Nicholas V. Perricone

Comparing metabolic effects of six different commercial trivalent chromium compounds.

Recent reports provide cogent evidence that the average individual becomes chromium deficient with age. Unfortunately, chromium deficiency is strongly associated with many aspects of the Metabolic Syndrome, including insulin resistance and type 2 diabetes. Since replacement of chromium, per os, often ameliorates many deleterious manifestations associated with insulin resistance and diabetes, it is not surprising that many different, commercial trivalent chromium compounds are available on the market. However, previous reports have shown that the form of trivalent chromium (negative charges) can influence effectiveness markedly. We compared various commercial forms of trivalent chromium commonly used alone or in formulations, to examine whether they are equally effective and non-toxic. In the first study, five different chromium products were examined - citrate, amino acid chelate (AAC), chelavite, polynicotinate (NBC), and nicotinate. In the second study, effects of NBC and picolinate were assessed. Results demonstrated that only chelavite and NBC improved insulin sensitivity, and only NBC decreased systolic blood pressure (SBP) significantly. In the second study, both picolinate and NBC significantly decreased SBP compared to control. NBC and picolinate decreased malonyldialdehyde concentrations (free radical formation) and DNA fragmentation in hepatic and renal tissues. No evidence of adverse effects was noted with any of the compounds tested. In conclusion, while all the trivalent chromium compounds tested seem safe, only three enhanced insulin sensitivity (NBC, chelavite, and picolinate) and only two decreased SBP significantly (NBC and picolinate). Furthermore, both NBC and picolinate were protective in lessening free radical formation and DNA damage in the liver and kidneys.

A combination of l-arabinose and chromium lowers circulating glucose and insulin levels after an acute oral sucrose challenge

BackgroundA growing body of research suggests that elevated circulating levels of glucose and insulin accelerate risk factors for a wide range of disorders. Low-risk interventions that could suppress glucose without raising insulin levels could offer significant long-term health benefits.MethodsTo address this issue, we conducted two sequential studies, the first with two phases. In the first phase of Study 1, baseline fasting blood glucose was measured in 20 subjects who consumed 70 grams of sucrose in water and subsequently completed capillary glucose measurements at 30, 45, 60 and 90 minutes (Control). On day-2 the same procedure was followed, but with subjects simultaneously consuming a novel formula containing l-arabinose and a trivalent patented food source of chromium (LA-Cr) (Treatment). The presence or absence of the LA-Cr was blinded to the subjects and testing technician. Comparisons of changes from baseline were made between Control and Treatment periods. In the second phase of Study 1, 10 subjects selected from the original 20 competed baseline measures of body composition (DXA), a 43-blood chemistry panel and a Quality of Life Inventory. These subjects subsequently took LA-Cr daily for 4 weeks completing daily tracking forms and repeating the baseline capillary tests at the end of each of the four weeks. In Study 2, the same procedures used in the first phase were repeated for 50 subjects, but with added circulating insulin measurements at 30 and 60 minutes from baseline.ResultsIn both studies, as compared to Control, the Treatment group had significantly lower glucose responses for all four testing times (AUC = P < 0.0001). Additionally, the Treatment was significantly more effective in lowering circulating insulin after 60 minutes from baseline (AUC = P = < 0.01). No adverse effects were found after acute sucrose challenge or in those who consumed LA-Cr daily for four weeks.ConclusionsAs compared to a placebo control, consumption of a LA-Cr formula after a 70-gram sucrose challenge was effective in safely lowering both circulating glucose and insulin levels.Trial RegistrationClinical Trials.gov, NCT0110743

Blood pressure lowering effects of niacin-bound chromium(III) (NBC) in sucrose-fed rats : Renin-angiotensin system

Excessive intake of sugars significantly elevates systolic blood pressure (SBP) in susceptible rats. Although the exact pathological mechanisms behind sugar-induced hypertension are uncertain and may be multiple, disturbances in the renin-angiotensin system (RAS) manifested by elevated circulating levels of angiotensin-2 may be involved. We attempted to confirm that the RAS was significantly involved in sugar-induced BP elevations and examined whether the ability of niacin-bound chromium (NBC) to ameliorate sugar-induced SBP elevations was due, at least in part, through effects on the RAS. Initially, 40 mature Sprague-Dawley rats (SD), male and female, were involved in the study comparing two methods to estimate rat blood pressure indirectly. Then 13 were selected to examine the effects of NBC on the RAS. All rats eventually ingested a diet heavy in sucrose (30%w/w). In addition to blood pressure readings, the following procedures were implemented: insulin and losartan challenges, evaluation of serum ACE activity, measurement of serum angiotensin-2 levels, blood chemistries, and LNAME challenge. While dietary sucrose raised SBP significantly in control, adding NBC to the treatment group lowered it back toward baseline. The treatment group was more sensitive to exogenous insulin challenge and showed decreased activity of the RAS estimated by less lowering of SBP after losartan challenge, decreased serum ACE (angiotensin-converting enzyme) activity, and lower levels of circulating angiotensin-2. The former two parameters showed statistical significance; and the latter, a trend toward statistical significance. A separate group receiving captopril served as a positive control and showed decreased ACE activity and circulating levels of angiotensin-2 compared to the control group. Our data suggest that the RAS plays a significant role in sugar-induced hypertension and that NBC lowers SBP, at least in part, via actions on the RAS. Other findings suggest that the NO system is important in sucrose-induced BP elevations as well.

Comparing Effects of Carbohydrate (CHO) Blockers and Trivalent Chromium on CHO-Induced Insulin Resistance and Elevated Blood Pressure in Rats

Objective: In Sprague-Dawley rats (SD), we compared two categories of natural dietary supplements that influence carbohydrate (CHO) metabolism via different basic mechanisms to ameliorate insulin resistance (IR) and elevated blood pressure (BP) associated with heavy sugar/starch consumption. Two dietary supplements (bean extract and l-arabinose) are often referred to as carb blockers (CBs), because they slow the gastrointestinal absorption of CHO. Trivalent chromium (CR) falls into a group of so-called insulin sensitizers, because its major effect is to enhance peripheral insulin sensitivity. Method: We divided 48 mature male SD into 4 groups of 12. The first group received powdered baseline diet alone (Con). The remaining 3 SD groups (groups 2–4) ingested regular rat chow containing 20% w/w sucrose and 20% w/w rice starch. The second group received only this CHO-enriched chow. To the high-CHO diets of the remaining two groups, either CB to slow CHO absorption (CHO + CB) (group 3) or an insulin sensitizer, trivalent CR (CHO + CR; group 4), was added. Results: Compared to Con group 1, adding high CHO content to the diet of group 2 significantly increased circulating glucose levels and systolic BP (SBP). Addition of CB or CR to the feed of groups 3 and 4 overcame the perturbations that occurred with high CHO challenge in group 2; that is, they lowered circulating glucose concentrations to Con levels, enhanced response to exogenous insulin, and overcame the gradual elevation of SBP. Compared to group 2, the two treatment groups (3 and 4) also showed decreased renin–angiotensin system activity, decreased serum angiotensin-converting enzyme activity, and enhanced nitric oxide activity. Conclusions: Our data indicate that high doses of CB and CR, despite their different mechanisms of action, can completely overcome CHO-induced IR and BP elevations. The data further suggest that CB and CR affect only the changes brought on by heavy CHO ingestion, because IR and SBP in groups 3 and 4 mirrored Con values (group 1), never producing values lower than baseline. Earlier use of CB and CR in the life cycle appears more effective in overcoming CHO-induced perturbations than later use.

In Vitro and In Vivo Effects of Two Coconut Oils in Comparison to Monolaurin on Staphylococcus aureus: Rodent Studies

Since monolaurin, a monoglyceride formed in the human body in small quantities, has proven effective both in vitro and in vivo against certain strains of Staphylococcus aureus, an important question arises whether consuming a substance high in lauric acid content, such as coconut oil could increase intrinsic monolaurin production to levels that would be successful in overcoming staphylococcal and other microbial invaders. Both a cup plate method and a microdilution broth culture system were employed to test bacteriostatic and bactericidal effects of the test agents in vitro. To test effectiveness in vivo, female C3H/he mice (10-12 per group) were orally administered sterile saline (regular control), vancomycin (positive control), aqueous monolaurin, or two varieties of coconut oil (refined, bleached, deodorized coconut oil and virgin coconut oil) for 1 week before bacterial challenge and 30 days after. A final group received both monolaurin and vancomycin. In contrast to monolaurin, the coconut oils did not show bactericidal activity in vitro. In vivo, the groups receiving vancomycin, monolaurin, or the combination showed some protection--50-70% survival, whereas the protection from the coconut oils were virtually the same as control--0-16% survival. Although we did not find that the two coconut oils are helpful to overcome S. aureus infections, we corroborated earlier studies showing the ability of monolaurin to do such.

Fraction SX of Maitake Mushroom Favorably Influences Blood Glucose Levels and Blood Pressure in Streptozotocin-Induced Diabetic Rats

We assessed whether fraction SX derived from maitake mushroom could play a beneficial role in the treatment of a laboratory model of type-1 diabetes by decreasing circulating glucose levels and lowering blood pressure (BP). We injected 50 mg/kg body weight (BW) streptozotocin (STZ) intraperitoneally (i.p.) into 48 male Sprague-Dawley rats (SD) to produce a laboratory model of type-1 diabetes. SD were divided into four groups of 12 SD. A control group ate straight pulverized rat chow. To three treatment groups, we added into the pulverized rat chow: gliclazide (10 mg/kg), pioglitazone (10-30 mg/kg), or maitake SX (2.5 g/kg). In addition to measuring BW, circulating glucose level, and BP, the following procedures were also carried out: insulin challenge (insulin sensitivity), losartan challenge (renin-angiotensin system activity), Nw-nitro-L arginine-methyl ester hydrochloride (LNAME) challenge (nitric oxide [NO] system activity), and evaluation of serum angiotensin converting enzyme (ACE) activity. All treatments compared with control generally decreased circulating glucose levels, but only the maitake SX consistently enhanced measured insulin sensitivity. We found that maitake SX could significantly lower systolic blood pressure (SBP) in diabetic SD. In general, only SD receiving maitake SX, not the two drugs, showed decreased activity of the renin-angiotensin system and increased NO system activity compared with control under the conditions examined. Our results suggest that maitake SX may be useful for treating perturbations in glucose-insulin metabolism and elevated BP in type-1 diabetes.

General Lack of Correlations between Age and Signs of the Metabolic Syndrome in Subjects with Non-diabetic Fasting Glucose Values

ABSTRACT Background: Insulin resistance and advancing age are well-recognized risk factors for metabolic syndrome. Recent reports indicate that fasting glucose levels in non-diabetic patients correlate appropriately with the development of certain elements in metabolic syndrome, which suggest a cause–effect relationship with insulin resistance. Objective: The present investigation assessed whether a significant association exists between chronological age and various elements of metabolic syndrome in this same group of subjects possessing non-diabetic fasting glucose levels. Methods: Baseline data were taken from 288 subjects (age 17–87 years) with fasting glucose levels ≤ 125 mg/dl. Correlations between chronological age and different metabolic parameters were assessed to determine any statistically significant relationships and compare these with previously demonstrated metabolic parameters. Results: With the exception of systolic blood pressure, the following correlations between age and components of metabolic syndrome were not significant or even significant in the opposite direction compared to those found in the same population using fasting glucose as the independent variable: body weight, body fat, diastolic blood pressure, white blood cell count (WBC)/neutrophil count, and circulating levels of insulin, high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Although systolic blood pressure still increased, it was to a lesser extent than might be expected. Conclusions: In the present investigation, a cross-sectional analysis was carried out over a wide age range of subjects. It is noteworthy that fasting glucose levels and the other major elements of metabolic syndrome did not change significantly with advancing age. These results demonstrate that decreasing insulin resistance and fasting glucose levels may be an important way to overcome the adverse effects and perturbations of advancing age-induced consequences of metabolic syndrome.

Influence of gel and powdered formulations of coenzyme Q10 on metabolic parameters in rats

The healthful benefits of two commercially available formulations of coenzyme Q10 (Co Q10), one in gel and the other in a powdered form, on a variety of metabolic parameters in Sprague–Dawley rats (SD) were compared to control. The principal metabolic parameters examined were systolic blood pressure (SBP), DNA fragmentation, and free radical formation in hepatic and renal tissues. Compared to control, the powdered formulation significantly decreased SBP in the normotensive SD, whereas both commercial formulations lowered hepatic and renal DNA fragmentation and free radical formation. The gel-formulation lowered hepatic DNA fragmentation more than the powdered-formulation. In conclusion, both gel- and powdered-formulations of Co Q10 significantly influenced the metabolic parameters assessed in a favorable fashion, with the powdered-formulation more effective on SBP and the gel-formulation more effective on overcoming hepatic DNA fragmentation. From the data, we conclude that the choice of the formulation containing Co Q10 to be used should be based on the desired healthful benefits.

A 7-Year Longitudinal Trial of the Safety and Efficacy of a Vitamin/Mineral Enhanced Plant-Sourced Calcium Supplement.

Objectives: The objective of this study was to examine the safety and efficacy of a vitamin–mineral enhanced plant-sourced calcium AlgaeCal calcium (AC) in female consumers who had taken the supplement from 1 to 7 years. Methods: Consumers who had completed at least one dual-energy x-ray absorptiometry (DEXA) bone mineral density (BMD) scan (N = 172) and/or blood chemistry test (N = 30) and purchased AC from 1 to 7 years were contacted and offered complimentary repeat tests. Safety and efficacy were examined by annualized changes in a 45-measurement blood chemistry panel and changes in BMD. Results: No adverse effects or safety concerns were found in any of the annualized within-group annualized changes in the 45 blood chemistries or in between-group changes in a similar control group (n = 5070) who completed the same measurements. With regard to BMD, consistent and statistically significant within-group increases were found for the 7-year study period and when compared to expected BMD changes in 3 large databases or the combination (N = 25,885) of the 3 databases. Data from this study suggest that AC supplement was associated with a significant annualized and linear increase in BMD of 1.04% per year, 7.3% over the 7-year study period. These results stand in marked contrast to normative or expected changes of −0.4%/y from 3 different databases or in a combination of all 3 databases (N = 16,289). Conclusions: No evidence was found in cardiovascular risk as measured by adverse changes in blood lipids, nor was any evidence found of a diminished efficacy over the 7-year study period because gains in BMD were consistent and linear over the 7-year study period, averaging 1.04% per year over the 7-year study. The results are also consistent with earlier short-term studies suggesting that this supplement can facilitate significant increases in total body BMD in contrast to studies suggesting that calcium supplements can only slow down age-related declines in BMD.