A review of the effectiveness of aspartame in helping with weight control

Summary Strategies to reverse the upward trend in obesity rates need to focus on both reducing energy intake and increasing energy expenditure. The provision of low‐ or reduced‐energy‐dense foods is one way of helping people to reduce their energy intake and so enable weight maintenance or weight loss to occur. The use of intense sweeteners as a substitute for sucrose potentially offers one way of helping people to reduce the energy density of their diet without any loss of palatability. This report reviews the evidence for the effect of aspartame on weight loss, weight maintenance and energy intakes in adults and addresses the question of how much energy is compensated for and whether the use of aspartame‐sweetened foods and drinks is an effective way to lose weight. All studies which examined the effect of substituting sugar with either aspartame alone or aspartame in combination with other intense sweeteners on energy intake or bodyweight were identified. Studies which were not randomised controlled trials in healthy adults and which did not measure energy intakes for at least 24 h (for those with energy intakes as an outcome measure) were excluded from the analysis. A minimum of 24‐h energy intake data was set as the cut‐off to ensure that the full extent of any compensatory effects was seen. A total of 16 studies were included in the analysis. Of these 16 studies, 15 had energy intake as an outcome measure. The studies which used soft drinks as the vehicle for aspartame used between 500 and about 2000 ml which is equivalent to about two to six cans or bottles of soft drinks every day. A significant reduction in energy intakes was seen with aspartame compared with all types of control except when aspartame was compared with non‐sucrose controls such as water. The most relevant comparisons are the parallel design studies which compare the effects of aspartame with sucrose. These had an overall effect size of 0.4 standardised difference (SD). This corresponds to a mean reduction of about 10% of energy intake. At an average energy intake of 9.3 MJ/day (average of adult men and women aged 19–50 years) this is a deficit of 0.93 MJ/day (222 kcal/day or 1560 kcal/week), which would be predicted (using an energy value for obese tissue of 7500 kcal/kg) to result in a weight loss of around 0.2 kg/week with a confidence interval 50% either side of this estimate. Information on the extent of compensation was available for 12 of the 15 studies. The weighted average of these figures was 32%. Compensation is likely to vary with a number of factors such as the size of the caloric deficit, the type of food or drink manipulated, and timescale. An estimate of the amount of compensation with soft drinks was calculated from the four studies which used soft drinks only as the vehicle. A weighted average of these figures was 15.5%. A significant reduction in weight was seen. The combined effect figure of 0.2 SD is a conservative figure as it excludes comparisons where the controls gained weight because of their high‐sucrose diet and the long‐term follow‐up data in which the aspartame groups regained less weight than the control group. An effect of 0.2 SD corresponds to about a 3% reduction in bodyweight (2.3 kg for an adult weighing 75 kg). Given the weighted average study length was 12 weeks, this gives an estimated rate of weight loss of around 0.2 kg/week for a 75‐kg adult. The meta‐analyses demonstrate that using foods and drinks sweetened with aspartame instead of sucrose results in a significant reduction in both energy intakes and bodyweight. Meta‐analyses both of energy intake and of weight loss produced an estimated rate of weight loss of about 0.2 kg/week. This close agreement between the figure calculated from reductions in energy intake and actual measures of weight loss gives confidence that this is a true effect. The two meta‐analyses used different sets of studies with widely differing designs and controls. Although this makes comparisons between them difficult, it suggests that the final figure of around 0.2 kg/week is robust and is applicable to the variety of ways aspartame‐containing foods are used by consumers. This review has shown that using foods and drinks sweetened with aspartame instead of those sweetened with sucrose is an effective way to maintain and lose weight without reducing the palatability of the diet. The decrease in energy intakes and the rate of weight loss that can reasonably be achieved is low but meaningful and, on a population basis, more than sufficient to counteract the current average rate of weight gain of around 0.007 kg/week. On an individual basis, it provides a useful adjunct to other weight loss regimes. Some compensation for the substituted energy does occur but this is only about one‐third of the energy replaced and is probably less when using soft drinks sweetened with aspartame. Nevertheless, these compensation values are derived from short‐term studies. More data are needed over the longer term to determine whether a tolerance to the effects is acquired. To achieve the average rate of weight loss seen in these studies of 0.2 kg/week will require around a 220‐kcal (0.93 MJ) deficit per day based on an energy value for obese tissue of 7500 kcal/kg. Assuming the higher rate of compensation (32%), this would require the substitution of around 330 kcal/day (1.4 MJ/day) from sucrose with aspartame (which is equivalent to around 88 g of sucrose). Using the lower estimated rate of compensation for soft drinks alone (15.5%) would require the substitution of about 260 kcal/day (1.1 MJ/day) from sucrose with aspartame. This is equivalent to 70 g of sucrose or about two cans of soft drinks every day.     

The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

Solid and papillary epithelial neoplasms of the pancreas: CT findings

Five female patients and one male patient with solid and papillary epithelial neoplasms of the pancreas were examined with computed tomography (CT). The mean age of the patients was 27 years (range, 13-46 years). All cases showed well-encapsulated, round or lobulated masses consisting of both cystic and solid areas. Cystic portions showed CT numbers that suggested hemorrhagic necrosis. There were no internal septations within the masses. In three tumors located in the head of the pancreas, dilatation of the biliary tree was absent or minimal, although the masses were large. Two tumors contained calcifications. One tumor demonstrated metastatic deposits in liver and lymph nodes. Metastatic masses appeared similar to the primary pancreatic mass. Solid and papillary neoplasm of the pancreas should be the primary diagnostic consideration when characteristic CT findings are detected in a young female patient.     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.      

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.