Effects of chromium supplementation on glycemic control in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: We aimed to investigate the effect of chromium supplementation on glycemic control indices in patients with type 2 diabetes (T2DM). METHODS: Randomized controlled trials examining the effect of chromium supplementation on glycemic control indices and published before February 2020 were detected by searching online databases, including PubMed, Scopus, Embase, Web of sciences and The Cochrane Library, using a combination of suitable keywords. Mean change and standard deviation (SD) of the outcome measures were used to estimate the mean difference between the supplementation group and the control group at follow-up. RESULTS: Twenty-eight studies reported fasting plasma glucose (FPG), insulin, hemoglobin A1C (HbA1C) and homeostatic model assessment for insulin resistance (HOMA-IR) as an outcome measure. Results revealed significant reduction in FPG (weighted mean difference (WMD): -19.00 mg/dl, 95% CI: -36.15, -1.85, P = 0.030; I2: 99.8%, p < 0.001), insulin level (WMD: -12.35 pmol/l, 95% CI: -17.86, -6.83, P < 0.001), HbA1C (WMD: -0.71 %, 95% CI: -1.19, -0.23, P = 0.004) and HOMA-IR (WMD: -1.53, 95% CI: -2.35, -0.72, P < 0.001; I2: 89.9%, p < 0.001) after chromium supplementation. CONCLUSION: The results of the current meta-analysis study might support the use of chromium supplementation for the improvement of glycemic control indices in T2DM patients.

miR-375 and miR-30d in the effect of chromium-containing Chinese medicine moderating glucose metabolism.

In China, TianMai Xiaoke tablet (TM) is used to treat type 2 diabetes. However, the exact mechanism of TM is not clear. This study is to investigate the effect of TM on glucose metabolism in diabetic rats and to identify whether TM takes a direct action through microRNAs on islet. Rats were divided into control group, diabetic group, low dose of TM group (TML), and high dose of TM group (TMH). Pancreas samples were analyzed using microRNA array and Q-PCR. Eight-week treatment with TM significantly decreased fasting blood glucose. The blood glucose was significantly reduced in TM-treated groups before and after oral glucose administration. Fasting insulin and HOMA-IR were suppressed in TM-treated groups. miR-448, let-7b, miR-540, miR-296, miR-880, miR-200a, miR-500, miR-10b, miR-336, miR-30d, miR-208, let-7e, miR-142-5p, miR-874, miR-375, miR-879, miR-501, and miR-188 were upregulated, while miR-301b, miR-134, and miR-652 were downregulated in TMH group. Through target gene analysis and real-time PCR verification, we found that these miRNAs, especially miR-375 and miR-30d, can stimulate insulin secretion in islet. Our data suggest that TM can improve blood glucose in diabetic rats which involved increasing the expression of miR-375 and miR-30d to activate insulin synthesis in islet.

Chromium: is it essential, pharmacologically relevant, or toxic?

Over fifty years ago, the element chromium (as the trivalent ion) was proposed to be an essential element for mammals with a role in maintaining proper carbohydrate and lipid metabolism. Evidence for an essential role came from dietary studies with rodents, studies on the effects of chromium on subjects on total parenteral nutrition, and studies of the absorption and transport of chromium. Over the next several decades, chromium-containing nutritional supplements became so popular for weight loss and muscle development that sales were second only to calcium among mineral supplements. However, the failure to identify the responsible biomolecules(s) that bind chromium(III) and their mode of action, particularly a postulated species named glucose tolerance factor or GTF, resulted in the status of chromium being questioned in recent years, such that the question of its being essential needs to be formally readdressed. At the same time as chromium(III)'s popularity as a nutritional supplement was growing, concerns over its safety appeared. While chromium has been conclusively shown not to have beneficial effects on body mass or composition and should be removed from the list of essential trace elements, chromium(III) compounds are generally nontoxic and have beneficial pharmacological effects in rodents models of insulin insensitivity, although human studies have not conclusively shown any beneficial effects. Mechanisms have been proposed for these pharmacological effects, but all suffer from a lack of consistent supporting evidence.

El té verde en la quimioprevención in vivo del daño genotóxico inducido por metales cancerígenos (cromo [VI]) / Green tea and its role on chemoprevention in vivo of genotoxic damage induced by carcinogenic metals (Chromium [VI])

Introducción: Debido a sus componentes antioxidantes, al consumo de infusiones de té verde se le ha asociado con efectos benéficos para la salud, ya que sus antioxidantes pueden jugar un papel importante en el riesgo y la patogénesis de algunas enfermedades crónicas, como algunos tipos de cáncer y enfermedades cardiovasculares. A su vez, se ha reportado que compuestos metálicos como los del Cr [VI] son carcinogénicos e inducen daño genotóxico mediante Estrés Oxidante (EOx). De ahí que, es posible que el té verde proteja del daño genotóxico inducido por estos compuestos. Objetivo: Se evaluó el efecto de la administración por vía oral del té verde sobre el daño genotóxico inducido por Cr [VI], mediante la cuantificación de micronúcleos (MN) en eritrocitos policromáticos (EPC). Material y método: Ratones de la cepa CD-1 fueron divididos en forma aleatoria en los siguientes grupos: (i) testigo, (ii) tratados con té verde, (iii) tratados con trióxido de cromo, (iv) tratados con té verde y trióxido de cromo. El té verde se administró por sonda intragástrica cada 12 horas durante dos días (4 dosis de 0,25 ml de infusiones de 1,6 g/7,5 ml) y ad libitum 5,6 ml/día durante 10 días de infusiones de 3,2 g/100 ml, mientras que, el trióxido de cromo se aplicó por vía intraperitoneal (20 mg/kg). Se obtuvieron muestras de sangre de la vena caudal, en las que se evaluó el número de MN en EPC a las 0, 24, 48 y 72 horas después de los tratamientos. Resultados: El grupo tratado con té verde no presentó cambios estadísticamente significativos en los promedios de MN. Por su parte, el grupo al que se le administró el trióxido de cromo mostró incrementos entre 4 y 8 MN, que resultaron estadísticamente significativos al compararlos con el grupo testigo, lo que corroboró el daño genotóxico. Cuando se combinaron los tratamientos del té verde y trióxido de cromo se observó una disminución en las frecuencias de MN del 31 y 62% a las 72 horas, del 20 y 35% a las 48 horas y del 18 y 31% a las 24 horas con los tratamientos intragástricos y ad libitum respectivamente, en comparación con el grupo tratado solo con el trióxido de cromo. Por lo que, el té verde redujo el daño genotóxico inducido por el trióxido de cromo, y la mayor protección se presentó a las 72 horas. Conclusiones: Nuestros hallazgos muestran un efecto protector del té verde contra el daño al material genético inducido por compuestos metálicos como los del Cr [VI], sugiriendo que sus componentes antioxidantes son los que tienen un efecto quimiopreventivo sobre el EOx generado por el Cr [VI] durante su reducción a Cr [III]. El hecho de que la mayor disminución de la frecuencia de MN se observe a las 72 horas y con el tratamiento ad libitum, sugiere que el efecto protector depende de la biodisponibilidad, farmacodinámica y farmacocinética del principio activo del té verde, por lo que la administración del té verde durante tiempos más prolongados antes de la exposición con compuestos de Cr [VI] podría tener un efecto preventivo más consistente (AU)

Background: Consumption of green tea, by its antioxidant properties, has been associated with beneficial health effects, because antioxidant may play a role in the risk and pathogenesis of several chronic diseases, especially cardiovascular disease and cancer. On the other hand, it has been reported that metal compounds such as chromium [VI] are carcinogenic and can induce genotoxic damage through the Oxidative Stress. Therefore, it is possible that green tea has a protective effect against the genotoxic damage induced by this compounds. Objective: To evaluate the effect of oral administration of green tea over the genotoxic damage induced by Cr [VI] by quantification of micronucleus (MN) in polychromatic erythrocytes (EPC). Materials and methods: We use mice of CD-1 strain that were randomly divided into the following groups: (i) control, (ii) treatment with green tea, (iii) treatment with chromium trioxide, (iv) treatment with green tea and chromium trioxide. The green tea was administrated via intragastric tube every 12 hours over two days (4 doses of 0.25 ml infusions 1.6 g/7.5 ml) and ad libitum (5.6 ml/day for 10 days infusions of 3.2 g/100 ml), while chromium trioxide was administrated via intraperitoneal (20 mg/kg). Blood samples were obtained from the caudal vein, the number of MN in EPC was assessed at 0, 24, 48 and 72 hours after the treatments. Results: The group treated with green tea showed no significant statistical changes in the average of MN. On the other hand, the group that was dosed with the chromium trioxide showed an increase between 4 and 8 MN, which was statistically significant when compared with control group, which confirmed the genotoxic damage. When the green tea treatment was administered before the application of chromium trioxide, there was a decrease in MN frequencies of 31 and 62% at 72 hours, 20 and 35% at 48 hours and 18 and 31% at 24 hours with intragastric and ad libitum respectively, compared with the group treated only with chromium trioxide. Hence, green tea reduced the genotoxic damage induced by chromium trioxide, and the highest protection was presented at 72 hours. Conclusions: Our findings support the protective effects of green tea against the damage of genetic material, induced by metal compounds such as chromium [VI], suggesting that its antioxidant compounds are those that have a chemopreventive effect on the EOX generated by the Cr [VI] during its reduction to Cr (III). The fact that the largest decrease in the frequency of MN was observed at 72 hours and ad libitum treatment, suggests that, the protective effect depends on the bioavailability, pharmacodynamics and pharmacokinetics of the active ingredient in green tea, so the administration of green tea for a long period of time before the exposure to Cr [VI] could have a more consistent preventive effect (AU)

The efficacy of chromium as a growth enhancer for mirror carp (Cyprinus carpio L): an integrated study using biochemical, genetic, and histological responses.

A growth trial was conducted on juvenile mirror carp (Cyprinus carpio L.) for 8 weeks to compare the efficacy of three chromium (Cr) compounds (Cr chloride, Cr picolinate, and Cr yeast) at a level 0.5 mg/kg as a potential growth enhancer. In addition, a high level of Cr (2.0 mg/kg) as Cr chloride has also been added in parallel for comparison. All Cr fortified diets at a level 0.5 mg/kg produced superior growth for carp compared to the control group and the group fed the high level of Cr chloride (2.0 mg/kg). Metabolic indicators measured included two of the key liver enzymes (hexokinase, HK) and (glucose-6-phosphate dehydrogenase, G6PD) activity. The results validated the positive effect of Cr at a level 0.5 mg/kg on enzyme activity and carbohydrate utilization producing significantly better growth performance for mirror carp. The study also included measurement of DNA strand breaks in the erythrocytes using the comet assay which revealed significantly (P < 0.05) increased DNA damage in fish fed on high level of Cr chloride (2.0 mg/kg) but the other treatments were not significantly different (P > 0.05) from the control groups. The concentration of Cr in the liver, gut, and whole fish tissues increased with increasing dietary Cr supplementation. Overall, Cr supplementation at a level 0.5 mg/kg from different sources may affect growth performance in carp by activation of some key liver enzymes (HK and G6PD).

Adjuvant treatment for early ovarian cancer: a randomized phase III trial of intraperitoneal 32P or intravenous cyclophosphamide and cisplatin--a gynecologic oncology group study.

PURPOSE: To conduct a prospective study of intraperitoneal radioactive chromic phosphate (32P) versus cyclophosphamide-cisplatin (CP) in women with early ovarian cancer at high risk for recurrence (International Federation of Gynecology and Obstetrics stage Ia or Ib grade 3 or Ic or stage II, no macroscopic residual disease) and to compare cumulative incidence of recurrence, overall survival, and relative toxicity. MATERIALS AND METHODS: A total of 251 patients were randomly assigned to treatment with 32P or CP. Twenty-two (8.7%) were ineligible following centralized pathology review. Of the 229 patients included in the analysis, 110 received 32P, and 119 received CP. RESULTS: The cumulative incidence of recurrence at 10 years was 35% (95% CI, 27% to 45%) for patients receiving 32P and 28% (95% CI, 21% to 38%) for those receiving CP. Patients receiving CP had a recurrence rate 29% lower than that of those receiving 32P (P =.15, two-tail test). The death rate for patients treated with CP was 17% lower than that for patients treated with 32P (difference not significant). Combining both arms, the 10-year cumulative incidence of recurrence for all stage I patients was 27% (95% CI, 20% to 34%) compared with 44% (95% CI, 32% to 56%) for stage II patients (P =.01). Both regimens were reasonably well tolerated, but problems with inadequate distribution (7%) and small-bowel perforation (3%) make the otherwise less toxic 32P less acceptable. CONCLUSION: Although there are no statistically significant differences in survival, the lower cumulative recurrence seen with CP and complications of 32P administration make platinum-based combinations the preferred adjuvant therapy for early ovarian cancer patients at high-risk for recurrence.

The safety and efficacy of high-dose chromium.

The data on the standards for chromium requirements and the safety of various chromium compounds and doses are reviewed. The 350-fold difference between the acceptable daily intake and the calculated reference dose for humans of 70 mg per day seems without precedent with respect to other nutritional minerals. Previous claims of mutagenic effects of chromium are of questionable relevance. While studies have found DNA fragmentation (clastogenic effects) by chromium picolinate, anecdotal reports of high-dose chromium picolinate toxicity are few and ambiguous. The beneficial effects of chromium on serum glucose and lipids and insulin resistance occur even in the healthy. Serum glucose can be improved by chromium supplementation in both types 1 and 2 diabetes, and the effect appears dose dependent. Relative absorption of various chromium compounds is summarized and the mechanism of low molecular weight chromium binding substance (LMWCr) in up-regulating the insulin effect eight-fold is discussed. There is evidence of hormonal effects of supplemental chromium besides the effect on insulin. Chromium supplementation does result in tissue retention, especially in the kidney, although no pathogenic effect has been demonstrated despite considerable study.

Adjuvant treatment for early epithelial ovarian cancer: results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P). G.I.C.O.G.: Gruppo Interregionale Collaborativo in Ginecologia Oncologica.

BACKGROUND: From 1983 to 1990, 271 consecutive patients with stage I ovarian cancer entered two randomised trials, aimed at assessing the role of adjuvant chemotherapy after radical surgery in early stages of ovarian cancer. Trial I compared cisplatin (50 mg/m2 with repeated courses every 28 days for 6 cycles) to no further therapy in F.I.G.O. stage Ia & b Grade II-III patients; trial II compared cisplatin (same dose and schedule) to 32P in Iaii & bii and Ic patients. METHODS: Both studies were multicentric and centrally randomized. Treatment was allocated by phone and stratified by center. All patients satisfying major eligibility criteria (histological and grade, no previous neoplasms) were analysed according to treatment allocated by randomisation. RESULTS: With a median observation time of 76 months, cisplatin significantly reduced the relapse rate by 65% (HR = 0.35; 95% CI = 0.14-0.89, p = 0.028; Cox Model) in trial I and 61% (HR = 0.39; 95% CI = 0.19-0.77, p = 0.007; Cox Model) in trial II. Survival was not significantly different (trial I - Kaplan-Meier overall 5-year survival: cisplatin = 88%, control = 82%, HR = 1.15; 95% CI = 0.44-2.98; p = 0.773; Cox Model); trial II - overall 5-year survival: cisplatin = 81%, 32P = 79%, HR = 0.72; 95% CI = 0.37-1.43; p = 0.354; Cox model). In both studies the risk of dying after relapse increased for patients originally randomized to the cisplatin arms: in trial I, 6 of 7 patients in the cisplatin relapsed arm and died of tumor compared with 8 of 14 patients in the control arm. In trial II 11 of 12 patients on cisplatin, and 18 of 26 on 32P succumbed to tumor recurrence. CONCLUSION: Adjuvant cisplatin treatment in early ovarian cancer significantly prevents relapse in comparison to 32P in stage IC patients or to no immediate treatment in earlier stage women. The impact of cisplatin adjuvant treatment on survival remains, however, unclear.

Adjuvant intraperitoneal chromic phosphate therapy in a woman with early ovarian carcinoma and pelvic infection with resulting catastrophic complications.

Women diagnosed with early stage ovarian cancer may be considered for adjuvant therapy. Intraperitoneal chromic phosphate (P-32) is commonly used in these patients with few complications. A woman found to have early stage ovarian cancer was given intraperitoneal P-32 in the presence of a lingering pelvic infection, which is usually not mentioned as a contraindication to its use. Radiation damage to the small bowel and cecum developed as did damage to the ureter and bladder, which then required surgery.