lunes, 22 de diciembre de 2014

Diabetes: The Sweetener Paradox

22. December 2014
There are strong hints that helping oneself to sweetener in high doses increases the risk of developing glucose intolerance. Scientists at the Weizman Institute of Science in Israel have found valid reasons for this association, something which at first glance appears very contradictory.
Sweeteners are superior to ordinary sugar in many ways: they impart a stronger sweetness, have a very low physiological calorific value and they cannot be metabolised by caries-causing bacteria. Therefore these sweet “miracle substances” are among those around the world most commonly added to foods.
Yet time and again the synthetically produced sweeteners end up the subject of criticism. Studies have already indicated that sweeteners increase appetite and thus may be leading to obesity. In addition, an increased risk of bladder cancer and vascular disease has already been discussed in relation to sweeteners.

Paradoxical link

Scientists at the Weizman Institute of Science in Rehovot, Israel, have now found evidence that sweeteners may even induce glucose intolerance. This sounds paradoxical, since a low-sugar diet actually should have many advantages, especially with respect to glucose tolerance. Obviously though the gastrointestinal microbiota also plays an important role in the development of glucose intolerance. And consumption of sweeteners apparently has substantial effects on the gut microbiota’s composition.

Sweeteners given to various mice results in glucose intolerance

The scientists first subjected healthy, lean mice to a glucose tolerance test. This makes it possible to check how well an organism is able to process a large amount of orally ingested glucose. With humans as well this test helps in detecting incipient diabetes. Following this the scientists adjusted the drinking water of the animals by adding the maximum recommended daily consumption dose of saccharin, aspartame or Sucralose. The control animals drank sugar water or unsweetened water. After eleven weeks, the researchers repeated the glucose tolerance test – with a clear result: during the experimental time period, all sweetener-drinking mice developed glucose intolerance, whereas none of the control mice did. Among animals that had been drinking saccharin-containing water, the precursor stage of type 2 diabetes was particularly pronounced. Further experiments with obese mice and animals of varied strains showed the same result: the consumption of sweeteners always led to glucose intolerance, a misregulated glucose metabolism. How does this happen?
“Most sweeteners pass through the gastrointestinal tract without being digested”, the researchers write. Therefore the substances act directly on bacterial colonisation and on the composition of the gut. The gut microbiota’s composition in turn plays a central role in the regulation of many physiological processes, including the metabolism of sugar.

Antibiotics neutralise the effect

In order to test whether the gastrointestinal flora of the animals is actually involved in glucose intolerance, the researchers administered high dosage of the broad-spectrum antibiotics ciprofloxacin and metronidazole, which act on Gram-negative bacteria, to both the leaner and obese animal subjects. During the antibiotic treatment, the animals continue to drink sweetener-containing water. Already after four weeks of therapy the researchers were barely able to detect glucose-intolerance test differences between the fatter and leaner animals drinking sweetener and the control animals. What’s more, Vancomycin, targeted at Gram-positive bacteria, also led to this effect.
“These results suggest that the sweetener-induced glucose intolerance is caused by changes in the gut flora and the different proportions of its bacterial representatives”, the study authors conclude.
A further test was used to confirm this assumption: the scientists transferred the bacteria of the gastrointestinal flora of sweetener-drinking mice to microbe-free control mice. Already six days after the faecal transplant these mice were also suffering from glucose intolerance. Here was yet another indication for the researchers that sweeteners, via the modulation of the intestinal flora, lead to a precursor form of type 2 diabetes.

Species composition shifted

Next, the scientists put the microbiome composition of the variously fed mice under the microscope. One DNA sequencing showed: among the sweetener-fed mice more bacteria of the genus Bacteroides were present as well as were some representatives of the Clostridiales. Other subgroups of the Clostridiales on the other hand had fallen significantly in frequency, among these the lactic acid bacteria Lactobacillus reuteri, universally present in healthy humans and animals, the researchers report. In the sweetener-fed mice the researchers were also able to detect a multitude of active metabolic pathways which are responsible for increased energy intake from food and thus promote the development of obesity.
With mice it seems that sweeteners are obviously directly related to the onset of glucose intolerance. Is this also true for humans though?

Consumer survey

In order to address this question, the scientists analysed data from a consumer survey. From among 381 non-diabetic participants, 40 regularly consumed some amount of sweeteners. In this group of people the scientists found “a significant positive correlation between the sweetener consumption and several clinical parameters associated with this metabolic syndrome”, they write. These parameters include, for example, elevated fasting blood glucose and HbA1C levels as well as poorer results in the glucose tolerance test.

Small pilot study

In a small pilot study, the researchers tested their findings on seven subjects who normally consume no sweetener. The subjects were for a week given a daily intake of saccharin of 5 milligrams per kilogram of body weight, the maximum amount recommended by the FDA, administered in three daily doses. Already after four days, the initially normal glucose tolerance had significantly deteriorated in four participants. And similarly to that in the mice, the composition of their gut microflora had also changed. In three subjects both glucose tolerance and the composition of the gut microbiomes remained unchanged. When the researchers transferred stool samples of the subjects to gastrointestinally bacteria-free mice, only those which had received the stool from among the four subjects who had reacted to the consumption of saccharin then developed glucose intolerance. “Depending on the composition of the gut flora, humans apparently react differently to the consumption of sweeteners”, the researchers conclude from their data.
“Sweeteners are supposed to protect humanity from obesity and high blood glucose levels. Along with other changes in the human diet, the number of diabetics and obese people has increased concurrently with the mass consumption of sweeteners”, the researchers write. Thus sweeteners have exactly done what they were actually supposed to prevent. Future food strategies should be adapted to the different composition of the intestinal flora of people, the scientists urge.

Effects even with “normal” consumption?

Although the scientists were able through their research to provide a wealth of powerful evidence for the association of sweetener consumption and the development of glucose intolerance, it remains unclear whether these effects are to be expected with moderate sweetener consumption. Also, the matter remains to be clarified as to which “gut type” would be better off in the future by renouncing sweeteners.

Original publication of the article:

viernes, 19 de diciembre de 2014

Where Does Your Fat Go When You Lose Weight?

December 17, 2014 | by Janet Fang

photo credit: Elena Shashkina /

We talk a lot about dieting and burning off fat, but we actually have a lot of misconceptions about weight loss. Some people think fat is converted into energy or heat—a violation of the law of conservation of mass—while others think that the fat is somehow excreted or even converted to muscle. I was told early on that you can never lose your fat cells (adipose) once you gain them...they just shrink if you work it off. 
Well, according to Andrew Brown from the University of New South Wales and Australian TV personality (slash former physicist) Ruben Meerman, when you lose weight, you exhale your fat. Their new calculations, based on existing knowledge about biochemistry, were published in the British Medical Journal this week. 
“There is surprising ignorance and confusion about the metabolic process of weight loss,” Brown says in a news release. “The correct answer is that most of the mass is breathed out as carbon dioxide,” Meerman adds. “It goes into thin air.”
Excess carbs and proteins are converted into chemical compounds called triglycerides (which consist of carbon, hydrogen, and oxygen) and then stored in the lipid droplets of fat cells. To lose weight, you’re attempting to metabolize those triglycerides, and that means unlocking the carbon that’s stored in your fat cells. 
Losing 10 kilograms of human fat requires the inhalation of 29 kilograms of oxygen, producing 28 kilograms of carbon dioxide and 11 kilograms of water. That’s the metabolic fate of fat. 
Then the duo calculated the proportion of the mass stored in those 10 kilograms of fat that exits as carbon dioxide and as water when we lose weight. By tracing the pathway of those atoms out of the body, they found that 8.4 of those kilograms are exhaled as carbon dioxide. Turns out, our lungs are the primary excretory organ for weight loss. The remaining 1.6 kilograms becomes water, which is excreted in urine, feces, sweat, breath, tears, and other bodily fluids.
So, for this upcoming post-holiday season, should we all just exhale more to shed those extra pounds? No. Breathing more than required by a person’s metabolic rate leads tohyperventilation, followed by dizziness, palpitations, and loss of consciousness. 

martes, 9 de diciembre de 2014

AHA: IMPROVE-IT Proves Ezetimibe Benefit

Published: Nov 17, 2014 | Updated: Nov 18, 2014

CHICAGO -- In high-risk patients, adding ezetimibe to statin therapy reduced LDL cholesterol by an average of 17 mg/dL and reduced cardiovascular events compared with statin therapy alone.
That finding from the 18,000-patient IMPROVE-IT trial marks the first time that adding a nonstatin lipid-lowering therapy to a statin demonstrated a clinical benefit, Christopher Cannon, MD, of Brigham and Women's Hospital, toldMedPage Today.

Completo aquí:

lunes, 8 de diciembre de 2014

Hallan grabado de 500,000 años de antigüedad


Hallan grabado de 500,000 años de antigüedad

HISTORIA 4/12/14
Hace medio millón de años, el Homo erectus en Java utilizaba conchas de mejillones de agua dulce como herramienta y como lienzo para grabados. Un equipo internacional de investigadores, liderados por el arqueólogo José Joordens, de la Universidad de Leiden, ha publicado el descubrimiento en el diario Nature. El descubrimiento provee una nueva perspectiva de la evolución del comportamiento humano.
Antes del descubrimiento se pensaba que grabados similares habían sido realizados únicamente por el humano moderno (Homo sapiens) en África, hace aproximadamente 100,00 años.
El equipo de 21 investigadores estudio cientos de caparazones fosilizados y asociaron los descubrimientos con el sitio del Homo erectus Trinil, en la isla indonesia de Java. Las conchas son parte de la Colección Dubois que ha permanecido desde el siglo XIX en el Centro de Biodiversidad Naturalis, fueron excavadas por el físico e investigador Eugène Dubois, quien descubrió el Pithecanthropus erectus  (ahora conocido como Homo erectus).
El descubrimiento del grabado con patrón geométrico en una de las conchas fue una sorpresa total. Puede ser observado únicamente con iluminación oblicua y es evidentemente más antiguo que los procesos de desgaste en la concha resultantes de la fosilización. El estudio excluyó la posibilidad de que el patrón hubiera sido causado por animales o desgaste de procesos climatológicos.
La investigación determinó que el grabado en el caparazón data de un mínimo de 430,000 años y un máximo de 540,000 años, esto quiere decir que es al menos cuatro veces más antiguo que los grabadas más antiguos que se conocían hasta ahora, descubiertos en África. Por el momento aún no se tienen pistas acerca del significado o propósito del hallazgo.

La precisión con la que esta especie similar al ser humano trabajaba es un indicativo de su habilidad e inteligencia. Los moluscos eran comidos y las conchas vacías utilizadas para crear herramientas, por ejemplo cuchillos.

El descubrimiento, que será exhibido en el museo Naturalis, en Holanda a partir del 4 de diciembre, arroja nuevos datos acerca de las aptitudes y comportamiento del Homo erectus e indica que Asia es un área que ha sido relativamente inexplorada en dónde se podrían encontrar nuevos artefactos.


European Study: Actos Doesn't Cause Cancer

Published: Dec 5, 2014

Despite FDA and EMA warnings to the contrary, a European study has found no link between pioglitazone (Actos) and bladder cancer.
In a large observational study, there was no increased risk of bladder cancer per 100 days of cumulative exposure, Helen Colhoun, MD, of the University of Dundee in Scotland, and colleagues reported online in Diabetologia.
"To fully resolve this controversy, future analyses are needed, involving longer follow-up of exposed persons and using methods to minimize allocation bias," they wrote.
In August, Actos drugmaker Takeda released initial data from its 10-year analysis of the potential link between its drug and bladder cancer, finding no increased risk, either with any exposure or with a long duration of use.
That result was in contrast to an earlier 5-year interim analysis that showed a significantly higher incidence of bladder cancer in long-term pioglitazone users.
Both the FDA and the EMA have warned against the use of pioglitazone in patients with bladder cancer, and urge cautious use in patients who've previously had bladder cancer. The drug was also pulled from the market in France and Germany.
Calhoun and colleagues wrote that several studies have also shown no link between pioglitazone and bladder cancer. But a potential mechanistic link exists. Pioglitazone and a sister drug rosiglitazone (Avandia) are peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists -- and this nuclear transcription factor is overexpressed in bladder tumors.
The researchers looked at data from about 1 million patients from British Columbia, Finland, Manchester, Rotterdam, Scotland, and the U.K. Clinical Practice Research Datalink, finding a total of 3,248 cases of bladder cancer.
They found no evidence of an association between bladder cancer and 100 days of cumulative exposure to pioglitazone in either men or women:
  • Men: RR 1.01, 95% CI 0.97 to 1.06
  • Women: RR 1.04, 95% CI 0.97 to 1.11
Nor was there any association between rosiglitazone and bladder cancer in either gender, they reported.
In a statement, the researchers said their analysis "is the only one to use identical methodology across international centers involving a large number of diabetic patients," but they still called for further research to "fully resolve this controversy."
The study was supported by the European Federation for the Study of Diabetes.
Colhoun reported financial relationships with Roche, Pfizer, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Sanofi, and Novartis.
Primary source: Diabetologia
Source reference: Levin D, et al "Pioglitazone and bladder cancer risk: A multipopulation pooled cumulative exposure analysis" Diabetologia 2014; DOI: 10.1007/s00125-014-3456-9.