Long-term metabolic effects of different doses of niacin-bound chromium on Sprague-Dawley rats.
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.
Perricone
N V
NV
Michigan State University College of Human Medicine, East Lansing, MI 48824-136, USA.
Bagchi
D
D
Echard
B
B
Preuss
Harry G
HG
D047228:Angiotensin II Type 1 Receptor Blockers / Q000378:metabolism; D000818:Animals; D001774:Blood Chemical Analysis; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002857:Chromium / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D004032:Diet; D019587:Dietary Supplements; D004326:Drinking; D004435:Eating; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D019808:Losartan / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009525:Niacin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D002857:Chromium; D009525:Niacin; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester