Omega-3 fatty acids improve cognitive flexibility in older adults at risk of late-onset Alzheimer's disease

A study of older adults at risk of late-onset Alzheimer's disease found that those who consumed more omega-3 fatty acids did better than their peers on tests of cognitive flexibility -- the ability to efficiently switch between tasks -- and had a bigger anterior cingulate cortex, a brain region known to contribute to cognitive flexibility.

 

[alpha-linolenic acid (ALA), an essential omega-3 fatty acid, (18:3Δ9c,12c,15c, which means a chain of 18 carbons with 3 double bonds on carbons numbered 9, 12, and 15)].

The analysis suggests, but does not prove, that consuming DHA and EPA, two omega-3 fatty acids found in fish, enhanced cognitive flexibility in these adults in part by beefing up the anterior cingulate cortex, the researchers report in the journal Frontiers in Aging Neuroscience.

"Recent research suggests that there is a critical link between nutritional deficiencies and the incidence of both cognitive impairment and degenerative neurological disorders, such as Alzheimer's disease," said University of Illinois neuroscience, psychology, and speech and hearing science professor Aron Barbey, who led the study with M.D./Ph.D. student Marta Zamroziewicz. "Our findings add to the evidence that optimal nutrition helps preserve cognitive function, slow the progression of aging and reduce the incidence of debilitating diseases in healthy aging populations."

The researchers focused on aspects of brain function that are sometimes overlooked in research on aging, Zamroziewicz said. "A lot of work in cognitive aging focuses on memory, but in fact cognitive flexibility and other executive functions have been shown to better predict daily functioning than memory does," she said.

"Executive function" describes processes like planning, reasoning, paying attention, problem solving, impulse control and task switching.

"These functions tend to decline earlier than other cognitive functions in aging," Zamroziewicz said.

The new research built on previous studies that found associations between omega-3 fatty acid consumption, cognitive flexibility and the size of the anterior cingulate cortex.

"There's been some work to show that omega-3 fatty acids benefit cognitive flexibility, and there's also been work showing that cognitive flexibility is linked to this specific brain region, the anterior cingulate. But there's been very little work actually connecting these pieces," Zamroziewicz said.

The new study focused on 40 cognitively healthy older adults between the ages of 65 and 75 who are carriers of a gene variant (APOE e4) that is known to contribute to the risk of developing late-onset Alzheimer's disease.

The researchers tested participants' cognitive flexibility, measured levels of the fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in their blood, and imaged their brains using MRI. Statistical analyses teased out the relationships between these factors.

"We wanted to confirm that higher omega-3 fatty acids related to better cognitive flexibility, and we did in fact see that," Zamroziewicz said. "We also wanted to confirm that higher omega-3 fatty acids related to higher volume in the anterior cingulate cortex, and we saw that. Finally, we were able to show that higher volume in the anterior cingulate cortex was an intermediary in the relationship between omega-3 fatty acids and cognitive flexibility."

 Docosahexaenoic acid

  Eicosapentaenoic acid

Omega-3 fatty acids improve cognitive flexibility in older adults at risk of late-onset Alzheimer's disease

Omega-3 and Omega-6 fatty acid intake may affect lupus outcomes

 

In continuation of my update on omega fatty acids

Higher intake of omega-3 fatty acids was associated with better sleep quality and a decrease in depressive symptoms in lupus patients, among other patient-reported outcomes, according to new research findings presented this week at the 2017 ACR/ARHP Annual Meeting in San Diego. 

Lupus is a chronic (long-term) inflammatory autoimmune disease in which an unknown trigger causes the body's immune system to attack its own healthy tissues. The most common type of lupus is systemic lupus erythematosus (SLE), a complex, multiple symptom disease that can cause inflammation, pain and damage to various parts of the body. While anyone can develop lupus, it occurs 9-10 times more often in women than in men, and is 2-3 times more common among women of color.

Omega fatty acids have an effect on inflammation in the body, with omega-3 fatty acids generally acting as an anti-inflammatory and omega-6 fatty acids acting as a pro-inflammatory. Western diets are often much higher in omega-6fatty acids, and they are suspected to contribute to chronic diseases.

While small studies show an association between omega-3 supplementation and reduced disease activity in lupus patients. Researchers at the University of Michigan in Ann Arbor examined their impact on patient-reported outcomes, or PROs. They performed a population-based, cross-sectional study to look for a possibleassociation between dietary intake of omega-3 and omega-6 fatty acidsand PROs in lupus patients. Data from the Michigan Lupus Epidemiology & Surveillance (MILES) program was used.

"Western diets are thought to contribute to an increase in people with chronic conditions including autoimmune diseases. Many small studies found that omega-3 supplementation was associated with an improvement in disease activity in SLE patients, but no studies have looked at omega-3 exposure through diet or its impact on PROs," said Prae Charoenwoodhipong, MS, a graduate student in the Department of
Nutrition Science at the University of Michigan School of Public Health in Ann Arbor. "Also, very few studies have looked at the impact of omega-6, an inflammatory fatty acid that is very common in U.S. diets. According to rheumatologists I've worked with, patients with SLE are always asking about what they might be able to do with supplements or their diet to help improve their health."

Omega-3 and Omega-6 fatty acid intake may affect lupus outcomes

Taking omega-3 supplements during pregnancy can reduce risk of childhood asthma by one third

In continuation of my update on omega 3 fatty acids

Taking certain omega-3 fatty acid supplements during pregnancy can reduce the risk of c

hildhood asthma by almost one third, according to a new study from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) and the University of Waterloo.

The study, published in the New England Journal of Medicine, found that women who were prescribed 2.4 grams of long-chain omega-3 supplements during the third trimester of pregnancy reduced their children's risk of asthma by 31 per cent. Long-chain omega-3 fatty acids, which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in cold water fish, and key to regulating human immune response.

"We've long suspected there was a link between the anti-inflammatory properties of long-chain omega-3 fats, the low intakes of omega-3 in Western diets and the rising rates of childhood asthma," said Professor Hans Bisgaard of COPSAC at the Copenhagen University Hospital. "This study proves that they are definitively and significantly related."

The study used rapid analytical techniques developed and performed at the University of Waterloo to measure levels of EPA and DHA in pregnant women's blood. The University of Waterloo is one of a few laboratories in the world equipped to run such tests.

"Measuring the levels of omega-3 fatty acids in blood provides an accurate and precise assessment of nutrient status," said Professor Ken Stark, Canada Research Chair in Nutritional Lipidomics and professor in the Faculty of Applied Health Sciences at Waterloo, who led the testing. "Our labs are uniquely equipped to measure fatty acids quickly, extremely precisely, and in a cost-efficient manner."

The testing also revealed that women with low blood levels of EPA and DHA at the beginning of the study benefitted the most from the supplements. For these women, it reduced their children's relative risk of developing asthma by 54 per cent.

"The proportion of women with low EPA and DHA in their blood is even higher in Canada and the United States as compared with Denmark. So we would expect an even greater reduction in risk among North American populations," said Professor Stark. "Identifying these women and providing them with supplements should be considered a front-line defense to reduce and prevent childhood asthma."

 

Researchers analyzed blood samples of 695 Danish women at 24 weeks' gestation and one week after delivery. They then monitored the health status of each participating child for five years, which is the age asthma symptoms can be clinically established.

"Asthma and wheezing disorders have more than doubled in Western countries in recent decades," said Professor Bisgaard. "We now have a preventative measure to help bring those numbers down."

Currently, one out of five young children suffer from asthma or a related disorder before school age.

https://uwaterloo.ca/news/news/omega-3-supplements-can-prevent-childhood-asthma

AHA: Adding Omega-3 Fatty Acids Does Not Cut High CV Risk

In continuation of my update on omega-3 fatty acids

A carboxylic acid formulation of eicosapentaenoic acid and docosahexaenoic acid (omega-3 CA) does not improve outcomes among statin-treated patients at high cardiovascular risk, according to a study published online Nov. 15 in the Journal of the American Medical Association to coincide with the American Heart Association Scientific Sessions 2020, held virtually from Nov. 13 to 17.

Stephen J. Nicholls, M.B.B.S., Ph.D., from Monash University in Melbourne, Australia, and colleagues conducted a double-blind trial comparing omega-3 CA to corn oil in 13,078 statin-treated patients with high cardiovascular risk, hypertriglyceridemia, and low high-density lipoprotein cholesterol from 675 academic and community hospitals in 22 countries. Participants were randomly assigned in a 1:1 ratio to either 4 g/day omega-3 CA or corn oil (6,539 to each) in addition to usual background therapies, including statins.

The trial was halted prematurely based on an interim analysis indicating low probability of clinical benefit of omega-3 CA, when 1,384 patients had experienced a primary end-point event. The researchers found that the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization) occurred in 12.0 and 12.2 percent of those treated with omega-3 CA and corn oil, respectively (hazard ratio, 0.99; 95 percent confidence interval, 0.90 to 1.09; P = 0.84).

"These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients," the authors write.

Several authors disclosed financial ties to pharmaceutical companies, including AstraZeneca, which funded the study.

AHA: Adding Omega-3 Fatty Acids Does Not Cut High CV Risk  

Omega-3 supplementation improves working memory in young adults

In continuation of my update on omega fatty acid

University of Pittsburgh researchers led by Rajesh Narendran of the Department of Radiology tested the effects of a supplement providing 930 milligrams eicosapentaenoic acid (EPA) and 750 milligrams docosahexaenoic acid (DHA) in 11 men and women between the ages of 18 and 25. Evaluation of working memory (via an "n-back test"), positron emission tomography (PET) imaging of the brain and tests for red blood cell fatty acid levels were conducted before and after the six month treatment period.

Participants experienced an increase in plasma omega-3 fatty acid levels and improvement in working memory at the end of six months. "What was particularly interesting about the presupplementation n-back test was that it correlated positively with plasma omega-3,"observed Bita Moghaddam, whose lab conducted the research. "This means that the omega-3s they were getting from their diet already positively correlated with their working memory."

"Before seeing this data, I would have said it was impossible to move young healthy individuals above their cognitive best," he remarked. "We found that members of this population can enhance their working memory performance even further, despite their already being at the top of their cognitive game."

Although the researchers had suggested increases in dopamine storage and a protein involved in decision making in a particular area of the brain as mechanisms supporting omega-3's effect on cognitive function, PET scan results failed to support the hypothesis. "It is really interesting that diets enriched with omega-3 fatty acid can enhance cognition in highly functional young individuals," Dr Narendran commented. "Nevertheless, it was a bit disappointing that our imaging studies were unable to clarify the mechanisms by which it enhances working memory."

Omega fatty acid supplements may improve ASD symptoms in toddlers born preterm, study shows

In continuation of my update on omega fatty acids

Researchers from Nationwide Children's Hospital have shown that omega fatty acid supplements may improve autism spectrum disorder symptoms in toddlers who were born very preterm (more than 11 weeks early). The study was published recently in the Journal of Nutrition.

"The trial had two goals. First, we wanted to confirm the feasibility of a large study of toddlers born very preterm and exhibiting symptoms often seen with ASD. Second, we wanted to see what the effects of omega fatty acids would be on parent-reported ASD symptoms and related behaviors," says Sarah Keim, Ph.D., lead author on the study and principal investigator in the Center for Biobehavioral Health in The Research Institute at Nationwide Children's.

Dr. Keim and her team conducted a study where 31 toddlers who were born prematurely participated. For 3 months, half of them took a daily dietary supplement that contained a special combination of omega-3 and omega-6 fatty acids, and the other half took a placebo, although families were unaware of which they received to make the study rigorous.

The group that took the daily omega fatty acid supplement exhibited a greater reduction in ASD symptoms than those who took the placebo, according to ratings provided by the children's parents.

"We found clinically significant improvements in ASD symptoms in the treatment group, although the benefits were confined to one measure we used," explains Dr. Keim. "We need to do a larger trial to further understand the potential impacts on a larger group of children."

The researchers suggest that observed benefits of omega fatty acid supplementation could be due to the role of these nutrients in inflammation in the body. ASD is generally considered a neuroinflammatory condition, and influencing inflammation through nutritional supplementation could improve behaviors in children with ASD symptoms.

Researchers hope that by giving omega fatty acids to children early when they first show symptoms and the brain is still actively developing may help them long-term.

"Currently, no medications are available to help children born prematurely with the developmental delays and behavior problems they often experience. For very young children, the medications that physicians sometimes try tend to have many side effects. And we don't know what effect those medications have on brains that are still developing," says Dr. Keim. "If using omega fatty acid supplementation helps, it would have a really huge impact for these kids."

Dr. Keim and her team plan to expand the work in a full-scale trial in the future. They recently received a grant from the National Institutes of Health to study the effect of omega fatty acids in children ages 2-6 year who have ASD.

Ref : https://academic.oup.com/jn/article-abstract/148/2/227/4913038?redirectedFrom=fulltext

Omega fatty acid supplements may improve ASD symptoms in toddlers born preterm, study shows

Omega-3 Fatty Acids for protecting the liver from damage caused by obesity and the insulin resistance it provoke...

(1)--alpha-linolenic acid (ALA),


(2)-eicosapentaenoic acid (EPA)





(3)-docosahexaenoic acid (DHA)

According to a recent study by Dr. Joan Claria and co workers, diets rich in omega-3 fatty acids (1, 2 & 3) protect the liver from damage caused by obesity and the insulin resistance it provokes. This research should give doctors and nutritionists valuable information when recommending and formulating weight-loss diets and help explain why some obese patients are more likely to suffer some complications associated with obesity. Omega-3 fatty acids can be found in canola oil and fish.

The researchers found that lipids called protectins and resolvins derived from omega-3 fatty acids can actually reduce the instance of liver complications, such as hepatic steatosis and insulin resistance, in obese people. The group claims that, two types of lipids in omega-3 fatty acids—protectins and resolvins—were the cause of the protective effect. These results are based on animal models of testing and hope this info will help dieticin to prepare list of diets to reduce the obesity, with reduced complications to the liver. More....

Supplement of polyunsaturated fatty acids may improve reading skills in children

Supplement of omega-3 and omega-6 fatty acids may improve reading skills of mainstream schoolchildren, according to a new study from Sahlgrenska Academy, at the University of Gothenburg, Sweden. Children with attention problems, in particular, may be helped in their reading with the addition of these fatty acids.

The study included 154 schoolchildren from western Sweden in grade 3, between nine and ten years old. The children took a computer-based test (known as the Logos test) that measured their reading skills in a variety of ways, including reading speed, ability to read nonsense words and vocabulary.

The children were randomly assigned to receive either capsules with omega-3 and omega-6, or identical capsules that contained a placebo (palm oil) for 3 months. The children, parents and researchers did not learn until the study was completed which children had received fatty acids and which had received the placebo. After three months, all children received real omega-3/6 capsules for the final three months of the study.

"Even after three months, we could see that the children's reading skills improved with the addition of fatty acids, compared with those who received the placebo. This was particularly evident in the ability to read a nonsense word aloud and pronounce it correctly (phonologic decoding), and the ability to read a series of letters quickly (visual analysis time)," says Mats Johnson, who is chief physician and researcher at the Gillberg Neuropsychiatry Centre at Sahlgrenska Academy, University of Gothenburg.

No children diagnosed with ADHD were included in the study, but with the help of the children's parents, the researchers could identify children who had milder attention problems. These children attained even greater improvements in several tests, including faster reading already after three months of receiving fatty acid supplements.

Polyunsaturated fats important for the brain

Polyunsaturated fats and their role in children's learning and behavior is a growing research area.

"Our modern diet contains relatively little omega-3, which it is believed to have a negative effect on our children when it comes to learning, literacy and attention," says Mats Johnson. "The cell membranes in the brain are largely made up of polyunsaturated fats, and there are studies that indicate that fatty acids are important for signal transmission between nerve cells and the regulation of signaling systems in the brain."

Previous studies in which researchers examined the effect of omega-3 as a supplement for mainstream schoolchildren have not shown positive results, something Mats Johnson believes may depend on how these studies were organized and what combination and doses of fatty acids were used. This is the first double-blind, placebo-controlled study showing that omega-3/6 improves reading among mainstream schoolchildren.

"Our study suggests that children could benefit from a dietary supplement with a special formula. To be more certain about the results, they should also be replicated in other studies," says Mats Johnson.

Supplement of polyunsaturated fatty acids may improve reading skills in children

Are Omega-3s Linked to Lower Risk for Fatal Heart Attack?

In continuation of my updates on omega-3 fatty acids

Regularly eating fish and other foods rich in omega-3 fatty acids may lower your risk of fatal heart disease, a new research review suggests.

"Our results lend support to the importance of fish and omega-3 consumption as part of a healthy diet," said senior study author Dr. Dariush Mozaffarian, dean of the Friedman School of Nutrition Science and Policy at Tufts University, in Boston.

"At a time when some but not other trials of fish oil supplementation have shown benefits, there is uncertainty about cardiovascular effects of omega-3s," Mozaffarian said in a university news release.

Fish are the main dietary sources of omega-3 fatty acids. Fatty fish, such as salmon, trout, anchovies, sardines and herring, are the richest source of these nutrients.

Walnuts, flaxseed oil, canola oil and some other seeds and nuts contain the plant-based omega-3 known as alpha-linolenic acid, according to the U.S. Department of Agriculture.

For the study, the researchers analyzed 19 studies from 16 countries that involved nearly 46,000 people. Of these people, nearly 8,000 suffered a first heart attack over time, which resulted in 2,781 deaths.

Plant-based and seafood-based omega-3s were not associated with a lower risk of non-fatal heart attacks. But they were linked with a roughly 10 percent lower risk of fatal heart attacks, although the study can't prove a direct cause-and-effect relationship.

"These new results, including many studies which previously had not reported their findings, provide the most comprehensive picture to date of how omega-3s may influence heart disease," said study leader Liana Del Gobbo, a postdoctoral research fellow at Stanford University School of Medicine. "Across these diverse studies, findings were also consistent by age, sex, race, presence or absence of diabetes, and use of aspirin or cholesterol-lowering medications."

Are Omega-3s Linked to Lower Risk for Fatal Heart Attack?  

Omega-3 could supplement anti-VEGF treatment in AMD

In continuation of my update on Omega 3 fatty acid

Pilot study findings suggest that taking omega-3 fatty acid supplements could increase the efficacy or reduce the needed frequency of anti-vascular endothelial growth factor(VEGF) treatment in patients with exudative age-related macular degeneration (AMD).

Researcher Flavio Rezende (University of Montreal, Quebec, Canada) and co-workers say that 5–10% of patients with wet AMD lose three lines or more of visual acuity, despite treatment, and that more frequent anti-VEGF injections are associated with side effects.

Omega-3 could supplement anti-VEGF treatment in AMD

Flaxseed lowers high cholesterol in men.....

Flax (also known as common flax or linseed) (Linum  usitatissimum) is a member of the genus Linum in the family Linaceae. It is native to the region extending from the eastern Mediterranean to India.  This is called as Agasi/Akshi in Kannada, Jawas/Javas (जवस) or Alashi (अळशी) in Marathi.  

Flax seeds come in two basic varieties brown yellow or golden. Most types have similar nutritional characteristics and equal amounts of short-chain omega-3 fatty acids. The exception is a type of yellow flax called Linola or solin, which has a completely different oil profile and is very low in omega-3. Although brown flax can be consumed as readily as yellow, and has been for thousands of years, it is better known as an ingredient in paints, fiber and cattle feed. Flax seeds produce a vegetable oil known as flaxseed or linseed oil, which is one of the oldest commercial oils and solvent-processed flax seed oil has been used for centuries as a drying oil in painting and varnishing. 

Flaxseeds are rich in alpha linolenic acid (ALA), an omega-3 fat that is a precursor to the form of omega-3 found in fish oils called eicosapentaenoic acid or EPA. Many benefits like 1. anti-iflammatory benefits, 2. omega-3-rich flaxseeds protect bone health, 3.protection against heart disease, cancer and diabetes, 4. flaxseeds help prevent and control high blood pressure. And even it helps to control some types of cancers.

Earlier report says,  Flaxseed provides comparable cholesterol-lowering benefits to statin drugs. Now this has been further substantiated by researchers from Iowa State University's (ISU) Nutrition and Wellness Research Center (NWRC).

Suzanne Hendrich, an ISU professor in food science and human nutrition, led a study that examined the effects of flaxseed lignan in 90 people diagnosed with high cholesterol. The results showed that consuming at least 150 milligrams of flaxseed lignans per day (about three tablespoons) decreased cholesterol in men, but not women, by just under 10 percent over the three months that they were given the flaxseed.  Suzanne concludes that though the result is  considerably less than the expected outcome from cholesterol-lowering drugs -- approximately 10 to20 percent for three months, depending on the individual -- it's still enough to make flaxseed a more natural option for some men. While the study found that the flaxseed lignans lowered cholesterol in men, it did not produce a significant change in women. More.... 

Ref : http://www.news.iastate.edu/news/2010/mar/flaxseed

(Those interested in knowing the other benefits of flax seed can read the article..)

Increase in EPA/DHA omega-3 intake linked to lower risk of all-cause mortality

A recent meta-analysis in Scientific Reports supports a link between EPA and DHA omega-3 intake and a reduced risk of death by any cause. The meta-analysis included 11 studies involving 371,965 participants and 31,185 death events, with a subset of the studies being used for different analyses.

DHA   EPA

In the analysis of n-3 LCPUFA intake, there was a 9% reduced risk of all-cause death associated with high versus low omega-3 intake. In the dose-response analysis, an increase in EPA/DHA intake of 300 mg/day was associated with a 6% lower risk of all-cause mortality. These findings suggest that both dietary and circulating n-3 LCPUFA are shown to be significantly associated with reduced risk of all-cause mortality.

According to study author Manfred Eggersdorfer, "The meta-analysis of 11 prospective observational studies demonstrates that each 1% increment of omega-3s in total fatty acids in blood may be associated with a 20% decrease in risk of all-cause mortality. This is an important finding for the potential contribution of adequate omega-3 intake to public health."

Flaxseed-fed chickens shed light on ovarian cancer.....

In continuation of my update on the benefits of  flax seeds,  I found this info interesting to share with. Researchers from College of Agricultural, Consumer and Environmental Sciences, lead by Prof. Janice Bahr, have come up with interesting info about flax seeds, i.e., hens fed a flaxseed-enriched diet for one year experienced a significant reduction in late-stage ovarian tumors.

The interesting part of the research lies in that fact that, chicken is the only animal that spontaneously develops ovarian cancer on the surface of the ovaries like humans and researchers  evaluated how a flaxseed-enriched diet affected 2-year-old laying hens (hens that have ovulated as many times as a woman entering menopause). As we know flaxseed is the richest plant source of alpha-linolenic acid, (omega-3 fatty acid). Several studies have already shown that flaxseed inhibits the formation of colon, breast, skin and lung tumors.

As per the claim by the researchers, hens fed the control diet had significantly more late-stage tumors that presented with fluid and metastases as compared to the hens fed a flaxseed diet. Though hens fed the flaxseed diet did not have a decreased incidence of ovarian cancer, they did experience fewer late-stage tumors and higher survival rates.

In addition, researchers found that hens fed the flaxseed diet had better weight control which is important because obesity increases cancer risk. Both diets had equal caloric content, however the flaxseed-fed hens weighed less at six months than the control-fed hens. But at 12 months, the flaxseed-fed hens were the same weight and the control-fed hens had loss significant weight, which was indicative of their failing health. Ultimately, the flaxseed-enriched diet helped the birds maintain a healthy weight and resulted in less sickness and death.

"Through this research, we have proven that flaxseed supplementation for one year is able to reduce the severity of ovarian cancer in hens," she said. "These findings may provide the basis for a clinical trial that evaluates the efficacy of flaxseed as a chemosuppressant of ovarian cancer in women."

Bahr believes this hypothesis is valid and is currently in the middle of a four-year study to determine if long-term dietary intervention with flaxseed will reduce the incidence of ovarian cancer development....

Ref : http://www.aces.uiuc.edu/news/stories/news5165.html

New combination drug controls tumor growth, metastasis in mice...

Researchers at UC Davis, University of      Massachusetts  and Harvard  Medical  School  have
created a combination drug that controls both tumor growth and metastasis. By combining a COX-2 inhibitor, similar to Celebrex, and an epoxide hydrolase (sEH) inhibitor, the drug controls angiogenesis (blood vessel formation), limiting a tumor's ability to grow and spread. The study appears today in the journal Proceedings of the National Academy of Sciences.

"We've   been   studying  the  effects of  COX  and  sEH  inhibitors, both    by themselves  and in combination, for several years," said senior author and UC Davis Distinguished Professor Bruce Hammock. "We were surprised to find that the dual inhibitor was more active than higher doses of each compound, either individually or together. By combining the two molecules into one we got much greater potency against several diseases and completely unique effects in terms of blocking tumor growth and metastasis."

Both COX and sEH enzymes control lipid signaling, which has long been associated with inflammation, cell migration, proliferation, hypertension and other processes. COX inhibitors block production of inflammatory and pain-inducing lipids, while sEH inhibitors preserve anti-hypertensive, anti-inflammatory and analgesic compounds. Separate COX and sEH inhibitors were previously found to work together in reducing inflammation and neuropathic pain.

After testing individual COX-2 and sEH inhibitors, the team synthesized the drug (PTUTB), the first combined COX-2/sEH inhibitor. They then tested the dual inhibitor against human lung and breast tumors, both in vitro and in mice. They found that PTUTB blocked angiogenesis, inhibiting the proliferation of endothelial cells, which are critical to blood vessel formation. This in turn limited tumor growth and metastasis, reducing lung and breast tumor growth by 70 to 83 percent. 

In breast and lung cancers, the dual inhibitor blocked angiogenesis, which blocked the growth of solid tumors," said Hammock. "This represents a new mechanism to control blood vessel and tumor growth."

Robert Weiss, a co-author and professor of nephrology at UC Davis, added that the combination drug achieved the results with minimal side effects and no cardiovascular or gastrointestinal effects.

"This is particularly important when administering COX-2 inhibitors, which have well-known cardiovascular risks," he said. "However, the added sEH  inhibitor appears to block COX-2's side effects."

The research was initiated by first author Guodong Zhang when he was a postdoctoral fellow in the Hammock laboratory. Zhang previously demonstrated that sEH inhibitors improve the power of omega-3 fatty acid (fish oil) diets to reduce tumor growth and metastasis, and implicated epoxides of the dietary supplement DHA as the causative agent.

New combination drug controls tumor growth, metastasis in mice