We all know the importance of a healthy diet. But what diet? The recent controversy surrounding the consumption of tomatoes and reduction in the risk of prostate cancer is a case in point. We are bombarded by contradictory advice.

Why is the field of nutrition so confusing? How does a study come to the conclusion that a certain food or food component is beneficial or ineffective for treating a particular disease? To answer some of these questions, we need to understand first how nutritional studies are conducted and their complexity.

1. Collection of dietary information
   Food frequency questionnaires are completed either with the help of the researcher or are self administered. They are often far from accurate and rather superficial. Reasons:
   • Individuals may under- or overestimate the amount of food they ate over a month or a year. (For example, can you recall exactly what and how much you ate last week?)
   • The calorie and nutrient content of many food items are uncertain. (For instance, how different is your chilli from my chilli?)
   • Dietary habits of an individual study participant may change during a long-term study
2. Bioavailability
   This is the actual amount of a nutrient that reaches a particular organ in the body. It is affected by how much is absorbed and how much is filtered out by the liver. Some determining factors include:
   • Absorption depends on how the food was prepared – cooked, baked, broiled, fried etc.
   • How well is the food digested
   • What other foods are eaten at the same time. The effect may be positive or negative. Positive effect: fat soluble substances are better absorbed when consumed with fatty food, e.g. beta carotene, the vitamins A, D, E and K, and lycopene. Negative effect: the compound is bound by another food component that limits its absorption, e.g. fatty acids bind calcium in the gut which prevents its absorption and results in calcium excretion in the stool.
   • A compound can have different spatial structures, one of which is better absorbed than the other. It may also be handled by the cells in the body differently
3. Biological effect at the cellular level Several components absorbed from the food, e.g. vitamins, minerals, phytochemicals, etc., may interact, strengthening or weakening each other’s functions.

4. Type of study

   There are many different types of studies, and the conclusions drawn from them may only be valid for that set-up and may not apply to humans. Or, the results may not be transferable to another setting.

• Cell culture:
  • A study may compare responses obtained from normal cells with those from cancer cells, or between animal cells and human cells. In cell cultures, the investigational compound can be applied directly and at very high concentrations to obtain certain results. This may not be achievable in the intact human body. The composition of the cell culture medium used in an experiment may also influence the results.
• Animal studies are models:
  • All animals in a study group are fed uniformly with a standard diet. The food compound under investigation is added to this basic nutrition.
  • Humans consume a mixed diet, which can mask the effect of the food compound under investigation.
  • Animal metabolism may be similar but not identical to that of humans. Animal cancer models are not necessarily identical to human cancers.

• There are several types of human studies:
  • All study designs have their strengths and weaknesses, the ease and difficulty of enrolling participants and the costs involved factors below
  • Epidemiological studies are excellent for drawing attention to associations, but offer no proof of a cause and effect relationship.
  • In case-control studies, participants are often volunteers who may be leading a healthier lifestyle than the average person. Severely ill patients may be reluctant to participate. Prospective case-control studies are of stronger design.
  • The size of the study is critical. Studies with small numbers of participants may have results due to chance and not to true difference.
  • Large prospective studies that follow participants for a number of years are the best tools to detect cause and effect, e.g. the cancer protective effect of a nutrient. However, some factors such as not enough participants to classify patients into sub-categories of adequate numbers, inadequate dietary information, and loss of participants for follow-up can jeopardize the results.

The case of tomato consumption and prostate cancer

Studies on tomato products and lycopene are typical examples of how different types of studies can draw contradictory and confusing conclusions for the consumer.

The Lycopene controversy

Based mainly on epidemiological studies, a strong advocacy for tomatoes and tomato products in the diet has developed. It was broadly publicized that tomato based foods, due to their lycopene content, can prevent prostate cancer. Lycopene supplements were also actively marketed.

Several companies applied to the US Food and Drug Administration Agency (FDA) for approval of the health claim that tomato products and lycopene supplements lower the risk of prostate cancer.

The FDA dismissed the request and published the evidence-based process that led to its decision. This was reviewed in the July 10th issue of the Journal of the National Cancer Institute, accompanied by two editorials. The media immediately picked up the news with catchy titles, emphasizing that lycopene has no role in preventing prostate cancer

Was this what the FDA report said? Is this the end of the lycopene story?

After reviewing more than 100 human studies (clinical intervention trials and observational studies) on the relationship between tomato products and/or lycopene intake, the FDA concluded that there was no credible evidence to support the health claim for an association between lycopene intake and a reduced risk of any of the cancers in question.

However, the report states that “Very limited and preliminary scientific research suggests that eating one-half to one cup of tomatoes and or tomato sauce a week may reduce the risk of prostate cancer.“

The FDA did not state that tomatoes and/or lycopene do not have a beneficial effect. It only says that at this time, there is not sufficient scientific evidence for a health claim. In one of the accompanying editorials, E. Giovannucci writes: “ Given the complexities of studying the relationship between tomato or lycopene intake and prostate cancer risk, both in terms of the exposures and the outcome, one should not be too surprised that no firm conclusionof benefit would be made in the FDA review. …Although it may be premature to espouse increased consumption of tomato sauce or lycopene for prostate cancer prevention, this area of research remains promising.“

Another editorial by PM Coates of the US National Institute of Health concludes that “… a systematic review can readily be updated toinclude emerging relevant data. It is possible, for example, that FDA could revisit the qualified health claim for tomatoes and lycopene and risk reduction for cancer if new studies were published that appeared to shed further light on the topic. In a field suchas this, new data appear regularly.“

According to David Yeung, professor emeritus, University of Toronto, there is inconsistent evidence about the effect of lycopene when taken on its own. However, sufficient evidence exists regarding whole foods that many health professionals strongly recommend including cooked tomato products in our diet.

Tomatoes or not? Some recommendations

1. According to the Canadian Cancer Society

“No one food or food compound can protect you from cancer, but a combination of foods from a diet rich in vegetables and fruit can.

Tomatoes have attracted particular attention from prostate cancer researchers because lycopene and its related compounds tend to concentrate in the prostate. In animal models, eating tomato compounds has been linked to large decreases in prostate cancer risk. In fact, studies that compare the diets and disease rates of different populations have repeatedly associated diets high in tomatoes with lower prostate cancer risk, as well as a lower risk of stomach and pancreatic cancers.“

2. According to nutritional scientists

Tomatoes should be seen as a food that belongs to an overall strategy of cancer prevention through diet. Tomato sauce is rich in lycopene and contains it in the most easily absorbed form. Eating two tomato sauce-based meals per week may lower your risk of developing prostate cancer by up to 25%.

Richard Beliveau of the Research Centre of the CHU Sainte-Justine in Montreal wrote in his book Foods that fight cancer, “A certain number of studies suggested that individuals who consume large quantities of tomatoes and tomato-based products had a reduced risk of developing prostate cancer. However, this has not been found in all studies.

The great variability of lycopene content associated with different tomato products makes the demonstration of the beneficial relationship difficult. The mechanism by which lycopene reduces the development of prostate cancer is not well understood. Lycopene is an excellent antioxidant, but whether this property influences its anti-cancer effect remains unclear.“

• “We know that antioxidants can help prevent disease... but whether or not a single antioxidant can do this is an open question. Each antioxidant has a unique set of chemical behaviours and biological properties. This diversity is important and allows the antioxidants to work together as an elaborate network.“

  Walter C. Willett wrote in his book Eat, Drink and Be healthy: The Harvard Medical School Guide to Healthy Eating, “Many observational studies show that people who choose to eat more fruits and vegetables high in carotenoids have, among other benefits, less cancers of the prostate. Unfortunately, randomized trials in which volunteers have taken specific antioxidants have not (so far) shown much reduction in risk of developing cancer or cardiovascular disease.“

  He explains that the contradiction could be the result of weak studies, or that a whole, complex network of antioxidants delivered by many fruits and vegetables is needed, not just a specific one. Or, perhaps the right food compound or combination has not been studied for long enough periods.

  “…every little bit helps. A nutritious diet that includes fruit and vegetables – is an important part of any stay healthy strategy,“ he says.

• The key to getting more lycopene is to increase intake of processed tomato products. Fat helps the body absorb the lycopene. “Drink tomato juice with a fat containing snack, such as nuts,“ suggest Liz Pearson and Marilyn Smith in their book Ultimate foods for ultimate health.

3. According to Canada’s Food Guide

A healthy diet rich in vegetables and fruit may help reduce the risk of cardiovascular disease and some types of cancer. It recommends eating at least one dark green and one orange vegetable each day because these are rich in important nutrients.

4. According to the American Cancer Society

The American Cancer Society does not endorse specific foods or supplements, but recommends a healthy lifestyle and balanced diet. Suggestions on diet include:

• Choose foods and beverages in amounts that achieve and maintain a healthy weight
• Consume a healthy diet, with an emphasis on plant sources
• Eat five or more servings of a variety of fruits and vegetables and fruits each day
• Limit consumptions of processed and red meats