Placebo-controlled Procedure Research Articles

Rehabilitation of stroke patients with plegic hands: Randomized controlled trial of expanded Constraint-Induced Movement therapy.

To evaluate the efficacy of an expanded form of Constraint-Induced Movement Therapy (eCIMT) that renders CIMT, originally designed for treating mild-to-moderate upper-extremity hemiparesis, suitable for treating severe hemiparesis. Twenty-one adults ≥1 year after stroke with severe upper-extremity hemiparesis (with little or no capacity to make movements with the more-affected hand) were randomly assigned to eCIMT (n = 10), a placebo-control procedure (n = 4), or usual care (n = 7). The participants who received usual care were crossed over to eCIMT four months after enrollment. The CIMT protocol was altered to include fitting of orthotics and adaptive equipment, selected neurodevelopmental techniques, and electromyography-triggered functional electrical stimulation. Treatment was given for 15 consecutive weekdays with 6 hours of therapy scheduled daily for the immediate eCIMT group and 3.5 hours daily for the cross-over eCIMT group. At post-treatment, the immediate eCIMT group showed significant gains relative to the combination of the control groups on the Grade-4/5 Motor Activity Log (MAL; mean = 1.5 points, P < 0.001, f = 4.2) and a convergent measure, the Canadian Occupational Performance Measure (COPM; mean = 2.3, P = 0.014, f = 1.1; f values ≥0.4 are considered large, on the COPM changes ≥2 are considered clinically meaningful). At 1-year follow-up, the MAL gains in the immediate eCIMT group were only 13% less than at post-treatment. The short and long-term outcomes of the crossover eCIMT group were similar to those of the immediate eCIMT group. This small, randomized controlled trial (RCT) suggests that eCIMT produces a large, meaningful, and persistent improvement in everyday use of the more-affected arm in adults with severe upper-extremity hemiparesis long after stroke. These promising findings warrant confirmation by a large RCT.

An Examination of Fluoxetine for the Treatment of Selective Mutism Using a Nonconcurrent Multiple-Baseline Single-Case Design Across 5 Cases.

This study examined the utility of fluoxetine in the treatment of 5 children, aged 5 to 14 years, diagnosed with selective mutism who also demonstrated symptoms of social anxiety. A nonconcurrent, randomized, multiple-baseline, single-case design with a single-blind placebo-controlled procedure was used. Parents and the study psychiatrist completed multiple methods of assessment including Direct Behavior Ratings and questionnaires. Treatment outcomes were evaluated by calculating effect sizes for each participant as an individual and for the participants as a group. Information regarding adverse effects with an emphasis on behavioral disinhibition and ratings of parental acceptance of the intervention was gathered. All 5 children experienced improvement in social anxiety, responsive speech, and spontaneous speech with medium to large effect sizes; however, children still met criteria for selective mutism at the end of the study. Adverse events were minimal, with only 2 children experiencing brief occurrences of minor behavioral disinhibition. Parents found the treatment highly acceptable.

Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines

RationaleSynaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans.ObjectivesHere, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity.MethodsFifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later.ResultsMethylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity.ConclusionsAltogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.

A Mixed Flavonoid-Fish Oil Supplement Induces Immune-Enhancing and Anti-Inflammatory Transcriptomic Changes in Adult Obese and Overweight Women-A Randomized Controlled Trial.

Flavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of this study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg epigallocatechin (EGCG) from green tea extract, 400 mg n3-PUFAs (omega-3 polyunsaturated fatty acid) (220 mg eicosapentaenoic acid (EPA) and 180 mg docosahexaenoic acid (DHA)) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 µg folic acid) would reduce complications associated with obesity; that is, reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Overweight and obese women (n = 48; age = 40–70 years) were assigned to Q-Mix or placebo groups using randomized double-blinded placebo-controlled procedures. Overnight fasted blood samples were collected at 0 and 10 weeks and analyzed for cytokines, C-reactive protein (CRP), F2-isoprostanes, and whole-blood-derived mRNA, which was assessed using Affymetrix HuGene-1_1 ST arrays. Statistical analysis included two-way ANOVA models for blood analytes and gene expression and pathway and network enrichment methods for gene expression. Plasma levels increased with Q-Mix supplementation by 388% for quercetin, 95% for EPA, 18% for DHA, and 20% for docosapentaenoic acid (DPA). Q-Mix did not alter plasma levels for CRP (p = 0.268), F2-isoprostanes (p = 0.273), and cytokines (p > 0.05). Gene set enrichment analysis revealed upregulation of pathways in Q-Mix vs. placebo related to interferon-induced antiviral mechanism (false discovery rate, FDR < 0.001). Overrepresentation analysis further disclosed an inhibition of phagocytosis-related inflammatory pathways in Q-Mix vs. placebo. Thus, a 10-week Q-Mix supplementation elicited a significant rise in plasma quercetin, EPA, DHA, and DPA, as well as stimulated an antiviral and inflammation whole-blood transcriptomic response in overweight women.

Serotonin transporter polymorphism alters citalopram effects on human pain responses to physical pain

Humans exhibit substantial inter-individual differences in pain perception, which contributes to variability in analgesic efficacy. Individual differences in pain sensitivity have been linked with variation in the serotonin transporter gene (5-HTTLPR), and selective serotonin reuptake inhibitors (SSRIs) such as citalopram have been increasingly used as treatments for multiple pain conditions. We combined genotyping, pharmacological challenge, and neuroimaging during painful electrical stimulation to reveal how serotonin genetics and pharmacology interact to influence pain perception and its underlying neurobiological mechanisms. In a double-blind, placebo-controlled procedure, we acutely administrated citalopram (30mgpo) to short/short (s/s) and long/long (l/l) healthy male 5-HTTLPR homozygotes during functional MRI with painful and non-painful electrical stimulation. 5-HTTLPR genotype modulated citalopram effects on pain-related brain responses in the thalamus, cerebellum, anterior insula, midcingulate cortex and inferior frontal cortex. Specifically, citalopram significantly reduced pain-related brain responses in l/l but not in s/s homozygotes. Moreover, the interaction between 5-HTTLPR genotype and pain-related brain activity was a good predictor of the citalopram-induced reductions in pain reports. The genetic modulations of citalopram effects on brain-wide pain processing were paralleled by significant effects on the Neurological Pain Signature, a multivariate brain pattern validated to be sensitive and specific to physical pain. This work provides neurobiological mechanism by which genetic variation shapes brain responses to pain perception and treatment efficacy. These findings have important implications for the types of individuals for whom serotonergic treatments provide effective pain relief, which is critical for advancing personalized pain treatment.

Therapy of post-stroke depression – a systematic review

SummaryWe performed a systematic review of randomized placebo-controlled pharmacological and non-pharmacological trials for the therapy and prevention of post-stroke depression that have been published between 1980 and 2011. We initially identified 2 260 records of which 28 studies were finally included into this review. A meta-analytic approach was hampered by considerable differences regarding the kinds of therapeutic regimens and the study durations. Modest effects favoring treatment of post-stroke depression could be found for pharmacological treatment as well as repetitive transcranial magnetic stimulation. For the prevention of post-stroke depression, antidepressant pharmacotherapy showed promising results. However, large-scale studies with better standardized study populations, optimized placebo control procedures in non-pharmacological studies, and replication in larger follow-up studies are still necessary to find the optimal therapeutic regimens to prevent and treat post-stroke depression.

Combination Effects of Capsicum Plaster at the Korean Hand Acupuncture Points K-D2 with Prophylactic Antiemetic on Postoperative Nausea and Vomiting after Gynecologic Laparoscopy

This study was done to evaluate the combination effects of capsicum plaster at the Korean hand acupuncture points K-D2 with prophylactic antiemetic on Postoperative Nausea and Vomiting (PONV). An experimental research design (a randomized, a double-blinded, and a placebo-control procedure) was used. The participants were female patients undergoing gynecologic laparoscopy; the control group (n=34) received intravenous prophylactic ramosetron 0.3mg, while the experimental group (n=34) had Korean Hand Therapy additionally. In the experimental group, capsicum plaster was applied at K-D2 of both 2nd and 4th fingers by means of Korean Hand Therapy for a period of 30 minutes before the induction of anesthesia and removed 8 hours after the laparoscopy. The occurrence of nausea, nausea intensity and need for rescue with antiemetic in the experimental group was significantly less than in the control group 2 hours after surgery. Results of the study show capsicum plaster at K-D2 is an effective method for reducing PONV in spite of the low occurrence of PONV because of the prophylactic antiemetic medication.

Effect of zinc supplementation on mood states in young women: a pilot study

The relation of zinc (Zn) nutriture to brain development and function has been elucidated. The purpose of this study is to examine whether Zn supplementation improves mood states in young women. The study used a double-blind, randomized and placebo-controlled procedure. The major outcomes were psychological measures, somatic symptoms and serum Zn. Thirty women were placed randomly and in equal numbers into two groups, and they ingested one capsule containing multivitamins (MVs) or MV and 7 mg Zn daily for 10 weeks. Women who took MV and Zn showed a significant reduction in anger-hostility score (P=0.009) and depression-dejection score (P=0.011) in the Profile of Moods State (POMS) and a significant increase in serum Zn concentration (P=0.008), whereas women who took only MV did not. Our results suggest that Zn supplementation may be effective in reducing anger and depression.

A double-blind, placebo-controlled test of 2 d of calorie deprivation: effects on cognition, activity, sleep, and interstitial glucose concentrations

BackgroundAnecdotal information and limited research suggest that short-term caloric deprivation adversely affects cognition. However, this issue has not been studied using double-blind, placebo-controlled procedures, because the formulation of a calorie-deficient feeding regimen identical to one with calories is impossible using ordinary foods. Therefore, test meals varying in caloric content, but indistinguishable in sensory characteristics, were formulated using hydrocolloid-based gels as the principal structural component. ObjectiveThe purpose of this study was to examine the effects of 2 d of near-total caloric deprivation on cognitive function, satiety, activity, sleep, and glucose concentrations in a controlled environment. DesignA double-blind, placebo-controlled crossover study of caloric deprivation was conduced in a controlled environment for 48 h. Cognitive function in 27 healthy young subjects was assessed repeatedly with standardized tests of vigilance, reaction time, learning, memory, logical reasoning, mood, and satiety. Wrist-worn monitors were used to assess ambulatory vigilance, activity, and sleep. Interstitial glucose concentrations were assessed continuously with a minimally invasive monitor. ResultsWhen the subjects received the near calorie-free diets, mean calorie consumption totaled 1311 kJ (313 kcal) over the testing period. During the fully fed treatment sessions, the subjects consumed a mean of 9612 kJ/d (2294 kcal/d), which matched their individual, daily energy requirements. Satiety and interstitial glucose concentrations were lower during the calorie-deprived diet (P < 0.001) than during the fully fed diet. There were no detectable effects of calorie deprivation on any aspect of cognitive performance, ambulatory vigilance, activity, or sleep. The mood states assessed, including fatigue, were not affected by calorie deprivation. ConclusionsCognitive performance, activity, sleep, and mood are not adversely affected in healthy humans by 2 d of calorie-deprivation when the subjects and investigators are unaware of the calorie content of the treatments.

The Effect of Methylphenidate and Placebo on Eye–Hand Coordination Functioning and Handwriting of Children with Attention Deficit Hyperactivity Disorder

Israeli children who were diagnosed as having attention deficit hyperactivity disorder participated in the study. The children were assessed three times in a specially constructed battery of tests. The battery of tests included variables assessing eye–hand coordination skills, writing, and behavioral assessment of the teacher. The design was in the format of a double blind, randomized, crossover, placebo-control procedure. The results showed that methylphenidate (MPH) improved some cognitive functions of eye–hand coordination slightly better than placebo. In addition, behavior variables assessed by the teachers improved only under the influence of MPH.

Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members

The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other plants such as Psychotria viridis, is growing in urban centers of Europe, South and North America in the last several decades. Despite this diffusion, little is known about its effects on emotional states. The present study investigated the effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that ingested ayahuasca for at least 10 consecutive years. The study was done in the Santo Daime church, where the questionnaires were administered 1 h after the ingestion of the brew, in a double-blind, placebo-controlled procedure. While under the acute effects of ayahuasca, participants scored lower on the scales for panic and hopelessness related states. Ayahuasca ingestion did not modify state- or trait-anxiety. The results are discussed in terms of the possible use of ayahuasca in alleviating signs of hopelessness and panic-like related symptoms.

235 Effects of three days magnesium supplementation on anaerobic exercise performance

Magnesium is reportedly important in energy production and therefore may play a role in both anaerobic and aerobic performance. Therefore, this study investigated the effects of dietary magnesium supplementation on repeated, anaerobic cycling performance. Thirteen (8 male, 5 female) healthy, active volunteers provided written informed consent to participate in the study (mean and range age, height and mass of 21 yr, 17-40 yr; 177.0 cm, 161.0-190.2 cm; 71.7 kg, 51.3-96.2 kg). A randomised, double-blind, placebo-controlled procedure was employed whereby the participants were tested at the same time of day, 7 d apart following 3 d supplementation with a commercially-available magnesium supplement (122 mg/d magnesium) or the equivalent dose of a placebo. Testing involved a 5 min warm up followed by two 60 s maximal cycling efforts separated by 3 min rest. Peak power, time to reach peak power, total work, rating of perceived exertion (RPE) and maximal HR were assessed during each exercise bout. Blood lactate was assessed at rest, following bout 1 and at 3 and 5 min after bout 2. Peak power, time to peak power, work and maximal HR all significantly decreased and RPE significantly increased from bout 1 to bout 2. However, magnesium supplementation did not significantly alter any of the measured variables during either exercise bout when compared to the placebo. Resting, mid-exercise and peak post-exercise lactates were also not affected by magnesium supplementation compared to the placebo. In conclusion, 3 d dietary magnesium supplementation did not enhance anaerobic exercise performance or recovery between bouts.

Hot flashes: behavioral treatments, mechanisms, and relation to sleep

Hot flashes are the most common symptom of the climacteric and occur in about 75% of perimenopausal and postmenopausal women in Western societies. Although hot flashes accompany the withdrawal of estrogen at menopause, the decline in estrogen levels is not sufficient to explain their occurrence. Elevated sympathetic activation acting through central alpha(2)-adrenergic receptors contributes to the initiation of hot flashes, possibly by narrowing the thermoneutral zone in symptomatic women. Hot flashes are then triggered by small elevations in core body temperature acting within this narrowed zone. A relaxation-based method, paced respiration, has been shown in 3 controlled investigations to significantly reduce objectively measured hot flash occurrence by about 50% with no adverse effects. In 6 studies of physical exercise, however, investigators did not find positive effects on hot flashes, possibly because exercise raises core body temperature, thereby triggering hot flashes. Although many epidemiologic studies have found increased reports of sleep disturbance during the menopausal transition, recent laboratory investigations have not found this effect, nor have they found that hot flashes produce disturbed sleep. Therefore, sleep complaints in women at midlife should not routinely be attributed to hot flashes or to menopause.

Reliability and Validity of the Upper-Extremity Motor Activity Log-14 for Measuring Real-World Arm Use

In research on Constraint-Induced Movement (CI) therapy, a structured interview, the Motor Activity Log (MAL), is used to assess how stroke survivors use their more-impaired arm outside the laboratory. This article examines the psychometrics of the 14-item version of this instrument in 2 chronic stroke samples with mild-to-moderate upper-extremity hemiparesis. Participants (n=41) in the first study completed MALs before and after CI therapy or a placebo control procedure. In addition, caregivers independently completed a MAL on the participants. Participants (n=27) in the second study completed MALs and wore accelerometers that monitored their arm movements for 3 days outside the laboratory before and after an automated form of CI therapy. Validity of the participant MAL Quality of Movement (QOM) scale was supported. Correlations between pretreatment-to-posttreatment change scores on the participant QOM scale and caregiver MAL QOM scale, caregiver MAL amount of use (AOU) scale, and accelerometer recordings were 0.70, 0.73, and 0.91 (P<0.01), respectively. Internal consistency (alpha>0.81), test-retest reliability (r>0.91), stability, and responsiveness (ratio>3) of the participant QOM scale were also supported. The participant AOU and caregiver QOM and AOU scales were internally consistent, stable, and sensitive, but were not reliable. The participant MAL QOM scale can be used exclusively to reliably and validly measure real-world, upper-extremity rehabilitation outcome and functional status in chronic stroke patients with mild-to-moderate hemiparesis.

Methylphenidate (‘Ritalin’) can Ameliorate Abnormal Risk-Taking Behavior in the Frontal Variant of Frontotemporal Dementia

The frontal variant of frontotemporal dementia is a significant neurological condition worldwide. There exist few treatments available for the cognitive and behavioural sequelae of fvFTD. Previous research has shown that these patients display risky decision-making, and numerous studies have now demonstrated pathology affecting the orbitofrontal cortex. The present study uses a within-subjects, double-blind, placebo-controlled procedure to investigate the effects of a single dose of methylphenidate (40 mg) upon a range of different cognitive processes including those assessing prefrontal cortex integrity. Methylphenidate was effective in 'normalizing' the decision-making behavior of patients, such that they became less risk taking on medication, although there were no significant effects on other aspects of cognitive function, including working memory, attentional set shifting, and reversal learning. Moreover, there was an absence of the normal subjective and autonomic responses to methylphenidate seen in elderly subjects. The results are discussed in terms of the 'somatic marker' hypothesis of impaired decision-making following orbitofrontal dysfunction.

Ethical framework for the use of sham procedures in clinical trials.

Ethical, professional, and financial considerations support the highest standards in demonstrating the safety and efficacy of new clinical interventions. Professional and regulatory mechanisms implemented to ensure that medical agents undergo a thorough process of systematic testing are lacking in the case of medical procedures. As a result, many procedures, including surgery, are rapidly introduced into the clinical setting without reliable evaluation of their efficacy. In many cases, a randomized, placebo-controlled procedure trial may be necessary to provide this data. We examine the major ethical objections to placebo-controlled procedure trials, including those involving sham surgery, and provide an ethical framework for assessing whether a placebo procedure is ethical to administer in the context of a clinical trial. A placebo-controlled trial of an invasive procedure can be ethically justified if: 1) there is a valuable, clinically relevant question to be answered by the research, 2) the placebo control is methodologically necessary to test the study hypothesis, 3) the risk of the placebo control itself has been minimized, 4) the risk of a placebo control does not exceed a threshold of acceptable research risk, 5) the risk of the placebo control is justified by valuable knowledge to be gained, and 6) the misleading involved in the administration of a placebo control is adequately disclosed and authorized during the informed consent process.

Sympathetic nerve activity after acupuncture in humans

The aim of the present study was to determine if acupuncture stimulation inhibits sympathetic nerve activity in humans. Multiunit efferent postganglionic sympathetic activity was recorded with a tungsten microelectrode inserted in a muscle fascicle of the peroneal nerve. Mean arterial pressure, heart rate and skin blood flow were also monitored. Pain thresholds were measured by electrical tooth pain stimulation. After a 30 min rest, acupuncture needles were inserted bilaterally into the Li 11 and the Li 4 acupuncture points, and manipulated until `chi' cramp-like sensation was reported. Electrical stimulation (2 Hz, 0.6–0.8 ms duration, maximal tolerated stimulation without discomfort) was delivered for 30 min and the physiological recordings were continued for 90 min after the end of acupuncture. In a placebo control experiment, the same procedure was followed, except that acupuncture needles were inserted subcutaneously and no manipulation or stimulation was given. The stimulator delivered pulses to an unconnected channel, hence, the same audiovisual stimuli were experienced as with acupuncture, and care was taken to ask the same questions about sensations in the placebo and the acupuncture groups. Electroacupuncture produced an increase in pain threshold which was paralleled by a transient increase in muscle sympathetic nerve activity. During acupuncture, there was a small increase in heart rate and mean arterial pressure, but there was no post-acupuncture hypotension. The placebo control procedure did not change pain threshold or sympathetic nerve traffic. The findings suggest that electroacupuncture produces moderate hypoalgesia in humans paralleled by a significant increase in muscle sympathetic nerve activity.

Eye movement desensitization and reprocessing treatment for posttraumatic stress disorder.

A qualitative review of experimental and quasi-experimental outcome studies of eye movement desensitization and reprocessing (EMDR) treatment for persons with posttraumatic stress disorder (PTSD) suggests that the treatment is effective for civilian but not combat PTSD. The current data indicate that additional research into EMDR's efficacy for PTSD is warranted. Further studies should include comparisons to placebo control procedures and existing validated treatments for PTSD, an adequate treatment dose, systematic efforts to establish and assess treatment integrity and quality, and long-term follow-up data. The therapeutic mechanisms underlying EMDR's observed benefits remain elusive. Whether the eye movement or some other type of stimulation is essential to EMDR's effects cannot be determined from the current data.

Supplemental growth hormone alters body composition, muscle protein metabolism and serum lipids in fit adults: characterization of dose-dependent and response-recovery effects

Using double-blind, placebo-controlled procedures, the effects of low and high therapeutic dosages of methionyl-human growth hormone (met-hGH) on body composition, muscle protein metabolism and serum lipids were studied in 7 fit adults without growth hormone (GH) deficiency. Dose-dependent changes in body composition were observed that in part appeared to be influenced by a response-recovery effect, as measured by responses factored according to the duration of washout between exposure to the low and high dosages of met-hGH (6 weeks vs. 12 weeks vs. 18 weeks). Increases in fat-free weight were accompanied by an increase in skeletal muscle protein metabolism. Basal levels of cholesterol were inversely related to peak levels of GH in response to exercise stimulation and IGF-I, while GH supplementation lowered levels of total cholesterol and high- and low-density lipoproteins. A dose-dependent effect occured for total cholesterol, and the percent change in cholesterol was related to the percent change in insulin-like growth factor I (IGF-I). Endogenous levels of GH were attenuated in response to stimulation and IGF-I levels were increased after treatment with GH, but no dose-dependent changes were observed. We conclude that met-hGH alters body composition and muscle protein metabolism, and decreases stored and circulating lipids in fit adults with a preexisting supranormal body composition. The physiological profile of the person was not as important as the treatment conditions in determining the somatic and physiological response outcomes.

Supplemental growth hormone increases the tumor cytotoxic activity of natural killer cells in healthy adults with normal growth hormone secretion

Using double-blind, placebo-controlled procedures, the effects of methionyl-human growth hormone (met-hGH) on the tumor cytotoxic activity of natural killer (NK) cells were studied in seven healthy adults using a repeated measures experiment. Subjects were assigned at random to either a placebo (bacteriostatic water) treatment condition or a met-hGH (16.0 mg/wk of Protropin) treatment condition, then crossed-over to the alternative treatment. Treatments were delivered on alternate days (3 d/wk) for 6 weeks. Without bias from the met-hGH treatment, there was no evidence for GH hyposecretion as measured by the peak circulating GH response to exercise stimulation (14.1 ± 3.1 ng/mL) or insulin-like growth factor (IGF-I) levels (0.82 ± 0.09 U/mL). When compared with placebo, met-hGH induced a significant overall increase in the percent specific lysis (%SL) of K562 tumor target cells (placebo 22.2 ± 1.7 v met-hGH 28.5 ± 2.1 %SL; P = .008). NK activity was increased within the first week of treatment and this level was maintained throughout the remaining period of supplementation. There was a trend ( P = .057) for the met-hGH-induced percent change in NK activity (NK%) to be inversely related to placebo IGF-I levels ( r = −.761), while there were significant positive correlations between NK% and the met-hGH-induced percent changes in IGF-I ( r = .727; P = .035), the fat-free mass (FFM)/fat mass (FM) ratio derived by hydrodensitometry ( r = .792; P = .012), and the endogenous GH response to exercise ( r = .469; P = .034). We conclude that supplemental GH increases NK activity in healthy adults with normal GH secretion and that this effect is interrelated to the body composition and IGF-I responses to the hormone. Since these findings were observed in the absence of GH hyposecretion, exogenous GH might be of benefit in states in which the normal anabolic processes in vivo are insufficient to overcome the taxing influence of disease and/or disuse.