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Updated: 1 day 17 min ago

Chokeberry extract 'boosts pancreas cancer chemo'

Thu, 2014-09-18 04:30

“Wild berries native to North America may have a role in boosting cancer therapy,” BBC News reports.

It has been found – in a laboratory study using pancreatic cancer cells – that chokeberry extract may help increase the powers of chemotherapy drugs in treating pancreatic cancer

Researchers tested an extract of chokeberry – a plant found on the eastern side of the continent – on pancreatic cancer cells. They examined what happened to these cells in the laboratory when they were treated with chemotherapy alone, chokeberry extract alone, or with a combination of both.

Researchers found that adding the chokeberry extract to gemcitabine (a chemotherapy drug used in the treatment of pancreatic cancer) was more effective at halting the growth of cancer cells than the drug alone.

Pancreatic cancer is a condition with notoriously poor prognosis, and the possibility of any new treatment on the horizon is encouraging. However, it is uncertain whether these positive lab results would translate to a real-world setting. It is expected that, based on these promising results, further studies will look into the possibility of human trial(s).

For now, people with pancreatic cancer should not consider taking these chokeberry extracts or supplements, based on this very early-stage research. "Herbal remedies" should never be assumed to be safe, and some can react unpredictably with chemotherapy drugs.


Where did the story come from?

The study was carried out by researchers from Middlesex University, University of Southampton, Portsmouth University and Kings College Hospital. It was funded by the Malaysian Ministry of Higher Education and a US charitable organisation called Have a Chance Inc.

The study was published in the peer-reviewed Journal of Clinical Pathology.

The BBC’s coverage was fair, pointing out that research was at an early stage and including independent comments from cancer experts on the need for human trials. The Daily Telegraph’s coverage only included comments from the study’s authors.


What kind of research was this?

This was a laboratory study, with scientists having conducted various experiments examining the effect of adding extracts of chokeberry to pancreatic cancer cells.

The researchers point out that pancreatic cancer has a very poor outlook and a high mortality rate, with only 1-4% of those with the cancer surviving to five years. Only 10-20% of people with pancreatic cancer are suitable for surgery, and pancreatic cancer cells are resistant to both chemotherapy and radiotherapy.

Researchers say that many studies have explored the use of dietary agents, particularly antioxidant substances called polyphenols, found in fruits and vegetables. This is because of their ability to promote apoptosis – programmed cell death – in a variety of cancer cells. Previous studies have also shown that a number of polyphenols, including those from chokeberry extracts, have potential anticancer properties in malignant brain tumours.

Chokeberry (aronia melanocarpa) is a shrub found in North American wet woods and swamps. Extracts and supplements are popular for their apparent health-giving qualities, including their high level of antioxidants.


What did the research involve?

Researchers used a line of pancreatic cancer cells called AsPC-1, which were cultured in the laboratory. In a number of experiments, they assessed how well the cells grew when treated with:

  • the chemotherapy drug gemcitabine alone at different doses (gemcitabine is one of the drugs sometimes given to people after they have had surgery to remove their pancreatic cancer, to try and prevent it returning)
  • differing levels of chokeberry extract
  • a combination of gemcitabine with chokeberry extract

They also carried out experiments to examine how chokeberry extract might cause the death of cancer cells, and at what concentration it caused cell death. As a control, they also tested chokeberry extract on the healthy cells that line blood vessels. These are taken from the veins of the umbilical cord and are often used in laboratory studies.


What were the basic results?

Researchers found that gemcitabine in combination with chokeberry extract was more effective at killing cancer cells than gemcitabine by itself. This difference in effect was also present when using lower doses of gemcitabine.

The analysis indicated that when incubated with gemcitabine for 48 hours, a concentration of one microgram per millilitre of chokeberry extract was required to induce cell death. Generally, the higher the concentration of chokeberry extract used in combination with gemcitabine, the more cancer cells were killed.

However, chokeberry extract alone without gemcitabine was not effective at killing the cancer cells at the concentrations tested.

Healthy cells were unaffected by chokeberry extract up to a concentration of 50 micrograms per millilitre.


How did the researchers interpret the results?

The researchers say that chokeberry extract and other micronutrients should be considered as part of cancer therapy. More specifically, they suggest that elements in chokeberry extract may have “supra-additive effects” when used in combination with at least one conventional anti-cancer drug.

In an accompanying press release, Bashir Lwaleed, at the University of Southampton, comments: "These are very exciting results. The low doses of the extract greatly boosted the effectiveness of gemcitabine when the two were combined. In addition, we found that lower doses of the conventional drug were needed, suggesting either that the compounds work together synergistically [where the whole is greater than the sum of its parts], or that the extract exerts a "supra-additive" effect. This could change the way we deal with hard-to-treat cancers in the future. "



It is now commonly thought that the antioxidants found in fruits and vegetables may have many health benefits, including reducing the risk of some cancers.

Pancreatic cancer is a condition with notoriously poor prognosis, and the possibility of any new treatment on the horizon is encouraging. This study found that when pancreatic cancer cells in the laboratory were directly treated with a combination of the chemotherapy drug gemcitabine and chokeberry extract, adding the extract enhanced the cancer-killing potential compared to the chemotherapy drug alone.

However, directly adding an extract to cells in the laboratory is a lot different from people actually taking chokeberry extracts themselves. Though these are promising findings, it is too early to say whether the micronutrients found in this extract could be effective in the treatment of pancreatic cancer. Further scientific study will be needed before initial developments could progress to the next stage of trials in people with pancreatic cancer, to see whether chokeberry extract might enhance the effects of chemotherapy. 

For now, as experts importantly highlight, people with pancreatic cancer should not consider taking these chokeberry extracts in the form of a herbal remedy or supplement, based on this very early-stage research.

Herbal remedies, just like pharmaceutical medicines, will have an effect on the body and can be potentially harmful.

They should therefore be used with the same care and respect as pharmaceutical medicines. Being "natural" doesn't necessarily mean they're safe to take.

Read more about herbal medicines and supplements.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Berries in cancer therapy trial. BBC News, September 18 2014

Study: Berries could boost standard cancer treatment. The Daily Telegraph, September 18 2014

Links To Science

Thani NAA, Keshavarz S, Lwaleed BA, et al. Cytotoxicity of gemcitabine enhanced by polyphenolics from Aronia melanocarpa in pancreatic cancer cell line AsPC-1. Journal of Clinical Pathology. Published online September 17 2014

Categories: News

Do artificial sweeteners raise diabetes risk?

Thu, 2014-09-18 04:00

"Artificial sweeteners may promote diabetes, claim scientists," reports The Guardian. But before you go clearing your fridge of diet colas, the research in question – extensive as it was – was mainly in mice.

The researchers' experiments suggest artificial sweeteners, particularly saccharin, change the bacteria that normally live in the gut and help to digest nutrients.

These changes could reduce the body's ability to deal with sugar, leading to glucose intolerance, which can be an early warning sign of type 2 diabetes.

Assessments in human volunteers suggested the findings might also apply to people. But human studies so far are limited.

The researchers only directly tested the effect of saccharin in an uncontrolled study on just seven healthy adults over the course of a week. It is far too early to claim with any confidence that artificial sweeteners could be contributing to the diabetes "epidemic".

In the interim, if you are trying to reduce your sugar intake to control your weight or diabetes, you can always try to do so without using artificial sweeteners. For example, drinking tap water is a far cheaper alternative to diet drinks.


Where did the study come from?

This study was carried out by researchers at the Weizmann Institute of Science and other research centres in Israel.

It was funded by the Weizmann Institute and the Nancy and Stephen Grand Israel National Center for Personalized Medicine, as well as grants from various research funders globally.

The study was published in the peer-reviewed medical journal Nature.

The Guardian covered this study well, avoiding sensationalising the results. The paper and other media outlets, including the Daily Mail, included balanced quotes from various experts that highlight the study's limitations.

However, The Guardian reports the daily amount of saccharin used in the study in humans "was enough to sweeten around 40 cans of diet cola", but it is unclear where this estimate came from. Saccharin is not commonly used in diet drinks any longer, with aspartame being the preferred choice of most manufacturers. 

The Daily Express only included quotes from the study author (for) and a representative of the British Soft Drinks Association (against), which – as you would expect – polarised the debate.


What kind of research was this?

This was animal and human research looking at the effect of artificial sweeteners on bacteria in the gut and how this influences glucose metabolism.

Animal research is often one of the first steps in investigating theories about the biological effects of substances. It allows researchers to carry out studies that could not be done in humans.

Because of differences between species, results in animals may not always reflect what happens in humans, but they allow researchers to develop a better idea of how things might work.

They can then use this knowledge to develop ways to test their theories using information that can be obtained in humans. This study has carried out both the animal and early human tests of their theories. But the human part of this study was relatively limited, as the focus was on the animal research.

The researchers carried out a cross-sectional analysis of artificial sweetener exposure and indicators of metabolic problems and gut bacteria. This approach is not able to determine whether the sweetener could be contributing to the outcomes seen, or vice versa.

The researchers also tested the short-term effect of saccharin on people who never consumed the sweetener, but without a control group.


What did the research involve?

The researchers compared the effect of consuming the artificial sweeteners against water, glucose and sucrose on glucose tolerance in lean mice and obese mice (mice eating a high-fat diet). Glucose tolerance testing assesses how quickly the body can clear glucose from the blood after glucose is eaten.

The body normally responds by quickly taking glucose up into cells for use and storage. If the body is slow to do this, this is called glucose intolerance. Very high glucose intolerance in humans indicates diabetes.

The researchers carried out various experiments to test whether the changes seen might relate to the artificial sweeteners having an effect on the bacteria in the gut, and exactly what these effects were.

They then carried out tests to see whether artificial sweetener consumption could have similar effects in humans. They did this by cross-sectionally assessing long-term artificial sweetener consumption and various indicators of glucose metabolism problems in a sample of 381 people who were not diabetic.

They also tested the effects of commercial saccharin given to seven healthy adult volunteers who did not normally consume saccharin. This was given over the course of six days at the US Food and Drug Agency's (FDA) maximum acceptable level (5mg per kg body weight), equivalent to 120mg a day.


What were the basic results?

The researchers found both lean and obese mice consuming the artificial sweeteners saccharin, sucralose or aspartame in their water over 11 weeks developed glucose intolerance, while those consuming just water, glucose or sucrose did not.

Saccharin had the greatest effect on glucose intolerance, and the researchers focused most of their experiments on this sweetener. It caused glucose intolerance within five weeks when given at a dose equivalent to the US Food and Drug Administration (FDA) maximum acceptable daily intake in humans.

The researchers found the mice consuming the artificial sweeteners did not differ in their liquid and food consumption or their walking and energy expenditure compared with the controls. These factors were therefore considered to not be causing the glucose intolerance.

However, treating mice with antibiotics stopped the artificial sweeteners having this effect. Mice with no gut bacteria developed glucose intolerance when the researchers transplanted gut bacteria taken from mice consuming saccharin or being treated with saccharin in the lab. These results suggest the sweeteners were having some effect on the gut bacteria, which was causing the glucose intolerance.

The researchers also found drinking saccharin changed the types of bacteria in the mice's guts. Drinking water, glucose or sucrose did not have this effect.

The bacteria in the gut are involved in helping to digest nutrients. The specific changes seen in mice consuming saccharin suggest the sweeteners could be increasing the amount of energy that could be harvested from these nutrients.

In their human studies, the researchers found:

  • Long-term artificial sweetener consumption in 381 people who were not diabetic was associated with greater waist circumference, waist to hip ratio, levels of glucose in the blood after fasting, and worse glucose tolerance.
  • People who consumed artificial sweeteners had a different gut bacteria composition from people who did not consume artificial sweeteners.
  • Four out of seven healthy adult volunteers who did not normally consume artificial sweeteners developed worse glucose tolerance after consuming the maximum US FDA-recommended level of saccharin for six days. These four people showed gut bacteria differences compared with the three people who did not show an effect, both before and after consuming the saccharin.
  • Transfer of gut bacteria from the volunteers showing a response to bacteria-free mice caused the mice to develop glucose intolerance. This was not seen if they transferred gut bacteria from the non-responding human volunteers to mice.


How did the researchers interpret the results?

The researchers concluded that consuming artificial sweeteners increases the risk of glucose intolerance in mice and humans by changing the gut bacteria and therefore affecting their function.

They say their findings suggest artificial sweeteners "may have directly contributed to enhancing the exact epidemic [obesity and diabetes] that they themselves were intended to fight".



This fascinating and controversial study in mice and humans suggests artificial sweeteners, particularly saccharin, could lead to glucose intolerance by having an effect on gut bacteria. The fact that both the animal and human experiments seem to support this adds some weight to the findings.

However, the researchers' investigations in humans are currently limited. They assessed the link between long-term artificial sweetener consumption and various indicators of metabolic problems, such as fat around the waist, using a cross-sectional design. This cannot establish which came first and therefore which could be influencing the other. Also, the only confounder in humans that seemed to be considered was body mass index.

The researchers also only directly tested the effect of one artificial sweetener (saccharin) in an uncontrolled study on just seven healthy adults over the course of a week. Saccharin is less commonly used than other artificial sweeteners, and the participants also consumed it at the maximum US FDA-recommended level (equivalent to 120mg a day).

The findings suggest – at least in the short term – saccharin may only affect glucose response in some people, depending on their gut bacteria. Larger studies, which also incorporate a control group, are needed to see whether they support the results and whether other sweeteners have similar effects.

Some earlier human studies have found links between artificial sweeteners and weight gain and increased diabetes risk. However, it has generally been assumed this is because the people who consume more artificial sweeteners because the sweeteners contain no calories already have problems with their weight, which is why they are at more risk, not vice versa (reverse causation).

This study raises the intriguing possibility that artificial sweeteners could also be directly affecting how our bodies respond to sugar. However, this research is only in its early stages, and we cannot say for certain whether artificial sweeteners are contributing to the diabetes epidemic.

In the interim, if you are trying to reduce your sugar intake, you can do so without replacing sugar with artificial sweeteners.

For people trying to lose weight and those with diabetes who are trying to control their blood sugar, it is important to do what works for them as this is more likely to be sustainable in the long term.

For some people, substituting food and drinks containing artificial sweeteners, rather than those containing sugar, may help with these goals.

At this stage, it is far too early to drop artificial sweeteners from the arsenal of sugar alternatives that could be used to fight the diabetes and obesity epidemic.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Artificial sweeteners may promote diabetes, claim scientists. The Guardian, September 17 2014

Sweeteners 'linked to rise in obesity and diabetes'. The Independent, September 17 2014

Low-calorie sweeteners found in diet drinks RAISE the risk of obesity and diabetes by affecting how the body processes sugar. Daily Mail, September 18 2014

Artificial food sweeteners linked to diabetes. Daily Express, September 17 2014

Sweeteners 'could cause obesity' scientists warn. The Daily Telegraph, September 17 2014

Artificial sweeteners linked to glucose intolerance. New Scientist. September 17 2014

Links To Science

Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. Published online September 17 2014

Categories: News