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Chromium Increases Insulin Internalization

Evans GW & Bowman TD. J Inorg Biochem (1992 Jun) 46(4): 243-50

The effects of chromium chloride, chromium nicotinate, and chromium picolinate on insulin internalization in cultured rat skeletal muscle cells was examined. Insulin internalization was markedly increased in cells cultured in a medium that contained chromium picolinate and the increased internalization rate was accompanied by a marked increase in the uptake of both glucose and leucine. The effect was specific for chromium picolinate since neither zinc picolinate nor any of the other forms of chromium tested was effective. The increased insulin internalization rate may result from an increase in membrane fluidity since chromium picolinate and to a lesser extent, chromium nicotinate, increased the membrane fluidity of synthetic liposomal membranes.

Longevity Effect of Chromium Picolinate

McCarty MF. Med Hypotheses (1994 Oct) 43(4): 253-65

The first rodent longevity study with the insulin-sensitizing nutrient chromium picolinate has reported a dramatic increase in both median and maximal lifespan. Although the observed moderate reductions in serum glucose imply a decreased rate of tissue glycation reactions, it is unlikely that this alone can account for the substantial impact on lifespan; an effect on central neurohormonal regulation can reasonably be suspected. Recent studies highlight the physiological role of insulin as a modulator of brain function. I postulate that aging is associated with a reduction of effective insulin activity in the brain, and this contributes to age- related alterations of hypothalamic functions that result in an 'older' neurohormonal milieu; consistent with this possibility, diabetes leads to changes of hypothalamic regulation analogous to those seen in normal aging. Conversely, promoting brain insulin activity with chromium picolinate may help to maintain the hypothalamus in a more functionally youthful state; increased hypothalamic catecholamine activity, sensitization of insulin- responsive central mechanisms regulating appetite and thermogenesis, and perhaps trophic effects on brain neurons may play a role in this regard. Since both the pineal gland and thymus are dependent on insulin activity, chromium may aid their function as well. Thus, the longevity effect of chromium picolinate may depend primarily on delay or reversal of various age-related changes in the body's hormonal and neural milieu. A more general strategy of hypothalamic 'rejuvenation' is proposed for extending healthful lifespan.

Chromium and other insulin sensitizers may enhance glucagon secretion: implications for hypoglycemia and weight control.

Med Hypotheses (ENGLAND) Feb 1996, 46 (2) p77-80

Increased pancreatic beta-cell secretory activity usually is associated with decreased alpha-cell activity; stimulated beta-cells release gamma-aminobutyric acid, which hyperpolarizes alpha-cells, inhibiting glucagon release. Thus, insulin secretion and glucagon secretion are usually inversely coupled. This suggests that chromium and other insulin-sensitizing modalities increase glucagon secretion. Such an effect might play a role in the documented therapeutic activity of supplemental chromium and biguanides in reactive hypoglycemia, and might also be of benefit to dieters.

Effects of chromium picolinate supplementation on body composition: A randomized, double-masked, placebo-controlled study

Current Therapeutic Research - Clinical and Experimental (USA), 1996, 57/10 (747-756)

To examine the effect of chromium picolinate (CrP) on body composition, a randomized, double-masked, placebo-controlled study was conducted. A total of 154 patients received either a placebo or 200 microg or 400 microg of CrP per day. Subjects were asked to consume at least two servings of a protein/carbohydrate nutritional drink a day that contained the different amounts of CrP. Subjects were free-living and were not provided with weight loss, dietary, or exercise guidance. Body composition was measured before and after the 72-day test period by using underwater testing (displacement method) with residual lung volumes determined by helium dilution. On completion of the posttest, a body composition improvement (BCI) index was calculated for each subject by adding the loss of body fat and gain in nonfat mass and subtracting fat gained and lean lost. Analysis of the prestudy data revealed that there were no significant differences in body composition between the three groups. After the test period, both the 200-microg and 400-microg groups had significantly higher positive changes in BCIs compared with placebo. A single-factor analysis of variance weighted linear trend was also highly significant. No significant differences in BCI were found between the 200- and 400-microg groups. Supplementation with a minimum of 200 microg/d of chromium (as CrP) can lead to significant improvement in body composition.

Chromium improves insulin response to glucose in rats.

Metabolism (UNITED STATES) Oct 1995, 44 (10)

The effects of chromium (Cr) supplementation on insulin secretion and glucose clearance (KG) during intravenous glucose tolerance tests (IVGTTS) were assessed in rats with impaired glucose tolerance due to dietary Cr deficiency. Male Wistar rats were maintained after weaning on a basal low-Cr diet containing 55% sucrose, 15% lard, 25% casein. American Institute of Nutrition (AIN)-recommended levels of vitamins, no added Cr, and an altered mineral content as required to produce Cr deficiency and impaired glucose tolerance. The Cr-supplemented group ([+Cr] n = 6) were provided with 5 ppm Cr as CrCl3 in the drinking water, and the Cr-deficient group ([-Cr]n = 5) received purified drinking water. At 12 weeks on the diet, both groups of rats were hyperinsulinemic (+Cr, 103 +/- 13; -Cr, 59 +/- 12 microU/mL) and normoglycemic (+Cr, 127 +/- 7; -Cr, 130 +/- 4 mg/dL), indicating insulin resistance. After 24 weeks, insulin levels were normal (+Cr, 19 +/- 5; -Cr, 21 +/- 3 microU/mL) and all rats remained normoglycemic (+Cr, 124 +/- 8; -Cr, 131 +/- 6 mg/dL). KG values during IVGTTS were lower in -Cr rats (KG = 3.58%/min) than in +Cr rats (KG = 5.29%/min), correlating with significantly greater 40-minute glucose areas in the -Cr group (P < .01). Comparisons of 40-minute insulin areas indicated marked insulin hyperresponsiveness in the -Cr group, with insulin-secretory responses increased nearly twofold in -Cr animals (P < .05). Chromium deficiency also led to significant decreases in cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (PDE) activity in spleen and testis (P < .01). In these studies, Cr deficiency was characterized by both beta-cell hypersecretion of insulin and tissue insulin resistance that were associated with decreased tissue levels of cAMP PDE activity.

Enhancing central and peripheral insulin activity as a strategy for the treatment of endogenous depression--an adjuvant role for chromium picolinate?

Med Hypotheses (ENGLAND) Oct 1994, 43 (4)

Depression is often associated with insulin resistance, owing to cortisol overproduction; conversely, many studies suggest that diabetics are at increased risk for depression. Recent evidence indicates that insulin is transported through the blood-brain barrier and influences brain function via widely distributed insulin receptors on neurons. These receptors are particularly dense on catecholaminergic synaptic terminals, and, while effects are variable dependent on brain region, several studies indicate that insulin promotes central catecholaminergic activity, perhaps by inhibiting synaptic re-uptake of norepinephrine. Additionally, it is well known that insulin enhances serotonergic activity in increasing blood-brain barrier transport of tryptophan. Since impaired monoaminergic activity in key brain pathways is believed to play an etiological role in depression, techniques which promote effective insulin activity, both centrally and peripherally, may be therapeutically beneficial in this disorder. This may rationalize anecdotal reports of improved mood in clinical depressives and diabetics receiving the insulin-sensitizing nutrient chromium picolinate. This nutrient, perhaps in conjunction with other insulin-sensitizing measures such as low-fat diet and aerobic exercise training (already shown to be beneficial in depression), should be tested as an adjuvant for the treatment and secondary prevention of depression.

Homologous physiological effects of phenformin and chromium picolinate.

Med Hypotheses (ENGLAND) Oct 1993, 41 (4)

The insulin-sensitizing drug phenformin, in addition to its clinical utility in type II diabetes, has been reported to lower blood lipids, reduce body fat, enhance cellular immunity, and--in rodents--to increase mean lifespan and retard the development of growth of cancer. Initial studies with the insulin-sensitizing nutrient chromium picolinate indicate that it aids glucose tolerance in type II diabetes, lowers elevated LDL cholesterol, reduces body fat while increasing lean mass, and--in rats--increases median lifespan. These effects are thus analogous to those reported for phenformin; chromium picolinate should be tested to determine whether it likewise has a favorable impact on cellular immunity and cancer risk. The ability of both phenformin and chromium picolinate to increase lifespan suggests that age-related insulin resistance may play a profound role in the aging process. It may not be coincidental that caloric restriction--the best documented technique for increasing lifespan--markedly increases insulin sensitivity. Safe, appropriate measures for promoting lifelong insulin sensitivity include a low-fat diet, exercise training, and supplemental chromium picolinate.

Chromium in human nutrition: a review

J Nutr (UNITED STATES) Apr 1993, 123 (4)

This review summarizes the results of 15 controlled studies supplementing defined Cr (III) compounds to subjects with impaired glucose tolerance. Three of these (3-4 mumol Cr/d for 2 mo) produced no beneficial effects: serum glucose, insulin and lipid concentrations remained unchanged. The remaining 12 interventions improved the efficiency of insulin or the blood lipid profile of subjects (ranging from malnourished children and healthy middle-aged individuals to insulin-requiring diabetics). In addition, three cases of impaired glucose tolerance after long-term total parenteral alimentation responding to Cr supplementation have been reported. Chromium potentiates the action of insulin in vitro and in vivo; maximal in vitro activity requires a special chemical form, termed Glucose Tolerance Factor and tentatively identified as a Cr-nicotinic acid complex. Its complete structural identification is a major challenge to chromium research. The development and validation of a procedure to diagnose chromium status is the second challenge. Such a test would allow the assessment of incidence and severity of deficiency in the population and the selection of deficiency in the population and the selection of chromium-responsive individuals. The third challenge is the definition of chromium's mode of action on parameters of lipid metabolism that have been reported from some studies but not others. Future research along these lines might establish whether chromium deficiency is a factor in the much discussed "Syndrome X" of insulin resistance. (49 Refs.)

Use of the artificial beta cell (ABC) in the assessment of peripheral insulin sensitivity: effect of chromium supplementation in diabetic patients.

Gen Pharmacol (ENGLAND) 1984, 15 (6)

The artificial beta cell (ABC), a closed-loop insulin delivery system, was used to determine insulin sensitivity. Progressively increasing glucose loads were administered after initial stabilization of the blood glucose at euglycemic levels such that the serum C-peptide was suppressed. The amount of insulin required to maintain euglycemia was considered a measure of sensitivity to insulin. Six stable maturity onset diabetics were studied before and after supplementation with chromium-rich brewer's yeast. All patients demonstrated an increase in sensitivity to insulin as indicated by a decrease in the fasting blood glucose concentration and a decrease in insulin requirement during the glucose challenge (P less than 0.02). The data obtained support the hypothesis that chromium or some other factor(s) present in brewer's yeast potentiates the peripheral effects of insulin. It remains to be established whether this effect occurs at the receptor or post-receptor level.

Effects of dietary chromium picolinate supplementation on growth, carcass characteristics, and accretion rates of carcass tissues in growing-finishing swine.

J Anim Sci (UNITED STATES) Nov 1995, 73 (11)

An experiment was conducted to evaluate the effects of chromium picolinate (CrP) on growth performance, carcass composition, and tissue accretion rates in pigs from 27 to 109 kg BW. Seven littermate sets of Yorkshire-Hampshire barrows, individually penned, were fed a fortified, corn-soybean meal basal diet (.95% lysine from 27 to 55 kg; .80% lysine from 55 to 109 kg) supplemented with 0 or 200 micrograms/kg of Cr from CrP. Addition of CrP increased (P < .09) ADG but did not affect ADFI or feed: gain ratio. Average and 10th rib backfat and longissimus muscle area were not affected by Cr supplementation. The right side of the carcass was physically dissected into muscle, fat, bone, and skin. Additionally, five pigs were killed for determination of initial body composition. Dietary CrP addition increased (P < .02) the percentage of muscle and decreased (P < .06) the percentage of fat. Total gain of dissected bone and skin were not different between treatments, but CrP increased (P < .06) the total gain of dissected muscle and decreased (P < .02) the total gain of dissected fat. Also, CrP increased the daily accretion rates of muscle (P < .05) and bone (P < .03) and decreased the daily accretion rate of fat (P < .05). The left side of the carcass was ground for determination of water, protein, lipid, and ash. The addition of CrP to the diet increased the percentage (P < .09) and accretion rate (P < .09) of water and increased the percentage (P < .004), total gain (P < .02), and accretion rate (P < .02) of protein while decreasing (P < .04) the percentage of lipid. Pigs fed CrP also had a decreased (P < .004) percentage of lipids in the dissected carcass muscle. Water, protein, and ash from the dissected muscle were not different between treatments. These results suggest that CrP supplementation throughout the entire growing-finishing phase increases the total gain and accretion rate of muscle while decreasing the total gain and accretion rate of fat. This results in carcasses with an increased percentage of muscle and decreased percentage of fat.

Anabolic effects of insulin on bone suggest a role for chromium picolinate in preservation of bone density.

Med Hypotheses (ENGLAND) Sep 1995, 45 (3) p241-6

Activation of osteoclasts by parathyroid hormone (PTH) is mediated by PTH stimulation of osteoblasts, and is dependent on a PTH-induced rise in protein kinase C activity. Physiological levels of insulin reduce the ability of PTH to activate protein kinase C in osteoblasts, suggesting that insulin may be a physiological antagonist of bone resorption. In addition, insulin is known to promote collagen production by osteoblasts. These findings imply that efficient insulin activity may exert an anabolic effect on bone, and rationalize the many clinical studies demonstrating reduced bone density in Type I diabetes. Recently, the insulin-sensitizing nutrient chromium picolinate has been found to reduce urinary excretion of hydroxyproline and calcium in postmenopausal women, presumably indicative of a reduced rate of bone resorption. This nutrient also raised serum levels of dehydroepiandrosterone-sulfate, which may play a physiological role in the preservation of postmenopausal bone density. The impact of chromium picolinate (alone or in conjunction with calcium and other micronutrients) on bone metabolism and bone density, merits further evaluation in controlled studies. (69 Refs.)

Effect of chromium picolinate on growth, body composition, and tissue accretion in pigs.

J Anim Sci (UNITED STATES) Jul 1995, 73 (7) p2033-42

An experiment was conducted to evaluate the effect of dietary chromium picolinate (CrP) on growth and body composition of pigs. Twenty-four barrows (three from each of eight litters) were randomly allotted within litter to one of three treatments: 1) basal (B) diet from 19.1 to 106.4 kg BW (Control); 2) B from 19.1 to 57.2 kg BW and then B + 200 ppb of chromium as CrP from 57.2 to 106.4 kg BW (CrP-F); and 3) B + 200 ppb of chromium as CrP from 19.1 to 106.4 kg BW (CrP- GF). Average daily gain and ADFI were reduced (P < .08) and first rib fat thickness was increased (P < .08) in pigs fed CrP-GF compared with pigs fed the Control diet. Specific gravity of the carcass was not affected (P .10) by treatment. Tenth rib fat was reduced (P < .01) in pigs fed CrP-F compared with pigs fed CrP-GF, and percentage of muscle was increased in pigs fed CrP-F (P < .09) compared with pigs fed either the Control or CrP-GF diets. Leaf fat (P < .05) and lung weights (P < .08) were reduced in pigs fed CrP-F compared with pigs fed CrP-GF. As determined by physical-chemical separation, pigs fed CrP-GF had an increased (P < .07) percentage of intermuscular fat compared with pigs fed the Control or CrP-F diets. Pigs fed CrP-F had a lesser (P < .07) percentage of total fat and a greater (P < .07) percentage of muscle than pigs fed the Control or CrP-GF diets. As determined by mechanical-chemical separation, pigs fed CrP-F had a greater (P < .10) percentage of moisture than pigs fed the Control diet and a lesser (P < .10) percentage of fat and a greater (P < .06) percentage of ash than pigs fed the Control or CrP-GF diets. Pigs fed CrP-GF had an increased (P < .04) daily fat accretion compared with pigs fed CrP-F. Sensory and shear force values were not affected by CrP, with the exception that meat from pigs fed CrP-GF had a greater (P < .10) shear force value than meat from pigs fed CrP-F. These results suggest that dietary supplementation of CrP in the finishing phase of pig production may increase muscle and decrease fat deposition; however, not all measures of muscling or fatness were improved by CrP.

Longevity effect of chromium picolinate--'rejuvenation' of hypothalamic function?

Med Hypotheses (ENGLAND) Oct 1994, 43 (4) p253-65

The first rodent longevity study with the insulin-sensitizing nutrient chromium picolinate has reported a dramatic increase in both median and maximal lifespan. Although the observed moderate reductions in serum glucose imply a decreased rate of tissue glycation reactions, it is unlikely that this alone can account for the substantial impact on lifespan; an effect on central neurohormonal regulation can reasonably be suspected. Recent studies highlight the physiological role of insulin as a modulator of brain function. I postulate that aging is associated with a reduction of effective insulin activity in the brain, and this contributes to age-related alterations of hypothalamic functions that result in an 'older' neurohormonal milieu; consistent with this possibility, diabetes leads to changes of hypothalamic regulation analogous to those seen in normal aging. Conversely, promoting brain insulin activity with chromium picolinate may help to maintain the hypothalamus in a more functionally youthful state; increased hypothalamic catecholamine activity, sensitization of insulin-responsive central mechanisms regulating appetite and thermogenesis, and perhaps trophic effects on brain neurons may play a role in this regard. Since both the pineal gland and thymus are dependent on insulin activity, chromium may aid their function as well. Thus, the longevity effect of chromium picolinate may depend primarily on delay or reversal of various age-related changes in the body's hormonal and neural milieu. A more general strategy of hypothalamic 'rejuvenation' is proposed for extending healthful lifespan.

Effects of chromium picolinate on beginning weight training students.

Int J Sport Nutr (UNITED STATES) Dec 1992, 2 (4) p343-50

Changes in body weight (BW), a sum of three body circumferences (sigma C), a sum of three skinfolds (sigma SF), and the one-repetition maximum (1RM) for the squat (SQ) and bench press (BP) were examined in 59 college-age students (37 males [M], 22 females [F]) over a 12-week weight lifting program. Using a double-blind protocol, half of the students were given 200 micrograms/day chromium (Cr) in the form of chromium picolinate (CrPic) while the other half received a placebo (P). Therefore four groups were randomly formed: F-CrPic (n = 12), F-P (n = 10), M-CrPic (n = 18), and M-P (n = 19). All groups had significant increases in sigma C and significant decreases in sigma SF. No treatment effects were seen for the strength measurements, although the males experienced greater absolute increases. The only significant treatment effect found was due to the F-CrPic group gaining more BW (p = 0.0048) than the other three groups. It was concluded that CrPic supplementation had a greater effect on the females than on the males.

Nutritional ergogenic aids: chromium, exercise, and muscle mass.

Int J Sport Nutr (UNITED STATES) Sep 1991, 1 (3) p289-93

Athletes who want to develop muscle mass have sought various ways to reach this goal. We are all too familiar with the abuse of anabolic steroids and growth hormone. Given the concern for such abuses, athletes and coaches are seeking new and safer means to achieve the same end. Within the last couple of years, advertisements for chromium supplements have been prominently displayed in body-building and strength-training magazines. These supplements are purported to be a safe alternative to anabolic steroids and are said to promote an increase in muscle mass. This brief review will focus on the theoretical basis for believing that chromium supplements will increase muscle mass, and on the current research regarding the relationship of chromium and exercise.

Efficacy of chromium supplementation in athletes: emphasis on anabolism

Int J Sport Nutr (UNITED STATES) Jun 1992, 2 (2) p111-22

As the biologically active component of glucose tolerance factor (GTF), the essential trace mineral chromium is now being marked to athletes. GTF potentiates insulin activity and is responsible for normal insulin function. Thus, insulin's effects on carbohydrate, fat, and protein metabolism are dependent upon the maintenance of adequate chromium stores. Due to excessive chromium loss and marginal chromium intake, athletes may have an increased requirement for chromium. Therefore, in some circumstances the dietary supplementation of a chromium compound may be efficacious. The restoration and maintenance of chromium stores via supplementation would promote optimal insulin efficiency, necessary for high-level athletic performance. However, potential anabolic effects of enhanced insulin function would likely be marginal, and reports of short-term anabolic increases from the supplementation of an organic chromium compound need to be confirmed. (87 Refs.)

Chromium and other insulin sensitizers may enhance glucagon secretion: Implications for hypoglycemia and weight control

Medical Hypotheses (United Kingdom), 1996, 46/2 (77-80)

Increased pancreatic beta-cell secretory activity usually is associated with decreased alpha-cell activity; stimulated beta-cells release gamma-aminobutyric acid, which hyperpolarizes alpha-cells, inhibiting glucagon release. Thus, insulin secretion and glucagon secretion are usually inversely coupled. This suggests that chromium and other insulin-sensitizing modalities, by down-regulating beta-cell activity, may increase glucagon secretion. Such an effect might play a role in the documented therapeutic activity of supplemental chromium and biguanides in reactive hypoglycemia, and might also be of benefit to dieters.

Age-related decreases in chromium levels in 51,665 hair, sweat, and serum samples from 40,872 patients - Implications for the prevention of cardiovascular disease and type II diabetes mellitus

Metabolism: Clinical and Experimental (USA), 1997, 46/5 (469-473)

This report shows, for the first time using modern analytical techniques, highly significant age-related decreases in chromium levels in 51,665 hair, sweat, and serum samples obtained from 40,872 patients referred by their physicians to an independent medical research clinic and laboratory (r = -. 598 to -. 762, P < .0001 for all correlations). Males were found to have significantly lower mean chromium levels than females (P < .05 to .0001). There was good correlation between chromium levels in hair, sweat, and serum (r = 536 to .729, P < .0001 for all correlations), indicating that hair and sweat chromium levels are valid additions to the serum levels in assessing chromium status. Chromium measurements in sweat, hair, and serum were performed using graphite furnace atomic absorption spectrophotometry. The influences that age-related decreases in chromium levels might have on increasing the risk to develop age-related impaired glucose metabolism, disordered lipid metabolism, coronary heart disease, arteriosclerosis, and type II diabetes mellitus are outlined, and the role that refined carbohydrates play in the development of compromised chromium status is presented.

Chromium oligopeptide activates insulin receptor tyrosine kinase activity

Biochemistry (USA), 1997, 36/15 (4382-4385)

A possible new mechanism for the amplification of insulin receptor tyrosine kinase activity in response to insulin has been identified. The chromium-containing oligopeptide low molecular weight chromium-binding substance (LMWCr) does not effect the tyrosine protein kinase activity of rat adipocytic membrane fragments in the absence of insulin; however, insulin- stimulated kinase activity in the membrane fragments is increased up to 8- fold by the oligopeptide. Using isolated rat insulin receptor, LMWCr has been shown to bind to insulin-activated insulin receptor with a dissociation constant of circa 250 pM, resulting in the increase of its tyrosine protein kinase activity. The ability of LMWCr to stimulate insulin receptor tyrosine kinase activity is dependent on its chromium content. The results appear to explain the previously poorly understood relationship between chromium and adult-onset diabetes and cardiovascular disease.

Effect of chromium nicotinic acid supplementation on selected cardiovascular disease risk factors

Biological Trace Element Research (USA), 1996, 55/3 (297-305)

The effects of daily supplemental chromium (200 microg) complexed with 1.8 mg nicotinic acid on plasma glucose and lipids, including total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, were assessed in 14 healthy adults and 5 adults with noninsulin-dependent diabetes mellitus (NIDDM) using a double-blind crossover study with 8-wk experimental periods. Eight of the 14 healthy subjects and all 5 subjects with NIDDM also underwent an oral glucose tolerance test with assessment of 90 min postprandial plasma glucose and insulin concentrations. No statistically significant effects of chromium nicotinic acid supplementation were found on plasma insulin, glucose, or lipid concentrations, although chromium nicotinic acid supplementation slightly lowered fasting plasma total and LDL cholesterol, triglycerides, and glucose concentrations, and 90-min postprandial glucose concentrations in individuals with NIDDM.

Chromium picolinate supplementation improves cardiac metabolism, but not myosin isoenzyme distribution in the diabetic heart

Journal of Nutritional Biochemistry (USA), 1996, 7/11 (617-622)

Because chromium (Cr) containing compounds are thought to improve glucose homeostasis, we hypothesized that chromium picolinate (CrP) could partially reverse diabetes-induced damage to cardiac tissue. Young, adult female rats were fed either a basal diet (CONT), a basal diet containing no CrP and made diabetic (DIAB-CONT), or a basal diet containing 600 ng/g of CrP (3 times the suggested daily chromium intake) and made diabetic (DIAB-CrP). Diabetes was induced by a single streptozotocin injection, 55 mg/kg i.p. After 8 weeks animals were sacrificed, hearts removed, and spectrophotometrically analyzed for citrate synthase (CS), hexokinase (HK), and beta hydroxyacyl CoA dehydrogenase activity (HOAD). Cardiac myosin isoenzymes were separated from crude myofibril extracts by PAGE electrophoresis. Diabetes did not alter CS activity relative to the CONT group, but did significantly (P < 0.05) reduce HK and HOAD activity and expression of the high ATPase myosin isoenzyme VI. In contrast, DIAB-CrP animals displayed normal HK activity and greater HOAD activity relative to CONT animals. Surprisingly, the addition of CrP to the diet further reduced expression of the VI myosin isoenzyme. These results demonstrate thet dietary CrP supplementation has diverse effects on the subcellular properties of the diabetic heart. The functional impact of these CrP-induced changes remains to be defined.

Vitamin and mineral deficiencies which may predispose to glucose intolerance of pregnancy

Journal of the American College of Nutrition (USA), 1996, 15/1 (14-20)

There is an increased requirement for nutrients in normal pregnancy, not only due to increased demand, but also increased loss. There is also an increased insulin resistant state during pregnancy mediated by the placental anti-insulin hormones estrogen, progesterone, human somatomammotropin; the pituitary hormone prolactin; and the adrenal hormone, cortisol. If the maternal pancreas cannot increase production of insulin to sustain normoglycemia despite these anti-insulin hormones, gestational diabetes occurs. Gestational diabetes is associated with excessive nutrient losses due to glycosuria. Specific nutrient deficiencies of chromium, magnesium, potassium and pyridoxine may potentiate the tendency towards hyperglycemia in gestational diabetic women because each of these four deficiencies causes impairment of pancreatic insulin production. This review describes the pathophysiology of the hyperglycemia and the nutrient loss in gestational diabetes and further postulates the mechanism whereby vitamin/mineral supplementation may be useful to prevent or ameliorate pregnancy-related glucose intolerance.

[The effect of chromium picolinate on the liver levels of trace elements]

Nutr Hosp (SPAIN) Nov-Dec 1995, 10 (6) p373-6

Chromium picolinate has been implicated as a lipid and carbohydrate reducing agent, and therefore it may be a valuable adjunct to the treatment and prevention of diabetes and heart disease. This compound is inexpensive and apparently nontoxic. In this work, we have determined the influence of its administration (100, 200, 500 micrograms Cr/ml, for 7 and 21 days) on hepatic content of Zn, Mn, Cu and Fe of male Wistar rats. The results show a variation of the levels of these elements after the administration of chromium picolinate, although the differences are only significantly (p < 0.01) in the case of Mn. This influence is dose-dependent, occurring at a decrease of 72% in the group treated with 500 micrograms/ml (Pic-500) respect to the content of control group.

Anabolic effects of insulin on bone suggest a role for chromium picolinate in preservation of bone density.

Med Hypotheses (ENGLAND) Sep 1995, 45 (3) p241-6

Activation of osteoclasts by parathyroid hormone (PTH) is mediated by PTH stimulation of osteoblasts, and is dependent on a PTH-induced rise in protein kinase C activity. Physiological levels of insulin reduce the ability of PTH to activate protein kinase C in osteoblasts, suggesting that insulin may be a physiological antagonist of bone resorption. In addition, insulin is known to promote collagen production by osteoblasts. These findings imply that efficient insulin activity may exert an anabolic effect on bone, and rationalize the many clinical studies demonstrating reduced bone density in Type I diabetes. Recently, the insulin-sensitizing nutrient chromium picolinate has been found to reduce urinary excretion of hydroxyproline and calcium in postmenopausal women, presumably indicative of a reduced rate of bone resorption. This nutrient also raised serum levels of dehydroepiandrosterone-sulfate, which may play a physiological role in the preservation of postmenopausal bone density. The impact of chromium picolinate (alone or in conjunction with calcium and other micronutrients) on bone metabolism and bone density, merits further evaluation in controlled studies. (69 Refs.)

Beneficial effect of chromium supplementation on serum triglyceride levels in NIDDM.

Diabetes Care (UNITED STATES) Dec 1994, 17 (12) p1449-52

OBJECTIVE--To investigate the effect of chromium picolinate supplementation on the lipid profile of the predominantly Hispanic population of non-insulin-dependent diabetes mellitus (NIDDM) patients in San Antonio, Texas.

RESEARCH DESIGN AND METHODSóA prospective, double-blind, placebo-controlled, crossover study was performed on 14 men and 16 women. Initially, each patient was randomly assigned to receive either chromium picolinate or placebo for 2 months. This initial treatment phase was followed by a 2-month washout period. Subjects were then crossed-over and received the alternate capsule for an additional 2 months. Fasting blood glucose, HbA1c, and serum lipids were compared at the end of each treatment phase.

RESULTS--Twenty-eight of the originally enrolled 30 patients completed the study. There were no adverse reactions to chromium reported. There were no differences noted between the control and chromium-treated subjects in glucose control, high-density lipoprotein cholesterol levels, or low-density lipoprotein cholesterol levels. Triglyceride (TG) levels were reduced significantly (17.4%; P < 0.05) during the 2 months of chromium supplementation.

CONCLUSIONS--Ours is the first report of a significant reduction in serum TGs in a group of NIDDM patients treated with chromium. The low cost and excellent safety profile of chromium make it an attractive lipid-lowering agent for this population. Long-term studies are needed to determine if the short-term changes in plasma lipids can be sustained.

Insulin resistance in Mexican Americansóa precursor to obesity and diabetes?

Med Hypotheses (ENGLAND) Oct 1993, 41 (4) p308-15

Mexican Americans appear to have a strong genetic predisposition to insulin resistance, android obesity, and type II diabetes, apparently as a function of Native American genetic heritage. Theoretical considerations suggest that insulin resistance may be a primary factor that plays a causative role in the induction of both obesity and diabetes. Measures which promote optimal insulin sensitivity--chromium picolinate, brewer's yeast, soluble fiber supplements, metformin, very-low-fat diet, exercise training--may have value for preventing, treating, or retarding the onset of obesity and diabetes, and merit clinical evaluation in this regard. Correction of insulin resistance may also lessen cardiovascular risk, in part by reducing LDL cholesterol and improving risk factors associated with Syndrome X. These comments are likely to be valid for other Native American groups at high risk for diabetes.

An expanded concept of "insurance" supplementation--broad-spectrum protection from cardiovascular disease.

Med Hypotheses (ENGLAND) Oct 1981, 7 (10) p1287-1302

The preventive merits of "nutritional insurance" supplementation can be considerably broadened if meaningful doses of nutrients such as mitochondrial "metavitamins" (coenzyme Q, lipoic acid, carnitine), lipotropes, and key essential fatty acids, are included in insurance supplements. From the standpoint of cardiovascular protection, these nutrients, as well as magnesium, selenium, and GTF-chromium, appear to have particular value. Sophisticated insurance supplementation would likely have a favorable impact on many parameters which govern cardiovascular risk--serum lipid profiles, blood pressure, platelet stability, glucose tolerance, bioenergetics, action potential regulation--and as a life-long preventive health strategy might confer substantial benefit.