Who knows about Fructose?

Lucas Cranach Adam & Eve
Lucas Cranach (1526). The Courtauld Gallery (extract)

Was it a sweet or sexy temptation?

The apple that Eve pluckedSweeter than honey from the tree was sweeter than honey, or to be perfectly accurate it had relatively more of the sweeter stuff than in honey. Apples contain more fructose than glucose, and fructose is much sweeter than either glucose or sucrose (the sugar in our pantry).

Aside from the creation story, the other theory predicts that some plants acquired an advantage by evolving biochemical pathways that generated more flavorsome sugar, like fructose, in their ripening fruit. Being more attractive to eaters, helped to disperse seeds to places where they could thrive. Eve is in the apple, as fructose.

‘Fructose’ has a healthy ring, from its Latin root for ‘fruit.’ We were advised to eat an apple a day to keep the doctor away, and fructose was recommended for people with diabetes because it has a low glycemic index. But it may not be such a good prescription, and has been losing its salubrious cachet ever since high fructose corn syrup was introduced forty years ago. Glucose still glitters, which is a differentiation that seems odd at first sight because the two molecules have the same number of carbon, hydrogen and oxygen atoms.

sugar
Glucose + Fructose = Sucrose

Having identical chemical formulas does not make them the same. They are no more the same substance than genetically identical twins are the same person. Glucose and fructose are monosaccharide sugars forming in equal amounts when their parent molecule, sucrose, is digested by enzymes breaking its oxygen bridge apart. The two ‘baby’ sugars have different shapes, but when it is their turn to be digested they generate the same number of calories. But not all calories are equal.

Shape matters. Consider another sugar-lover. When yeast cells feed on the sugary mixture in unfermented grape ‘must’ they mostly prefer glucose, and as alcohol increases in the liquor more undigested fructose is left behind. That can make a wine too sweet for taste. Vintners are therefore choosy because some strains of yeast have a greater affinity for fructose which makes a drier product. Not all yeasts are equal.

Of these twins, only glucose is essential for life, although we don’t need to eat it raw because it is created by digestion of more complex carbohydrates and fats. We manage perfectly well without fructose in our diet too. Even sperm, which are nourished in fructose-rich semen, are equally satisfied when provided with only glucose.

More interestingly, our body handles the two sugars very differently. Glucose is rapidly absorbed into the bloodstream from the small intestine via a special transporter (GLUT4). It then races through the liver for delivery to every corner of the body. Under strict control by the hormone, insulin, glucose provides fuel for metabolism and growth in cells, and any surplus is converted to fat and stored in adipose tissue.

On the other hand, fructose is absorbed slowly from the gut and by a different transporter (GLUT5), and even more poorly in infants where it can cause diarrhea. Once it reaches the hepatic portal vein it stops at the liver where it is taken up into cells by a process that doesn’t involve insulin. Once inside, it is handled differently to glucose, forming glycerol as a backbone for making triglycerides.  Several studies have shown that fructose-rich diets raise both triglyceride levels and LDL small particles while lowering HDL-cholesterol, which are thought to be unhealthy signs. Since fructose is lipidinous, it potentially contributes to metabolic syndrome, including diabetes and obesity, and there is additional evidence of a role in fatty liver, gout, and inflammatory conditions. Eve was wise to offer Adam only one apple.

Until a little over a century ago, dietary sugar could only be afforded by the wealthy and powerful. No longer. Growing up with cheap and omnipresent sugar, it is easy to equate abundance with beneficence. The longest aisles in supermarkets are stacked with sodas and sports drinks full of sugars, and rows of ‘healthy’ apple juice contain a whopping 100 grams of fructose per liter. Those are the most visited aisles in stores, and conveniently located near cash registers.

sweet drinks aisle
Longest aisle in the supermarket

At home, grocery products lining pantry and fridge shelves are also saturated with sugars. But it’s hard to know how much sugar we consume by reading labels. How can we accurately compare it in different foods or brands when labels describe amounts as ‘serving sizes’ instead of ounces or grams? How much sugar is added versus natural? How much is glucose versus fructose versus sucrose? As consumers buy more processed foods instead of using raw ingredients for home cooking we are locked into choices made by manufacturers. They spoon in the sugar to increase shelf-life and palatability (Eve’s temptation).

I know how hard it is to resist sweet stuff, and harder still to give up. Perhaps fructose is hardest of all, being so sweet and stealthy. Our gut absorbs it more rapidly as we become used to it, and it doesn’t suppress the hunger hormone (ghrelin) as glucose does. We get hooked, without being satisfied.

When we were introduced to tea and coffee as children our ration was a measly half-teaspoon of sugar to make them more palatable. As soon as we started savoring the beverages, mother weaned us off the sugar, and a few weeks later the sweetness was so repellent that if we sipped Dad’s tea by mistake it made us heave. It took much longer to adjust him to unsweetened drinks. In that age, when sweetness was well-regarded in every way, children could surprise visiting aunts and uncles by teasing them: “We are teatotal, and saving our sugar ration for chocolate!”

It is now cool to cut sugar and worry about fructose, and the stigma is sticking. Robert Lustig has over five million viewers for his YouTube diatribe against fructose, and Michelle Obama was quoted as saying,”Our kids don’t choose to make food products with tons of sugar and sodium in supersized portions, and then to have those products marketed to them everywhere they turn.” We must stop blaming the fat boys and girls in class for being gluttons. With choices made for them and sweet temptations at every turn, they are casualties of a food and drinks industry focused on annual financial performance. And since the FDA is unlikely to regulate sugar in foods, the sweet tide continues to rise.

High fructose corn syrup is gradually replacing sugar from cane and beet because it is so cheap. Produced by industrial hydrolysis of starch, HFCS55 and HFCS42 are the main products for foods and beverages, while HFCS90 finds specialty uses. The number represents the percentage, so the fructose hit in HFCS is similar to 50 in granulated pantry sugar. There are important differences, however, in the source, process, farm acreage, economic and environmental impacts of subsidized corn for HFCS.

While HFCS is regarded as a new dietary demon, we have been exposed to fiendish fructose for eons, although not in any quantity until recent generations. It is unavoidable, but lower exposure through smaller serving sizes, home cooking, dilution of fruit juices, etc. can be managed over time because there is no physical addiction to sugar. Perhaps it will become the new tobacco.

Animal studies show that it would take an impossibly large serving of fructose to kill us, but that doesn’t deny a toxicity that is cumulative and insidious over time. Even the most benign substances that life depends on, like water and oxygen, can harm us when we are overexposed to them.

I imagine a naïve man visiting the seaside for the first time. He sets up his deckchair on the beach at the low water mark so his toes are wetted by a gentle ripple at the ocean edge. Two hours later, he is enjoying the warm water washing around his calves while he is engrossed in an anthology of Robert Browning. When five more hours have gone by, the soothing water is up to his waist and the open book flops on his chest at the Paracelsus poem as he dozes off. But after ten hours, a wave splashing his face wakens him, but too late to swim back.

Perhaps the metaphor is too strong, but Paracelsus would argue otherwise. He was a sixteenth century doctor and the father of toxicology. A great deal of nonsense has been attributed to him, but he rightly pointed out that “the poison is in the dose.”

Next Post: Virginia Nature Journal for January

Sweet and Sickly

Everything in moderation, including moderation. That’s Wilde … but did he really mean everything, including sugar, or was Oscar teasing us? What would he say since we consume immoderate amounts of the sweet stuff? And does it matter anyway?

granulated sugar
Sugar for a man-year

Some twenty years ago, I asked my students in Edinburgh to keep a food diary for their physiology class. Two weeks later they calculated their daily average rations of protein, fat, carbs, and micronutrients. Some of the young men consumed half of their carbs as sugar—equivalent to a 3 lb bag (1.4 kg) every week—mainly in candies, cakes, sodas, juices, bread, processed foods, and, of course, ad libitum volumes of beer. At that rate they swallowed four tons of refined sugar in a lifetime, contributing over 20 % to their total calories. The women consumed rather less of everything, but some were nonetheless so shocked that they abruptly changed their food choices, and sugar was first for the axe.

Scotland has been the land of “bread and buns” since Greenock became a Sugaropolis on the River Clyde. Ships docking after plying the Atlantic trade route from the West Indies provided a bustling trade that made sugar cheap enough for everyone to afford to excess. You can find it added to most things on your pantry and fridge shelves—from apple juice to zucchini in cans—often unnecessarily or excessive. Sugar consumption boomed throughout much of the Western World, and there was hardly ever a whimper of reproach.

Why would anyone protest? Isn’t a sweet gift a token of love? Parents, friends, and guests would buy candies, chocolate, ice cream, and candy floss (“candy cotton”) for us children, and more recently (if only in Scotland), deep fried Mars bars with a whopping 1,000 sweet, greasy calories. We were told that candy was good because it “gave us energy” (as if we were not hyperkinetic enough), and no one accused the gift-bearer of harming children. It was good for school dentists too, who labored like road workers inside our gaping mouths with jackhammers and caterpillar excavators. Ever since Queen Elizabeth I smiled a row of blackened stumps, “British teeth” have been synonymous with crumbling ruins for North American dentists.

Raw Mars bar before deep frying
Raw Mars bar before deep frying

Apart from the black mark of caries, ‘sweetness’ has resonated in our language for centuries with everything wholesome and beautiful— a sweet girl/ boy/ spirit/ victory/ life/ air/ scent/ friendship.  And Hamlet’s mother in her adieu, “Sweet to the sweet, farewell.”

Sweetness and sugar are interchangeable and both sound positive in almost every way, including financially. Sugar futures are safe bets for investors because the commodity reaches multiple markets—food, drink, fuel. And when Great Grandpa Francis took a retirement job as chairman of the International Sugar Council he was in a sweet spot. Harrowing memories of slave labor had faded, and there were none of the modern worries about environmental and nutritional impacts.

Neither did our doctors ever condemn a sweet tooth, as far as I can remember. However, unknown to us and yet not far from home there was a maverick fighting a single-handed battle against sugar interests.

John Yudkin
A book pulled from the dustbin

John Yudkin (1910- 1995), a London professor of physiology, published Pure, White and Deadly in 1972 (Sweet and Dangerous in the USA). The title reads like an Agatha Christie arsenic plot, but his book claimed that sugar is a slow poison, and that did not endear him to his profession or the industry. They strenuously barred him from guest lectureships and expert panels, although with typical British understatement, he wrote that, “relations with one or two friends in industry have occasionally become rather strained.” He also had the rare distinction of his book being condemned even before it was published: “(this book) is science fiction … and for your dustbin” (The World Sugar Research Organization).  The criticism must have pained him, because he was a “jolly man” according to one of my colleagues.

If World Sugar represented the bitter enemy in industry, Ancel Keys at the University of Minnesota was his bête noire in academia (blogpost December 21, 2014). After President Dwight Eisenhower suffered a series of heart attacks in 1955, American epidemiologists focused on the growing epidemic of heart disease, and Dr. Keys led the campaign against saturated dietary fat and for lowering blood cholesterol. Keys made the front cover of Time magazine and leaves a legacy of official dietary advice and food choices in our supermarkets.

Yudkin was a rare critic of Keys’ famous Seven Countries study of health and diet, and much else that claimed to prove a case against animal fat. He argued that the choice of countries was arbitrary, and sometimes the link with disease and obesity was stronger with sugar than fat. Moreover, the Canadian Inuit and African Masai subsisted on high fat diets (>50% of calories) consisting of meat, blood, blubber, and milk without developing heart disease, or at least until they adopted a Western diet. It was a similar story for Sephardic Jews before and after migration from Yemen to Israel. And the acclaimed Mediterranean diet, which is poor in ‘bad fats’ and rich in ‘good’ ones, happens to be low in sugar.

Rather accusingly, he said the low fat bandwagon was based on the elementary error of assuming that a correlation proves causation, and after it started rolling it was propelled by vested interests. As far as I know, he never met its architect, Ancel Keys, which was probably merciful because they might have come to blows, verbally if not worse. The bitterness went deeper than an esoteric tiff between academics because Keys had brought round his government, much of the medical profession, and the food industry to his cause. If he was wrong, there was blood on his hands—bad dietary advice to the nation would fail to roll back the tide of heart disease, and this has not happened after fifty years. As if to rub salt in a wound, Yudkin showed the correlation with disease is better for TV ownership, which is not as ironic as first sight. Heart disease is associated with all the hallmarks of affluence—sedentary lifestyle, obesity, smoking, fatty and sugary diets. The story is complex.

Perhaps he deliberately exaggerated as prophets are wont to do. He had to struggle to get attention from a profession and authorities who had turned their backs on him. Not only did he single out sugar as a chief cause of the triad of heart disease, obesity, and adult-type diabetes, but claimed it might be responsible for a mixed bag of gout, diverticulitis, dermatitis, duodenal ulcers, vision problems, and even cancer. In claiming sugar was the bogeyman of so many ailments he gave opponents a better chance to ridicule him. He wasn’t taken seriously until after his death, when another outsider stepped forward to carry the baton.

Gary Taubes in a New York Times magazine article (July, 2002) asked, What if fat doesn’t make you fat? Like his predecessor, he thought the triad was more likely caused by hormonal changes.

When glucose is absorbed into the bloodstream it stimulates insulin secretion from the pancreas. Insulin keeps glucose in check by a ‘handshake’ with a receptor on cells that opens a gate for glucose to enter where it is burnt for energy or stored as fats, to excess if sugar and insulin remain high. How the metabolic balancing act leads to a spectrum of disease is still being worked out, but its disorders seem to be related to the aging process. While studying worms in her lab at the University of California, Cynthia Kenyon found that insulin-like genes switched on by a sugary diet shorten their lifespan. After her discovery, she switched to a low glycemic diet.

Mother’s rule at the meal table was wiser than she knew. My brothers and I regarded the savory course as something to struggle through before we were rewarded with a sweet dessert. We were never allowed to reverse the order. The protein and fat lying heavy in our stomachs when the sugar came down the chute delayed gastric emptying, slowing its path into the small intestine for absorption and curbing a rush of glucose into the blood. Likewise, she forbad candy between meals, which avoids an unnecessary glucose spike, although her rationale was to dodge the dentist.

Yudkin also admitted struggling with a sweet tooth when young and an expanding waistline in mid-life. He slimmed by switching to a low-carb diet, which was a long time before we heard about the Atkins diet. But he wasn’t the pioneer of low carbs; that credit belongs to a Victorian Londoner, who, as a coffin-maker, knew something about corpulence. William Banting (1796-1878) found a low-carb diet helped him to slim, and he broadcast his discovery in a book that sold well, if not in medical circles. By an odd twist of history, one of his descendants won the Nobel Prize in 1923 for the discovery of insulin. Banting’s formula was close to the modern paleo diet, which I will return to in another blogpost.

Yudkin might chuckle now that sugar is portrayed as the new tobacco. You know the climate of science has changed when America’s First Lady and Dr. Oz have taken theories on board, even if the originator is forgotten.

But how could so many experts be so wrong for so long? Science is the most objective path to knowledge, but still a human endeavor. When a complicated case is heard in the court of science the judgment depends not only on the evidence presented but on the outcome of a clash between the prosecutor and defending attorney. Ancel Keys would have made a very persuasive trial lawyer and, more importantly, nutritional science makes hard cases.

Nutrition has been called kitchen science as one of the softer life sciences. It may look like a pure, white meringue with a hard crust, but squeeze it and you find a soft, gooey center. The more complicated the subject the greater the uncertainty, and the chemical complexity of food is compounded by the genetics and lifestyles of diners. And unlike testing a new drug, it is almost impossible for a study to strictly control the diet of its subjects long enough to reveal divergences in health. Consequently, we have a smorgasbord of slimming diets and food fads which are hard to prove or dismiss.

I favor Michael Pollan’s commonsense philosophy: “Eat food/ Not too much/ Mostly vegetables” (In Defense of Food). He applauds food that is not highly processed, farming practices with environmental integrity, and diets based on moderate food choices that reduce glycemic carbs. But it may not have appealed to Oscar Wilde who loved sweetmeats, and his father, Dr. Sir William Wilde, made his fortune in the sugar industry.

Next Post: Who knows about Fructose?