Michigan State University College of Human Medicine, East Lansing, MI 48824-136, USA.
Mol Cell Biochem. 2010 May;338(1-2):91-103. doi: 10.1007/s11010-009-0342-8. Epub 2009 Dec 11.
We simultaneously assessed benefits and risks of niacin-bound chromium (NBC) intake at varying doses over a prolonged period of time (>1.2 years) in male and female Sprague-Dawley (SD) rats. We performed the study in two phases. First, we followed 60 male and 60 female SD rats, each gender divided into six groups. Through day 150 (phase 1A), all SD rats received a high sucrose diet (30% w/w) with or without different concentrations of NBC. The male/female groups were: 1] control without NBC n = 10, 2] low NBC (2.8 ppm, n = 10), 3] medium NBC (8.7 ppm, n = 20), 4] high NBC (28.0 ppm, n = 20). Based on dosing, we refer to the three treatment groups as 1X, 3X, and 10X. During days 151-312 (phase 1B), NBC was removed from diets of one half of the 3X and 10X groups. These are referred to as 3X satellite and 10X satellite. In phase 2 (days 313-460), males from groups 1X, 3X, 10X, 3X satellite, and 10X satellite received the same 3X dose of NBC (8.7 ppm). The last two groups also ingested different doses of a formulation of natural products in addition to NBC. We examined blood pressure, the renin-angiotensin system (RAS), nitric oxide (NO), and insulin systems and inflammatory parameters. Results in male and female SD rats were comparable. NBC lowered systolic blood pressure (SBP) in a dose-dependent fashion; however, after 200 days, the SBP of the low dose group (1X) began to rise and returned to baseline control. After raising the dose of NBC to 3X, the SBP in the 1X group decreased significantly once more. When half the test rats (3X and 10X) were deprived of NBC, SBP rose gradually to control levels after 2 to 3 months. However, the SBP decreased significantly once more when each satellite group returned to the 3X dose. Special testing suggests that NBC at adequate dosing increases insulin sensitivity, lowers HbA1C, decreases activity of the RAS, at least in part, through ACE inhibition, enhances NO activity, and is without signs of toxicity. The addition of a formula composed of antioxidants and immune modulators to the chromium regimen caused even faster and more profound changes in SBP than with NBC alone. We conclude that NBC at adequate dosing is effective in male and female SD rats on certain metabolic parameters over a prolonged period, effects that disappear over months after NBC is removed. When dosing is returned, the effectiveness of NBC returns. Low doses of NBC may lose their effect over time. No signs of toxicity were observed.
我们同时评估了烟酸结合铬（NBC）在长时间（> 1.2 年）内以不同剂量摄入对雄性和雌性 Sprague-Dawley（SD）大鼠的益处和风险。我们分两个阶段进行了这项研究。首先，我们跟踪了 60 只雄性和 60 只雌性 SD 大鼠，每只动物分为 6 组。到第 150 天（第 1A 阶段），所有 SD 大鼠都接受了高蔗糖饮食（30%w/w），同时摄入或不摄入不同浓度的 NBC。雄性/雌性组为：1]无 NBC 对照组 n = 10，2]低 NBC（2.8 ppm，n = 10），3]中 NBC（8.7 ppm，n = 20），4]高 NBC（28.0 ppm，n = 20）。基于剂量，我们将这三个治疗组称为 1X、3X 和 10X。在第 151-312 天（第 1B 阶段），NBC 从 3X 和 10X 组一半的饮食中去除。这些被称为 3X 卫星组和 10X 卫星组。在第 2 阶段（第 313-460 天），1X、3X、10X、3X 卫星和 10X 卫星组的雄性接受了相同的 3X NBC 剂量（8.7 ppm）。最后两组除了 NBC 外，还摄入了不同剂量的天然产物配方。我们检查了血压、肾素-血管紧张素系统（RAS）、一氧化氮（NO）和胰岛素系统以及炎症参数。雄性和雌性 SD 大鼠的结果相当。NBC 以剂量依赖性方式降低收缩压（SBP）；然而，200 天后，低剂量组（1X）的 SBP 开始上升并恢复到基线对照。当 NBC 剂量提高到 3X 时，1X 组的 SBP 再次显著下降。当一半的试验大鼠（3X 和 10X）被剥夺 NBC 时，SBP 在 2 到 3 个月后逐渐升高至对照水平。然而，当每个卫星组恢复到 3X 剂量时，SBP 再次显著下降。特殊测试表明，在适当剂量下，NBC 可增加胰岛素敏感性，降低 HbA1C，降低 RAS 活性，至少部分通过 ACE 抑制，增强 NO 活性，且无毒性迹象。将由抗氧化剂和免疫调节剂组成的配方添加到铬方案中，可使 SBP 的变化比单独使用 NBC 更快、更明显。我们得出结论，在雄性和雌性 SD 大鼠中，NBC 在长时间内对某些代谢参数有效，NBC 去除数月后，这些效果消失。当再次给予 NBC 时，NBC 的有效性会恢复。低剂量的 NBC 可能会随着时间的推移而失去作用。未观察到毒性迹象。
