Salba-chia (Salvia hispanica L.) in the treatment of overweight and obese patients with type 2 diabetes: A double-blind randomized controlled trial.

BACKGROUND AND AIM: Preliminary findings indicate that consumption of Salba-chia (Salvia hispanica L.), an ancient seed, improves management of type 2 diabetes and suppresses appetite. The aim of this study was to assesse the effect of Salba-chia on body weight, visceral obesity and obesity-related risk factors in overweight and obese adults with type 2 diabetes. METHODS: A double-blind, randomized, controlled trial with two parallel groups involved 77 overweight or obese patients with type 2 diabetes (HbA1c: 6.5-8.0%; BMI: 25-40 kg/m2). Both groups followed a 6-month calorie-restricted diet; one group received 30 g/1000 kcal/day of Salba-chia, the other 36 g/1000 kcal/day of an oat bran-based control. Primary endpoint was change in body weight over 6-months. Secondary endpoints included changes in waist circumference, body composition, glycemic control, C-reactive protein, and obesity-related satiety hormones. RESULTS: At 6-months, participants on Salba-chia had lost more weight than those on control (1.9 ± 0.5 kg and 0.3 ± 0.4 kg, respectively; P = 0.020), accompanied by a greater reduction in waist circumference (3.5 ± 0.7 cm and 1.1 ± 0.7 cm, respectively; P = 0.027). C-reactive protein was reduced by 1.1 ± 0.5 mg/L (39 ± 17%) on Salba-chia, compared to 0.2 ± 0.4 mg/L (7 ± 20%) on control (P = 0.045). Plasma adiponectin on the test intervention increased by 6.5 ± 0.7%, with no change observed on control (P = 0.022). CONCLUSIONS: The results of this study, support the beneficial role of Salba-chia seeds in promoting weight loss and improvements of obesity related risk factors, while maintaining good glycemic control. Supplementation of Salba-chia may be a useful dietary addition to conventional therapy in the management of obesity in diabetes. REGISTRATION: clinicaltrials.gov identifier: NCT01403571.

Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial.

STUDY DESIGN: Randomized controlled trial with single-blinded primary outcome assessment. OBJECTIVES: To determine the efficacy and safety of autologous incubated macrophage treatment for improving neurological outcome in patients with acute, complete spinal cord injury (SCI). SETTING: Six SCI treatment centers in the United States and Israel. METHODS: Participants with traumatic complete SCI between C5 motor and T11 neurological levels who could receive macrophage therapy within 14 days of injury were randomly assigned in a 2:1 ratio to the treatment (autologous incubated macrophages) or control (standard of care) groups. Treatment group participants underwent macrophage injection into the caudal boundary of the SCI. The primary outcome measure was American Spinal Injury Association (ASIA) Impairment Scale (AIS) A-B or better at ≥6 months. Safety was assessed by analysis of adverse events (AEs). RESULTS: Of 43 participants (26 treatment, 17 control) having sufficient data for efficacy analysis, AIS A to B or better conversion was experienced by 7 treatment and 10 control participants; AIS A to C conversion was experienced by 2 treatment and 2 control participants. The primary outcome analysis for subjects with at least 6 months follow-up showed a trend favoring the control group that did not achieve statistical significance (P=0.053). The mean number of AEs reported per participant was not significantly different between the groups (P=0.942). CONCLUSION: The analysis failed to show a significant difference in primary outcome between the two groups. The study results do not support treatment of acute complete SCI with autologous incubated macrophage therapy as specified in this protocol.

A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics.

STUDY DESIGN: Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). OBJECTIVES: Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. SETTING: Subjects were recruited to one of six international study centers. METHODS: Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. RESULTS: Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. CONCLUSION: The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

Viscosity of fiber preloads affects food intake in adolescents.

BACKGROUND AND AIMS: Dietary fiber that develops viscosity in the gastrointestinal tract is capable of addressing various aspects of food intake control. The aim of this study was to assess subsequent food intake and appetite in relation to the level of viscosity following three liquid preloads each containing 5 g of either a high (novel viscous polysaccharide; NVP), medium (glucomannan; GLM), or low (cellulose; CE) viscosity fiber. METHODS AND RESULTS: In this double-blind, randomized, controlled and crossover trial, 31 healthy weight adolescents (25 F:6 M; age 16.1+/-0.6 years; BMI 22.2+/-3.7 kg/m(2)) consumed one of the three preloads 90 min prior to an ad libitum pizza meal. Preloads were identical in taste, appearance, nutrient content and quantity of fiber, but different in their viscosities (10, 410, and 700 poise for CE, GLM, and NVP, respectively). Pizza intake was significantly lower (p=0.008) after consumption of the high-viscosity NVP (278+/-111 g) compared to the medium-viscosity GLM (313+/-123 g) and low-viscosity CE (316+/-138 g) preloads, with no difference between the GLM and CE preloads. Appetite scores, physical symptoms and 24-h intake did not differ among treatment groups. CONCLUSION: A highly viscous NVP preload leads to reduced subsequent food intake, in terms of both gram weight and calories, in healthy weight adolescents. This study provides preliminary evidence of an independent contribution of viscosity on food intake and may form a basis for further studies on factors influencing food intake in adolescents.

Comparison of flax (Linum usitatissimum) and Salba-chia (Salvia hispanica L.) seeds on postprandial glycemia and satiety in healthy individuals: a randomized, controlled, crossover study.

BACKGROUND/OBJECTIVES: Flax and Salba-chia seeds have risen in popularity owing to their favorable nutrient composition, including a high fiber content. Despite having comparable nutritional profiles, preliminary observations suggest differences in gelling properties, an attribute that may alter the kinetics of food digestion. Thus, we compared the effect of two seeds on postprandial glycemia and satiety scores. SUBJECTS/METHODS: Fifteen healthy participants (M/F: 5/10; age: 23.9±3 years; BMI: 22.2±0.8 kg/m2) were randomized to receive a 50 g glucose challenge, alone or supplemented with either 25 g ground Salba-chia or 31.5 g flax, on three separate occasions. Blood glucose samples and satiety ratings were collected at fasting and over 2-h postprandially. In addition, in vitro viscosity of the beverages was assessed utilizing standard rheological methodology. RESULTS: Both Salba-chia and flax reduced blood glucose area under the curve over 120 min by 82.5±19.7 mmol/l (P<0.001) and 60.0±19.7 mmol/l (P=0.014), respectively, relative to a glucose control. Salba-chia reduced peak glucose (-0.64±0.24 mmol/l; P=0.030) and increased time to peak (11.3±3.8 min; P=0.015) compared with flax. Salba-chia significantly reduced the mean ratings of desire to eat (-7±2 mm; P=0.005), prospective consumption (-7±2 mm; P=0.010) and overall appetite score (-6±2 mm; P=0.012), when compared with flax. The viscosity of Salba-chia, flax and control was 49.9, 2.5, and 0.002 Pa·s, respectively. CONCLUSIONS: Despite the similarities in nutritional composition, Salba-chia appears to have the ability to convert glucose into a slow-release carbohydrate and affect satiety to a greater extent than flax, possibly due to the higher fiber viscosity. Incorporation of either flax or Salba-chia into the diet may be beneficial, although use of Salba-chia may confer additional benefit.

A systematic review and meta-analysis of randomized controlled trials of the effect of barley ß-glucan on LDL-C, non-HDL-C and apoB for cardiovascular disease risk reductioni-iv.

BACKGROUND/OBJECTIVES: There has been recent interest in barley as a therapeutic food owing to its high content of beta-glucan (ß-glucan), a viscous soluble fiber recognized for its cholesterol-lowering properties. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the cholesterol-lowering potential of barley ß-glucan on low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apoB) for cardiovascular disease (CVD) risk reduction. METHODS: MEDLINE, Embase, CINAHL and the Cochrane CENTRAL were searched. We included RCTs of ⩾3-week duration assessing the effect of diets enriched with barley ß-glucan compared with controlled diets on LDL-C, non-HDL-C or apoB. Two independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed by the Cochran Q-statistic and quantified by the I2 statistic. RESULTS: Fourteen trials (N=615) were included in the final analysis. A median dose of 6.5 and 6.9 g/day of barley ß-glucan for a median duration of 4 weeks significantly reduced LDL-C (MD=-0.25 mmol/l (95% CI: -0.30, -0.20)) and non-HDL-C (MD=-0.31 mmol/l (95% CI: -0.39, -0.23)), respectively, with no significant changes to apoB levels, compared with control diets. There was evidence of considerable unexplained heterogeneity in the analysis of non-HDL-C (I2=98%). CONCLUSIONS: Pooled analyses show that barley ß-glucan has a lowering effect on LDL-C and non-HDL-C. Inclusion of barley-containing foods may be a strategy for achieving targets in CVD risk reduction.

Nutrition principles and diabetes. A role for "lente carbohydrate"?

The current nutrition recommendations of the American Diabetes Association (ADA) represent a thoughtful synthesis of much current data. They depart from tradition by not advocating specific figures for total fat and carbohydrate intake. Rather, since many issues are still topics of scientific debate, they endorse the principle of individualization and set guidelines accordingly. One topic that may be worthy of further debate is the principle of "spreading the nutrient load," or lengthening the absorption time. This principle covers the effects of altered meal frequency, viscous dietary fibers, low-glycemic index foods, and inhibitors of carbohydrate absorption. In its simplest form it is illustrated by studies of altered meal frequency ("nibbling versus gorging"). Reducing the size and increasing the frequency of meals has been shown acutely to result in lower mean blood glucose and insulin levels over the day in type II diabetes and to result in reduced 24-h urinary C-peptide losses. In the longer term in nondiabetic subjects, total and low-density lipoprotein cholesterol levels are reduced, together with fasting apolipoprotein B and serum uric acid levels, as additional risk factors for coronary heart disease. These and other physiological effects make slowing carbohydrate absorption ("lente carbohydrate") a potentially useful therapeutic modality. However, of the possible ways of slowing absorption, only alteration in meal frequency was of general interest in the current ADA nutrition recommendations. Nevertheless, the effects of slowing carbohydrate absorption by various means may have beneficial metabolic effects in diabetes and may support the use of ethnic foods in diets compatible with further modifications identified more favorably in the current nutrition recommendations (e.g., increased use of monounsaturated fat).

Starchy foods and glycemic index.

Different starchy foods produce different glycemic responses when fed individually, and there is some evidence that this also applies in the context of the mixed meal. A major reason appears to relate to the rate at which the foods are digested and the factors influencing this. A similar ranking in terms of glycemic response to specific foods is seen independent of the carbohydrate tolerance status of the groups tested. Potentially clinically useful starchy foods producing relatively flat glycemic responses have been identified. Many of these are considered ethnic or traditional and include legumes; pasta; grains such as barley, parboiled rice, and bulgur (cracked wheat); and whole-grain breads such as pumpernickel. Specific incorporation of these foods into diets has been associated with reductions in low-density lipoprotein cholesterol and triglyceride levels in hyperlipidemia and with improved blood glucose control in insulin-dependent diabetic patients. To facilitate identification of such foods, it has been suggested that the glycemic response should be indexed to a standard (e.g., white bread) to allow comparisons to be made between the glycemic index of foods tested in different groups of subjects. The scope of application of this principle is subject to further investigation. It may be used to expand the range of possibly useful starchy foods for trial in the diets of diabetic patients.

Glycemic response to wheat products: reduced response to pasta but no effect of fiber.

The blood glucose response to feeding 50-g carbohydrate portions of white and wholemeal bread and white spaghetti was studied in a group of nine diabetic subjects. Blood glucose rises after white and wholemeal bread were identical, but the response after spaghetti was markedly reduced. These results emphasize that food form rather than fiber may be important in determining the glycemic response and that pasta may be a useful source of carbohydrate in the diabetic diet.

Glycemic response to pasta: effect of surface area, degree of cooking, and protein enrichment.

To see whether food form, the degree of cooking, or protein enrichment affected the glycemic response to pasta, we gave test-meal breakfasts to 13 diabetic patients. Macaroni had a significantly greater glycemic index (GI) (68 +/- 8) than spaghetti (45 +/- 6, P less than .01); the GI of star pastina was intermediate (54 +/- 6). The GI of spaghetti was not significantly affected by cooking for 5 or 15 min (45 +/- 6 and 46 +/- 5, respectively), or by protein enrichment (38 +/- 4). The GI of spaghetti was similar in 11 non-insulin-dependent and 6 insulin-dependent diabetic patients (49 +/- 7 compared with 57 +/- 8). We conclude that different types of pasta may produce different glycemic responses but that these are not necessarily related to differences in cooking or surface area.

Beneficial effect of low-glycemic index diet in overweight NIDDM subjects.

OBJECTIVE: To determine whether low-glycemic index (GI) diets have clinical utility in overweight patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Six patients with NIDDM were studied on both high- and low-GI diets of 6-wk duration with metabolic diets with a randomized crossover design. Both diets were of similar composition (57% carbohydrate, 23% fat, and 34 g/day dietary fiber), but the low-GI diet had a GI of 58 compared with 86 for the high-GI diet. RESULTS: Small and similar amounts of weight were lost on both diets: 2.5 kg on high-GI diet and 1.8 kg on low-GI diet. On the low-GI diet, the mean level of serum fructosamine, as an index of overall blood glucose control, was lower than on the high-GI diet by 8% (P less than 0.05), and total serum cholesterol was lower by 7% (P less than 0.01). CONCLUSIONS: In overweight patients with NIDDM, reducing diet GI improves overall blood glucose and lipid control.

Glycemic index of foods in individual subjects.

We studied 12 subjects with diabetes to determine how well the glycemic index (GI) predicted the ranking of glycemic responses of different foods in individuals. All subjects ate three mixed meals (bread, rice, or spaghetti with GIs of 100, 79, and 61, respectively) four times in a randomized complete block design. The mean glycemic response areas of the different meals ranked according to the predicted GI in every individual. The observed mean +/- SD GI values of the meals were significantly different from each other (bread 100 +/- 7, rice 75 +/- 9, spaghetti 54 +/- 9), with no significant difference in response between subjects. It is concluded that individuals share common mean GI values for different foods. Within confidence limits determined by the variability of glycemic responses, the number of repeated tests conducted, and the expected GI difference, the GI can be used to predict the ranking of the mean glycemic responses of mixed meals taken by individuals.

Expression of the thrombin receptor in developing bone and associated tissues.

Thrombin, a serine protease with a central role in thrombosis and hemostasis, is also a specific agonist for a variety of cellular responses in osteoblasts and stimulates bone resorption in organ culture. Cultured osteoblast-like cells express the proteolytically activated thrombin receptor, but the significance of this finding in vivo remains unknown. Immunohistochemistry was used to investigate the normal tissue distribution of the proteolytically activated thrombin receptor in developing rat bones and associated tissues. In hind limbs, the receptor was first observed on embryonic day 16 and became more abundant within the limb as gestation progressed. Thrombin receptor staining was detected on osteoblasts, macrophages, muscle cells, and endothelial cells, but not osteoclasts. Similarly, osteoblasts in developing calvariae stained positively for the thrombin receptor. The pattern of receptor expression by primary osteoblast cultures and freshly isolated macrophages and osteoclasts corresponded to that observed in vivo. The observed pattern of thrombin receptor expression in bone cells supports the hypothesis that cell-mediated thrombin-induced bone resorption is mediated by osteoblasts.

The glycemic index: methodology and clinical implications.

There is controversy regarding the clinical utility of classifying foods according to their glycemic responses by using the glycemic index (GI). Part of the controversy is due to methodologic variables that can markedly affect the interpretation of glycemic responses and the GI values obtained. Recent studies support the clinical utility of the GI. Within limits determined by the expected GI difference and by the day-to-day variation of glycemic responses, the GI predicts the ranking of the glycemic potential of different meals in individual subjects. In long-term trials, low-GI diets result in modest improvements in overall blood glucose control in patients with insulin-dependent and non-insulin-dependent diabetes. Of perhaps greater therapeutic importance is the ability of low-GI diets to reduce insulin secretion and lower blood lipid concentrations in patients with hypertriglyceridemia.

Dietary fiber and blood lipids: treatment of hypercholesterolemia with guar crispbread.

Eleven hyperlipidemic patients took an average of 13 g guar in crispbread form over 2- to 8-week periods. Eight weeks' treatment (seven patients) reduced total serum cholesterol by 13% (P less than 0.002) while high-density lipoprotein cholesterol was unchanged. A 13% nonsignificant reduction was also seen in serum triglyceride. Comparison of blood lipid changes over 2-week periods showed guar crispbread to be as effective as guar given in hydrated (eight patients) or semihydrated form (four patients). In addition total serum cholesterol was lowered significantly (11%, P less than 0.05) in five patients where cholestyramine was ineffective. Due to its acceptability, guar crispbread is likely to prove a useful cholesterol-lowering agent.

Relationship between polyphenol intake and blood glucose response of normal and diabetic individuals.

Five leguminous and eight nonleguminous foods were analyzed for polyphenol concentration by the Prussian Blue and the Folin Denis methods and correlated with blood glucose response (glycemic index) in normal or diabetic volunteers. Polyphenol concentrations and intakes per 50 g available carbohydrate portions were higher in the leguminous foods than those in the nonleguminous foods. In both normal and diabetic individuals, a negative correlation was observed between glycemic index and the concentration or total intake of polyphenols. Polyphenols, especially the large polymeric type or condensed tannins, appear to be responsible in part for the reduced glycemic response to carbohydrate foods and in part to lower blood glucose response to legumes compared with cereal products.

Low glycemic index: lente carbohydrates and physiological effects of altered food frequency.

Many factors influence carbohydrate absorption. Slower rates of absorption may have advantages in reducing postprandial glycemia and insulinemia and, in time, reduce serum low-density-lipoprotein (LDL) cholesterol and apolipoprotein B concentrations. Foods high in viscous fiber or antinutrients, or foods that are resistant to gelatinization, show slower rates of digestion and absorption and may be called low glycemic index or lente carbohydrate foods. Specific enzyme inhibitors may also cause lente effects. Certain small-intestinal effects of lente carbohydrate may be mimicked by altering feeding frequency (eg, nibbling vs gorging). Increased meal frequency reduces post-prandial insulin and glucose responses in people with non-insulin-dependent diabetes and in nondiabetic volunteers and lowers serum concentrations of LDL cholesterol and apolipoprotein B. Reduced hepatic cholesterol synthesis has been reported. Increased meal frequency may also slow small-intestinal absorption in the treatment of conditions such as diabetes, hyperlipidemia, and possibly obesity.

Low glycemic response to traditionally processed wheat and rye products: bulgur and pumpernickel bread.

To look at the effect of processing wheat and rye on blood glucose responses with special reference to bulgur and pumpernickel bread, groups of 9-12 Noninsulin-dependent (NIDDM) and 5-6 Insulin-dependent diabetic volunteers (IDDM) were fed test meals containing 50 g carbohydrate portions of four wheat and three rye products. Glycemic indices for IDDM and NIDDM combined, calculated as the incremental area under the blood glucose response curve, where white bread = 100, demonstrated values of 96 +/- 5 for wholemeal wheat bread, 89 +/- 6 for wholemeal rye bread, 78 +/- 3 for pumpernickel bread, 65 +/- 4 for bulgur, 63 +/- 6 for whole wheat kernels and 48 +/- 5 for whole rye kernels. Results for IDDM and NIDDM were similar (r = 0.96, p less than 0.01). It is concluded that traditional processing of cereals, such as parboiling (bulgur) or the use of wholegrains in bread (pumpernickel) may result in the low GI value associated with the unmilled cereal. Cereal foods processed in these ways may form a useful part of the diet where a reduction in postprandial glycemia is required.

The effect of starch-protein interaction in wheat on the glycemic response and rate of in vitro digestion.

To determine the effect on blood glucose of removal of protein from wheat products, healthy volunteers took test meals of white bread made from either regular or gluten-free flour. After bread made from gluten-free flour, the blood-glucose rise was significantly greater. This corresponded with a significantly more rapid rate of digestion in vitro and reduced starch malabsorption in vivo as judged by breath-H2 measurements. Addition of gluten to the gluten-free bread mix did not reverse these effects. Factors associated with unprocessed wheat flour, such as the natural starch-protein interaction, may therefore be important in wheat products in reducing both their rate of absorption and glycemic response. They may have implications in the dietary management both of diabetes and of diseases where small intestinal absorptive capacity is impaired.

Wheat-bran and oat-bran supplements' effects on blood lipids and lipoproteins.

To compare the effects of oat-bran fiber on blood lipids, we studied 84 healthy middle-aged men and women who were placed on metabolic diets, for 2 wk, that were supplemented with either wheat bran (n = 42) or oat bran (n = 42). Fiber supplementation was 1.6 micrograms dietary fiber/J (6.8 g dietary fiber/1000 kcal) to a maximum of 16.4 g fiber/d. Significantly greater decrease with oat than with wheat were seen in total cholesterol (0.56 +/- 0.08 mmol/L and 0.29 +/- 0.08 mmol/L, P = 0.022) and low-density-lipoprotein cholesterol (0.39 +/- 0.07 mmol/L and 0.15 +/- 0.07 mmol/L, P = 0.024). No significant differences were seen in high-density lipoprotein, apolipoproteins A-1 and B, or triglyceride. We conclude that oat bran has an advantage over wheat bran in lowering serum lipids when tested in metabolic diets on large numbers of individuals with an initial mean serum cholesterol concentration above the desirable range, at 5.61 +/- 0.16 mmol/L.