Unit 15. Food

Script 46. Diet and the evolution of the brain

Fish and no chips

The wonders of docosahexaenoic acid.

To pin one big evolutionary shift on a particular molecule is ambitious. To pin two on it is truly audacious. Yet doing so was just one of the ideas floating around at "A Celebration of DHA" in London this week. The celebration in question was a scientific meeting, rather than a festival. It was definitely, however, a love-in. It was held on May 26th and 27th at the Royal Society of Medicine to discuss the many virtues of docosahexaenoic acid, the most important of that fashionable class of dietary chemicals, the omega-3 fatty acids.

DHA is a component of brains, particularly the synaptic junctions between nerve cells, and its displacement from modern diets by the omega-6 acids in cooking oils such as soya, maize and rape is a cause of worry. Many researchers think this shift and the change in brain chemistry that it causes explains the growth in recent times of depression, manic-depression, memory loss, schizophrenia and attention-deficit disorder. It may also be responsible for riising levels of obesity and thus the heart disease which often accompanies being overweight.

Michael Crawford, a researcher at the Institute of Brain Chemistry and Human Nutrition in London, believes, however, that DHA is even more important than that. He suggests that it was responsible for the existence of nervous systems in the first place, and that access to large quantities of the stuff was what permitted the evolution of big brains in mankind's more recent ancestors.

According to Dr Crawford, DHA's first job was to convert light into electricity in single-celled organisms. This gave them a crude form of vision, allowing them to move in response to light and shade, but also brought into biology a way of controlling electrical potential. If organisms are to be multicellular, cells must be able to talk to each other. Electrical potentials, the basis of every nervous system, are one way of doing this. And DHA was the enabler.

The molecule is certainly ubiquitous. Some 600m years after animals became multicellular, more than half of the fatty acid molecules in the light-sensitive cells of the human eye are still DHA, and the proportion of DHA in the synapses of the brain is not far short of that, despite the fact that similar molecules are far more readily available. Indeed, Dr Crawford thinks that a shortage of DHA is a long-term evolutionary theme. The molecule is most famously found in fatty fish. He suggests this might explain why, for example, dolphins have brains that weigh 1.8kg whereas zebra brains weigh only 350g, even though the two species have similar body sizes. Furthermore, he argues that the dramatic increase of the size of the brains of humanity's ancestors that happened about 6m years ago was not because apes came out of the trees to hunt on the savannahs, but because they arrived at the coast and found a ready supply of DHA in fish.

Not everyone, it must be said, agrees with this interpretation of history. For one thing, humanity's ancestors do not seem to have been exclusively coastal. What they do agree about, though, is that substituting DHA with other, superficially similar molecules is a bad idea.

Joseph Hibbeln, a researcher at America's National Institutes of Health, has been looking at the supply to babies of DHA from breast milk and at genetic variation in the ability to produce this molecule from other omega-3s. A study that began in the early 1990s has shown that children who are breastfed have the same range of IQs, regardless of whether they have the ability to make their own DHA. In the case of those fed on formula milk low in DHA, though, children without the DHA-making ability had an average IQ 7.8 points lower than those with it.

Nor is intelligence the only thing affected by a lack of DHA. There is also a body of data linking omega-3 deficiencies to violent behaviour. Countries whose citizens eat more fish (which is rich in DHA) are less prone to depression, suicide and murder. And new research by Dr Hibbeln shows that low levels of DHA are a risk factor for suicide among American servicemen and women. Actual suicides had significantly lower levels of DHA in the most recent routine blood sample taken before they killed themselves than did comparable personnel who remained alive. More worryingly, 95% of American troops have DHA levels that these results suggest put them at risk of suicide.

America's department of defence has taken note. It will soon unveil a programme to supplement the diets of soldiers with omega-3s. The country's Food and Drug Administration may change one of its policies, too. Thomas Brenna, a professor of nutrition at Cornell University, has written a letter (co-signed by many of the scientists at the meeting) urging the agency to revise its advice to pregnant and fertile women that they limit their consumption of fish. This advice, promulgated in 2004, was intended to protect fetuses from the malign effects of methyl mercury, which accumulates in fish such as tuna. The signatories argue that this effect is greatly outweighed by the DHA-related benefits of eating fatty fish.

They may, however, be swimming against the tide. The popularity of omega-6-rich foods based on cheap vegetable oils will be difficult to reverse. Indeed, if another of Dr Hibbeln's studies proves true of people as well as rodents, it may be self-fulfilling.

In this experiment he fed rats diets that were identical except that in one case 8% of the calories came from linoleic acid (an omega-6 fatty acid) while in the other that value was 1%. These percentages reflect the shift in the proportion of omega-6s in the American diet between 1909 and the early 21st century.

In the 8% diet, levels of rat obesity doubled. It turns out that in rats (and also in humans) linoleic acid is converted into molecules called endocannabinoids that trigger appetite. Those who eat omega-6s, in other words, want to eat more food. And since, in the human case, omega-6-rich food is much cheaper than omega-3-rich food, that is what they are likely to consume.

The way out of this vicious circle is not obvious. Eating fish is all very well, but the oceans are under enough pressure as it is. Biotechnology might be brought to bear creating genetically modified crops such as soyabeans with higher levels of DHA. Until that day, though, the best advice is probably that which was posted over the oracle at Delphi: "Nothing in excess". (From The Economist, May 29, 2010)

Script 47. Nutrition and health

Protection racket

Eating lots of fruit and vegetables may not help stave off cancer, after all.

For snivelling children and recalcitrant carnivores, requests that they should eat five portions of fruit and vegetables every day have mostly fallen on deaf ears. But those who did comply with official advice from charities, governments and even the mighty World Health Organisation (WHO), could remind themselves, rather smugly, that the extra greens they forced down at lunchtime would greatly reduce their chances of getting cancer. Until now, that is. Because a group of researchers led by Paolo Boffetta, of the Mount Sinai School of Medicine in New York, have conducted a new study into the link between cancer and the consumption of fruit and vegetables, and found it to be far weaker than anyone had thought.

In the past, veggie-associated reductions of cancer-risk rates as high as 50% had been reported. But it appears that some of these early investigations may have been biased by the use of "case-control" studies. Such studies try to identify the factors contributing to cancer by comparing people who have the disease with those who do not, but are otherwise similar. The problem is that they can easily be biased if researchers do not adequately establish that the two groups being compared are, indeed, otherwise similar. Walter Willet, at the Harvard School of Public Health, says it appears that earlier investigations were more likely to use health-conscious people as their controls. These types of people are, unsurprisingly, more likely to agree to be interviewed about their health than slobby couch potatoes.

Dr Boffetta and his colleagues have therefore carried out a different kind of study, known as prospective cohort study, which they report in the journal of the National Cancer Institute. Their work follows a group of individuals over time and looks at how different factors contribute to different outcomes - in this case, the development of cancer. Analysis of dietary data from almost 500,000 people in Europe found only a weak association between high fruit and vegetable intake and reduced overall cancer risk.

According to Susan Jebb, of the British Medical Research Council's Collaborative Centre for Human Nutrition Research in Cambridge, the new study suggests that if Europeans increased their consumption of fruit and vegetables by 150g a day (about two servings, or 40% of the WHO's recommended daily allowance), it would result in a decrease of just 2.6% in the rate of cancer in men and 2.3% in women. Even those who eat virtually no fruit and vegetables, the paper suggests, are only 9% more likely to develop cancer than those who stick to the WHO recommendations.

On the face of it, that is quite a blow to the smug salad eaters, and the health lobby's spin-doctors were out in force in the wake of the paper's publication, to play down its conclusions. Before racing to the food-recycling bin with the contents of an ageing fruit bowl, they pointed out, there are a number of other factors that nutritionists would urge that you consider.

One is that this kind of study has attempted to adjust for every possible factor that might contribute to the relationship, and isolate only the contribution that fruit and vegetables make. This means that if people who turn away from fruit and vegetables end up eating more processed meats or foods high in fat instead, they probably will increase their cancer risk, even though the direct cause is not the consumption of less fruit and veg.

More importantly, there is still good evidence that fruit and vegetables protect against heart disease and strokes by reducing blood pressure. A separate investigation of the people involved in Dr Boffetta's study suggests that those who eat five servings a day of fruit and vegetables have a 30% lower incidence of heart disease and strokes than those who eat less than one and a half servings. It is also possible that some specific foods, such as tomatoes, broccoli and other cruciferous vegetables, do offer protective effects against particular kinds of cancer.

As a consequence, the best advice is probably still to eat your five a day. But for snivelling children and recalcitrant carnivores the fleeting thought that you might not have to was nice while it lasted. (From The Economist, April 10, 2010)

Script 48. Obesity

Does light make you fat?

When-not just what-mice eat affects how much weight they put on.

The blame for rising obesity rates has been pinned on many things, including a more calorific diet, the spread of processed food, a lack of exercise and modern man's generally more stressful lot. Something else may soon be included in the list: brighter nights.

Light regulates the body's biological clock - priming an individual's metabolism for predictable events such as meals and slumber. Previous research has shown that, in mice at least, the genes responsible for this can be manipulated so as to make the animals plumper and more susceptible to problems associated with obesity, including diabetes and heart disease. It was not known, though, whether simply altering ambient light intensity might have similar effects.

A team of researchers led by Laura Fanken of Ohio State University has cleared the matter up. As they report in the Proceedings of the National Academy of Sciences, they examined how nocturnal light affects weight, body fat and glucose intolerance (the underlying cause of late-onset diabetes) in male mice. They found that persistent exposure to even a little nighttime light leads to increases in all three.

To reach this conclusion Dr Fonken split her murine subjects into three groups. Some were kept in cages lit constantly, so as to resemble a never-ending overcast day. A second group lived in conditions akin to their natural habitat, with 16 hours of overcast day-like light, followed by eight hours of darkness. The remaining rodents were also exposed to a cycle, but the dark was replaced with a dim glow equivalent to the twilight at the first flickers of dawn.

Over the eight-week period of the experiment the mice in the first and third groups gained almost 50% more weight than those exposed to the natural light-dark cycle. They also put on more fat and exhibited reduced tolerance of glucose, despite eating comparable amounts of food and moving around just as much.

The only thing that seemed to differ was when the mice ate. In the wild, mice are nocturnal. Unsurprisingly, then, those in the quasi-natural conditions consumed only about a third of their food in the "day" phase. For a mouse exposed to the twilight cycle, however, the figure was over 55%.

In a follow-up experiment, Dr Fonken looked at whether the timing of food consumption alone could explain the observed differences. It turned out that those forced to eat during the "day" - i.e., out of whack with their biological clock - did indeed gain about 10% more weight than those fed at "night" (be it dark or just dim) or those with uninterrupted access to grub.

How this might relate to people will require further investigation. Mice and humans are physiologically alike, so a similar effect might be expected for people, but the fact that mice are nocturnal and humans diurnal is a serious complicating factor. It is true, though, that the spread of electric lighting means many people eat their main meal when natural daylight is long gone - the obverse of a mouse eating during daylight hours. And that tendency to eat late, though it has never been tested properly, is believed by many nutritionists to be a factor in putting on weight.

When the full explanation for the modern epidemic of obesity has emerged, it is unlikely that the spiead of artificial lighting will be the whole of it But this work suggests it might be a part. When you eat could be as important as what you eat. (From The Economist, October 16, 2010)

Script 49. The epigenetics of fat

Altered states

Limbering up does not just help shed fat. It also changes how fatty tissue works.

Exercise is the closest thing medicine has to a panacea. Though hitting the treadmill is more effort than swallowing a pill, the benefits are worth it. Even modest amounts of exercise protect against diseases ranging from diabetes and osteoporosis to heart attacks and senility.

Exercise works its magic in many ways. It improves the power and efficiency of the heart; it boosts the release of certain neurotransmitters (the chemicals nerve cells use to talk to each other); and it stimulates cells' garbage-disposal machinery. Now a group of researchers led by Charlotte Ling of Lund University, in Sweden, has discovered another effect of exercise. It alters the way genes work in the tissue that stores fat.

In a paper published in the Public Library of Science, Dr Ling and her colleagues report the effects of six months of moderate exercise on 23 male couch-potatoes who were in their 30s and 40s. The men were supposed to attend three workouts a week. In the event, they managed an average of 1.8. Nevertheless, besides finding the usual effects - reduced heart rate, lowered blood pressure and a drop in cholesterol levels - the researchers also observed changes in the men's adipose tissue, the place where fat is stored. Specifically, the way fat cells in this tissue expressed their genes had altered.

This is epigenetics, a rapidly developing branch of biology that focuses not on the genes themselves but rather on how particular genes behave in specific cells. Which genes are active in a cell can be changed by making chemical alterations (known as epigenetic markers) to their DNA. Such alterations let the body finetune its response to the environment, and modern gene-sequencing techniques can detect them without too much difficulty.

Dr Ling, who is interested in adult-onset diabetes (often associated with too much body fat), knew that exercise stimulates epigenetic changes in muscle cells. These alter how muscle processes sugar. When she and her colleagues looked for similar alterations in their charges' adipose tissue, they found lots – 18,000 markers distributed across 7,663 genes. This matters, because adipose tissue is not just a passive store of energy, it is also an organ in its own right, producing a range of biologically active chemicals that have all manner of effects on the rest of the body.

What all these epigenetic markers are doing remains obscure. But among the altered genes were 18 known to be associated with obesity and another 21 linked with adult·onset diabetes. When Dr Ling's colleagues picked two such altered genes and silenced them completely in laboratory grown fat cells, the cells changed, becoming more efficient at processing and depositing fat. That leads, Dr Ling notes, to the hypothesis that one reason exercise is good for you is because it improves the ability of fatty tissue to do its job. Lipids thus get stored in the right place instead of settling elsewhere in the body, where they do harm. As she observes, if you do have surplus fat it is better to have it stored in fatty tissue than in the liver or the pancreas.

This study is only a beginning. Working out which epigenetic changes wrought by exercise are important, and which incidental, will take time. But, given worries about how overweight people are becoming, and the incessant message from many governments that their citizens should take more exercise, studies like Dr Ling's should help by shining light on the way exercise actually works its magic. (From The Economist, July 13, 2013)