Movember

It's Movember, and so I think that it is only fitting that I dedicate a post to prostate cancer. As it so happens, the latest update on the SELenium and vitamin E Cancer Prevention trial (SELECT) was recently published [1]. An excellent summary of this study by it's primary funder (provided $129,687,000 - ouch), the National Cancer Institute, is available online here.

Before reviewing the study, lets hop in the DeLorean and head back to 2001. It was a much simpler time - no Facebook, HP and LOTR were just hitting the big screen, Jean Chretien is PM, and Dan Cloutier is the Canuck netminder. The incidence (# of new cases) of prostate cancer has increased dramatically in the last decade, which is mainly attributable to increases in screening including the widespread availability of the prostate-specific antigen (PSA) test. Interesting side note, the routine screening for prostate cancer using PSA is highly debated today amongst expert organizations (for: American Urological Association / American Cancer Society; against: U.S. Prevention Services Task Force) [2]. Back in 2001, there is a growing body of evidence that dietary antioxidants may be able to prevent certain cancers. Two clinical trails, neither designed to measure prostate cancer, are published indicating a large benefit of supplementation with vitamin E [3], and selenium [4] for the prevention of prostate cancer:

[3] The Alpha-Tocopherol, Beta-Carotene (ATBC) trial was designed to evaluate the effect of supplementing antioxidants, vitamin E (aka alpha-tocopherol) and beta-carotene (precursor for vitamin A), on lung cancer prevention in male Finnish smokers 50-69 years old. Interestingly, this study [5], along with the CARET study [6], are often cited as warnings against the use of antioxidants supplements. However, further analysis of the ATBC study found a 36% reduction in prostate cancer incidence in the group receiving vitamin E.

[4] The Nutrition Prevention of Cancer (NPC) study is a secondary prevention study that was designed to evaluate the effect of selenium supplementation on preventing the recurrence of basal or squamous cell carcinoma (skin cancer) among patients referred to dermatology centers in the U.S. with non-malignant skin cancer. Although there was no benefit for preventing skin cancer recurrence, the group receiving selenium had 0.35 times the risk (2.85-fold decrease in risk) of developing prostate cancer.

Overall, the data at the time suggested (quite convincingly) that both vitamin E and selenium supplementation might be able to reduce the occurrence of prostate cancer. I'd like to take a moment to acknowledge that my previous sentiments regarding the paramount importance of coming up with a catchy acronym for research studies are well supported in this literature - SELECT, ATBC, CARET, NPC.

Flashback to the present, the SELECT study. It was a 2x2 clinical trial of selenium (200 mcg/d) and vitamin E (400 IU/d), meaning that participants were randomly allocated to one of four treatment groups:

1 - selenium and placebo

2 - vitamin E and placebo

3 - selenium and vitamin E

4 - placebo and placebo

This was relatively large trial, including 35,533 older men from US, Canada and Puerto Rico with 2,279 incident (new) cases of prostate cancer. In 2008, a preliminary analysis of the data indicated that it was very unlikely that a significant beneficial effect of supplementation would be detected, and that there might even be an increased risk of prostate cancer in the group receiving vitamin E. Consequently, subjects were instructed to stop taking their supplements, but were invited to continue to participate in monitoring. Last month, they published an updated analysis that including the time since stopping supplementation, and noted the following:

This graph depicts just the raw data - how many men were diagnosed with prostate cancer (total) in each of the groups. By year nine, the number of men with prostate cancer was lowest in the placebo group (n = 529) and highest in the vitamin E group (n = 620). After the initial release of data in 2008 (approximately year 6 in the above graph), the number of men still participating in the study decreased (year 6 = 19,218; year 7 = 12,129; year 8 = 5,483; year 9 = 186), which introduced bias into the results. This is best demonstrated by looking at the annual risk of developing prostate cancer by year:

As can be seen, for most years, close to 1% of the men in the study developed prostate cancer with the exception of year 9, where apparently there was a prostate cancer outbreak (not really). If we remove the 9th year from this table, it is possible to look at the annual risk by groups more closely:

As you can see, the risk of prostate cancer by group was similar each year with a slight, but statistically significant greater risk in the vitamin E group when adding all the years up. Overall, men receiving vitamin E were found to be 1.17 times more likely to be diagnosed with new cases of prostate cancer. This increased risk may sound like a lot, but it translates into an additional 1.6 new cases of prostate cancer annually per 1,000 men taking 400IU/day of vitamin E.

So why the disappointing results - the easiest and perhaps most accurate response is we don't know. The study populations of the previous clinical trials that showed considerable promise were smokers and individuals with skin cancer, both conditions that may be related to oxidative stress that benefits from antioxidants. Another possibility is that the previous research findings were false. In research, the convention is to allow for a 5% probability that the results could have happened by chance alone - when data mining a study like the ATBC trial, looking at hundreds of different outcomes that weren't part of the initial research question, it is reasonable to assume that statistically significant relationships may appear by chance or bias alone. For example, one of the initial findings from the SELECT study in the 2008 analysis was that participants in the selenium group trended towards increased risk of developing diabetes. This will undoubtedly be cited as a reason for future research into the possibility that selenium supplementation may increase the risk of diabetes in older men.

Perhaps the most compelling explanations for why vitamin E appeared to increase the risk of developing prostate cancer was the dose used. The dose was 400 IU/day, which greatly exceeds the amount of vitamin E that is estimated to meet the needs of 98% of healthy adult males (22.4 IU/day). The 'more is better' approach to nutrients is pervasive in our society, yet these mega-doses beyond what is normally found in food are not without risks. Below is a classic diagram relating to essential nutrients that most (presumably all) dietitians in Canada are quite familiar with:

This U-shaped curve describes the relationship between intake of an essential nutrient and health. I use the term "essential nutrient" quite deliberately because only essential nutrients results in adverse events at inadequate intakes. It may surprise some to learn that many of the nutrients that are advertised on food labels (ie. plant sterols for cholesterol lowering) are not required in the diet for health. These nutrients are more akin to drugs, and are the driving force behind the ever-growing nutraceutical (aka pharmaconutrition) and functional food industries.

The SELECT study seems destined to serve as another cautionary tale for supplement users. Attempts to identify and encapsulate the roughly 5,000+ bioactive phytonutrients (nutrients found in plants), and determine who will benefit from supplementation and at what dose will surely keep nutritionists such as myself occupied and employed for a long time to come. Until we know more, I would recommend that healthy adults aim to get their antioxidants from food with the appreciation that more isn't always better.

[1] Klein et al. Vitamin E and the risk of prostate cancer: The selenium and vitamin E cancer prevention trial (SELECT). JAMA 2011; 306(14): 1549-56.

[2] Hoffman RM. Screening for prostate cancer. NEJM 2011; 365: 2013-9.

[3] Heinonen et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: Incidence and mortality in a controlled trial. JNCI 1998; 90: 440-6.

[4] Clark et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: A randomized controlled trial. JAMA 1996; 276(24): 1957-63.

[5] Heinonen et al. The effect of vitamin E and beta-carotene on the incidence of lung cnacer and other cancers in male smokers. NEJM 1994; 330: 1029-35.

[6] Omenn et al. Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. NEJM 1996; 334: 1150-5.

The Industrial Food System

The future of the food system is probably not something that is going to keep most Canadians up tonight. Thanks to technology, cheap inputs, externalization, and the economies of scale, the average Canadian spends only a small fraction (~10%) of their income on food, and consequently is content to live in blissful ignorance of where their food comes from and how it came to be in their grocery store, restaurant, etc. By isolating ourselves from the food system, we place the responsibility for our food supply in the hand of a relatively few large corporations, aka the food industry. For most commodities and services, the conventional capitalistic model, while morally heinous, functions. Although the current entrepreneurial approach to the food system appears to be working well, it is really a matter of perspective.

So how is the food industry different, and why is it deserving of special consideration? The simplest and most obvious reason is that that we all dependent upon a steady supply of food for our continued survival as individuals and as a species. Another, and perhaps more important point, is that the demand for food as a commodity is relatively finite. According to Statistics Canada, the Canadian population has grown less than 5% in the last five years. This inherent limitation of the food system expansion, the stomach factor, does not exist in other industries.

The stomach factor places an incredible amount of strain on food companies to find other ways to increase profits, which they must do. The options include, but is not exclusive to:

1. Get people to eat more
2. Increase their share of the market
3. Sell their products for more
4. Produce the products for less
5. Find other uses for their products

All of these options are potential threats to food security,

a basic human right that is upheld when all individuals in society have access to safe, nutritious and affordable food that is culturally-appropriate, sustainably-produced (ecologically, economically and socially), and is obtained in a manner that upholds the dignity of the individual

It goes without saying that food security is something that the Canadian government does very little to guarantee (a topic for another day).

1. Get people to eat more:

This has been a "big" success. According to a Statistics Canada report, estimated per capita calorie consumption rose ~1-3% each year between 1993 and 2003; however, a more recent report indicates that this trend has appeared to plateau since then. The success of this method is apparent by our expanding waistline and diminished health. I recently shared a case study of a 2-year old child that was consuming ~3,000-4,000 kcal/day with consequent liver disease. Sadly, the up-and-coming generation of increasing obese children is a real boon for the food industry who actually can measure profits in pounds. Not only will they likely require more calories, they will lend support the "niche" market of weight loss products in their almost futile attempts to look like _______ (insert celebrity name).

The burden of their success is that obesity is now on the radar of most people, and serious efforts are underway to stigmatize overeating, limit portion sizes, and make people more calorie-savvy. It is possible that the simultaneous attempts to increase physical activity (if successful) could help to curb the decreases in food consumption related to living healthier. Another way around this problem is to alter the composition of the calorie-providing nutrients in food to make it so we can't absorb them (aka fat and sugar substitutes). The added advantage of this approach is that the corresponding products can be sold for more - nothing like having your Splenda cake and eating it to.

2. Increase their share of the market:

Ultimately, it is difficult to know for sure whether this will be a good thing or a bad thing. If people start consuming more fresh fruits and vegetables at the expense of convenience foods, it would be wonderful. However, I cannot really remember the last time that I saw an advertisement for broccoli. This is partly because there isn't a lot you can do with fresh broccoli to increase value (pre-chopped for convenience?), making it a poor investment for food manufacturers. Yet, this doesn't correspond to a cheaper, more competitive product that is able to dominate the market. As most people have become aware, the cheapest foods are often those that are mass produced with excessive inputs, and are heavily processed and packaged. These products maintain the lowest price in spite of the costs related to manufacturing and advertising. This paradox is made possible by government subsidies, which permit the sale of certain crops, those that drive the food manufacturing industry (mostly corn and soy), at less than the cost of production. With all foods lobbying for position in our stomachs, when a select few crops start to dominate, our food supply loses its diversity. This has implications for both the sustainability of the food system and the nutritiousness of the food supply. One of the tenets of healthy eating is to eat a variety of foods - this is meant to decrease the likelihood that a nutrient is deficient and/or provided in excess.

A related battle is between food we prepare ourselves and that which we eat outside the home. If a greater proportion of the food was prepared by ourselves from scratch, it would undoubtedly be healthier for us and better for the environment. Again, your stove doesn't advertise, but the restaurant industry that would like to increase its share of the market will, and convincingly. We are so convinced that we consume the majority of our meals outside the home. The downside of this is that, unlike in your home, the restaurant industry wants you to eat more of their food, and will attempt to accomplish this by increasing portion sizes and/or providing incentives for eating more - would you like to increase that to a large for just 25 cents more?

Assuming that the proportion of the food market occupied by convenience foods and restaurants continues to increase, the problem will propagate itself by increasing their political clout and nefarious advertising, and perhaps most concerning, by reducing our self-efficacy for meal preparation. As we lose the ability and confidence in preparing meals from scratch, we become more dependent of the food industry to feed us, and relinquish our control of what goes into our food. The current excess consumption of salt is just one example of an additive that we are unlikely to use so liberally in meals prepared at home.

3. Sell their products for more:

This has typically been accomplished by adding value to products, usually in the form of nutritionism and/or convenience. Unfortunately, it is usually the least healthy products that have the most perceived value, and are able to be sold for more. For example, adding fish oil to sugar-sweetened yoghurt and advertising it as important for a child's brain development. Sometimes the added value is nothing at all. Most recently, I bought some raison that are "cholesterol-free". For those who aren't aware, no plant-based food contains cholesterol, but it certainly sounds good.

Another interesting approach, which I have noticed more often, is providing low-calorie (smaller) versions of products for the health conscious consumer. My favorite is the 100 kcal chocolate bars that are sold for almost the same price as the regular chocolate bar, although the 100 kcal yoghurts are a close second. I'm guessing somewhere in the proprietary world of research there was a study demonstrating that consumers viewed 100 kcal as being a healthy snack amount. Either way, I suspect that these smaller portioned products that are able to be sold for almost the same price as their larger counterparts are going to become more pervasive in our food supply in the years to come.

4. Produce the products for less:

Cost-saving measures are almost never going to be beneficial for all involved. Attempts to streamline agriculture processes have resulted in the current landscape of massive monocultures and factory farms, both of which are vulnerable and generate large amounts of wastes. They are made vulnerable by both a lack of genetic diversity, but also by the fact that should the inevitable happen (food borne illness, mad cow disease, etc.), literally millions of pounds of food need to be pulled from supermarket shelves. Case in point, in 2008, 143 million pounds of ground beef was recalled following an animal cruelty scandal at the slaughterhouses. That same year, several lives were lost, and over a 1 million pounds of meat was recalled following the listeria outbreak from Maple Leaf. While the likelihood of these events may be similar in a small operation (unlikely), the consequences are greatly reduced.

Probably the most effective way to reduce the cost of production is to increase biomass disproportionate to the increase in cost, which is made possible in conventional agriculture thanks to cheap inputs. However, as the cost of energy increases, so does the cost of conventional agriculture, and the amount of government subsidies needed to maintain the current system of cheap, processed foods.

5. Find other uses for their products:

This relatively recent venture is mostly limited to the crops that are so well subsidized that other industries want to take advantage of the cheap inputs. In particular, the deconstruction of crops such as canola into basic chemical components allows us to do almost anything with it, most notably producing plastics and fuel. This new market has been great for producers as the increase demand drives up the price. However, given the limited amount of arable land, this trend towards growing crops for non-food uses places greater strain on the available land and food industries.

I have discussed 5 ways that the food corporations can continue to thrive in a capitalistic model. Most of these approaches contribute to food insecurity, something that future generations will probably have to deal with. It is unlikely that we can stop the food industry machine as too much of our food supply is tied up in it. However, it may be possible to regain back some of the control that we have lost over our food by simply ensuring that each and every day that majority of things we put in our face are actually food that we prepared. It won't save us money and will take time out of our busy day, but it will be healthier (in most cases), and will provide hope for the future of food.