Data Diva: Sugar Metabolism & Homeostasis

sugarData Diva: A series in which I attempt to apply science, fact, and most of all, common sense, to dietary issues of the day.

The Sugar Series

Chances are, if you’re alive and in the world today, you’re heard a lot of alarming “facts” about what happens to the food that you eat once it enters your body. Sugar that you eat turns directly to fat! Carbs turn into sugar! Fructose is making you fat! High fructose corn syrup is killing you! Like all great lies, these “facts” tend to have a kernel of truth, just enough to make it believable, wrapped up in a festive package of hyperbole, fear-mongering and guilt-shaming. Why? Because fear sells.

Do me a solid: the next time you read one of those sensationalist articles about how wheat makes you stupid or legumes are poisonous, look for the man behind the curtain. Chances are, he’s got something to sell you. A diet plan, a book, “nutritional supplements,” meal replacement shakes, an iPhone app: you name it, if it’s related to food and how we eat, you can make money off of it. And the best way to make money? Fear. (X food is killing you!) Guilt. (X food is killing your family!) Shame. (How can you still be eating X food?!) The holy trinity of modern marketing. Now, I’m not saying that everyone who has a book to sell (or blog traffic to promote) is a lying, manipulative quack. What I am saying is that, if they are using fear as a primary motivator, they are a lying, manipulative quack.

science-newsThe good news is, it’s not so hard to tell the truth from the quackery: you just need a little knowledge. Knowledge is power, as they say, and in this case, it’s the power to turn that fear into eyebrow-raising skepticism (and in some cases, a full-on snort-guffaw). To gain some insight into what happens to sugar after you eat it, we turn to our good friend biology and her BFF chemistry. If you’ve read Part I, you understand the basic chemistry behind sugars & carbohydrates. Now, it’s time to understand the biology: what happens to those illustrious monosaccharides, glucose & fructose, once they enter the body?

CARBOHYDRATE METABOLISM & HOMEOSTASIS

Glucose is the primary energy source for all living cells. Therefore, carbohydrate metabolism and blood glucose concentrations are tightly controlled, with layers and layers of redundancy and series of complex chemical reactions that can overlap, interact, and proceed in both directions. Many of the “truths” that spawn wild theories about sugar’s role in the body come from examining a small snippet of the whole process in detail; as such we need to drill down in some detail to examine whether the claims have any basis.

Say you enjoy a tasty snack of an apple and a handful of pretzels. In a simplified overview, here’s what happens:

  1. Digestive enzymes in your mouth and small intestine begin to break down (catabolize) starch in the pretzels and sucrose in the apple into monosaccharides (glucose and fructose).
  2. Glucose is absorbed through the gut wall, rapidly distributed to cells in the body, and either: broken down via glycolysis to yield energy (ATP); converted to glycogen for storage (primarily in liver and muscle); or converted to fat via glycolysis and fatty acid synthesis and stored as adipose tissue. Postprandial (after a meal) increases in blood glucose trigger release of insulin from the pancreas: insulin mediates glucose disposition.
  3. Fructose is absorbed through the gut wall and primarily taken up by the liver. From there, fructose can be either: converted to glycogen for storage in the liver; converted to fructose-1-phosphate and enter the glycolysis pathway to yield glucose or ATP; or converted to triglycerides, transported out of the liver, and stored as fat. Insulin is not involved in fructose metabolism or disposition.
  4. Blood glucose concentration is tightly controlled by the hormones insulin & glucagon, produced by the pancreas: insulin is responsible for lowering blood sugar, by distribution to cells and other mechanisms, while glucagon is responsible for raising blood sugar, by promoting the breakdown of liver glycogen and the production of new glucose (gluconeogenesis).

heroinKERNEL OF TRUTH: carbohydrates turn into sugar.

Yes, they do. As long as you take “turns into” to mean “already are.” Because, as we know, simple carbohydrates are sugar, and complex carbohydrates, like those in pasta, bread, potatoes and rice, are starches made up of many, many sugar molecules, which are broken down by digestive enzymes to monosaccharides (mainly glucose) prior to absorption across the gut wall.

So, yes: carbohydrates turn into sugar just as protein turns into amino acids (which can also turn into sugar) and fat turns into fatty acids (which can also turn into sugar). Basically, everything turns into sugar, or in this case, glucose. For which we should be profoundly grateful.

KERNEL OF TRUTH: glucose and fructose are metabolized and used differently by the body. Therefore, fructose is evil.

Yes, it’s true: despite sharing the same chemical formula, C6H12O6, and similar chemical structures, glucose and fructose are treated quite differently once they enter the gut. Glucose is the golden child: the most important fuel for the human body (and, indeed, for all living organisms), glucose gets the VIP treatment, ushered behind the velvet rope of the gut wall by active transporters (sodium-glucose transport proteins, or SGLT1/2) that make sure that no dietary glucose goes to waste. Once glucose is within the epithelial cell of the small intestine, the bouncer at the back door (GLUT2) is quick to let her pass into the bloodstream, a process that is independent of how much glucose is already there (i.e. blood or plasma glucose concentration).

Graphic from Biochemistry for Medics.

Graphic from Biochemistry for Medics.

Fructose, on the other hand, is the Jan Brady of monosaccharides. While glucose gets the white glove treatment, hustled through the gut wall and into the bloodstream by solicitous (and highly paid, in terms of energy use) handlers SGLT1/2, fructose has to make do with gradient-mediated diffusion (i.e. when there is more fructose in the gut than in the blood stream, fructose will move across the gut wall into the blood), facilitated by the unpaid intern GLUT5. Because energy derived from fructose is not nearly as important to the body as that derived from glucose, fructose absorption is capacity-limited: i.e. when you run out of unpaid interns to shepherd fructose across the gut wall, any excess fructose in the gut is eliminated as waste. Studies suggest that an average person can absorb about 25 grams of fructose at one time, about the amount in a cup of apple juice or a can of soda.

Image from Fructose in perspective byRichard D Fein man and Eugene J Fine.

Image from Fructose in perspective byRichard D Fein man and Eugene J Fine.

Glucose, once absorbed, is rapidly taken up by cells in the body, primarily muscle, brain & CNS, a process that is mediated by insulin, and within those cells, converted to energy through glycolysis (smooth-jazz-rap optional) or stored as glycogen. The  majority of fructose, however, is taken up by the liver and metabolized by the enzyme fructokinase, which converts fructose to fructose-1-phosphate, which in turn enters biochemical pathways to become glucose (>50%), glycogen, or triglycerides.

From “Fructose in Perspective” by Richard Feinman:

Whether dietary fructose… has unique effects separate from its role as carbohydrate, or, in fact, whether it can be considered inherently harmful, even a toxin, has assumed prominence in nutrition. Much of the popular and scientific media have already decided against fructose and calls for regulation and taxation come from many quarters.
In terms of public health, a rush to judgement analogous to the fat-cholesterol-heart story is likely to have unpredictable outcome and unintended consequences. …Also, nothing in the biochemistry suggests that sugar is a toxin.

Preach it, brother. Yes, glucose and fructose metabolism is different. But at least half of dietary fructose ends up as glucose, another chunk gets converted to glycogen for storage in the liver (just like glucose does), and the rest becomes triglycerides. A misunderstood half-evil/half-golden child? Maybe there should be an X-Men character named “Fructose.”

sugar-lickKERNEL OF TRUTH: dietary sugar turns into fat.

Yes, it’s true. Technically. But a more accurate way to put it would be to say that excess dietary sugar is stored as fat. That is: absorbed glucose will first be distributed to cells (via insulin) to satisfy cell energy needs; remaining glucose after immediate energy needs are satisfied will be stored as glycogen; remaining glucose after that will be converted to fatty acids and stored as fat. It’s obviously not that simplistic: there are complex feedback mechanisms, regulated by various hormones, and complex biochemical pathways that overlap and interact. But the body’s first priority is to supply adequate energy to cells: energy stores are a relative luxury.

It’s important to remember: the same general process can be applied to every food you eat, whether it is carbohydrate, fat or protein. When you consume excess calories – that is, more calories than your body needs to satisfy energy requirements (exercise, activity, and the energy required to maintain your bodily functions at rest, a.k.a. the resting metabolic rate) – that extra energy will be stored, no matter what form of calories were consumed. Excess energy will be stored first as glycogen, then, once the cells’ relatively small storage capacity for glycogen is full, as fat.

There is a persistent myth that excess dietary protein cannot be turned into fat. Pardonnez mon français, but: bullshit. As we learned above, any consumed food that is not immediately necessary for bodily functions can be converted to glucose and stored as glycogen or fat. Protein is no exception: excess amino acids that are not required to build proteins for use in the body can (and will) be converted to glucose and stored as glycogen or fat. Amino acids cannot be stored directly in the body, thus they are degraded (in a complex web of 20 potential pathways) prior to storage.

citrus-layer-cakeKERNEL OF TRUTH: blood sugar spikes will kill you.

Yes, it’s possible: if you’re diabetic. And you can’t bring that blood glucose concentration down with insulin or one of the many other glucose-controlling medications prescribed to diabetics. If you are not diabetic, which, despite the high incidence of diabetes in the US still accounts for >90% of Americans, blood sugar “spikes” will be controlled by insulin.

Once glucose is absorbed into the blood, the resulting increase in blood glucose concentration triggers the release of insulin from the pancreas. Insulin and glucagon are at opposite ends of the hormonal homeostasis see-saw that works to keep blood glucose at a relatively constant, ideal concentration (typically between 70 – 100 mg/dL in a fasted healthy adult, with increases up to 140 mg/dL after a meal). Insulin is like your bossy, OCD, overachiever friend; the one who makes 42 perfectly-rolled fondant cupcakes for the school bake sale and manages to close a multi-million dollar deal via satellite phone while on a yoga retreat in Papua New Guinea. Her job is to make sure blood glucose concentrations don’t get too high (another Kernel of Truth: high blood glucose concentrations are indeed toxic), while glucagon’s mission is to keep blood glucose from getting too low (also dangerous).

Insulin, like any good multitasker, has a number of ways to get her job done: 1) in the liver, insulin stimulates production and prevents breakdown of glycogen; 2) in the liver, insulin also stimulates glycolysis (the breakdown of glucose) and inhibits gluconeogenesis (the formation of new glucose molecules from component parts within the liver); 3) muscle represents an important “sink” for glucose storage, absorbing 80 – 95% of sudden increases in plasma glucose; insulin facilitates this glucose storage by translocating GLUT4 transporters to the plasma membrane of muscle cells, thereby allowing a massive increase in glucose uptake and subsequent decrease in circulating blood glucose levels; 4) in adipose tissue, insulin stimulates glucose uptake by increasing the rate of transport and the number of transporters (GLUT4 and GLUT1) on adipose cells. Phew! Insulin deserves a cocktail. Maybe two.

While there is some evidence that intermittent spikes of high blood sugar can cause damage to the insulin-secreting ability of rat pancreatic beta cells, let’s put this in perspective: the high concentration of glucose applied to the rat islet cells (16.7 mmol/L) is approximately equivalent to a blood glucose concentration of   300 mg/dL. In a person with a normally functioning pancreas, even a whopping 75-gram load of glucose (from a clinical diagnostic test known as an oral glucose tolerance test, or OGTT) produces only 120 – 140 mg/dL glucose concentrations. A similar oral glucose dose in a diabetic typically produces blood glucose around 200 mg/dL. A concentration as high as 300 mg/dL can result in shortness of breath, vomiting, and loss of consciousness.

my-brain-hurtsConfused yet? Well, take your time: read it over once or twice, give it time to sink in. Feel free to ask me questions: I’ll answer them if I can, or point you in the right direction for further learning. And be sure to tune in for Part 3 when we tackle the Main Event: Sugar & Disease. Fasten your seat belts!

Notes: As much as possible, I’ve linked key data or assertions to relevant sources. I’ve tried to avoid Wikipedia, but sometimes it does offer the most succinct and cogent overview for the non-scientist. All images that are not mine are linked directly to their source. I’ve read this through at least a dozen times, but it’s a complex topic and there may be an error here or there. Feel free to shout it out if you catch one and I’ll be happy to correct.

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11 comments

  1. I am thoroughly enjoying this series. I have a son who is a vegan, eating mostly raw fruits and veggies, some cooked. He also eats some pasta, rice and beans on occasion because he could not get full no matter how many bananas and smoothies he ate and drank (I bet you’ve seen those ads that tell you bananas will make you fat – well, my son goes through a almost a case of them every week and it’s not enough)! Then I have a daughter and granddaughters who eat way too much sugar in the form of candy and sweets like cake and cookies. Allergies are a problem with one of them allergic to fruits and most veggies (my son’s diet) and does not like meat. All that’s left is pasta, rice, potatoes and sweets! Two are sensitive to wheat and one is a vegetarian (skipping many of the veggies but eating lots of bread). Polar opposites just about with me right in the middle. I keep waiting to see who gets fat, who does not, who gets sick and who does not. My daughter is a bit overweight and I am about 20 pounds over my ideal weight. The girls and my son are all very lean and almost skinny. Sugar is brought up as totally evil by my son and my daughter’s husband and his family (desserts were NEVER served in my son-in-law’s family home! I know my daughter could serve more nutritious food than she often does and they do eat an enormous amount of candy as compared to many people. I guess I am rambling. I just want to say I appreciate your series. Sugar plays a very large role in my family and it’s nice to be armed with real knowledge about it.

    • Oh my! Family meals at your house must be challenging at best.

      I think part of the problem is that people want absolutes: sugar is BAD, protein is GOOD, salt is BAD, water is GOOD. The point is, biology just doesn’t work that way. Most things have a sweet spot – the tip of a bell-shaped curve – that is optimal: too little is not good for you, too much is not good for you, the Goldilocks Zone is just right. In reality, the age-old advice “everything in moderation” would serve us all quite well. It’s just that nobody wants to hear it.

      And you’re right: I can remember (back when the Zone diet was big, maybe?) when bananas were declared “evil.” Pretty sure a snort-guffaw was involved. :)

    • cel

      I follow the 801010 lifestyle by dr douglas garaghm and it sounds like the diet you son is eating! fruits and veg have all the sugar, minerals and nutrients we need to thrive and glow. i eat a high carb/high sugar low fat diet and im the leanest, fittest and healthiest ive ever been! thank you for debunking the ‘horrors’ of sugar. those on paleo diets or low carb deprivtion are starving their bodies from natural fruit/sugars needed to survive a healthy and high energy life!

  2. I can’t say much for the science, but this was a fantastically informative and honest take on the whole sugar “problem”. What might you have to say about the psychology of eating sugar more generally (Addictive qualities wether real or imagined, the whole idea of a meal after the meal that is sweet–desserts, etc). You have dove into the science (chemistry and biology) and media frenzies on the topic, but what about the socio-behavioural aspects? Perhaps your Berry cartoon says it all, heroin or carbs.

    My sister and I just took on a one week, no sweet food or no added sugar challenge, which was insanely difficult. Without a doubt the difficulties we faced during this challenge, that is essentially trying to get to that point of moderation which you insist on and I would concur, are excruciatingly difficult to overcome. I have no doubt that the main challenge here was our own habitual patterns (socially or personally instilled) of consuming “sweets”.

    • Sugar as “addiction” is definitely on the table for the next installment, and you touch upon an important point: addiction itself is difficult to define, and experts continue to argue about whether it is physical, psychological, social or all of the above. Psychology Today does a nice job of briefly explaining the issue: http://www.psychologytoday.com/basics/addiction

      I do know that almost all habits are hard to break “cold turkey.” I don’t see why sugar should be any different. Personally, I’ve never had much of a sweet tooth: I enjoy sweets, but rarely crave them. But I know that my palate has become more sensitive to sugar in the last 6 or 7 years of eating locally. Eating a primarily local diet does include lots of home-cooking and very little (if any) supermarket food. So while I will make cookies & scones, cakes and desserts now and then, and I enjoy them, when I have something that I used to enjoy years ago (like a recent Good & Plenty binge) I tend to find it MUCH sweeter than I remember.

      I often tell people who are trying to make a change in their diet to allow themselves the thing that they are craving: just make it from scratch. I love, love, love potato chips, but if I could only have them made from scratch, I’d probably only eat them 2 or 3 times a year. Somehow, I think knowing that you CAN have cinnamon rolls or cake or brownies any time you want them – you just have to make them yourself – takes half of the urgency away from the craving. And then, if you do go ahead and make brownies and enjoy them; well, what’s so wrong with homemade brownies? Not much, IMO. Not much at all.

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  4. Marisa

    I am so grateful for this series. I have been abiding by the everything in moderation approach for a while-I ferment things here and there, soak this and that, and try to cook with less refined sugar overall. At the same time, I want my kids to be able to eat at a friend’s house without getting sick because they’re not used to the food. I love the Hank Shaw line “Homo sapiens is designed to eat a little of a lot, not a lot of a little”.
    I will need to read and reread this series to try to better understand it-hopefully take in 10% at a time-it’s pretty overwhelming!! I’m wondering if you are familiar with/have an opinion on Gary Taubes’ work? He spoke at a behavior analysis convention I attended for work, and the case he presented over the hour he spoke was pretty compelling, and it seemed to have scientific validity, yet I’m always worried that I don’t employ enough eyebrow-raising skepticism. Thanks again!

  5. EL

    Love the p-value on the first cartoon. Despite what the cartoon says, I would say that there’s no correlation with that one — poor stats and science!!

  6. EL

    Hi Kayla:
    So there is a new study just out in Nature, linking sugar substitutes with obesity thanks to the intestinal microbiome (which I study). It is really cool (but also really disturbing). In light of this study, it may make sense that the form that sugar takes could affect how it is used/absorbed (and all because of the denizens in your gut. . . ).

    Thought you might like this and it does go here, even if this is old now.

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