247CNOREPORT19AUG2017
CNO Report # 247
Release Date 26 AUG 2017
Draft Report Compiled by
Ralph Turchiano
In This Issue:
1. Natural compound coupled with specific gut microbes may prevent severe flu
2. Eating habits affect skin’s protection against sun
3. Compounds in desert creosote bush could treat giardia and ‘brain-eating’ amoeba infections
4. In a nutshell: Walnuts activate brain region involved in appetite control
5. Antibiotics found to weaken body’s ability to fight off disease
6. Latency of seizures determined by diet
7. Vitamin C may encourage blood cancer stem cells to die
8. Studies explore the potential benefits of red raspberries
9. Caffeine tempers taste, triggering temptation for sweets
10. Understanding how omega-3 dampens inflammatory reactions
11. Omega-3 intake reduces cardiac death risk according to comprehensive new study
12. Antioxidant/zinc supplement cost saving and effective for degenerative eye disease
Public Release: 3-Aug-2017
Natural compound coupled with specific gut microbes may prevent severe flu
Mouse study reveals how gut microbes fight influenza
Washington University School of Medicine
Microbes that live in the gut don’t just digest food. They also have far-reaching effects on the immune system. Now, a new study shows that a particular gut microbe can prevent severe flu infections in mice, likely by breaking down naturally occurring compounds — called flavonoids — commonly found in foods such as black tea, red wine and blueberries.
The research, conducted in mice by scientists at Washington University School of Medicine in St. Louis, also indicates that this strategy is effective in staving off severe damage from flu when the interaction occurs prior to infection with the influenza virus. This work also could help explain the wide variation in human responses to influenza infection.
The study is published Aug. 4 in the journal Science.
“For years, flavonoids have been thought to have protective properties that help regulate the immune system to fight infections,” said first author Ashley L. Steed, MD, PhD, an instructor in pediatrics who treats intensive care patients at St. Louis Children’s Hospital. “Flavonoids are common in our diets, so an important implication of our study is that it’s possible flavonoids work with gut microbes to protect us from flu and other viral infections. Obviously, we need to learn more, but our results are intriguing.”
Influenza — characterized by fever, cough and body aches — is a common and sometimes deadly viral infection of the upper respiratory tract. Older adults, pregnant women, young children and people with chronic health problems such as asthma and heart disease are most prone to serious flu complications. Since 2004, an average of 113 children have died from influenza in the U.S. each year, according to the Centers for Disease Control and Prevention. Around the world, the World Health Organization estimates there are 250,000 to 500,000 flu-related deaths annually.
Previous evidence suggests that the gut microbiome may be important in protecting against severe influenza infections, so in this study, the researchers aimed to identify just what gut microbes might provide that protection. In addition, for years, nutritionists have explored potential health benefits linked to foods loaded with flavonoids.
“It’s not only having a diet rich in flavonoids, our results show you also need the right microbes in the intestine to use those flavonoids to control the immune response,” said the study’s senior author, Thaddeus S. Stappenbeck, MD, PhD, the Conan Professor of Pathology & Immunology. “We were able to identify at least one type of bacteria that uses these dietary compounds to boost interferon, a signaling molecule that aids the immune response. This prevented influenza-related lung damage in the mice. It is this kind of damage that often causes significant complications such as pneumonia in people.”
As part of the study, the researchers screened human gut microbes looking for one that metabolized flavonoids. Stappenbeck and Steed identified one such microbe that they suspected might protect against flu damage. The microbe, called Clostridium orbiscindens, degrades flavonoids to produce a metabolite that enhances interferon signaling.
“The metabolite is called desaminotyrosine, otherwise known as DAT,” Steed said. “When we gave DAT to mice and then infected them with influenza, the mice experienced far less lung damage than mice not treated with DAT.”
Interestingly, although the lungs of DAT-treated mice didn’t have as much flu damage, their levels of viral infection were identical to those in mice that didn’t get the treatment.
“The infections were basically the same,” Stappenbeck said. “The microbes and DAT didn’t prevent the flu infection itself; the mice still had the virus. But the DAT kept the immune system from harming the lung tissue.”
That’s important because annual flu vaccines aren’t always effective at preventing infections.
“But with DAT, it may be possible to keep people from getting quite as sick if they do become infected,” Steed said. “This strategy doesn’t target the virus. Instead, it targets the immune response to the virus. That could be valuable because there are challenges with therapies and vaccines that target the virus due to changes in the influenza virus that occur over time.”
Next steps include identifying other gut microbes that also may use flavonoids to influence the immune system, as well as exploring ways to boost the levels of those bacteria in people whose intestines aren’t adequately colonized with those microbes. As those future studies are planned, the researchers said it might not be a bad idea to drink black tea and eat foods rich in flavonoids before the next flu season begins.
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Steed AL, Christophi GP, Kaiko GE, Sun L, Goodwin VM, Jain U, Esaulova E, Artyomov MN, Morales DJ, Holtzman MJ, Boon ACM, Lenschow DJ, Stappenbeck TS. The microbial metabolite desaminotyrosin protects from influenza through type 1 interferon. Science. Aug. 4, 2017.
This work was supported by the Pediatric Scientist Development Program and funded by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH), grant numbers 5K12 HD000850-30 and T32 DK007130-43. Additional funding was provided by the Crohn’s & Colitis Foundation and the Helmsley Charitable Trust.
The authors have applied for a patent for desaminotyrosine stimulation of type 1 IFNs.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.
Public Release: 15-Aug-2017
Eating habits affect skin’s protection against sun
UT Southwestern Medical Center
DALLAS – Aug. 15, 2017 - Sunbathers may want to avoid midnight snacks before catching some rays.
A study in mice from the O’Donnell Brain Institute and UC Irvine shows that eating at abnormal times disrupts the biological clock of the skin, including the daytime potency of an enzyme that protects against the sun’s harmful ultraviolet radiation.
Although further research is needed, the finding indicates that people who eat late at night may be more vulnerable to sunburn and longer-term effects such as skin aging and skin cancer, said Dr. Joseph S. Takahashi, Chairman of Neuroscience at UT Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute.
“This finding is surprising. I did not think the skin was paying attention to when we are eating,” said Dr. Takahashi, also an Investigator with the Howard Hughes Medical Institute.
The study showed that mice given food only during the day – an abnormal eating time for the otherwise nocturnal animals – sustained more skin damage when exposed to ultraviolet B (UVB) light during the day than during the night. This outcome occurred, at least in part, because an enzyme that repairs UV-damaged skin – xeroderma pigmentosum group A (XPA) – shifted its daily cycle to be less active in the day.
Mice that fed only during their usual evening times did not show altered XPA cycles and were less susceptible to daytime UV rays.
“It is likely that if you have a normal eating schedule, then you will be better protected from UV during the daytime,” said Dr. Takahashi, holder of the Loyd B. Sands Distinguished Chair in Neuroscience. “If you have an abnormal eating schedule, that could cause a harmful shift in your skin clock, like it did in the mouse.”
Previous studies have demonstrated strong roles for the body’s circadian rhythms in skin biology. However, little had been understood about what controls the skin’s daily clock.
The latest research published in Cell Reports documents the vital role of feeding times, a factor that scientists focused on because it had already been known to affect the daily cycles of metabolic organs such as the liver.
The study found that besides disrupting XPA cycles, changing eating schedules could affect the expression of about 10 percent of the skin’s genes.
However, more research is needed to better understand the links between eating patterns and UV damage in people, particularly how XPA cycles are affected, said Dr. Bogi Andersen of University of California, Irvine, who led the collaborative study with Dr. Takahashi.
“It’s hard to translate these findings to humans at this point,” said Dr. Andersen, Professor of Biological Chemistry. “But it’s fascinating to me that the skin would be sensitive to the timing of food intake.”
Dr. Takahashi, noted for his landmark discovery of the Clock gene regulating circadian rhythms, is researching other ways in which eating schedules affect the biological clock. A study earlier this year reinforced the idea that the time of day food is eaten is more critical to weight loss than the amount of calories ingested. He is now conducting long-term research measuring how feeding affects aging and longevity.
The UV study was supported by the Irving Weinstein Foundation, the National Institutes of Health, the China Scholarship Council, and the National Science Foundation Graduate Research Fellowship.
The Skinny on Sun, Skin, and Snacking
New research suggests that skin cancer cells are more likely to develop in mice with abnormal eating schedules, due to a disruption in the skin’s biological clock.
Discovery: A new study shows that feeding schedules affect how well the skin is protected from the sun’s harmful UV rays. Eating at abnormal times disrupts the skin’s circadian rhythms and weakens the daytime potency of a protective enzyme.
Why it matters: People who eat late at night may be more vulnerable to sunburn and longer-term effects such as skin aging and skin cancer.
Quotable: “This is surprising. I did not think the skin was paying attention to when we are eating.” – Dr. Joseph Takahashi, UT Southwestern.
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Related findings: Dr. Joseph Takahashi collaborated on a 2017 study that reinforced the idea that when we eat is more critical to weight loss than the amount of calories ingested. He is now conducting long-term research measuring how feeding affects aging and longevity. Learn more here:
· Calories and Circadian Rhythms
Other resources:
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year.
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Public Release: 15-Aug-2017
Compounds in desert creosote bush could treat giardia and ‘brain-eating’ amoeba infections
University of California – San Diego
Researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego and the University of Colorado Anschutz Medical Campus have found that compounds produced by the creosote bush, a desert plant common to the Southwestern United States, exhibit potent anti-parasitic activity against the protozoa responsible for giardia infections and an amoeba that causes an often-lethal form of encephalitis.
The findings, published online August 9 in PLOS Neglected Tropical Diseases, offer a starting point for widening the arsenal of antimicrobial agents, effective against deadly parasitic infections, scientists said.
The World Health Organization estimates giardiasis, a diarrheal illness, is linked to approximately 846,000 deaths around the world each year. Infection usually occurs through ingestion of contaminated water or food. Though rarely lethal in the U.S., it’s estimated there are more than 1 million cases of giardiasis in the country annually. Standard treatment usually involves antibiotics and anti-parasitic drugs.
“The significance and intrigue of our study is that it shows the value of prospecting for new medicines from plants traditionally used by indigenous people as medicine,” said co-principal investigator Anjan Debnath, PhD, an assistant adjunct professor at Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego.
The creosote bush (Larrea tridentata), also known as greasewood, or gobernadora in Spanish, is a tough evergreen bush with small waxy leaves, yellow flowers and a distinctive turpentine-like scent. Native Americans in both the U.S. and Mexico have long used the plant for a variety of ailments, including intestinal complaints. There is also an existing body of scientific work documenting the plant’s pharmacologically active compounds, notably nordihydroguaiaretic acid (NDGA). NDGA has antiviral, antibacterial, anti-inflammatory and anticancer properties, and is a liver toxin at high doses.
The study is the first to show that NDGA and five other compounds (four lignans and one flavonoid) are active against the pathogenic protozoa Giardia lamblia and Naegleria fowleri.
G. lamblia causes giardiasis. N. fowleri is a water-borne amoeba that enters the brain through the nasal passage, causing a type of brain damage known as primary amoebic meningoencephalitis (PAM). Though relatively rare, PAM has a greater than 95 percent fatality rate.
In addition to documenting the compounds’ anti-parasitic activity, the research team investigated the mechanisms by which the compounds work. Two compounds were of particular interest because of their 1.5 times greater potency against N. fowleri than the current first-line therapy miltefosine, a broad-spectrum antimicrobial.
“We think the compounds inhibit cysteine protease (an enzyme) that helps the amoeba invade host tissue,” Debnath said. “Our next step is to test the activity of potent compounds in animal models of infection and also explore the possibility of combining these compounds with the currently used drug to see if their activity is further enhanced against Naegleria infection.”
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Study co-authors include Bharat Bashyal, Linfeng Li, and Daniel V. LaBarbera, University of Colorado, Aurora; and Trpta Bains, UC San Diego.
Written by Christina Johnson.
Public Release: 16-Aug-2017
In a nutshell: Walnuts activate brain region involved in appetite control
First-of-its-kind study reveals mechanism of walnuts’ documented ability to decrease hunger
Beth Israel Deaconess Medical Center
BOSTON – Packed with nutrients linked to better health, walnuts are also thought to discourage overeating by promoting feelings of fullness. Now, in a new brain imaging study, researchers at Beth Israel Deaconess Medical Center (BIDMC) have demonstrated that consuming walnuts activates an area in the brain associated with regulating hunger and cravings. The findings, published online in the journal Diabetes, Obesity and Metabolism, reveal for the first time the neurocognitive impact these nuts have on the brain.
“We don’t often think about how what we eat impacts the activity in our brain,” said the study’s first author Olivia M Farr, PhD, an instructor in medicine in the Division of Endocrinology, Diabetes and Metabolism at BIDMC. “We know people report feeling fuller after eating walnuts, but it was pretty surprising to see evidence of activity changing in the brain related to food cues, and by extension what people were eating and how hungry they feel.”
To determine exactly how walnuts quell cravings, Farr and colleagues, in a study led by Christos Mantzoros, MD, DSc, PhD hc mult, director of the Human Nutrition Unit at Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical School, used functional magnetic resonance imaging (fMRI) to observe how consuming walnuts changes activity in the brain.
The scientists recruited 10 volunteers with obesity to live in BIDMC’s Clinical Research Center (CRC) for two five-day sessions. The controlled environment of the CRC allowed the researchers to keep tabs on the volunteers’ exact nutritional intake, rather than depend on volunteers’ often unreliable food records – a drawback to many observational nutrition studies.
During one five-day session, volunteers consumed daily smoothies containing 48 grams of walnuts – the serving recommended by the American Diabetes Association (ADA) dietary guidelines. During their other stay in the CRC, they received a walnut-free but nutritionally comparable placebo smoothie, flavored to taste exactly the same as the walnut-containing smoothie. The order of the two sessions was random, meaning some participants would consume the walnuts first and others would consume the placebo first. Neither the volunteers nor the researchers knew during which session they consumed the nutty smoothie.
As in previous observational studies, participants reported feeling less hungry during the week they consumed walnut-containing smoothies than during the week they were given the placebo smoothies. fMRI tests administered on the fifth day of the experiment gave Farr, Mantzoros and the team a clear picture as to why.
While in the machine, study participants were shown images of desirable foods like hamburgers and desserts, neutral objects like flowers and rocks, and less desirable foods like vegetables.
When participants were shown pictures of highly desirable foods, fMRI imaging revealed increased activity in a part of the brain called the right insula after participants had consumed the five-day walnut-rich diet compared to when they had not.
“This is a powerful measure,” said Mantzoros. “We know there’s no ambiguity in terms of study results. When participants eat walnuts, this part of their brain lights up, and we know that’s connected with what they are telling us about feeling less hungry or more full.”
This area of the insula is likely involved in cognitive control and salience, meaning that participants were paying more attention to food choices and selecting the less desirable or healthier options over the highly desirable or less healthy options. Farr and Mantzoros next plan to test different amounts, or dosages, of walnuts to see whether more nuts will lead to more brain activation or if the effect plateaus after a certain amount. This experiment will also allow researchers to test other compounds for their effect on this system.
Similar studies could reveal how other foods and compounds, such as naturally-occurring hormones, impact the appetite-control centers in the brain. Future research could eventually lead to new treatments for obesity.
“From a strategic point of view, we now have a good tool to look into people’s brains – and we have a biological read out.” said Mantzoros. “We plan to use it to understand why people respond differently to food in the environment and, ultimately, to develop new medications to make it easier for people to keep their weight down.”
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The study was supported by Harvard Clinical and Translational Science Center grant UL1RR025758 from the National Center for Research Resources and by NIH DK081913. The California Walnut Commission (CWC) supported the study through an investigator-initiated grant. The CWC approved funding the study, but had no role in study design; conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.
About Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding.
BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www.bidmc.org.
Public Release: 17-Aug-2017
Antibiotics found to weaken body’s ability to fight off disease
University of Virginia Health System
Adding another reason for doctors to avoid the overuse of antibiotics, new research shows that a reduction in the variety of microbes in the gut interferes with the immune system’s ability to fight off disease.
Researchers at the University of Virginia School of Medicine have found that antibiotic use made neutrophils, a type of immune cell, less effective in fighting infections and weakened the intestinal barrier against invading bugs.
“Neutrophils play an important role as a first-line ‘innate immune response’ when foreign pathogens invade,” said researcher Koji Watanabe, PhD. “We found that antibiotic disruption of the natural microbes in the gut prevented this from happening properly, leaving the gut susceptible to severe infection.”
Antibiotics and the Microbiome
The researchers were seeking to understand the role of the gut microbiome — the microorganisms that live within us — in amebic colitis, a potentially deadly parasitic infection common in developing countries. They analyzed stool samples collected from children in the urban slums of Dhaka, Bangladesh, and determined that children with more severe infections had less diversity in their gut microbiome. (Antibiotic use, the researchers note, is widespread in low- and middle-income countries, with children often getting more than two dozen treatments by age 2.)
The researchers then used lab mice to determine how the decrease in natural intestinal flora might be worsening the disease. They found that antibiotics disrupted the mice’s gut microbiomes, decreasing the activity of neutrophils and blocking these important white blood cells from responding when needed. This left the gut insufficiently protected. In essence, the gut’s guards did not respond when called and the invaders could march right in.
In addition, the intestinal barrier that protects against disease was compromised. The disruption of the microbiome reduced production of a key cellular protein vital to the barrier’s effectiveness.
“I think the take-home is that this is another important reason not to use antibiotics unless they are clearly needed,” said researcher Bill Petri, MD, PhD, the chief of UVA’s Division of Infectious Diseases. “Unwise use of antibiotics not only increases the risk of multi-drug resistant bacteria and the risk of C. difficile infection but also impairs white blood cell function.”
In addition to shedding light on the role of the microbiome in protecting our health, the work could prove important in the efforts to develop a vaccine for amebic colitis, also known as amebiasis. The discovery might offer a way to enhance the effectiveness of such a vaccine, the researchers noted.
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Findings Published
The researchers have published their findings in the scientific journal PLOS Pathogens. The team consisted of Watanabe, Carol A. Gilchrist, Md Jashim Uddin, Stacey L. Burgess, Mayuresh Abhyankar, Shannon N. Moonah, Zannatun Noor, Jeffrey R. Donowitz, Brittany N. Schneider, Tuhinur Arju, Emtiaz Ahmed, Mamun Kabir, Masud Alam, Rashidul Haque (who led the Bangladesh efforts), Patcharin Pramoonjago, Borna Mehrad and Petri.
The Bangladesh work represented a collaboration of UVA with the icddr,b, a group based in Dhaka dedicated to solving public health problems in low- and middle-income countries through scientific research.
The work was supported by the National Institutes of Health, grant R01 AI026649-28, and the Henske Foundation.
Petri was named one of Virginia’s Outstanding Scientists earlier this year. The honor was announced by the state’s governor, Terry McAuliffe, and the Science Museum of Virginia.
Public Release: 17-Aug-2017
Latency of seizures determined by diet
Estrogen-mediated brain protection directly linked to intake of fatty acids found in oils
Hiroshima University
Scientists are increasingly appreciating estrogen’s role in brain health. Now for the first time, production of estrogen in the brain has been directly linked to the presence of docosahexaenoic acid (DHA).
DHA is found in abundance in fish oils and is also synthesized from alpha-linolenic acid, an omega-3 fatty acid found in some vegetable-based oils.
The latest research from Hiroshima University connecting DHA synthesis to estrogen production, and consequentially brain health, backs up further the old adage that a daily intake of fish oil is good for you.
Assistant Professor Yasuhiro Ishihara, from HU’s Laboratory of Molecular Brain Science, keenly aware of both the growing understanding of estrogen’s role in brain health – and also DHA’s ability to reduce epileptic seizures, wanted to determine if there was any link between the two phenomenon.
His research, recently published in Scientific Reports, and involving collaborators from Japan and USA, investigated how three groups of mice fed on different oil based diets reacted to induced seizures.
One group was fed a diet consisting of soybean oil, another on cottonseed oil, and a third on cottonseed oil in addition to DHA supplements.
These two oils used were chosen due to the differing yields of DHA obtained from them, i.e. the body produces more DHA from soybean oil than cottonseed oil. The third group were also fed on cottonseed oil, but also crucially along with DHA supplements.
After 28 days on these diets, the three groups were exposed to seizure inducing drugs. The group fed on soybean oil took longer to exhibit seizures, and when they did occur they were of a shorter duration than those fed on cottonseed oil. However, the mice fed on cottonseed oil with DHA supplementation, took far longer for seizures to take hold – proving that dietary sourced DHA was a key contributing factor.
When the researchers examined the brains of these mice they found that the soybean oil fed ones had over twice the concentration of estrogen present as those fed solely on cottonseed oil. The mice fed on cottonseed with DHA supplementation had even higher levels of the hormone, suggesting that estrogen production affects seizures, and that this is directly connected to DHA’s presence.
In order to prove this link between estrogen concentration in the brain and omega-3 fatty acid intake/DHA-synthesis, a second experiment was carried out.
This time, one group of mice were again fed on cottonseed oil, and another group on cottonseed oil with DHA supplementation. In addition, a third group was fed on cottonseed oil with DHA supplements – and also Letrozole – a drug which prevents estrogen synthesis.
When seizures were induced this time round, the group exposed to Letrozole were found to have seizures much earlier than those fed on cottonseed fortified with DHA, thus confirming estrogens importance in preventing seizures.
This research from Hiroshima University is the first time that brain estrogen, the synthesis of which is activated by dietary sourced DHA, has been shown to determine seizure latency.
It is expected that these findings will contribute to the development of medication for treating epilepsy, as well as furthering our understanding of the relationship between lipid intake and brain health.
Due to a lack of high DHA-yielding fish oils in many Western diets it should also be of interest to dieticians, and influence the development of future brain boosting supplements.
Public Release: 17-Aug-2017
Vitamin C may encourage blood cancer stem cells to die
NYU Langone Health / NYU School of Medicine
Vitamin C may “tell” faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers. This is the finding of a study led by researchers from Perlmutter Cancer Center at NYU Langone Health, and published online August 17 in the journal Cell.
Certain genetic changes are known to reduce the ability of an enzyme called TET2 to encourage stem cells to become mature blood cells, which eventually die, in many patients with certain kinds of leukemia, say the authors. The new study found that vitamin C activated TET2 function in mice engineered to be deficient in the enzyme.
“We’re excited by the prospect that high-dose vitamin C might become a safe treatment for blood diseases caused by TET2-deficient leukemia stem cells, most likely in combination with other targeted therapies,” says corresponding study author Benjamin G. Neel, MD, PhD, professor in the Department of Medicine and director of the Perlmutter Cancer Center.
Changes in the genetic code (mutations) that reduce TET2 function are found in 10 percent of patients with acute myeloid leukemia (AML), 30 percent of those with a form of pre-leukemia called myelodysplastic syndrome, and in nearly 50 percent of patients with chronic myelomonocytic leukemia. Such cancers cause anemia, infection risk, and bleeding as abnormal stem cells multiply in the bone marrow until they interfere with blood cell production, with the number of cases increasing as the population ages.
Along with these diseases, new tests suggest that about 2.5 percent of all U.S. cancer patients – or about 42,500 new patients each year – may develop TET2 mutations, including some with lymphomas and solid tumors, say the authors.
Cell Death Switch
The study results revolve around the relationship between TET2 and cytosine, one of the four nucleic acid “letters” that comprise the DNA code in genes. Every cell type has the same genes, but each gets different instructions to turn on only those needed in a given cellular context.
These “epigenetic” regulatory mechanisms include DNA methylation, the attachment of a small molecule termed a methyl group to cytosine bases that shuts down the action of a gene containing them.
The back- and-forth attachment and removal of methyl groups also fine-tunes gene expression in stem cells, which can mature, specialize and multiply to become muscle, bone, nerve, or other cell types. This happens as the body first forms, but the bone marrow also keeps pools of stem cells on hand into adulthood, ready to become replacement cells as needed. In leukemia, signals that normally tell a blood stem cell to mature malfunction, leaving it to endlessly multiply and “self-renew” instead of producing normal white blood cells needed to fight infection.
The enzyme studied in this report, Tet methylcytosine dioxygenase 2 (TET2), enables a change in the molecular structure (oxidation) of methyl groups that is needed for them to be removed from cytosines. This “demethylation” turns on genes that direct stem cells to mature, and to start a count-down toward self-destruction as part of normal turnover. This serves as an anti-cancer safety mechanism, one that is disrupted in blood cancer patients with TET2 mutations, says Neel.
To determine the effect of mutations that reduce TET2 function in abnormal stem cells, the research team genetically engineered mice such that the scientists could switch the TET2 gene on or off.
Similar to the naturally occurring effects of TET2 mutations in mice or humans, using molecular biology techniques to turn off TET2 in mice caused abnormal stem cell behavior. Remarkably, these changes were reversed when TET2 expression was restored by a genetic trick. Previous work had shown that vitamin C could stimulate the activity of TET2 and its relatives TET1 and TET3. Because only one of the two copies of the TET2 gene in each stem cell is usually affected in TET2-mutant blood diseases, the authors hypothesized that high doses of vitamin C, which can only be given intravenously, might reverse the effects of TET2 deficiency by turning up the action of the remaining functional gene.
Indeed, they found that vitamin C did the same thing as restoring TET2 function genetically. By promoting DNA demethylation, high-dose vitamin C treatment induced stem cells to mature, and also suppressed the growth of leukemia cancer stem cells from human patients implanted in mice.
“Interestingly, we also found that vitamin C treatment had an effect on leukemic stem cells that resembled damage to their DNA,” says first study author Luisa Cimmino, PhD, an assistant professor in the Department of Pathology at NYU Langone Health. “For this reason, we decided to combine vitamin C with a PARP inhibitor, a drug type known to cause cancer cell death by blocking the repair of DNA damage, and already approved for treating certain patients with ovarian cancer.”
Researchers found that the combination had an enhanced effect on leukemia stem cells, further shifting them from self-renewal back toward maturity and cell death. The results also suggest that vitamin C might drive leukemic stem cells without TET2 mutations toward death, says Cimmino, given that it turns up any TET2 activity normally in place.
“Our team is working to systematically identify genetic changes that contribute to risk for leukemia in significant groups of patients,” says corresponding author Iannis Aifantis, PhD, professor and chair of the Department of Pathology at NYU Langone Health. “This study adds the targeting of abnormal TET2-driven DNA demethylation to our list of potential new treatment approaches.”
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Along with Neel, Aifantis and Cimmino, Igor Dogalev, Yubao Wang, Gaëlle Martin, Jingjing Wang, Victor Ng, Bo Xia, Matthew Witkowski, Marisa Mitchell-Flack, Isabella Grillo, Sofia Bakogianni, Delphine Ndiaye-Lobry, Maria Guillamot-Ruano, Robert Banh, Christopher Park, and Aristotelis Tsirigos in the Department of Pathology at NYU School of Medicine and Perlmutter Cancer Center, were study authors. Several authors were also part of the Center for Health Informatics and Bioinformatics at NYU School of Medicine. Also authors were Akihide Yoshimi and Omar Abdel-Wahab with the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College; Miguel Torres MartÃn, Maria Figueroa, and Mingjiang Xu at the University of Miami’s Miller School of Medicine; and Ross Dickins with the Australian Center for Blood Diseases at Monash University in Australia.
The research was supported by the National Institutes of Health grants RO1 CA216421, R01 CA194923, R01 CA169784, R01 CA133379, R01CA149655, 5R01CA173636 and R01 CA49132, Leukemia & Lymphoma Society grants TRP#6340-11 and LLS#6373-13, New York State Department of Health grant CO030132, and a Feinberg Lymphoma pilot grant, as well as by The Chemotherapy Foundation, The V Foundation for Cancer Research, Alex’s Lemonade Stand Foundation for Childhood Cancer, St. Baldrick’s Cancer Research Foundation, and the Howard Hughes Medical Institute.
NYU School of Medicine is one of the nation’s top-ranked medical schools. For 175 years, NYU School of Medicine has trained thousands of physicians and scientists who have helped to shape the course of medical history and enrich the lives of countless people. An integral part of NYU Langone Health, the School of Medicine at its core is committed to improving the human condition through medical education, scientific research, and direct patient care. For more information, go to med.nyu.edu.
Public Release: 24-Aug-2017
Studies explore the potential benefits of red raspberries
Eight studies — including human trials — explore potential for satiety, blood sugar control, and anti-inflammatory properties of raspberries
Wild Hive
Lynden, WA – August 24, 2017 – Initial findings from several studies – including both human subjects and animals – on the potential health benefits of red raspberries were presented earlier this year at the 2017 Experimental Biology conference in Chicago. Participants in short-term human trials experienced an improvement in glucose control and increased satiety, while longer-term animal trials revealed promising effects on the gut microbiota after red raspberry intake. The observations from animal and in vitro studies provided insights that support future hypotheses for red raspberry research exploring potential beneficial effects on pathways related to reducing inflammation, obesity, and type 2 diabetes risk.
“We are excited about this new flurry of studies, which builds on previously published research aimed to better understand the potential health benefits of red raspberries,” said Tom Krugman, Executive Director of the National Processed Raspberry Council (NPRC). “Our Council is committed to delivering the highest quality nutrition and health science that consumers can use to make informed choices when aiming for a healthy diet.”
While additional research, particularly in humans, is warranted, preliminary evidence from these studies suggests that the actions of essential nutrients, fiber, and polyphenolic phytochemicals found in red raspberries may play a role in supporting key metabolic functions, including anti-inflammatory, anti-oxidative and metabolic stabilizing activity. While this emerging research is promising, and contributes to the overall understanding of the health benefits of red raspberries, conclusions cannot be drawn at this time.
Blood Sugar Control
In this human trial, investigators from the Center for Nutrition Research at the Illinois Institute of Technology looked at two study groups: obese individuals with impaired fasting glucose and hyperinsulinemia (PreDM) and healthy weight individuals with normo-glycemia and insulinemia. Participants experienced a significant reduction in postprandial glucose when 2 cups (250g) of red raspberries were consumed with meals compared to no raspberries. The glucose lowering was accompanied with less insulin suggesting improved insulin sensitivity in individuals with pre-diabetes and insulin resistance.
* Xiao, D. Huang, Y. Park, E. Edirisinghe, I. and Burton-Freeman, B. Red Raspberries and Insulin Action: Understanding the Role of Red Raspberry Consumption on Postprandial Metabolic Indices. The FASEB Journal, April 2017, vol. 31 no. 1 Supplement 973.9. http://bit.ly/PostprandialMetabolicIndices
Satiety
In a secondary objective of the blood sugar control study, researchers found that subjects in the PreDM group who reported the highest level of hunger at baseline experienced greater satiety after the control meal compared to raspberry containing meals (p<0.05). In contrast, the healthy weight participants experienced significantly greater hunger suppression and wanted to eat less after a breakfast containing 2 cups (250g) of red raspberries compared to a calorie-matched control meal without raspberries. Because this study was limited to three meals, further research is needed to determine the factors that influenced outcomes.
* Huang, L. Xiao, D. Park, E. Edirisinghe, I. and Burton-Freeman, B. The Effect of Red Raspberry on Satiety. The FASEB Journal, April 2017, vol. 31 no. 1 Supplement 794.8. http://bit.ly/RaspberriesSatiety
Gut Health
In an eight-week pilot study, researchers from the Institute for Food Safety and Health from the Illinois Institute of Technology examined the impact of consumption of red raspberry purée or fructo-oligosaccharide on the gut microbiota and the subsequent bioavailability of red raspberry polyphenols in healthy volunteers. Consumption of the red raspberry puree and the fructo-oligiosaccharide for 4 weeks resulted in decreased Firmicutes and increased Bacteroidetes, which was more pronounced after red raspberry intake. Additionally, a type of bacteria called Akkermansia that has been associated with metabolic health was increased during red raspberry intake only. These preliminary results are promising. Further research is needed to support the hypothesis that the consumption of raspberry puree may change the composition of the gut microbiota.
* Zhang, X. Sandhu, A. Schill, K. Edirisinghe, I. and Burton-Freeman, B. The Reciprocal Interactions between Red Raspberry Polyphenols and Gut Microbiome Composition: Preliminary Findings. The FASEB Journal, April 2017, vol. 31 no. 1 Supplement 965.29. http://bit.ly/GutMicrobiomeComposition
Dr. Giuliana Noratto and colleagues of the Department of Food and Nutrition Science at Texas A&M University studied if dietary supplementation with red raspberries could modulate the fecal microbiota of obese mice with diabetes and dyslipidemia. In this animal study, raspberry supplementation was associated with higher levels of Lachnospiraceae – a family of bacteria that can be depleted during diseases of the intestinal tract, such as inflammatory bowel disease. These findings provide a basis for formulating hypotheses for conducting additional studies, particularly in human trials.
* Noratto, G. Garcia-Mazcorro, J. Chew, B. and Mertens-Talcott, S. Dietary Supplementation with Raspberry Whole Fruit Modifies the Relative Abundance of Fecal Microbial Communities in Obese Diabetic (db/db) Mice. The FASEB Journal, April 2017, vol. 31 no. 1 Supplement 965.19. http://bit.ly/MicrobialCommunities
Type 2 Diabetes
In an animal study, mice fed 5% freeze dried raspberry for 12 weeks, showed signs of improved insulin resistance and reduced inflammation in skeletal muscle while consuming a high-fat diet. These data corroborate a short-term study in humans reported by Xiao and colleagues at the same meeting supporting further work in humans to provide additional insight into these findings.
* Min Du, Tiande Zou, Bo Wang, Xingwei Liang, and Mei-Jun Zhu. Raspberry intake reduces skeletal muscle lipid accumulation and improves insulin sensitivity in mice fed high fat diet. The FASEB Journal, April 2017, vol. 31 no. 1 Supplement 972.19. http://bit.ly/MuscleLipidAccumulation
A research team from the University of Michigan studied the potential biologically active properties of red raspberries with in vitro assays including antioxidant and anti-inflammatory capacities. Follow-up research explored the potential relationship between feeding freeze-dried whole raspberry powder and cardiometabolic risk in obesity prone rats. Red raspberries were found to upregulate the expression of specific cardiac-protective molecular proteins (myocardial adiponectin, its receptor 2, and apolipoprotein E). Rats fed the red raspberries also experienced altered nicotinamide phosphoribosyltransferase mRNA, a protein associated with multiple functions in conditions related to obesity and type 2 diabetes. More research is needed to determine if compounds in red raspberries play a role in human cardiometabolic pathways.
* Kirakosyan, A. Seymour, EM. Gutierrez, E. and Bolling, S. Associations of Dietary Intakes of Red Raspberry Fruits with Risk of Type 2 Diabetes Mellitus. The FASEB Journal, April 2017, vol. 31 no. 1 Supplement 973.4. http://bit.ly/RiskofType2Diabetes
Inflammation
In a mouse model, red raspberry supplementation of 5% dry feed weight was found to suppress inflammation and facilitate epithelium repair compared to mice with induced colitis (inflammation of the colon) and fed a standard chow diet. These observations are not conclusive, and further research is needed to determine if red raspberry supplementation supports epithelial function in humans.
* Bibi, S. Du, M. Kang, Y. Sun, X. Xue, Y. Soussa Moraes, LF. and Zhu, M. Dietary Red Raspberry Enhances Intestinal Epithelium Repair in Chronic Colitis. The FASEB Journal, April 2017, vol. 31 no. 1 Supplement 972.19. http://bit.ly/IntestinalEptheliumRepair
Anthocyanin Profiles of Processed Raspberries
Anthocyanin profiles among common processed forms of raspberries (frozen, juice concentrate, seeded puree, and seedless puree) on the U.S. market were investigated. Thirty-four samples – both domestic and imported – were reviewed. Seven individual anthocyanins were identified in the samples. While anthocyanin profiles varied slightly, contents varied considerably. This may reflect differences in varieties, origins, processing methods among other influential factors.
* Wu, X. Sun, J. Ahuja, J. Haytowitz, DB. Burton-Freeman, B. Chen, P. Pehrsson, PR. Anthocyanin profiles and contents in processed raspberries on the U.S. market. The FASEB Journal, April 2017, vol. 31 no. 1 Supplement 454.6. http://bit.ly/AnthocyaninProfiles
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About The Raspberry Council
Created in 2013, the National Processed Raspberry Council (NPRC) represents the processed raspberry industry and is supported by assessments from both domestic producers and importers. NPRC’s mission is to conduct nutrition research and promote the health benefits of processed raspberries. The NPRC is responsible for marketing processed raspberries in the U.S. and is committed to promoting the growth of the entire industry. Processed raspberries are frozen at the peak of ripeness to lock in flavor and nutrition. Visit redrazz.org for more information, and follow us on our social media channels
Public Release: 24-Aug-2017
Caffeine tempers taste, triggering temptation for sweets
Cornell University
ITHACA, N.Y. – Caffeine, the widely consumed stimulant and igniter of sluggish mornings, has been found to temper taste buds temporarily, making food and drink seem less sweet, according to new Cornell University research.
Caffeine is a powerful antagonist of adenosine receptors, which promote relaxation and sleepiness. Suppressing the receptors awakens people but decreases their ability to taste sweetness — which, ironically, may make them desire it more.
The research demonstrates taste modulation in the real world, said senior author Robin Dando, assistant professor of food science: “When you drink caffeinated coffee, it will change how you perceive taste — for however long that effect lasts. So if you eat food directly after drinking a caffeinated coffee or other caffeinated drinks, you will likely perceive food differently.”
Dando, along with lead authors Ezen Choo and Benjamin Picket published, “Caffeine May Reduce Perceived Sweet Taste in Humans, Supporting Evidence That Adenosine Receptors Modulate Taste,” in the Journal of Food Science.
In the blind study, one group sampled decaffeinated coffee with 200 milligrams of caffeine added in a laboratory setting, making a strong cup of coffee. The stimulant was added to make that group’s coffee consistent with real-life amounts of caffeine. The other group drank just decaffeinated coffee. Both groups had sugar added. Panelists who drank the caffeinated brew rated it as less sweet.
In a secondary part of the study, participants disclosed their level of alertness and estimated the amount of caffeine in their coffee. Further, panelists reported the same increase in alertness after drinking either the caffeinated or decaffeinated samples, all the while panelists could not predict if they had consumed the decaffeinated or the caffeinated version.
“We think there might be a placebo or a conditioning effect to the simple action of drinking coffee,” said Dando. “Think Pavlov’s dog. The act of drinking coffee – with the aroma and taste – is usually followed by alertness. So the panelists felt alert even if the caffeine was not there,” said Dando.
“What seems to be important is the action of drinking that coffee,” Dando said. “Just the action of thinking that you’ve done the things that make you feel more awake, makes you feel more awake.”
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Cornell University has television, ISDN and dedicated Skype/Google+ Hangout studios available for media interviews. For additional information, see this Cornell Chronicle story
Public Release: 24-Aug-2017
Understanding how omega-3 dampens inflammatory reactions
Norwegian University of Science and Technology
Omega-3 supplements may help slow the development of diseases like cancer, Alzheimer’s and multiple sclerosis.
Omega-3 fatty acids, which we primarily get through eating fatty fish, have long been thought to be good for our health. Many dietary studies have suggested that high intake is associated with a reduced risk of various disorders. Clinical trials have also shown beneficial anti-inflammatory effects in patients taking omega-3 supplements.
Recent research from NTNU supports previous discoveries, and has also found new, useful effects of omega-3 supplements and how these lipids dampen harmful inflammatory reactions in the body.
Effects little known
Despite numerous published dietary and clinical studies, we still don’t fully understand how omega-3 fatty acids affect our cells and if this varies from person to person, between healthy and ill individuals, or whether the mechanism of action varies in different tissues and cells. What we are most sure of is that omega-3 fatty acids can dampen inflammatory reactions. Inflammatory reactions are very important in combating infections, but they can be harmful if activated too strongly or in the absence of bacteria and viruses, like in autoimmune diseases and organ transplants.
Macrophages, which are immune cells that live in all tissues and organs, play a key role in coordinating inflammatory reactions in the body and monitor everything that happens in our tissues. The macrophages convert the information they obtain through various sensors or receptor on their surface to secretion of various hormone-like signal substances that control all parts of inflammatory reactions.
Inflammation can be harmful
We have increasingly become aware that macrophages can be more or less potent in activating inflammatory reactions. So-called sterile inflammatory reactions, such as autoimmune diseases, are often directly harmful.
The ability of macrophages to stimulate inflammatory reactions depends on processes within the macrophage.
Autophagy is one of the processes within macrophages that is important for whether a macrophage is calm or hyperactive. Autophagy (meaning “self-eating”) is a key process for degradation of dysfunctional or unnecessary proteins and other components within our cells.
In the last few years, we’ve learned a lot about how important this process is, say the researchers. The Nobel Prize in Physiology or Medicine 2016 was given to Yoshinori Ohsumi for his discovery of the key genes that control autophagy.
Autophagy is constantly going on in all cells and increases if the cells are starving or injured. We hypothesized that omega-3 fatty acids could dampen inflammatory reactions by elevating autophagy in macrophages. If so, we surmised that this effect might change the signal transformation in the macrophage and as a result, suppress activation of inflammatory reactions.
Activates self-cleaning process
By studying macrophages isolated from mice and humans, we found that the omega-3 fatty acids activated the autophagy and specifically affected some proteins that transform the signals from the environment. Furthermore, we found that omega-3 fatty acids dampened many inflammatory mechanisms within the macrophages, but especially reduced what is known as the type 1 interferon response.
The factor CXCL-10, which macrophages secrete as part of this interferon response following many types of stimuli, was the most clearly reduced factor after adding omega-3 to the cells.
We then examined blood samples from a clinical study in cardiac transplant patients where we knew that omega-3 supplements improved their clinical status. In these cases, we found that omega-3 fatty acids reduced the level of CXCL-10.
Supplements beneficial
Autophagy thus changes in macrophages in response to omega-3 fatty acids and specifically inhibits the secretion of inflammatory factors that belong to the interferon response, with CXCL-10 showing the clearest reduction. The results of this study are being published in the journal Autophagy.
These findings indicate that omega-3 fatty acid supplements may be particularly beneficial in patients who have conditions that are driven or aggravated by a strong interferon response and CXCL-10.
Our research group hopes that this one day will benefit patients with different forms of cancer, meningitis, multiple sclerosis, Alzheimer’s disease or jaundice. But we must emphasize that a lot of work remains.
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The work being published by PhD candidate Jennifer Mildenberger and colleagues was conducted at CEMIR and at NTNU’s Department of Biomedical Laboratory Science in the Faculty of Natural Science. In addition, researchers in St. Louis, USA carried out important sub studies. The blood tests were from a clinical trial conducted at Oslo University Hospital.
Article author Geir Bjørkøy is a professor in the Department of Biomedical Laboratory Science at NTNU.
Article author Jennifer Mildenberger works for NTNU-Cemir.
Source: N-3 PUFAs induce inflammatory tolerance by formation of KEAP1-containing SQSTM1/p62-bodies and activation of NFE2L2. Autophagy. http://www.tandfonline.com/doi/full/10.1080/15548627.2017.1345411
Public Release: 23-Aug-2017
Omega-3 intake reduces cardiac death risk according to comprehensive new study
Greater risk reduction seen in subjects with high cholesterol or triglycerides
GOED
IMAGE: This is a table assessing meta analysis results.
Credit: Maki et al
Results from a new study published in the Journal of Clinical Lipidology showed that in 14 randomized, controlled trials (RCTs) of 71,899 people, consumption of EPA and DHA omega-3s reduced the risk of cardiac death by a statistically-significant average of 8 percent. Cardiac death accounts for about two-thirds (about 405,000) of all cardiovascular disease deaths in the United States, and 42 percent (7.4 million) globally, each year (1,2). This is the first published meta-analysis to include cardiac death (also known as “coronary mortality”) as a primary endpoint, and the most comprehensive review of the evidence to date.
The meta-analysis showed even greater — 17 percent — risk reduction in groups who had elevated triglycerides or LDL cholesterol. These results are consistent with the hypothesis that EPA and DHA omega-3s may be most useful for reducing cardiac death in higher risk individuals (see table), which is important since The National Center for Health Statistics estimates that 25 percent of adults in the US have triglyceride levels ≥150 mg/dL (3) and 27 percent have LDL cholesterol levels ≥130 mg/dL (4). The greatest reduction in cardiac death rates — an almost 30% risk reduction — was observed in trials that utilized dosages of more than 1 gram of EPA and DHA per day.
The RCTs reviewed were longer than six months in length, and investigated cardiac death as the primary outcome, comparing frequencies of cardiac death events between the omega-3 and control groups. The researchers reviewed studies published through December 2016 that included both dietary supplement and pharmaceutical omega-3 interventions. In the omega-3 groups, 1,613 cardiac deaths were recorded (4.48 percent of subjects) compared to 1,746 cardiac deaths in the control groups (4.87 percent of subjects). This study did not review the effects of EPA and DHA consumption from fish on cardiac death risk because no randomized, controlled trials exist, but observational studies on EPA and DHA from fish also support a benefit in risk reduction (5).
“It’s important to note that these results align with the conclusions in the recent Science Advisory from the American Heart Association, which states that EPA and DHA omega-3 treatment ‘is reasonable’ for secondary prevention of coronary heart disease and sudden cardiac death,” said Dr. Kevin Maki, lead study author and Chief Scientist for Midwest Biomedical Research’s Center for Metabolic and Cardiovascular Health. “One notable feature of EPA and DHA omega-3 supplementation is the low risk associated with its use. Because of the low risk for adverse effects, even a modest benefit is clinically meaningful.”
“This study is important because it explored the effects of omega-3s on a specific outcome of coronary heart disease,” said Dr. Harry B. Rice, VP of Regulatory and Scientific Affairs at GOED, which funded the study. “A number of studies in recent years have questioned omega-3 benefits in cardiovascular diseases. In order to understand the role omega-3s play in the cardiovascular system, however, research has to focus on a specific disease rather than all cardiovascular outcomes together. This is an important nuance that this meta-analysis helps clarify.”
Consuming sufficient amounts of EPA and DHA is part of eating a well-balanced diet and leading a healthy lifestyle. The Dietary Guidelines for Americans and the American Heart Association recommend consuming seafood/fatty fish each week (6,7). Two servings per week supplies 250-500 mg of EPA and DHA per day. In addition, the AHA also recommends 1 gram of EPA and DHA per day for those with diagnosed heart disease. Increasing omega-3 intake is easy and inexpensive, with omega-3 supplement costs ranging from $10-$60/month and fatty fish ranging from $10-$25+/month depending on the type of fish. Omega-3 are also widely viewed as safe; the U.S. FDA allows up to 3 grams per day and EFSA, the European Food Safety Authority, reports no safety issues with up to 5 grams per day. If consumers are allergic to fish or would like to take higher doses, they should consult their physicians.
A limitation of the results from the present meta-analysis is that several of the studies included were small, or had suboptimal trial designs. For example, two of the largest trials, GISSI-Prevenzione and JELIS, were controlled but did not utilize placebos. While this does raise the possibility of bias/confounding, this is less likely to be a concern with a fatal outcome, and removing individual studies from the analysis did not result in any changes in findings. Additionally, baseline and post-intervention omega-3 levels were not available in most studies, making it difficult to determine how much of an increase in blood levels actually occurred through supplementation.
The meta-analysis was funded by the Global Organization for EPA and DHA Omega-3s (GOED), but GOED was not involved in the design or interpretation of the results.
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About EPA and DHA Omega-3s
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 fatty acids that the body uses to help cells function optimally. They are typically found in fatty fish such as salmon, tuna or mackerel, but are also readily available in omega-3 supplements from fish oil, krill oil or algae, or in fortified foods. The two nutrients play a key role in heart health, brain health and eye health throughout life and the FDA has allowed a qualified health claim in the U.S. which states, “Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.” Many governments and scientific organizations recommend consuming 250-500 mg of EPA and DHA per day (8).
About GOED
The Global Organization for EPA and DHA Omega-3s (GOED) is a trade association representing approximately 200 companies worldwide active in the EPA and DHA omega-3 industry. GOED’s membership includes all segments of the omega-3 supply chain from fishing and seafood companies, to refiners, supplement manufacturers, food and beverage marketers and pharmaceutical companies. GOED’s members agree to adhere to product quality and ethical standards that are as strict, or more strict, than any set of regulations in the world. GOED focuses specifically on addressing the insufficient consumption of EPA and DHA in the human diet by promoting global consumption of EPA and DHA and protecting the consumer by making sure members produce quality products.
References:
1. https://www.cdc.gov/heartdisease/facts.htm
2. http://www.who.int/mediacentre/factsheets/fs317/en/
3. https://www.cdc.gov/nchs/products/databriefs/db198.htm
4. https://www.cdc.gov/nchs/products/databriefs/db117.htm
5. http://www.mayoclinicproceedings.org/article/S0025-6196(16)30681-4/fulltext
6. https://health.gov/dietaryguidelines/2015/
7. http://circ.ahajournals.org/content/106/21/2747.long?
8. https://drive.google.com/file/d/0B9qT6KspMkCJdEpUNlp4V2VOTG8/view
Public Release: 23-Aug-2017
Antioxidant/zinc supplement cost saving and effective for degenerative eye disease
NHS should fund this for people with ‘wet’ age-related macular degeneration, say researchers
BMJ
A supplement that combines antioxidants with zinc and copper is a relatively inexpensive and effective means of halting the progression of a certain type of degenerative eye disease, concludes research published online in the British Journal of Ophthalmology.
Given the costs and side effects of the current range of drugs used to treat the ‘wet’ form of age related macular degeneration (nAMD), the NHS should fund this treatment in people who already have the condition in one eye, say the researchers.
In ‘wet’ AMD, abnormal blood vessels grow underneath the retina. These vessels can leak fluid and blood, which can damage the macula–the part of the retina responsible for central vision.
But the drugs (anti-VEGF therapies) currently used to ‘wet’ AMD are expensive and have been linked to heightened risk of inflammation of the inside of the eye (endophthalmitis) and possibly stroke as well.
The researchers base their findings on data from the Age Related Eye Disease Study (AREDS) as well as UK treatment costs and AMD prevalence figures for people over the age of 55.
AREDS concluded that a daily supplement combining high dose antioxidants and zinc lowered the risk of developing ‘wet’ AMD after assessing the effectiveness of two types of supplement for treating people with early stage disease in one (category 4) or both (category 3) eyes.
Formulation 1 contained high doses of vitamins C and E, beta carotene, zinc and copper; in formulation 2, beta carotene was replaced with lutein and zeaxanthin, but the other constituents remained the same. Both formulations are commercially available.
The researchers applied a statistical approach (Markov Model) to all the data to predict outcomes in those given one or other supplement compared with those not given them.
Their analysis showed that both formulations are cost effective for treating patients with early stage ‘wet’ AMD, but they were more cost effective for those with the condition in just one eye.
Over the course of a lifetime, the researchers calculated that these patients would need nearly eight fewer injections of anti-VEGF therapies into their eye. This represents a cost saving to the NHS of nearly £3000 per patient, adding up to around £131 million a year.
And these patients would gain additional time lived without impaired vision, known as QALYs (10.59 compared with 10.43 for those not given the supplements).
“Given the burden and cost of treatment, prevention of nAMD seems, therefore, an attractive strategy to avoid the chronic and costly anti-VEG therapies and preserve visual function,” write the researchers.
The beneficial costs and outcomes do assume that people with wet AMD in one eye would be highly motivated to keep on taking the supplements to stave off vision loss in the second eye, acknowledge the researchers.
While there would still be savings to be made by giving supplements to people with intermediate stage wet AMD in both eyes, the argument for funding them for people with the condition in one eye is extremely strong, they say.
“AREDS supplements are a dominant cost-effective intervention for category 4 AREDS patients, as they are both less expensive than standard care and more effective, and therefore should be considered for public funding,” they conclude.