Effects of Chitin-Glucan on Oxidized Low-Density Lipoprotein (LDL)

Cardiovascular diseases (CVDs), especially atherosclerotic coronary heart disease and stroke, are the leading causes of death globally. Important risk factors for CVDs include elevated serum levels of total cholesterol, low-density lipoprotein(LDL)-cholesterol, triglycerides, and low high-density lipoprotein (HDL)-cholesterol. Elevated "oxidized" LDL, a pro-inflammatory villain, has also emerged as an important risk factor for the development of CVDs. There is a growing need to identify safe and effective nutritional interventions that offer a clinical benefit aimed at reducing one more of the risk factors for CVDs. Data from many studies in humans have shown various health benefits provided by dietary fiber intake, including an inverse association with the risk of developing cardiovascular disease. The primary purpose of this study is to determine whether daily consumption for 6 weeks of chitin-glucan, a fiber purified from a microorganism, is effective at reducing the amount of oxidized LDL in humans with borderline-to-high LDL-cholesterol. The effects of chitin-glucan on other cardiovascular risk factors will also be evaluated.

Cardiovascular diseases (CVDs), especially atherosclerotic coronary heart disease and stroke, are the leading causes of death globally. Important risk factors for CVDs include elevated serum levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and low high-density lipoprotein (HDL)-cholesterol levels. Oxidized LDL has also been identified as a risk factor for CVDs. There is a growing need to identify safe and effective interventions that offer a clinical benefit aimed at reducing one more of the risk factors for CVDs. Oxidized LDL is a unique plaque-specific protein produced in the arterial wall by the oxidative modification of the apoB-100 moiety of native LDL mediated by reactive oxygen species. Oxidized LDL is a powerful atherogenic protein, which is directly involved in the initiation and progression of atherosclerosis, the main cause of coronary artery disease (CAD). It is now widely believed that for native LDL to be atherogenic, it must be converted to oxidized LDL. Oxidized LDL is found in atherosclerotic lesions and in the circulation, but not in normal arteries. Oxidized LDL is both a biomarker of accelerated atherosclerosis and a mediator of the atherosclerotic disease process. In 1998, Holvoet et al demonstrated for the first time that elevated circulating levels of oxidized LDL were found in most untreated patients with both stable CAD and acute coronary syndromes (unstable angina; acute myocardial infarction). In this landmark study, oxidized LDL levels were measured in plasma with an ELISA procedure using the oxidized LDL-specific, murine monoclonal antibody, 4E6. Mercodia's commercially available oxidized LDL ELISA kits use Holvoet's monoclonal antibody, 4E6, which is specific for oxidatively modified LDL. The 4E6 antibody is directed against a conformational epitope in the apoprotein(apo)B-100 moiety of LDL that is generated as a consequence of aldehyde substitution of the lysine residues of apoB-100. Data from epidemiological studies have shown various health benefits provided by dietary fiber intake, including an inverse association with the risk of CVDs. As shown in several well-controlled clinical trials, various water-soluble dietary fibers reduced total cholesterol and LDL-cholesterol while HDL-cholesterol and triglycerides were not significantly influenced. Recently, the European Food Safety Authority (EFSA) authorized a health claim related to the maintenance of normal blood cholesterol concentrations for soluble cereal fibres, particularly beta-glucans from oat and barley. The beta-glucans in these cereals are non-starch polysaccharides consisting of (1→3,1→4)-beta-D-linked glucose units. Few studies have addressed potential favorable effects of beta-glucans from micro-organisms on CVD risk factors. One clinical study examined the effects of yeast-derived beta-glucan, a glucose polymer with beta-(1→3,1→6) linkages, on serum lipids in 15 hypercholesterolemic obese men. At the end of the 8-week treatment period (15 g fiber/day in addition to the normal diet), total cholesterol levels were decreased whereas HDL-cholesterol, LDL-cholesterol and triglycerides did not differ significantly from the baseline values. A number of animal studies showed that consumption of fungi or fungal extract can lower blood cholesterol or reduce aortic atherosclerotic lesions in rabbits fed a high-cholesterol diet or in atherosclerosis-susceptible apolipoprotein E-deficient mice fed a normal. It should be noted that the fungal component(s) causing these effects have not been identified or characterized (whole mushrooms or an impure extract were tested). Chitin-glucan is a natural component of the cell wall of microscopic fungi. Chitin-glucan can be regarded as an insoluble dietary fiber. In hamsters fed an atherogenic diet, chitin-glucan mixed with food lowered plasma triglycerides and markedly reduced the diet-induced formation of aortic fatty streak lesions. It also reduced aortic cholesterol, cardiac superoxide anion production and hepatic malondialdehyde, and increased hepatic antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase). Although oxidized LDL was not measured in this study, data from an early clinical trial indicated that consumption of chitin-glucan for 28 days decreased circulating oxidized LDL by approximately 26% in healthy, normo-cholesterolemic young males. To confirm these results in a randomized, double-blind, placebo-controlled study using males and females with broader inclusion criteria, chitin-glucan will be evaluated alone (at 1.5 and 4.5 grams per day), and in combination with olive extract (chitin-glucan at 1.5 gram per day + olive extract at 135 mg per day). There is a large body of evidence that indicates that olive oil recapitulates many of the beneficial effects on human health, including a reduced risk for developing CVDs, that are reported for intake of the Mediterranean Diet. Numerous studies performed in vitro and in vivo have concluded that polyphenolic compounds present in extra virgin olive oil play an important role in the prevention of atherosclerotic damage through their inhibition of LDL oxidation. Tyrosol and hydroxytyrosol show dose-dependent activity in this regard and are considered potent antioxidants, demonstrating activity in the micromolar range. Thus, there is a solid scientific and clinical rationale to evaluate both chitin-glucan alone and in combination with olive extract for their ability to reduce oxidized LDL.