Omega-3

(Oldest post first…please scroll down for updates.)
 
April 9 2008 post. The April 1 issue of “Blood” has an interesting study that examines the role played by n-3 polyunsaturated fatty acids (PUFAs, gotta love that acronym! Oh, “n” stands for omega, by the way) in angiogenesis, which, in just a few words, is a process whereby tumours develop a blood supply and are able to grow and live as happily as clams at high tide. So clearly one of our goals should be to block the blood ( = food) supply to tumours. As we have seen, a couple of simple ways we can do that is to take curcumin and drink coffee (probably not at the same time, though I haven’t tried doing that, I admit…).
 
The full study (abstract: http://tinyurl.com/2nvqnm), which I was able to read thanks to Sherlock tells us that n-3 PUFAs inhibit the formation of new blood vessels (angiogenesis), a critical process that affects tumor growth and dissemination. So we can now add n-3 to our list of angiogenesis inhibitors. Excellent.

But what about n-6 fatty acids? The abstract tells us that n-6 PUFAs stimulate angiogenesis. Does that make n-6 one of the bad guys? That’s what I thought, at first. But no, we need both these fatty acids in order to be healthy, so eliminating n-6s from our diet would be a very VERY bad move.

What we lack is BALANCE between the two omegas. Read this: In terms of the consequences for human health, it has been shown that Japanese who migrated to the United States and acquired the local dietary habits leading to an increase in the dietary n-6/n-3 PUFA ratio of 16:1 resulted in health problems in the migrants similar to those that already existed in the local population. Sixteen to one! That’s astounding. Even more astounding: the ideal balance should be 1:1, at the most 4:1. But the average North American diet, and probably European by now, ranges from 11:1 to 30:1. Yikes!

According to Andrew Weil, M.D., This dietary imbalance may explain the rise of such diseases as asthma, coronary heart disease, many forms of cancer, autoimmunity and neurodegenerative diseases, all of which are believed to stem from inflammation in the body. The imbalance between omega-3 and omega-6 fatty acids may also contribute to obesity, depression, dyslexia, hyperactivity and even a tendency toward violence.(see: http://tinyurl.com/4s32fc; see also: http://tinyurl.com/565h8n).

Now, what happens when we ingest n-3s and n-6s? They get converted by so-called PUFA bioconversion enzymes. Otherwise, these fatty acids would not be of any use to us at all. The researchers state that their findings suggest that n-6 and n-3 PUFAs compete for enzymes involved in PUFA biotransformation. It is widely believed that PUFA bioconversion enzymes have a greater affinity for n-3 PUFAs so that their biotransformation is favored when the dietary n-3 PUFA intake is high. This simply means that the two omegas compete for the attention of these bioconversion enzymes, and n-3s happen to be the winners.

Hmmm, interesting little fact that I didn’t know: n-3 PUFAs inhibit NF-kappaB AND Bcl-2. Well, well. Another good reason to include them in our diet.

At any rate, our bodies are not able to produce these fatty acids from scratch, and in fact that is why they are called “essential” (essential for health, but cannot be made inside the body), so we need to get them from our food.

Dietary sources of n-3s: mainly cold water fish such as salmon, herring, anchovies, but be careful about the potential presence of heavy metals, PCBs and dioxin (!); also, but to a lesser degree, flax, pumpkin seeds, walnuts, pecans, butternuts, nut oils, as well as the seeds of: chia sage, kiwi, lingonberry, black raspberry. For more info: http://en.wikipedia.org/wiki/Omega_3. By the way, today I learned that mercury does not get stored in fish oil (only in the tissue). How about that? I also learned that some manufacturers are able to purify fish oil via molecular distillation, which increases the cost, but who wants to be swallowing dioxin or pesticides, after all? I would rather pay more for a high quality product. So, do your research, watch what you buy, and don’t go for el cheapo.

Fanatic Cook tells us that walnuts, soy and canola oil contain more n-6 than n-3. She has some excellent pages on n-3, including this one (http://tinyurl.com/22xd95), where she informs us that only a TINY part of n-3s from nuts and non-animal sources has anti-inflammatory effects. She explains why. N-3 has to be converted, and, as she notes, if you want to make sure you’re getting enough of the active forms of n-3, it’s best to eat an animal that has done the conversion for you. Interesting. Okay, I am beginning to see more fish in my future. We are lucky to get our fish from a small Tuscan fishing cooperative, so we can be sure that the fish is fresh and that no mass fish slaughters take place in the Tyrrhenian Sea. That’s always a consideration for my tender heart.

Dietary sources of n-6s: poultry, eggs, cereals, whole-grain breads, baked goods, most plant-based cooking oils (sunflower, corn etc.), nuts, borage oil. See also: http://en.wikipedia.org/wiki/Omega_6

In sum, have I reached any conclusions? Well, more research is needed, but I think I will switch from flaxseed oil to fish oil or, perhaps even better, krill oil. The diet of cold water fish consists mainly of krill (a step down the food chain), and the main advantage of swallowing krill oil is that it contains fewer pollutants; a disadvantage is that it has less n-3 compared to its predators. Oh well, we can’t have everything!

July 7 2008 post: According to a recent Science Daily article (see: http://tinyurl.com/5v6xxo), researchers at Brigham and Women’s Hospital and Harvard Med School have discovered a molecule called resolvin E1 (RvE1) produced by the body from omega-3 fatty acids that helps resolve and prevent respiratory distress in laboratory mice. This molecule is found in cold-water fish (salmon, mackerel and, ugh, anchovies) and is produced by the body in response to the onset of inflammation. The abstract can be read here: http://xrl.us/kj8qf.

The experts still do not completely understand why fish oil is so effective against inflammation: increased levels of omega-3 fatty acids are associated with lower asthma prevalence in people, but the mechanisms to support that observation are poorly understood.

 

But the main thing is: omega-3 fatty oils are effective against asthma.

 

One thing led to another, and I found myself involved in a bit of research that I hadn’t intended to do (happens a lot to me…Smiley face). Completely by chance, in fact, I came upon a study by a team of Japanese researchers on the same topic–asthma, mice and RvE1–a study published in March 2008 (see: http://tinyurl.com/6xaddo), that is, a few months before the publication of the study reported in Science Daily. The Japanese researchers discovered the exact same thing about RvE1.

 

So, just for the heck of it, I did a search on PubMed for RvE1 and asthma, and found another study (full version available for free here: http://tinyurl.com/5d64sa) published back in 2005 (!!!) on the protective anti-inflammatory effect of this molecule, and on the role it has in preventing (drum roll!) osteoclast-mediated bone destruction in periodontitis (= a severe form of gum disease).

Osteoclasts? Why, those are the hyperactive bone-destroyers in multiple myeloma…! At that point, I had a look at the full study, where I read that bone loss in periodontitis is caused by osteoclast activity. The researchers discovered that the animals (sigh) with periodontitis that were treated with RvE1 had only a few osteoclasts compared to the untreated ones. Conclusion: RvE1 inhibits osteoclasts. Well, well! (I just hope that the “animals” involved in this study were tiger mosquitoes…)

 

Another excerpt tells us that periodontitis has pathogenic features similar to those observed in other inflammatory diseases such as arthritis. And read this: Resolvins are a new family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammatory signals. Because it is now increasingly apparent that local inflammation plays a critical role in many diseases, including cardiovascular disease, atherosclerosis, and asthma, experiments were undertaken to evaluate the actions of the newly described EPA-derived Resolvin E1 (RvE1) in regulation of neutrophil tissue destruction and resolution of inflammation. The results were that RvE1, used as a topical pharmacologic agent, was found to prevent the progression of tissue destruction

 

Treatment with RvE1 was more effective and less damaging than the chronic use of antibiotics. Interesting. The researchers propose that regulating inflammation with molecules such as RvE1 is a rational new therapeutic approach to the treatment of osteoclast-mediated bone disease. Aha!!!

It turns out that there are 32 studies in PubMed on RvE1. The earliest study dealing with the specific anti-inflammatory activity of these so-called resolvins, as far as I can tell, dates to 2004. But the above-mentioned Science Daily article led me to believe that RvE1 was a startling NEW discovery. Why would that be? Well, I have learned my lesson. From now on, whenever I see exclamations such as “exciting new discovery…,” I will do a background check. There just might be a less publicized precedent…as happened with the IRF4 studies… 

 

Now for my own personal experience. I have suffered from asthma for years. I know the main source of my trouble: cats. I am very allergic to cats, but I am also a huge cat-lover (life is unfair, sometimes…!) and now have four cats. When Stefano and I went to Northumberland in April I didn’t have one asthma attack, not even with all the walking we did. I didn’t use my cortisone inhaler or my Ventolin. Why? No cats. Simple. 

 

My non-cat loving friends think I’m nuts. They don’t understand that the benefits of having cats in my life far outweigh the inconvenience of having to use a cortisone inhaler once a day (I would like to mention that in the pre-curcumin period I was much worse off, and used cortisone and Ventolin quite a lot).

 

Recently, though, I haven’t needed to use my inhaler. As for Ventolin, well, I haven’t used it in a long time. Is it a coincidence that I have started taking a fish oil supplement in recent months? After reading about RvE1, I think the answer to that question is ”no.”

So my fish oil intake is probably inhibiting my overly eager osteoclasts…and it has gotten rid of my asthma…at least for now…brilliant!  

 
July 21 2008 post: This morning I took a bit of time off to go through a few of my piled-up Science Daily newsletters, and, after reading about the extraordinary discovery of a 700-year-old Mexican mummy suffering, when alive of course (an alive mummy…), from a Helicobacter pylori infection (remember my MGUS and H. pylori post?), I came across a study (see the Science Daily July 11th issue: http://tinyurl.com/5qjf2f) on the importance of omega 3 and brain functioning: “Food is like a pharmaceutical compound that affects the brain,” said Fernando Gómez-Pinilla, a UCLA professor of neurosurgery and physiological science who has spent years studying the effects of food, exercise and sleep on the brain.
 

Omega 3 fatty acids can not only improve learning and memory, they can also combat brain disorders ranging from depression to dementia. Another excellent reason to take ‘em! And, if our diet doesn’t have enough of these fatty acids, we are in for trouble (oh bother, I wish I had eaten more fish in the past!).

  

The following excerpt reminded me of the post I wrote on Prof. Gang and curcumin, basil and ginger (July 16th post): Getting omega-3 fatty acids from food rather than from capsule supplements can be more beneficial, providing additional nutrients, Gómez-Pinilla said. Food, not capsules, eh?…hmmm, I predict more fish in my future…but I will also continue to take my purified fish oil capsules.

 

And read this: Recent research also supports the hypothesis that health can be passed down through generations, and a number of innovative studies point to the possibility that the effects of diet on mental health can be transmitted across generations, Gómez-Pinilla said. Wowie.

 

So the saying “you are what you eat” should perhaps be modified to the rather more alarming ”your grandchildren are what you eat.” Since Stefano and I don’t have children, that modified saying doesn’t worry me too much, but still…diet and DNA…who would have thought?!!!

November 11 2008 post. UPDATE. A blog reader, thank you!, sent me a study titled Dietary Fish Intake and Risk of Leukaemia, Multiple Myeloma, and Non-Hodgkin Lymphoma, published in “Cancer Epidemiology, Biomarkers & Prevention” in April 2004. The full study is available online, so I won’t load the post up with details that you can read for yourself, right here: http://tinyurl.com/5wugks.

But, as always, a quick overview. The study is based on questionnaires, which always makes me wary, since there could be a million other unmentioned factors involved. But I decided to have a look at it anyway, since the findings might be relevant to us.

The researchers examined a total of 4175 controls, 914 leukemia cases, 287 myeloma cases, and 1408 NHL cases; these were participants in a study carried out between 1994 and 1998 in Canada. Interestingly, compared to controls, myeloma folks were older and less likely to have ever smoked. I have never smoked in my life, but I found this mention of non smoking rather puzzling. It almost seems to imply that smokers are more protected against getting myeloma…weird! As for the second point mentioned, I was diagnosed with MGUS in 1999, at age 38, then with SMM in 2005, at age 44 (okay, okay, so 44 is “older” compared to 38…!).

 

Now, for most of my life, my fish intake has been limited to occasional cans of tuna. Dreadful, I know. If only I could go back in time, I would eat tons of fish! Fact is, growing up, I simply didn’t like the taste of it…until I met Stefano, who is a gourmet cook…yes, the rather annoying but also wonderful type who can peer inside a nearly-empty fridge and come up with a scrumptious meal within minutes. Gotta love the guy. And boy, can he cook fish!

Anyway, back to the study. The Canadian researchers discovered that people who consumed greater proportions of their total energy intake from fresh fish had a significantly lower risk of each of the three types of cancer, and there was a significant dose-response for risk of leukemia and NHL. Furthermore, Those in the highest quartile for percentage of fat intake from fish were at lowest risk […].

 

Basically, the higher your weekly fish intake, the lower your risk of developing one of the LH cancers (=the three cancers combined).

 

Attention-grabber: There was no association between level of education and cancer status. Well, phew!, that is indeed comforting. Until now, I had been absolutely convinced there must be an association between my undergrad years at Harvard University, my subsequent grad school career and my myeloma… ;-)

 

Discussion part of the study: The major conclusion of this paper is that increasing proportions of total energy and fat obtained from fresh fish seems to protect against the development of leukemia, NHL, and myeloma. For all cancer types, the strongest reduction in risk was associated with increasing proportion of total fat obtained from fresh fish. This supports the hypothesis that dietary fats provided by fish are the key to the protective effect of fish intake against LH and other cancers. Aha!

The study ends as follows: In summary, in a very large case-control study, we have found a strong protective effect of fresh fish intake for leukemia, myeloma, and NHL which is consistent with previous literature.

Okay, but here is a good question: how can we know if our freshly caught fish is contaminated or not? (Go read the part about the myeloma-attacked Japanese village on p. 5.) Indeed, for that matter, how do we know that anything we eat isn’t contaminated? Does the label “organic” (biologico, in Italian) really protect us enough? But I am getting off track, and besides, the implications of that question would provide enough fodder for an entirely separate post.

 

Interesting titbit: Animal studies have found that consumption of fish oils increases survival of animals with cancer. I glanced at the particular animal study (full text: http://tinyurl.com/67cwaw) listed in the bibliography, and it implies that fish oil, i.e., not fish fillets or whole bits of fish, was given to dogs with lymphoma. Fish oil

That is why I will stick to my free-from-contamination (!) daily fish oil capsules. But, about once a week, I will also eat fish caught by a small fishing cooperative off the coasts of Tuscany. At least, contaminated or not, the fish is fresh!

 

UPDATE. April 9 2009 post. A Science Daily article (http://tinyurl.com/cu7a6x) titled “Omega-3 Kills Cancer Cells” discusses specifically the omega-3 acid known as DHA, or docosahexaenoic acid. It is contained in fish oil but not flaxseed oil (which instead contains alpha-linolenic acid, related to DHA but not the same thing). See this Mayo Clinic write-up: http://tinyurl.com/3c7298 A vegetarian source of DHA is seaweed, as I recall.

 

Well, it turns out that not only does DHA kill solid tumor cells on its own, it also enhances the killing effects of the chemo drug cisplatin, while limiting its harmful side effects. Chemopreventive, huh? Good stuff!

 

The Science Daily article is an interesting read, please go have a look. It reminded me that I really must look into maximum tolerated fish oil doses. As of now, I take 2 grams of fish oil (capsule form) a day. The studies I found this morning, after a quick bit of preliminary research, show that much higher doses have been tested and found to be okay. Hmmm. Does anyone here take more than 2 grams of fish oil a day?

October 11 2011 post. The title of a new study says it all: “Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis” (see abstract: http://tinyurl.com/3yllblr). I was concerned when I first read of this study because I take two grams of fish oil per day, and I certainly do not want to take anything that might hurt me…

So I asked a friend (thanks!) to get the full study for me. I wanted to read more details about doses, the type of fish oil administered to this unfortunate group of mice and any other pertinent information. Let’s see…In a nutshell, four weeks after being infected with Helicobacter hepaticus (which gave them mild colitis and increased their risk of developing colon cancer…), mice consuming relatively high doses of dietary fish oil, as we will see in a second, were worse off than those in the control group.

Well, I have to admit that my first draft of this post was jam-packed with technical details about colon cancer, colitis, IBD (=irritable bowel disease), the mice, their diets and whatnot. But, after getting to the Discussion part of the study, I had second thoughts about going overboard with too many details. After all, what we really need to know can be found in the final paragraph, as follows:

Investigations regarding FO supplementation in human IBD have used FO doses ranging between 500 mg/d and 7 g/d. Our diets mimicked 1 g/d (0.75%), 3 g/d (2.25%), 5 g/d (3.75%), and 8 g/d (6.00%) DFO when calculated as a component of a 2,000 kcal human diet. We observed inflammatory and dysplastic changes at the 3, 5, and 8 g equivalent. The most dramatic increase was observed at the 8 g/d dose. Currently, efforts are under way to establish dietary reference intakes for EPA and DHA due to substantial evidence supporting beneficial effects of FO consumption in the prevention of common diseases such as coronary artery disease and cognitive decline. Consumer intakes of DHA and EPA continue to increase with growing FO supplement consumption and addition of n-3 PUFAs to foods (i.e., functional food). Studies from our group and others’ advocate establishing a tolerable upper limit for FO consumption to protect certain immunocompromised sectors of the population who may be at risk for pathogen-associated enteric inflammation and gastrointestinal cancers.

Now, the mice that developed inflammatory problems belonged to the groups that had a high daily intake of fish oil–the human equivalent of 3 to 8 grams/day. The more they took, the worse off they were. Another point: as we read the abstract/study, let’s not forget that these mice were not healthy little things. No, they had been infected with a nasty virus that can lead to the development of colon cancer…

Two more considerations (apart from the obvious one that, as far as I know!, I am not a…mouse! ): 1. I have never taken more than 2 grams of fish oil per day; 2. I live in Italy, where foods are not (yet!) fortified with dietary PUFAs or even vitamins. Therefore, it appears that my daily intake of fish oil is perfectly safe, especially since I do not suffer from colitis or IBD…

As always, though, it is best to be cautious. And so I will continue to take two grams of fish oil per day…but no more than that.

2 Comments

  1. Your. information concerning fish and Omega 3 fish oil is very informative. could you please recommend a good brand of Omega 3
    supplements? I really appreciate it. thank you. blessings!

  2. I use Udo’s Oil- usually available at Health stores in the refrigerated section.
    Made in Canada, I believe–organic
    excellent

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