AndiBB emailed me about the report that Omega 3 increases prostate cancer risk and particularly high grade cancer, which seems to have caused considerable concern.
Karen z sorry about the delay - I have started but not yet finished a response - things have been a bit hectic.
This was the paper,
http://jnci.oxfordjournals.org/conte...jt174.abstract
which I consider in more depth below. The title of the press release of the nested Select trial was:
“Study confirms link between high blood levels of omega-3 fatty acids and increased risk of aggressive prostate cancer - Consumption of fatty fish and fish-oil supplements linked to 71 percent higher risk ”
This was the press release
http://www.fhcrc.org/en/news/release...te-cancer.html
Sadly publicity is often important to research organisations; the media respond to ‘results’ that people will talk about and are clear cut or appear as such; human nature dictates in consequence media departments; self evidently non-specialists, are at risk of over egging results, and the result is public ends up getting very confused by potentially misleading messages.
Apart form a few basic truths about the need for essential nutrients for life, the reality is things in cell biology are very rarely simple.
There is a lot of work that suggests that Omega 3 intake is associated with lower rates of prostate cancer. There are a number of biological mechanisms that would explain why Omega 3 may reduce prostate
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676993/ and some other cancer risks, and a number of observations suggest this is the case. In contrast some papers do not support this generality as is the case in this paper and its predecessor, but closer reading of the Select paper raises a host of questions as to the conclusion, some of which I raise below.
My first thought based on wider reading of reports from the mid 1900s, was that cancers were low in historic populations on non-western diets, which prompted the thought do people like Inuit who eat loads of Omega 3s have higher prostate cancer rates; the answer is no; they actually appear to have very low rates of prostate cancer.
http://cebp.aacrjournals.org/content/12/9/926.long In the summary this paper includes the following statement
“the prevalence of latent carcinoma is extremely low among Inuits compared with other populations”. The introduction includes the following comment "In Greenland, the age-standardized incidence rate for the 1969–1988 period was 1.7/100 000, and only four cases were diagnosed." Intriguingly the one prostate cancer case they found in the study was in a man with an unusually (for Inuit) poor Omega 3:6 ratio.
Historically population groups on non-western diets who ate significant amounts of fish also had relatively low rates of prostate cancer, and this paper, although having limitations, looking at 6272 Swedish men over 30 years found men that ate no fish had a two to three times greater risk of prostate cancer .
http://www.sciencedirect.com/science...40673600048893 http://ajcn.nutrition.org/content/77/3/532.full
There is also a genetically created mouse called fat1, that unlike normal mammals can convert Omega 6 to Omega 3, and even if fed Omega 6 tends to make enough Omega 3 to balance the Omega 6 in it's diet. Prostate cancer invasion and proliferation was significantly inhibited in fat1 mice.
https://www.google.co.uk/search?q=fa...fflb&gws_rd=cr Ok this is in rather special mice but the generality of the result goes against the suggestion that Omega 3s increase prostate cancer risk.
The fact traditional fish eaters appear to have very low or low incidence of prostate cancer suggests that whatever the Select trial was picking up, it is not as simple as dietary Omega 3s increases the risk of prostate cancer.
What might the above Select paper and its predecessor actually have detected? Unfortunately that is a pretty big question; the studies did not look at participants diet they just assumed that changed levels of long chain Omega 3 EPA and DHA in the blood must be the result of dietary intake of fish or fish oil, but these two fats are also made in the body from the plant based Omega 3 linolenic acid. As discussed below men do this pretty poorly but a host of things could alter conversion rates including hormonal changes. So the results could be down to a host of reasons excluding dietary intake, or may be due to dietary intake, as we have no idea what these people ate we simply do not know. Let us look at things in a bit more detail.
The latest Select trial was a subset of the original Select Trial which looked at the question did a particular form and dosage of Vitamin E (synthetic all rac-α-tocopheryl acetate), and or a particular form of selenium reduce prostate cancer
http://jama.jamanetwork.com/article....ticleid=183163 . The result was that no real change was seen for the type of selenium selected, and those that took the form of vitamin E chosen had higher rates of aggressive prostate cancer.
The particular form is important because different forms may be differently absorbed and act in different ways in the cells. Other papers have shown other forms of Vitamin E and Selenium to reduce the risk of prostate cancer.
http://jnci.oxfordjournals.org/content/92/24/2018.short The dosage may also be an important factor as positive results have been seen with lower doses of some forms of vitamin E.
In the Select trial they selected those with high grade prostate cancer from all participants, including those taking selenium and vitamin E. They did not breakdown those with high Omega 3 in the blood high and high grade prostate cancer by treatment group, so we do not know if most or conversely few of the them were taking vitamin E, but we do know from the main trial that vitamin E was found to increase the risk of high grade prostate cancer, and the majority of the participants were taking vitamin E. We also know that there were more people with high BMIs in the high grade cancer group, and a greater number were taking asprin. We also know that vitamin E can block
http://cancerres.aacrjournals.org/content/57/12/2410 http://www.sciencedirect.com/science...71531799001554 or sometimes increase the process of apoptosis (cell death) depending on what type it is and what the dosage is.
Some forms of vitamin E at high dosages may reduce cell death because they protect polyunsaturated fats from oxidation; the oxidation of polyunsaturated fats have important roles in process of cell death, so reducing oxidation may reduce cell death, which may be great in some circumstances, but not so good if you are wanting to kill damaged or cancerous cells.
The conclusion to the Select paper should maybe have been vitamin E in the synthetic all rac-α-tocopheryl acetate form at the dosage selected, increases high grade prostate cancer, and the increase in high grade cancer was also linked with high levels of Omega 3 in the blood, but the groups were not separated out to determine if the effect of high Omega 3 was dependent on the presence of either Vitamin E or selenium in the forms selected – which would not have grabbed much media attention ! The trial is telling us something but exactly what is not clear. It is clear the press release headline should not have been the bald simplistic press statement that dietary Omega 3 increases the risk of high grade prostate cancer.
The predecessor trial looking at Omega 3s
http://en.wikipedia.org/wiki/Finasteride and its original primary purpose was to look at the use of a product called finasteride
http://en.wikipedia.org/wiki/Finasteride to reduce prostate cancer. The result was that finasteride may reduce prostate cancer but also may ? increase the risk of high grade cancers. Again the researchers used the same study population group including those who took the finasteride and looked at their Omega 3 status; again they found a link between Omega 3s and high grade cancers, but consideration of the effect of Omega 3 on prostate cancer risk is tainted by the fact at least part of the selected group was taking finasteride which may? increase the risk of high grade prostate cancer; did Omega 3 add to the finasteride risk; maybe, but we do not know from the information available; we cannot separate out and quantify from the information the effects of finasteride and long chain Omega 3s (be that from the diet or improved conversion) so the observed result cannot justify a conclusion that Omega 3 on its own increases the risk of high grade prostate cancer, or even that or that higher amounts of long chain Omega 3s in the plasma originated in the diet rather than by increased conversion.
As neither trial actually asked people what they were eating let alone if their Omega 3 came from fish or fish oil, we cannot even begin to differentiate the effects of fish intake or supplementation in the form of fish or krill oil on prostate cancer risk, or indeed determine if the higher levels of long chain Omega 3 in the blood was due to dietary intake, or some metabolic differences in the rate of conversion of plant based Omega 3 to long chain Omega 3. Interestingly one of the factors that affect the rates of conversion of the plant based to the longer chain Omega 3s and 6s is hormonal status; women convert much better than men, with oestrogen primarily with help from progesterone arguably increasing, and conversely testosterone arguably decreasing, conversion rates. So we do not actually know why these men had higher long chain Omega 3 in the blood; higher EPA and DHA could even for example be a marker of hormonal changes such as falling testosterone or rising oestrogen due to treatment protocols or changes in metabolism with onset of prostate cancer, or it might be what they ate, or a combination of both.
In conclusion there is no doubt the Select and Finasteride papers are telling us something; maybe long chain Omega 3 plus vitamin E, higher BMI, and aspirin use together, increase the risk of prostate cancer, or finasteride and Omega 3 further increase the risk of prostate cancer in those taking finasteride, or hormone levels change in aggressive cancers, or treatments affect hormones, so impacting on Omega 3 and 6 plant based fat conversion to long chain fats; but I suggest the basis of the trial and consequent results simply do not justify the bald title of the press release namely “Study confirms link between high blood levels of omega-3 fatty acids and increased risk of aggressive prostate cancer - Consumption of fatty fish and fish-oil supplements linked to 71 percent higher risk” which in the circumstances is not a conclusion which can in anyway be definitely drawn from the study.
It is important not to forget that Omega 3 and 6 along with many other nutrients are fundamental to cell function, and in nature are more of less in balance in the diet. Many men are very poor converters, and some population groups are genetically less efficient converters. If you are not very good at making long chain Omega 3 from plant based Omega3 you have to get it from food or supplements.
Our massive intake of Omega 6 fats increases the requirements for Omega 3s; reducing Omega 6 intake is a better strategy that taking lots of Omega 3 to compensate. Taking higher amounts of Omega 3s in the short term may be a good way to initially try and help rebalance the bodies Omega 3 / 6 status, so reducing inflammatory, replenishing tissue, displacing Omega 6s etc, but as ever the body is complex and ultimately there are down as well as upsides to all supplementation, and particularly so large amounts in the longer term.
In summary looking at the biology of the body you cannot escape the fact Omega 3 is essential to cellular function, nervous system and brain function, vision, and indeed arguably life; on which basis there is no question that in the absence of adequate dietary supply, supplementation will be of benefit. Based on a raft of reasons I recommend marine whole food sources over fish oil; but many do not eat fish, and pressure on fish populations is a fast increasing issue. Ultimately there is no question that marine oil supplementation has a place; taking fish oil is better than being Omega 3 deficient due to dietary deficiencies, and or genetic or other common dietary factors leading to poor conversion of plant based to long chain fats. Many do not get adequate dietary plant based Omega 3, even if they could efficiently convert it, and I repeat men are generally very poor converters.
In conclusion long chain Omega supplementation definitely for some has a place, because it is a healthier option than being deficient; but not as good as getting adequate long chain Omega 3s from whole foods ( and this really means quite a lot of marine foods as the way we grow our animals means they too are often low in Omega 3s eg eggs, and we no longer eat the Omega 3 rich parts like brain)
PS Martie Whittekin, impassioned health journalist, and talk show host, includes some excellent links on the Omega 3 prostate issue in the second section of her weekly diary
http://www.radiomartie.com/newsletter/2013/072513.htm
(One of the papers suggests an increased risk of prostate cancer with fried fish, which on the balance of probabilities may actually contain little Omega 3 and a lot of Omega 6 if fried in vegetable oil, and more if in batter. Fried foods absorbs considerable amounts of frying oils)