Niacin-bound Chromium Research Articles

Efficacy of a novel, natural extract of (–)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX, niacin-bound chromium and Gymnema sylvestre extract in weight management in human volunteers: a pilot study

In this pilot study, the efficacy of a novel, natural extract of a highly bioavailable, calcium-potassium salt of (–)-hydroxycitric acid (HCA-SX) alone and in combination with a niacin-bound chromium (NBC) and Gymnema sylvestra extract (GSE) was evaluated for weight loss in moderately obese subjects by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and serotonin levels, and enhanced excretion of urinary fat metabolites. Garcinia cambogia-derived (–)-hydroxycitric acid (HCA) has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has shown the ability to restore insulin function, metabolize fat, turn protein into muscle, and convert sugar into energy, which plays a role in appetite regulation and facilitates weight loss. Gymnema sylvestre is a traditional herb that helps to promote weight loss possibly through its ability to reduce cravings for sweets and control blood sugar levels. A randomized, double-blind, placebo-controlled human clinical study was conducted in thirty obese subjects (ages 21-50, BMI>26 kg/m 2) for eight weeks in Elluru, India. The subjects were randomly divided into three groups (10 subjects/group) and given HCA-SX 4,667 mg (60% HCA providing 2,800 mg HCA/day) (Group A), a combination of HCA-SX 4,667 mg, NBC 4 mg (providing 400 μg elemental Cr) and GSE 400 mg (providing 100 mg gymnemic acid) (Group B), or placebo (Group C) daily in 3 equally divided doses 30-60 min before each meal. This HCA-SX dose was extrapolated from previously conducted in vitro and in vivo studies. In addition, subjects received 2,000 kcal diet/day and underwent a 30 min/day supervised walking program, 5 days/week. At the end of 8 weeks, body weight and BMI decreased by 6.3%, respectively, in Group A. Food intake was reduced by 4%. Total cholesterol, LDL and triglycerides levels were reduced by 6.3%, 12.3% and 8.6%, respectively, while HDL and serotonin levels increased by 10.7% and 40%, respectively. Serum leptin levels were decreased by 36.6%, and the enhanced excretion of urinary fat metabolites, including malondialdehyde (MDA), acetaldehyde (ACT), formaldehyde (FA) and acetone (ACON), increased by 125-258%. Under these same conditions, Group B reduced body weight and BMI by 7.8% and 7.9%, respectively. Food intake was reduced by 14.1%. Total cholesterol, LDL and triglyceride levels were reduced by 9.1%, 17.9% and 18.1%, respectively, while HDL and serotonin levels increased by 20.7% and 50%, respectively. Serum leptin levels decreased by 40.5% and enhanced excretion of urinary fat metabolites increased by 146-281%. Group C reduced body weight and BMI by only 1.6% and 1.7%, respectively, food intake was increased by 2.8%, and LDL, triglycerides and total cholesterol decreased by 0.8%, 0.2% and 0.8%, respectively. HDL were reduced by 4.1% while serum leptin levels were increased by 0.3%, and excretion of urinary fat metabolites did not change in MDA, ACT and FA, and marginally increased in the case of ACON. No adverse effects were observed. Results demonstrate that HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as safe weight management supplements.

Effects of niacin-bound chromium, Maitake mushroom fraction SX and (-)-hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats.

Previous studies in our laboratories have demonstrated that niacin-bound chromium (NBC), Maitake mushroom and (-)-hydroxycitric acid (HCA-SX) can ameliorate hypertension, dyslipidemias and diabetes mellitus, and therefore may be useful in weight management. In the present study, we used aged, diabetic Zucker fatty rats (ZFR) (70-75 weeks) in order to determine whether NBC, fraction SX of Maitake mushroom (MSX) and 60% (-)-hydroxycitric acid (HCA-SX) from Garcinia cambogia, alone or in combination, can affect certain aspects of the metabolic syndrome. Syndrome X or metabolic syndrome has been described as a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, which are associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease. Four groups of eight ZFR were gavaged daily with different supplements. For the initial three weeks, the control group of ZFR received only water, the second group received NBC 40 mcg elemental chromium/day, the third group received MSX 100 mg/day and the last group received HCA-SX 200 mg/day. During weeks 4-6, the doses of each treatment were doubled. The control animals lost approximately 50 g body weight (BW) per rat over 6 weeks of treatment, which is characteristic of these animals in declining health. In contrast, eight ZFR receiving NBC lost approximately 9 g BW per rat, while rats consuming MSX lost 16 g BW per rat. However, ZFR receiving HCA-SX simulated the pattern in the control group because these animals lost approximately 46 g BW per rat. The wide individual variations resulted in a lack of statistical significance among groups. Nevertheless, 75% of the ZFR in the control group lost more than 50 g BW over the 6 weeks duration, whereas none of the ZFR receiving NBC, 25% of the ZFR receiving MSX and 57% of the ZFR receiving HCA-SX lost over 50 g BW over the 6 weeks of the study. ZFR in all 3 treatment groups showed significantly lower blood pressures as compared to control, which seemed to be dose related. The general trend was for renal and liver blood parameters, hepatic and renal lipid peroxidation and DNA fragmentation to improve due to the supplementation of these natural products. Treatment of animals with a combination of these three novel supplements resulted in a lower SBP and maintenance of BW compared to control animals. These results demonstrate that elderly diabetics and even aging individuals might benefit from a similar regimen.

Cytotoxicity and oxidative mechanisms of different forms of chromium

Chromium exists mostly in two valence states in nature: hexavalent chromium [chromium(VI)] and trivalent chromium [chromium(III)]. Chromium(VI) is commonly used in industrial chrome plating, welding, painting, metal finishes, steel manufacturing, alloy, cast iron and wood treatment, and is a proven toxin, mutagen and carcinogen. The mechanistic cytotoxicity of chromium(VI) is not completely understood, however, a large number of studies demonstrated that chromium(VI) induces oxidative stress, DNA damage, apoptotic cell death and altered gene expression. Conversely, chromium(III) is essential for proper insulin function and is required for normal protein, fat and carbohydrate metabolism, and is acknowledged as a dietary supplement. In this paper, comparative concentration- and time-dependent effects of chromium(VI) and chromium(III) were demonstrated on increased production of reactive oxygen species (ROS) and lipid peroxidation, enhanced excretion of urinary lipid metabolites, DNA fragmentation and apoptotic cell death in both in vitro and in vivo models. Chromium(VI) demonstrated significantly higher toxicity as compared with chromium(III). To evaluate the role of p53 gene, the dose-dependent effects of chromium(VI) were assessed in female C57BL/6Ntac and p53-deficient C57BL/6TSG p53 mice on enhanced production of ROS, lipid peroxidation and DNA fragmentation in hepatic and brain tissues. Chromium(VI) induced more pronounced oxidative damage in multiple target organs in p53 deficient mice. Comparative studies of chromium(III) picolinate and niacin-bound chromium(III), two popular dietary supplements, reveal that chromium(III) picolinate produces significantly more oxidative stress and DNA damage. Studies have implicated the toxicity of chromium picolinate in renal impairment, skin blisters and pustules, anemia, hemolysis, tissue edema, liver dysfunction; neuronal cell injury, impaired cognitive, perceptual and motor activity; enhanced production of hydroxyl radicals, chromosomal aberration, depletion of antioxidant enzymes, and DNA damage. Recently, chromium picolinate has been shown to be mutagenic and picolinic acid moiety appears to be responsible as studies show that picolinic acid alone is clastogenic. Niacin-bound chromium(III) has been demonstrated to be more bioavailable and efficacious and no toxicity has been reported. In summary, these studies demonstrate that a cascade of cellular events including oxidative stress, genomic DNA damage and modulation of apoptotic regulatory gene p53 are involved in chromium(VI)-induced toxicity and carcinogenesis. The safety of chromium(III) is largely dependent on the ligand, and adequate clinical studies are warranted to demonstrate the safety and efficacy of chromium(III) for human consumption.

Protective effects of a novel niacin-bound chromium complex and a grape seed proanthocyanidin extract on advancing age and various aspects of syndrome X.

Aging is the progressive accumulation of changes with time that are responsible for the ever-increasing likelihood of disease and death. The precise cascade of pathological events mainly responsible for aging are still not clearly understood, but enhanced production of free radicals and its deleterious effects on proteins, nucleic acids, and fats, as well as enhanced glycosylation of proteins and DNA are prevalent during aging. Insulin resistance may be a common etiology, at least in part, behind the pathobiological alterations of advancing age. Prevalent age-related disorders such as cardiovascular diseases, obesity, and cancer have been associated with impaired glucose/insulin metabolism and its consequences. This leads to future strategies to combat the aging process and chronic disorders such as the components of syndrome X associated with aging. Increasing the intake of antioxidants and/or substances recognized to enhance insulin sensitivity is a natural means of combatting the glucose/insulin perturbations and free radical damage. Accordingly, ingestion of niacin-bound chromium and natural antioxidants such as grape seed proanthocyanidin extract has been demonstrated to improve insulin sensitivity and/or ameliorate free radical formation and reduce the signs/symptoms of chronic age-related disorders including syndrome X. These natural strategies possess a highly favorable risk/benefit ratio.

Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacin-bound chromium in a hamster atherosclerosis model.

Atherosclerosis is a disease of the arteries in which fatty plaques develop on the inner arterial wall, which eventually obstructs blood flow. Identified risk factors for atherosclerosis include genetics, diet, lifestyle, smoking, circulating lipid and cholesterol levels, and molecular and circulating signals of chronic vascular inflammation. The link between flavonoids and atherosclerosis is based partly on the evidence that some flavonoids possess antioxidant properties and have been shown to be potent inhibitors of LDL oxidation in vitro. Hypercholesterolemia, a significant cardiovascular risk factor is prevalent in the American population. Grape seed proanthocyanidin extracts are known to exhibit a broad spectrum of chemopreventive and cardioprotective properties against oxidative stress. A recent study has shown that a combination of IH636 grape seed proanthocyanidin extract (GSPE) and a niacin-bound chromium (NBC) can decrease total cholesterol, LDL and oxidized LDL levels in hypercholesterolemic human subjects. In this study, we assessed the efficacy of GSPE supplementation in hamsters, singly and in combination with NBC, since these animals have a similar lipid profile to hypercholesterolemic humans when fed a hypercholesterolemic diet of 0.2% cholesterol and 10% coconut oil (HCD). After 10 weeks of feeding HCD, these animals developed foam cells, which is a biomarker of early stages of atherosclerosis. Atherosclerosis (% of aorta covered with foam cells) was reduced by approximately 50% and 63% following supplementation of these animals with 50 mg/kg and 100 mg/kg of GSPE, respectively, in conjunction with a HCD, while approximately 32% reduction was observed following supplementation of GSPE plus NBC. A range of 7-9 animals was used in each study group. GSPE alone and in combination with NBC exerted a pronounced effect on the cholesterol, and triglyceride levels, as well as oxidative lipid damage as demonstrated by the formation of thiobarbituric acid reactive substances (TBARS). This data demonstrates that GSPE and NBC may provide significant health benefits by dramatically ameliorating the incidence of atherosclerosis as demonstrated by reducing the formation of foam cells.

Antihypertensive and metabolic effects of whole Maitake mushroom powder and its fractions in two rat strains.

Maitake mushroom has been reported to favorably influence hypertension and diabetes mellitus. The purpose of this study was to compare the effects of whole Maitake mushroom powder and two extracts designated as ether soluble (ES) and water soluble (WS) on Zucker fatty rats (ZFR), a model of insulin resistance, and on spontaneously hypertensive rats (SHR), a model of genetic hypertension. In the initial study, we followed four groups of eight ZFR and SHR receiving special diets: a baseline diet (BD), BD + whole Maitake mushroom powder (20% w/w), BD + fraction ES (0.10% w/w), and BD + WS (0.22% w/w). Different effects of these dietary regimens on the 2 rat strains were found. At 35 days, only consumption of the ES diet significantly decreased systolic BP (SBP) in SHR (average 197 vs. 176 mm Hg, p < 0.001), while in ZFR only the groups consuming the whole Maitake and WS diets showed significantly decreased SBP (138 vs. 120-125 mm Hg, p < 0.001). A challenge test with losartan (an angiotensin II receptor blocker) indicates that angiotensin II does not play a major role in SBP regulation of ZFR, but does in SHR where consumption of ES relative to other groups significantly lowered activity of this system. In SHR, glucose, cholesterol, circulating insulin and HbA1C were virtually similar among all dietary groups; but whole Maitake (-22%), ES (-120%) and WS (-80%) diets were associated with decreased triglycerides, and the ES diet with lowered serum creatinine (-29%). In ZFR, circulating insulin and HbA1C were significantly decreased in the whole Maitake powder and ES groups, and tended to be lower in the WS group compared to control. In the ensuing studies, we gavaged ZFR once daily with water (control), 44 mg fraction WS, or 44 mg fraction WS plus 100 microg niacin-bound chromium (NBC). Oral gavage of WS clearly lowered SBP and circulating glucose concentrations, more so with the addition of chromium. We conclude that the examined forms of Maitake mushroom have antihypertensive and antidiabetic potential which differ among rat strains. The ES fraction may decrease SBP in SHR via alteration in the renin-angiotensin system.