I had seen the previous incarnation of this study (1) a few years ago, so when I saw the follow up study on the physiology feeds the other night, I thought ‘Meh’ and wasn’t going to write about it. But yesterday as soon as the media got their indelicate mitts upon it and spun up headlines such as ‘Omega 3 Raise Risks of Prostate Cancer’, I received a number of queries from concerned folk. So let’s take a look at this in a less tabloid-esque sensationalistic manner.
The first and most important take-away is that the study (2), despite what the media and sadly one of the research team suggests, does not, in fact cannot, make this definite claim. The study is based on a type of statistical science what is known as epidemiology. Epidemiological studies look at patterns and trends to begin to seek out links between factors. In the right hands this can be a very powerful tool, which can help us find which areas to focus upon and investigate further with more specific and generally more expensive methods. It does have its problems though.
A basic example of this problem can be though of as thus:
In the summer time, more people suffer from sunburns.
Ice-cream sales increase in the summer time.
From this could we conclude that: Ice-cream causes sun-burn?
And this is the problem. The idea that because two factors ‘sun-burn’ and ‘Ice-cream’ happen to occur at the same time, doesn’t mean that one necessarily ‘causes’ the other. In this case the forgotten factor was the sun. There’s a very simple, but underappreciated maxim that says ‘Correlation doesn’t imply causation’. That is, just because there is a link between factors doesn’t mean that one factor leads onto the other factor. It ‘may’ but that is why further studies need to be done accounting for all of the factors.
This current study suggests that there is a link between high plasma omega 3 and the more aggressive subset of prostate cancer. Now ‘link’ at this stage, refers to a correlation i.e. Ice-cream, not a ‘causation’, so unlike the media let’s not jump the gun.
This correlation could be because as the paper suggests (I’ll cover one of the ways this ‘may’ happen in a later Bite-size piece) that higher levels of omega 3 are influencing the development (not initiating) of a more aggressive form of prostate cancer, or, and this ‘may’ likely be the case, those who have prostate cancer, especially those with the more aggressive subset have higher levels of plasma omega 3. Although these appear to be the same statement, they’re in fact totally different.
The study used subjects whose ages ranged from 55-85, and this is important. By the age of 50 almost all men have symptoms of prostate disease, which is usually in the form of recurrent bouts of prostatitis (inflammation of the prostate, often caused by infection), or as Benign Prostatic Hyperplasia (BPH, overgrowth of the prostate gland, linked to inflammation), some poor souls have both. By age 85, over 90% of men have developed prostate cancer. I’m not suggesting a causal relationship between the two, but there’s certainly a correlation between prior inflammation in the prostate and the development of prostate cancer. We also know that oxidative stress is part and parcel of the inflammatory response, but we’ll come back to that in a moment as it muddies the water slightly.
So we have a cohort in the right age range for those who are displaying symptoms of some form of prostate disease, whether it’s an ‘–itis’, benign hyperplasia or cancer. And we know that the first two of these are intimately intertwined with inflammation, as is the third. We also know that one of the most potent anti-inflammatory substances we can get via nutrition is omega 3. So it doesn’t take much thought, to see that those people who are displaying symptoms of prostate disease, may have taken the route of upping their omega 3 consumption to reduce inflammation in hope of quenching the flames. And the worse the symptoms the more someone is likely to do all they can to combat them.
I say ‘all’, but that’s with some reservation. Although omega 3 do have anti-inflammatory properties, they are far outweighed by the excess amounts of omega 6 in the diet, which can be both anti-, and pro-inflammatory. However, because of the way our standard diets are set-up the pathway generally only runs down the pro-inflammatory route. One of the key switches which select the pathway that is used, is Insulin. There are many influences upon Insulin, but the two biggies are high glycemic index carbohydrates and fructose. Fructose can definitely be implicated, but again it will make the picture too complicated. High glycemic index carbohydrates on the other hand, are a little easier to associate (again correlation, not causation). High GI carbohydrates are generally found as grains, which just so happen to also be a rich source of omega 6, so we have a foodstuff that loads the gun by providing the raw material for pro-inflammatory substances and pulls the trigger by it’s production of Insulin and thus the diverting of the cascade towards the pro-inflammatory track.
Take a look at the newest rendition of dietary advice (the EatWell Plate); one of the largest food groups pushed by dietetics is grains and other high glycemic carbohydrates. The current diet has a ratio of omega 6:3 of, on average, 15:1; to put this in perspective our ancestor’s diets would’ve been closer to 1:1 - 1:2. A gram or so of long chain omega 3 is a drop in the ocean compared to the amounts of omega 6 we now consume. Maybe a better idea would be to lower the intake of omega 6?
Think of it this way, if you began running a tap and realised you had a blocked sink, would the ‘first’ thing you do be: a) call a plumber to come and fix the blockage, or b) turn off the tap? Now replace the tap with omega 6, the blockage with inflammation and the plumber with omega 3.
The study also pointed to associations that the higher grade cases were more likely to be being treated with finasteride (an alpha-5-reductase inhibitor that prevents the conversion of testosterone into dihydrotestosterone) and the lower grade case had less diabetes in their history. Another two factors that point towards Insulin and inflammation as being pivotal.
So, when it comes to the study those who have the more aggressive form of prostate cancer, and thus are more symptomatic, lo and behold, have the highest plasma levels of omega 3. Just as an aside, the difference between the two levels of omega 3 was about the difference between one and two high omega 3 fish (salmon etc) meals per week. This situation (taking in more omega 3 in an attempt to reduce inflammation) could be one conclusion that can be drawn from the study. There are many others which is why the media have done such a hatchet job on ‘reporting’ this study.
The reason why omega 3’s are so potent is that they are so biologically active, this is how they work in the body, they are highly reactive, but it’s a double edged saw, as this activity also allows them to be easily damaged. And this is why they are difficult to get in the diet, as they can’t be implemented into processed foods without becoming rancid (omega 6 are more robust and survive a lot better in the manufacturing process), so people often use an omega 3 supplement. Companies who produce fish oil (the most widely used omega 3 supplement) have to protect the omega 3 in order to prevent them becoming damaged. The way most companies do this is to encapsulate them, thus protecting them from air (and thus oxygen), use opaque containers to protect the oil from light, and if the company is good, keeps the product refrigerated to prevent damage by heat. To up the ante, most companies also add an anti-oxidant to the mix, and since fish oil is a lipid, the most relevant type of anti-oxidant is lipid soluble and for many reasons vitamin E fits the bill perfectly…almost.
The study in question is part of larger project called the SELECT trial, which had already suggested that vitamin E (the synthetic dl- racemic form) was associated with a 17% increase in the risk of prostate cancer.(3) But as we know the Big G likes to dwell in the details.
Vitamin E is one of the four fat-soluble vitamins that cannot be made by the human body, so must be ingested. Vitamin E is made by plants in eight different iso-forms divided into two classes of four iso-forms. These usually come as mixed tocopherols and tocotrienols in nature however most of the research is on the D-alpha tocopherol form of natural vitamin E, which is the most biologically active.
Synthetic vitamin E, is DL-alpha-tocopherol, the laboratory produced form of the naturally occurring, D-alpha tocopherol. Having both the D and the L isomers, and this is key, renders it ineffective, as the L isomer does not occur in nature, and our DNA does not recognise it.
Two of Vitamin E’s functions are to 1) form part of the cellular membrane (membranes are the surrounding seal of the cell) and defend it against oxidation, and 2) within the cell, and within its organelles such as the mitochondria, vitamin E is the first line of defence against lipid peroxidation. This is where the issue ‘may’ also be occurring.
The use of synthetic vitamin E in the omega 3 supplements may be exposing the membranes of the prostate cells to oxidative damage (by virtue of not being the right tool for the job) and this may be compounded by the incorporation of easily oxidised omega 3 into the membrane (which is usually a good thing) allowing a chain reaction of oxidative damage to occur. It ‘may’ also allow mitochondrial damage to proceed and this is a biggie, since the mitochondria actually uses re-dox (which oxidation forms the –ox part) pathways to dispose the body of damaged cells and cell components.
This is only half of the problem, even if you’re taking in sources (food or supplements) of natural forms of vitamin E (which, by the way, are associated with lower incidence of prostate cancer (4,5), taking single nutrients is never suggested by anyone who knows anything about nutrition, doing so, especially with what are termed ‘anti-oxidants’ may increase oxidative stress, even using the natural forms that are supposed to be present in the Human body. Nutrients, and especially anti-oxidants (more properly termed ‘re-dox agents’) always work in synergy. This is why a wide variety of ‘real’ food is promoted by those in the know, to hopefully obtain ‘all’ of the nutrients that work in cohesion.
There’s much more to this story than the media have reported, but to discuss all of the factors would become encyclopaedic. But here’s my take, like all disease the incubation period is usually a long span of time, so the best time to work on preventing disease is decades ago, the second best time is today, before the rot sets in. Prostate cancer; like many diseases, are mostly down to lifestyle factors. This is not a judgement it is merely a fact. If you wish to avoid disease, clean up your lifestyle, and the earlier, the better. Once disease is present and established, good nutrition is definitely helpful; if not imperative, but sorry, it’s not a cure. This is where we graciously ask the skilled and amazing health care professionals to step in and use their methods of fighting back diseased states. With their help, we can hopefully get another stab at life. This is where nutrition can come back into play as the star player, doing what it does best: slowly building a body that is resilient to disease. Nutrients aren’t drugs, let’s not use them as though they are.
References:
1- Brasky, TM et al. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial. Am J Epidemiol. 2011 June 15; 173(12): 1429–1439. Published online 2011 April 24. doi: 10.1093/aje/kwr027
2- Brasky, TM et al. Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. JNCI J Natl Cancer Inst (2013) doi: 10.1093/jnci/djt174. First published online: July 10, 2013
3- Nicastro, HL and Dunn, BK. Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Nutrients. 2013 April; 5(4): 1122–1148. Published online 2013 April 3. doi: 10.3390/nu5041122
4- Israel, K et al. RRR-α-tocopheryl succinate inhibits the proliferation of human prostatic tumor cells with defective cell cycle/differentiation pathways. Nutrition and Cancer, 1995;24:161-169
5- Eichholzer, M., Stähelin, H. B., Gey, K. F., Lüdin, E. and Bernasconi, F. (1996), Prediction of male cancer mortality by plasma levels of interacting vitamins: 17-year follow-up of the prospective Basel study. Int. J. Cancer, 66: 145–150. doi: 10.1002/(SICI)1097-0215(19960410)66:2<145::AID-IJC1>3.0.CO;2-2
