Role of Incretins in Muscle Functionality, Metabolism, and Body Composition in Breast Cancer: A Metabolic Approach to Understanding This Pathology.

A poorly studied issue in women with breast cancer is the role of incretins (GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1)) in the quantity and quality of muscle mass in lean and obese individuals. The current report aims to analyze the patterns of association and the role of incretin in muscle functionality and body composition in women with cancer compared with healthy women (mammography BI-RADS I or II) to elucidate whether GIP and GLP-1 can be used to estimate the risk, in conjunction with overweight or obesity, for breast cancer. We designed a case-control study in women with a breast cancer diagnosis confirmed by biopsy in different clinical stages (CS; n = 87) and healthy women with a mastography BI-RADS I or II within the last year (n = 69). The women were grouped according to body mass index (BMI): lean (<25 kg/m2BS), overweight (≥25-<30 kg/m2BS), and obese (≥30 kg/m2BS). We found that GLP-1 and GIP levels over 18 pg/mL were associated with a risk of breast cancer (GIP OR = 36.5 and GLP-1 OR = 4.16, for the entire sample), particularly in obese women (GIP OR = 8.8 and GLP-1 OR = 6.5), and coincidentally with low muscle quality indexes, showed an association between obesity, cancer, incretin defects, and loss of muscle functionality.

Phase Angle in Head and Neck Cancer: A Sex-Differential Analysis from Biological and Clinical Behavior to Health-Related Quality of Life.

Head and neck cancer (H&NC) is a diverse category of tumors related to malignancies in the common aerodigestive pathway, with high metabolic rate, poor nutritional and treatment outcomes, and elevated mortality despite the best standard treatment. Herein, we focus on determining how the phase angle (PA) differs across sex as a predictor of poor prognosis, low quality-of-life (QoL) scores, and mortality in patients with head and neck cancer. This follow-up study presents a sex-differential analysis in a prospective cohort of 139 head and neck cancer patients categorized by sex as male (n = 107) and female (n = 32). Patients were compared in terms of nutritional, biochemical, and quality-of-life indicators between low and normal PA in women (<3.9° (n = 14, 43.75%) and ≥3.9°) and men (<4.5° (n = 62, 57.9%) and ≥4.5°). Our results show that most patients were in locally advanced clinical stages (women: n = 21 (65.7%); men: n = 67 (62.6%)) and that patients with low PA had a lower punctuation in parameters such as handgrip strength, four-meter walking speed, albumin, C-reactive protein (CRP), and CRP/albumin ratio (CAR), as well as the worst QoL scores in functional and symptomatic scales in both the male and female groups. A comparison between sexes revealed significant disparities; malnourishment and tumor cachexia related to an inflammatory state was more evident in the women's group.

Phase Angle and Nutritional Status: The Impact on Survival and Health-Related Quality of Life in Locally Advanced Uterine Cervical Cancer.

The phase angle, an indicator of muscle mass status and membrane cell integrity, has been associated with low survival, poorer clinical outcomes, and worse quality of life among cancer patients, but information on women with uterine cervical cancer (UCCa) is scarce. In this prospective study, we used a bioelectrical impedance analyzer to obtain the PA of 65 women with UCCa. We compared the health-related quality of life and inflammatory and nutritional indicators between low PA and normal PA. The mean age was 52 ± 13. The low PA and normal PA groups differed in terms of the C-reactive protein (15.8 ± 19.6 versus 6.82 ± 5.02, p = 0.022), glucose (125.39 ± 88.19 versus 88.78 ± 23.08, p = 0.021), albumin (3.9 ± 0.39 versus 4.37 ± 0.30, p = 0.000), EORTC QLQ-C30 loss of appetite symptom scale score (33.33 (0.0-100.00) versus 0.0 (0.0-0.0), p = 0.005), and EORTC QLQ-CX24 menopausal symptoms scale score (0.0 (0.0-33.33) versus 0.0 (0.0-100.0), p = 0.03). The main finding of the present study is the interaction between PA and obesity as critical cofactors in the UCCa adeno and adenosquamous histologic variants, to a greater extent than cervical squamous cell carcinoma.

Phase Angle, a Cornerstone of Outcome in Head and Neck Cancer.

In patients with head and neck cancer, malnutrition is common. Most cases are treated by chemo-radiotherapy and surgery, with adverse effects on the aerodigestive area. Clinical and biochemical characteristics, health-related quality of life, survival, and risk of death were studied. The selected subjects were divided into normal- and low-phase-angle (PA) groups and followed up for at least two years. Mean ages were 67.2 and 59.3 years for low and normal PA, respectively. Patients with PA < 4.42° had significant differences in age, anthropometric and biochemical indicators of malnutrition, and inflammatory status compared to patients with PA > 4.42°. Statistical differences were found in the functional and symptom scales, with lower functional scores and higher symptom scores in patients with low PA. Median survival was 19.8 months for those with PA < 4.42° versus 34.4 months for those with PA > 4.42° (p < 0.001).The relative risk of death was related to low PA (2.6; p < 0.001). The percentage of living patients (41.7%) is almost the same as the percentage of deceased subjects (43.1%; p = 0.002), with high death rates in patients with PA < 4.42°. Phase angle was the most crucial predictor of survival and a risk factor for death in the studied cases.

Adipocytokines and Insulin Resistance: Their Role as Benign Breast Disease and Breast Cancer Risk Factors in a High-Prevalence Overweight-Obesity Group of Women over 40 Years Old.

Insulin levels, adipocytokines, and inflammatory mediators trigger benign breast disease (BBD) and breast cancer (BC). The relationship between serum adipocytokines levels, overweight-obesity, metabolic disturbs, and BC is unclear. Methods: To analyze the serum levels of the adipocytokines, insulin, and the HOMA IR in women without breast disease, with BBD or BC, and the role of these as risk factors for benign breast disease or breast cancer. Results: Adipsin values > 0.91 and visfatin levels > 1.18 ng/mL represent a risk factor to develop BBD in NBD lean women (OR = 18; and OR = 12). Data in overweight-obese women groups confirm the observation due to insulin levels > 2.6 mU/mL and HOMA IR > 0.78, with OR = 60.2 and 18, respectively; adipsin OR = 26.4, visfatin OR = 12. Breast cancer risk showed a similar behavior: Adipsin risk, adjusted by insulin and visfatin OR = 56 or HOMA IR and visfatin OR = 22.7. Conclusion: Adipose tissue is crucial for premalignant and malignant tissue transformation in women with overweight-obesity. The adipocyte−breast epithelium interaction could trigger a malignant transformation in a continuum, starting with BBD as premalignant disease, especially in overweight-obese women.

Quality of Life and Functionality of Head and Neck Cancer Patients Are Diminished As a Function of Sarcopenia and Obesity.

BACKGROUND: Health-related quality of life (QoL) is a measure that allows us to know the patient's perception of well-being and how it is affected by their disease and treatments. In cancer patients, sarcopenia has been associated with low scores on various instruments used to assess the QoL; however, little information is available on the effects of sarcopenia and sarcopenic obesity on the QoL of patients with head and neck cancer (H&NC). METHODS: In this cross-sectional study with 71 H&NC patients aged between 40 and 80 years, we describe the scores on the instruments EORTC QLQ C-30 and EORTC QLQ-H&N35 according to the sarcopenia phenotype (NSG, nonsarcopenic group; SG, sarcopenic group; and SOG, sarcopenic obesity group), hand-grip strength, gait speed, total lymphocyte count, albumin, cholesterol and C-reactive protein, and the relationships between these variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 48% and 28%, respectively. The QoL analysis showed that NSG had higher scores on the physical functioning scale [NSG 93 (83-100); SG 73 (52-88); SOG 83 (53-93), P = .009] and lower scores on the fatigue scale [NSG 11 (0-22); S 39 (30-67); SOG 44 (14-56); P = .004]. The NSG had a higher hand-grip strength (31.1 kg) than SG (24.1 kg, P = .007) and SOG (26.3 kg, P = .001), and a lower C-reactive protein. The SG and SOG showed no differences between them. CONCLUSIONS: Patients with sarcopenia or sarcopenic obesity have lower physical performance and a higher level of fatigue than nonsarcopenic patients. This loss of function can maintain or worsen sarcopenia due to the patient's self-restraint in physical exertion that encourages an increase in muscle tissue.

Body Composition and Biochemical Parameters of Nutritional Status: Correlation with Health-Related Quality of Life in Patients with Colorectal Cancer.

Up to 60% of colorectal cancer (CRC) patients develop malnutrition, affecting treatment effectiveness, increasing toxicity, postoperative complications, hospital stay, and worsening health-related quality of life (HRQOL). This cross-sectional study analyzed data from 48 women and 65 men with CRC. We correlated scores of the scales from the questionnaires EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Core 30 (QLQ)-C30 and Colorectal Cancer module Colorectal 29 (QLQ-CR29) with patients' body composition and clinical and biochemical indicators of nutritional status. Results: Scores on quality of life were negatively associated with the lymphocyte count (rP = -0.386) and the fat trunk percentage (rP = -0.349) in the women's group. Scores on the physical and role functioning were inversely associated with the adiposity percentage (rP = -0.486 and rP = -0.411, respectively). In men, total skeletal muscle mass (SMM) was positively associated with emotional functioning (rP = 0.450); the trunk SMM was negatively related to fatigue (rP = -0.586), nausea and vomiting (rP = -0.469), pain (rP = -0.506), and financial difficulties (rP = -0.475); additionally, serum albumin was positively related to physical, emotional, and social functioning scales (rPs = 0.395, 0.453, and 0.363, respectively) and negatively to fatigue (rP = -0.362), nausea and vomiting (rP = -0.387), and appetite loss (rP = -0.347). Among the men, the reduced SMM and biochemical, nutritional parameters were related to low scores on the EORTC QLQ-C30 and QLQ-CR29 functioning scales. In conclusion, in patients with CRC, malnourishment could have a profound effect on the patients' functionality and QoL (quality of life).

Impact of age, sex, and global function on normal aortic hemodynamics.

PURPOSE: To examine the effects of age, sex, and left ventricular global function on velocity, helicity, and 3D wall shear stress (3D-WSS) in the aorta of N = 100 healthy controls. METHODS: Fifty female and 50 male volunteers with no history of cardiovascular disease, with 10 volunteers per age group (18-30, 31-40, 41-50, 51-60, and 61-80 years) underwent aortic 4D-flow MRI. Quantification of systolic aortic peak velocity, helicity, and 3D-WSS distribution and the calculation of age group-averaged peak systolic velocity and 3D-WSS maps ("atlases") were computed. Age-related and sex-related changes in peak velocity, helicity, and 3D-WSS were computed and correlated with standard metrics of left ventricular function derived from short-axis cine MRI. RESULTS: No significant differences were found in peak systolic velocity or 3D-WSS based on sex except for the 18- to 30-year-old group (males 8% higher velocity volume and 3D-WSS surface area). Between successively older groups, systolic velocity decreased (13%, <1%, 7%, and 55% of the aorta volume) and 3D-WSS decreased (21%, 2%, 30%, and 62% of the aorta surface area). Mean velocity, mean 3D-3D-WSS, and median helicity increased with cardiac output (r = 0.27-0.43, all P < .01), and mean velocity and 3D-WSS decreased with increasing diameter (r > 0.35, P < .001). Arch and descending aorta systolic mean velocity, mean 3D-WSS, and median helicity increased with normalized left ventricular volumes: end diastolic volume (r = 0.31-0.37, P < .01), end systolic volume (r = 0.27-0.35, P < .01), and stroke volume (r = 0.28-0.35, P < .01). CONCLUSION: Healthy aortic hemodynamics are dependent on subject age, and correlate with vessel diameter and cardiac function.

Breast benign disease and breast cancer risk. Overweight-obesity, biochemical, anthropometry. / Enfermedad mamaria benigna y riesgo de cáncer de mama: sobrepeso-obesidad, bioquímica, antropometría.

BACKGROUND: The immunologic, metabolic and anthropometric disturbances of overweight-obesity phenomena are risk factors to breast cancer (BC), particularly in proliferative benign breast disease women (PBBD). OBJECTIVE: To describe the adipocytokine levels, metabolic alteration and anthropometric characteristics in PBBD and its role as risk estimator to BC in a population with high overweight-obesity prevalence. MATERIAL AND METHODS: A cross-sectional study. We realized nutritional diagnosis, anthropometry, and we calculated the waist-height rate (WHR); serum measurement of adipocytokines, insulin and glucose and, HOMA IR determination in 27 PBBD and 27 BC women. We calculated mean, standard deviation, Pearson and Spearman correlation coefficients, Odds Ratio (OR) and confidence intervals through logistic regression as risk estimators of BC; p < 0.05 values were considered significant. RESULTS: Mean age in the PBBD group was minor than BC group, the humeral diameter was greater in BC group women. We did not find differences in anthropometry or adipocytokine levels; in both groups, the predominant somatotype was the endo-mesomorphic. We found higher insulin levels in BC group and a higher percentage of women with WHR > 0.5 too. The WHR > 0.5 + age over 50 were considered risk estimators to develop breast cancer in PBBD women group. CONCLUSION: The WHR >0.5 in women with PBBD over 50 years old could be considered an anthropometric risk estimator to develop BC.

INTRODUCCIÓN: La inflamación, las alteraciones metabólicas y antropométricas del fenómeno sobrepeso-obesidad son factores de riesgo para cáncer de mama (CaM) particularmente en mujeres con enfermedad mamaria benigna proliferativa (EMBP). OBJETIVO: Describir los niveles de adipocitocinas, alteraciones metabólicas y antropométricas en la EMBP y su papel como estimadores de riesgo para CaM en una población con prevalencia de sobrepeso-obesidad de más del 70%. MATERIAL Y MÉTODOS: Estudio transversal analítico en 27 mujeres con CaM y 27 con EMBP. Se realizó diagnóstico nutricional, antropometría y cálculo del índice cintura-talla (ICT); determinación sérica de adipocitocinas, insulina, glucosa y estimación de HOMA IR. Se calcularon promedio y desviaciones estándar, correlaciones de Pearson y Spearman; Odds Ratio (OR) e intervalos de confianza mediante regresión logística como estimadores de riesgo de CaM. Se consideró significativo un valor de p < 0.05. RESULTADOS: La edad del grupo EMBP fue menor. No se observaron diferencias en adipocitocinas ni antropometría (excepto el diámetro humeral fue mayor en CaM). Se observaron mayores niveles de insulina en CaM, y mayor porcentaje de mujeres con ICT > 0.5. El ICT > 0.5 + edad > 50 fueron estimadores de riesgo para CaM. CONCLUSIÓN: Un ICT > 0.5 en mujeres mayores de 50 años podría ser un estimador antropométrico de riesgo de CaM en mujeres con EMBP.

Comparación de las anastomosis intestinales realizadas en emergencia con engrapadora versus manuales en el Hospital Nacional Rosales en el periodo del 1 de Enero de 2017 al 31 de Diciembre de 2018 / Comparison of intestinal anastomoses performed in emergency with stapler versus manual at Hospital Nacional Rosales in the period from January 1, 2017 to December 31, 2018

Al extirpar un segmento intestinal, la confección de la continuidad se denomina anastomosis. Esta puede realizarse de forma manual o sutura o con engrapadora. Estudios que comparan ambas técnicas en cirugía electiva reportan un aumento en el riesgo absoluto de estenosis con engrapadora en esófago y colorecto y de mortalidad, pero menos fugas (OR 0,28, p = 0,01). En estudios en trauma los resultados son controversiales. El Objetivo del estudio fue Comparar las complicaciones y los beneficios del uso de engrapadoras versus el uso de sutura manual en la realización de anastomosis intestinales en cirugía de emergencia. Materiales y métodos. Se utilizó un diseño de cohortes retrospectivo con fuentes documentales en pacientes sometidos a cirugía de emergencia en el Hospital Nacional Rosales que necesitaron anastomosis intestinal en el periodo del 1ero de enero 2017 al 31 de agosto 2018. Resultados. Se incluyeron 28 pacientes en el periodo de estudio: 23 con sutura manual y 5 con mecánica. Hubo diferencias entre grupos por ASA y presión arterial media (PAM). No se encontró ninguna diferencia de beneficio o riesgo entre los métodos de anastomosis. Mortalidad del 17.85% (5 sujetos) de los cuales 3 fueron por causas de complicaciones de la anastomosis y 2 sistémicas. Se encontró como factores de riesgo de muerte la edad del paciente, el ASA y la Presión Arterial Media. Conclusión. Con la muestra incluida en el estudio no encontramos ninguna diferencia de beneficio o complicaciones de ninguna de las dos técnicas sobre la otra.

Obesity and adipocytokines in breast cancer and benign breast disease / Obesidad y adipocitocinas en cáncer de mama y enfermedad mamaria benigna

Background: There is a relationship between obesity and the development of breast cancer; adipocytokines are among the mechanisms related. Objective: To describe the impact of obesity in leptin, adiponectin, resistin and tumor necrosis factor-alpha (TNF-alpha) serum levels in women with breast cancer (BC) and benign breast disease (BBD). Methods: A cross-sectional study was carried out with a sample of 54 individuals divided into two groups: BC (n = 27) and BBD (n = 27). Serum levels of leptin, adiponectin, resistin and TNF-alpha were determined. Body mass index (BMI) was calculated. Statistical analysis included mean, standard deviation, median and interquartile range; the differences between groups were determined by Student´s t test, Mann-Whitney U and Kruskall Wallis test to identify differences between the groups. Results: We didn't find any significant differences related to anthropometric characteristics between BC and BBD groups, or to leptin, adiponectin, resistin and TNF-alpha serum levels (p = NS). We found higher leptin serum levels in obese women with BBD compared with non-obese women with BC (med 22.26 versus 4.34 ng/mL; p = 0.028). Adiponectin serum levels in non-obese women from the BC group were higher than serum levels found in non-obese women with BBD (med 7.10 versus 2.22 ng/mL; p = 0.038) Conclusion: We found higher leptin serum levels and lower adiponectin serum levels in BBD women than BC women in this population with high frequency of obesity.

Introducción: existe relación entre la obesidad y el desarrollo de cáncer de mama (CaM); entre los mecanismos implicados están las adipocitocinas. Objetivo: establecer el efecto de la obesidad sobre los valores séricos de leptina, adiponectina, resistina y el factor de necrosis tumoral-alfa (TNF-alfa) en mujeres con CaM y enfermedad mamaria benigna (EMB). Métodos: estudio transversal analítico. Se determinaron los niveles séricos de leptina, adiponectina, resistina y TNF-alfa, así como el índice de masa corporal (IMC) de 27 mujeres con CaM incidente y 27 con EMB. Se utilizaron promedios, desviaciones estándar, medianas (Me) y rangos intercuartílicos, así como las pruebas t de Student, U de Mann-Whitney y Kruskall-Wallis para identificar diferencias entre los grupos. Resultados: no se encontraron diferencias antropométricas, ni en niveles séricos de TNF-alfa, leptina y resistina entre los grupos (p = NS). Los niveles de leptina de las mujeres con EMB y obesidad fueron significativamente superiores que en las mujeres con CaM no obesas (Me 22.26 frente a 4.34 ng/mL; p = 0.028). Los niveles de adiponectina en mujeres con CaM con IMC sin obesidad fueron mayores que los encontrados en pacientes con EMB con IMC y sin obesidad (Me 7.10 frente a 2.22 ng/mL; p = 0.038). Conclusión: en esta población con elevada frecuencia de obesidad, se encontraron niveles mayores de leptina en mujeres con EMB con respecto a las mujeres con CaM; asimismo, se encontró un patrón inverso en adiponectina.

[Maternal metabolic diseases related to pre-pregnancy overweight and obesity in mexican women with high risk pregnancy]. / Enfermedades metabólicas maternas asociadas a sobrepeso y obesidad pregestacional en mujeres mexicanas que cursan con embarazo de alto riesgo.

INTRODUCTION: Pre-pregnancy obesity has been proposed as a risk factor related to gestational diabetes and hypertensive disorders during pregnancy. OBJECTIVES: Identify pregnancy related diseases associated with pre-pregnancy obesity as a risk factor ina high risk preganancy patient population. METHODS: 600 patients whose pre-pregnancy obesity had been assessed as a high risk factor were included in the study. The means, standard deviation, median, interquartile intervals, Pearson and Spearman correlation and logistic regression to estimate risk with the odds ratio and 95% confidence intervals were calculated. RESULTS: The mean pre-pregnancy body mass index was 29.59 ± 6.42 kg/m2. The mean for recommended pregnancy weight gain was 2.31 ± 1.03 kg, but the mean of real weight gain was 8.91 ± 6.84 kg. A significant correlation between pre-pregnancy obesity and family history of diabetes mellitus (p=0.000), systemic hypertension (p=0.003), cardiac diseases (p=0.000), dyslipidemia (p=0.000) and obesity (p=0.000) was identified. Pre-pregnancy obesity was identified as a risk factor for the development of gestational diabetes (OR: 1.95; IC95%: 1.39 to 2.76; p=0.000) in this kind of patient. DISCUSSION AND CONCLUSION: 75% of high risk pregnancy women in a high specialty hospital in West Mexico are overweight or obese when they become pregnant. These are risk factors in the development of gestational diabetes.

Simultaneous spontaneous coronary and vertebral artery dissection in a postpartum woman.

Spontaneous coronary and vertebral artery dissection are rare but life-threatening conditions. They are more prevalent in pregnant and postpartum women with few atherosclerotic risk factors than in the general population. The pathophysiology of spontaneous arterial dissections remains ambiguous and the management may be challenging. We present a case of simultaneous spontaneous coronary and vertebral artery dissection in a postpartum woman. We review the presentation, diagnosis, clinical course and management and place this in context with the existing literature.

Urine nicotine metabolite concentrations in relation to plasma cotinine during low-level nicotine exposure.

INTRODUCTION: Plasma or saliva cotinine concentrations are used widely as biomarkers of secondhand smoke (SHS) exposure and have been associated with the risk of SHS-related disease. Concentrations of cotinine and other nicotine metabolites are considerably higher in urine than in plasma or saliva, making chemical analysis easier. In addition, urine is often more convenient to collect in some SHS exposure studies. The optimal use of nicotine metabolites in urine, singly or in combination, with or without correction for urine creatinine concentration, to estimate plasma cotinine concentration with low-level nicotine exposure has not been determined. METHODS: We dosed 36 nonsmokers with 100, 200, or 400 microg deuterium-labeled nicotine (simulating exposure to SHS) by mouth daily for 5 days and then measured plasma and urine cotinine and metabolites at various intervals over 24 hr. RESULTS: A plasma cotinine concentration of 1 ng/ml corresponds on average to a daily intake of 100 microg nicotine. Cotinine concentrations in urine averaged four to five times those in plasma. Correction of urine cotinine for creatinine concentration improved the correlation between urine and plasma cotinine. Measuring multiple cotinine metabolites in urine did not improve the correlation with plasma cotinine, compared with the use of urine cotinine alone. DISCUSSION: Measurement of urine cotinine corrected for creatinine concentration appears to be the best predictor of plasma cotinine.

Nicotine intake and dose response when smoking reduced-nicotine content cigarettes.

OBJECTIVES: The progressive reduction of the nicotine content of cigarettes has been suggested as a way to wean smokers from nicotine and tobacco. As a first step in evaluating this strategy, we studied smokers smoking cigarettes containing tobacco with differing nicotine content. METHODS: Twelve healthy smokers participated in a semiblinded, within-subject, crossover study. Subjects were asked to smoke 1 of their usual brand of cigarette and then on 5 subsequent occasions to smoke a research cigarette, each with differing nicotine content. The research cigarettes contained 0.6 to 10.1 mg nicotine per cigarette. Plasma nicotine and blood carboxyhemoglobin levels, as well as subjective and cardiovascular responses, were measured after smoking. Systemic nicotine intake per cigarette was estimated by use of plasma nicotine concentrations over time and clearance data from the general population. RESULTS: Systemic nicotine intake (0.26-1.47 mg per cigarette) varied with nicotine content of the cigarette (r = 0.82, P < .001). Compensation when smoking single low-nicotine content cigarettes ranged from -1% (95% confidence interval, -23% to 21%) to 34% (95% confidence interval, -39% to 107%) for 1-mg to 8-mg research cigarettes. Carbon monoxide intake and estimated tar exposure were similar across cigarettes. Low-nicotine content cigarettes were rated as being of lower quality and less satisfying than the 12-mg research cigarette or the usual brand (P < .05 for both comparisons). Cigarette smoking increased heart rate and decreased skin temperature, but the nicotine dose-response curve flattened at higher doses, with a maximal response being observed in cigarettes at a nicotine content level of about 8 mg. CONCLUSIONS: Our study suggests that reduced-nicotine content cigarettes are reasonable candidates for trying to reduce the level of nicotine addiction in smokers. The flat nicotine dose-cardiovascular response curve is consistent with other studies demonstrating tolerance to the cardiovascular effects of nicotine.

Mentholated cigarette smoking inhibits nicotine metabolism.

Smoking mentholated cigarettes has been suggested to convey a greater cancer risk compared with smoking nonmentholated cigarettes. Two of the possible mechanisms by which mentholated cigarette smoking could increase risk are by increasing systemic exposure to tobacco smoke toxins and by affecting the metabolism of nicotine or tobacco smoke carcinogens. To examine these possibilities, we performed a crossover study in 14 healthy smokers, one-half of whom were African-Americans and one-half whites. Subjects were randomly assigned to smoke mentholated or nonmentholated cigarettes for 1 week, then to cross over to the other type of cigarettes for another week. Subjects were confined to a Clinical Research Center for 3 days of each week, during which time blood levels of nicotine and carbon monoxide were measured throughout the day and an intravenous infusion of deuterium-labeled nicotine and cotinine was administered to determine the rate and pathways of nicotine metabolism. The systemic intake of nicotine and carbon monoxide was, on average, not affected by mentholation of cigarettes. Mentholated cigarette smoking did significantly inhibit the metabolism of nicotine (clearance: 1289 versus 1431 ml/min, two sided, p = 0.02). Inhibition of nicotine metabolism occurred both by slower oxidative metabolism to cotinine and by slower glucuronide conjugation. Our data do not support the hypothesis that mentholated cigarette smoking results in a greater absorption of tobacco smoke toxins. Our finding of impaired metabolism of nicotine while mentholated cigarette smoking suggests that mentholated cigarette smoking enhances systemic nicotine exposure.