Madelyn H. Fernstrom

Tyrosine, Phenylalanine, and Catecholamine Synthesis and Function in the Brain

Aromatic amino acids in the brain function as precursors for the monoamine neurotransmitters serotonin (substrate tryptophan) and the catecholamines [dopamine, norepinephrine, epinephrine; substrate tyrosine (Tyr)]. Unlike almost all other neurotransmitter biosynthetic pathways, the rates of synthesis of serotonin and catecholamines in the brain are sensitive to local substrate concentrations, particularly in the ranges normally found in vivo. As a consequence, physiologic factors that influence brain pools of these amino acids, notably diet, influence their rates of conversion to neurotransmitter products, with functional consequences. This review focuses on Tyr and phenylalanine (Phe). Elevating brain Tyr concentrations stimulates catecholamine production, an effect exclusive to actively firing neurons. Increasing the amount of protein ingested, acutely (single meal) or chronically (intake over several days), raises brain Tyr concentrations and stimulates catecholamine synthesis. Phe, like Tyr, is a substrate for Tyr hydroxylase, the enzyme catalyzing the rate-limiting step in catecholamine synthesis. Tyr is the preferred substrate; consequently, unless Tyr concentrations are abnormally low, variations in Phe concentration do not affect catecholamine synthesis. Unlike Tyr, Phe does not demonstrate substrate inhibition. Hence, high concentrations of Phe do not inhibit catecholamine synthesis and probably are not responsible for the low production of catecholamines in subjects with phenylketonuria. Whereas neuronal catecholamine release varies directly with Tyr-induced changes in catecholamine synthesis, and brain functions linked pharmacologically to catecholamine neurons are predictably altered, the physiologic functions that utilize the link between Tyr supply and catecholamine synthesis/release are presently unknown. An attractive candidate is the passive monitoring of protein intake to influence protein-seeking behavior.

Body image and quality of life in post massive weight loss body contouring patients.

Objective: Because post‐bariatric surgery patients undergo massive weight loss, the resulting skin excess can lead to both functional problems and profound dissatisfaction with appearance. Correcting skin excess could improve all these corollaries, including body image. Presently, few data are available documenting body image and weight‐related quality of life in this population.

A Wearable Electronic System for Objective Dietary Assessment

Dietary reporting by individuals is subject to error (1–3). Therefore, a research program has been initiated to develop a small electronic device to record food intake automatically. This device, which contains a miniature camera, a microphone, and several other sensors, can be worn on a lanyard around the neck. It collects visual data immediately in front of the participant and stores them on a memory card in the device. The data are transferred regularly to the dietitian’s computer for further processing and analysis. The device is designed to be almost completely passive to the participant, and thus hopefully will not intrude on or alter the participant’s eating activities. In addition to this function, in the future the device will have other functions, such as the measurement of physical activity, human behavior, and environmental exposure (e.g., pollutants).

A classification of contour deformities after bariatric weight loss: the Pittsburgh Rating Scale.

Background: Contour deformities after massive weight loss are diverse and often severe in nature. Current progress has necessitated a valid, accessible, and comprehensive rating system that correlates appearance and appropriate surgical treatment. Presently, no existing rating system addresses the breadth and variety of deformities that can occur or allows for adequate postsurgical evaluation. Methods: The authors reviewed full-body photographs of over 300 female patients seen between October of 2002 and May of 2004. The authors targeted body areas most frequently demonstrating skin and soft-tissue laxity and ptosis. A 10-region, four-point grading system was designed to describe the common deformities found in each region of the body. To validate the scale, 12 trained observers applied the rating scale to photographs of 25 patients who showed the 10 regions. Each grading scale ranged from 0, indicating normal, to 3, indicating the most severe deformity. Repeat testing was performed at 2 weeks. Interobserver validity and test-retest reliability were determined using weighted κ analysis. Results: In all 10 categories, the κ value was 0.6 or higher (0.6 = threshold for good validity), with a mean κ value of 0.68 (range, 0.61 to 0.78) and an overall agreement of 69 percent over two sessions. All 12 observers scored an individual mean κ value of greater than 0.6, indicating good interobserver validity. A given observer had a mean 67 percent agreement, indicating reasonable test-retest reliability. Conclusions: The Pittsburgh Rating Scale is a validated measure of contour deformities after bariatric weight loss. This scale may have applications in preoperative planning and evaluating surgical outcomes.

Antidepressant-induced weight gain: A comparison study of four medications

Body weight change was monitored in 73 hospitalized depressed patients treated with one of four antidepressants for 1 month. After a 2-week medication-free period, patients were randomly assigned to treatment with amitriptyline, nortriptyline, desipramine, or zimelidine. By the end of 1 month, treatment with all three tricyclic compounds promoted weight gain, with the greatest increase observed during amitriptyline treatment; less weight was gained by patients treated with nortriptyline and desipramine. In contrast, most patients treated with zimelidine showed no weight gain and, in many cases, demonstrated weight loss. Weight change during treatment was not associated with age, sex, severity of depression, obesity, weight loss during depression, or clinical response.

Acute effects of nicotine on hunger and caloric intake in smokers and nonsmokers

The inverse relationship between smoking and body weight may be due in part to nicotines effects on reducing hunger and eating. Male smokers and nonsmokers (n=10 each), abstinent overnight from smoking and food, participated in four sessions, involving consumption of a liquid caloric load or water followed by nicotine (15 µg/kg) or placebo via nasal spray every 20 min for 2 h. Hunger and satiety (“fullness”) ratings were obtained prior to each dose presentation. At the end of the two sessions involving the caloric load (simulating breakfast), subjects were also presented with typical lunch/snack food items varying in sweet taste and fat content for ad lib consumption. Results indicated that, for both smokers and nonsmokers, the hunger-reducing effects of nicotine occurred only following caloric load consumption, and there was no effect of nicotine on hunger after water consumption. Smokers unexpectedly reported greater satiation than nonsmokers following the caloric load regardless of nicotine or placebo condition. Nicotine also resulted in less caloric intake during the meal, and the decrease was not specific to consumption of sweet, high-fat foods. These results indicate that nicotine reduces appetite, possibly helping to explain the influence of smoking on body weight.

Acute tyrosine depletion reduces tyrosine hydroxylation rate in rat central nervous system

An amino acid cocktail was devised that would rapidly reduce central nervous system (CNS) tyrosine levels in rats following gastric intubation. The effect of this treatment on in vivo tyrosine hydroxylation rate was examined. Serum tyrosine (TYR) levels, the serum ratio of TYR to the sum of its transport competitors, and CNS TYR concentrations fell substantially within 60 minutes of intubation and remained low for at least 3 hr. In vivo tyrosine hydroxylation rate, evaluated in hypothalamus and retina 2 hr after amino acid intubation, also declined significantly. The results suggest that an amino acid mixture can be devised that will cause an acute reduction in TYR levels and hydroxylation rate in rat CNS. This procedure may ultimately prove applicable to humans to examine functional consequences in particular CNS regions of reducing neuronal catecholamine synthesis.

Meal ingestion, amino acids and brain neurotransmitters: effects of dietary protein source on serotonin and catecholamine synthesis rates.

Carbohydrate ingestion raises tryptophan uptake and serotonin synthesis in rat brain. The addition of protein is generally believed only to block such increases. However, some recent evidence suggests dietary protein may not be limited to this action. In the present studies, we fed rats single meals containing one of 5 proteins (zein, wheat gluten, soy protein isolate, casein, lactalbumin, 17% by weight) or no protein, and killed them 2.5 h later, 30 min after the injection of m-hydroxybenzylhydrazine, to allow serotonin and catecholamine synthesis rates to be measured in brain. Blood and cerebral cortex samples were analyzed for tryptophan and other large, neutral amino acids; 5-hydroxytryptophan and dihydroxyphenylalanine were measured in hypothalamus, hippocampus and cerebral cortex as indices of serotonin and catecholamine synthesis, respectively. An 8-fold variation occurred in cortex tryptophan: a marked decline followed zein ingestion, and modest reductions after casein or gluten. A large rise in cortex tryptophan occurred after lactalbumin consumption, and smaller increases after soy protein or carbohydrate (no protein). In the brain regions examined, a 4-8-fold range in serotonin synthesis occurred which closely followed the tryptophan alterations. No effects were observed in regional catecholamine synthesis rates. Cortical concentrations of leucine showed small changes; leucine has been linked to mTOR (mammalian target of rapamycin) signaling in brain circuits regulating food intake. The data suggest that tryptophan concentrations and serotonin synthesis in brain neurons are remarkably sensitive to which protein is present in a meal. Conceivably, this relationship might inform the brain about the nutritional quality of the protein ingested.

Twenty-four-hour food intake in patients with anorexia nervosa and in healthy control subjects ☆

Ad libitum feeding over 24 hours was assessed in underweight restrictor anorectic (RAN) women (n = 8) and matched healthy control subjects (n = 9) in a relatively naturalistic laboratory setting. RAN consumed 828 +/- 210 kcal/day (20 +/- 6 kcal/kg/day); controls ingested 2274 +/- 564 kcal/day (41 +/- 13 kcal/kg/day). Expressed as macronutrient consumption, RAN, compared to healthy controls, ate less fat (13% vs 31%), more carbohydrate (73% vs 57%), and similar amounts of protein (14% vs 12%). RAN initiated fewer eating episodes than controls (4 vs 7). This study quantitatively confirms the growing body of evidence suggesting that RAN avoid fat-containing foods. Such persistent fat avoidance may significantly contribute to the difficulty RAN experience in gaining and maintaining body weight.

Effects of acute tryptophan depletion on mood in bulimia nervosa

BACKGROUND The present study investigated the role of serotonin in the pathophysiology of bulimia nervosa (BN) by studying the affective and appetitive responses of women ill with BN to an acute tryptophan depletion (ATD) paradigm. METHODS Twenty-two women with BN and 16 healthy control women (CW) were studied on 2 separate days during the follicular stage of the menstrual cycle. Participants drank a control mix of essential amino acids (100 g + 4.6 g tryptophan) on one day and a tryptophan deficient (100 g - 4.6 g tryptophan) mixture (ATD) on the other in a double-blind fashion. Mood/appetite ratings and blood samples were taken at baseline and at intervals up to 420 minutes. Participants were then presented with an array of foods and were allowed to binge and vomit if they desired. RESULTS CW and BN women had a similar and significant reduction in plasma tryptophan levels and the tryptophan: LNAA ratio after ATD. After ATD, the BN women had a significantly greater increase in peak (minus baseline) depression, mood lability, sadness and desire to binge compared to the CW. BN subjects and CW had similar peak changes in mood after the control amino acid mixture. BN subjects and CW consumed similar amounts of food after the two amino acid treatments. CONCLUSIONS Women with BN seem more vulnerable to the mood lowering effects of ATD, suggesting they have altered modulation of central 5-HT neuronal systems.