SummaryLow-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer. This risk may be overlooked by current regulatory practices and needs to be vigorously investigated.

The effect of ascorbic acid on cancer has been a subject of great controversy. This is a follow-up review of the 1979 article by Cameron, Pauling, and Leibovitz published in Cancer Research. In this updated version, the authors address general aspects of ascorbic acid and cancer that have been presented before, while reviewing, analyzing, and updating new existing literature on the subject. In addition, they present and discuss their own mechanistic hypothesis on the effect of ascorbic acid on the cancer cell. The objective of this review is to provide an updated scientific basis for the use of ascorbic acid, especially intravenously as adjuvant treatment in pharmacological nutritional oncology.

Female athymic nude mice were implanted subcutaneously with human breast carcinoma MDA-MB231. Seven to ten days later, the mice were divided into groups and fed a purified diet containing the following types of fat (% of diet): (i) 20% corn oil (CO); (ii) 15% CO:5% fish (menhaden) oil (FO); (iii) 10% CO:10% FO; (iv) 5% CO:15% FO; (v) 1% CO:19% FO; and (vi) 1% CO:19% FO plus antioxidants (alpha-tocopherol acetate, 2000 IU/kg diet and tertiary butyl-hydroquinone, 2% of total fat). The linoleic acid levels (% of diet) of the groups were 12.0, 9.1, 6.2, 3.3, 0.9 and 0.9%, respectively. After 6-8 wk, the carcinomas were assessed for tumor volume (cm3) and assayed for thiobarbituric acid reactive substances (TBARS). Human breast carcinoma growth was suppressed in mice consuming FO diets without antioxidants as compared to mice fed CO; the greater the amount of dietary FO fed, the greater the carcinoma growth suppression (P < 0.05). The addition of antioxidants to the FO diet significantly (P < 0.05) reversed the FO-induced carcinoma growth suppression. Concentrations of TBARS in the human breast carcinomas were increased in all the FO (without antioxidants) fed mice, compared to mice fed CO; the level of increase in TBARS was directly related to the increase in the level of FO fed (P < 0.05). The addition of antioxidants to the FO diet significantly (P < 0.05) reduced the concentration of TBARS in the breast carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

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, acetyi-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metforrnin, an © 2011 Bentham Science Publishers * Address correspondence to this author at the Room 420, School of Pharmacy Medical Sciences Campus-University of Puerto Rico, PO Box 365067, San Juan, Puerto Rico; Tel: (787) 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.

No abstract

No abstract

Functional defects in growth hormone (GH) secretion and its efficacy as a complementary treatment have been suggested for fibromyalgia. This study investigated the efficacy and safety of low-dose GH as an add-on therapy in patients with both severe FM and low insulin-like growth factor 1 levels. A total of 120 patients were enrolled in a multicenter, placebo-controlled study for 18 months. They were randomly assigned to receive either 0.006 mg/kg/day of GH subcutaneously (group A, n=60) or placebo (group B, n=60) for 6 months (blind phase). The placebo arm was switched to GH treatment from month 6 to month 12 (open phase), and a follow-up period after GH discontinuation was performed until month 18. Standard treatment for fibromyalgia (selective serotonin re-uptake inhibitors, opioids, and amitriptyline) was maintained throughout the study. Number and intensity of tender points, Fibromyalgia Impact Questionnaire (FIQ) with its subscales, and EuroQol 5 dimensions test (EQ5D) with visual analogue scale (VAS) were assessed at different time points. At the end of the study, 53% of group A patients obtained fewer than 11 positive tender points, vs 33% of group B patients (P<.05). 39.1% vs 22.4% reached more than 50% improvement in VAS (P<.05). Group A patients showed significantly improved FIQ scores (P=.01) compared with group B. Although GH discontinuation worsened all scores in both groups during follow-up, impairment in pain perception was less pronounced in the GH-treated group (P=.05). In this largest and longest placebo-controlled trial performed in FM (NCT00933686), addition of GH to the standard treatment is effective in reducing pain, showing sustained action over time.