Michael J. Gonzalez
Universidad de Puerto Rico Rio, Public Health, Faculty Member
Research Interests:
Descriptive epidemiologic data suggest a relationship between consumption of high fat diets and breast cancer; although these data can be potentially confounded by other causative exposures. Results of published case-control and cohort... more
Descriptive epidemiologic data suggest a relationship between consumption of high fat diets and breast cancer; although these data can be potentially confounded by other causative exposures. Results of published case-control and cohort studies are inconclusive. Nevertheless, dietary fat significantly affects mammary tumorigenesis in mice and rats in laboratory experiments. We will review current epidemiologic and animal studies, explain the possible mechanisms of how dietary fat may affect breast cancer, and provide preliminary dietary recommendations.
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Diets high in unsaturated fatty acids, especially those containing high levels of linoleic acid, e.g., corn oil, enhance mammary gland tumorigenesis in experimental animals. In contrast, diets high in long-chain polyunsaturated fatty... more
Diets high in unsaturated fatty acids, especially those containing high levels of linoleic acid, e.g., corn oil, enhance mammary gland tumorigenesis in experimental animals. In contrast, diets high in long-chain polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic (DHA), e.g. menhaden oil, appear to have a suppressive effect on this tumorigenic process. Many mechanisms have been proposed to explain the tumor inhibitory action exerted by menhaden oil and other fish oils, e.g., differences in prostaglandin metabolism, energy efficiency, alterations of the immune system, changes in lipid peroxidation, etc. Fundamental to a mechanistic understanding of this phenomenon, however, is an understanding as to whether or not the tumor inhibitory activities of dietary fish oil is mediated via an inhibition of tumor cell proliferation or mediated via an enhancement of tumor cell loss. Whether the amount of dietary fat or the type of fat effects mammary tumorigenic proce...
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Ethical issues pertaining research and counseling in nutritional sciences will be arising in this new century. This issue will be of great importance especially in the area of nutraceutical supplementation and disease (pharmacological... more
Ethical issues pertaining research and counseling in nutritional sciences will be arising in this new century. This issue will be of great importance especially in the area of nutraceutical supplementation and disease (pharmacological nutrition). Steps to insure bioethical correctness are discussed in this paper.
Research Interests:
The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human... more
The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human transmission cycle. It is associated with severe arthritis/arthralgias, myalgias, high fever, headache, and maculopapular rash. Joint ache appears to be symmetrical. The virus has an incubation period of 2 to 7 days, where the high fever is typically presented. It is followed by arthralgias and myalgias, and rashes, which last for 3 to 5 days. However, the arthralgias can persist for months after the infection, which can contribute to severe arthritis. As of now, no vaccine exists for the virus and no official treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol), and non-steroidal anti-inflammatory drugs. This is a case report of a 54-year old Hispanic individual that reported left shoulder pain, left knee pain and fever. The symptoms started on a Saturday in September 2014 in middle of the night. The patient was treated with high doses of intravenous vitamin C over two days. The symptoms resolved after the infusions without any side effects. Based on the positive outcome in this case, we propose that intravenous vitamin C should be studied further as a potential treatment for acute viral infections.
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Frei et... more
Frei et al's 2012 review entitled "Authors' Perspective: What is the Optimum Intake of Vitamin C in Humans" is both flawed and misleading. RCTs are ill suited to determining the RDA, it is debatable that there is sufficient scientific evidence to determine the optimum intake of vitamin C in humans, observations regarding high-doses of ascorbate have been ignored, and there are inaccuracies of fact with respect to the saturation of blood plasma following low dose intake. Until the limitations of current knowledge are recognised it is unwise to set limits on the dose.
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Folate deficiency is one of today's most common vitamin deficiencies in women. Women who consume a low level of folate during pregnancy are at risk for poor pregnancy outcomes including neural tube defects (NTD). However, other... more
Folate deficiency is one of today's most common vitamin deficiencies in women. Women who consume a low level of folate during pregnancy are at risk for poor pregnancy outcomes including neural tube defects (NTD). However, other factors such as heredity, social class, maternal age, birth order, maternal diet, length of time between pregnancies, maternal zinc deficiency, use of anticonvulsant drugs, abnormal homocysteine metabolism and the use of oral contraceptives, have also been implicated as causes of NTD. Animal studies have shown that fetuses are highly dependent on the folate status of the mother. In addition, several retrospective and prospective human studies have provided evidence that folate lowers the incidence of NTD.
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Origin of the Problem Maximum or optimal health requires metabolic harmony. The multiplicity of criti-cal functions of vitamins, minerals and other nutrients at the cellular level, and especially their role as cofactors in enzyme... more
Origin of the Problem Maximum or optimal health requires metabolic harmony. The multiplicity of criti-cal functions of vitamins, minerals and other nutrients at the cellular level, and especially their role as cofactors in enzyme reactions that protect genes from mutations and re-pair gene damage is probably unrecognized or unappreciated by most health profession-als. It can be argued that the true impor-tance of vitamins in human biochemistry is far from fully elucidated, simply due to the high complexity of cellular processes. What is commonly ignored and not fully appreci-ated is the essential role that various min-erals play in human biochemistry. Critical enzymes require such metals as copper, zinc, manganese, selenium, etc. as an integral part of their molecular structure or mechanism of action. Enzymes play a critical role in regulating and orchestrating the rates of the multitude of biochemical reactions that take place in living organisms. Metabolic nutrition is generally r...
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Antioxidants have been associated with cancer prevention. Since this association was established, a plethora of controversies, contradictions and paradoxes have arisen. In this article we will try to provide an in- sight into the... more
Antioxidants have been associated with cancer prevention. Since this association was established, a plethora of controversies, contradictions and paradoxes have arisen. In this article we will try to provide an in- sight into the complexity involved with anti- oxidants, pro-oxidants and cancer in the free radical biology area.
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The use of alternative/complementary medicine has been increasing considerably. Conventional medicine must begin to address issues related to the use, safety, regulation, research and education of alternative/complementary medicine.... more
The use of alternative/complementary medicine has been increasing considerably. Conventional medicine must begin to address issues related to the use, safety, regulation, research and education of alternative/complementary medicine. Integrative medicine combines conventional medicine and alternative complementary practices. Integrative medicine is an innovative approach to medicine and medical education. It involves the understanding of the interaction of the mind, body and spirit and how to interpret this relationship in the dynamics of health and disease. Integrative medicine shifts the orientation of the medical practice from disease based approach to a healing based approach. It does not reject conventional medicine nor uncritically accepts unconventional practices. Integrative medicine is an effective, more fulfilling human approach to medicine based on the benefit of the patient by following good medicine practices in a scientific manner.
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Ethical issues pertaining research and counseling in nutritional sciences will be arising in this new century. This issue will be of great importance especially in the area of nutraceutical supplementation and disease (pharmacological... more
Ethical issues pertaining research and counseling in nutritional sciences will be arising in this new century. This issue will be of great importance especially in the area of nutraceutical supplementation and disease (pharmacological nutrition). Steps to insure bioethical correctness are discussed in this paper.
Research Interests:
Research Interests:
The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human... more
The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human transmission cycle. It is associated with severe arthritis/arthralgias, myalgias, high fever, headache, and maculopapular rash. Joint ache appears to be symmetrical. The virus has an incubation period of 2 to 7 days, where the high fever is typically presented. It is followed by arthralgias and myalgias, and rashes, which last for 3 to 5 days. However, the arthralgias can persist for months after the infection, which can contribute to severe arthritis. As of now, no vaccine exists for the virus and no official treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol), and non-steroidal anti-inflammatory drugs. This is a case report of a 54-year old Hispanic individual that reported left shoulder pain, lef...
Research Interests:
Cell loss is a biological phenomenon that occurs in normal and neoplastic tissue and is an important kinetic factor which contributes to the dynamic state of tumor growth. This relevant phenomenon which was introduced by tumor biologists... more
Cell loss is a biological phenomenon that occurs in normal and neoplastic tissue and is an important kinetic factor which contributes to the dynamic state of tumor growth. This relevant phenomenon which was introduced by tumor biologists in the early 1970s while studying tumor growth kinetics has been largely neglected in cancer therapy, although with adequate research it may hold potential for future strategies in cancer treatment. Cell loss occurs through various mechanisms which include exfoliation, metastasis, differentiation and cell death. Methods used for measuring cell loss will be examined and the importance of cell loss in tumor growth will be discussed.
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Reactive oxygen metabolites can pro- mote carcinogenesis by damaging DNA. vi- tamin C is a redox chemical with antioxi- dant and pro-oxidant properties that may produce radical species depending on the presence of various conditions.... more
Reactive oxygen metabolites can pro- mote carcinogenesis by damaging DNA. vi- tamin C is a redox chemical with antioxi- dant and pro-oxidant properties that may produce radical species depending on the presence of various conditions. Nevertheless, evidence presented herein discourages the consideration of any mutagenic or carcino- genic activity of vitamin C. In contrast, it substantiates a protective and anti
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Stress refers to a reaction given a particular stimulus. Stress is a common problem in most modern societies. Stress creates greater physiologic demands. Unhealthy eating patterns will only result in an increased level of stress, followed... more
Stress refers to a reaction given a particular stimulus. Stress is a common problem in most modern societies. Stress creates greater physiologic demands. Unhealthy eating patterns will only result in an increased level of stress, followed by further health problems if in the future if the issues are not resolved. Prolonged stress increases the metabolic needs of the body and causes many other changes. The increased metabolism can also cause an increase in the use and excretion of many nutrients. Although stress alters nutrient needs, if marginally deficient in a nutrient, stress can make that deficiency even worse.
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Purified corn and fish oil diets with different types and concentrations of antioxidants were evaluated for oxidation products. In addition, a determi nation of different organ and carcass oxidation product levels was performed. Peroxide... more
Purified corn and fish oil diets with different types and concentrations of antioxidants were evaluated for oxidation products. In addition, a determi nation of different organ and carcass oxidation product levels was performed. Peroxide value and thiobarbituric acid assays were performed on the diets immediately after mixing (0 h) and 24, 48 and 72 h after being fed to mice. The AIN-recommended level of antioxidant ad dition (butylated hydroxytoluene, 0.02 g/100 g oil) and even the addition of 100 times this level (2 g/100 g oil), although decreasing the level of oxidation products, failed to totally prevent oxidative deterioration in diets high in fish oil. Furthermore, other antioxidants added in excess to the fish oil diets also failed to completely suppress oxidative deterioration of the diets and, in ad dition, when fed daily to mice for a period of 4 wk, caused an accumulation of lipid peroxidation products in certain organs (e.g., heart, skeletal muscle, mammary glands) and ...
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RESUMEN Este ensayo aborda la posibilidad de que, mediante modificaciones dietarias simples, se puedan disminuir las conductas antisociales, agresivas o violentas. El factor alimentario requiere ser tomado en consideración con el... more
RESUMEN Este ensayo aborda la posibilidad de que, mediante modificaciones dietarias simples, se puedan disminuir las conductas antisociales, agresivas o violentas. El factor alimentario requiere ser tomado en consideración con el propósito de identificar los factores relevantes al cambio conductual. Si bien no se pueden derivar conclusiones definitivas sobre los efectos de dietas o de determinados nutrientes en conductas antisociales o criminales, los estudios revisados proveen suficientes datos como para explorar su ...
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Despite the significant number of in vitro and in vivo studies to assess vitamin C effects on cancer following the application of large doses and its extensive use by alternative medicine practitioners in the USA; the precise schedule for... more
Despite the significant number of in vitro and in vivo studies to assess vitamin C effects on cancer following the application of large doses and its extensive use by alternative medicine practitioners in the USA; the precise schedule for successful cancer therapy is still unknown. Based on interpretation of the available data, we postulate that the relationship between Vitamin C doses and plasma concentration x time, the capability of tissue stores upon distribution, and the saturable mechanism of urinary excretion are all important determinants to understand the physiology of high intravenous vitamin C dose administration and its effect on cancer. Practitioners should pay more attention to the cumulative vitamin C effect instead of the vitamin C concentrations to account for observed discrepancy in antitumor response. We suggest that multiple, intermittent, short-term intravenous infusions of vitamin C over a longer time period will correlate with greater antitumor effects than do single continuous IV doses of the same total exposure. This approach would be expected to minimize saturation of renal reabsorption, providing a continuous “dynamic flow” of vitamin C in the body for optimal systemic exposure and clinical outcomes. This prevents the “systemic saturation” phenomena, which may recycle vitamin C and render it less effective as an anticancer agent. Nonetheless, more pharmacokinetic and pharmacodynamic studies are needed to fully understand this schedule-dependence phenomenon.
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Introducción: la desnutrición es un factor negativo en el manejo del paciente con cáncer. Objetivo: evaluar la influencia del tratamiento oncológico en la evolución del estado nutricional del paciente diagnosticado con cáncer de cabeza y... more
Introducción: la desnutrición es un factor negativo en el manejo del paciente con cáncer. Objetivo: evaluar la influencia del tratamiento oncológico en la evolución del estado nutricional del paciente diagnosticado con cáncer de cabeza y cuello. Métodos: estudio descriptivo, longitudinal, prospectivo y correlacional. Muestra de 36 pacientes, mediante técnica no probabilística a conveniencia. Se utilizó un instrumento con variables demográficas, clínicas, antropométricas, presencia de complicaciones y vía de alimentación; se aplicó estadístico descriptivo con media, desviación estándar, frecuencias y porcentaje. Como estadística inferencial se utilizó la técnica de Fisher, con significancia del valor p < 0,05. Resultados: Se tuvieron 36 pacientes. De los cuales 19(52,7%) fueron del sexo masculino. No hay correlación significativa entre IMC y el tratamiento oncológico, p=0,074; tampoco entre IMC y vía de alimentación, p=0,796. No hay correlación significativa entre la albúmina sérica y las complicaciones durante el tratamiento oncológico, p=0,278; y las complicaciones después del tratamiento oncológico,p=0,877. Discusión: Se obtiene la vía oral como la vía de alimentación predominante, en menor medida la sonda. Existe algún grado de correlación entre la albúmina sérica y la aparición de alguna complicación postoperatoria, estos resultados son en el vólvulo del sigmoide. Conclusiones: No hay una correlación significativa entre IMC y el tratamiento oncológico, tampoco entre el IMC y la vía de alimentación. Entre la albúmina sérica no hay una correlación significativa con las complicaciones durante y después del tratamiento oncológico.
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A healthy physiology depends on a plethora of complex interdependent biochemical reactions. In order for these reactions to occur suitably, the enzymes and cofactors that regulate their flow must be present in the proper balance. The term... more
A healthy physiology depends on a plethora of complex interdependent biochemical reactions. In order for these reactions to occur suitably, the enzymes and cofactors that regulate their flow must be present in the proper balance. The term metabolic correction is used to describe a biochemical–physiological process that improves cellular biochemistry as a means to an individual's achieving metabolic or physiological optimization. Part 2 discusses how metabolic correction, through the increase of cofactors, can supply unmet enzyme needs and compensate for nutritional deficiencies induced by improper nutritional intake or by the increased demand for nutrients caused by genetics, health conditions, medications, or physical or environmental stressors. Nutrient insufficiencies are causing an increase in morbidity and mortality, at great cost to our society. In summary, metabolic correction improves enzymatic function and satisfies the increasing demand for nutrients. Metabolic correction can have a significant impact on the reduction of morbidity and mortality and their financial cost to our society and contribute to improving health and well-being. [P R Health Sci J 2015;34:9-13]
Diabetes is a leading cause of mortality and morbidity worldwide. Diabetes complications produce profound impact on patient's quality of life and represent very significant economic cost to patients, their family, the government and... more
Diabetes is a leading cause of mortality and morbidity worldwide. Diabetes complications produce profound impact on patient's quality of life and represent very significant economic cost to patients, their family, the government and society as a whole. Metabolic correction has been proposed as an efficient method to improve clinical outcomes and reduce costs in diabetes. Metabolic correction is a concept that supports health maintenance and promotes the healing processes by improving the body's biochemical-physiological mechanisms. This is done by helping activate the metabolic enzymes necessary to facilitate key physiological pathways. A group of 50 patients followed a simple metabolic correction strategy based on hydration, diet, and magnesium supplementation during a 6 months period.
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of... more
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effe...
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In most cases, disease results when the individual elects a lifestyle or diet that alters the expression of the genes in such a way that the weakness or uniqueness of inheritance factors result in a phenotype we call disease. That is why... more
In most cases, disease results when the individual elects a lifestyle or diet that alters the expression of the genes in such a way that the weakness or uniqueness of inheritance factors result in a phenotype we call disease. That is why we can consider chronic degenerative diseases as inborn errors of metabolism. Metabolic Correction seems as a very logical approach toward attaining the healthy state.
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Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of... more
Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyl-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metformin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk of developing DPN and how metabolic correction can reduce these risks.
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Essential fatty acids (EFA) have an important role in complex metabolic reactions. The metabolism of essential polyunsaturated fatty acids (PUFA) appears to be one of the critical targets in the complex metabolic stages that lead to, or... more
Essential fatty acids (EFA) have an important role in complex metabolic reactions. The metabolism of essential polyunsaturated fatty acids (PUFA) appears to be one of the critical targets in the complex metabolic stages that lead to, or are associated with cancer. The goal of our research was to analyze the erythrocyte specific types of membrane fatty acid content, level and distribution in cancer patients as compared to non-cancer patients. Changes in fatty acid composition may affect different aspects of cell structure and function, including proliferation. Analyses of RBCs membrane fatty acids were performed for 255 patients with different types of cancer (breast, prostate, liver, pancreas, colon, and lung), 2,800 non-cancer patients and 34 healthy volunteers. Our research study demonstrated a lower level of stearic acid and an increased content of oleic acid in RBC of cancer patients in comparison with control and non-cancer patients. According to the results of this investigati...
Research Interests: Humans, Fatty acids, Female, Male, Membrane Lipids, and 5 moreAged, Middle Aged, Adult, Neoplasms, and Erythrocyte Membrane
Case studies suggest that vitamin C, given intravenously at doses of 10-100 grams/day can improve patient well being and in some cases, reduce tumor size. While ascorbate is generally considered safe, clinical data on high intravenous... more
Case studies suggest that vitamin C, given intravenously at doses of 10-100 grams/day can improve patient well being and in some cases, reduce tumor size. While ascorbate is generally considered safe, clinical data on high intravenous doses is limited. Twenty-four late stage terminal cancer patients were given continuous infusions of 150 to 710 mg/kg/day for up to eight weeks. Blood chemistry and blood count profiles were obtained at roughly one-week intervals while patient health, adverse events and tumor progression were monitored. The majority of patients were vitamin C deficient prior to treatment. Intravenous infusions increased plasma ascorbate concentrations to a mean of 1.1 mM. The most common adverse events reported were nausea, edema, and dry mouth or skin; and these were generally minor. Two Grade 3 adverse events 'possibly related' to the agent were reported: one patient with a history of renal calculi developed a kidney stone after thirteen days of treatment and...
Research Interests: Vitamins, Humans, Female, Male, Ascorbic Acid, and 3 moreNeoplasms, Terminal care, and Pilot Projects
High dose intravenous(i.v.) ascorbic acid (AA) has been used as therapy for infectious disease from bacterial and viral origin and adjuvant therapy for cancer. In this publication we describe a clinical protocol that has been developed... more
High dose intravenous(i.v.) ascorbic acid (AA) has been used as therapy for infectious disease from bacterial and viral origin and adjuvant therapy for cancer. In this publication we describe a clinical protocol that has been developed over the past twenty years utilizing high dose i.v. AA as therapy for cancer. This includes principles of treatment, rationale, baseline workup, infusion protocol, precautions and side effects.
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Ascorbic Acid (AA) has been used in the prevention and treatment of cancer with reported effectiveness. Mitochondria may be one of the principal targets of ascorbate's cellular activity and it may play an important role in the... more
Ascorbic Acid (AA) has been used in the prevention and treatment of cancer with reported effectiveness. Mitochondria may be one of the principal targets of ascorbate's cellular activity and it may play an important role in the development and progression of cancer. Mitochondria, besides generating adenosine triphosphate (ATP), has a role in apoptosis regulation and in the production of regulatory oxidative species that may be relevant in gene expression. At higher concentrations AA may increase ATP production by increasing mitochondrial electron flux, also may induce apoptotic cell death in tumor cell lines, probably via its pro-oxidant action In contrast, at lower concentrations AA displays antioxidant properties that may prevent the activation of oxidant-induced apoptosis. These concentration dependent activities of ascorbate may explain in part the seemingly contradictory results that have been reported previously.
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A series of seven cases are presented in which intravenous vitamin C has been used as antineoplastic agent in the treatment of different types of cancers. The cancers cases reviewed are the following: Renal cell carcinoma (2), Colorectal... more
A series of seven cases are presented in which intravenous vitamin C has been used as antineoplastic agent in the treatment of different types of cancers. The cancers cases reviewed are the following: Renal cell carcinoma (2), Colorectal cancer (1), Pancreatic cancer (1), Non-Hodgkin's lymphoma (2) and breast cancer (1). Toxic reactions were not observed at these high doses of intravenous Vitamin C. All patients were prescreened for Glucose 6--phosphate dehydrogenase deficiency before administering intravenous Vitamin C in order to prevent hemolysis.
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Research Interests:
Many mathematical models have been proposed to study tumor growth parameters in vivo. Nevertheless most of the medical models have given variable results even when experimental conditions are exactly the same. There are multiple factors... more
Many mathematical models have been proposed to study tumor growth parameters in vivo. Nevertheless most of the medical models have given variable results even when experimental conditions are exactly the same. There are multiple factors that are capable of affecting tumor growth that should be taken into account when proposing a mathematical model for tumor growth in vivo. We discuss here own proposed model for tumor growth kinetics utilizing a modified Gompertz function that better responds to the growth characteristic of in "vivo" tumors.
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Reactive oxygen metabolites can pro- mote carcinogenesis by damaging DNA. vi- tamin C is a redox chemical with antioxi- dant and pro-oxidant properties that may produce radical species depending on the presence of various conditions.... more
Reactive oxygen metabolites can pro- mote carcinogenesis by damaging DNA. vi- tamin C is a redox chemical with antioxi- dant and pro-oxidant properties that may produce radical species depending on the presence of various conditions. Nevertheless, evidence presented herein discourages the consideration of any mutagenic or carcino- genic activity of vitamin C. In contrast, it substantiates a protective and anti
Research Interests:
There is a strong advocacy movement for large doses of vitamin C. Some authors argue that the biological half-life for vitamin C at high plasma levels is about 30 minutes, but these reports are the subject of some controversy. NIH... more
There is a strong advocacy movement for large doses of vitamin C. Some authors argue that the biological half-life for vitamin C at high plasma levels is about 30 minutes, but these reports are the subject of some controversy. NIH researchers established the current RDA based upon tests conducted 12 hours (24 half lives) after consumption. The dynamic flow model refutes the current low-dose recommendations for dietary intakes and links Pauling's mega-dose suggestions with other reported effects of massive doses of ascorbate for the treatment of disease. Although, a couple of controlled clinical studies conducted at The Mayo Clinic did not support a significant benefit for terminal cancer patients after 10 grams of once-a-day oral vitamin C, other clinical trials have demonstrated that ascorbate may indeed be effective against tumors when administered intravenously. Recent studies confirmed that plasma vitamin C concentrations vary substantially with the route of administration. ...
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Twenty-eight fatty acids (C8:0 to C24:l n-9) were measured by gas chromatography in four normal cell lines (C3H / 10T1 / 2, CCD-18Co, CCD-25SK and CCD-37Lu) and seven cancer cell lines (C-41, Caov-3, LS-180, PC-3, SK-MEL-28, SK-MES-1 and... more
Twenty-eight fatty acids (C8:0 to C24:l n-9) were measured by gas chromatography in four normal cell lines (C3H / 10T1 / 2, CCD-18Co, CCD-25SK and CCD-37Lu) and seven cancer cell lines (C-41, Caov-3, LS-180, PC-3, SK-MEL-28, SK-MES-1 and U-87 MG). Results show differences in the content and proportions of fatty acids when comparing cancer cell lines with their normal counterparts. Cancer cell lines showed lower C20: 4 n-6, C24:1 n-9, polyunsaturated fatty acids (PUFA's) and ratios of C20:4 n-6 to C20:5 n-3 and C16:0 to C18:1 n-9 and stearic to oleic (SA/OA) than their normal counterparts. All cancer cell lines had SA/OA ratios lower than 7.0 while normal cell lines had ratios greater than 0.7 (p<0.05). In addition, the ratios of total saturated fatty acids (SFA) to PUFA'S and the concentration of C18:1 n-9, C18:2 n-6, C20:5 n-3 were higher in cancer cell lines as compared to normal cell lines. A positive correlation was detected between C16:0 and longer SFA'S (r = +0....
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We report a case of jellyfish envenomation in a 39 year old male. He was stung extensively on both lower limbs by an unidentified jellyfish. This occurred in shallow waters of a beach in the vicinity of Labuan Island, Malaysia. The... more
We report a case of jellyfish envenomation in a 39 year old male. He was stung extensively on both lower limbs by an unidentified jellyfish. This occurred in shallow waters of a beach in the vicinity of Labuan Island, Malaysia. The patient received ambulatory treatment with parenteral and oral ascorbate with remarkable recovery.
Research Interests: Treatment Outcome, Antioxidants, Humans, Animals, Male, and 4 moreAscorbic Acid, Adult, Scyphozoa, and Bites and Stings
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The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human... more
The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human transmission cycle. It is associated with severe arthritis/arthralgias, myalgias, high fever, headache, and maculopapular rash. Joint ache appears to be symmetrical. The virus has an incubation period of 2 to 7 days, where the high fever is typically presented. It is followed by arthralgias and myalgias, and rashes, which last for 3 to 5 days. However, the arthralgias can persist for months after the infection, which can contribute to severe arthritis. As of now, no vaccine exists for the virus and no official treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol), and non-steroidal anti-inflammatory drugs. This is a case report of a 54-year old Hispanic individual that reported left shoulder pain, lef...
Research Interests:
Despite the significant number of in vitro and in vivo studies to assess vitamin C effects on cancer following the application of large doses and its extensive use by alternative medicine practitioners in the USA; the precise schedule for... more
Despite the significant number of in vitro and in vivo studies to assess vitamin C effects on cancer following the application of large doses and its extensive use by alternative medicine practitioners in the USA; the precise schedule for successful cancer therapy is still unknown. Based on interpretation of the available data, we postulate that the relationship between Vitamin C doses and plasma concentration x time, the capability of tissue stores upon distribution, and the saturable mechanism of urinary excretion are all important determinants to understand the physiology of high intravenous vitamin C dose administration and its effect on cancer. Practitioners should pay more attention to the cumulative vitamin C effect instead of the vitamin C concentrations to account for observed discrepancy in antitumor response. We suggest that multiple, intermittent, short-term intravenous infusions of vitamin C over a longer time period will correlate with greater antitumor effects than do...
Research Interests:
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A dietary supplement combination consisting of vitamins, minerals and fibers was studied to determine its safety and efficacy on weight/fat loss, cholesterol and triglycerides in children between ages 7-13. This open label trial measured... more
A dietary supplement combination consisting of vitamins, minerals and fibers was studied to determine its safety and efficacy on weight/fat loss, cholesterol and triglycerides in children between ages 7-13. This open label trial measured total body weight, body fat percentage, waist circumference, total cholesterol, triglycerides before and after 6 weeks of treatment. The study population consisted of 25 mildly to moderate obese, otherwise healthy children of both sexes. After 6 weeks of treatment, the combination supplement had a statistically significant (p < 0.05) weight reducing effect. This weight reduction was associated with a corresponding statistically significant (p < 0.0001l) decrease in body fat percentage. In addition, significant decreases in total cholesterol (p < 0.0001) and triglycerides (p < 0.0001) were obtained, plus reductions in waist measurements. We conclude that the combination supplement studied herein is a safe and effective way to assist child...
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Sodium ascorbate is preferentially toxic to tumor cells at high concentrations. It has not been established, however, whether sufficient intra-tumor ascorbate concentrations are safely achievable in vivo. We administered sodium ascorbate... more
Sodium ascorbate is preferentially toxic to tumor cells at high concentrations. It has not been established, however, whether sufficient intra-tumor ascorbate concentrations are safely achievable in vivo. We administered sodium ascorbate subcutaneously or orally for eighteen days to Sewall-Wright strain-2 guinea pigs bearing intradermal L-10 hepatocarcinoma tumors. Tumor masses and intra-tumor ascorbate concentrations were determined at necropsy. L-10 cells formed tumors that metastasized to the lymph nodes, with tumor burdens reaching nearly 50 grams in untreated animals. Subcutaneous injections of ascorbate (500 mg/kg/day) inhibited tumor growth by as much as sixty-five percent, with oral supplementation reducing it by roughly fifty percent. Tumor growth correlated inversely with intra-tumor ascorbate concentration, the latter exceeding 2 mM in some cases. Ascorbate concentrations sufficient to kill tumor cells can be safely achieved in solid tumors in vivo, suggesting a possible ...
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We tested a dietary supplement formulated with a synergistic combination of vitamins, minerals, herbals in a group of 15 patients with uncontrolled diabetes type II. The supplement was given for 30 days. Fasting blood glucose was measured... more
We tested a dietary supplement formulated with a synergistic combination of vitamins, minerals, herbals in a group of 15 patients with uncontrolled diabetes type II. The supplement was given for 30 days. Fasting blood glucose was measured prior to the supplementation and at the end of the 30 days treatment period. Blood glucose was significantly reduced in all patients with no adverse effects. This orthomolecular correction of faulty glucose metabolism with a combination of nontoxic, safe and fairly inexpensive nutraceuticals needs to be further substantiated. Nervertheless the idea of correcting metabolism with micronutrients is a new concept of genetic nutritioneering that seems appealing and cost effective.
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Plant materials represent promising sources of anti-cancer agents. We developed and tested a novel extract from the ubiquitous plant Convolvulus arvensis. Convolvulus arvensis components were extracted in boiling water, and small... more
Plant materials represent promising sources of anti-cancer agents. We developed and tested a novel extract from the ubiquitous plant Convolvulus arvensis. Convolvulus arvensis components were extracted in boiling water, and small molecules were removed by high-pressure filtration. The extract's biological activity was assessed by measuring its effects on S-180 fibrosarcoma growth in Kun Ming mice and on heparin-induced angiogenesis in chick embryos. We also examined the extract's effects on lymphocytes ex vivo and tumor cell growth in vitro. The extract (primarily proteins and polysaccharides) inhibited tumor growth in a dose-dependent fashion when administered orally. At the highest dose tested, 200 mg/kg/day, tumor growth was inhibited by roughly seventy percent. Subcutaneous or intraperitoneal administration at 50 mg/kg/day also inhibited tumor growth by over seventy percent. The extract's acute LD50 in Kun Ming mice was 500 mg/kg/day when injected, indicating that tu...
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We tested the effect of different concentrations of ascorbic acid (AA), 50, 100, 250 mg/500 mg/dL) with copper sulfate (CS), 10 mg/dL) on human breast carcinoma (MDA-MB231) cell proliferation in vitro. Cell proliferation was measured... more
We tested the effect of different concentrations of ascorbic acid (AA), 50, 100, 250 mg/500 mg/dL) with copper sulfate (CS), 10 mg/dL) on human breast carcinoma (MDA-MB231) cell proliferation in vitro. Cell proliferation was measured using a colori-metric assay (Cell proliferation kit II (XTT), Boehringer, NJ). The results of the mean absorbance of the tissue culture at different AA concentrations and a constant CS concentration were as follow: 0.82 +/- 0.03 (control, mean +/- SE), 0.64 +/- 0.02 (CS above); 0.48 +/- 0.03 (50 mg/dL) AA), 0.21 +/- 0.02 (100 mg/dL), 0.08 +/- 0.01 (250 mg/dL) AA, 0.60 +/- 0.05 (500 mg/dL). These results show that a combination of AA and CS inhibits human breast carcinoma cell proliferation in vitro. This cell proliferation inhibitory effect is directly proportional to the AA concentration with the exception of the 500 mg/dL AA dose. This chemotherapeutic effect was optimally enhanced when AA was added at a concentration of 250 mg/dL. The AA concentratio...
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The use of alternative/complementary medicine has been increasing considerably. Conventional medicine must begin to address issues related to the use, safety, regulation, research and education of alternative/complementary medicine.... more
The use of alternative/complementary medicine has been increasing considerably. Conventional medicine must begin to address issues related to the use, safety, regulation, research and education of alternative/complementary medicine. Integrative medicine combines conventional medicine and alternative complementary practices. Integrative medicine is an innovative approach to medicine and medical education. It involves the understanding of the interaction of the mind, body and spirit and how to interpret this relationship in the dynamics of health and disease. Integrative medicine shifts the orientation of the medical practice from disease based approach to a healing based approach. It does not reject conventional medicine nor uncritically accepts unconventional practices. Integrative medicine is an effective, more fulfilling human approach to medicine based on the benefit of the patient by following good medicine practices in a scientific manner.
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Human physiology depends on countless biochemical reactions, numerous of which are co-dependent and interrelated. The speed and level of completion of reactions usually depend on the availability of precursors and enzymes. The enzymatic... more
Human physiology depends on countless biochemical reactions, numerous of which are co-dependent and interrelated. The speed and level of completion of reactions usually depend on the availability of precursors and enzymes. The enzymatic activity depends on the bioavailability of micronutrient cofactors such as vitamins and minerals. In order to achieve a healthy physiological state, the organism requires that biochemical reactions occur at a controlled rate. To achieve this state it is required that metabolic reactions reach what can be considered an optimal metabolic equilibrium. A combination of genetic makeup, dietary patterns, trauma, disease, toxins, medications, and environmental stressors can elevate the demand for the nutrients needed to reach this optimal metabolic equilibrium. In this, part 1, the general concept of metabolic correction is presented with an elaboration explaining how this concept is increasing in importance as we become aware of the presence of genetic var...
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Despite the significant number of in vitro and in vivo studies to assess vitamin C effects on cancer following the application of large doses and its extensive use by alternative medicine practitioners in the USA; the precise schedule for... more
Despite the significant number of in vitro and in vivo studies to assess vitamin C effects on cancer following the application of large doses and its extensive use by alternative medicine practitioners in the USA; the precise schedule for successful cancer therapy is still unknown. Based on interpretation of the available data, we postulate that the relationship between Vitamin C doses and plasma concentration x time, the capability of tissue stores upon distribution, and the saturable mechanism of urinary excretion are all important determinants to understand the physiology of high intravenous vitamin C dose administration and its effect on cancer. Practitioners should pay more attention to the cumulative vitamin C effect instead of the vitamin C concentrations to account for observed discrepancy in antitumor response. We suggest that multiple, intermittent, short-term intravenous infusions of vitamin C over a longer time period will correlate with greater antitumor effects than do...
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Research Interests: Prostate Cancer, Humans, vitamin C, Male, Shell Half-Life, and 3 moreAged, Ascorbic Acid, and Area Under Curve
Research Interests: Prostate Cancer, Humans, vitamin C, Male, Shell Half-Life, and 3 moreAged, Ascorbic Acid, and Area Under Curve
Research Interests: Skeletal muscle biology, Biology, Transcription Factors, Medicine, Signal Transduction, and 15 moreCell and Molecular Biology, Biological Sciences, Dexamethasone, Cell line, Spinal Muscular Atrophy, Mutation, Mice, Animals, Phosphorylation, Molecular Cell Biology, Transcription Factor, Denervation, Skeletal Muscle, Ubiquitin ligase, and Glucocorticoids
International Journal of Human Nutrition and Functional Medicine: Best of 2014 1) Assessment of the Diagnostic Accuracy of Recently Introduced DNA Stool Screening Test, Gingras, Duncan, Schueller, Schreckenberger 2) Chronic Diseases as... more
International Journal of Human Nutrition and Functional Medicine: Best of 2014
1) Assessment of the Diagnostic Accuracy of Recently Introduced DNA Stool Screening Test, Gingras, Duncan, Schueller, Schreckenberger
2) Chronic Diseases as Inborn Errors of Metabolism: The Metabolic Correction Therapy Approach, Gonzalez, Miranda-Massari, Duconge, Arroyo
3) ISIFMC* Position Paper on the HPS2-THRIVE Study (*International Society of Integrative, Functional and Metabolic Cardiovascular Medicine), Houston, Guarneri, Kahn
4) Unifying Antiviral Strategy, Vasquez
1) Assessment of the Diagnostic Accuracy of Recently Introduced DNA Stool Screening Test, Gingras, Duncan, Schueller, Schreckenberger
2) Chronic Diseases as Inborn Errors of Metabolism: The Metabolic Correction Therapy Approach, Gonzalez, Miranda-Massari, Duconge, Arroyo
3) ISIFMC* Position Paper on the HPS2-THRIVE Study (*International Society of Integrative, Functional and Metabolic Cardiovascular Medicine), Houston, Guarneri, Kahn
4) Unifying Antiviral Strategy, Vasquez
Research Interests: Laboratory Medicine, Cardiovascular disease, Orthomolecular Medicine, Influenza virus, Clinical Laboratory, and 9 moreGut Microbiome, Human Microbiome, Functional Medicine, Ebola, Medical Laboratory Sciences, Immunology of chronic viral infections, Viral Immunology, Viral Infections, and Viral and Bacterial Pathogenesis
1. Bol Asoc Med P R. 1991 Jun;83(6):264-6. Fat and breast cancer: a mini-review of experimental data on rodents. González MJ, Rodríguez JR. Michigan State University, East Lansing 48823. High dietary fat has been consistently ...
Nine young female S 5B/P1 rats, 340 days of age, and 9 old female S 5B/P1 rats, 840 days of age, were evaluated for food intake, body composition, 3 fat depot weights and organ weights. Old and young rats had the same percentage of body... more
Nine young female S 5B/P1 rats, 340 days of age, and 9 old female S 5B/P1 rats, 840 days of age, were evaluated for food intake, body composition, 3 fat depot weights and organ weights. Old and young rats had the same percentage of body fat and protein. Inguinal, ...
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Publikationsansicht. 5386077. Effect of dietary fat on the growth of human breast carcinoma transplanted to the athymic nude mice :--role of lipid peroxidation in this growth process /--by Michael J. Gonzalez. (1993). Gonzalez, Michael J.... more
Publikationsansicht. 5386077. Effect of dietary fat on the growth of human breast carcinoma transplanted to the athymic nude mice :--role of lipid peroxidation in this growth process /--by Michael J. Gonzalez. (1993). Gonzalez, Michael J. Abstract. Thesis (Ph. ...
Go to AGRIS search. Nutrition reports international (Jan 1988). Inhibition of sarcoma tumorigenesis in Balb/C mice by supplemented selenium. ...
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1. PR Health Sci J. 1996 Dec;15(4):309-10. The effect of ascorbic acid on human T cells. González MJ, Nazario CM. Comment on: PR Health Sci J. 1996 Mar;15(1):21-6. PMID: 9097346 [PubMed - indexed for MEDLINE] Publication Types: Comment;... more
1. PR Health Sci J. 1996 Dec;15(4):309-10. The effect of ascorbic acid on human T cells. González MJ, Nazario CM. Comment on: PR Health Sci J. 1996 Mar;15(1):21-6. PMID: 9097346 [PubMed - indexed for MEDLINE] Publication Types: Comment; In Vitro; Letter. MeSH Terms: ...
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The recent publication by the Levine group of the National Institutes of Health (NIH)1 reporting that pharmacologic concentrations of ascorbic acid selec-tively kill cancer cells has received worldwide atten-tion. The reason for this is... more
The recent publication by the Levine group of the National Institutes of Health (NIH)1 reporting that pharmacologic concentrations of ascorbic acid selec-tively kill cancer cells has received worldwide atten-tion. The reason for this is that vitamin C (ascorbic acid, ascorbate) is a ...
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Research Interests: Treatment Outcome, Antioxidants, Humans, Animals, Male, and 4 moreAscorbic Acid, Adult, Scyphozoa, and Bites and Stings
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A pilot case-control study was conducted to examine the possible association between dietary fat intake and the development of postmenopausal breast cancer. Studies regarding the association between dietary fat intake and the development... more
A pilot case-control study was conducted to examine the possible association between dietary fat intake and the development of postmenopausal breast cancer. Studies regarding the association between dietary fat intake and the development of breast cancer among postmenopausal women are lacking in Puerto Rico. Eighteen cases and eighteen controls were interviewed to obtain sociodemographic information, medical history and dietary fat intake. A semiquantitative food frequency questionnaire containing 67 food items was used to collect the dietary information. Unadjusted odds ratios (OR) and their 95% confidence intervals (CI) showed a non-significant positive association for total fat intake and the development of postmenopausal breast cancer (OR = 1.57; 95% CI: 0.42-5.90, p = 0.25). The same non significant positive association was found for saturated fat intake (OR = 1.57; 95% CI: 0.42-5.90, p = 0.25). Polyunsaturated fat (OR = 1.25; 95% CI: 0.34-4.64, p = 0.37) and monounsaturated fat (OR = 1.25; 95% CI: 0.34-4.64, p = 0.37) were also positively associated with postmenopausal breast cancer, although the associations were not statistically significant. These results are consistent with other case-control studies that have shown non-significant positive associations between total fat and the different components of dietary fat and postmenopausal breast cancer.
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1. PR Health Sci J. 1995 Mar;14(1):11-6. Regional differences in fat cell lipolytic mechanisms: a critical review. Petersmark K, Rodríguez JR, Matos MI, González MJ. Michigan State University, Department Food Science and Human Nutrition,... more
1. PR Health Sci J. 1995 Mar;14(1):11-6. Regional differences in fat cell lipolytic mechanisms: a critical review. Petersmark K, Rodríguez JR, Matos MI, González MJ. Michigan State University, Department Food Science and Human Nutrition, East Lansing 48823, USA. ...
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Research Interests: Prostate Cancer, Humans, vitamin C, Male, Shell Half-Life, and 3 moreAged, Ascorbic Acid, and Area Under Curve
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Folate deficiency is one of today&amp;amp;amp;amp;#39;s most common vitamin deficiencies in women. Women who consume a low level of folate during pregnancy are at risk for poor pregnancy outcomes including neural tube defects (NTD).... more
Folate deficiency is one of today&amp;amp;amp;amp;#39;s most common vitamin deficiencies in women. Women who consume a low level of folate during pregnancy are at risk for poor pregnancy outcomes including neural tube defects (NTD). However, other factors such as heredity, social class, maternal age, birth order, maternal diet, length of time between pregnancies, maternal zinc deficiency, use of anticonvulsant drugs, abnormal homocysteine metabolism and the use of oral contraceptives, have also been implicated as causes of NTD. Animal studies have shown that fetuses are highly dependent on the folate status of the mother. In addition, several retrospective and prospective human studies have provided evidence that folate lowers the incidence of NTD.
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Research Interests: Vitamins, Humans, Female, Male, Ascorbic Acid, and 3 moreNeoplasms, Terminal care, and Pilot Projects
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Human breast carcinoma cell lines MCF-7 and MDA-MB231 were transplanted s.c. to female athymic nude mice at 3-4 weeks of age. At 7-10 days after transplantation, the mice were divided into groups and fed for 6-8 weeks one of the following... more
Human breast carcinoma cell lines MCF-7 and MDA-MB231 were transplanted s.c. to female athymic nude mice at 3-4 weeks of age. At 7-10 days after transplantation, the mice were divided into groups and fed for 6-8 weeks one of the following semi-purified diets containing different amounts and types of fat, i.e. 5% corn oil, 20% corn oil, 20% butter, 19% beef tallow/1% corn oil and 19% fish (Menhaden) oil/1% corn oil. In addition experiments, the fish oil diets were supplemented with antioxidants (vitamin E, 8 g or 2000 IU/kg diet plus tertiary butyl hydroquinone, TBHQ, 4 g/kg diet) or ferric citrate (3 g/kg diet). Tumor peroxidation product levels were assessed by measuring 2-thiobarbituric acid reactants (TBA assay). At the termination of the studies (6-8 weeks of diet feeding) mean human breast carcinoma volume (MCF-7 and MDA-MB231) was the largest in mice fed the 20% corn oil diet, intermediate in mice fed the butter or beef tallow diets and the least in mice fed the fish oil diet. The difference in mean tumor volumes among mice fed the 20% corn oil diet and those fed the fish oil diet was significant (P less than 0.01). When comparing low (5% corn oil) and high (20% corn oil) fat diets, numerical increases in human breast carcinoma volume (MCF-7 and MDA-MB231) were consistently observed in the high-fat diet groups but these differences were not always significant. Tumor lipid peroxidation product levels were determined on the MDA-MB231 tumors; tumor lipid peroxidation levels were significantly (P less than 0.01) increased only in mice fed the fish oil diets. Supplementation of the fish oil diets with antioxidants (vitamin E + TBHQ) significantly reduced the level of tumor peroxidation products and significantly increased tumor volume (P less than 0.05). When tumor lipid peroxidation product levels in the fish oil plus antioxidant fed mice were reduced to the level of that observed in the tumors of the corn oil fed mice, no significant differences in tumor volumes were observed in these two groups. In contrast, supplementation of the fish oil diets with ferric citrate, significantly (P less than 0.05) increased tumor lipid peroxidation product levels and decreased tumor volume. Thus, the type of dietary fat can clearly affect the growth of human breast carcinomas (MCF-7 and MDA-MB231) maintained in athymic nude mice.(ABSTRACT TRUNCATED AT 400 WORDS)