January 14, 2009
If you have trouble keeping weight off and you’re wondering why – the surprising answer may well be the cheeseburgers you ate – when you were a toddler.
Surprising new research by University of Calgary, Faculty of Kinesiology researcher Dr. Raylene Reimer, published in an international journal, indicates a direct connection between an adult’s propensity to put on weight and our early childhood diet.
Reimer is a leader in a growing field of study that examines the developmental origins of health and disease. Researchers in this area believe our pre-natal and early childhood environment influences our future risk of developing conditions like cardio vascular disease, obesity and diabetes.
“My research has shown that the food we eat changes how active certain genes in our body are – what we call genetic expression. In particular we believe that our diet has a direct influence on the genes that control how our bodies store and use nutrients,” says Reimer. “There’s a growing body of work that indicates a relationship between our health as adults and our early diet, and even our mother’s diet. This research shows for the first time that our early childhood diet may have a huge impact on our health as adults.”
Reimer’s study published in the current Journal of Physiology (London,) compares three groups of rats. At a very young age the rats were weaned onto three separate diets. One group was fed a high protein diet; one group was fed a high fibre diet and a third group was fed a control diet. When the rats became adults, they were switched to a high fat, high sugar diet, which reflects the reality of the typical western diet.
The results were astonishing. The group of rats who were reared on the high protein diet as packed on much more weight and body fat than the rats who had ‘grown up’ eating the high-fibre diet, who put on the least amount of weight and body fat.
“I believe this study clearly shows that the composition of early childhood diet may have a direct lifelong impact on genes that control metabolism and obesity risk,” says Reimer. “This study clearly indicates that diet composition alone can change the trajectory of circulating satiety hormones and metabolic pathways that influence how we gain weight or control blood sugar as adults.”
The 2005 Canadian Community Health Survey conducted by Statistics Canada revealed that a majority of Canadians are now overweight. 36.1% of the population is officially overweight and an additional 23.1% of the population is officially obese (BMI of 30 or more.)
What is meant by the term ‘epigenetics’ or gene expression?
Epigenetics refers to inherited changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence. These changes may last for multiple generations. There is no change in the underlying DNA sequence/code of the organism instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently. Epigenetic changes permit adaptation to environmental conditions by silencing or increasing the expression of certain genes.
Gene expression is the process by which the DNA code we inherited from our parents (about 30,000 different genes) is converted into a functioning gene product, such as a protein (like an enzyme or a hormone).
These studies are done with rats – does this really have any relevance to human beings?
Definitely, there are many similarities between the rat models we use and humans in terms of how obesity and diabetes develop. Because it is unethical to perform all of the necessary work in humans to fully understand developmental programming, it is essential that we do this foundational work in rats.
Why did you choose high fibre and high protein diets for the young rats?
The area of developmental programming was first observed in relation to under-nutrition and low protein diets from the Dutch Famine that occurred during WWII. That is one of the few human examples that we have in the research. Dutch mothers were given carefully monitored rations during the war; as a result we know exactly how many calories were being consumed during pregnancy, and researchers could see what impact this diet had on the babies as they aged. In that case they found a strong association between the famine state and the risk of an individual developing diabetes as an adult.
Much more relevant to today’s nutritional environment in North America is over-nutrition and increased intakes of select nutrients. We selected high fiber because we know that Canadians eat only about half of the fibre that they should. We also knew lots about the detriment of a low protein diet but not as much about the implications of a high protein diet – which may be more topical given the popularity of the Atkin’s and South Beach type diets. We hypothesized it would likely be detrimental but didn’t know for sure until we saw the striking results of the study.
What do scientists mean by the developmental origins of health and disease?
A quote from a NEJM article: “At first glance, it may seem implausible that your mother's exposure to stress or toxins while she was pregnant with you, how she fed you when you were an infant, or how fast you grew during childhood can determine your risk for chronic disease as an adult. Mounting evidence, however, indicates that events occurring in the earliest stages of human development — even before birth — may influence the occurrence of diabetes, cardiovascular disease, obesity, asthma, cancers, osteoporosis, and neuropsychiatric disorders.”
The developmental origins of health and disease is a fundamental shift in the way we look at the causes of heart disease, obesity and type 2 diabetes. It is no longer thought that just your genetic pre-disposition or your adult lifestyle causes you to develop these diseases – it is also early life events that affect our biology and subsequent risk.
Do you believe that once these metabolic pathways are set, they’re set for life?
Much of the evidence in rats suggests that these changes are permanent changes. It is interesting to note however that there are small pockets of evidence emerging that some very specific treatments at very defined times during development can reverse some of the negative effects. This will be one of the most exciting new areas of inquiry in this field. And of course a person can always battle their susceptibility to any chronic disease with vigorous exercise and strict diet, but the programmed susceptibility makes the task so much more difficult.
Have any studies ever been done correlating pre-natal or early childhood diets with adult health?
Yes, there are many studies that have addressed pre-natal (fetal) diet and diet during suckling (equivalent to the period of breast-feeding in humans). This work has again largely addressed low protein diets and under-nutrition. There is also some work in childhood describing a high rate of growth to increase risk of obesity in adulthood.
Why this study is novel and published in a high profile journal is that we show that high protein is detrimental and high fiber protective when consumed from weaning (first solid foods in infancy) through childhood and into early adulthood. We have described a new phenomenon in terms of altering diet composition during two of the three ‘most plastic’ times of development. Plastic refers to the periods in life when the body is most adaptable to its environment and makes changes in biology based on the environment it is experiencing. The three plastic phases of life are fetal, childhood and adolescence.
How does diet change the way your genetics work?
Diet does not affect our genetics in terms of changing our DNA sequence. What it does is to change the way our genes are expressed. For example we know that eating a high fiber diet increases your expression of the proglucagon gene. This gene is then used in the body to make a hormone that decreases your food intake. In terms of diet’s influence on epigenetics (which really means changes in addition to genetics) it changes the way the DNA code can be accessed by the machinery necessary to convert genes to their gene products (for example again the proglucagon gene producing GLP-1, the hormone that decreases food intake).
What do you believe is the significance of this research?
The significance is I think 2-fold. Firstly, in North American the rise in obesity rates has occurred far too quickly to be attributable to changes in our DNA sequence – it is much more plausible that there have been changes in the way our DNA code is expressed.
This is where epigenetics come in to play in that it helps to explain how our body adapts to the changing dietary environment we are exposed to by silencing or increasing the expression of certain genes. It is a means for our bodies to adapt in a way that it thinks is appropriate – many times it is not – and that is why obesity is increasing so rapidly.
The second significant implication is to the increased epidemic of obesity in developing countries. These are countries which have, throughout history, been impoverished and therefore many women and children who were undernourished during development are now faced with a very different nutritional environment reflecting a western influence.
The very rapid increase in obesity has been postulated to be linked to the epigenetic changes in these individuals. Their bodies were programmed to a low nutrient/calorie diet and now the high calorie/high fat diet they have available to them unmasks the increased risk of obesity. Our study provides evidence for this - albeit in a rat model. But the mechanisms may be the same as in humans.
What would your take-away message be for mothers?
Our best advice continues to be that mothers follow the Canadian National Guidelines for the Childbearing Years. These can be found on the Dietitians of Canada website and provide sound advice for healthy eating during pregnancy in into infancy and childhood.
From the animal work that has been done to date it also highlights again the old saying that moderation is best. Both a low and high protein diet are detrimental. Both low birthweight and high birthweight are associated with increased risk. Therefore, it is advisable not to undertake any extreme diets during pregnancy or during development.
There are ethical and moral questions arising because of our increasing knowledge in the epigenetics field as well. From the standpoint of the researchers doing the work, there is no thought to laying blame on mothers for the rising obesity epidemic - but those who debate ethical issues in medicine will be forced to deal with questions of whether or not a parent will one day be held legally responsible for a future illness of its offspring if that
parent ignored advice based on established links between diet/lifestyle and epigenetics. If a company or employer finds out that an individual was exposed to a certain toxin or diet during development will they now be denied insurance or charge much higher rates due to their increased susceptibility to chronic disease.