Researchers discover a protein that protects against fatty liver

A team co-headed by scientists at the Institute for Research in Biomedicine and the IDIBAPS Biomedical Research Institute has revealed the capacity of the CPEB4 protein to prevent fatty liver disease.

January 18, 2017

Mouse fatty liver. Credit: C. Maíllo, IRB Barcelona

This condition generally leads to chronic inflammation (non-alcoholic steatohepatitis), which can trigger fibrosis, cirrhosis and ultimately liver cancer. This study on the basic biology of the liver paves the way to examine therapeutic strategies to fight and prevent fatty liver disease. The results have appeared in Nature Cell Biology this week.

CPEB4 and fatty liver

Non-alcoholic fatty liver is characterised by the accumulation of fat deposits in hepatocytes. The development of this condition is determined by many factors that have not been well described to date. However, obesity and lifestyle, as well as aging, are associated with an increase in the incidence of this disease. Also, a number of large-scale genomics studies have linked variants of the CPEB4 gene with the impairment of fat metabolism.

The scientists at IRB Barcelona depleted CPEB4 expression in mouse livers in order to study the function of this protein. They observed that the mice developed fatty liver as they aged. Furthermore, young CPEB4-depleted mice fed a high-fat diet also developed this condition in a more pronounced manner.

Carlos Maíllo, first author of the article and PhD student at IRB Barcelona has described the molecular function of CPEB4. He reveals that this protein is essential to drive the liver stress response.

Specifically, under stress, such as that caused by uncontrolled ingestion of fats, for example, the endoplasmic reticulum—a cell organelle associated with protein synthesis and folding and lipid metabolism—stops its activity in order to re-establish cell equilibrium. This "clean-up" mechanism is orchestrated by CPEB4 and varies in function of the time of day—being more active in humans during the day (when the liver has most work) and dropping off at night.

Staining of mouse liver sections showing steatosis of the liver (fatty liver), with accumulation of fat, lipid droplets (in red), within cells. Cell nuclei stain blue. Credit: C. Maillo, IRB Barcelona

Without CPEB4, the endoplasmic reticulum is unable to activate the stress response, thus causing hepatocytes to accumulate the lipids produced by the fatty liver.

New treatments?

Raúl Méndez, ICREA researcher at IRB Barcelona and co-leader of the study, explains that "knowledge of the hepatic function of CPEB4 could be useful as a predictive marker for those people with variants of this protein, thus serving to prevent this condition, for example, through improvements in diet and better choice of eating times. Such knowledge could also contribute to the development of treatments that boost the clean-up process".

The researchers have managed to reverse fatty liver disease in mice by treatment with a drug called Tudca, which is currently used for other disorders. This drug exerts the same function as the proteins that are activated by CPEB4 and that are responsible for cleaning up the cell, namely chaperones. "In the future, it may be possible to design molecules like Tudca that specifically target CPEB4, thus enhancing the liver clean-up process," says Méndez.

"This basic research study does not have a direct and immediate clinical application, but it lays down the foundation for the applied science that follows," says Mercedes Fernández, co-leader of the study and head of the group at IDIBAPS and the Biomedical Research Networking Center of Hepatic and Digestive Diseases (CIBEREHD).

Fernández warns, "Given the obesity epidemic in the U.S. and worldwide, an increase in those affected by non-alcoholic fatty liver disease is expected in the coming decades and we still do not have a suitable treatment for this condition; A fundamental understanding of this medical problem is therefore essential for development of novel treatment strategies."

It is estimated that between 80 and 100 million people in the U.S. alone suffer from fatty liver disease. People with this disease have an increased risk of cirrhosis and liver cancer. Moreover, liver cancer incidence has more than tripled since 1980 and is the primary cause of death in patients with cirrhosis.

 Explore further: Unveiling the biology behind nonalcoholic fatty liver disease

More information: Carlos Maillo et al. Circadian- and UPR-dependent control of CPEB4 mediates a translational response to counteract hepatic steatosis under ER stress, Nature Cell Biology (2017). DOI: 10.1038/ncb3461 

Journal reference: Nature Cell Biology  

Provided by: Institute for Research in Biomedicine (IRB Barcelona)

https://medicalxpress.com/news/2017-01-protein-fatty-liver.html

https://www.sciencedaily.com/releases/2017/01/170117101838.htm

How science ruined tomatoes, and how it can fix them

Some things really were better in the good old days. It’s not just nostalgia but scientific fact, for example, that tomatoes used to taste a lot better. Somewhere over the course of the late 20th century, they lost their tomato flavor.

February 10, 2017

When faced with the choice of costly heirloom tomatoes that taste great or cheaper
mass-cultivated ones that look good but lack flavour, consumers will still opt for the latter.

How tomatoes went from a sweet-savoury summer treat to something watery and bland presents not just a chemical and genetic mystery, but an economic and cultural one. Call it a fruit (the botanically correct term), or a vegetable (the way it’s regarded in American and European cooking), and either way, the tomato is a global favourite. When the flavour disappeared, why didn’t consumers rebel, the way they do when soda-makers change their formulas and the new version disappoints?


The answer is emerging from the field and the lab. In late January, a group of biologists from the United States and China unveiled the results of a multi-year study retracing the former flavour of the popular salad staple.


The scientists isolated not just the chemistry of the tomato’s lost taste but the genetics – opening up the possibility of creating the perfect 21st-century tomato, one that combines the high yields of today with the taste of yesteryear.


One of the study’s leaders, plant biologist Harry Klee of the University of Florida, said they couldn’t have done it without a large contingent of Chinese colleagues. Tomatoes are beloved in China, he said, which is by far the world’s largest producer.

Tomatoes in the form of a sauce on pizza.

In his travels to China, Klee encountered tomatoes served for dessert, on fruit plates. In this context, the flavour deficiency might stand out more than it does in America, where people eat tomatoes pulverised and seasoned into pizza sauce, slathered in ranch dressing, or wedged into Big Macs.
But Klee sees a trend in America toward appreciation of flavour – from the rise of gourmet coffee and craft beer to the increasing number of heirloom tomatoes found in farmers’ markets. Those have given many consumers a sense of what they’d been missing.

Sensory burnout

The study involved 398 varieties of tomatoes, ordinary and heirloom, and about 100 taste-testing volunteers, he said. The project took years, because people can reliably rate the flavour of only about five tomatoes in a sitting before they get sensory burnout.


The researchers analysed the chemistry of the tomatoes and found 13 compounds associated with good flavour. They also studied the DNA, and found the genes that allowed the good-tasting tomatoes to produce those compounds.

Roma tomatoes growing on the vine.

Why tomatoes used to taste so good goes back to their wild roots as sweet little berries that depended on birds or other animals to disperse their seeds. Tomatoes originated in Central and South America, where native people were cultivating them before the arrival of Columbus and the introduction of tomatoes to Europeans.


The flavour seems to have gone missing in the latter part of the 20th century, said Klee, when growers started to focus on other priorities – especially yield and shelf life. This wasn’t all bad, according to Ann Powell, a biochemist at the University of California, Davis.


“It’s hard to put blame on breeders,” she said. “They’ve given us attractive products that are palatable and fairly nutritious year round.”


They ship well, she said, and can be found almost anywhere.


But evolution is a trade-off, whether it happens by breeding or natural selection. Back when they were being eaten by birds or grown by small-scale farmers, good taste was essential for tomato survival.

A tomato plant.

When modern growers focused on yield and sturdiness, they inadvertently bred plants with random mutations in genes that don’t influence yield, but do influence the chemistry of the fruit.


“There’s no feedback to the farmers whether they produce a tomato that tastes like cardboard or one that tastes like an heirloom from your backyard,” Klee said.


The transformation probably didn’t happen all at once. More likely, one flavour compound disappeared at a time. It happened quietly, not with the kind of fanfare that accompanies a new recipe for fast food or soft drinks.

Bird brains

As for consumers, our brains are tuned like those of birds and other fruit-eating animals to respond to colour. When faced with costly heirloom tomatoes and bright red, ripe-looking regular ones at a quarter of the price, most will go for the cheap ones. They don’t look bland.


Danielle Reed, a taste geneticist at the Monell Chemical Senses Center in Philadelphia, said the findings open up the possibility of growing big, beautiful tomatoes that ship well and also taste delicious.


By retracing how tomato flavour got lost, she said, the researchers showed it didn’t have to be that way. She’d like to see similar analysis done on carrots, she said, which have been bred to be sweeter but to her seem unappealingly sugary.


Klee said the plan is to restore the flavour compounds to produce a better tomato. The biggest challenge, however, is making mass-produced tomatoes as sweet as their ancestors.


The sweetness comes from sugars the plant produces through photosynthesis, he said. If a plant makes only four tomatoes, it can pump a lot of nutrition into them. If the same plant is bred to produce 20 tomatoes, it can’t keep up, and so it makes each tomato more diluted.


The most efficient, precise way to make a better tomato would be to take advantage of genetic technology, he said, transferring genes from better-tasting varieties, or using the newer technology known as gene editing.


“If I could use GMO technology, I could make a fabulous tomato,” he added. That’s unlikely to happen, he said. There’s too much public resistance to genetically modified foods, despite a green light from a number of scientific panels.


Still, people tend to associate GMOs with large-scale farming and a trend toward diminished taste and nutrition. Some might feel differently about a product engineered to bring something back. – Bloomberg/Faye Flam

http://www.star2.com/living/science-technology/2017/02/10/how-science-ruined-tomatoes-and-how-it-can-fix-them/

Exclusive Report from the American Association for Cancer Research Conference

Most cancers are preventable with lifestyle alterations. Scientists at the annual meeting of the American Association for Cancer Research report on a variety of research topics relating to reducing cancer risk and improving oncology treatments.

September 2016

By Ben Best

Most forms of cancer are almost entirely preventable. No more than 10% of cancer cases can be attributed to inherited genetic factors, while 90%-95% are caused by lifestyle and environmental factors.1

Tobacco alone accounts for 25%-30% of cancer deaths, diet for 30%-35%, infections for 15%-20%, and radiation (including ultraviolet light) up to 10%.1 Being overweight or obese is estimated to cause 4%-20% of cancer deaths.2 All of these factors create or lead to chronic inflammation,3 the most common cause of cancer.1,4

Cells in body tissues are normally “good citizens” that cooperate with other cells to facilitate body function. Cancer cells, by contrast, have no purpose other than to grow and multiply, contributing nothing to body function.

Many cancers are based on abnormal DNA or chromosomes, usually due to lifestyle or environmental DNA damage, but some are the result of inherited mutations.5 For example, although mutations in the BRCA1 gene are not common for the general population,6,7 for those having it, the risk of breast or ovarian cancer before the age of 70 is 65% or 39%, respectively.8 (It’s possible that lifestyle differences have some bearing on which BRCA1 carriers do or do not get cancer, but this has not been well studied.)

The two broad classes of genetic defects underlying cancer are (1) overactive oncogenes (genes that accelerate growth and multiplication), and (2) inactivated tumor suppressor genes (genes that normally prevent cancer).

Two of the most common oncogenes are PIK3CA (which promotes cell growth, survival, and motility)9 andKRAS (which greatly increases cell glucose uptake).10 The most common tumor suppressor gene is p53(which causes cells with defective DNA to self-destruct or stop replicating).11

Cancer begins with gene mutations that increase abnormal growth and replication. Factors that assist these processes enable cancer cells to immortalize, or promote the formation of new blood vessels to nourish the tumor. In more advanced stages, mutations allow cancer to spread to other organs, a process called metastasis. More than 90% of cancer deaths are due to metastasis.12 To reach the metastatic stage typically requires at least several mutations.13 The risk of cancer before age 40 is only about 2%, but by age 80 the risk increases to 50%.14

In the United States, the six most frequently diagnosed cancers are, in decreasing order: breast, lung, prostate, colorectal, bladder, and skin. The six most common causes of cancer death in the United States are, in decreasing order: lung, colorectal, pancreas, breast, prostate, and liver.15 Thanks to aggressive efforts to detect breast and prostate cancer in early stages, they are often cured. Pancreatic cancer, by contrast, is usually only detected in more advanced stages.

Normal cells generate most of their energy from glucose and oxygen in the mitochondria. Cancer cells, however, obtain their energy by glucose metabolism outside the mitochondria through glycolysis. Although it is 18 times more efficient to derive energy from glucose in mitochondria,16 cancer cells compensate by absorbing massive amounts of glucose, with rates of glycolysis up to 200 times greater than normal cells.17

Cancer cells use glucose primarily as a source of material for building cellular components, rather than for energy.17,18 High glucose utilization is so characteristic of cancer that cancer imaging with PET scans is based on detection of high glucose utilization.19

Dichloroacetate (DCA), a non-patented compound, counteracts a protective mechanism used by cancer cells that prevents glucose products from entering mitochondria, which would send the mitochondria into overdrive, resulting in cell death.18 Life Extension Foundation® is funding clinical trials to treat cancer patients with DCA.

With this background, let’s review the American Association for Cancer Research annual meeting, which was held April 18-22, 2015, in Philadelphia.

Colorectal Cancer

Grivennikov

Sergei Grivennikov, PhD, assistant professor, Fox Chase Cancer Center, Philadelphia, is a specialist in cancers of the large intestine and rectum. He provided insights on the most frequently mutated gene in colorectal cancer, the adenomatous polyposis coli (APC) gene. This defect is seen in 75% of sporadic colorectal cancers, but is due to an inherited mutation in less than 1% of cases.20

Chronic inflammation, characterized by the release of inflammatory cytokines (proteins) and DNA-damaging oxidants is typically the cause of colorectal gene mutations. Chronic inflammation not only contributes to the initiation of cancer mutations, but to tumor growth and metastasis.12 Inflammation leads to infiltration of bacteria into tumors, which enhances the inflammation by releasing endotoxins.21-23 A high-fat diet can result in excessive pro-inflammatory bile acids, which can increase cancer-causing bacteria.24 Calcium can help remove toxic bile acids.25,26

Trinchieri

Giorgio Trinchieri, MD, director for the Cancer and Inflammation Program, National Cancer Institute, Bethesda, Maryland, is concerned with the fact that inflammation contributes to abnormal bacteria in the gut, and that the abnormal bacteria interfere with anticancer chemotherapy.27 Dr. Trinchieri would like to alter the gut microbiota to improve cancer treatment.28 He recommends the use of probiotics, prebiotics, and transplantation of feces from healthy persons into cancer patients.29 The FDA has been blocking fecal transfer by insisting that human stools are a drug which will require FDA approval before it can be given to patients.30

Jobin

Christian Jobin, PhD, professor of medicine, University of Florida, Gainesville, is concerned with how inflammation induces colorectal cancer. Death from colorectal cancer is at least twice as high in persons with ulcerative colitis or Crohn’s Disease as for the general population.31 Dr. Jobin suggests that inflammation encourages expansion of gut microorganisms that can induce cancer,32 including more toxic strains of E. coli bacteria.33 Even without increasing the number of E. coli, inflammation can increase the propensity of E. coli to induce colorectal cancer.34 Dr. Jobin wants to develop bacteria-killing viruses that are specific for the toxic strains of E. coli most responsible for inflammation and cancer.

Aspirin against Colorectal Cancer

Andrew Chan, MD, program director, Gastroenterology, Massachusetts General Hospital, Boston, has investigated the use of aspirin to prevent colorectal cancer and to improve survival in colorectal cancer patients. Dr. Chan found that women who took the largest amounts of aspirin (325 mg more than 14 times per week) had the greatest (53%) reduction in risk of colorectal cancer.35 But he also found that those women had the highest risk of gastrointestinal bleeding.36 Dr. Chan discovered that aspirin increased survival in colorectal cancer patients with a PIK3CA mutation, but not in patients lacking this mutation.37 Dr. Chan has done genetic screening to better identify colorectal cancer patients who would or would not benefit from aspirin.38 Editor’s note: Studies using lower dose aspirin reduce cancer risk, but not as effectively (by 53%) as reported by Dr. Chan.98,99

Cervical Cancer

Douglas Lowy, MD, acting director, National Cancer Institute, Bethesda, Maryland, works on vaccination against human papillomavirus (HPV). HPV is nearly always the cause of cervical cancer,39 which is the second most common cause of cancer in women worldwide.40 HPV is almost twice as common in less developed countries compared to developed countries,41 and is the most common sexually transmitted infection, although symptoms are not usually manifest.42 A school HPV vaccination program for girls aged 12-17 was introduced in Australia in 2007. Prevalence of the types of HPV vaccinated against dropped to less than a quarter of the initial value in young women by 2011,43 and genital warts among women under 21 dropped from over 11% to less than 1%.44 DNA testing for HPV provides 60%- 70% better screening than Pap smears.45

The PIK3CA Oncogene Mutation

Vanhaesebroeck

Bart Vanhaesebroeck, PhD, professor, University College London Cancer Institute, London, England, is interested in the PIK3CA subset of PI3K ( PhosphoInositide 3-kinase) as one of the most frequently mutated genes in cancer, occurring in up to 40% of breast cancer cases, more than a third of cancers of the uterus, up to a third of colon cancers, and about a quarter of stomach cancers (among other cancers).46These mutations in PIK3CA result in excessive cell growth, multiplication, metastasis, and inhibition of apoptosis (cell suicide).9 PIK3CA mutations are one of the most common oncogene mutations in breast cancer (especially cases associated with increased estrogen response).47 PIK3CA-inhibiting substances can not only reduce PIK3CA activity,48 but normalize blood vessels, thereby facilitating delivery of other chemotherapeutic agents.49

Cancer Stem Cells

Kolev

Vihren Kolev, PhD, senior scientist, Verastem, Inc., Cambridge, Massachusetts, is attempting to eliminate cancer by targeting cancer stem cells. These cells are hard to eliminate. Often, apparently successful eradication of tumors by chemotherapy ultimately ends in failure because surviving cancer stem cells create a new, more resistant tumor. He described markers of cancer stem cells, such as focal adhesion kinase50 and aldehyde dehydrogenase 1,51,52 which have the possibility of making stem cells easier to locate and identify, and thus eliminate.

SIRT6 Protects Against Cancer

Mostoslavsky

Raul Mostoslavsky, MD, PhD, associate professor of Medicine, Harvard Medical School, is an expert in sirtuin proteins,53 the most well-known of which is SIRT1. SIRT1 extends the lifespan of yeast, worms, and flies when stimulated by resveratrol.54 Dr. Mostoslavsky, however, is most interested in the effect of SIRT6 on cancer. SIRT6 is localized at the telomeres at the end of chromosomes. It helps to maintain genetic stability, and prevents cellular aging.55 Dr. Mostoslavsky has demonstrated that SIRT6 maintains genetic stability by assisting with repair of damaged DNA.56 Cancer cells are greatly dependent on glycolysis to support rapid growth and multiplication. Dr. Mostoslavsky has shown that SIRT6 opposes this process, that reduction of SIRT6 fosters glycolysis, and that many cancers repress SIRT6.57 Life Extension Foundation is funding Dr. Vera Gorbunova to find SIRT6-activating therapies.

Enhancing the Immune System against Cancer

Schumacher

Ton Schumacher, PhD, professor, Netherlands Cancer Institute, Amsterdam, Netherlands, works on using the immune system to fight cancer. The role of the immune system in preventing cancer is apparent from the fact that AIDS victims and transplant recipients taking immune suppressant drugs have an increased risk of cancer.58,59 Cancer cells are able to evade or suppress the immune system. The journal Science called cancer immunotherapy the “breakthrough of the year” in 2013 because of the discovery of ways to prevent cancer from blocking the immune system.60 Cancer that has spread from its tissue of origin (metastatic cancer) is generally incurable. Metastatic melanoma has shown rapid tumor regression in nearly a third of patients receiving these kinds of immunotherapies (checkpoint inhibitors) that prevent cancer from blocking the immune system.60 Dr. Schumacher was part of a team that analyzed nearly five million mutations in over 7,000 cancers. Melanoma and lung cancer were found to have the highest frequency of mutations.61 Cancer cells that have the highest number of mutations, such as melanoma, are the most vulnerable to this type of (checkpoint inhibitor) immunotherapy.62

CRISPR Gene Editing to Fight Cancer

 

Tyler Jacks, PhD, director, Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts, has been using the new CRISPR/Cas9 technology, which was developed for editing the human genome in 2013.63,64 CRISPR/Cas9 is based on a system used by bacteria to defend themselves against viruses. When bacteria are invaded by viruses, the bacteria store part of the virus’s DNA in the genome of their cell, called CRISPR. RNA copied from the CRISPR is attached to a Cas9 cutting enzyme. The RNA then guides the Cas9 enzyme to the virus to cut (and thereby destroy) the virus. CRISPR/Cas9 has been applied to gene editing by designing guide RNAs for specific DNA locations to be edited.63

Dr. Jacks has worked on a team that used CRISPR/Cas9 to cure an inherited disease in a mouse.65 He has also used CRISPR/Cas9 to create a mouse model of cancer.66 Such models can be used to study the features of many cancer types, and to experiment with potential therapies. Cancer cells can have a high mutation rate, although only a few of the mutations are thought to drive the cancer. CRISPR/Cas9 can be used to distinguish between mutations that drive cancer and mutations which do not. Dr. Jacks anticipates that CRISPR/Cas9 will be used to design immune system cells that target specific cancers.67

Conclusions/Interpretations

 

It is an unfortunate fact that almost all of modern medicine is based on treatment of disease, rather than on prevention, most tragically exemplified by cancer, which is so highly preventable. The key to prevention is better lifestyle. Unconventional health practices have the potential to reduce cancer incidence even more than the lifestyle changes advocated by conventional medicine. As I wrote in the December 2015 issue of Life Extension Magazine®, a low carbohydrate ketogenic diet can provide energy while depriving cancer cells of the amount of glucose they require.

Conventional medicine too often discounts the value of supplements, but many scientific studies demonstrate that supplements can substantially reduce cancer incidence.1

The key to more curative treatment is early detection. Good breast and prostate examination practices explain why the diagnosis rate for these cancers greatly exceeds the rate of fatality. Colon cancer would be more effectively treated if more people had regular colon examinations. Liver cancer is often due to chronic inflammation resulting from hepatitis. The hepatitis B virus can be prevented by vaccination.68 Hepatitis C virus is usually transmitted by unsafe intravenous drug or transfusion practices and unprotected sex, but is now controlled in over 90% of cases.69,70 Pancreatic cancer has been difficult to detect in early stages, which is why it is so often fatal. Cancer cells often release DNA into the bloodstream, which means that detecting cancer through blood tests (“liquid biopsies”) may be done in the future if standardized techniques can be developed.71

Notes on Cancer Prevention

There appears to be a link between salt intake and the bacterium Helicobacter pylori, which is associated with stomach cancer. It is possible that these two factors contribute to the development of the disease. In addition, salt intake and other dietary components are likely to damage the stomach mucosal lining, increasing the risk of stomach cancer.72 Risk of stomach cancer, colon cancer, and rectal cancer is probably increased by damage to mucous membranes from iron or N-nitroso compounds (NOCs) in red or processed meat.73-75Further damage is caused when cooking at high temperatures as this contributes to the formation of cancer-causing heterocyclic amines.76 Mucosal damage is also a reason why consuming more than two drinks of alcohol daily increases colorectal cancer risk.77 Any amount of alcohol consumption increases the risk of breast cancer in women because alcohol can convert estrogen into carcinogenic forms.78-81 For women with a BRCA1 mutation, surgical removal of the breasts can result in a reduced breast cancer risk.82,83

Animals that eat plants and fish that eat fish have increased concentrations of toxic metals in their flesh84,85and increased concentrations of organic toxins in their fat.86-88 Organic toxins like PCBs (polychlorinated biphenyls) persist in the environment and thus accumulate in fat tissue, increasing by many times the risk of melanoma skin cancer (for example).89 Because these toxins can damage DNA and cause cancer, a plant-based diet is safer than an animal-based diet. Chlorophyllin supplements can reduce the cancer-causing potential of toxin exposure.90,91 (See the December 2015 issue of Life Extension Magazine for more details.)

Selenium supplementation has been shown to reduce cancer incidence.92 A double-blind, randomized study showed that zinc supplements improved survival of cancer patients receiving radiation therapy.93 Vitamin D supplementation has been shown to reduce breast cancer incidence.94 Curcumin has been shown to inhibit breast cancer metastasis in mice.95 Higher quercetin intake is associated with reduced lung cancer incidence.96 A randomized, placebo-controlled trial of omega-3 fatty acid (EPA) supplementation showed significantly reduced polyp formation in subjects having an inherited predisposition to colon cancer.97 Life Extension Magazine has published many articles about nutrients which can reduce DNA damage by preventing inflammation and adverse gene expression changes, so the above is merely a sampling.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

http://www.lifeextension.com/Magazine/2016/9/Exclusive-Report-from-the-American-Association-for-Cancer-Research-Conference/Page-01

Is Your Olive Oil Counterfeit?

Olive oil is a critical part of the Mediterranean diet. Higher consumption of extra virgin olive oil has been shown to reduce risk of all-cause mortality by 23%, cardiovascular events by 28%, and stroke incidence 40%. Startling findings reveal many brands are diluted with cheap omega-6 fats. These fats not only create health problems, but deprive consumers of beneficial polyphenols from pure extra virgin olive oil.

September 2016

By Michael Downey

 

The Mediterranean diet with its high content of olive oil is well-documented to reduce cardiovascular disease and overall mortality.1-3

Scientists have discovered a range of beneficial compounds naturally found in extra virgin olive oil, depending on the brand selected.

Recent research shows that olive oil’s potent effects are dependent not only on its monounsaturated fatty acids, but also on constituents known as polyphenols. Levels of polyphenols vary with the source and method of olive fruit processing.

Compared to other food oils (corn, cottonseed, safflower, etc.), olive oil is more expensive. This has created a situation whereby olive oil is being diluted with cheaper oils to generate greater profits at the expense of public health.

As we found when investigating this scandal, a large percentage of products labeled as “extra virgin olive oil” are not what consumers think and some are outright counterfeit.4-6

Fortunately, a source of extra virgin olive oil has emerged that is tested to deliver high polyphenols—and to have zero adulteration or mishandling.

Researchers continue to confirm that those who follow a Mediterranean diet have a longer life expectancy and a lower risk of heart disease, high blood pressure, and stroke.1-3

Olive oil has built a strong reputation for defending against diabetes, cancer, rheumatoid arthritis, and other diseases. Newly released studies demonstrate that incorporating olive oil into one’s daily diet may protect against other conditions such as Alzheimer’s, osteoporosis, and skin aging as well as premature death.7-14

A 2013 study found that these benefits are greater when extra virgin olive oil is substituted for regular olive oil.15 This study found that many of the beneficial effects of the Mediterranean diet can be ascribed largely to the quality of its extra virgin olive oil.7

Results from a 2015 study point to the superiority of extra virgin olive oil for cooking. A comparison of different cooking methods found that the use of extra virgin olive oil for cooking not only preserved the antioxidants found in vegetables, it also boosted their content.16

Extra virgin olive oil is a rich source of monounsaturated fatty acids, along with various polyphenol compounds such as oleocanthal, oleuropein, hydroxytyrosol, and tyrosol.7 These substances are believed to modulate nearly 100 human genes8 that favorably control cell signaling9 and age-associated processes.7

The health benefits of olive oil consumption vary widely, however, depending on the choice of product. Those not consuming the right type or amount of olive oil might not be getting much benefit at all.

This is due to two problems. First is that the overall polyphenol content of any olive oil is inconsistent among brands. Second, most olive oil products on the market have been shown to be seriously adulterated.

Let’s delve into each of these two issues, which are critical to understanding biological effects of this remarkable oil.

WHAT YOU NEED TO KNOW

The Benefits of Extra Virgin Olive Oil

• Scientists are finding varying cardiovascular benefits from extra virgin olive oil, depending on the brand tested.
• Olive oil’s potent effects have now been shown to be dependent on its levels of constituents known as polyphenols.
• Vast differences in polyphenol levels are due to extraction and handling differences, as well as to widespread adulteration of olive oil products. Up to 80% of oils sold in the US as extra virgin olive oil are adulterated.
• Fortunately, an extra virgin olive oil has been identified that is tested to be vastly superior in polyphenol content as well as 100% adulteration-free.

Polyphenol Levels are Critical

Originally, olive oil’s high content of monounsaturated fatty acids was credited with its health benefits. Abundant levels of one particular monounsaturated fatty acid known as oleic acid have been demonstrated to increase high-density lipoprotein (HDL) or “good” cholesterol and decrease low-density lipoprotein (LDL) or “bad” cholesterol.17

Scientists initially thought that if oleic acid were responsible for the bulk of olive oil’s cardiovascular and other health benefits, they would see the same benefits with oleic acid itself. But that is not what they found.18

Instead, an explosion of research strongly suggests that many of olive oil’s benefits are attributable to its polyphenols, which are compounds naturally occurring that inhibit oxidation and extend shelf-life. The presence of disease-fighting polyphenols in olive oil appears to explain why other monounsaturated-rich oils don’t come close to matching olive oil’s health benefits.19

Hydroxytyrosol is one of the polyphenols found in the highest amounts in olive oil—and it has been demonstrated to provide key cardiovascular benefits.20,21 This polyphenol and others that are abundant in extra virgin olive oil—including tyrosol and verbascoside—neutralize free radicals, lower blood pressure, and slow atherosclerosis.21 Over 30 different polyphenols (also called phenolics) are found in extra virgin olive oil, including lignans and the secoiridoids known as oleuropein and oleocanthal.21,22

A recent meta-analysis, including 32 studies and 841,211 subjects, clarified that the benefits of olive oil consumption far exceed the benefits of other rich sources of monounsaturated fatty acids—underscoring that olive oil’s beneficial effects derive from polyphenols.23

This meta-analysis showed that when evaluating olive oil separately, olive oil itself reduced the risk for all-cause mortality by 23%, cardiovascular events by 28%, and stroke incidence by 40%. Monounsaturated fatty acid intakes that came from a general mix of animal and plant origins did not reveal any significant risk reduction for all-cause mortality, cardiovascular events, or stroke.23

As University of California at Davis scientists reported regarding this meta-analysis, extra virgin olive oil “… is the only oil that is high both in monounsaturated fat and phenol content, and comparable health benefits would not be provided by other oils or foods.”24

As a result, it is now broadly recognized that the high polyphenol content of extra virgin olive oil (not its high monounsaturated fat content) is an important driver of its documented reduction in cardiovascular disease risk and other benefits.18,19,23

THE VASCULAR PROTECTIVE EFFECTS OF OLIVE OIL POLYPHENOLS

Recent focus on the link between extra virgin olive oil’s polyphenol content and its potent health effects has cast new light on its cardiovascular benefits—highlighting the critical impact of the polyphenols.

Higher-polyphenol olive oil shows a better ability to boost beneficial HDL cholesterol.26

A human crossover study provided the first direct evidence that high-polyphenol olive oil enhances HDL function. A three-week intake of 25 ml/d (about 1.7 tablespoons) of high-polyphenol olive oil produced a 3.05% increase in what is known as cholesterol efflux capacity, while a low-polyphenol olive oil produced only a 2.34% decrease.28 Cholesterol efflux capacity is a measure of how well HDL cholesterol removes bad cholesterol from white blood cells (macrophages) so that it can be eliminated from the body, reducing overall cholesterol.35 Another human trial revealed that olive oil polyphenols enhance the expression of genes that trigger this process.36

High-polyphenol olive oil was also shown to make HDL particles bigger, enhancing their ability to remove cholesterol from arterial plaque.28

A group of researchers found that 2 tablespoons of high-polyphenol olive oil daily for four months substantially improved endothelial function in adults with atherosclerosis.37 Endothelial dysfunction interferes with arteries’ ability to maintain healthy blood flow and normal blood pressure.38

In another human study, scientists determined that a higher polyphenol intake over one year, as a result of increased extra virgin olive oil consumption, decreased blood pressure in participating adults aged 55 to 80. Higher polyphenol intake, confirmed by increased urine polyphenol excretion, was linked directly to increases in plasma nitric oxide, which signals blood vessels to relax and thus lower blood pressure.39

Beyond cardiovascular effects, the polyphenols in extra virgin olive oil have been found to suppress cancer.40,41 For instance, the major extra virgin olive oil polyphenols have been shown to cause cells with the breast cancer-promoting gene HER2 to self-destruct.41

Although not specifically tied directly to polyphenols, olive oil also quells inflammation, protects stomach health, and inhibits other diseases—including Alzheimer’s and premature death.7-14

Olive Polyphenols Regulate Blood Lipids

The amount of cholesterol in one’s blood and its breakdown of “bad LDL” and “good HDL” remains a hallmark by which conventional authorities assess vascular disease risk.

Olive oil favorably modulates these blood lipid levels.

A flurry of studies reveals differences between higher-polyphenol and lower-polyphenol olive oils for a variety of cardiovascular markers. Olive oils richer in polyphenols were found to produce:

• Reduced LDL,25
• Improved LDL density,25
• Increased HDL,26,27
• Improved HDL function,28
• Reduced LDL oxidation,26,29 and
• Improved postprandial hemostatic (blood flow-inhibiting) profile to a less thrombogenic (clot-promoting) state.30,31

These favorable changes in blood markers of cardiovascular risk show the value of ingesting lots of olive oil polyphenols.

What’s been overlooked until recently is the variation in polyphenol content among olive oil products on the market. A key study that measured levels of one particular polyphenol demonstrated that some olive oil brands on the United States market provide five times as much of this polyphenol as some others.32

In response to data indicating the importance of olive oil polyphenols, a specific source of extra virgin olive oil has been identified that contains consistently high levels of total polyphenols.

We’ll return to this exciting and potentially life-saving oil later. But first, let’s examine the other hurdle when it comes to deriving olive oil’s full benefits—rampant product adulteration.

WHAT ARE POLYPHENOLS?

Polyphenols are naturally occurring compounds found largely in fruits, vegetables, tea, wine, and cocoa. They are secondary metabolites of plants, generally defending them against ultraviolet radiation or aggression by pathogens. More than 8,000 polyphenolic compounds have been identified in various plant species.42

The polyphenolic content of foods is greatly affected by environmental factors such as soil type, sun exposure, and rainfall. The degree of ripeness considerably affects the concentrations and proportions of polyphenols. A critical factor affecting polyphenol content of any food is storage time and type, which affects polyphenol oxidation. Exposure to light, heat, or air can destroy polyphenols.43

Polyphenols are anti-inflammatory and free-radical scavengers. Some have anticarcinogenic and cardioprotective effects. Polyphenols have beneficial effects on the endothelial lining of blood vessels by increasing the availability of nitric oxide and by preventing the lipid oxidation underlying atherosclerosis.

Numerous studies suggest that polyphenols from different plants may work synergistically to protect against cardiovascular disease, cancer, diabetes, endothelial dysfunction, osteoporosis, and neurodegenerative and other chronic diseases—without any known side effects.42

The typical Western diet lacks sufficient amounts and variety of plant polyphenols to be of optimal benefit.

Polyphenols give extra virgin olive oil its unique fresh-fruity and spicy-peppery taste and improve its shelf life, with some versions containing several times the polyphenols of others. So potent are these compounds that, cooking with extra virgin olive oil not only fully preserves the antioxidant value of the food, it also boosts the food’s antioxidant content.

Do you want to know what polyphenols “feel” like? Take a slow sip of extra virgin olive oil and wait for the sudden tingling at the extreme back of the throat. This is the tell-tale sign of an extra virgin olive oil that’s polyphenol-rich.

Olive Oil Adulteration is Widespread

The United States is the world’s third-largest consumer of olive oil, and standards for the top grade—“extra virgin”—have been established by the International Olive Council and United States Department of Agriculture (USDA).33

However, there are numerous ways to cheat, and enforcement is virtually nonexistent. An estimated 50% of extra virgin olive oil brands sold in Italy—and 75% to 80% of extra virgin olive oil brands sold in the United States—do not even meet the legal grades to be called extra virgin.6

The most common fraud involves diluting extra virgin olive oil with lower-quality oils from North Africa and other areas. Worse, many bottles labeled extra virgin olive oil contain almost no olive oil at all—just a seed oil such as sunflower, altered with chlorophyll and beta-carotene to convey the same appearance and fragrance.6 Some use an inert liquid fat as a base, adding just a little olive oil to pass it off as genuine. Others deodorize rancid oil using chemicals and heat, killing off its health properties.34

In addition to laboratory measured standards for “extra virgin,” the International Olive Council and USDA have established sensory standards—indicators that detect when oils are oxidized, low-quality, lacking characteristic fruity flavor, or adulterated with cheap, refined oils.33

Using these sensory tests, University of California at Davis scientists analyzed 186 extra virgin olive oil samples from several countries, all selected randomly from retail shelves in California. They found that 73%—imported and local—failed. The extent to which each failing brand failed its sensory tests ranged from 56% to 94%. The majority of samples tested exhibited one or more of the following:33

• Oxidation by exposure to high temperatures, light, or aging,
• Adulteration with cheaper, refined olive oil, or
• Poor quality from processing flaws, improper storage, or use of damaged and overripe olives.

Experts advise consumers to check for the authentic fresh-fruity and spicy-peppery tastes, but how can people be fully certain that they’re unleashing the potency of the real thing?

Fortunately, our scientific investigators have identified a source that surpasses the lab measurement and sensory standards of pure, fresh, extra virgin olive oil—while delivering polyphenols at the highest end of the scale!

COOKING AND STORAGE CONDITIONS FOR EXTRA VIRGIN OLIVE OIL

There is a great deal of confusion amongst consumers as to what is the best oil to cook with. In order to make the best decision, we need to discuss two things: first, smoke point, or the temperature at which an oil begins to break down, loses its taste and nutritional benefits and releases harmful chemicals, and second, the tendency to oxidize or go rancid.

There’s a general belief that regular olive oil isn’t an optimal oil for sautéing due to having a low smoke point. But high quality extra virgin olive oil has a high smoke point of 400ºF. If olive oil in general has gotten a bad rap for use in cooking, it’s probably because up to 80% of the oils sold in the US as extra virgin olive oil are counterfeit. Most people who think they’re using it are actually using inferior oils.

The low acidity of high quality extra virgin olive oil allows it to have a longer shelf life since it tends to oxidize more slowly.44,45 Even so, proper storage conditions are important in order to minimize oxidization. Accordingly, high quality extra virgin oil should be kept in a cool, dark place and in a dark bottle away from light, oxygen, and heat as these factors can reduce the nutritional value of the oil in the long run. Cooking with genuine, unadulterated high quality extra virgin olive oil presents no problem for general cooking.

High-Polyphenol, Adulteration-Free Olive Oil

Refining causes a reduction in the polyphenol content of olive oil. Extra virgin olive oil is less refined.

Even among authentic extra virgin olive oils, a host of factors interact to determine polyphenol content. These include olive variety, weather type, timing of harvest, promptness of pressing, pressing method, handling, distance to market, and storage.32

An investigation has found an olive oil brand that is both polyphenol-packed and completely pure and unadulterated, making it possible for Americans to derive the full health benefits of extra virgin olive oil.

This is especially critical in light of research reporting that it is the polyphenol content of olive oils that unleashes the full health benefits, including reduction in all-cause mortality.18,23,25-31

This California-derived extra virgin olive oil meets all conditions for purity. The olives are grown on a family farm, providing the Mediterranean-like climate needed for nutrient-rich olives while avoiding the long transit time involved in importing Mediterranean-derived oil. The non-GMO olives are harvested early in the season and handpicked to exclude leaves and avoid the bruising caused by mechanical harvesters. They are crushed within hours of harvest rather than days, and the resulting oil is then cold-extracted and not filtered, which preserves its raw qualities, after which it is stored in temperature-controlled stainless steel tanks until it’s poured into dark bottles to protect it from light.

NEW ANALYSIS HIGHLIGHTS THE CARDIAC DANGERS OF CORN OIL

Over thirty years ago, Life Extension® identified corn oil, which is loaded with the omega-6 fatty acid linoleic acid, as pro-inflammatory.

The journal The BMJ (formerly The British Medical Journal) published a recently rediscovered clinical data set from between 1968 and 1973, with a study population of more than 9,000 people.46

Control subjects were fed saturated-fat rich meals that included red meat, milk and cheese. The intervention group had most of their saturated fats replaced by corn oil rich in the pro-inflammatory omega-6 fatty acid linoleic acid. The goal of the analysis was to evaluate the theory that omega-6 rich corn oil would protect people against heart disease and lower their mortality. What the researchers found, however, was that the use of corn oil to replace saturated fats in the diet lowered cholesterol but increased the risk of death from heart disease.

This new analysis of old data validates what Life Extension pointed out over thirty years ago, when we warned the public to select vegetable oils with care in order to avoid the pro-inflammatory omega-6 fatty acids like linoleic acid found in corn oil and other high omega-6 vegetable oils.

Heart-healthy vegetable oils with low amounts omega-6 linoleic acid and low saturated fat are far better options than corn oil rich in omega-6 linoleic acid.47 Whenever possible, be sure to look for extra virgin, cold pressed in order to receive the full benefits of these healthy oils. For salad dressings, olive oil and flaxseed are reasonable options. Flaxseed oil should always be refrigerated, and should never be used for frying. For sautéing, olive oil is a far better choice than corn oil.48

• Extra virgin olive oil contains oleic acid and is rich in heart-healthy polyphenols including oleuropein, hydroxytyrosol, tyrosol, and verbascoside.17,20,21
• Avocado oil, rich in monounsaturated fatty acids, carotenoids, and phytosterols is a healthy option.49
• Flaxseed oil, high in healthy omega-3, alpha-linolenic acid is another healthy option.50

Summary

Olive oil’s beneficial effects are highly dependent on its polyphenols.

There are huge differences in polyphenol content of commercially sold olive oil brands. This can occur because of variable growing conditions and from extraction and handling differences.

Most troubling, however, is widespread adulteration. Studies show that between 75% and 80% of oils sold in the United States as “extra virgin olive oil” are adulterated or diluted.

A California grown extra virgin olive oil has been identified that is lab-tested to be superior in polyphenol content with no adulteration.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

IMPACT ON BODY WEIGHT

A new study published in the journal Lancet Diabetes & Endocrinology lends further credence to the sterling reputation of extra virgin olive oil and its remarkable benefits for health and weight loss.51

In a randomized, controlled study, scientists analyzed the waist circumference and weight of 7,447 subjects who consumed three different diets over five years. They concluded that a Mediterranean diet, in which extra virgin olive oil is heavily featured, is more conducive to weight loss than low-fat diets. The findings held true for a variety of different groups, including those with type II diabetes, the elderly and people who are overweight or even obese.

Subjects were divided into three groups. One group had a Mediterranean diet featuring extra virgin olive oil, the second group had a Mediterranean diet that featured a mix of nuts, and the third group was instructed to simply avoid all fats. In the end, the olive oil group lost the most weight—an approximate two pounds, while the low-fat group averaged a 1.3-pound loss. The group that ate a Mediterranean diet with nuts lost an amount comparable to the low-fat group.

What may not be appreciated by this study is that adults tend to gain significant weight as they age. The fact that those who consumed the most extra virgin olive oil lost weight over a 5-year period makes it clear that olive oil is the type of fat to consume for those concerned about body weight.

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