity associated either with glucose intolerance, hyperinsulinemia or hypoinsulinemia, plasma TRP/LNAA ratios were reduced by 25%. One hundred twenty minutes after a 100 g glucose load plasma TRP/LNAA had not been normalized. Based on animal data, these results suggest there may be diminished 5-HT neurotransmission in obese diabetics. The implications of these findings for the cravings of obese for carbohydrate-rich foods is discussed.

Breakfast meal composition influences plasma tryptophan to large neutral amino acid ratios of healthy lean young men.

The effect of a carbohydrate, a 20% protein, or a carbohydrate +0.3% tryptophan TRP breakfast on plasma large neutral amino acid ratios was studied in 6 healthy men. The carbohydrate-rich meal produced shifts in plasma amino acid concentrations such that plasma TRP/LNAA ratios increased from 0.13 to 0.15 (p less than 0.04) and the protein meal decreased the ratio from 0.14 to 0.11 (p less than 0.04) after 1 hour. Addition of 0.3% TRP to the carbohydrate-rich meal increased plasma TRP/LNAA ratios more than 2-fold. The TRP containing meal was thus the only one likely to influence brain 5-HT synthesis, although the difference between the plasma TRP/LNAA ratios after carbohydrate and protein breakfasts suggests that the brain may distinguish, by synthesizing more or less 5-HT, the composition of breakfast meals.

Strategies of protein selection by weanling and adult rats.

Weanling and adult male rats were offered pairs of diets containing either 0 and 20%, 0 and 40%, 0 and 60%, or 10 and 40% casein. Initially they preferred the lower protein diets, and then after one to ten days abruptly switched to adequate levels of protein choice. After 14 days, the diets were changed so that the first group received 10 and 40%, the second 20 and 60%, the third 10 and 40%, and the fourth 0 and 60% casein. Following the change, all weanling rats showed significant and systematic shifts in percentage of total energy chosen as protein (%P-E); most adults did not. Within each group, the variability in %P-E selected between different rats was higher than the day-to-day variability of individuals. In the adults no significant correlations were observed between protein selection and brain serotonin metabolism. We conclude that protein intake in rats is regulated in the sense that all animals learnt to eat sufficient protein to maintain growth, and most animals ate a constant amount of protein each day. On the other hand, the range of protein intake between individuals, and the shifts in selection among the weanlings when diet choices were changed seem to preclude the existence of a mechanism which precisely regulates protein intake.

Behavioural strategies in the regulation of food choice.

The maintenance of nutrient and energy balance in the body depends on both metabolic and behavioural mechanisms, and is integrated by the brain. The regulatory system was developed by natural selection and not by mechanical engineers. Thus, rather than having unitary mechanisms regulating intake of each nutrient, evolution has incorporated and used a multitude of behavioural traits and metabolic adaptations. The criterion for inclusion was that each one conferred a persisting advantage in the prevailing environment. Behavioural strategies in food choice include: innate preference for sweetness and an aversion towards bitter tastes, a hesitancy towards unknown foods, preference for variety among familiar foods, and a special ability (long delay learning) to acquire information about both positive and negative metabolic consequences of eating different foods. In man, these more basic mechanisms interact with and are complemented by cognitive, social and cultural influences on food choice. In a very few cases, such as regulation of energy, sodium and (perhaps) protein intakes, feeding behaviour is also guided by signals from specific internal receptors. However, for most nutrients, appetites seem to be non-specific and learned. Using studies on the regulation of protein intake from our own and other laboratories as examples, this review illustrates how innate preferences, learning, social interactions, metabolic adaptation and diet-induced changes in brain neurotransmitter metabolism can all play a role in subjective decisions about what to eat.

Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man.

The effect of an aqueous extract of valerian (Valeriana officinalis L.) root on subjectively rated sleep measures was studied on 128 people. Each person received 9 samples to test (3 containing placebo, 3 containing 400 mg valerian extract and 3 containing a proprietary over-the-counter valerian preparation). The samples, identified only by a code number, and presented in random order, were taken on non-consecutive nights. Valerian produced a significant decrease in subjectively evaluated sleep latency scores and a significant improvement in sleep quality: the latter was most notable among people who considered themselves poor or irregular sleepers, smokers, and people who thought they normally had long sleep latencies. Night awakenings, dream recall and somnolence the next morning were relatively unaffected by valerian. With the proprietary valerian-containing preparation, the only change was a significant increase in reports of feeling more sleepy than normal the next morning. Thus the questionnaire, simple to use and non-invasive, provides a sensitive means for detecting the effects of mild sedatives on different aspects of sleep in man. It also allows identification within the test population of the subgroups most affected.

Plasma amino acid responses in humans to evening meals of differing nutritional composition.

The effect of a carbohydrate or a 20% protein (HP) or a carbohydrate + 0.4% tryptophan (TRP) evening meal on plasma amino acids and on plasma neutral amino acid (NAA) ratios was studied in eight healthy men. After consumption of the protein meal, plasma amino acids rose after 1 h and remained at the same level at 2 h. The dietary profile of the essential amino acids, except for TRP, was retained in the plasma. The plasma profile of nonessential amino acids was not related to the dietary pattern. Glutamic acid and aspartic acid increased several-fold less and alanine several-fold more than would be expected from their dietary concentrations. The tyrosine/NAA and phenylalanine/NAA ratios were not altered by any of the meals and the TRP/NAA ratio was increased only by the carbohydrate + 0.4% TRP meal. The leucine/NAA and isoleucine/NAA ratios were decreased by the carbohydrate and carbohydrate + TRP and increased by the 20% protein meals, while valine/NAA was decreased by the carbohydrate + TRP and HP but increased by the carbohydrate meal. From these data it is concluded that if brain neurotransmitter synthesis is controlled by the same mechanisms as in rats, then the evening meal containing added TRP was the only one of the meals likely to affect brain neurotransmitter (serotonin) synthesis.

Phosphatidyl choline and avoidance performance in 17 month-old SEC/1ReJ mice.

Male SEC/1ReJ mice aged 6 or 17 months were fed diets containing 0, 2, 4, and 8% added phosphatidyl choline. After 4 days on the test diets they were given 5 daily sessions of 100 trials each in the shuttle-box. The younger mice rapidly acquired an avoidance response and reached high, stable levels of performance. The older mice learned more slowly and reached significantly lower performance levels (p less than 0.01). Phosphatidyl choline had no effect on performance of young mice, while in the older mice the highest dose level of phosphatidyl choline increased avoidance performance by nearly 30% (p less than 0.05).

Quantifying the effects of mild sedatives.

In quantifying the effects of mild sedatives both physiological and subjective aspects of sleep must be taken into account. A questionnaire analysis on a mild sedative (400 mg of an aqueous extract of Valeriana officinalis L.) showed that by subjective criteria it is sedative (i.e. it significantly decreased perceived sleep latencies and night awakenings, and improved sleep quality). In an EEG study on the same preparation the pattern of results tended to confirm the subjective evaluation (i.e. shorter mean sleep latency, increased mean latency to first awakening) but the changes did not reach statistical significance. The discussion critically examines some of the approaches used to test putative mild sedatives and suggests a rational approach to analysing their effects.

Diet-induced mood changes in normal populations.

Using an 11-item questionnaire and a double-blind experimental design, changes in mood, hunger and food preference after taking caffeine (100 mg), tryptophan (500 mg), tyrosine (500 mg) or placebo, were investigated in 60 volunteers. At the end of the study, volunteers also ranked the four treatments on a sedation/stimulation scale. Caffeine significantly increased scores for wakefulness, vigor, clarity of mind, energy, feeling full of ideas, feeling full of go and feeling efficient. Caffeine was also ranked as the most stimulating treatment (p less than 0.001). Tyrosine produced no changes, while tryptophan shifted mean scores towards somnolent and lethargic, and was ranked most sedating (p less than 0.05). None of the treatments changed hunger ratings or carbohydrate/protein preference.

The sensitivity of urinary enzyme measurements for detecting renal injury.

The relative sensitivity of urinary enzyme measurements for detecting renal damage was determined for two nephrotoxins. Injection of a single dose of sodium phosphate (10 mmoles/kg) caused damage to the proximal tubules and led to a 15 fold increase in lactate dehydrogenase (LDH) activity excreted into the urine. In contrast to this change the serum LDH remained normal. Similar results were obtained following the injection of cephaloridine (2 g/kg) with an 18 fold increase in urinary LDH and a marginal increase in urinary glutamate dehydrogenase (GDH). By contrast the serum LDH was unchanged. Urinary enzymes are therefore more sensitive for detecting renal injury than enzymes. The four enzymes investigated are located in specific regions of the cell so that the involvement of the organelles and regions of the cell can be followed. Damage to the organelles does not appear to occur as the excretion of the lysosomal enzymes remained normal and only in the case of cephaloridine were marginal changes in the mitochondrial GDH excretion seen. The average alkaline phosphatase was also normal suggesting no gross damage to the plasma membrane although a few individual rats excreted abnormal activities of alkaline phosphatase. These rats however, also excreted high activities of LDH. This suggests that damage to the membrane causes leakage of LDH and in severe cases release of the plasma membrane enzyme alkaline phosphatase. The administration of cephaloridine at various doses showed that urinary enzyme measurements were as sensitive as histology for demonstrating renal damage and that of these enzymes, LDH was by far the most useful.