Acute alcohol consumption disrupts the hormonal milieu of lactating

Abstract Despite the lack of scientific evidence to support the claim that alcohol is a galactagogue, lactating women have been advised to drink alcohol as an aid to lactation for centuries. To test the hypothesis that alcohol consumption affects the hormonal response in lactating women, we conducted a withinsubjects design study in which 17 women consumed a 0.4 g/kg dose of alcohol in orange juice during one test session and an equal volume of orange juice during the other. Changes in plasma prolactin, oxytocin, and cortisol levels during and after breast stimulation, lactational performance, and mood states were compared under the two experimental conditions. Oxytocin levels significantly decreased, whereas prolactin levels and measures of sedation, dysphoria, and drunkenness significantly increased, during the immediate hours after alcohol consumption. Changes in oxytocin were related to measures of lactational performance such as milk yield and ejection latencies, whereas changes in prolactin were related to self-reported measures of drunkenness. Although alcohol consumption resulted in significantly higher cortisol when compared with the control condition, cortisol levels were not significantly correlated with any of the indices of lactational performance or self-reported drug effects. Moreover, cortisol levels steadily decreased on the control day, indicating that the procedures were not stressful to the subjects. In conclusion, recommending alcohol as an aid to lactation may be counterproductive. In the short term, mothers may be more relaxed, but the Correspondence to: Julie A. Mennella. Address all correspondence and requests for reprints to: Julie A. Mennella, Ph.D., 3500 Market Street, Philadelphia, Pennsylvania 19104-3308. E-mail: [email protected] hormonal milieu underlying lactational performance is disrupted, and, in turn, the infant's milk supply is diminished. THE TRADITIONAL WISDOM of many cultures relates that women can optimize the quality and quantity of their milk to meet the needs of their infants through diet and psychological well-being. Each culture claims some milk-producing (galactogenic) substances, and many cultures claim alcohol to be such a substance (1). Such beliefs were so ingrained in American tradition that, in 1895, Anheuser-Busch Company, a major U.S. brewery, produced MaltNutrine, a low-alcoholic beer that was sold exclusively in drugstores and prescribed by physicians as a tonic for pregnant and lactating women (2). Even in more modern times, a popular book for nursing mothers hailed the virtues of alcohol as a galactagogue, claiming ". . . this is one time in life when the therapeutic qualities of alcohol are a blessing " (3). Such claims have not gone unchallenged. In 1987, the Journal of the American Medical Association published a letter from a physician asking whether there was any scientific basis for prescribing a daily beer to lactating women (4). The scientific basis, it was declared (5), can be found in the finding that the consumption of beer, unlike other alcoholic beverages, increases serum prolactin (5,6). There are several problems with this conclusion, however. First, the subjects in these research studies were men and nonlactating women. No study to date had examined the effects of alcohol consumption on the hormonal milieu of lactating women, additionally highlighting the lack of evidence-based practice related to recommendations regarding alcohol consumption during lactation. There has been considerable research in animal models (for review, see Ref. 7), however. Although the vast majority of these studies reported that ethanol administration decreased suckling-induced prolactin, the most recent study, which extended the observation period Second, the rise in prolactin levels after alcohol consumption was observed after the consumption of different types of alcoholic beverages (9,10) and was not specific to beer consumption, as the folklore suggested (2,4,5). Moreover, if alcohol does indeed increase prolactin levels in maternal circulation, it is not apparent whether such increases affect lactational performance. Although prolactin appears to be essential for the initiation of lactation and its maintenance in the long term (11), no clear temporal correlation exists between plasma prolactin levels and milk yield of a particular breastfeed in humans (12). Third, it is perplexing that one would argue that alcohol enhances lactational performance when this same drug, at similar or slightly higher doses, was used in the not-so-distant past to treat premature labor Fourth, research conducted during the past decade refutes the lore that alcohol is a galactagogue. Rather, lactating mothers produced less milk without changes in the caloric content of their milk (16), and, in turn, infants consumed less breast milk and less calories during the immediate hours after maternal consumption of beer as well as other types of alcoholic beverages NIH-PA Author Manuscript The present study tested the hypothesis that the alcohol-induced depression in milk production in lactating women was due to disruptions in the hormonal milieu. Oxytocin and prolactin responses were evaluated when lactating women consumed a moderate dose of alcohol, one that was equivalent to one to two drinks and represents the average amount of alcohol lactating women reported consuming during a drinking occasion (20). Subjects and Methods Subjects Seventeen nonsmoking, healthy lactating women (six primiparous and 11 multiparous), who were exclusively nursing infants between the ages of 2 and 4 months, were recruited from ads in local newspapers and newsletters. One additional woman began testing but was excluded because of procedural difficulties. During initial screening, women were excluded if they were lifetime alcohol abstainers, on any medication including oral contraceptives, or had resumed menstruation, because there is some suggestion that both basal and peak prolactin levels are lower in such women (21). All procedures were approved by the Office of Regulatory Affairs at the University of Pennsylvania, and each subject gave informed written consent before testing. The women (10 Caucasian, five African American, one Asian, and one from another ethnic group) were, on average, 31.9 ± 1.2 yr of age, with a mean body mass index of 26.4 ± 1.1 kg/ m 2 . They reported that alcohol intake was low during pregnancy (mean = 0.2 ± 0.1 standard drinks per month) but significantly increased to, on average, 1.5 ± 0.6 drinks per month during lactation [paired t-test (16df) = -2.14; P = 0.048]. These numbers likely underestimate alcohol usage (22). Procedures A within-subjects design study that controlled for time of day was employed because milk composition and hormonal responses vary throughout the day. Using methodologies developed for the study of neurally mediated hormonal responses in humans (23), women were tested at the General Clinical Research Center (GCRC) at the University of Pennsylvania on 2 d separated by 1 wk (±2 d). After abstaining from alcohol for at least 3 d, all subjects arrived at the GCRC at 0800 h (±30 min) after an overnight fast and remained fasted during the entire testing procedures, because prolactin levels can be potentiated by certain gastrointestinal hormones and high blood glucose levels (24). Mothers were not allowed to watch television, sleep, or talk, as well as read about food or infants throughout the entire testing session because these behaviors may affect the hormones under study. Instead, they were able to read magazines or novels or to converse on other topics. Moreover, infants were not present because the mere sound, sight, or smell of the baby often stimulates milk let-down or leaking (25). Breast stimulation was provided by an electric breast pump because prior work revealed that infants ′ sucking intensity changes when their mothers′ milk contains alcohol (20). Approximately 30 min after arrival, an iv line was inserted into the antecubital vein of an arm. Because prolactin is very stress labile and rises during the first half-hour after a needle prick (26), subjects acclimated in a private testing room for 45 min. After acclimatization, blood samples were obtained at fixed intervals (-40, -25, and -10 min) before drinking a 0.4 g/kg dose of alcohol in orange juice (15% vol/vol) on one testing day (alcohol condition) and an equal volume of orange juice on the other day (control condition). During both conditions, 3 ml of alcohol were pipetted onto the surface of the cup to serve as a smell and flavor mask (27). The order of testing was randomized between subjects. The beverage was aliquoted into two equal volumes, and each aliquot was consumed within consecutive 5-min periods. As shown in Blood alcohol concentrations (BAC; g/liter) were estimated by having subjects breathe into an Alco-Sensor III (Intoximeters, Inc., St. Louis, MO) throughout the test sessions ( Hormone assays Plasma samples were measured in duplicate by double-antibody RIAs for oxytocin and cortisol and by immunoradiometric assay for prolactin. Standards were run with each assay. All samples from a given subject from both days (alcohol and control) of testing were run within the same assay to reduce interassay variability. Cortisol levels were monitored on the control day to ensure that alterations in hormonal responses were not related to the stress of the procedures (10). Intraassay variation was 2.8, 3.0, and 1.3%, and interassay variation was 1.9, 8.9, and 10.2% for oxytocin, prolactin, and cortisol, respectively. All assays were performed by the Diabetes Research Center of the University of Pennsylvania. Oxytocin was assayed without extraction by using a competitive RIA, with materials supplied by Phoenix Pharmaceuticals, Inc. (Belmont, CA). The antiserum cross-reactivity with arginine vasopressin, GH, α-atrial natriuretic peptide (1-28), methionine-enkephalin, GH-releasing factor, somastatin, TRH, vasoactive intestinal peptide, and pituitary adenylate cyclaseactivating polypeptide 27-NH 2 is 0%. The minimal detectable concentration was 10 pg/ml (8 pmol/liter). Prolactin was assayed by a direct, two-site immunoradiometric assay without extraction, using materials supplied by ICN Diagnostics (Costa Mesa, CA). The antiserum cross-reactivity is less than 0.01% for human chorionic gonadotropin, TSH, LH, and FSH. The minimal detectable concentration was 2.5 ng/ml (108.8 pmol/liter). Cortisol was measured without extraction by a competitive double-antibody RIA kit from ICN Diagnostics. The antiserum cross-reacts 12.3% with 11-deoxycortisol, 5.5% with corticosterone, and less than 2.7% with all other steroids tested. Data analyses Separate repeated measures mixed ANOVA were conducted to determine whether there were significant differences in prolactin, oxytocin, cortisol, and BAC levels, as well as various measures of self-reported drug effects with experimental condition (alcohol and control) and time as the within-subjects factors. When significant, post hoc Fisher least significant difference analyses were conducted. Because there were no significant differences in the basal values for oxytocin [F(2,32df) = 2.17; P = 0.13] and prolactin [F(2,32df) = 0.50; P = 0.61], we calculated changes in prolactin and oxytocin from respective baseline value (mean of three baseline samples) for each subject. There was a significant effect of time on cortisol baseline samples [F(2,32df) = 60.77; P < 0.0001]. Therefore, the last sample (t =-10 min) was used as the baseline value. We then determined the peak value for each hormone when compared with baseline and calculated the area under the curve (AUC) values by using a point-to-point method (OriginLab Corporation, Northampton, MA) from baseline to the end of the test session (t = 140 min). The areas for each hormone and for each subject were calculated independently. Paired t-tests were used to compare the peak value of each hormone and the AUC between experimental conditions, respectively. The critical value for significance was P < 0.05, and all P values represent two-tailed tests. Results Hormonal responses and lactational performance Oxytocin. There was a significant interaction between condition and time on oxytocin levels [F(15,240df) = 1.83; P = 0.03]. As shown in Although there were no significant correlations with oxytocin AUC during breast stimulation and milk ejection latency Twelve of the 17 women produced less oxytocin during breast stimulation on the alcohol day when compared with the control day (P < 0.05). These women also had lower milk yields during the 16 min of pumping when compared with the remaining women [F(1,15df) = 9.35; P = 0.008]. They produced, on average, 13 ± 7% less milk during these 16 min of pumping (control vs. alcohol, 131 ± 10 vs. 113 ± 11 ml). There were no significant relationships between the oxytocin AUCs or oxytocin levels on either the control or alcohol day and any of the selfreported measured indices of drug effects (all P values >0.10). Prolactin. There was a significant interaction between condition and time on prolactin plasma levels [F(15,240df) = 3.31; P < 0.001]. As shown in NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript = 3.52; P = 0.003]. This enhanced response was observed in 76% of the women tested (P = 0.02). Although there were no significant relationships on the control day between prolactin levels and milk ejection latency or amount of milk expressed (all P values > 0.10), prolactin AUCs during breast stimulation were significantly correlated with milk ejection latencies on the day women consumed alcohol ( Cortisol. Although the repeated measure mixed ANOVA analysis revealed only a tendency for an interaction effect between condition and time for cortisol levels [F(15,240df) = 1.63; P = 0.07], there were significant effects of condition [F(1,16df) = 5.91; P = 0.03] and time [F (15,240df) = 4.39; P < 0.001] on cortisol levels. As shown in Ethanol pharmacokinetics and self-reported drug effects BAC peaked approximately 43-51 min after alcohol consumption and decreased thereafter. As shown in Discussion Moderate alcohol consumption disrupted the two key hormones underlying lactational performance. During the immediate hours after alcohol consumption, oxytocin levels significantly decreased, whereas prolactin levels significantly increased both during and after breast stimulation. The magnitude and persistence of the hormonal response in lactating women is more robust when compared with men and nonlactating women (5,6,9,10), further highlighting the dynamics of the system under study. The diminished oxytocin response was significantly related to decreases in milk yield and milk ejection. These latter findings suggest that such changes in hormonal responses mediate the diminished milk production by lactating women (16) and disruption in their infants′ suckling behaviors and milk intake observed in prior research In contrast to the response observed for oxytocin, prolactin levels significantly increased after alcohol consumption both during and after periods of breast stimulation. The alcohol-induced increases in prolactin were related to self-reported perceptions of drunkenness. Women also reported increased feelings of sedation and dysphoria during the immediate hours after alcohol consumption. Because sleep deprivation increases feelings of sedation and dysphoria (32), we hypothesize that sleep deprivation, which is common among mothers of young infants, contributed to the increased feelings of sedation and dysphoria observed on the day lactating women consumed alcohol, as discussed herein. Although prolactin levels during breast stimulation were related to milk ejection latency on the day women consumed alcohol, it should be emphasized that no relationships were observed between prolactin levels or AUCs and the amount of milk produced on either test day. This is consistent with prior research revealing that although prolactin appears to be essential for the initiation of lactation and its maintenance in the long term (11), no clear temporal correlation exists between plasma prolactin levels and milk yield of a particular breastfeed in humans (12). It remains to be determined whether the relationship between alcohol-induced changes in prolactin and milk ejection latency was a spurious correlation and secondary to the effect of alcohol on other mediating factors underlying ejection. Cortisol levels were also increased during the test session in which women consumed the alcoholic beverage, a finding that is consistent with research from animal models (33) and some human studies (34). However, such changes in cortisol were not related to changes in oxytocin or prolactin, measures of lactational performance, or mood states. The production, secretion, and ejection of milk are the result of highly synchronized endocrine and neuroendocrine processes, which are governed, in part, by the frequency and intensity of the infants′ sucking. Breast stimulation resulted in transient release of both oxytocin and prolactin to levels previously observed by other researchers (35). Although these two key hormones usually behave in tandem under normal conditions, alcohol consumption resulted in differential and divergent responses. We hypothesize that alcohol acts at the central nervous system level through a general depression or by inhibiting synaptic transmission of afferent impulses to the hypothalamus. Such depression or inhibition would decrease oxytocin levels (36), but, because projections from the hypothalamus exert an inhibitory control of prolactin, prolactin levels would increase (37). Whether the enhanced prolactin response is also due to alcohol′s simulation of extrapituitary tissues such as the mammary glands (38), which are capable of producing prolactin, is not yet known. Animal studies suggest that alcohol, directly or indirectly via estrogens, may elevate prolactin by stimulating activity of lactotropes in the adenohypophysis (38). Recent studies indicate that one fourth of the women surveyed reported that they were encouraged by health professionals to drink once they began lactating (1,39). Advice ranged from the recommendation that drinking alcohol shortly before nursing will facilitate let-down and milk production to the belief that by drinking such milk, the infant will relax, become less "colicky," and obtain warmth. Some health professionals promote moderate drinking (1,39), whereas others caution that extremely high doses (≥1.0 g/kg) inhibit the milk ejection reflex (40). The present findings, which employed more sensitive measures and controls than research conducted in the 1960-1970s (15), revealed that lower doses of alcohol have similar effects on hormonal milieu and lactational performance. Several explanations, not mutually exclusive, may shed light on why the folklore that alcohol consumption enhances lactational performance has persisted for centuries. First, because difficulties with lactational performance are often attributed to stress, alcohol is then prescribed as an aid to lactation because of its anxiolytic and sedative properties. The present study revealed that relatively low BACs produce slight, but significant, alterations in feelings of drunkenness, dysphoria, and sedation. However, paralleling these mood changes are disruptions in the hormonal milieu that may impair lactational performance. Second, the lactating mother does not have an immediate means of assessing milk yield or intake. Although breast-fed infants consumed, on average, 20% less milk after mothers′ consumption of the Mennella et al

Advice given to women in Argentina about breast-feeding and the use of alcohol Consejos dados a las mujeres en Argentina acerca de la lactancia materna y el consumo de alcohol

OBJECTIVE: To explore the types of advice that women in Argentina received from health professionals, family members, and friends about drinking alcoholic beverages and about alcohol usage during pregnancy and lactation. METHODS: In December 2001 and December 2002, structured interviews were conducted with a total of 167 women who were then breast-feeding or who had recently breast-fed their infant. Mothers were asked about the type of advice, if any, that they had received about the use of alcohol from health professionals and from family members and friends. Also included were questions related to the usage of the traditional Argentine beverage "mate" (an infusion widely consumed in South America that is prepared from the leaves of the Ilex paraguayensis plant) and the types of advice the women had received about breast-feeding and neonatal care in general. RESULTS: Of the 167 women studied, 96.4% of them reported that their physician had advised them to breast-feed their infant. In addition, 93.4% of the women said they had treated their infant's umbilical cord stump with alcohol. Fewer than half of the women (46.7%) reported that their physician had advised them about drinking alcoholic beverages during pregnancy, and even fewer (25.7%) received such advice during lactation. Family and friends were about equally likely to give advice about the consumption of alcoholic beverages during pregnancy (42.6%) and during lactation (47.9%). However, the type of advice changed, with the family and friends being significantly more likely to encourage drinking when the women were lactating than when they were pregnant (P < 0.001). Family members and friends also encouraged the drinking of mate to increase milk production. CONCLUSIONS: As in other cultures, in Argentina the belief exists that alcohol enhances lactation. However, the majority of women whom we interviewed had not been counseled by their health professional about the consumption of alcoholic beverages during pregnancy and lactation. There is a need for professional development strategies that will address women's awareness of the risks of alcohol consumption and alcohol usage.<br>OBJETIVO: Explorar el tipo de consejos que los profesionales de la salud, parientes y amigos le dieron a una muestra de mujeres en Argentina acerca del consumo de bebidas alcohólicas y el uso de alcohol durante el embarazo y la lactancia. MÉTODOS: En diciembre de 2001 y diciembre de 2002 se llevaron a cabo entrevistas estructuradas con un total de 167 mujeres que estaban amamantando o que habían amamantado recientemente. A las madres se les preguntó qué tipo de consejos, en caso de haberlos, les dieron los profesionales de la salud y sus parientes y amistades acerca del consumo de alcohol. También se plantearon preguntas sobre la bebida tradicional argentina, el mate -infusión muy popular en América del Sur que se prepara con las hojas de la planta Ilex paraguayensis- y la clase de consejos que recibieron las mujeres acerca de la lactancia materna y los cuidados neonatales en general. RESULTADOS: De las 167 mujeres estudiadas, 96,4% indicaron que el médico les había aconsejado que amamantaran a su hijo. Además, 93,4% afirmaron que habían frotado con alcohol el muñón umbilical del niño. Menos de la mitad de las mujeres (46,7%) indicaron haber recibido del médico asesoramiento acerca del consumo de bebidas alcohólicas durante el embarazo, y un porcentaje aun menor (25,7%) indicó haber recibido este tipo de asesoramiento durante la lactancia. Los parientes y amigos mostraron aproximadamente la misma propensión a aconsejar acerca del consumo de bebidas alcohólicas durante el embarazo (42,6%) y la lactancia (47,9%). No obstante, el tipo de consejo fue distinto en uno y otro caso, en el sentido de que los parientes y amigos mostraron una proclividad mayor (en grado estadísticamente significativo) a alentar a la mujer a consumir bebidas alcohólicas durante la lactancia que durante el embarazo (P < 0,001). Los parientes y amigos también alentaron el consumo de mate para estimular la producción de leche. CONCLUSIONES: Como en otros contextos culturales, en Argentina existe la creencia de que el alcohol mejora la lactancia. Sin embargo, la mayoría de las mujeres entrevistadas no habían recibido asesoramiento profesional acerca del consumo de bebidas alcohólicas durante el embarazo y la lactancia. Se necesitan estrategias profesionales orientadas a lograr que las mujeres cobren mayor conciencia de los riesgos asociados con el consumo y uso del alcohol

Age modifies the genotype-phenotype relationship for the bitter receptor <it>TAS2R38</it>

Abstract Background The purpose of this study was to investigate the effect of TAS2R38 haplotypes and age on human bitter taste perception. Results Children (3 to 10 yrs), adolescents (11 to 19 yrs) and adults (mostly mothers, 20 to 55 yrs (N = 980) were measured for bitter taste thresholds for 6-n-propylthiouracil (PROP) and genotyped for three polymorphisms of the AS2R38 gene (A49P, V262A, I296V). Subjects were grouped by haplotype and age, as well as sex and race/ethnicity, and compared for PROP thresholds. Subjects with the same haplotype were similar in bitter threshold regardless of race/ethnicity (all ages) or sex (children and adolescents; all p-values > 0.05) but age was a modifier of the genotype-phenotype relationship. Specifically, AVI/PAV heterozygous children could perceive a bitter taste at lower PROP concentrations than could heterozygous adults, with the thresholds of heterozygous adolescents being intermediate (p 0.05) perhaps because there is less variation in taste perception among these homozygotes. Conclusions These data imply that the change in PROP bitter sensitivity which occurs over the lifespan (from bitter sensitive to less so) is more common in people with a particular haplotype combination, i.e., AVI/PAV heterozygotes.</p

Variant in a common odorant-binding protein gene is associated with bitter sensitivity in people

Deeper understanding of signaling mechanisms underlying bitterness perception in people is essential for designing novel and effective bitter blockers, which could enhance nutrition and compliance with orally administered bitter-tasting drugs. Here we show that variability in a human odorant-binding protein gene, OBPIIa, associates with individual differences in bitterness perception of fat (oleic acid) and of a prototypical bitter stimulus, 6-n-propylthiouracil (PROP), suggesting a novel olfactory role in the modulation of bitterness sensitivity