Analyzing Blood Pressure Ascent during Aging in Non-Diabetics: Focusing on Links to Insulin Resistance and Body Fat Mass.

BACKGROUND: A gradual upward progression of blood pressure (BP) occurs regularly in most humans during aging. This is unfortunate, because it is generally recognized that elevation of BP, even when relatively mild, is eventually detrimental to human health. Accordingly, considerably more understanding of the pathophysiology behind such a phenomenon is important in order to institute the correct remedies. Two components of the ubiquitous metabolic syndrome (MS) with nutritional implications, elevated insulin resistance (IR) and excess body fat mass (FM), are often postulated to be critical driving forces behind the elevated BP that is common with aging. The current study, therefore, focuses on the presence and importance of IR and/or body FM in BP regulation of non-diabetics over the lifespan. METHODOLOGY: In cross sectional analyses, baseline data obtained from healthy, non-diabetic volunteers involved in prior clinical studies were analyzed by examining links between FBG measurements used as a surrogate for IR and body FM through their individual and combined effects on BP. RESULTS: A significant positive correlation was found between FBG and FM and also between each employed individually as independent variables to the dependent BP and heart rate (HR) variables. In volunteers with higher body FM compared to lower, average systolic BP (SBP) values are increased to some extent at the same FBG measurement suggesting that other factors related to FM in addition to IR are the basis for slight pressure differences. Considering quartiles based upon levels of FM and FBG, low FM-low FBG display significantly reduced average SBP, diastolic blood pressure (DBP), and HR compared to the upper FM-FBG quartiles. While readings of FBG and FM display a decline in elderly subjects after age 70 years (aging paradox), such does not occur with SBP. CONCLUSIONS: IR is a major driving force behind BP regulation even in non-diabetics. FM influences BP substantially through its relationship with IR and also via other mechanisms directly linked to FM.

Interplay Between Insulin Resistance and Body Fat Mass in Evolution of Perturbations Linked to the Metabolic Syndrome in Non-Diabetics: Emphasis on Inflammatory Factors.

OBJECTIVE: Many medical disorders comprising the metabolic syndrome (MS) are becoming increasingly prominent worldwide. Accordingly, much more knowledge is necessary to design the best preventive and therapeutic regimens to combat them effectively. This investigation examines the manner and magnitude of any interplay between body fat mass (FM) and insulin resistance (IR) in the evolution of these disorders using fasting blood glucose (FBG) as the latter's surrogate. Two components of MS, IR and body FM, appear to be particularly important because they have been postulated to be primary driving forces behind the other coexisting entities. Whether and how these two components interact is uncertain to some extent. METHOD: Baseline data obtained from healthy, non-diabetic volunteers involved in a number of prior clinical studies were analyzed by examining links between FBG and FM through their individual as well as combined effects on various components of MS. RESULTS: The present study consists of three phases. Phase 1 establishes that FM, similar to FBG, acting as an independent variable correlates significantly with various components of MS. The results even imply that FM offers a better measure for estimating generalized inflammation. Further, implied from findings in phase 2 is that FM influences inflammation not only by further augmenting IR but by additional means as well. In phase 3, where quartiles were developed based upon FBG and FM levels, the combination of relatively low FM/low FBG possesses significantly less proclivity for intensifying metabolic risk factors compared to the high FM/high FBG subset. CONCLUSIONS: Body FM through augmenting IR as well as another mechanism(s) markedly influences optimal fitness in seemingly normal healthy, non-diabetic volunteers. Maintaining the lowest reasonable levels of IR or body FM should bring one closer to long-term, ideal health, but improving the two jointly is an even better option.

Correlating Circulating Vitamin D3 with Aspects of the Metabolic Syndrome and Nonalcoholic Fatty Liver Disease in Healthy Female Volunteers.

Background: Significant inverse correlations between circulating vitamin D3 and the presence and strength of common clinical entities influenced by insulin resistance (IR) have been reported. Among these entities are common maladies such as the metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD). Since hypovitaminosis D3 is considered a common worldwide health disturbance, the consequences emanating from such relationships once soundly established might reasonably be ameliorated by vitamin replacement. Accordingly, a need exists for definitive confirmatory support for the existence of these linkages particularly in ordinary, relatively healthy individuals.Methodology: Many aspects of MS and NAFLD were examined in healthy females via linear regression analyses to determine significant correlations mainly using vitamin D3 and fasting blood glucose (FBG), the latter a surrogate for IR, as independent variables.Results: A descending linear regression between vitamin D3 and FBG did not reach full statistical significance, but a negative correlation of vitamin D3 with HbA1C was statistically significant and that with circulating insulin concentrations showed a downward statistical trend. These findings are consistent with previous ones by others suggesting an ameliorating effect of vitamin D3 on IR. Body weight, body mass index (BMI), and body fat correlated statistically significantly with vitamin D3 levels, as did systolic blood pressure. Again, these correlations were negative instead of positive unlike the case when FBG was the independent variable. The significant negative correlation of ALT with vitamin D3 was also consistent with previous reports that higher circulating vitamin D3 favorably influences the extent and intensity of NAFLD.Conclusions: Employing FBG as a surrogate for IR and ALT for status of NAFLD, linear correlations reasonably suggest that increasing circulating vitamin D3 can favorably influence the initial development of and/or strength of risk factors for MS including NAFLD in relatively fit females.

Reflecting on Concepts Relevant to Contemplating the Relationships Between Glucose-Insulin Perturbations, Nutrition, and Aging.

Background: Medical professionals attribute a crucial role in the development of several age-related, chronic health maladies to glucose-insulin perturbations - particularly, discernible insulin resistance (IR). However, little information is available concerning the degree to which relatively minor changes in IR participate over time in overall aging population, e.g., when circulating glucose and/or insulin concentrations are consistently within the higher end of normally accepted ranges. Objective: Obtaining precise knowledge is important, because proper nutritional management has the distinct capability of ameliorating the consequences. Methods: Five key concepts are suggested to underpin current thinking as to the applicable mechanisms and these are (1) the practical use of fasting blood glucose (FBG) levels as an estimate of IR, (2) the potential role of even slightly aberrant insulin regulation over time in the aging process, (3) the implementation of "continuum of risks" rather than checkpoints in considering prevention, (4) the presence and meaning of an aging paradox discovered in a recent study, and (5) the importance nutritional considerations in the "deadly triangle" as key factors in aging. Conclusions: Maintaining relatively low levels of FBG representing IR during aging via nutritional means has the potential to deliver a longer, more healthful lifespan as well as ameliorate many adverse manifestations of aging.

Circulating ALT Levels in Healthy Volunteers Over Life-Span: Assessing Aging Paradox and Nutritional Implications.

Background: Two facts are generally recognized: (1) development of nonalcoholic fatty liver disease (NAFLD) is consistently linked to insulin resistance which has dietary implications and (2) circulating alanine aminotransferase (ALT) levels are reasonable markers predicting NAFLD status. In a recent cross-sectional study employing nondiabetic subjects, ALT values rose steadily within a normal range early in the life cycle but begin decreasing steadily around age 65 years.Objectives: Because of important nutritional implications, the association between ALT levels and aging in a significantly larger population of healthy volunteers was examined for corroborative purposes. A secondary goal was to gain further knowledge concerning mechanisms behind any age-related decline in ALT activity.Methods: Baseline data from over 10,000 physician-approved, nondiabetic subjects (age 21-84 years) of both genders who had volunteered for previous clinical investigations were assessed.Results: In this cross-sectional examination, the line of best fit (weighted) for average yearly circulating ALT levels displayed an upward surge from ages 21 to 64 years with a discernible steady downward decline around 65 years-mimicking earlier results. Examining linear lines of correlation in the younger and older age groups, the following calculations were determined: a significant positive slope for 21 to 64 years, r = 0.42, n = 44, p < 0.005, and a trending negative slope for 65 and beyond, r = -0.43, n = 20, p < 0.057. Using this same datum base, the correlations between age and fasting blood glucose (FBG) mimicked the ALT results by once more showing a similar upward rise in the younger and a steady decline the older group of volunteers.Conclusions: A paradoxical downward age-related (≥ 65 years) decline of circulating ALT coinciding with a comparable steady decrease in FBG levels was replicated in a larger population of volunteers. The close association of these two chemistries along with other findings suggest that altered glucose-insulin metabolism may participate via "survivor bias" in the ubiquitously found age-related decline of serum ALT-suggesting that nutritional measures could advance optimal health over the life-span.

Discordance Between Body Mass Index (BMI) and a Novel Body Composition Change Index (BCCI) as Outcome Measures in Weight Change Interventions.

OBJECTIVE: A general assumption is that the body mass index (BMI) reflects changes in fat mass (FM). However, it fails to distinguish the type of weight that is lost or gained-fat mass (FM) or fat-free mass (FFM). The BMI treats both changes the same although they have opposite health consequences. The objective of this study was to propose a more precise measure, a body composition change index (BCCI), which distinguishes between changes in FM and FFM, and this study compares it with using the BMI as an outcome measure. METHODS: Data were obtained from 3,870 subjects who had completed dual-energy x-ray absorptiometry (DEXA) total body scans at baseline and end-of-study when participating in a variety of weight-loss interventions. Since height remained constant in this adult cohort, changes in the BMI corresponded with scale weight changes (r = 0.994), allowing BMI changes to be converted to "lbs." to match the statistic used for calculation of the BCCI. The BCCI is calculated by scoring increases in FFM (lbs.) and decreases in FM (lbs.) as positive outcomes and scoring decreases in FFM and increases in FM as negative outcomes. The BCCI is the net sum of these calculations. Differences between scale weight changes and BCCI values were subsequently compared to obtain "discordance scores." RESULTS: Discordance scores ranged from 0.0 lbs. to >30.0 lbs. with a mean absolute value of between the two measures of 7.79 lbs. (99% confidence interval: 7.49-8.10, p <0.00001), SD = 7.4 lbs. Similar discordance scores were also found in subgroups of self-reported gender, ethnicity, and age. CONCLUSIONS: A significant difference of 7.79 lbs. was found between the BCCI and the BMI to evaluate the efficacy of weight loss interventions. If assessing changes in body composition is a treatment goal, use of the BMI could result in significantly erroneous conclusions.

Longitudinal Examination of Links Between Risk Factors for the Metabolic Syndrome and Both Age and Fasting Glucose Levels in Nondiabetic Subjects.

BACKGROUND: Previous evaluations in nondiabetic subjects revealed statistically significant correlations between fasting blood glucose (FBG) levels used as an estimate of insulin resistance and many components constituting the metabolic syndrome. Similar significant correlations were not found employing chronological age as the independent variable in the same nondiabetic individuals. OBJECTIVE: The major purpose here was to replicate as well as corroborate the previous cross-sectional observations, emphasizing results obtained from data collected longitudinally. METHODS: Material was assessed from 99 nondiabetic volunteers who had undergone 2 separate baseline measurements carried out over a minimum of 5 and up to a maximum of 20 years. RESULTS: Findings from the starting baseline measurements mimicked many observations perceived in the earlier published cross-sectional material. The following correlations with elements constituting the metabolic syndrome using FBG as an independent variable were once more statistically significantly positive: scale weight, fat mass, circulating levels of triglycerides and high-sensitivity C-reactive protein (hsCRP). High-density lipoprotein (HDL) cholesterol was once again appropriately significant in a negative direction. In contrast, the same correlations were generally nonsignificant when age replaced FBG as the independent variable. Examining the 2 data sets over the 5-20-year intervals, FBG increased statistically significantly over time. However, the average increase clinically was relatively minor: -92.1 mg/dL ± 1.1 (SEM) vs 95.1 mg/dL ± 1.1 (SEM), p < 0.007. When the actual changes (delta) in the dependent parameters were correlated with the individual passages of time (intervals in years), only downward changes in aspartate aminotransferase (AST) levels were statistically significant. Fat-free mass showed a trend downward, whereas fat mass, trunk fat, and triglycerides merely demonstrated trends upward. CONCLUSION: Current findings gathered over years are consistent with the original hypothesis that maintaining relatively low, stable circulating glucose levels during aging retards the development and intensity of many common manifestations of the metabolic syndrome.

Examining the Relationship Between Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome in Nondiabetic Subjects.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is considered by some to be the hepatic manifestation of the metabolic syndrome (MS). However, others believe NAFLD is a distinct entity that actually initiates MS. Whichever is true, a definite linkage exists between both is generally accepted based upon the frequency of common occurrence and realization that insulin resistance (IR) is and realization that. The objective is to better understand the relationship between NAFLD and MS. Specifically, is there any concrete evidence that development of NAFLD precedes MS or vice versa? Another goal was to better comprehend capabilities of circulating aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and their ratio used commonly for diagnosis of NAFLD. METHODS: Data from 288 participants with fasting blood glucose (FBG) levels below the diabetic level (<125 mg/dL) and AST and ALT values in the normal range (<40 U/L) were examined. Correlations between ALT and AST and their ratio as independent variables with a variety of metabolic parameter were evaluated and compared. RESULTS: Like FBG, many significant positive correlations among glucose-insulin indices, body composition, blood pressure, dyslipidemias, and inflammation were discovered using ALT, and less so with AST, as the independent variable. In some cases, even stronger correlations in a negative direction with IR and MS were found with the ratio AST/ALT. Corroboration occurred when values in the lowest and highest quartiles of ALT and AST/ALT readings showed appropriate statistically significant differences. CONCLUSIONS: The findings here suggest that both NAFLD and the MS very early in development have a common inciting mechanism(s)-most likely IR. Accordingly, the early concurrent temporal results are consistent with the concept that NAFLD is a hepatic manifestation of the IR associated with the MS. They do not exclude the possibility that once some liver functional adjustments take place, several aspects of the MS are bolstered further, perhaps via intensified heightening of IR.

Blood Pressure Regulation: Reviewing Evidence for Interplay Between Common Dietary Sugars and Table Salt.

A popular concept is that the significant global progression in prevalence and intensification of elevated blood pressure (BP) levels is due in part to dietary indiscretions. Excess intake of several food sources causing overweight/obesity plays an important role in BP perturbations. However, certain nutrients are involved in ways other than via body fat accumulation, particularly table salt (sodium chloride) and popular refined carbohydrates like dietary sugars (sucrose, fructose, high fructose corn syrup). In nondiabetics and diabetics, several functions of salt and sugar influence BP and metabolism. For example, salt intake is linked to volume expansion, insulin resistance, and hypertension, while sugar intake is associated with enhanced salt sensitivity via urinary sodium retention, insulin resistance, and hypertension. The key postulate evaluated here is that when two popular nutrients-salt and dietary sugars-are consumed together in adequate amounts, their respective individual BP effects are significantly amplified. In previous laboratory studies, a sugar challenge did not increase BP in the face of marked sodium depletion, and combining sugar and salt challenges caused a synergistic BP elevation. Among examples of amplification on the clinical side, the greatest increases in BP following sugar challenges were seen in diabetic subjects having the highest sodium excretion. Interplay between table salt and common dietary sugars in BP regulation is a reasonable postulate and should be carefully considered when developing optimal prevention and treatment regimens to ameliorate the worldwide crisis arising from harmful elevated BP levels.

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

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.

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.

Safety and Efficacy of Banaba-Moringa oleifera-Green Coffee Bean Extracts and Vitamin D3 in a Sustained Release Weight Management Supplement.

This 60-day, 30-subject pilot study examined a novel combination of ingredients in a unique sustained release (Carbopol matrix) tablet consumed twice daily. The product was composed of extracts of banaba leaf, green coffee bean, and Moringa oleifera leaf and vitamin D3. Safety was assessed using a 45-measurement blood chemistry panel, an 86-item self-reported Quality of Life Inventory, bone mineral density, and cardiovascular changes. Efficacy was assessed by calculating a body composition improvement index (BCI) based on changes in dual energy X-ray absorptiometry measured fat mass (FM) and fat-free mass (FFM) as well as between the study group (SG) and a historical placebo group. No changes occurred in any blood chemistry measurements. Positive changes were found in the Quality of Life (QOL) inventory composite scores. No adverse effects were observed. Decreases occurred in FM (p = 0.004) and increases in FFM (p = 0.009). Relative to the historical placebo group, the SG lost more FM (p < 0.0001), gained more FFM (p = <0.0001), and had a negative BCI of -2.7 lb. compared with a positive BCI in the SG of 3.4 lb., a 6.1 discordance (p = 0.0009). The data support the safety and efficacy of this unique product and demonstrate importance of using changes in body composition versus scale weight and BMI.

Konjac Glucomannan Dietary Supplementation Causes Significant Fat Loss in Compliant Overweight Adults.

OBJECTIVES: Changes in body composition and blood chemistries between overweight adult subjects receiving a supplement containing either 3 g of konjac glucomannan/300 mg calcium carbonate or a placebo containing only 300 mg of calcium carbonate were compared as the primary objective. A secondary objective was to compare outcome differences between compliant and partially compliant subjects. METHODS: A total of 83 overweight adults (66 women and 17 men) completed a randomized, double-blind, placebo-controlled protocol in which they received either a glucomannan or placebo supplement for 60 days. Dual-energy x-ray absorptiometry (DEXA) total body scans and a 42-measurement blood test were completed at baseline and 60 days later. Compliance was assessed by rating self-reports of (1) how many tablets were taken, (2) adherence to taking the tablets 30 minutes before eating, and (3) a sum of the ratings for (1) and (2). An anonymous poststudy questionnaire and telephone calls were also completed by 80 (96%) of the participants who were used as the study cohort. RESULTS: No statistically significant differences were found between the groups on changes from baseline on the DEXA and blood tests. However, when subjects were classified as either compliant or partially compliant using the compliance measures, statistically significant reductions in scale weight, percentage body fat, fat mass, total cholesterol, and low-density lipoprotein (LDL) cholesterol were found in the glucomannan group compared to the placebo group. CONCLUSIONS: This study supports the efficacy glucomannan supplementation to reduce body weight, body fat, and circulating cholesterol levels without the concomitant loss of lean mass and bone density often associated with weight loss. However, these positive outcomes were not observable until corrections for compliance were applied.

Probing the Relationship Between Declining Renal Glomerular Filtration Over the Life Span and General Biological Aging: Does the Former Provide Means to Estimate the Latter?

While a consistent, gradual decline in the renal glomerular filtration rate (GFR) is a characteristic occurrence over the human life span, the exact pathophysiology behind this event remains unresolved. Evidence to date suggests that the endogenous glucose-insulin system could be involved at some level. Diabetic-induced nephropathy, one of the most prevalent chronic renal diseases, is closely linked to a severe form of insulin resistance (IR). Nevertheless, it is less certain that the ubiquitous milder forms of IR in nondiabetics ascribed customarily to routine, poor choices in diet and exercise management can over time diminish GFR and adversely influence other renal functions to any perceptible extent.Baseline data for cross-sectional analyses were obtained from a cohort of healthy, nondiabetic volunteers (fasting blood glucose [FBG] ≤ 125 mg/dL) involved in prior clinical studies. Slope-based rather than threshold analyses were mainly employed. These measurements were applied for the most part to correlate age, FBG levels used as an estimate of IR activity, and systolic blood pressure (SBP) to a variety of metabolic parameters during aging with a primary focus on GFR.Considering cause and effect, FBG and SBP correlate positively with the diminishing GFR over a major part of the life span. The decline in GFR begins somewhere around the mid-20s and coincides with key temporal increases in FBG and SBP levels.A close time-based setting suggests that IR plays a prominent role in the declining GFR that occurs over the life span. This is perhaps due in part through deleterious effects of rising levels of insulin, glucose, and SBP individually or combined that are also popular proposed causative factors for human aging in general. On the philosophical side, the latter fact suggests that the declining GFR might provide a practical way to estimate the rate of overall human biological aging.

A review of the efficacy and safety of banaba (Lagerstroemia speciosa L.) and corosolic acid.

Banaba (Lagerstroemia speciosa L.) extracts have been used for many years in folk medicine to treat diabetes, with the first published research study being reported in 1940. This review summarizes the current literature regarding banaba and its constituents. The hypoglycemic effects of banaba have been attributed to both corosolic acid as well as ellagitannins. Studies have been conducted in various animal models, human subjects and in vitro systems using water soluble banaba leaf extracts, corosolic acid-standardized extracts, and purified corosolic acid and ellagitannins. Pure corosolic acid has been reported to decrease blood sugar levels within 60 min in human subjects. Corosolic acid also exhibits antihyperlipidemic, antioxidant, antiinflammatory, antifungal, antiviral, antineoplastic and osteoblastic activities. The beneficial effects of banaba and corosolic acid with respect to various aspects of glucose and lipid metabolism appear to involve multiple mechanisms, including enhanced cellular uptake of glucose, impaired hydrolysis of sucrose and starches, decreased gluconeogenesis and the regulation of lipid metabolism. These effects may be mediated by PPAR, MAP K, NF-κB and other signal transduction factors. No adverse effects have been observed or reported in animal studies or controlled human clinical trials. Banaba extract, corosolic acid and other constituents may be beneficial in addressing the symptoms associated with metabolic syndrome, as well as offering other health benefits.

Assessing Genders Separately in Nondiabetic Persons Regarding Links Between Insulin Resistance and Fat Mass With Elements Related to the Metabolic Syndrome.

OBJECTIVE: Initial results gathered from previously published observations dealing with nondiabetic volunteers reveal that both the fasting blood glucose (FBG) level employed as a surrogate for insulin resistance (IR) and the amount of body fat mass (FM) correlate significantly with the strength and pathological direction of many harmful elements making up the metabolic syndrome (MS). These initial results were obtained using combined data from both females and males. How the two markers correlate with specific metabolic parameters in each gender separately was not established. METHOD: Baseline data from more than 700 volunteers were examined mainly using correlations to compare whether the breadth of IR estimated by FBG levels and/or the accumulation of body FM on the early development and progression of many chronic metabolic derangements differ to any meaningful extent between nondiabetic females and males. RESULTS: The following significant positive correlations were found in the data on females employing either FBG or FM as independent variables regarding development of elements associated with MS: in body composition (scale weight, fat free mass [FFM]); in blood chemistries (triglycerides, high-sensitivity C-reactive protein [hsCRP], alanine aminotransferase [ALT]); and in blood counts (white blood cells [WBC], neutrophils). Also consistent with MS, high-density lipoprotein cholesterol levels declined significantly. In males, findings with FBG as the independent variable differ from females in some respects. These major exceptions are lack of significant correlations with FFM and high-density lipoprotein cholesterol as well as a weaker link with ALT. Despite a positive hsCRP linkage, a poorer response of WBC and neutrophils appeared in males when correlations were made. The latter disassociations disappeared when FM replaced FBG as the independent variable. CONCLUSIONS: Progression of many chronic metabolic derangements differ only slightly in females and males.

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

BACKGROUND: A 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. METHODS: To 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. RESULTS: In 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. CONCLUSIONS: As compared to a placebo control, consumption of a LA-Cr formula after a 70-gram sucrose challenge was significantly more effective in safely lowering both circulating glucose and insulin levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01107431.

Changes in total body bone mineral density following a common bone health plan with two versions of a unique bone health supplement: a comparative effectiveness research study.

BACKGROUND: The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans that: (1) improve nutrition, (2) increase health literacy and, (3) increase physical activity. This study is a response to this call to action. METHODS: After signing an informed consent, 158 adults agreed to follow an open-label bone-health plan for six months after taking a DXA test of bone density, a 43-chemistry blood test panel and a quality of life inventory (AlgaeCal 1). Two weeks after the last subject completed, a second group of 58 was enrolled and followed the identical plan, but with a different bone-health supplement (AlgaeCal 2). RESULTS: There were no significant differences between the two groups in baseline bone mineral density (BMD) or in variables related to BMD (age, sex, weight, percent body fat, fat mass, or fat-free mass). In both groups, no significant differences in BMD or related variables were found between volunteers and non-volunteers or between those who completed per protocol and those who were lost to attrition.Both groups experienced a significant positive mean annualized percent change (MAPC) in BMD compared to expectation [AlgaeCal 1: 1.15%, p = 0.001; AlgaeCal 2: 2.79%, p = 0.001]. Both groups experienced a positive MAPC compared to baseline, but only AlgaeCal 2 experienced a significant change [AlgaeCal 1: 0.48%, p = 0.14; AlgaeCal 2: 2.18%, p < 0.001]. The MAPC in AlgaeCal 2 was significantly greater than that in AlgaeCal 1 (p = 0.005). The MAPC contrast between compliant and partially compliant subjects was significant for both plans (p = 0.001 and p = 0.003 respectively). No clinically significant changes in a 43-panel blood chemistry test were found nor were there any changes in self-reported quality of life in either group. CONCLUSIONS: Following The Plan for six months with either version of the bone health supplement was associated with significant increases in BMD as compared to expected and, in AlgaeCal 2, the increase from baseline was significantly greater than the increase from baseline in AlgaeCal 1. Increased compliance was associated with greater increases in BMD in both groups. No adverse effects were reported in either group. TRIAL REGISTRATION: ClinicalTrials.gov NCT01114685.

A comparative effectiveness study of bone density changes in women over 40 following three bone health plans containing variations of the same novel plant-sourced calcium.

BACKGROUND: The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans incorporating components of (1) improved nutrition, (2) increased health literacy, and (3) increased physical activity. OBJECTIVE: To conduct a Comparative Effectiveness Research (CER) study comparing changes in bone mineral density in healthy women over-40 with above-average compliance when following one of three bone health Plans incorporating the SG's three components. METHODS: Using an open-label sequential design, 414 females over 40 years of age were tested, 176 of whom agreed to participate and follow one of three different bone-health programs. One Plan contained a bone-health supplement with 1,000 IUs of vitamin D(3 )and 750 mg of a plant-sourced form of calcium for one year. The other two Plans contained the same plant form of calcium, but with differing amounts of vitamin D(3) and other added bone health ingredients along with components designed to increase physical activity and health literacy. Each group completed the same baseline and ending DXA bone density scans, 43-chemistry blood test panels, and 84-item Quality of Life Inventory (QOL). Changes for all subjects were annualized as percent change in BMD from baseline. Using self-reports of adherence, subjects were rank-ordered and dichotomized as "compliant" or "partially compliant" based on the median rating. Comparisons were also made between the treatment groups and two theoretical age-adjusted expected groups: a non-intervention group and a group derived from a review of previously published studies on non-plant sources of calcium. RESULTS: There were no significant differences in baseline BMD between those who volunteered versus those who did not and between those who completed per protocol (PP) and those who were lost to attrition. Among subjects completing per protocol, there were no significant differences between the three groups on baseline measurements of BMD, weight, age, body fat and fat-free mass suggesting that the treatment groups were statistically similar at baseline. In all three treatment groups subjects with above average compliance had significantly greater increases in BMD as compared to the two expected-change reference groups. The group following the most nutritionally comprehensive Plan outperformed the other two groups. For all three groups, there were no statistically significant differences between baseline and ending blood chemistry tests or the QOL self-reports. CONCLUSIONS: The increases in BMD found in all three treatment groups in this CER stand in marked contrast to previous studies reporting that interventions with calcium and vitamin D(3) reduce age-related losses of BMD, but do not increase BMD. Increased compliance resulted in increased BMD levels. No adverse effects were found in the blood chemistry tests, self-reported quality of life and daily tracking reports. The Plans tested suggest a significant improvement over the traditional calcium and vitamin D(3) standard of care.

Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes.

Bitter orange (Citrus aurantium) extract is widely used in dietary supplements for weight management and sports performance. Its primary protoalkaloid is p-synephrine. Most studies involving bitter orange extract and p-synephrine have used products with multiple ingredients. The current study assessed the thermogenic effects of p-synephrine alone and in conjunction with the flavonoids naringin and hesperidin in a double-blinded, randomized, placebo-controlled protocol with 10 subjects per treatment group. Resting metabolic rates (RMR), blood pressure, heart rates and a self-reported rating scale were determined at baseline and 75 min after oral ingestion of the test products in V-8 juice. A decrease of 30 kcal occurred in the placebo control relative to baseline. The group receiving p-synephrine (50 mg) alone exhibited a 65 kcal increase in RMR as compared to the placebo group. The consumption of 600 mg naringin with 50 mg p-synephrine resulted in a 129 kcal increase in RMR relative to the placebo group. In the group receiving 100 mg hesperidin in addition to the 50 mg p-synephrine plus 600 mg naringin, the RMR increased by 183 kcal, an increase that was statistically significant with respect to the placebo control (p<0.02). However, consuming 1000 mg hesperidin with 50 mg p-synephrine plus 600 mg naringin resulted in a RMR that was only 79 kcal greater than the placebo group. None of the treatment groups exhibited changes in heart rate or blood pressure relative to the control group, nor there were no differences in self-reported ratings of 10 symptoms between the treatment groups and the control group. This unusual finding of a thermogenic combination of ingredients that elevated metabolic rates without corresponding elevations in blood pressure and heart-rates warrants longer term studies to assess its value as a weight control agent.