Too BOLD

This week in seminar we were presented with data from the Beef in an Optimal Lean Diet (BOLD) Study recently published this month in the American Journal of Clinical Nutrition (2012; 95: 9-16).

The BOLD study was generously brought to us by our friends at the Beef Checkoff Programwho's efforts include "working to continue growth in beef demand" in part by developing "informational and promotional projects ... based on research relating to nutritional value of beef and beef products". I'm confident that this research funding as well as the travel grants and honoraria that came with it had no influence on the design, implementation, interpretation and presentation of the study, but lets take a quick look at the methodology anyway, just in case.

The author's claim in their discussion that their "study population was representative of a large portion of the US population ... and thus, the findings have broad applicability". According to the methods, they recruited healthy men and women that were 30 to 65 years old that had elevated LDL-cholesterol (bad cholesterol). They had a few other restrictions worth noting:

Inclusion Criteria	Exclusion Criteria
Body Mass Index 18.5-37 kg/m2 Triglycerides <3.95 mmol/L Blood pressure <140/90 mmHg Nonsmoking	Cardiovascular, liver, kidney, and autoimmune diseases, or diabetes Taking cholesterol or lipid lowering medications or supplements Pregnant or lactating Recent weight loss (>10%/6mo) Vegetarian

Of the 968 people who responded to the advertising for the study, 42 of them met the criteria and were enrolled - that's 4.3% of the subset of the population that would respond to such a study - aka, a representative sample. This also overlooks the 17 to 21% non-completion rate in the study.

The BOLD study employed a particularly interesting design known as crossover. In a crossover study, subjects are exposed to each of the study treatments. This approach has two distinct advantages:

1. It increases the sample size because each participant contributes data to more than one exposure groups (as in a randomized trial)
2. It emulates the counterfactual ideal by comparing people with themselves

The counterfactual ideal is a theoretical model of the perfect study design for determining causality. In the counterfactual ideal, the exposure of interest would be compared to the non-exposure in the same group of individuals, over the same time period (like a do-over). Because each person would be re-living that same time period over again, all of the factors that might affect that results are controlled for, and any differences in outcome would be solely due to the change in exposure. This is obviously not possible, but the crossover design mimics this scenario by having subjects serve as their own comparison between exposure groups. It is important to recognize that it does so imperfectly - external factors will be different, and there is a possibility that the first exposure may have an effect on subsequent exposures in predictable or unforeseen ways. Two commonly known order effects are:

1. Learning - if the outcome is something that can be learned, the results will likely be better the second time around
2. Carryover - the effect of the first exposure on the outcome of interest "carries over" to the second exposure, so that the starting point of the subsequent exposures is not the same

It is possible to limit the order effects by equally and randomly allocating subjects to start with different exposures, and by having a grace (washout) period between the exposures to allow the subjects to return to a baseline state. When done well, a crossover study is one of the better designs for assessing causality, particularly when the source population for recruitment is small.

The BOLD study examined four different feeding regimens of 5-weeks duration, and used a washout period of 1-week between feeding regimens:

1. Healthy American Diet (HAD)
2. Dietary Approaches to Stop Hypertension (DASH)
3. Diet Beef in an Optimal Lean Diet (BOLD)
4. Beef in an Optimal Lean Diet Plus Protein (BOLD+)

The above diagram depicts what participation in this study would look like for a subject.

Remember, the washout period in a crossover study is used to return subjects to a baseline-like state (to mimic the counterfactual ideal) before beginning the next treatment. This reduces the chances of a carryover effect from one treatment to the next. Given the reductions in LDL-cholesterol from 3.6 to ~3.22-3.44 mmol/L that were observed in this study, I find it highly unlikely that carryover did not occur with a washout period of only 1-week. It makes intuitive sense that the effect size of a lipid lowering diet plan will be proportional to the baseline LDL-cholesterol concentration (it is harder to lower someone's cholesterol if it is already in the normal range). The authors' provide no rationale for the brief washout period, and do not comment on, or provide data regarding the carryover effect. If carryover occurred, and there is no way of knowing if it did, then the order of the dietary treatments would have been very important.

Thankfully, subjects were randomly assigned the order in which they were placed on the four feeding regimens. Simple randomization ensures that there is an equal opportunity of a feeding regimen being 1st, 2nd, 3rd or 4th in this study for each subject. However, it does not guarantee that the groups are the same at the beginning of each of the feeding regimen. This is where "Table 1" comes in - the first table in almost any published article provides the baseline characteristics of the subjects. In studies where groups are being compared with one another, particularly if there is a possibility of bias, it is convention and good scientific practice to display the group baseline characteristics separately for the purpose of comparison. This transparency provides other researchers with piece of mind (not a guarantee) that the groups are similar before treatment, indicating that the simple randomization was effective, and that any differences in outcome are due to the exposure of interest.

In the BOLD study, there were 36 subjects and 4 treatment groups. This is an very small sample size considering the primary outcome of interest, LDL-cholesterol, ranged from 2.46 to 4.84 mmol/L at baseline. Consequently, there is a good chance that the randomization to feeding regimen order resulted in a bias for one or more groups. However, instead of providing baseline characteristics according to feeding regimen, the subjects were grouped according to gender, so that we can compare males and females. Apparently the males had a higher BMI at baseline - I fail to see the use of this information in a small crossover study where each participant acts as their own control.

While we are on the topic of randomization and sample size, lets discuss power. Not the ability to influence others, but the likelihood of wrongful conclusions. Have you ever wondered how researchers determine how many subjects they should recruit? It is actually one of the more important considerations when planning a study - too many subjects is a waste of resources and places undue burden on participants, whereas too few subjects increases the probability of interpretation errors. There are two types of interpretation errors:

1. You determine that the exposure had an effect on the outcome of interest, when it actually doesn't (called an "alpha" error)
2. You determine that the exposure didn't have an effect on the outcome of interest, when it actually does (called a "beta" error)

Both errors can have serious implications, but we are generally more conservative when it comes to alpha errors - meaning we would rather miss an actual effect than say one exists where it doesn't. There is still the prospect of chance to take into consideration - as a convention, we generally permit a 5% chance of making an alpha error, and a 20% chance of making a beta error, and this dictates the sample size needed. It makes sense that as a study increases in sample size from 2 subjects per treatment group to 30 subject per treatment group that the probability of an error occurring by chance alone decreases significantly. When sample sizes aren't large enough to prevent interpretation errors, we say that they are "underpowered", and of the two, a beta error is most likely to occur. In fact, the "power" of a study is defined as simply the opposite of the chance of a beta error (ie. a 0.2 probability of beta error = a power of 0.8).

So how did the BOLD study do? Well, they did a power analysis - check!

"Analysis used the following assumptions: power was set at 0.8, alpha was set at 0.05, and 2-tailed tests were used. It was estimated that a sample size of 40 was sufficient to test the primary LDL-cholesterol hypothesis while allowing for a 10% dropout rate"

As per the convention, there was a 20% chance of beta errors and 5% chance of alpha errors with a sample size of 36. However, due to a higher than anticipated dropout rate (21%), only 33 people completed all four feeding regimens (I think). Oddly enough, some feeding regimens had reported sample sizes of 34 and 35. Apparently, they weren't going to let a little thing like dropout stop them from including the data from people who completed only some of the feeding regimens and not others - so much for the counterfactual ideal.

Before leaving this topic, I would like to take a moment to mention the dataset that they used for their power analysis, the original DASH trial. Because the findings in the DASH trial were used to calculate sample size in the BOLD study, it is essential that they comparable. There are several differences between the two studies, including the fact that the DASH trial was an 8-week dietary intervention, not 5-weeks. I fully acknowledge that there is rarely good pilot data available for determining sample size, and researchers need to guesstimate. In these circumstances, it is generally preferred to error on the side of too many people.

The authors' conclude that:

"The results of the BOLD study provide convincing evidence that lean beef can be included in a heart-healthy diet that meets current dietary recommendations and reduced [cardiovascular disease]"

The statistical tests used in this study are designed to detect significant difference between groups, allowing for a 5% chance of making an alpha error. The ability to claim that two groups were similar on the other hand, as was done here, is a reflection of power. If the BOLD study had the intended a sample size of 36 (which it didn't), an adequate washout period (which it didn't), and a similar design as the DASH study (which it didn't), the probability that their findings could have occurred by chance were still 1 in 5 - apparently that is "convincing evidence". It makes you wonder if they welcomed the possibility of beta errors, and the justification to suggest that lean meats are "clinically-proven" to be part of a "heart-healthy diet".

These design flaws are somewhat unfortunate because Penn State University has a Metabolic Diet Study Center, allowing them to prepare all of the meals from scratch, which provides excellent control over the dietary exposure of interest. Moreover, subject compliance with the prescribed diets was reported to be 93%, which, although unconfirmed, is quite good.

The feeding regimens themselves left something to be desired. The so-called "Healthy American Diet" (HAD), which served as a control group in this study, wasn't so much "healthy" as it was typical - high in saturated fat and cholesterol, and low in fiber - these factors are all associated with higher LDL-cholesterol. This is a common research approach, used to ensure that the findings will be positive (see my previous post "Supply, Meet Demand - The Future of Food Science" for a more detailed description of this concept). The DASH diet feeding regimen in the BOLD study was considerably better than the HAD, but was not consistent with the spirit or the letter of the true DASH diet, as shown below:

Dietary Component	Original DASH Study	BOLD Study
Fruits	5.2	4.1
Vegetables	4.4	4.3
Grains	7.5	4.5
Low-Fat Dairy	2.0	2.3
Regular-Fat Dairy	0.7	0.1
Nuts, Seeds and Legumes	0.7	2.1
Beef, Pork and Ham	0.5	1.0
Poultry and Fish	1.1	3.7
Fats and Oils	2.5	4.0

The table above compares the different DASH diets that were used in the original DASH diets used to determine sample size, and the BOLD study DASH diet. As can be seen, the BOLD study DASH diet is lower in fruits, grains and regular-fat dairy, and higher nuts, seeds and legumes, meat, and fat. The DASH diet is meant to be a plant-based diet, yet there is an average daily provision of 4.7 oz of meat. This importance of this issue becomes clearer as we look at a comparison of the DASH diet and BOLD diet feeding regimens in the BOLD study:

Dietary Component	DASH Diet	BOLD Diet
Fruits	4.1	4.5
Vegetables	4.3	3.9
Grains	4.5	5.6
Low-Fat Dairy	2.3	1.8
Regular-Fat Dairy	0.1	0.0
Nuts, Seeds and Legumes	2.1	1.3
Beef	1.0	4.0
Poultry, Pork and Fish	3.7	1.0
Fats and Oils	4.0	4.3

The difference in servings of meat was 4.7 oz/d (DASH) and 5.0 oz/d (BOLD). So, what this essentially compared was two relatively healthy diets, one with mostly poultry, pork and fish, and one with lean beef. And when I say lean, I'm talking 95% lean ground beef, which is leaner than the extra lean ground beef that I purchase at my grocery store.

This brings me to my final complaint about this study, which is the implications, the message that we be sent, and how it will be received by the public. I understand that the beef industry is feeling unfairly prosecuted for its excessive use of energy, land and water, its massive production of waste and greenhouse gases, its contribution to antibiotic resistant bacteria, its unethical treatment of animals, and for potentially causing cardiovascular disease, cancer and death in humans. Even if all of these things are true, in our capitalistic, individualistic society, they have as right, nay a responsibility (to their stakeholders), to do what they can to get people to eat more beef.

It's a relatively straightforward process:

1. Finance research that can cast doubt about the "eat less beef" messages by creating scape goats and caveats so that they can externalize the responsibility onto you, the consumer. The BOLD study attributes heart disease risk from eating beef on saturated fat - check!
2. Create oversimplified, misleading messaging, and distribute it as widely as you can. Consumption of lean beef is an important part of a heart-healthy diet - check!

This creates a distinction in the minds of consumers between their product, beef, and the cause of heart disease, saturated fat. Now, it is up to the consumers to choose the beef cuts that are lower in saturated fat - it's another form of individual responsibility (or person blaming). Assuming that this was the case, that it is the saturated fat in beef, not beef itself, that contributes to heart disease. Beef is still a major source of saturated fat in our diet. Telling people to consume lean cuts of beef is shortsighted, weak health messaging that serve industry interests rather than the public. It is not as if they take off the lean cuts and throw out the rest - it all makes its way through the food system and into our diets.

There were many design flaws in the BOLD study, and the AJCN should be embarrassed to have done such a poor job editing it (Table 1, aggregate information, uneven numbers in a crossover study, unwarranted conclusions, etc.). However, more concerning is the messages that are sure to pour out from the beef industry - they definitely got their money's worth.

Supply, Meet Demand - The Future of Science?

The scientific method is meant to be a circle, a continuous cycle of:

It's an imperfect system, and there are many issues, including:

• flaws in study design (ie. small sample size)
• data mining / cleaning / fabrication
• unwarranted conclusions
• the failure to publish all details / results
• the failure to publish negative findings
• inappropriate citing of previous research

Many of these issues could be addressed by careful editing of article submissions, a topic that I plan to cover in a future post. For now, I want to discuss the influence of the food industry in nutrition research. The inspiration for this post came from a colleague's review of a study by Bassaganya-Riera et al. on punicic acid, the main fatty acid (or fat) found in the arils (or seeds) of pomegranates .

I'll begin with the bad news - nutritionists haven't been entirely honest with you. We often group nutrients together based on physiochemical properties with full knowledge that they include a broad range of compounds that are not therapeutically equivalent. However, consumers cannot be expected to differentiate between beta-glucans and fructo-oligosaccharides (both soluble dietary fibers), or alpha-linolenic acid and docosahexaenoic acid (both omega-3 fatty acids), so we just let them believe they are all the same - rest assured, they aren't.

With this in mind, lets discuss punicic acid (depicted above). As you can see, it is 18 carbons long, with 3 sites of unsaturation (double bonds). It makes up the majority of the fatty acids (~75%) in pomegranate seed oil, and is being investigated in this study for "anti-inflammatory" properties for the prevention of inflammatory bowel disease (IBD). I have circled the double bond that is in trans orientation, and is responsible for its designation as a trans fat.

Yes, it belongs to the family of dreaded "trans fats" that are being banned in supermarkets and restaurants (and with good reason). But this is a different trans fat - one that is found "naturally" in the food. Both milk and meat contain another group of "natural" trans fats, collectively known as conjugated linoleic acid (CLA), which are coincidentally also believed to have health-enhancing properties. The more commonly known trans fats that are linked with several risk factors for coronary heart disease are actually a subset of trans fatty acids that are man-made, usually through a chemical process called hydrogenation. But, I digress.

The study randomized mice to two separate diets, which differed only in fat composition - fat provided about 15% of total calories, 86% of which came from soybean oil. The remaining 14% was either linoleic acid (control group) or pomegranate oil (treatment group). This is the foundation of an experimental study, the assignment of the exposure of interest while attempting to keep all other variables similar between groups. When this is done right, any differences can be assumed to have been "caused" by the exposure.

According to the authors, "the optimal doses of PUA included in these diets were the result of time course and dose titration studies designed to elucidate the optimal anti-inflammatory efficacy of PUA performed previously (data not shown)". I'm admittedly not loving the lack of transparency in that process - moving on.

Interesting that the "optimal dose" was 14% of total fat intake - lets translate:

If a person consumes 2,000 calories per day, and 30% of my calories comes from fat (this is a low fat diet by Canadian standards), then I am consuming 600 calories as fat. There are 9 calories per 1 gram of fat, so I would be consuming ~67 grams of fat. If 14% of this fat was from pomegranate oil, then I would need to consume roughly 9 grams of pomegranate oil every day. This amount could quite conceivably be consumed in a supplement, although you would likely need to take 6-9 of them (1-1.5 grams each) for them to be swallowable by a human.

Equally important in this process is the choice of reference group for comparison. There are many options available, and rarely is there is a clear best choice when it comes to nutrition. In the case of inflammation, certain fats are better than others. Arguably, the most well-studied fat is the pro-inflammatory omega-6 fatty acid, linoleic acid, which is also the major fatty acid in soybean oil. Anyone who studies nutrition knows this, begging the question, why would you design a study that uses soybean oil as your background diet and linoleic acid as your comparison group? The answer is simple - effect size.

Statistical tests that look for differences between groups take into consideration three things: a) variance, b) sample size, and c) effect size. Effect size is the absolute difference between the two groups. So, if I really wanted to demonstrate that my treatment was effective, I would compare it to the worst possible substance that I could reasonably get away with, thus maximizing my effect size. Then, I could advertise my product as being "clinically-proven".

The author's of this study concluded that:

"these data indicate that PUA ameliorates experimental IBD by down-modulating inflammation in mucosal immune and epithelial cells"

In reality, all that this study demonstrates is that, in this mouse model fed this background diet, providing 14% of the fat as punicic acid reduces certain inflammatory markers / outcomes compared to providing 14% of fat as linoleic acid. Unfortunately, no where in the results or discussion do the authors acknowledge the pro-inflammatory effects of linoleic acid - perhaps they assume that the readers are aware of this fact.

This study was funded by Lipid Nutrition, a company that produces and sell fatty acid supplements. Moreover, the primary author has filed a patent related to punicic acid. Although this information was provided (in small print at the end of the paper), given the obvious conflicts of interest, I doubt that objectivity could be maintained here - perhaps explaining the limitations discussed. Negative results would have been very hard to publish.

Why was this experiment conducted in the first place? It is possible that punicic acid is just a really promising fat, and that the good people at Lipid Nutrition believe that it may be useful for disease treatment and/or prevention. However, at the risk of sounding cynical, I think that the real reason is far less scientific and selfless. Pomegranates have recently become recognized as a "super food" thanks to their high anti-oxidant levels. I feel that it has gotten to a point where I could add a few drops of pomegranate juice to iced tea, and sell it for a dollar more as a health drink.

While we are on the topic, there are no "super foods" - it's a genuinely stupid idea that people really need to get out of their minds. All real foods are super, and with adequate funding and time, I am confident that researchers could extract hundreds of different nutrients from any real food, and design a study that would demonstrate some health-enhancing property. I use the term real food intentionally to differentiate it from the other edible foodstuff that can be purchased at the supermarket.

Back to the matter at hand. The pomegranate juice and the seeds are kind of a package deal, so as the demand for juice increases, there is going to be a surplus of cheap seeds. This creates an opportunity for companies that are able to find a use for them. Turning them into expensive fatty acid supplements is almost poetic, and I would commend their efforts if they weren't so unnecessary and underhanded. The consumers that buy pomegranate juice for its anti-oxidants are likely the same ones that would purchase punicic acid supplements for its anti-inflammatory properties. If only there were a single product that had it all for less.

It is not surprising that the formation of juice would result in the loss of important nutrients, and lends further support to the notion that you should not drink your fruits and vegetables. Although I must admit that it is far more profitable for food manufacturers to sell plants in their individual bioactive components, I'm not convinced that this is in any way better for the otherwise healthy consumer. As for nutrition as a science, I imagine that it will continue to go where the money is, providing the evidence required to create the demand needed by the food industry.

Bassaganya-Riera J, DiGuardo M, Climent M, et al. Activation of PPARg and d by dietary punicic acid ameliorates intestinal inflammation in mice. Br J Nutr 2011; 106: 878-86.

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.