Fish oil inhibits chemotherapy??? Hmmm…

Yesterday morning, before leaving for work, thanks to a MMA list member (who posted the link), I read a BBC article that simply floored me. At first, that is. You see, the headline that my early-morning-&-still-sleepy brain registered was: “FISH OIL INHIBITS CHEMOTHERAPY.”

Say, whaaat? HOLY CATS! Boy, that really woke me up!!! 😉

But then I began reading the article, which discusses a recent study showing that a couple of components in fish oil apparently inhibit the anticancer effects of cisplatin, a chemo drug used also to treat myeloma patients. Click here to read it: http://goo.gl/IDKEt Ah, so it’s just one drug, I thought.

Well, as I was driving to work, something in the back of my mind kept bugging me. So when I got home I had a look at what I’d written on omega 3s…And in one of my posts (April 9 2009: http://margaret.healthblogs.org/2009/04/09/omega-3-and-hot-tea/) I found what I had been looking for: a study stating that one of the main omega-3 fatty acids, DHA, in addition to having strong chemopreventive effects by itself, also “enhances the killing effects of the chemo drug cisplatin, while limiting its harmful side effects.”

HUH? Wait a sec. How can fish oil make cisplatin work better…but also inhibit it…at the same time??? Makes no sense.

Let’s have a look at an excerpt from the BBC article: Prof Emile Voest, lead researcher at University Medical Centre Utrecht, said: “We show that the body itself secretes protective substances into the blood that are powerful enough to block the effect of chemotherapy. These substances can be found in some types of fish oil. (I won’t even comment on the fact that our own body secretes fatty acids that help our cancer cells become resistant to chemo drugs…!!!!!!!!)

These resistance-causing fatty acids can also be found in “some types of fish oil”? Well, hey, WHICH “types”? And do these unspecified “types of fish oil” block the effects of every single kind of chemo drug or just the effects of cisplatin? If you read some of the blaring headlines online, it seems as though fish oil blocks ALL chemo drugs…

Clearly, I needed to read the full study. So, instead of relying on summaries written by others (who perhaps didn’t even bother to check the source, as frequently happens…grrr grrr grrr), that’s exactly what I did…. You can read the abstract here: http://goo.gl/yPaMR

The full study opens with an interesting discussion of “microenvironment,” that is, a cancer cell’s (or a tumor’s) immediate surroundings, which enable it to survive and resist treatments. Studies have shown that cancer cells/tumors cannot survive if this friendly-to-cancer microenvironment is somehow eliminated. When that happens, the cells become sensitive to chemo drugs…

It’s as though cancer cells surround themselves with a sort of protective bubble, like the “bubbles” I saw in the Eden Project in Cornwall. If you are able to pop the bubble (=i.e., the microenvironment), you can get to the cell and exterminate it. Problem is, cancer cells are constantly recruiting friends to help preserve their toxic little bubbles. A group of these important cancer friends are found mostly in the bone marrow (hah) and are called mesenchymal stem cells, or MCMs. And they happen to be the main object of this Dutch study.

Growing tumors, the study authors tell us, really need these bone marrow-derived MCMs, which, in a cancerous environment, turn into evil thugs, shooting down any cancer foes and promoting some really bad events—metastasis, tumor growth…you name it. And they also help cancer cells develop resistance to chemo drugs…Bad stuff, clearly.

As for fatty acids, let’s have a look at a relevant excerpt from the full study: MSCs, activated by platinum-based chemotherapy, secrete unique fatty acids that, in minute quantities, confer resistance to multiple types of chemotherapy. The researchers identified two specific fatty acids, called KHT and 16:4(n-3). I’d never heard of them, I confess. However, and this is important!, other polyunsaturated fatty acids, namely EPA, didn’t block the chemo…but we’ll talk more about that later on…

So here is what happens, in a nutshell.

  1. A tumor’s cry for help gets answered by these blasted MSC thugs, which come zooming down from the bone marrow in large quantities.
  2. MSCs get activated by platinum-based chemo drugs, namely cisplatin. The tumor soon becomes resistant to these drugs.
  3. MSCs secrete those two above-mentioned fatty acids in the presence of these platinum drugs.
  4. The authors think, but are not sure, that the two fatty acids could be part of the resistance-to-chemo problem.

So let’s see. Here’s the gist, as best as I can understand it. The chemoresistance problem that seems to be provoked by these two specific fatty acids seems to happen only in the presence of platinum-based chemo drugs. Oh, I suppose it’s obvious, but in case it’s not, I should probably mention that these are drugs are obtained from platinum, the metal. From what I read online, platinum damages a cancer cell’s DNA and stops it from dividing. Okay, anyway…so that restricts the field to cisplatin and a few others that I’d never even heard of, but which apparently have fewer side effects (than cisplatin, I mean): carboplatin and oxaliplatin. Incidentally, cisplatin and carboplatin put you at an elevated risk of developing leukemia. ‘Nuff said!

Another important point. Three other chemo drugs were also tested in this study: doxorubicin, irinotecan and paclitaxel. Results: the trio didn’t have the same effect as the platinum-based chemo in releasing the two mischievous fatty acids. Eh. Not even close. The authors therefore say that This shows that the platinum-based chemotherapeutics are most powerful in inducing the release of 16:4(n-3), and that that effect is dose dependent.

Okay then. Only the platinum drugs provoke this very bad resistance-to-drugs outcome. Three other chemotherapeutic drugs do NOT. This is crucial information, I’d say.

As for fish oils, let’s read this excerpt (sorry it’s so long, but sometimes it’s best to quote the exact words): Fatty acids are also present in various food products and supplements. We found that our identified PIFA 16:4(n-3) is abundantly present in commercially available fish oil products (0.4–0.6mM 16:4(n-3)) and algae extracts (27mM 16:4(n-3)). Fish oil products are frequently used by cancer patients because of their perceived positive health effects, such as preventing cachexia and cardiovascular events, anti-inflammatory properties, prevention of tumor growth, and reduction of chemotherapy- induced side effects […]. We hypothesized that the use of fish oil containing our identified fatty acids may have an adverse effect on the antitumor effects of chemotherapy. To test this, we fed tumor-bearing mice either purified PIFAs or commercially available fish oil products and treated them with cisplatin. We found that orally administered, pure PIFAs induced resistance to cisplatin in our tumor models […]. Furthermore, a single oral dose of 100 ml of either two different commercially available fish oil products or algae extracts resulted in a neutralization of the antitumor effects of cisplatin in both C26 and LLC tumors […]. Administration of only fish oils or algae did not alter tumor growth […]. Orally administered EPA, the main component of most fish oil products, that served as a control in both tumor models had no effect. Importantly, both fish oil products and the algae extract induced a complete resistance to chemotherapy at doses similar to the advised daily dose in humans. These results provide additional support for the clinical relevance of these fatty acids in the development of resistance to chemotherapy.

I’d like to highlight a couple of key sentences: 1. Administration of only fish oils or algae did not alter tumor growth. 2. Orally administered EPA, the main component of most fish oil products, that served as a control in both tumor models had no effect. Number two is very important. I don’t know about y’all, but my fish oil capsules have purified DHA and EPA in ‘em. Nothing more, as far as I know…

Now, what is the difference between the above-mentioned “fish oil products,” which induced chemoresistance, and “fish oils,” which did not? I’m not 100% sure, but it seems to me that it could be the difference between fish oil supplements (capsule form, e.g.) and fish, real fish that you cook on a grill or whatever. The same is true for the above-mentioned algae extracts and algae. That is, if you take an algae supplement while on cisplatin, you might not be doing yourself a favour. But if you swallow a bunch of seaweed with your miso soup, you should be okay. So go ahead and enjoy your sardine, anchovy and seaweed pie (yuuuuck)! 🙂

Another point: when you read the word “chemotherapy” in any of these excerpts, don’t forget that the authors are referring to cisplatin and platinum-based drugs here, not all types of chemo. That point seems to have been completely missed by some of the folks who wrote the online medical summaries of this study…harumph!

So here is the point: cancer patients who are being treated with non-platinum-based sorts of chemo are now being warned against taking fish oil supplements, which might instead be really beneficial for them and which, let’s not forget!, possess chemopreventive effects of their own. I mean, last night I read a newspaper article that went so far as to warn cancer patients against eating sardines and anchovies.

Does that make any sense?

No, I didn’t think so, either…

8 Comments

  1. Thank you Margaret! I have had one cisplatin treatment, and have taken cod liver oil consistently. I, too, have not been able to find if these fatty acids are present in cod liver oil or krill oil—or, for that matter, chlorella. BTW, why don’t oncologists raise the alarm about decadron, the steroid that has shown in many research articles to reduce the effects of chemo? If you google cisplatin and decadron, you’ll find that the standard dosage resulted in damaging the cancer cells, but they regrouped and survived, whereas cisplatin alone killed them. Of course this is in vitro…but it certainly sounds like “resistance’ to chemo.
    Thanx again. I had the same questions you had…

  2. Margaret, when I also picked up on another paper that looked at DHA and cisplatin (http://www.ncbi.nlm.nih.gov/pubmed/19341447). To quote from the abstract:

    “Further, this study is the first to reveal that DHA can obliterate the lethal CP[Cisplatin]-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress.”

    As always we need to read between the lines, and also excercise caution when reading shock-horor headlines from journalists who don’t.

  3. You said what I was thinking. I would love to see just what effect which type of cancer, which type of onco-proteins and mutations, pathway signaling and which chemotherapy mode of operations are affected which way by exactly what.
    I have seen nothing in there writeup that tells me anything about whether or not the fish oil has any negative effects on my use of Gleevec against c-kit melanoma.

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