Health Research Report
165th Issue Date 5 OCT 2013
Compiled By Ralph Turchiano
In This Issue:
1. Melatonin helps control weight gain as it stimulates the appearance of ‘beige fat’
2. Folic acid deficiency can affect the health of great, great grandchildren
3. Mouse studies reveal promising vitamin D-based treatment for MS
4. Organized screening for prostate cancer does more harm than good
5. Niacin, the fountain of youth
6. Red wine chemical remains effective against cancer after the body converts it
7. Component of citrus fruits found to block the formation of kidney cysts
Melatonin helps control weight gain as it stimulates the appearance of ‘beige fat’
Melatonin is a natural hormone segregated by the body and melatonin levels generally increase in the dark at night. It is also found in fruit and vegetables like mustard, Goji berries, almonds, sunflower seeds, cardamom, fennel, coriander and cherries.
Spanish scientists have discovered that melatonin consumption helps control weight gain because it stimulates the appearance of ‘beige fat’, a type of fat cell that burns calories in vivo instead of storing them. White adipose tissue stores calories leading to weight gain whereas ‘beige fat’ (also known as ‘good or thinning fat’) helps regulate body weight control, hence its metabolic benefits.
In the Journal of Pineal Research, scientists from the University of Granada Institute for Neuroscience, the Hospital Carlos III, Madrid, and the University of Texas Health Science Center in San Antonio (USA) have revealed, for the first time, the previously unknown enigma of why melatonin has metabolic benefits in treating diabetes and hyperlipidemia.
In earlier publications, the researchers analysed the effects of melatonin on obesity, dyslipidemia, high blood pressure and type 2 diabetes mellitus associated with obesity in young obese diabetic Zucker rats—an experimental model of metabolic syndrome.
In view of their most recent results, it seems the key lies in the fact that chronic melatonin consumption not only induces the appearance of ‘beige fat’ in obese diabetic rats, but also increases its presence in thin animals used as a control group. ‘Beige fat’ cells are found in scattered lentil-sized deposits beneath the inguinal skin in obese diabetic Zucker rats.
Melatonin is a natural hormone segregated by the human body itself and melatonin levels generally increase in the dark at night. It is also found in small quantities in fruit and vegetables like mustard, Goji berries, almonds, sunflower seeds, cardamom, fennel, coriander and cherries. These findings, together with the pharmacologically safe profile of melatonin, mean it is a potentially useful tool both in its own right and to complement the treatment of obesity. Sleeping in the dark and consuming these foodstuffs could help control weight gain and prevent cardiovascular diseases associated with obesity and dyslipidemia.
The study—coordinated by University of Granada lecturer Ahmad Agil—showed that chronic administration of melatonin sensitizes the thermogenic effect of exposure to cold, heightens the thermogenic effect of exercise and, therefore, constitutes excellent therapy against obesity. The fact is that one of the key differences between ‘beige fat’, which appears when administering melatonin, and ‘white fat’, is that ‘beige fat’ cell mitochondria express levels of UCP1 protein, responsible for burning calories and generating heat.
The study—authored by Aroa Jiménez-Aranda, Gumersindo Fernández-Vázquez, Daniel Campos, Mohamed Tassi, Lourdes Velasco-Perez, Tx Tan, Russel J. Reiter and Ahmad Agil—has been part-financed and supported by the Granada Research of Excellence Initiative on BioHealth (GREIB), the University of Granada Vice-Rectorate for Scientific Policy and Research, and the regional government of Andalusia research group CTS-109.
Given the importance of this discovery, the researchers are confident they will obtain the funding needed to continue their work—says principle researcher Ahmad Agil—”and be able to achieve their final objective: to confirm these findings in humans, by administering melatonin to help combat obesity and diabetes”.
Folic acid deficiency can affect the health of great, great grandchildren
Deficiencies associated with spina bifida, heart defects and placental abnormalities
Folic acid deficiency can cause severe health problems in offspring, including spina bifida, heart defects and placental abnormalities. A study out today reveals that a mutation in a gene necessary for the metabolism of folic acid not only impacts the immediate offspring but can also have detrimental health effects on the next several generations. The new research, which also sheds light on the molecular mechanism of folic acid (also known as folate) during development, was published today in the journal Cell.
“Although our research focused on genetic mutations which disrupts the break down and metabolism of folic acid, we believe that folic acid deficiency in the diet would have a similar multi-generational impact on health,” said Dr Erica Watson from the Centre for Trophoblast Research at the University of Cambridge, who led the study.
The detrimental effects of folic acid deficiency on development are quite well known. As a result, many countries, to include Canada and the US, have implemented folate fortification programmes which require folic acid to be added to cereal products. However, until now, very little was known about how folic acid deficiency caused the diverse range of health problems in offspring.
“Fortification programmes have reduced the risk of health effects but not eliminated them completely,” said Dr Watson. “Based on our research, we now believe that it may take more than one generation to eliminate the health problems caused by folate deficiency.”
The researchers, from the Universities of Cambridge and Calgary, used mice for the study as they metabolize folic acid very similarly to humans and because folic acid deficiency or mutations in the same genes required to break down folic acid in humans result in similar developmental abnormalities and diseases in mice. This enabled the researchers to explore how the molecular mechanism of folic acid deficiency impacted development, thereby causing health problems.
For the study, the scientists used mice in which a gene called Mtrr was specifically mutated. The gene is key to the normal progression of the folic acid cycle and, when mutated, it results in abnormal folic acid metabolism causing similar effects to dietary folic acid deficiency. The researchers found that when either the maternal grandmother or the maternal grandfather had this Mtrr mutation, their genetically normal grandchildren were at risk of a wide spectrum of developmental abnormalities. These developmental abnormalities were also seen in the fourth and fifth generations of mice.
Through another experiment which involved transferring the embryo from the third generation into a normal healthy female mouse, they discovered that these developmental abnormalities were not passed down genetically. Instead, the serious defects were the result of epigenetic changes which had been inherited.
Epigenetics is a system which turns genes on and off. It occurs when chemicals, such as methyl groups, bind to the DNA at specific locations to control which genes are expressed and when they are expressed. (Interestingly, the folic acid cycle is required to make sure that the cell has enough methyl groups for normal gene expression.) Epigenetic inheritance refers to the passing of these epigenetic marks from one generation to the next – despite the epigenome, for the most part, being ‘wiped clean’ after each generation.
The researchers hypothesize that, for a yet unknown reason, some of these abnormal epigenetic marks caused by the Mtrr mutation may escape this normal erasure and are inherited by the next generation. If these abnormal epigenetic marks that regulate genes important for development are inherited, then these generations may develop abnormalities as a result of the wrong genes being turned on or off.
“It surprised us to find that the great, great grandchildren of a parent who has had a folic acid deficiency could have health problems as a result – suggesting that the ‘sins of your maternal grandparents’ can have an effect on your development and your risk for disease,” said Dr Watson.
“More importantly, our research shows that disease in general can be inherited through epigenetic means rather than genetic means, which has huge implications for human health. Environmental factors that influence epigenetic patterns – e.g., diet, epigenetic disruptors in the environment such as chemicals, etc. – may also have long term, multigenerational effects.”
Mouse studies reveal promising vitamin D-based treatment for MS
MADISON — A diagnosis of multiple sclerosis (MS) is a hard lot. Patients typically get the diagnosis around age 30 after experiencing a series of neurological problems such as blurry vision, wobbly gait or a numb foot. From there, this neurodegenerative disease follows an unforgiving course.
Many people with MS start using some kind of mobility aid — cane, walker, scooter or wheelchair — by 45 or 50, and those with the most severe cases are typically bed-bound by 60. The medications that are currently available don’t do much to slow the relentless march of the disease.
In search of a better option for MS patients, a team of University of Wisconsin-Madison biochemists has discovered a promising vitamin D-based treatment that can halt — and even reverse — the course of the disease in a mouse model of MS. The treatment involves giving mice that exhibit MS symptoms a single dose of calcitriol, the active hormone form of vitamin D, followed by ongoing vitamin D supplements through the diet. The protocol is described in a scientific article that was published online in August in the Journal of Neuroimmunology.
“All of the animals just got better and better, and the longer we watched them, the more neurological function they regained,” says biochemistry professor Colleen Hayes, who led the study.
MS afflicts around 400,000 people nationwide, with 200 new cases diagnosed each week. Early on, this debilitating autoimmune disease, in which the immune system attacks the myelin coating that protects the brain’s nerve cells, causes symptoms including weakness, loss of dexterity and balance, disturbances to vision, and difficulty thinking and remembering. As it progresses, people can lose the ability to walk, sit, see, eat, speak and think clearly.
Current FDA-approved treatments only work for some MS patients and, even among them, the benefits are modest. “And in the long term they don’t halt the disease process that relentlessly eats away at the neurons,” Hayes adds. “So there’s an unmet need for better treatments.”
While scientists don’t fully understand what triggers MS, some studies have linked low levels of vitamin D with a higher risk of developing the disease. Hayes has been studying this “vitamin D hypothesis” for the past 25 years with the long-term goal of uncovering novel preventive measures and treatments. Over the years, she and her researchers have revealed some of the molecular mechanisms involved in vitamin D’s protective actions, and also explained how vitamin D interactions with estrogen may influence MS disease risk and progression in women.
In the current study, which was funded by the National Multiple Sclerosis Society, Hayes’ team compared various vitamin D-based treatments to standard MS drugs. In each case, vitamin D-based treatments won out. Mice that received them showed fewer physical symptoms and cellular signs of disease.
First, Hayes’ team compared the effectiveness of a single dose of calcitriol to that of a comparable dose of a glucocorticoid, a drug now administered to MS patients who experience a bad neurological episode. Calcitriol came out ahead, inducing a nine-day remission in 92 percent of mice on average, versus a six-day remission in 58 percent for mice that received glucocorticoid.
“So, at least in the animal model, calcitriol is more effective than what’s being used in the clinic right now,” says Hayes.
Next, Hayes’ team tried a weekly dose of calcitriol. They found that a weekly dose reversed the disease and sustained remission indefinitely.
But calcitriol can carry some strong side effects — it’s a “biological sledgehammer” that can raise blood calcium levels in people, Hayes says — so she tried a third regimen: a single dose of calcitriol, followed by ongoing vitamin D supplements in the diet. This one-two punch “was a runaway success,” she says. “One hundred percent of mice responded.”
Hayes believes that the calcitriol may cause the autoimmune cells attacking the nerve cells’ myelin coating to die, while the vitamin D prevents new autoimmune cells from taking their place.
While she is excited about the prospect of her research helping MS patients someday, Hayes is quick to point out that it’s based on a mouse model of disease, not the real thing. Also, while rodents are genetically homogeneous, people are genetically diverse.
“So it’s not certain we’ll be able to translate (this discovery to humans),” says Hayes. “But I think the chances are good because we have such a broad foundation of data showing protective effects of vitamin D in humans.”
The next step is human clinical trials, a step that must be taken by a medical doctor, a neurologist. If the treatment works in people, patients with early symptoms of MS may never need to receive an official diagnosis.
“It’s my hope that one day doctors will be able to say, ‘We’re going to give you an oral calcitriol dose and ramp up the vitamin D in your diet, and then we’re going to follow you closely over the next few months. You’re just going to have this one neurological episode and that will be the end of it,'” says Hayes. “That’s my dream.”
Organized screening for prostate cancer does more harm than good
Prostate cancer screening using the prostate-specific antigen (PSA) test is widely used in France despite a lack of evidence showing that it reduces cancer deaths. Now, researchers have shown that men experience more harm than good from routine PSA screening, according to research to be presented on Monday by Professor Mathieu Boniol, at the 2013 European Cancer Congress (ECC2013) .
Prof Boniol, Research Director at the International Prevention Research Institute (iPRI) and Professor at the Strathclyde Institute for Global Public Health at iPRI, Lyon, France, will tell the congress that the total harm men experience in terms of impotence and incontinence, and the side-effects from prostate cancer treatments, severely affects their quality of life, and should further discourage the use of PSA testing for prostate cancer screening.
Prof Boniol will say: “The test measures PSA protein levels, which are produced by the prostate gland, in a man’s blood, and may help detect early cancer. However, we believe that PSA testing should be used as an additional aid in the diagnosis and management of prostate cancer rather than as the major entry point for prostate biopsy and further examinations. PSA testing should be reduced and more attention should be given to the harmful effects of screening related to the use of the test.
“We wanted to provide clinicians with a better idea of the consequences of organised PSA screening and we thought that providing numbers for the different side-effects following PSA testing would be easiest to interpret. Therefore, we estimated the total harm that men could endure if exposed to PSA testing by applying different side-effect estimates to a virtual population of 1,000 men aged 55 years. We also included a group of 1,000 men who were not screened for prostate cancer for comparison,” he says.
“We estimated the total harm that men should endure if exposed to PSA testing by applying different side-effect estimates to a virtual population of 1,000 men aged 55-69 years. We also included a group of 1,000 men who were not screened for prostate cancer for comparison.”
Using data from the European Randomized Study of Screening for Prostate Cancer (ERSPC), which was the only trial to show that PSA testing was associated with a significant reduction in prostate cancer deaths, information on the number of men needed to undergo a prostate biopsy and the number of prostate cancer cases diagnosed was extracted. These data were combined with other published data on side-effects associated with biopsy and with the surgery used to remove prostate tumours.
“Overall, the death rates due to prostate cancer were in the same order of magnitude between the two groups of men: we estimated that 5.17 deaths due to prostate cancer would occur in the group of unscreened men compared to 4.1 deaths in the group who underwent PSA screening.
“Yet in order to prevent one death from prostate cancer in the 1,000 men screened for PSA, the number of biopsies would double with 154 additional prostate biopsies, and, of 35 additional prostate cancers diagnosed, 12 additional cases of impotence and three additional cases of incontinence would occur. Thus, the harm from routine PSA testing can have a serious effect on the quality of life of patients and provides additional evidence against the use of organised screening for prostate cancer,” he says.
Currently, the PSA test is used widely throughout Europe for prostate cancer screening, although there in insufficient evidence to support its utility and there is no organised, population-based prostate cancer screening programme. According to European Union Cancer Database (EUCAN) estimates, over 73,600 new cases of prostate cancer were diagnosed in France in 2012 and around 8,600 men died from the disease .
“Approximately 75% of men aged 60 in France have had a PSA test done within the previous three years and despite no national recommendation to promote PSA testing, nor any national organisation, it may partly explain the reported high incidence rates of prostate cancer throughout France,” Prof Boniol says.
“All available evidence suggests that PSA testing for prostate cancer should not be routinely recommended for asymptomatic men in Europe. When discussing the use of the PSA test with patients, physicians should make them aware of the limitations of the test and the likelihood of it causing harm. We hope that our research findings will help clinicians to make decisions as to when to propose a PSA test, and to help the patient to decide whether or not to accept this recommendation,” he will say.
Prof Boniol will also present results from research investigating the harm associated with prostate cancer surgery, in which investigators found that in France the risk of dying 60 days after an operation tripled in men aged 70 years or older.
Removal of the entire prostate gland is the surgical procedure used to treat prostate cancer and it is called a radical prostatectomy. It can be performed by open (laparotomy) or keyhole (laparoscopic) surgery. The procedure is associated with a risk of dying after the surgery. However, the degree of increased risk is unknown and Prof Boniol says it needs to be considered when evaluating the harm linked with prostate cancer treatment.
Records for men aged over 40 who had undergone a radical prostatectomy between 2007 and 2011 were retrieved from the French Technical Agency for Information on Hospitalization database. A total of 120,333 prostate cancer surgeries were performed among the 637 hospitals included in the database, of which 68,106 were open surgery and 52,227 were keyhole surgery.
The researchers found that a high percentage of prostate cancer surgery (18%) was performed in men older than 70. They also found that 60 days after prostate cancer surgery there were 183 deaths (0.15%). The risk of dying was 0.11% for men aged 40 years and increased to 0.36% for men aged 70 years or older, 60 days post surgery.
Prof Boniol will say: “We found that a high number of prostate cancer surgical procedures were performed on older men, over 70 years of age, a group of individuals where surgery should be viewed with extreme caution as the potential to provide a few additional years of life is also associated with a very high risk of premature death. In this group of men, the risk of dying following radical prostatectomy was much higher than with younger men.
“The results of this research also question the use of prostate cancer surgery. One of the main problems with using PSA testing for prostate cancer screening is over-diagnosis. An over-diagnosed prostate cancer patient is labelled as a prostate cancer case, but he will never suffer from the disease although he will experience the potential side-effects of prostate cancer treatment. Our findings show that elderly men are over-treated for prostate cancer, and that, for them, surgery is unlikely to provide any benefit.
“We hope that expert committees evaluating new clinical guidelines for the management of prostate cancer will request that the benefits and harm of prostate cancer surgery be assessed, especially in relation to the use of PSA testing.”
President of ECCO, Professor Cornelis van de Velde, commented: “Screening for prostate cancer is controversial and recommendations exist against PSA-based screening. Despite this, it is widely used especially in France. This national study indicates that it causes more harm than good, especially in men aged 70 or older who have triple the risk of younger men of dying after the operation. These results should lead to stricter guidelines and registries to evaluate the over-treatment of prostate cancer.”
Co-scientific chair of ECC2013 and ESMO spokesperson, Professor Cora Sternberg, commented: “PSA screening holds the promise of early diagnosis when cancer is localised to the prostate and treatment is curative. Screening has, however, also led to many false positive results, over-diagnosis of disease and significant morbidity as demonstrated in this French study, particularly in men over 70 years of age.
“International recommendations vary on the value of routine PSA screening. The European Association of Urology says that current evidence is insufficient to recommend the adoption of population screening for prostate cancer as a public health policy due to the large overtreatment effect. The American Urological Association suggests that for men aged 55 to 69 years, PSA screening involves weighing the benefits of preventing prostate cancer mortality in one man for every 1,000 men screened over a decade against the known potential harms associated with screening and treatment. Men are urged to talk with their doctors about benefits and harms of testing. Along the lines of this French study, the American Cancer Society also suggests discussion with the physician regarding the benefits and hazards of early detection.” 
 The 2013 European Cancer Congress is the 17th congress of the European CanCer Organisation (ECCO), the 38th congress of the European Society for Medical Oncology (ESMO) and the 32nd congress of European Society for Therapeutic Radiology and Oncology (ESTRO).
 European Journal of Cancer, Vol 49, issue 6 (April 2013), pages 1374-403.”Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012.” Available from: http://eco.iarc.fr. Accessed on 01 July 2013.
 Professor Sternberg is Chief of the Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
 The work was funded by the International Prevention Research Institute, Lyon, France.
Niacin, the fountain of youth
The vitamin niacin has a life-prolonging effect, as Michael Ristow has demonstrated in roundworms. From his study, the ETH-Zurich professor also concludes that so-called reactive oxygen species are healthy, not only disagreeing with the general consensus, but also many of his peers.
Who would not want to live a long and healthy life? A freely available food supplement could help in this respect, scientists from ETH Zurich have demonstrated in roundworms. Vitamin B3 – also known as niacin – and its metabolite nicotinamide in the worms’ diet caused them to live for about one tenth longer than usual.
As an international team of researchers headed by Michael Ristow, a professor of energy metabolism, has now experimentally demonstrated, niacin and nicotinamide take effect by promoting formation of so-called free radicals. “In roundworms, these reactive oxygen species prolong life,” says Ristow.
“No scientific evidence for usefulness of antioxidants”
This might seem surprising as reactive oxygen species are generally considered to be unhealthy. Ristow’s view also contradicts the textbook opinion championed by many other scientists. Reactive oxygen species are known to damage somatic cells, a condition referred to as oxidative stress. Particular substances, so-called antioxidants, which are also found in fruit, vegetables and certain vegetable oils, are capable of neutralising these free radicals. Many scientists believe that antioxidants are beneficial to health.
“The claim that intake of antioxidants, especially in tablet form, promotes any aspect of human health lacks scientific support,” says Ristow. He does not dispute that fruit and vegetables are healthy. However, this may rather be caused by other compounds contained therein, such as so-called polyphenols. “Fruit and vegetables are healthy, despite the fact that they contain antioxidants,” says the ETH-Zurich professor. Based on the current and many previous findings he is convinced that small amounts of reactive oxygen species and the oxidative stress they trigger have a health-promoting impact. “Cells can cope well with oxidative stress and neutralise it,” says Ristow.
Substance mimics endurance sport
In earlier studies on humans, Ristow demonstrated that the health-enhancing effect of endurance sports is mediated via an increased formation of reactive oxygen species – and that antioxidants abolish this effect. Based on the present study, he concludes that niacin brings about a similar metabolic condition to exercise. “Niacin tricks the body into believing that it is exercising – even when this is not the case,” says Ristow. Such compounds are known as “exercise mimetics”.
The researchers conducted their experiments on the model organism Caenorhabditis elegans. This worm, which is merely one millimetre in length, can be easily maintained and has a lifespan of only a month, making it the ideal model organism for ageing research.
Also relevant for humans
The results of the study may also be of relevance for humans, says Ristow. After all, the metabolic pathway initiated by niacin is very similar in roundworms and higher organisms. Whether niacin has similar effects on the life expectancy of mice is the subject of Ristow’s current research. Previous studies also suggest a health-enhancing effect of niacin in humans with elevated blood cholesterol levels.
Niacin and nicotinamide have been approved as dietary supplements for decades. Ristow could easily envisage the substances being used broadly for therapeutic purposes in the future. A whole series of foods naturally contain niacin, including meat, liver, fish, peanuts, mushrooms, rice and wheat bran. Whether nutritional uptake is sufficient for a health-enhancing or lifespan-extending effect, however, remains to be demonstrated, says Ristow.
Disputed impact of enzymes
The latest study on the effects of niacin and nicotinamide is based on a particular class of enzymes, the sirtuins, which convert niacin into nicotinamide. Moreover, they are also involved in gene regulation, helping to down regulate the activity of certain genes. Until today, scientists have been disputing whether sirtuins have a life-prolonging impact.
Ristow and his team’s work now suggests that the activity of sirtuins actually prolongs life in roundworms. According to the study, however, the life-prolonging effect is not down to gene regulation, as has often been supposed in the past. Instead, the effect is due to the conversion of niacin into nicotinamide. Studying genetically modified roundworms that were unable to convert nicotinamide into certain other metabolic products, the scientists did not observe any lifespan extension, even after overexpression of sirtuins, which otherwise lead to an increased life expectancy.
Schmeisser K et al.: Role of Sirtuins in Lifespan Regulation is Linked to Methylation of Nicotinamide. Nature Chemical Biology, 2013, Advance Online Publication, doi: 10.1038/nchembio.1352
Red wine chemical remains effective against cancer after the body converts it
Paper by University of Leicester scientists shows resveratrol can still be used in the body after it has been metabolized
A chemical found in red wine remains effective at fighting cancer even after the body’s metabolism has converted it into other compounds.
This is an important finding in a new paper published in the journal Science Translational Medicine by Cancer Research UK-funded researchers at the University of Leicester’s Department of Cancer Studies and Molecular Medicine.
The paper reveals that resveratrol – a compound extracted from the skins of red grapes – is not rendered ineffective once it is metabolised by the body.
This is an important development, as resveratrol is metabolised very quickly – and it had previously been thought that levels of the extracted chemical drop too quickly to make it usable in clinical trials.
The new research shows that the chemical can still be taken into
cells after it has been metabolised into resveratrol sulfates.
Enzymes within cells are then able to break it down into resveratrol again – meaning that levels of resveratrol in the cells are higher than was previously thought.
In fact, the results appear to show resveratrol may be more effective once it has been generated from resveratrol sulfate than it is if it has never been metabolised because the concentrations achieved are higher.
The team, led by University of Leicester translational cancer research expert Professor Karen Brown, administered resveratrol sulfate to mice models.
They were subsequently able to detect free resveratrol in plasma and a variety of tissues in the mice.
This is the first direct sign that resveratrol can be formed from resveratrol sulfate in live animals, and the researchers think it may help to show how resveratrol is able to have beneficial effects in animals.
The study also showed that resveratrol generated from resveratrol sulfate is able to slow the growth of cancer cells by causing them to digest their own internal constituents and stopping them from dividing.
Professor Karen Brown said: “There is a lot of strong evidence from laboratory models that resveratrol can do a whole host of beneficial things – from protecting against a variety of cancers and heart disease to extending lifespan.
“It has been known for many years that resveratrol is rapidly converted to sulfate and glucuronide metabolites in humans and animals – meaning the plasma concentrations of resveratrol itself quickly become very low after administration.
“It has always been difficult to understand how resveratrol is able to have activity in animal models when the concentrations present are so low, and it has made some people skeptical about whether it might have any effects in humans.
“Researchers have hypothesized for a long time that resveratrol might be regenerated from its major metabolites in whole animals but it has never been proven.
“Our study was the first to show that resveratrol can be regenerated from sulfate metabolites in cells and that this resveratrol can then have biological activity that could be useful in a wide variety of diseases in humans.
“Importantly, we did all our work with clinically achievable concentrations so we are hopeful that our findings will translate to humans.
“Overall, I think our findings are very encouraging for all types of medical research on resveratrol. They help to justify future clinical trials where, previously, it may have been difficult to argue that resveratrol can be useful in humans because of the low detectable concentrations.
“There is considerable commercial interest in developing new forms of resveratrol that can resist or overcome the issue of rapid metabolism. Our results suggest such products may not actually be necessary to deliver biologically active doses of resveratrol to people.”
Dr Sarah Williams, Cancer Research UK health information officer, said: “This interesting study supports continued research into resveratrol as a therapeutic molecule, but it’s important to note that any benefits from the molecule don’t come from drinking red wine. It’s well established that drinking any type of alcohol, including red wine, increases the risk of developing cancer.”
Component of citrus fruits found to block the formation of kidney cysts
A new study published today in British Journal of Pharmacology has identified that a component of grapefruit and other citrus fruits, naringenin, successfully blocks the formation of kidney cysts.
Known as polycystic kidney disease, this is an inherited disorder which leads to the loss of kidney function, high blood pressure and the need for dialysis. Few treatment options are currently available.
The team of scientists from Royal Holloway University, St George’s, University of London and Kingston University London used a simple, single-celled amoeba to identify that naringenin regulates the PKD2 protein responsible for polycystic kidney disease and as a result, blocks formation of cysts.
“This discovery provides an important step forward in understanding how polycystic kidney disease may be controlled,” said Professor Robin Williams from the School of Biological Sciences at Royal Holloway.
“In the study, we have demonstrated how effective the amoeba Dictyostelium is in the discovery of new treatments and their targets. Having previously applied the same method of testing in our work into epilepsy and bipolar treatments, it is clear that this new approach could help us reduce reliance on animal testing and provide major improvements.”
To test how this discovery could apply in treatments, the team used a mammalian kidney cell-line, and triggered the formation of cysts in these cells. They were then able to block the formation of the cysts by adding naringenin and saw that when levels of the PKD2 protein were reduced in the kidney cells, so was the block in cyst formation, confirming that the effect was connected.
Dr Mark Carew, from the School of Pharmacy and Chemistry at Kingston University, said: “Further investigation is underway to understand the action of naringenin at the molecular level. This work will entail looking at the function of the PKD2 protein as a cell growth regulator.”
“Indeed, this study provides a good example of how chemicals identified in plants can help us develop new drugs for the treatment of disease,” added Professor Debbie Baines from St George’s, University of London.
“Autosomal dominant polycystic kidney disease affects between 1 in 10 people on dialysis and 1 in 8 with a kidney transplant. Kidney Research UK welcomes this publication that may provide hope for a future new treatment for polycystic kidney disease, alongside its own on-going research focusing on tackling this common genetic kidney disease,” said Elaine Davies, Head of Research Operations at Kidney Research UK.
The research was funded by a SWan (SouthWest London Academic Network) research grant.