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'New wonder pill' hard to swallow

  • 3 Comments

The Daily Mail has today hailed “an all-in-one treatment that works against obesity, diabetes, heart disease and cancer”.

The news is based on lab tests of a synthetic compound called SRT1720, which was found to improve survival, motor function, insulin sensitivity and organ health in mice that were fed a high-fat diet. SRT1720 is thought to activate an enzyme that has been shown to increase lifespan in lower organisms such as worms and yeast.

Although the results of this trial show that this chemical may be of some interest, it should be noted that even if these results in mice are applicable to humans, mice fed the drug alongside a high-fat diet still had worse markers of health and reduced lifespan compared to mice on a standard diet. Also, the Daily Mail’s headline implied that SRT1720 could be used as an ingredient in a ‘red wine pill’ due to its similarity to the resveratrol compound found in red grapes. However, results on resveratrol research itself have been inconsistent.

This early-stage research in mice has very limited current implications. A cure-all pill for all cardiovascular diseases and cancers - if such a thing could ever exist - is an extremely long way off in the future.

Where did the story come from?

The study was carried out by researchers from a number of organisations, including the US National Institute on Aging, US National Institutes of Health, and Sirtris, a company owned by the GlaxoSmithKline pharmaceutical company. The research was funded by Sirtris, the National Institute on Aging and National Institutes of Health. Sirtris manufactures the SRT1720 drug tested in this research.

The study was published in the peer-reviewed scientific journal, Scientific Reports.

This story was unrealistically reported in the Daily Mail. The Daily Mail reports that the drug would allow people “to eat as much as they like without putting on a pound,” which is a puzzling claim since the mice treated with SRT1720 in this study actually put on weight while on the high-fat diet. The Mail also reported that the drug could be a treatment for diabetes, heart disease and cancer, conditions that were not investigated in the study.

It is unclear why the Mail hailed the “red wine pill” as a potential cure for “everything from obesity to cancer”. The likely reason is that the research paper says that SRT1720 has similar effect to resveratrol, a chemical found in the skin of red grapes. However, there is no consensus on whether resveratrol itself has clear benefits for health.

 What kind of research was this?

This was a laboratory-based study examining a synthetic compound called SRT1720, which was identified for its ability to activate Sirt1 in mice fed a high fat diet. Sirt1 is an enzyme which has been shown to extend the lifespan in lower organisms such as worms and flies. It also improves metabolism and delays the onset of age-related diseases in mammals.

 What did the research involve?

One-year-old male mice were fed either:

  • a standard diet
  • a high-fat diet
  • a high-fat diet with a low daily dose of SRT1720 (30mg/kg bodyweight)
  • a high-fat diet with a high daily dose of SRT1720 (100mg/kg bodyweight)

The researchers wanted to examine how these diets affected lifespan; fat mass; weight of the organs and their structure and function; serum levels of high-density lipoprotein, glucose and insulin; metabolism; and movement of the mice. They also monitored a variety of other measures, including motor function, insulin sensitivity, organ health and metabolic activity, as well as the genes expressed by the mice on the different diets.

The researchers then performed experiments to support their hypothesis that the SRT1720 chemical acts by activating an enzyme called Sirt1.

 What were the basic results?

There were no indications that SRT1720 was toxic to the mice.

Mice on the high-fat diet had a reduced lifespan compared to mice on the standard diet. Despite the fact that all mice on the high-fat diet put on similar amounts of weight, SRT1720 treatment increased both the average and maximum lifespan of mice on the high-fat diet. Whole-body fat mass of mice on the high-fat diet was double that of mice on the standard diet. However, despite putting on equal amounts of weight, the fat masses of the mice on the high-fat diet were significantly reduced by treatment with a high dose of SRT1720.

The different diets had different effects on organ weight. The high-fat diet significantly increased the weight of the liver, heart and kidneys of the mice. Treatment with both doses of SRT1720 reduced this increase in organ weight, although the weight of the liver was still significantly greater than in mice fed the standard diet. Heart function was similar between the mice on the different diets.

However, SRT1720 reduced the accumulations of lipid (fat) droplets in the liver cells and protected against the increases in pancreas islet size experienced by mice on the high-fat diet (islet cells produce insulin, so increased size indicates increased production of insulin, which would occur if the body’s cells had developed insulin resistance).

Serum levels of high-density lipoprotein (‘good’ fat), which is positively associated with cardiovascular health, was increased in mice treated with the high dose of SRT1720 compared to all other diet groups. Circulating glucose levels were similar in all diet groups, although the insulin levels in mice fed the high-fat diet were double those of mice fed the standard diet. The high dose of SRT1720 reduced the insulin levels back to normal. Tests of insulin resistance produced similar results.

To examine metabolism, the researchers monitored the volume of oxygen consumed by the mice. This displayed the expected pattern of increased oxygen consumption during the dark period, when mice are active and feeding. Mice on the high-fat diet had increased oxygen consumption compared to mice on the standard diet. This was reversed by intake of either dose of SRT1720. Mice on the high-fat diet were less active, and this was improved by a high dose of SRT1720.

Treatment with SRT1720 caused the genes expressed in the liver to be different in mice on a high-fat diet. SRT1720 treatment suppressed genes that have previously been shown to correlate with ageing in studies on kidney and brain. SRT1720 also decreased expression of several gene sets associated with inflammatory changes.

Consistent with this hypothesis were the results of experiments that were conducted in order to examine whether SRT1720 acts by activating Sirt1.

How did the researchers interpret the results?

“These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.”

Conclusion

In this study, a synthetic compound called SRT1720 was tested in mice fed a high-fat diet due to its ability to activate Sirt1. Sirt1 has previously been shown to extend the lifespan in lower organisms such as worms and yeast, and to improve metabolism and delay the onset of age-related diseases in mammals.

The results of this long-term mouse study support the beneficial effects of SRT1720 in mice fed a high-fat diet. Although the results of this study show this chemical may have potential, there are several considerations to be taken into account:

  • This study was performed in mice. Much further study will be required before it is known whether a version of this drug will be available for human testing. Despite the promising effects of this drug, Sirtris is not putting it into clinical trials. Instead, a number of similar compounds are being developed.
  • The effects of this drug were seen on mice fed a high-fat diet (16% of calories from carbohydrate, 23% from protein and 61% from fat). In this study, the researchers did not investigate the effects of the drug on mice that were fed a normal diet.
  • This drug, even if a version were developed for human use, would not be an excuse for an unhealthy diet. In mice fed on the high-fat diet, even when given a high dose of SRT1720, markers of health were still worse than in mice fed on a standard diet.
  • As stated above, this study had nothing to do with red wine as the Mail’s headlines imply, and it did not investigate effectiveness against the prevention of cancer.

This early stage research in mice has very limited current implications. A cure-all pill for all cardiovascular diseases and cancers - if such a thing could ever exist - is an extremely long way off in the future.

  • 3 Comments

Readers' comments (3)

  • Your article is comprehensive and it is understandable that you came to the conclusions that you did.

    Still I disagree. Since men in my family have tended to die at a below average age I have been interested in hopefully raising that age for myself.

    I have been taking very large amounts (approx 2.5 gms) daily since 2006. I understand that my statements are anecdotal but the weight of the evidence at least points in a direction.

    I lost 14 lbs in two weeks when I started this, then I plateaued. I noticed an improvement in my energy levels. (yes that is subjective) My grey facial hair turned salt and peeper. A modest amount of hair regrew on my bald head. My Cholesterol dropped my hdl rose, fatty liver issues went, and my blood pressure went down.

    A friend who would have been considered obese who has numerous health issues, experienced similar effects as he lost 4.5 lbs per month, his blood sugar levels stabilized (diabetic) also had some hair regrowth. His docotrs wanted to know what he was doing.

    Since some of these effects seem to paralleled those found with the above resveratrol variants I am inclined to suggest that one can find related substances over the counter that might have similar effects. It certainly is true that due to the amount of time that research and development take it will be a while for a prescription drug to be developed, but it seems one can find similar substances (if you are willing to make yourself a proverbial Guinea pig) at this time. Certainly a person should be careful when taking supplements and it is best discussed with your doctor although in some cases you might be aware of things your Dr is not. Oh yes 2.5 years after telling my doctor about this he and his wife started to doctor it. He was satisfied that it was not going to cause harm and might be beneficial.

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  • Your statement that results have been inconsistent is highly misleading and unrepresentative of the actual state of research on resveratrol. In all of the human clinical trials undertaken so far, and the vast majority of in vitro studies, of which there are over 5,000 now, the results have been remarkably consistent and extraordinarily positive. The pill, Transmax, which is the extract used in almost all human clinical trials, was shown in the Albert Einstein Medical College clinical trial to substantially increase glucose tolerance, enhance mitochondrial efficiency and lower blood plasma glucose levels. This study has been replicated 4 times with virtually identical results. In a study done at Northumbria University on 24 students using Bioforte, cerebral blood flow was increased by up to 200% when the students were challenged with a computer math exam. In the Ottawa Hospital study Transmax improved mitochondrial function. The largest human clinical trial to date is about to commence in Denmark using a time release version of transmax and will investigate 50 subjects to ascertain the effect of resveratrol on diabetes, inflammation, and liver health. The Imperial College of London has been awarded a patent for use of resveratrol for COPD. I can site additional studies but this is not the proper forum for such and elaborate discussion.

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  • The study cited here is an old one and was not done using actual trans-resveratrol. If you do a scholar google search you will see thousands of peer reviewed published studies which do confirm the health effects of resveratrol. In addition to the human trials using the supplements transmax and bioforte, there have been human clinical trials at the University of Texas, Torino University, the University of Ferrara, Stanford, the Mayo Clinic and many others which confirm the transmax studies. Some early investigations into the use of resveratrol for treatment of pancreatic cancer have returned extremely positive results, and clinical trials published in January of this year conclude that resveratrol performs at least as well as Metformin in modulating blood glucose in type 2 diabetics. I understand that you can not be an expert in everything and that some of the human trials are not available to non researchers at this point however the tone of your article implies that resveratrol is not what the Mail represented it to be when in fact, based upon the research to date, it is more likely much more than the Daily Mail article implies.

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