Gabriela Gutiérrez-Salmeán

Obesity, Metabolic Syndrome, and Dietary Therapeutical Approaches with a Special Focus on Nutraceuticals (Polyphenols): A Mini-Review

More than half of all global deaths in 2010 were related to non-communicable diseases, including obesity, cancers, diabetes, and cardiovascular illnesses. It has been suggested that the alarming increase in the incidence of cardiovascular disease is the epidemiologic result of a nutrition transition characterized by dietary patterns featuring an increase in the intake of total fat, cholesterol, sugars, and other refined carbohydrates, concomitant with low consumption of polyunsaturated fatty acids and fiber. Although traditional dietary approaches have proven successful as part of the treatment for obesity and cardiometabolic derangements within clinical trial scenarios, they lack effectiveness in the long term, mainly due to poor compliance. Research has thus turned its attention to nutraceutics, nutrients that have the ability to modulate physiological and pathophysiological molecular mechanisms, thus resulting in favorable health outcomes. Polyphenols have been considered as among the bioactive molecules as they are thought to yield beneficial effects by exerting antioxidant activity; however, there are other--and even more robust--metabolic pathways through which polyphenols enhance cardiovascular health, such as via promoting vasodilatory, anti-atherogenic, antithrombotic, and anti-inflammatory effects. No standard dose has yet been determined, as the effects greatly vary among polyphenols and food sources; thus, there is an imperative need to generate more evidence in order to support dietary recommendations aimed at the prevention and therapeutics of obesity and its associated cardiometabolic diseases.

Effects of (−)-epicatechin on molecular modulators of skeletal muscle growth and differentiation

Sarcopenia is a notable and debilitating age-associated condition. Flavonoids are known for their healthy effects and limited toxicity. The flavanol (-)-epicatechin (Epi) enhances exercise capacity in mice, and Epi-rich cocoa improves skeletal muscle structure in heart failure patients. (-)-Epicatechin may thus hold promise as treatment for sarcopenia. We examined changes in protein levels of molecular modulators of growth and differentiation in young vs. old, human and mouse skeletal muscle. We report the effects of Epi in mice and the results of an initial proof-of-concept trial in humans, where muscle strength and levels of modulators of muscle growth were measured. In mice, myostatin and senescence-associated β-galactosidase levels increase with aging, while those of follistatin and Myf5 decrease. (-)-Epicatechin decreases myostatin and β-galactosidase and increases levels of markers of muscle growth. In humans, myostatin and β-galactosidase increase with aging while follistatin, MyoD and myogenin decrease. Treatment for 7 days with (-)-epicatechin increases hand grip strength and the ratio of plasma follistatin/myostatin. In conclusion, aging has deleterious effects on modulators of muscle growth/differentiation, and the consumption of modest amounts of the flavanol (-)-epicatechin can partially reverse these changes. This flavanol warrants its comprehensive evaluation for the treatment of sarcopenia.

NUTRITIONAL AND TOXICOLOGICAL ASPECTS OF SPIRULINA (ARTHROSPIRA).

Undernutrition constitutes a public health problem particularly in developing countries. The utilization of algae, particularly Spirulina, as a functional food was suggested decades ago due to the fact that it is not only a protein-dense food source, but because its amino acid profile is considered as of high biologic-value protein content. Spirulina provides essential fats (e.g., gamma-linolenic oleic acids), concomitant to low content nucleic acids. It also has an exceptionally high content of vitamin B12, is a good source of beta-carotene, iron, calcium and phosphorous. Moreover, Spirulina has also proven to have good acceptance as of its organoleptic properties (thus making it a possible prospect for food or a nutrition supplement) and it has not exhibited neither acute nor chronic toxicities, making it safe for human consumption.

Effect of antioxidant supplementation over oxidative stress and quality of life in cervical cancer

BACKGROUND Mexico has a high rate of cervical cancer which represents an important public health issue. The treatment for this disease depends on the extension of the tumor; for the initial stages surgery is recommended, and for locally advanced tumors, a combination of chemotherapy and radiotherapy is used. All this process affects natural antioxidant consumption and Quality of Life (QoL). OBJECTIVE To find out the effect that supplementation with antioxidants (β-carotene, vitamin C y vitamin E) has on oxidative stress, and quality of life in patient diagnosed with cervical cancer during treatments with cisplatin and radiotherapy. MATERIALS AND METHODS We conducted a randomized, blind clinical trial in women with cervical cancer whose antineoplasic treatment was radiotherapy in and radiotherapy with cisplatin. Patients were randomly assigned to receive antioxidant therapy or a placebo. Plasma concentrations of malondialdehyde (MDA), free carbonyls, dityrosines, and carbonyl/protein rate in two different moments, before oncologic therapy, and after finishing oncology treatment, we also evaluated food consumption by using a validated food frequency questionnaire and a QOL questionnaire before treatment and after it was over. The effect of the antioxidant treatment was assessed by the use t-student test for independent and paired samples, as well as frequencies and X² for categorical variables. RESULTS We evaluated 103 patients who were randomly assigned to receive treatment with antioxidants 49 (47.60%) and placebo 54 (52.40%). We did not find statistically significant differences in food or antioxidant consumption according to the food frequency questionnaires. Most of the patients consumed more energy than needed to meet their requirement, but they did not consume enough of most of the antioxidants according to the Recommended Dailiy Allowance (RDA) recommendation. Serum levels of plasma free carbonyls and carbonil/mg of protein ratio were statistically significant (p < 0.009) which shows protein protection regarding oxidative stress in the supplemented group, this information was similar to the one found in the QOL questionnaire, which showed that Global QOL was better in the supplemented group (p < 0.025). Most of the patients had lower α-tocopherol and retinol plasma levels than the recommended values. CONCLUSIONS Antioxidant supplementation showed to be effective in reducing oxidative stress in proteins, but it did not on food ingestion, patients did not meet their antioxidants requirement in their diets, in spite of an excess in energy consumption. Antioxidant plasma levels in most of the patients were lower than normal. QoL score was better in the supplemented group.

Testosterone metabolites mediate its effects on myocardial damage induced by ischemia/reperfusion in male Wistar rats

The role of testosterone in cardiovascular (CV) homeostasis is in controversy, and the exact effects of testosterone on the cardiovascular system remain poorly understood. Testosterone is metabolized by aromatase into 17β-estradiol and by 5α-reductase into dihydrotestosterone (DHT). Thus, identification of these metabolites in the heart may help to explain the controversy regarding the cardiovascular effects of testosterone. We analyzed the expression patterns of these testosterone-metabolizing enzymes and assessed the effect of its enzymatic activity inhibition on ischemia (40 min)/reperfusion (4h, I/R) via the left anterior descendent coronary artery in intact and gonadectomized male rats. Myocardial damage was measured as percentage of infarcted area vs. area at risk. Aromatase and 5α-reductase protein expression was found in the left ventricle of intact and orchidectomized rats. Exogenous testosterone had no effect on I/R induced myocardial damage in intact male rats, meanwhile exogenous testosterone protects against I/R injury in orchidectomized rats. However, enzymatic inhibition of aromatase increased myocardial damage in the presence of testosterone, while enzymatic inhibition of 5α-reductase significantly decreased the level of myocardial damage. Our results also showed that sub-chronic inhibition of 5α-reductase resulted in myocardial protection in both groups. Furthermore, in orchidectomized and intact male rats IV treatment with DHT induces a significant increase in the myocardial damage induced by I/R. Thus, the effect of testosterone on cardiovascular pathophysiology could be related, at least in part to changes in the balance of testosterone 5α-reduction and aromatization.

A randomized, placebo-controlled, double-blind study on the effects of (−)-epicatechin on the triglyceride/HDLc ratio and cardiometabolic profile of subjects with hypertriglyceridemia: Unique in vitro effects

BACKGROUND Cardiometabolic disruptions such as insulin resistance, obesity, high blood pressure, hyperglycemia, and dyslipidemias, are known to increase the risk for cardiovascular and metabolic diseases such as type 2 diabetes mellitus and atherosclerosis. Several screening tools for assessing cardiometabolic risk have been developed including the TG/HDLc ratio, which has been, demonstrated to possess a strong association with insulin resistance and coronary disease. Dietary modifications, together with regular moderate exercise have proven to be effective in attenuating cardiometabolic disruptions. However, they often exhibit poor long-term patient compliance. Nutraceutics, including (-)-epicatechin (EPI), have gained increasing interest as coadjuvant effective and safe therapies that are able to attenuate hypertension, hyperglycemia, hyperinsulinemia, hypertriglyceridemia and hypoalphalipoproteinemia. METHODS The aims of this study were: 1) to compare the in vitro effect of EPI vs. (+)-catechin on fructose induced triglyceride accumulation and mitochondrial function in Hep2 cells in culture, 2) to evaluate the efficacy of EPI treatment in reducing fasting blood triglycerides and improving the TG/HDLc ratio in hypertriglyceridemic patients with a total daily dose of 100mg of EPI. Secondary clinical variables included total cholesterol, LDLc, fructosamine, glucose, insulin, and high sensitivity C-reactive protein blood levels. RESULTS AND CONCLUSION Our results provide preliminary evidence as to favorable effects of EPI on glycemia homeostasis, lipid profile and systemic inflammation such bioactive actions are not class-effects (i.e. limited to their antioxidant potential) but instead, may result from the specific activation of associated downstream signaling pathways since catechin has no effects.

Cardiovascular risk factors in a Mexican middle-class urban population: The Lindavista Study. Baseline data

INTRODUCTION AND OBJECTIVE The aim of this communication is to describe the cardiovascular risk factors affecting a Mexican urban middle-class population. METHODS A convenience sample of 2602 middle class urban subjects composed the cohort of the Lindavista Study, a prospective study aimed to determine if conventional cardiovascular risks factors have the same prognosis impact as in other populations. For the baseline data, several measurements were done: obesity indexes, smoking, blood pressure, fasting serum glucose, total cholesterol, HDL-c, LDL-c and triglycerides. This paper presents the basal values of this population, which represents a sample of the Mexican growing urban middle-class. RESULTS The mean age in the sample was 50 years; 59% were females. Around 50% of the entire group were overweighed, while around 24% were obese. 32% smoked; 32% were hypertensive with a 20% rate of controlled pressure. 6% had diabetes, and 14% had impaired fasting glucose; 66% had total cholesterol ≥ 200 mg/dL; 62% showed HDL-c levels<40 mg/dL; 52% triglycerides>150 mg/dL, and 34% levels of LDL-c ≥ 160 mg/dL. Half of the population studied had the metabolic syndrome. CONCLUSION These data show a population with a high-risk profile, secondary to the agglomeration of several cardiovascular risk factors.

The Protective Effect of Dietary Arthrospira (Spirulina) maxima Against Mutagenicity Induced by Benzo[alpha]pyrene in Mice

Benzo[alpha]pyrene (B[α]P) was used to test the possible antimutagenic effects of Arthrospira (Spirulina) maxima (SP) on male and female mice. SP was orally administered at 0, 200, 400, or 800 mg/kg of body weight to animals of both sexes for 2 weeks before starting the B[α]P (intraperitoneal injection) at 125 mg/kg of body weight for 5 consecutive days. For the male dominant lethal test, each male was caged with two untreated females per week for 3 weeks. For the female dominant lethal test, each female was caged for 1 week with one untreated male. All the females were evaluated 13-15 days after mating for incidence of pregnancy, total corpora lutea, total implants and pre- and postimplant losses. SP protected from B[α]P-induced pre- and postimplant losses in the male dominant lethal test, and from B[α]P-induced postimplantation losses in treated females. Moreover, SP treatment significantly reduced the detrimental effect of B[α]P on the quality of mouse semen. Our results illustrate the protective effects of SP in relation to B[α]P-induced genetic damage to germ cells. We conclude that SP, owing mainly to the presence of phycocyanin, could be of potential clinical interest in cancer treatment or prevention of relapse.

ANTHROPOMETRIC TRAITS, BLOOD PRESSURE, AND DIETARY AND PHYSICAL EXERCISE HABITS IN HEALTH SCIENCES STUDENTS; THE OBESITY OBSERVATORY PROJECT

BACKGROUND Obesity and the metabolic syndrome affect a considerable segment of the population worldwide, including health professionals. In fact, several studies have reported that physicians tend to have more cardiovascular risk factors than their patients. The present cross-sectional study assessed whether the Health Sciences students had a healthier lifestyle, thus could have a more preventive attitude towards chronic diseases than the general population. MATERIALS AND METHODS Students of the medical-biological areas were surveyed by answering a questionnaire about familiar cardiovascular risk factors, personal smoking, alcohol drinking, dietary and exercise habits. Blood pressure was also measured, along with weight, height, and abdominal circumference. RESULTS 23.4% of the participants were overweight and 10% obese. Parental obesity was the most frequent risk factor, followed by social drinking and smoking. We found high consumption of animal derived foods, breakfast- like cereals, pastries, white bread and sweetened beverages; while low intake of fruit and vegetables were reported. More than half the sample reported to practice very little or no exercise at all. DISCUSSION AND CONCLUSIONS We found similar or even higher rates of risk factors than the average population, that may eventually lead to the development of chronic cardiometabolic diseases. Thus we can infer that biomedical education is inefficient in inducing healthy lifestyles among biomedical students, which could have impact in their future practice as they will most probable become obese health-professionals, thus fail to effectively treat their own patients.

Is Local Nitric Oxide Availability Responsible for Myocardial Salvage after Remote Preconditioning

Background: Remote ischemic preconditioning (RIPC) represents an attractive therapy for myocardial protection, particularly when ischemic events can be anticipated. Although several hypothetic mechanisms have been proposed, no definite molecular pathways have been elucidated. Objective: We evaluated the effect of brachial circulation cuff occlusion on myocardial ischemic tolerance, necrosis, and nitric oxide (NO) in patients with ischemic heart disease undergoing elective percutaneous coronary interventions (PCI). Methods: 46 patients were randomly allocated into two groups: control and RIPC before PCI procedures. Electrocardiographic analysis, serum concentrations of troponin I (cTn-I) were measured at baseline and 24 hours after PCI. A blood sample from the atherosclerotic plaque was drawn to determine nitrate and nitrites. Results: RIPC increased the availability of NO in the stented coronary artery. Control patients presented a small but significant increase in cTn-I, whilst it remained unchanged in preconditioned group. The preconditioning maneuver not only preserved but also enhanced the sum of R waves. Conclusions: RIPC induced an intracoronary increase of NO levels associated with a decrease in myocardial damage (measured as no increase in cTn-I) with electrocardiographic increases in the sum of R waves, suggesting an improved myocardium after elective PCI.