Encouraged by the potential health benefits of higher dietary intake of substances with beneficial properties, the use of supplements containing these compounds has increased steadily over recent years. The effects of several of these, many of which are antioxidants, have been supported by data obtained in vitro, in animal models, and often by human studies as well. However, as carefully controlled human supplementation trials have been conducted, questions about the efficacy and safety of these supplements have emerged. In this Educational Paper, three different supplements were selected for consideration of the benefits and risks currently associated with their intake. The selected supplements include β-carotene, selenium, and genistein. The use of each is discussed in the context of preclinical and clinical data that provide evidence for both their use in reducing disease incidence and the possible liabilities that accompany their enhanced consumption. Variables that may influence their impact, such as lifestyle habits, baseline nutritional levels, and genetic makeup are considered and the application of these issues to broader classes of supplements is discussed.
"Genistein (Gen; 5,7,4′-trihydroxyisoflavone), a soybean-derived isoflavone, has been identified as a potential cause for the low incidence of certain types of tumors, such as lung , breast, gastric, colon, and prostate cancers, and HCC [9,15-19]. Gen is also a principal chemopreventive component of soy and exerts a wide array of chemopreventive activities in each stage of multistep carcinogenesis [20,21]. Previous studies [20,22] showed that Gen is a promising agent for inhibiting the metastatic potential of HCC. "
[Show abstract][Hide abstract] ABSTRACT: Genistein (Gen) exhibits anti-mutagenic and anti-metastatic activities in hepatoma cell lines. Gen has suppressive effects on tumor growth and angiogenesis in nude mice. Gen suppresses the enzymatic activity of matrix metalloproteinase (MMP)-9; however, the mechanism underlying its anti-invasive activity on hepatocellular carcinoma (HCC) cells is unclear.
In this study, the possible mechanisms underlying Gen-mediated reduction of 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and inhibition of secreted and cytosolic MMP-9 production in human hepatoma cells (HepG2, Huh-7, and HA22T) and murine embryonic liver cells (BNL CL2) were investigated.
Gen suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and nuclear factor-kappa B (NF-kappaB) activity. Gen suppressed TPA-induced AP-1 activity through inhibitory phosphorylation of extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and TPA-stimulated inhibition of NF-kappaB nuclear translocation through IkappaB inhibitory signaling pathways. Moreover, Gen suppressed TPA-induced activation of ERK/phosphatidylinositol 3-kinase/Akt upstream of NF-kappaB and AP-1.
Gen and its inhibition of multiple signal transduction pathways can control the invasiveness and metastatic potential of HCC.
BMC Complementary and Alternative Medicine 01/2014; 14(1):26. DOI:10.1186/1472-6882-14-26 · 2.02 Impact Factor
"Iron-deficient people typically need to take iron supplements. Yet there are reports that there exists a tendency toward the increased consumption of dietary supplements in developed countries, and this may result in overdoses of certain nutrients, including iron . The taking of dietary supplements is often connected with improper dietary habits, characterized by the high intake of fat, sugar, salt, red meat, and refined grains. "
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the metabolic and physiological changes in rats fed a diet high in fat, fructose, and salt, and with excess iron level. Mineral status was also estimated. Wistar rats were assigned to groups fed either a standard control diet (C) or a diet high in fat, fructose, and salt. The noncontrol diets contained either normal (M) or high level (MFe) of iron. After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized. The kidneys and gonads were collected, and blood samples were taken. Serum levels of insulin, nitric oxide, and iron were measured. The iron, zinc, copper, and calcium concentrations of tissues were determined. It was found that the M diet led to a significant increase in the relative kidney mass of the rats compared with the control group. Among the rats fed the M diet, markedly higher serum level of iron and lower levels of zinc and copper were observed in tissues, while significantly higher calcium levels were found in the gonads. The MFe diet resulted in decreased obesity index, insulin level, and nitric oxide serum concentration in the rats, when compared with both the M and C diets. The high iron level in the modified diet increased the relative mass of the gonads. The excess iron level in the diet disturbed the zinc, copper, and calcium status of tissues. The decrease in insulin and nitric oxide in rats fed the diet high in iron, fat, fructose, and salt was associated with disorders of zinc, copper, and calcium status, as well as with an increase in the relative mass of the gonads.
Biological trace element research 11/2012; 151(2). DOI:10.1007/s12011-012-9548-9 · 1.75 Impact Factor
"Safety is the overarching issue in drug development today, but little was done historically to determine if the antioxidant being tested for an inflammatory-mediated cardiovascular manifestation is safely tolerated at the levels required to provide therapeutic relief [71, 72]. Since the high standards of chemistry, manufacturing, and controls (CMC) required for pharmaceutical drugs are unlikely to be applied to nutraceutical or dietary-supplement-type products, many of the questions regarding safety and efficacy of antioxidants will most likely be answered in the future related to the development of proprietary prodrugs seeking regulatory approval. "
[Show abstract][Hide abstract] ABSTRACT: Inflammation triggered by oxidative stress is the cause of much, perhaps even most, chronic human disease including human aging. The oxidative stress originates mainly in mitochondria from reactive oxygen and reactive nitrogen species (ROS/RNS) and can be identified in most of the key steps in the pathophysiology of atherosclerosis and the consequential clinical manifestations of cardiovascular disease. In addition to the formation of atherosclerosis, it involves lipid metabolism, plaque rupture, thrombosis, myocardial injury, apoptosis, fibrosis and failure. The recognition of the critical importance of oxidative stress has led to the enthusiastic use of antioxidants in the treatment and prevention of heart disease, but the results of prospective, randomized clinical trials have been overall disappointing. Can this contradiction be explained and what are its implications for the discovery/development of future antioxidant therapeutics?
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