The Mediterranean Zone (18 page)

I
n 2005 an article in the
New England Journal of Medicine
predicted that the potential lifespan of children born in the twenty-first century would be less than their parents’. The authors of the study further estimated that one out of every three children born after 2000 will likely develop diabetes. If this projection is valid, then by 2050 about one-third of adult Americans may have diabetes compared to the current 11 percent today. Since diabetes will most likely continue to develop at a much earlier age, this means a longer duration of the disease. As a consequence, many of those children born after 2000 who develop diabetes are also more likely to develop Alzheimer’s. This may represent the breaking point for an already overwhelmed health-care system by 2050. So how did we get into this morass in which each generation seems to become fatter and sicker?

The answer may lie in the strange new science of trans-generational epigenetics in which diet-induced inflammation is transmitted and amplified from one generation to the next.

Epigenetics refers to changes in gene function that do not involve direct changes (such as mutations) in the DNA sequence of our genetic code. Like a molecular light switch, epigenetics allows genes to be modified
sometimes temporarily, sometimes permanently by environmental factors such as diet. Epigenetics also explains how the future expression of the genes of an unborn child can be altered by the diet of his parents and possibly his grandparents to have exaggerated inflammatory responses throughout the rest of his life. Our growing obesity epidemic in the young and the earlier development of diabetes may be indications that the genes of our children are being reprogrammed with potentially very adverse future health consequences. But to truly understand the importance of epigenetics, we have to go back in time to when we thought that genetics was much simpler to understand.

In 2000 it was announced with great fanfare that the human genetic code had been finally sequenced. Genetics was going to usher in a new era of personalized medicine. There was new potential hope for seeing into the future to determine what diseases were lurking in your genome and taking steps to prevent them, or at least find the right drug to treat them more effectively when they did arise. After the initial hype faded, it turns out there were still a lot of unanswered questions about our genes. It didn’t appear that the human genome was all that different from that of a chimpanzee. In fact, many plants (such as wheat and corn) had a far greater number of genes than we do. Additionally, there seemed to be a lot of “junk” DNA (actually 98 percent of the DNA) in the human gene that didn’t appear to do anything useful such as make proteins. After all, that’s what twenty-five thousand “real” genes in human DNA do.

Now we know genetics is a lot more complicated than we imagined. The number of human genes aren’t all that much greater in number or uniquely different from other species; however, it does appear that our genes can be turned on and off with far greater precision and speed than in other animals (or plants). Much of that increased sophisticated gene activity is due to the presence of microRNA fragments found within all that “junk” DNA. Finally, many of the gene transcription factors that turn on or off selected gene sequences of your DNA (such as those that control the production of inflammatory proteins or anti-oxidant proteins) seem to be affected by key nutrients such as omega-3 fatty acids and polyphenols.

Your DNA doesn’t exist in an isolated form. Proteins called histones surround the DNA. If these histones are tightly wrapped around the DNA, it can’t be replicated. If the histones are looser, then DNA can be replicated. What controls the opening and closing of histones are chemical modifications
along their surface. In addition, there can also be transitory chemical modifications of the DNA itself. If a section of the DNA is chemically altered, then it becomes silent and can’t be replicated. These epigenetic chemical modifications don’t change the actual gene structure, but they do determine whether or not that section of the DNA can make proteins based on the code of the DNA. Finally there is the role of microRNAs, which come from all that “junk” DNA. Although these microRNA fragments can’t be used as a template to make proteins coded by the genes, they can inhibit the synthesis of potential proteins by interfering with the processing necessary for the synthesis of that particular protein. It is best to think of your DNA as the hardware in your genes, and epigenetics and gene transcription factors as its software.

The complexity of epigenetics in humans gives us a tremendous flexibility to live in a wide number of climates, from the Arctic to the Amazon. It represents a very elegant control system that allows slight genetic adjustments to changes in dietary, environmental, and stress levels. But it also makes our genes prone to being hijacked by an inflammatory diet.

The one time in your life that your environment has the greatest effect on your future gene expression via epigenetics is while you are in the womb. The mother’s diet establishes many of these epigenetic chemical marks on the fetal DNA to prepare it for the world that awaits it after birth. If there is a mismatch of the epigenetic programming taking place in the womb and the environment the newborn child actually experiences, there will be trouble ahead, usually in the form of the increased likelihood of obesity, diabetes, and heart disease.

The first indication that dietary changes could affect future populations came during World War II. As the German troops were retreating from the Netherlands in the winter of 1944, they took all available food with them, creating a severe famine for the Dutch citizens left behind. It was estimated that the average calorie intake per person during what was known as the Dutch Famine was about 600 calories per day. After the war, both prosperity and food quickly returned to the Netherlands and all seemed well. Then in 1999 researchers began studying the population records of the women who were in their last trimester of pregnancy during the Dutch Famine. Their children were more obese and had higher rates of diabetes and heart disease compared to children who were born either before or after the Dutch Famine. It became apparent that the calorie restriction experienced
by their mothers more than fifty years earlier had resulted in negative health consequences for their children in the womb. Scientists call this fetal programming. It is especially powerful in the last trimester of pregnancy when the mother’s diet greatly influences the epigenetic changes to the fetal DNA to prepare them for what their new environment will be outside the womb. During the Dutch Famine there was a complete mismatch of the mother’s diet during their pregnancy relative to what the dietary environment their child would experience after their birth. The result was these children had an altered metabolism—one that was suited to famine conditions, rather than abundance. This epigenetic mismatch resulted in increased incidence of obesity, diabetes, and heart disease. The fact that all these conditions (obesity, diabetes, and heart disease) are linked by increased diet-induced inflammation suggests that some of those epigenetic changes taking place during the Dutch Famine may also have turned on selected genes that resulted in enhanced diet-induced inflammation once adequate food was available. This is because the fetus was programmed in the womb for highly restricted calorie intake conditions, which was totally mismatched for abundance of calories available after the birth.

At the same time as the Dutch Famine, similar famine conditions were occurring in Leningrad. However, after the war there was not any greatly increased food supplies in Russia. As a result, there was no increase in obesity, diabetes, or heart disease in their children as they became adults. The fetal programming that took place in the wombs of Russian mothers during these famine conditions was ideally matched to the dietary environment their children were born into.

During the first two years of life you are very susceptible to laying down diet-induced epigenetic marks on your DNA. This may be one of the reasons breast-fed children seem to have both better health and higher IQs compared to those children raised on infant formulas. If you look at the composition of virtually every infant formula (another product of the industrialization of food), you will see they are primarily composed of sugar and omega-6 fatty acids. This is a sure-fire prescription for increased diet-induced inflammation primed to do even more epigenetic mischief.

These epigenetic marks established in fetal programming or early postnatal eating patterns can last a lifetime. Furthermore, they can be transmitted and even amplified from one generation to the next, depending on
the dietary environment in which the next generation of parents consumes. If epigenetic changes can increase inflammation, then is it possible that diet-induced inflammation can induce epigenetic changes? Unfortunately, the answer may be yes.

Animal models demonstrate all too clearly the genetic consequences of a continuing inflammatory diet on future generations. In one very disturbing study published in 2009, researchers took genetically identical mice and split them into two colonies. The diets of the mice were identical in terms of calories, protein, carbohydrate, and total fat. The only difference was that in one group the fat content was richer in omega-6 fatty acids and poorer in omega-3 fatty acids. This was a seemingly minor change, especially since both sets of mice were on low-fat diets. These colonies were maintained under these same dietary conditions for three generations. The weight gain wasn’t instantaneous in the first generation of the mice getting higher omega-6 fatty acid intake, but by the third generation, those mice consuming the higher levels of omega-6 fatty acids were grossly obese compared to their genetically identical cousins. These changes were induced by cellular inflammation caused by the change to the proportion of omega-6 fatty acids to omega-3 fatty acids in their diet. In subsequent studies, the same researchers demonstrated that if you increase the levels of omega-6 fatty acids in the diet of the mice to the same levels in the current American diet, the faster the obesity develops.

More ominously, there were also significant metabolic changes being transmitted from one generation to the next. By the third generation of mice getting the higher levels of omega-6 fatty acids, there were significant indications of pre-diabetes, indicated by fatty deposits in the liver and early signs of heart disease, indicated by enlarged hearts.

So let’s look at the rise in obesity in the American population during the time in which similar changes in the ratio of omega-6 to omega-3 fatty acids were also changing in the American diet.

1960: 13%
1980: 15%
1994: 23%
2000: 31%
2010: 36%

This nearly 300 percent increase in obesity in three generations suggests that Americans seem to be following the same trans-generational epigenetic trend as seen in the animal studies as a consequence of increased intake of omega-6 fatty acids and corresponding decrease in omega-3 fatty acids.

Unfortunately, the industrialization of food in the last three generations has become a powerful force in changing the epigenetic marks that control the genetic future of our children as well as ourselves. Perhaps not surprisingly, the fastest growing group of obese individuals in America is children born after the year 2000. The odds of them achieving a normal weight and having a healthy future were stacked against them before they ever left the womb.

This is also true of neurological outcomes. If you make mice deficient in omega-3 fatty acids for several generations, they become increasingly more anxious, less focused, and less intelligent compared to their genetically identical cousins who were getting adequate levels of omega-3 fatty acids during the fetal period and thereafter. No wonder ADHD, anxiety, and depression are becoming epidemic in America’s children.

Epigenetic changes may become permanent if the environmental factors (such as an inflammatory diet) are maintained. The growth of the industrialization of the American food supply may be a driving force in an epigenetic shift in our genes that could be responsible for the epidemic rise of obesity, diabetes, and eventually Alzheimer’s.

There is no easy way of out this genetic storm, because it takes about two to three generations to totally erase these epigenetic marks from DNA, and that’s assuming you have removed the offending dietary causes in the first place. That’s why following the Mediterranean Zone may be the best possible “drug” we have to cope with diet-induced epigenetic changes in ourselves, our children, and their future children. The Mediterranean Zone can hold back many of the epigenetic changes leading to increases to our inflammatory genes induced by prior fetal programming. For each succeeding generation following the Mediterranean Zone, there will be a continuing reduction in those epigenetic markers laid down generations earlier. Within three generations, those epigenetic changes induced by pro-inflammatory diets in the past should be erased completely. The dietary changes needed to follow the Mediterranean Zone are comparatively small compared to the future health benefits for generations to come.

N
utrition is complex, and yet we seem to continually try to dumb it down in the media by using political-like slogans based on simplistic thinking that is often not supported by the facts. In the late twentieth century, saturated fat caused heart disease. Today, the recent campaigns against new single classes of nutrients (fructose, dairy, gluten) completely miss the point as to why the health of Americans is rapidly deteriorating. I wish it were possible to simply remove one food ingredient from the American diet and suddenly return our population to the land of milk and honey (oops, two of the “evil ones”), but it’s not possible.

Nutrition is not like mathematics where you deal in certainties and elegant proofs. Nutrition is based on probabilities. There are some dietary statements that I think have different degrees of probability.