Neuroblastoma - a fishy fix

As I mentioned late last week, this year has brought with it some interesting research regarding fish oil, most specifically DHA, and the treatment of neuroblastoma. I have been following the research of this group since 2006 and I think it was time to provide an update. (Please note that James Street wrote an excellently easy to follow summary of the following study which I have pasted parts of below)

Scientists from the Karolinska Institute in Sweden recently published an important paper on the positive impact of omega-3 fatty acids (which are found mainly in fish oil) on neuroblastoma (Gleissman 2010). These scientists had previously shown that DHA (the most unsaturated form of fatty acid in fish oil) could cause apoptosis (i.e., programmed cell death) in cancer cells. They have now extended their work to experimental animals, showing that fish oil supplementation caused either stabilization or actual regression of tumors in these animals. As they state, DHA “is a promising new agent for cancer treatment and prevention of minimal residual disease” (ibid).

The paper encompasses two parts, one on treatment, the other on prevention. In the prevention half, they gave DHA as a food supplement to rats before the animals were implanted with human neuroblastoma cells. (Because they lack a thymus, the rats in question are unable to reject tissue from a foreign species.) In the treatment half of the study, athymic rats that already had established neuroblastomas were force fed DHA daily and their tumor growth and DHA levels were then monitored. The authors concluded that “untreated control animals developed progressive disease, whereas treatment with DHA resulted in stable disease or partial response.” The response depending on the dose of DHA.

There appears to be a very special relationship between DHA and nerve tissue. For instance, a deficiency of DHA will lead to delayed neural development. Compared to normal nerve tissue, neuroblastoma is “profoundly deficient in DHA,” whereas the level of the competing omega-6 fatty acid arachidonic acid (AA) is increased. This suggested to the authors that “an imbalance between omega-3 and omega-6 fatty acids may serve as an adaptation mechanism in nervous system tumors.” Logically, then, one might expect the addition of DHA to slow or even stop the growth of neuroblastoma.

This is indeed what happened when they gave DHA supplements. The authors reported: “In the DHA-supplemented group the mean time to tumor take was significantly delayed compared to the control group” (ibid.). One rat receiving the DHA-enriched diet did not develop tumors at all. In the treatment part of the study, the median tumor volume index at the end of the experiment (day 12) was 3.72 for animals receiving one gram of DHA per kilogram of body weight, 5.47 for animals receiving half a gram per kilogram of DHA, and 9.48 in the control animals. The results were statistically significant. Put another way, a high dose of DHA decreased normal tumor growth by about two-thirds. As was predicted in the authors’ ‘omega-3 deficiency’ theory, the level of DHA in the tumor tissue tripled in the higher-dose treatment group vs. the controls

The finding that DHA supplements cut the amount of tumor formation by two-thirds in experimental rats was astonishing, but not exactly new. It was in line with previous findings that a fish oil-enriched diet could inhibit the formation of various other kinds of tumors, including papillomas (Akihisa 2004), breast cancer (Manna 2008, Yuri 2003, Noguchi 1997), cancers of the large and small intestines (Toriyama-Baba 2001) lungs (Toriyama-Baba 2001), colon cancer (Takahashi 1993, Iigo 1997), sarcoma (Ramos 2004), and prostate cancer (Kelavkar 2006). Other studies have shown that omega-3 is strongly associated with a decreased risk of aggressiveness in prostate (Fradet 2006), kidney (Wolk 2006) and breast cancer (Kim 2009).
But DHA supplementation worked better at preventing the occurrence or recurrence of tumors than at treating established tumors. “Our study shows that DHA given as a daily oral supplement displays a moderate capacity to reduce neuroblastoma growth in the majority of treated animals,” Judith Gleissman and her Karolinska coworkers wrote, “but not in all.” Some animals simply did not incorporate DHA into their tumor tissue, and it was precisely those animals that did not respond to the treatment.

Do these recent Swedish findings have relevance to cancers in humans, including, but not limited to, children with neuroblastoma? I believe they do. The authors point to a study in an Inuit population of Alaska, which has a DHA intake several-fold higher than typical Caucasians. In one study, this group’s neuroblastoma rate was one-tenth that of a comparable lower-48 American population (Dewailly 2001). Alarmingly, in most of America, the ratio of omega-3 to omega-6 fatty acids has “dropped precipitously” over the past few decades. This bodes ill for American children and their parents and loved ones. Although, I must wonder, have we seen an associated increase in neurobalstoma?

Regardless, eating more fatty fish seems, even more than ever, a prudent thing to do. Children, too, should be encouraged to increase their DHA intake through fatty fish consumption. Given that fatty fish is usually not high on the menu for children, high quality supplements of DHA and EPA may therefore be the best solution for many. For vegetarians, getting sufficient amounts of DHA and EPA can be a challenge. The best sources are walnuts, flaxseeds and flaxseed oil, olive oil, canola (rapeseed) oil, and avocado. DHA supplements derived from microalgae, not fish, are also readily available. There are also three or four clinical trials underway to test the effect of DHA and other omega-3 fatty acids in various kinds of cancer, such as lung, breast and lymphoma. Readers can find out about these by entering the terms “DHA,” “EPA” and cancer into the Clinicaltrials.gov database.

Now the important question to answer for most of you is: Should I be giving my child with neuroblastoma high doses of fish oil? First off, you should never give any type of high dose supplement to your child while they are undergoing therapy. Period. Supplements can impact the effectiveness of chemotherapy and other treatments. Supplementation could very easily make treatments that are proven to be effective absolutely worthless. So, don't do it. Secondly, you should always discuss any type of supplementation with your oncologist. While there is some pretty hopeful preclinical research regarding DHA and neuroblastoma this still has not been proven in human beings. However, with that being said, that does not mean that you should not be working towards trying to establish a healthy omega-3 /omega-6 balance in your child. I would work (and have worked) to try to establish the healthiest anti-neuroblastoma diet possible.

Finally, there is more good news here. While the rats utilized in the study above were given 1g/kg of DHA, you may be thinking that would require a ton of fish oil to reach the equivalent amount in children. Not as much as you might think, the good news is that it is not a linear relationship. Dose translation into humans using a commonly accepted BSA (body surface area) calculation means that a 25kg child would only need about 6g to achieve an equivalent dose. Bottom line, that is achievable. Now, I still would not run out to the store and stuff my child full of 6 grams of fish oil per day. But, it is seeming possible that this is achievable in humans which makes me feel even stronger that this should be one of those items that is carried forward.

I would like to see this in trial.

So, what do you think, how fishy is this purpose?