The antioxidant/anticancer potential of phenolic compounds isolated from Olive Oil
JoAnn Guest Mar 06, 2005 18:47 PST
Eur J Cancer Jun00;36(10):1235-47
http://www.mindfully.org/Health/Olive-Oil-Phenolic.htm
Owen RW, Giacosa A, Hull WE, Haubner R, Spiegelhalder B, Bartsch H
Division of Toxicology and Cancer Risk Factors, German Cancer Research
Centre, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany.
r.o-@dkfz-heidelberg.de
In our ongoing studies on the chemoprevention of cancer we have a
particular interest in the health benefits of the Mediterranean diet, of
which olive oil is a major component. Recent studies have shown that
extravirgin olive oil contains an abundance of phenolic antioxidants
including simple phenols (hydroxytyrosol, tyrosol), aldehydic
secoiridoids, flavonoids and lignans (acetoxypinoresinol, pinoresinol).
All of these phenolic substances are potent inhibitors of reactive
oxygen species attack on, e.g. salicylic acid, 2-deoxyguanosine.
Currently there is growing evidence that reactive oxygen species are
involved in the aetiology of fat-related neoplasms such as cancer of the
breast and colorectum.
A plausible mechanism is a high intake of omega-6 polyunsaturated fatty
acids which are especially prone to lipid peroxidation initiated and
propagated by reactive oxygen species, leading to the formation (via
alpha,beta-unsaturated aldehydes such as trans-4-hydroxy-2-nonenal) of
highly pro-mutagenic exocyclic DNA adducts.
Previous studies have shown that the
colonic mucosa of cancer patients
and those suffering from predisposing inflammatory conditions such as
ulcerative colitis and Crohn's disease generates appreciably higher
quantities of reactive oxygen species compared with normal tissue.
We have extended these studies by developing accurate high performance
liquid chromatography (HPLC) methods for the quantitation of reactive
oxygen species generated by the faecal matrix.
The data shows that the faecal matrix supports the generation of
reactive oxygen species in abundance.
As yet, there is a dearth of evidence linking this capacity to actual
components of the diet which may influence the colorectal milieu.
However, using the newly developed methodology we can demonstrate that
the antioxidant phenolic compounds present in olive oil are potent
inhibitors of free radical generation by the faecal matrix.
This indicates that the study of the inter-relation between reactive
oxygen species and dietary antioxidants is an area of great promise for
elucidating mechanisms of colorectal carcinogenesis and possible future
chemopreventive strategies.
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MORE INFORMATION ON USING OMEGA-3 FATTY ACIDS
Too much omega6 in the diet is associated with ADHD, depression, diabetes, prostate cancer, skin cancer, etc, etc, etc.
http://www.krispin.com/omega3.html
* Omega-6 fats in amounts more than essential promote cancer, heart disease, autoimmune disorders including arthritis, diabetes, allergy and asthma.
* Omega-6 fats must be drastically reduced. Eliminate all obvious sources.
* Omega-3 are protective and may -prevent or reverse listed conditions.
* Omega-3 fatty acids from flax or perilla are not well converted to the needed EPA and DHA in many person.
* Omega-3 is available from fish but adequate daily intake is problematic due to chemical toxicity from pesticides, etc.
* Fats are incorporated into skin- you are what you eat- a combination of omega-3 fats and natural saturated fats including coconut oil, butter and non-hydrogenated lard offer the best protection from disease, including skin cancer.
* Omega-6 fats, in high amounts, promote inflammation of tissue so that the skin, linings of the lungs, gut, breast, prostate, and bone are more susceptible to damage from UV light, carcinogens, mutagens, allergens and toxins
* Omega-3 fats including all parts of the fish oil, both DHA and EPA and even the cholesterol it contains protect these same cells.
* HDL cholesterol in its own right has powerful antioxidant activity.
* Omega-6 decreases and omega-3 increases HDL cholesterol.
* Omega-3 DHA is the major fat in the eye and is replaced (if available) every 10 days. Increasing omega-3 with fish oil improves night vision and color vision.
* Omega-3 fats are associated with the ability to smell and for seniors who have lost their sense of smell fish oil may restore it in 1-2 months.
* Omega-3 fats improve memory. Just two days after increasing omega-3 the phosphatidylserine content of the brain may triple.
High-linoleate (omega-6) oils are inappropriate for human use as foods. For deep-frying and preservation purpose, high-oleate vegetable oils are useful but all the high-oleate vegetable oils and hydrogenated vegetable oils we have examined so far exhibited the survival time-shortening activity, and I cannot recommend people to have these oils in large quantities. Instead, lard was safe for this animal model, and could be used in quantities not to induce obesity; animal fats as well as a high-LA vegetable oil intake caused insulin resistance in a NIDDM model of rats.
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http://researchnews.osu.edu/archive/omega-3.htm
OMEGA-3 FATTY ACIDS AFFECT RISK OF DEPRESSION, INFLAMMATION
"...A new study suggests that people whose diets contain dramatically more of one kind of polyunsaturated fatty acid than another may be at greater risk for both clinical
Depression and certain inflammatory diseases....
.........The study, conducted in OSU's Institute for Behavioral Medicine Research, focused on a group of 43 middle-aged to elderly men and women, nearly half of which were the caregiver spouses of people with Alzheimer's or other dementias. By including caregivers who typically report greater stress and more
Depression than similar ad ults who are not caregiving, the researchers could look at how
Depression and diet might interact to affect inflammation.
Blood samples were drawn from each person in the study and tested for interleukin-6 (IL-6), tumor necrosis factor -alpha (TNF-alpha ) and the receptor molecule for IL-6. Participants also completed a survey questionnaire that gauged their level of depression.
The analysis showed that participants who had much more omega-6 -- compared to omega-3 -- fatty acids, and who also were reporting more symptoms of depression, had much higher levels of IL-6 and TNF-alpha, two cytokines which enhance inflammation.
“In this study, we're looking at the intersection of behavior, immune function and diet. In past experiments, we concentrated only on the first two. It now appears that diet is a very important variable in the equation as to how people respond to depression and stress.”
“The data suggest that higher depression and a poorer diet in terms of omega-3 can work together to promote inflammation. Other researchers have shown that clinically depressed people -- those with more severe depression -- often have lower omega-3 levels in their blood, and several studies have shown that supplementing diets with omega-3 improves depression,” Kiecolt-Glaser said, although the reason isn't clear.
“People who are depressed don't eat well, or it might be that there is something about depression that affects how well people process such foods.”
In recent years, research has shown that an increase in omega-3 fatty acids in the diet has specific health benefits, especially in patients with depression, cardiovascular disease and inflammatory and autoimmune diseases....."
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ADHD
http://www.icpa4kids.org/research/children/add.htm
"Children with attention-deficit hyperactivity disorder (ADHD) have problems paying attention, listening to instructions, and completing tasks; they also fidget and squirm, are hyperactive, blurt out answers, and interrupt others.
It is conservatively estimated that 3-5% of the school-age population has ADHD. Although drugs, such as Ritalin, are frequently used to treat ADHD, they are fraught with complications. Disadvantages include possible side effects, including decreased appetite and growth, insomnia, increased irritability, and rebound hyperactivity when the drug wears off.
One would not expect to find that a single cause or even a handful of factors could explain why ADHD appears to be so rampant in our society. Because it is accepted that both genetic and environmental factors play a role in ADHD, many other factors-both intrinsic and extrinsic-could influence an individual's fatty acid status.
Inefficient Conversion of ALA (Flax Oil) To EPA And DHA
A possible cause for the low fish oil status of the ADHD children may be impaired conversion of the fatty acid precursors LA and ALA to their longer and more highly unsaturated products, such as EPA and DHA (fish oil fats).
It appears that children with ADHD just are not able to chemically convert the plant omega-3, ALA to fish oil very well. The problem is further worsened when omega-6 fats are consumed and the ideal omega-6:3 ratio of 1:1, progresses to the typical standard American ratio of 15:1. Many of these children have ratios which are even worse and can be as high as 50:1.
This study provides the research evidence supporting the use of the omega-3 fats found in fish oils to effectively address the underlying deficiency that is present in most of these children and appears to be contributing to the ADHD..."
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http://www.psychresearch.com/depression.html
"Needless to say, most mainstream doctors will quickly prescribe an antidepressant drug to treat depression in their older patients. But a recent study from the Netherlands demonstrates that depression in people over the age of 60 can often be addressed with a simple change in nutrition.
An increased intake of omega-3 fatty acids has been shown to alleviate symptoms of depression. With that in mind, researchers at the Erasmus Medical Centre in Rotterdam, Netherlands, created a study to examine how the ratio of omega-6 and omega-3 fatty acids might be associated with depression in older subjects.
The optimum omega-6 to omega-3 ratio is 1:1. But because omega-6 is abundant in processed foods (while the primary dietary source of omega-3 is fish) the omega-6 to omega-3 ratio of a typical diet is by some estimates more like 20:1; a ratio that has been shown to be associated with depression.
The Rotterdam team recruited more than 260 subjects with symptoms of depression. Each subject was 60 or older, and 106 subjects in the group were diagnosed with depressive disorders. Blood samples revealing omega-6 and omega-3 levels from all of these subjects were measured against a control group of 461 randomly selected subjects.
After analyzing the results, researchers found what they called a "direct effect of fatty acid composition on mood." Subjects with depressive disorders had a significantly higher ratio of omega-6 to omega-3 fatty acids. This is not a surprise, of course, but rather a confirmation that a low intake of omega-3 fatty acids may be at the root of depression, especially among older people.
Dietary sources like walnuts and flaxseed deliver omega-3 fatty acids, but only fish contains both eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA). When combined, these two essential fatty acids have been shown to help prevent depression, as well as heart disease, Alzheimer's disease, arthritis, influenza, hyperactivity, and even some forms of cancer.
The drawback with fish (as I've also mentioned several times in the past) is the mercury content present in exactly the types of fish that contain the highest concentration of omega-3: dark meat fish such as tuna, swordfish, and salmon. Fortunately, fish oil supplements don't contain mercury and provide an easy way to insure a good intake of omega-3 fatty acids."
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http://biopsychiatry.com/lipidsmood.htm
"Brain membranes have a very high content in essential polyunsatured fatty acids for which they depend on alimentation. Any dietary lack of essential polyunsatured fatty acids has consequences on cerebral development, modifying the activity of enzymes of the cerebral membranes and decreasing efficiency in learning tasks. Epidemiological data - The prevalence of depression seems to increase continuously since the beginning of the century. Though different factors most probably contribute to this evolution, it has been suggested that it could be related to an evolution of alimentary patterns in the Western world, in which polyunsatured w3 fatty acids contained in fish, game and vegetables have been largely replaced by polyunsatured w6 fatty acids of cereal oils. Some epidemiological data support the hypothesis of a relation between lower depression and/or suicide rates and a higher consumption of fish. These data do not however prove a relation of causality. Cholesterol and depression - Several cohort studies (on nondepressed subjects) have assessed the relationship between plasma cholesterol and depressive symptoms with contradictory results. Though some results found a significant relationship between a decrease of total cholesterol and high scores of depression, some other did not. Studies among patients suffering from major depression signalled more constantly an association between low cholesterol and major depression. Besides, some trials showed that clinical recovery may be associated with a significant increase of total cholesterol. Cholesterol and suicidal behaviour - The hypothesis that a low cholesterol level may represent a suicidal risk factor was discovered accidentally following a series of epidemiological studies which revealed an increase of the suicidal risk among subjects with a low cholesterol level. Though some contradictory studies do exist, this relationship has been confirmed by several subsequent cohort studies. These findings have challenged the vast public health programs aimed at promoting the decrease of cholesterol, and even suggested to suspend the administration of lipid lowering drugs. Recent clinical studies on populations treated whith lipid lowering drugs showed nevertheless a lack of significant increase of mortality, either by suicide or accident. In addition, several controlled studies among psychiatric patients revealed a decrease of the concentrations of plasma cholesterol among patients who had attempted suicide in comparison with other patients. Polyunsaturated fatty acids and depression - In major depression, all studies revealed a significant decrease of the polyunsaturated w3 fatty acids and/or an increase of the w6/w3 ratio in plasma and/or in the membranes of the red cells. In addition, two studies found a higher severity of depression when the level of polyunsaturated w3 fatty acids or the ratio w3/w6 was low."
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http://eurheartjsupp.oxfordjournals.org/cgi/content/refs/3/suppl_D/D37
"This article reviews the connection between dietary omega-6 fatty acids and atherosclerosis, carcinogenesis and insulin resistance. These polyunsaturated fatty acids (PUFAs) may be likened to ‘double-edged swords’: on one hand they are considered essential for membrane function and eicosanoid formation necessary for vascular, immune and inflammatory cell function, while on the other they lead to increased susceptibility to lipid oxidation, stimulating neoplastic cell growth in culture and impairing insulin activity. Omega-6 function should not be considered in isolation but as part of a complex of nutrient interactions together with omega-3 fatty acids (shared enzymatic pathways) and antioxidants. Insulin sensitivity might be the common factor relating disease to fatty acid metabolism - both within and between the fatty acid pathways. A high linoleate to arachidonate concentration occurs in insulin resistance, in diabetic complications and also in some tumours. Since the interaction between the omega-6 and omega-3 pathways in neither linear nor stochastic, specific dietary recommendations have to await clarification of these relationships. Adipose tissue fatty acid composition and function may be a suitable biomarker with which to study these questions. Current epidemiological and clinical evidence supports the regular consumption of cold-water fish as part of a balanced diet, in which attention to lifestyle and the quantities eaten (to prevent obesity and the insulin resistance syndrome) may be more critical than the nature of the fatty acids consumed."
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http://www.sciencedaily.com/releases/2005/08/050802123505.htm
Omega-6 Fatty Acids Cause Prostate Tumor Cell Growth In Culture
"Working with human prostate cancer cells in tissue culture, Hughes-Fulford and her fellow researchers identified for the first time a direct chain of causation: When introduced into prostate tumor cells in culture, omega-6 fatty acid causes the production of cPLA2, which then causes the production of the enzyme COX2. In turn, COX2 stimulates the release of PGE2, a hormone-like molecule that promotes cell growth.
"What's important about this is that omega-6 fatty acids are found in corn oil and most of the oils used in bakery goods," says Hughes-Fulford, who is also an adjunct professor of medicine at the University of California, San Francisco (UCSF). "Which means that if you're eating a diet high in omega-6 fatty acids, it's possible that you're turning on this cancer cascade, which has been shown to be a common denominator in the growth of prostate, colorectal, and some
Breast Cancer s."
The study points out that 60 years ago in the United States, the dietary ratio of omega-6 to omega-3, a beneficial fatty acid, was 1 to 2. Today, the ratio is 25 to 1. Over that same 60 years, the incidence of prostate cancer in the U.S. has increased steadily."
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http://adsabs.harvard.edu/abs/2001PNAS...98.7510L
Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells
Epidemiological and animal-based investigations have indicated that the development of skin cancer is in part associated with poor dietary practices. Lipid content and subsequently the derived fatty acid composition of the diet are believed to play a major role in the development of tumorigenesis. Omega 3 (3) fatty acids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can effectively reduce the risk of skin cancer whereas omega 6 (6) fatty acids such as arachidonic acid (AA) reportedly promote risk. To investigate the effects of fatty acids on tumorigenesis, we performed experiments to examine the effects of the ω3 fatty acids EPA and DHA and of the ω6 fatty acid AA on phorbol 12-tetradecanoate 13-acetate (TPA)-induced or epidermal growth factor (EGF)-induced transcriiption activator protein 1 (AP-1) transactivation and on the subsequent cellular transformation in a mouse epidermal JB6 cell model. DHA treatment resulted in marked inhibition of TPA- and EGF-induced cell transformation by inhibiting AP-1 transactivation. EPA treatment also inhibited TPA-induced AP-1 transactivation and cell transformation but had no effect on EGF-induced transformation. AA treatment had no effect on either TPA- or EGF-induced AP-1 transactivation or transformation, but did abrogate the inhibitory effects of DHA on TPA- or EGF-induced AP-1 transactivation and cell transformation in a dose-dependent manner. The results of this study demonstrate that the inhibitory effects of ω3 fatty acids on tumorigenesis are more significant for DHA than for EPA and are related to an inhibition of AP-1. Similarly, because AA abrogates the beneficial effects of DHA, the dietary ratio of ω6 to ω3 fatty acids may be a significant factor in mediating tumor development.
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http://www.drbriffa.com/blog/2007/04/18/fatty-acid-imbalance-linked...
"One of the most significant dietary changes we have seen in the modern-day diet is an increase in our consumption of what are referred to as ‘omega-6’ fats such as something known as ‘linoleic acid’ found in many vegetable oils including corn, safflower and sunflower oil. Within the body, such fats tend to encourage inflammation, constrict blood vessels and make the blood more likely to clot. So-called omega-3 fats, on the other hand, tend to have quite the opposite effects. And what this essentially means is that for optimal health, we require a balance of these two types of fat in the body.
The problem is, the rise in omega-6 intake in recent times, coupled with a general decline in omega-3 consumption, may well be causing physiological and biochemical disharmony that might be contributing to a range of disease processes including heart disease and stroke [1], Type 2 diabetes [2] and autoimmune diseases (conditions where the body’s immune system reacts against its own tissues) such as
Rheumatoid Arthritis [3].
The most recent study to explore the biological significance of a high omega-6:omega-3 ratio was published on-line in the journal Psychosomatic Medicine [4]. In this study, higher omega-6:omega-3 ratios were found to be associated with an increased risk of depression, and the higher the ratio, the greater the depressive symptoms tended to be. This research suggests that getting the balance between omega-6 and omega-3 in the diet may be important not just for the physical health, but mental health too.
Omega-6 fats are found most plentifully in refined vegetables oils (e.g. cooking oil), but can also be found in foods such as margarine, baked good and snack foods. Eating less of such foods will help to prevent any surfeit of omega-6 fat in the body and brain. Another approach, of course, is to increase intake of omega-3 fats via foods such as oily fish and walnuts and/or omega-3 containing supplements. Fish oil, cod liver oil and flaxseed oil are all appropriate choices in this respect."
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http://newsletter.vitalchoice.com/e_article000640081.cfm?x=b7TDVrT,...
Fish Fats Called Credible Foes of Skin Aging and Skin Cancer
New evidence review makes the case; Growing evidence points to benefits of omega-3s from seafood and damaging effects of ubiquitous omega-6 fats
by Craig Weatherby
"Aside from causing sunburn, the sun’s ultraviolet (UV) rays can also cause wrinkles, sags, leathery skin, eye cataracts, and other generally non-fatal ills.
But, more importantly, UV rays are major perpetrators of DNA-distorting, cancer-promoting cell damage. And, ironically, the human immune system’s inflammatory response to UV-induced cell damage often makes matters worse.
According to a new report from the World Health Organization, up to 60,000 people worldwide die every year from skin
Key Points
* Omega-3s from fish may reduce sun-related skin damage by reducing levels of pro-inflammatory chemicals in people’s skin and blood.
* Omega-3s may reduce the risk of certain skin cancers (carcinomas) by curbing cancerous changes in skin cells and by inhibiting the formation of skin tumors generated in response to UV sunrays.
* Supplemental omega-3s could help make longer sun exposure safer, thereby allowing people to raise their body levels of cancer-fighting vitamin D."
MORE INFORMATION
JAMA 2006;295:403-415
http://www.jama.com
Omega-3 vs Omega-6
Olive Oil contains the two essential fatty acids. There is currently debate about how much omega-3 versus omega-6 one should have in their diet. The two fatty acids compete for space in the cell membranes. Studies show that there are benefits and risks to too much of either. While more of the omega-3 alpha Linolenic acid can help prevent heart disease, studies have suggested it may increase prostate cancer and macular degeneration7. According to the Merck Manual, an authoritative medical text, essential fatty acids should make up 1-2% of the dietary calories for adults with a suggested ratio of 10:1 for omega-6:omega-3 fatty acids.
Olive oil is about 10% linoleic acid (an omega-6 oil) and about 1% linolenic acid (an omega-3 oil), therefore the ratio is 10:1
If you were using only olive oil for your dietary fat and fats represented 30% of the calories in your diet, then you would be getting 3% of your calories in the form of essential fatty acids in a 10:1 ratio. Other more recent studies suggest closer to a 5:1 ratio may be more beneficial.