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Placebos are not inert, but exert measurable biological effects. The placebo response in psychiatric illness is important and clinically relevant, but remains poorly understood. In this paper, we review current knowledge about the placebo response in psychiatric medicine and identify research directions for the future. We argue that more research is needed into the placebo response in psychiatric medicine for three broad reasons. First, awareness of factors that cause placebo response, for whom, and when, within clinical trials will allow us to better evidence efficacy of new treatments. Second, by understanding how placebo mechanisms operate in the clinic, we can take advantage of these to optimise the effects of current treatments. Finally, exploring the biological mechanisms of placebo effects might reveal tractable targets for novel treatment development.
The purpose of the present study was to compare next-morning responses of RMR and appetite to pre-sleep consumption of casein protein (CP) in pre- and postmenopausal women. The study was a randomised, crossover, double-blind, placebo-controlled trial. Seven sedentary premenopausal (age: 19·9 (sd 1·2) years; BMI: 23·1 (sd 2·6) kg/m2) and seven sedentary postmenopausal (age: 56·4 (sd 4·9) years; BMI: 26·3 (sd 3·5) kg/m2) women participated. During visit one, anthropometrics and body composition were measured. Following visit one, subjects consumed either CP (25 g) or placebo (PL) ≥2 h after their last meal and ≤30 min prior to sleep on the night before visits two and three. Visits two and three occurred ≥1 week after visit one and were 48 h apart. During visits two and three, RMR (VO2), RER and appetite were measured via indirect calorimetry and visual analogue scale, respectively. Anthropometrics and body composition were analysed by one-way ANOVA. RMR and measures of appetite were analysed using a 2 × 2 (menopause status × CP/PL) repeated-measures ANOVA. Significance was accepted at P ≤ 0·05. RMR was significantly lower in postmenopausal compared with premenopausal women under both conditions (P = 0·003). When consumed pre-sleep CP did not alter RMR, RER or appetite compared with PL when assessed next morning in pre- and postmenopausal women. These data contribute to growing evidence that pre-sleep consumption of protein is not harmful to next-morning metabolism or appetite. In addition, these data demonstrate that menopause may not alter next-morning RMR, RER or appetite after pre-sleep consumption of CP.
Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder (MDD).
In this randomized, double-blind trial, patients age ≥ 18 meeting DSM-IV criteria for MDD were randomized to placebo (N = 99), duloxetine 80 mg/day (N = 93), duloxetine 120 mg/day (N = 103), or paroxetine 20 mg/day (N = 97). The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression (HAMD17) total score after 8 weeks of treatment; a number of secondary efficacy measures also were assessed. Safety and tolerability were assessed via collection and analysis of treatment–emergent adverse events (TEAEs), vital signs, and weight. The Arizona sexual experiences scale was used to assess sexual functioning. Patients who had a ≥ 30% reduction from baseline in the HAMD17 total score at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase; efficacy and safety/tolerability outcomes were assessed during continuation treatment.
More than 87% of patients completed the acute phase in each treatment group. Duloxetine-treated patients (both doses) showed significantly greater improvement (P < 0.05) in the HAMD17 total score at week 8 compared with placebo. Paroxetine was not significantly different from placebo (P = 0.089) on mean change on the HAMD17. Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures (six of nine) compared with placebo while duloxetine 80 mg/day (three of nine) and paroxetine (three of nine) were significantly superior to placebo on fewer secondary measures. HAMD17 mean change data from this study and an identical sister study were pooled as defined a priori for the purposes of performing a non-inferiority test versus paroxetine. Both duloxetine doses met statistical criteria for non-inferiority to paroxetine. TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases.
The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated. Tolerability, as measured by TEAEs, and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD.
The onset of action of antidepressant drugs was investigated on the basis of two independent multicenter, double-blind efficacy studies comparing amitriptyline (n = 120), oxaprotiline (n = 120), imipramine (n = 506) and moclobemide (n = 580) with placebo (n = 189 + 191). The samples consisted of in- and outpatients diagnosed, according to Diagnostic and Statistical Manual (DSM)-III criteria, as suffering from major depressive disorder. Measures of efficacy criteria were the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A) and the Zung Self-Rating Depression scale. By using the Sustained Relative Improvement (SRI) criterion, onset of action was determined in each individual patient as that time point in the 30 day observation period at which a 20% baseline score reduction was achieved without subsequent deterioration. Analogously, a response to treatment was defined as a 50% baseline score reduction. As expected, highly significant differences between active drugs and placebo were found with respect to the total number of improvers and responders. Significant differences between treatment modalities surfaced in the percentage rate as well as the time distribution of premature withdrawals. Yet, unexpectedly, among improvers, the time spans to onset of improvement were found to be independent of treatment modality as indicated by virtually identical cumulative percentages of improvers throughout the whole observation period. The picture was essentially the same for the HAM-A and Zung assessments, except for a significant time lag between observer- and self-ratings. In particular, our analyses revealed no evidence for a delayed onset of action under various antidepressants with large biochemical and pharmacological differences in comparison to placebo. Moreover, the early onset of improvement was highly predictive of later outcome: on average, 70% of the patients showing improvement within the first 14 days became responders. Applying survival-analytical methods, we found that differences between active treatments and placebo emerged within the first 5 days and reached a point of maximum distinction around day 14. After this time point, differences between treatment modalities remained constant until the end of the observation period. According to our data, 20–25% of the patients were, on average, ‘true’ drug responders, thus suggesting that the therapeutic qualities of antidepressants do not lie in the suppression of symptoms, but rather are related to their ability to elicit and maintain certain conditions which allow recovery in a subgroup of patients who would otherwise remain non-responders.
The use of a placebo control group in the evaluation of a new product is today considered by most as a necessary condition of experimental drug research. Placebo response is an essential consideration in all clinical trials. If not properly controlled, incorrect and dangerous conclusion may be inferred for a product efficacy and safety profile. However, the inclusion of a placebo group in clinical trials in neuropsychiatric research raises several ethical and scientific questions. Whereas in certain indications, such as suicidal patients and severe and psychotic depression, the use of a placebo is generally not accepted, it is difficult to assess drug efficacy. This article discusses the concept of placebo in clinical trials, the occurrence of adverse events after placebo treatment and the high response rate of placebo in neuropsychiatric clinical research. The experimental methodology to adequately control all the factors involved is also analysed and discussed.
There is a tension between the need for scientifically valid trials of new psychotropic drugs and concern about conducting placebo-controlled trials, the trials psychopharmacologists consider the gold standard trial, when this requires that some patients be denied existing effective therapy. This paper will review the scientific principles supporting the need for placebo-controlled trials in depression and schizophrenia, and will provide preliminary data on failure rates of placebo-controlled trials for these disorders, as illustrations of the application of these principles. Next, the ethical issues pertinent to the conduct of placebo-controlled trials for these two serious psychiatric disorders will be reviewed. Preliminary data on suicides in placebo-controlled depression and schizophrenia trials will be presented to argue for the ethical acceptability of the conduct of placebo-controlled trials in these two conditions.
Clinical trials of new antidepressants usually compare a new drug to a reference antidepressant and to a placebo. The placebo is intended to validate the trial in the case of a no-difference outcome, i.e., it helps in assessing equivalence. The aim of the present paper is to test whether placebo has indeed helped establish equivalence of effect in comparative trials of new antidepressants. We carried out an example of sample size determination first in a trial to show a difference between the new and control drug, and second in a trial to assess equivalence between two competing drugs. Finally, we retrospectively calculated the maximum difference accepted as equivalence of effect in published trials of new antidepressants. Assuming a response rate to antidepressants of 70%, 294 subjects for each treatment group are needed to show a 10% difference between two antidepressant drugs and more than 1,300 to assess equivalence at a 5% level of δ, the maximum difference acceptable as equivalence of effect. The level of δ in published trials of new antidepressants ranges between 12 and 43%, suggesting they cannot claim to demonstrate equivalence of effect. Therefore, the presence of a placebo arm for comparison didn’t help establish whether both drugs really worked the same way. Comparative trials of new antidepressants should adopt a two-arm design, a suitable number of patients and a high standard in the experimental design in order to minimise possible control-event rate variation.
In the course of the international development of tianeptine (T), depressed patients were recruited by 15 centres from Belgium, Italy, Portugal, Spain and Switzerland in a double-blind parallel group study versus placebo (P) and imipramine (I). Efficacy and safety of tianeptine are evaluated in the treatment of major depressions (single episode or recurrent) and depressed bipolar disorders. The initial severity of the depression is controlled by a MADRS score equal to or greater than 25. Rapid placebo responded are excluded during a placebo pre-inclusion period (duration: 1 week). After an increasing daily dose period (3 days), depressed patients are treated, until the 14th day (D14), at a constant daily dose (T: 37.5 mg; I: 150 mg; P: 3 capsules). After D14 and until the end of the 6th week, a flexible dosage can be used in accordance with the therapeutic efficacy and/or the potential adverse events (T: 25–50 mg; I: 100–200 mg; P: 2–4 capsules). The antidepressant efficacy is regularly evaluated by rating scales (MADRS, HSCL). Anxiety linked to depression is evaluated by the Hamilton Anxiety Rating Scale. The safety is controlled by clinical examination, laboratory parameters and a check-list of side-effects. Preliminary results are presented and discussed showing the interest of surveillance of trials in progress.
A review of the literature on placebo-controlled studies in schizophrenia reveals, that the percentage of placebo responders in short-term trials amounts to 0–40%; on active treatment the response rate is 40–60%. In relapse prevention studies 18–100% of patients on placebo relapsed as compared to 0–40% on active treatment. Factors of importance for the variability between studies are discussed. Desirable designs of explanatory and pivotal studies, the importance of placebo controlled relapse prevention studies, and more rigorous assessment methods, eg video-taped and structured interviews for diagnostic and symptom rating purposes, are proposed as a means to improve the quality of the clinical documentation of new drugs.
In the course of the international development of tianeptine (T), depressed patients were recruited by 18 centres from Belgium, Italy, Mexico, Portugal, Spain and Switzerland in a double-blind parallel group study versus placebo (P) and imipramine (I). Efficacy and safety of tianeptine were evaluated in 187 depressed inpatients (56% female, 44% male), who fulfilled criteria for either major depression, single episode (24.6%) or recurrent (66.8%), or depressed bipolar disorder (8.6%). After a seven-day run-in placebo pre-inclusion period, patients were treated in double-blind conditions with tianeptine (37.5 mg/d) or imipramine (150 mg/d) or placebo for 14 days, including an increasing daily dose period of three days. After the fourteenth day and until the end of the sixth week of treatment, a flexible dosage was introduced in accordance with the therapeutic efficacy and/or the potential adverse events (T: 25–50 mg/d; I: 100–200 mg/d; P; 2–4 capsules). Discontinuation of treatment occurred in 57 patients (30.5%) with more inefficacy on placebo and tianeptine (P: 16/23; T: 11/17; I: 7/17), and more side-effects on imipramine (P: 1/23; T: 1/17; I: 7/17). Final MÅDRS scores in intention-to-treat analysis were 22.3 ± 1.5, 17.3 ± 1.6 and 18.4 ± 1.5 for placebo, tianeptine and imipramine, respectively. Statistical analysis demonstrated the antidepressive efficacy of tianeptine and imipramine versus placebo (P = 0.012 and P = 0.034, respectively), and no difference between tianeptine and imipramine. In patients treated for 42 days (n = 129) the MÅDRS scores dropped from 62.3% on tianeptine, 54.2% on imipramine and 48.5% on placebo. These results confirmed the efficacy of tianeptine (37.5 mg/d) in the treatment of major depression and depressed bipolar disorder when compared to placebo. No difference was found between tianeptine and imipramine (150 mg/d) for the efficacy and between tianeptine and placebo for all safety criteria. The following adverse events were significantly more frequent with imipramine than with tianeptine or placebo: dry mouth (P < 0.001), constipation (P = 0.007), and hot flushes (P = 0.011). No difference in adverse events was found between tianeptine and placebo. While the usual cardiovascular signs of tricyclic antidepressants were observed in the imipramine group, no difference between tianeptine and placebo was shown in respect to heart rate or blood pressure (supine or standing). The assessment of haematological, renal, metabolic and hepatic parameters confirmed the safety of tianeptine.
Meta-analysis of several double-blind, placebo-controlled studies, including 1277 patients, has been performed in order to compare the efficacy of moclobemide, a new reversible and selective MAO-A inhibitor (RIMA) and imipramine. The main interest of the analysis was to test the time course of improvement and the impact of the pre-defined outcome criteria (50% reduction of total HAMD score) on the response to treatment, if initial severity of depression and drop-outs due to inefficacy are taken into consideration. In order to analyze the interdependence of the severity of the disease and outcome, patient sample was subdivided into three HAMD (17 items) baseline score groups: low- (score ≤ 21), medium- (22-27) and high (≥ 28) scorers. We found that reliable assessment of the point in time at which a drug begins to show therapeutic effect in each individual is a critical factor in the determination of the time course of improvement. We defined therefore the onset of improvement as the time point of a significant decrease (20%) of HAMD baseline score without subsequent deterioration. The threshold for the distinction between a significant change and spontaneous fluctuations, or error variations due to instrument or observer, was the natural variability of the HAMD score during the first two observation days. The results of the analysis replicated our earlier findings and confirmed that in treatment responders the time course of improvement is identical under placebo and antidepressants. Neither the time-points of the onset of effect, nor the time-points at which a 50% decrease of HAMD was reached, differed between the groups. In particular, no treatment- Specific time lag showed up in the onset of action. The difference in efficacy between antidepressants and placebo was evident only in the total number of responders and non-responders. Moreover, onset of improvement within the first 10 days of treatment, which was observed in 40-50% of patients, was highly predictive of the final response to treatment. The rate of correctly predicted responders in our sample was 70% for all three treatment modalities. With respect to the severity of the disease, a slight shift towards earlier onset of improvement was found for more severe cases. This finding was true for placebo and drug responders hut there was no clear-cut other interdependence with the treatment outcome. Drop-out rales due to inefficacy were in this study similar under all treatments (20-24%) anil occurred mostly during the first two weeks of the trial (64-71%.).
A short review of placebo response in double-blind placebo-controlled therapeutic panic disorder studies published since 1985 is given. The main result is that the inefficacy-related drop-out rate of the placebo group of almost all clinical studies grows to more than 30% after 4-5 weeks of treatment and that often the results of placebo responders do not widely differ from that of the treatment groups. Except in some studies with very large sample sizes, the described response of the placebo group will not lead to significant differences between placebo and drug in completer analysis, making last observation carried forward (LOCF) analysis necessary. However, the large drop-out rates may lead to invalid efficacy results in later stages of the studies. As it can be shown that the inefficacy-related drop-out rates between placebo and target drug groups are as good an efficacy characteristic as any other, more conventional efficacy parameters, it is proposed to use the inefficacy related drop-out rate as the main efficacy parameter in placebo-controlled panic disorder studies of more than 4-5 weeks.
Risperidone is a common psychopharmacological treatment for irritability in autism spectrum disorder (ASD). It is not well-established how effective risperidone is across the initial symptom severity range. This study aims to examine the influence of baseline severity on the efficacy of risperidone in the treatment of ASD.
Participants were from the NIMH funded RUPP multisite, randomized, double-blind trial that compared risperidone to placebo to treat autistic disorder with severe tantrums, aggression, or self-injury. Participants were aged 5 to 17, and randomly assigned to risperidone (n = 49) or placebo (n = 52). Baseline and change scores were computed with the Aberrant Behavior Checklist (ABC) parent assessed scales with irritability as the primary outcome, as well as the clinician assessed ABC Irritability subscale, and Clinical Global Impression Scale.
The relationship between baseline severity and change scores for the risperdone and placebo groups was examined with eight competing three-level mixed-effects models for repeated measure models. Significant (P < 0.01) interactions between treatment and baseline severity were observed for parent ABC ratings of irritability and lethargy only. Greater magnitudes of the differences between risperidone and placebo were observed from moderate to very severe baseline severity on irritability and lethargy. Initial severity values over approximately 30 had a strong effect on symptom change [irritability: effect size (ES) = 1.9, number needed to treat (NNT) = 2, lethargy ES = 0.9, NNT = 5].
Parents may expect benefits of risperidone on irritability and lethargy with moderate to severe symptoms of ASD.
Given the common view that pre-exercise nutrition/breakfast is important for performance, the present study investigated whether breakfast influences resistance exercise performance via a physiological or psychological effect. Twenty-two resistance-trained, breakfast-consuming men completed three experimental trials, consuming water-only (WAT), or semi-solid breakfasts containing 0 g/kg (PLA) or 1·5 g/kg (CHO) maltodextrin. PLA and CHO meals contained xanthan gum and low-energy flavouring (approximately 122 kJ), and subjects were told both ‘contained energy’. At 2 h post-meal, subjects completed four sets of back squat and bench press to failure at 90 % ten repetition maximum. Blood samples were taken pre-meal, 45 min and 105 min post-meal to measure serum/plasma glucose, insulin, ghrelin, glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations. Subjective hunger/fullness was also measured. Total back squat repetitions were greater in CHO (44 (sd 10) repetitions) and PLA (43 (sd 10) repetitions) than WAT (38 (sd 10) repetitions; P < 0·001). Total bench press repetitions were similar between trials (WAT 37 (sd 7) repetitions; CHO 39 (sd 7) repetitions; PLA 38 (sd 7) repetitions; P = 0·130). Performance was similar between CHO and PLA trials. Hunger was suppressed and fullness increased similarly in PLA and CHO, relative to WAT (P < 0·001). During CHO, plasma glucose was elevated at 45 min (P < 0·05), whilst serum insulin was elevated (P < 0·05) and plasma ghrelin suppressed at 45 and 105 min (P < 0·05). These results suggest that breakfast/pre-exercise nutrition enhances resistance exercise performance via a psychological effect, although a potential mediating role of hunger cannot be discounted.
The aim of this study was to investigate the combined effect of n-3 fatty acids (EPA and DHA, at an EPA:DHA ratio of 150:500) and phytosterol esters (PS) on non-alcoholic fatty liver disease (NAFLD) patients. We conducted a randomised, double-blind, placebo-controlled trial. Ninety-six NAFLD subjects were randomly assigned to the following groups: the PS group (receiving 3·3 g/d PS); the FO group (receiving 450 mg EPA + 1500 mg DHA/d); the PS + FO combination group (receiving 3·3 g/d PS and 450 mg EPA + 1500 mg DHA/d) and the PO group (a placebo group). The baseline clinical characteristics of the four groups were similar. The primary outcome was liver:spleen attenuation ratio (L:S ratio). The percentage increase in liver–spleen attenuation (≤1) in the PS + FO group was 36 % (P = 0·083), higher than those in the other three groups (PS group, 11 %, P = 0·519; FO group, 18 %, P = 0·071; PO group, 15 %, P = 0·436). Compared with baseline, transforming growth factor-β (TGF-β) was significantly decreased in the three study groups at the end of the trial (PS, P = 0·000; FO, P = 0·002; PS + FO, P = 0·001) and TNF-α was significantly decreased in the FO group (P = 0·036), PS + FO group (P = 0·005) and PO group (P = 0·032) at the end of the intervention. Notably, TGF-β was reduced significantly more in the PS + FO group than in the PO group (P = 0·032). The TAG and total cholesterol levels of the PS + FO group were reduced by 11·57 and 9·55 %, respectively. In conclusion, co-supplementation of PS and EPA + DHA could increase the effectiveness of treatment for hepatic steatosis.
Psychiatric treatments have specific and non-specific components. The latter has been addressed in an extensive literature on the placebo-effect in pharmacology and on common factors in psychotherapy. In the practice of mental health care, pharmacological, psychotherapeutic and social treatments are combined in complex interventions. This paper aims to review non-specific components across diverse psychiatric treatments and consider implications for practice and research.
We conducted a non-systematic review of non-specific components across psychiatric treatments, their impact on treatment processes and outcomes, and interventions to improve them.
The identified research is heterogeneous, both in design and quality. All non-specific components capture aspects of how clinicians communicate with patients. They are grouped into general verbal communication – focusing on initial contacts, empathy, clarity of communication, and detecting cues about unspoken concerns – non-verbal communication, the framing of treatments and decision-making. The evidence is stronger for the impact of these components on process measures – i.e. therapeutic relationship, treatment satisfaction and adherence than on clinical outcomes – i.e. symptoms and relapse. A small number of trials suggest that brief training courses and simple methods for structuring parts of clinical consultations can improve communication and subsequently clinical outcomes.
Methodologically, rigorous research advancing current understandings of non-specific components may increase effectiveness across different treatments, potentially benefitting large numbers of patients. Brief training for clinicians and structuring clinical communication should be used more widely in practice.
Information conveyed on the price tag or label of a consumable packaged good is widely thought to change the consumer's sensory experience of consuming the good. Can the positive “placebo” effects of high prices and negative “nocebo” effects of low prices on consumer experience be isolated and observed in a controlled experiment without using deception? In a pilot wine experiment using a method I call “half-blind tasting,” I observe that the nocebo response to a $5 price tag is stronger than the placebo response to a $50 price tag. To interpret these preliminary results, I borrow some insights from prospect theory. (JEL Classifications: C91, D81, L66, M31, Q11)
The functional significance of pomegranate (POM) supplementation on physiological responses during and following exercise is currently unclear. This systematic review aimed (i) to evaluate the existing literature assessing the effects of POM supplementation on exercise performance and recovery; exercise-induced muscle damage, oxidative stress, inflammation; and cardiovascular function in healthy adults and (ii) to outline the experimental conditions in which POM supplementation is more or less likely to benefit exercise performance and/or recovery. Multiple electronic databases were used to search for studies examining the effects of POM intake on physiological responses during and/or following exercise in healthy adult. Articles were included in the review if they investigated the effects of an acute or chronic POM supplementation on exercise performance, recovery and/or physiological responses during or following exercise. The existing evidence suggests that POM supplementation has the potential to confer antioxidant and anti-inflammatory effects during and following exercise, to improve cardiovascular responses during exercise, and to enhance endurance and strength performance and post-exercise recovery. However, the beneficial effects of POM supplementation appeared to be less likely when (i) unilateral eccentric exercise was employed, (ii) the POM administered was not rich in polyphenols (<1·69 g/l) and (iii) insufficient time was provided between POM-ingestion and the assessment of physiological responses/performance (≤1 h). The review indicates that POM has the potential to enhance exercise performance and to expedite recovery from intensive exercise. The findings and recommendations from this review may help to optimise POM-supplementation practice in athletes and coaches to potentially improve exercise-performance and post-exercise recovery.
The purpose of this study was to determine the effect of a whole-food protein (cottage cheese, CC) consumed before sleep on next-morning resting energy expenditure (REE), RER and appetite compared with an isoenergetic/isonitrogenous casein protein (CP) supplement and placebo (PL) in active women. In a beverage-blinded, randomised, cross-over design, ten active women (age, 23·1 (sd 1·9) years; body fat, 22·0 (sd 4·6) %) consumed pre-sleep CC (30 g of protein, 10 g of carbohydrate and 0 g of fat) or energy- and protein-matched liquid CP or PL (0 kJ). Participants arrived at 18.00 hours for an overnight stay in the laboratory. At 30–60 min before normal bed time (2 h post standard meal), participants consumed CC, CP or PL before measurement of REE. Upon waking (05.00–08.00 hours), REE was repeated and subjective appetite was recorded. Statistical analyses were conducted using repeated-measures ANOVA (SPSS). Significance was accepted at P≤0·05. There were no significant differences in acute REE (CC, 7217 (sd 1368); CP, 7188 (SD 895); PL, 7075 (sd 1108) kJ/d, P=0·95), acute RER (0·79 (sd 0·05), P=0·56), morning REE (CC, 5840 (sd 1225); CP, 5694 (sd 732); PL, 5991 (sd 903) kJ/d, P=0·79) or morning RER (0·77 (sd 0·03), P=0·52). Subjective measures of appetite were not different between groups. In active women, pre-sleep consumption of CC does not alter REE or RER more than a CP or PL beverage. These data suggest that the metabolic response from whole-food protein do not differ from the metabolic response of liquid protein.
Beetroot juice (BJ) consumption has been associated with improved cardiovascular health owing to an increase in NO bioconversion. This study evaluates the effect of BJ consumption on macrovascular endothelial function (flow-mediated dilation (FMD)) and muscle oxygen saturation (StO2) parameters in pregnant women within a randomised, crossover, double-blind design in which twelve pregnant women consumed a single dose (140 ml) of BJ or placebo (PLA). Urinary nitrate was assessed before (T0) and 150 min after BJ/PLA consumption. FMD was used to evaluate macrovascular endothelial function, and near-IR spectroscopy was used to evaluate muscle StO2 parameters during the occlusion and reperfusion phases, which were taken at baseline (PRE) and 120 and 140 min after BJ/PLA consumption, respectively. A significant increase in urinary nitrate was observed at 150 min after BJ consumption when compared with T0 (BJ: 0·20 (sd 0·13) v. T0: 0·02 (sd 0·00), P=0·000) and PLA intervention (PLA: 0·02 (sd 0·00), P=0·001). FMD improved after BJ consumption when compared with PRE (BJ: 11·00 (sd 1·67) v. PRE: 5·53 (sd 1·17), P=0·000) and PLA (5·34 (sd 1·31), P=0·000). No significant difference between PLA and PRE in FMD (P=1·000) was observed. In StO2 parameters, a difference was not observed after BJ consumption compared with PRE and PLA intervention. The data demonstrate that a single dose of 140 ml of BJ consumption improves macrovascular endothelial function, but not StO2 parameters.