Jorge R. Miranda-Massari

Metabolic Correction in the Management of Diabetic Peripheral Neuropathy: Improving Clinical Results Beyond Symptom Control

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

Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

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.

Metabolic Correction As a Proposed Approach for Reduction of Complications and Costs of Diabetes Care in Puerto Rico

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis.

Role of treatment-modifying MTHFR677C>T and 1298A>C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy

Jorge R. Miranda-Massari1 Michael J. González3* Francisco J. Jiménez Ramírez1 Jorge Duconge2 Heriberto Marín4 Myriam Z. Allende-Vigo5 Ricardo Aguirre6 Miguel J. Berdiel7 Iván Paz ND8 Carlos Cidre MD9 1Department of Pharmacy Practice, School of Pharmacy, Medical Sciences Campus, UPR, San Juan, PR 2Department of Basic Science, School of Pharmacy, Medical Sciences Campus, UPR, San Juan, PR 3Department of Human Development, School of Public Health, Medical Sciences Campus, UPR, San Juan, PR 4Department of Administration of Health Services, School of Public Health, Medical Sciences Campus, UPR, San Juan, PR 5Division of Endocrinology, School of Medicine, Medical Sciences Campus, UPR, San Juan, PR 6Department of Business Administration, Sagrado Corazón University, San Juan, PR 7Clínica Berdiel, Ponce, PR 8Clínica Novis, San Juan, PR 9Clínica Dr Cidre, Guaynabo, PR

Inflammatory Sequelae After Chikungunya Virus Infection: Proposed Nutritional Treatment

Abstract Background: The study was conducted to investigate potential association between MTHFR genotypes and diabetic peripheral neuropathy (DPN) in Puerto Ricans with type-2 diabetes mellitus (T2DM) treated with metformin. The prevalence of major MTHFR polymorphisms in this cohort was also ascertained. Methods: DNAs from 89 metformin-treated patients with T2DM and DPN were genotyped using the PCR-based RFLP assay for MTHFR677C>T and 1298A>C polymorphisms. Frequency distributions of these variants in the study cohort were compared to those reported for three reference populations (HapMap project) and controls (400 newborn specimens). Chi-square (or Fischer’s exact) tests and odds ratios (OR) were used to assess association with DPN susceptibility risk (patients vs. controls) and biochemical markers (wild types vs. carriers). Results: Sixty-seven percent (67%) of participants carry at least one of these MTHFR polymorphisms. No deviations from Hardy-Weinberg equilibrium were detected. The genotype and allele frequencies showed statistically significant differences between participants and controls (p<0.0001 and p=0.03, respectively). Results suggest that 1298A>C but not 677C>T is associated with DPN susceptibility in this cohort (p=0.018). Different patterns of allelic dissimilarities are observed when comparing our cohort vs. the three parental ancestries. After sorting individuals by their carrier status, no significant associations were observed between these genetic variants (independently or combined) and any of the biochemical markers (HbA1c, folate, vitamin B12, homocysteine). Conclusions: Prevalence of major MTHFR variants in Puerto Rican patients with T2DM is first time ever reported. The study provides further evidence on the use of this genetic marker as an independent risk factor for DPN.

High dose intravenous vitamin c and metastatic pancreatic cancer: Two cases

Patients infected with chikungunya virus (CHIKV) exhibit specific characteristics, including high fever, rigors, headache, photophobia, petechial rash or maculopapular rash, and incapacitating joint pain. It is thought that the presence of CHIKV immunoglobulin M (IgM) and IgG antibodies play an important role in a new type of rheumatoid arthritis reported in 2009. It has been reported that 97% of patients with CHIKV infection complain of recurrent symptoms for 6 months. Fatigue was considered to be totally disabling in 4.6% of patients and very disabling in 42.8% of patients. Only 10% of patients considered their mood normal, whereas 37.8% felt demoralized and 43.9% considered their mood weakened. This article presents our review of the literature in which we looked for an effective nutritional approach for the treatment of CHIKV infection and its sequelae. It has been reported that the use of omega-3 fatty acids, intravenous vitamin C, bromelain, and curcumin plays an important role in decreasing the inflammatory response during an acute viral illness and other inflammatory processes, such as rheumatoid arthritis. Our general recommendation based on the current evidence, is that the use of omega-3 fatty acids, intravenous vitamin C, bromelain, and curcumin could be an effective treatment option for the inflammatory sequelae of CHIKV infection.

Diet and Stress

Pancreatic cancer is considered an incurable disease. The survival rate of patients in all stages of the disease is poor. Overall, median survival is 3-5 months with a 12month survival rate of 10% and a 5-year survival rate less than 5%. Case report: We report a rare case of a long term survivor (2 years) of metastatic adenocarcinoma of the pancreas controlled with high dose intravenous Vitamin C with an acceptable performance status and quality of life.

A Pilot Clinical Study of Continuous Intravenous Ascorbate in Terminal Cancer Patients

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.