Reactive Hypoglycemia

When we think about blood glucose, we usually think about hyperglycemia, or excess blood glucose. But sometimes we can have too little glucose in our blood. The symptoms are lightheadedness, anxiety, and hunger. Low glucose can even produce shakiness and heart palpitations. This post discusses one of the causes of low blood glucose, reactive hypoglycemia.

Reactive hypoglycemia is important because it can be one of the steps on the path to type 2 diabetes. It is one of the possible responses to a six-hour glucose tolerance test, illustrated in the graph above. The normal person, represented by the red line, has ingested a large bolus of glucose at zero hours. The beta cells of his pancreas have released the appropriate amount of insulin, and while the amount of glucose in his blood has spiked a little, within 2.5 to 3 hours it has come back into the normal range of 70-110 mg/dl, which corresponds to a value between 4 and 6 mmol/L on the graph above. Once the extra glucose has been safely stored, insulin levels decline and the liver takes over.

As discussed in the previous post, the liver can release its stored glycogen in the the form of glucose, and it can also make glucose by gluconeogenesis. Between meals, the liver uses these two processes to keep blood glucose in the range between 70-100 mg/dl or 4-6 mmol/L.

After a person eats carbohydrates, his liver shuts down its production of glucose via glycogenolysis and gluconeogenesis. That makes sense. If the person is ingesting glucose, why would he want to add more glucose to that amount?

When a person eats protein, the situation is a little different. Insulin must be released to store the amino acids building blocks of the protein. But insulin is nonspecific. As it promotes the storage of amino acids, it will also drive glucose from the blood. Without some compensatory mechanism, the process of storing the amino acids would also produce severe hypoglycemia. In steps the pancreas. This time the alpha cells of the pancreas release the hormone glucagon. Glucagon tells the liver to release some of its glycogen in the form of glucose. The liver also begins to do gluconeogenesis to make more glucose. Thanks to the liver, glucose levels can be maintained while insulin is busy telling the body to store its new supply of amino acids. Once the nutrients are stored, the liver goes back to its baseline functions and enables the blood sugar to continue in its normal range.

So far, so good. But as diabetes develops, the liver is one of the organs that becomes insulin resistant. When the liver becomes insulin resistant, its production of glucose becomes dysregulated. The liver can no longer turn off its glucose output in response to carbs, or regulate its glucose output properly in response to protein.

Think about that. The person with insulin resistance may not be eating carbs, but his liver is making carbs (that is, glucose) all the time. In order to control the resultant high blood sugar, the pancreas must produce more insulin. That will get the blood sugar down in the short term, but in the long term it will make the liver more insulin resistant. Eventually, still more unwanted glucose will be produced by the liver, and even more insulin will need to be released by the pancreas.

In the process, the pancreas itself starts to suffer insulin resistance. It releases insulin erratically. Sometimes it allows the blood sugar to go too high. At other times the pancreas overshoots the required amount of insulin and the blood sugar drops too low. This leads to the phenomenon called reactive hypoglycemia, which is shown in the black line in the graph above. The person represented by the black line has ingested a large amount of glucose, but his pancreas has responded by releasing too much insulin, and his blood glucose has fallen below the normal range. Over time, reactive hypoglycemia can eventually progress and intensify to the condition of the person represented by the brown line, which is prediabetes.

We tend to think of type 2 diabetes as a condition characterized by high blood sugar. It is, but for many people, one of the steps on the road to type 2 diabetes is actually low blood sugar. If a person is not a diabetic but is experiencing episodes of low blood sugar, it might be time for him to consult a physician. It could be a important warning sign and an indication that he might need to make some changes in his lifestyle.

The figure is from the Hypoglycemic Health Association of Australia.

Glucose, Glycogen and Gluconeogenesis

We have glucose in our blood at all times. Where does it come from?

The first and most obvious source is from the carbohydrates in our food. Most of the complex carbs we eat, from sugar to pasta, can be broken down into glucose monosaccharides and will be absorbed into the circulation in that form. The illustration above is taken from page 329 of Lippincott's Illustrated Reviews-Biochemistry. It shows the effect of a meal of 100 grams of pure glucose. The large spike of glucose is metabolized or stored within about three hours.

If we do not eat any more food after that 100 grams of glucose, our blood glucose levels nevertheless must be maintained. If we are well-fed, our livers store about 80-100 grams of glucose as glycogen. The liver is able to convert glycogen back into glucose by means of a process called glycogenolysis. The blue line on the graph shows that, over the next few hours, the liver releases glucose back into the blood on an as-needed basis.

What if we continue to fast? Eventually, we run out of liver glycogen. If you look at the green line in the graph, you'll see that it gradually rises. This line represents gluconeogenesis, which we have discussed before. In the absence of ingested carbohydrates, and even after our liver glycogen is depleted, our liver is able to make glucose out of glycogenic amino acids and the glycerol backbones of fatty acids. It takes several hours or even days for this process to ramp up.

What if we are not fasting but are simply low-carbing? The ramping-up of gluconeogenesis is one of the reasons that people who are new to low-carbing experience something called the "Atkins flu" when they start eating 20 grams of carbs or less per day for the first time. They are not starving, but their bodies have to get used to manufacturing new glucose out of amino acids and glycerol rather than absorbing ready-made glucose from the gut. Once gluconeogenesis is established, our bodies can readily make glucose from the protein we eat.

However, even when it is well established, gluconeogenesis is not a quick-response system. Because it takes us several hours to digest a protein meal into its constituent amino acids, followed by more time to convert the amino acids into glucose, the process of gluconeogenesis is relatively slow. However, the glucose we produce can be used to replenish the glycogen in the liver, and liver glycogen is a quick-response system.

Once we are adapted to a low intake of carbohydrates, we have two means of stabilizing our blood sugar. Gluconeogeneis provides a baseline of glucose production from the protein we eat. Because the fuel needed for gluconeogenesis ebbs and flows, the new glucose made by this process ebbs and flows. Fortunately our stored liver glycogen is available to make up the difference, assuring a steady stream of glucose for baseline functions for our brain, red blood cells and other tissues that require glucose as fuel. If we need an extra burst of energy, or if a big protein meal causes our insulin to spike and our glucose to plummet, our stored liver glycogen is also there to step in the gap and provide the glucose necessary to keep our blood glucose within normal limits.

When we first start low-carbing, it's hard to understand that (if we choose to) we never need to eat another gram of carbohydrate again. But once our good friend the liver is adapted to the process, it can provide all the carbs we need through gluconeogenesis and glycogenolysis.

Comfort Food

Even though the media and the medical commmunity have generally been skeptical of the low-carb lifestyle, many people now know that low-carbing is a healthy way to live and an excellent way to lose weight.

But what about people who know that low-carbing is a healthy lifestyle and DON'T choose to follow it, even though the consequences are significant? Why would they go ahead and indulge in food that is high in carbohydrate and low in nutrition instead of being careful about their food choices? Specifically, how can a person deliberately choose:

• Comfort food plus diabetic retinopathy (i.e.,blindness)?
  
  
• Comfort food plus erectile dysfunction?
  
  
• Comfort food plus a lifetime of diabetes medication?
  
  
• Comfort food plus death from heart disease?
  
  
• Comfort food plus a degree of obesity that puts their livelihood in jeopardy?

People who understand low-carbing, understand that low-carbing has a good track record of improving all of those health conditions. In light of that, why do so many of them either not follow or stop following the low-carb lifestyle? The answer could be serotonin. Serotonin is a neurotransmitter, or signaling molecule, found in the brain. It has many actions, but one of them is modulation of mood. If we don't have enough serotonin, one result is that we can become depressed.

Serotonin is manufactured in our bodies from a large neutral amino acid called tryptophan. Tryptophan is one of the amino acids found in the protein we eat. So if we're depressed, why can't we just eat more tryptophan to drive the production of more serotonin?

As you might expect, it is not that simple. Tryptophan is too large to diffuse into the cells in our brain by itself. For our brain cells to take it up, tryptophan must be carried into the cells by means of a transporter. The problem is, tryptophan has to compete for transport with the other large neutral amino acids--phenylalanine, tyrosine, isoleucine, leucine and valine. Tryptophan tends to get lost in the shuffle.

How, then, can we get extra tryptophan into our brain? Amazingly, the answer is insulin. If we eat a meal or a food high in carbohydrate, insulin will be released and will sweep the other large neutral amino acids out of the blood and into our muscles. However, tryptophan is different. It will tend to stay behind and bind to albumin in the blood. But once the albumin-bound tryptophan reaches the capillaries of the brain, the transporters there will be ready to take up the tryptophan, increase the brain concentration of it, and drive the synthesis of serotonin. The result? A pervasive feeling of sleepiness and contentment.

For people who are anxious or depressed, this is a hard feeling to walk away from. What if we knew that a temporary fix for our bad feelings was right inside the freezer or refrigerator or cupboard? No prescription necessary. The comfort food found in our pantries might not be the best choice for us in the long run, but we have to realize that sometimes our eyes won't stay focused on the long run. The bad feelings will come. The comfort foods will always be available. Recognizing that, this might be a time for all of us good low-carbers to sit down and plan a strategy that provides comfort when we need it, but doesn't rely on comfort food.

Is the Tide Turning?

See that logo? The New England Journal of Medicine is one of the premier scientific journals in the world. It is in the top tier of the top tier of medical journals.

Contrary to popular opinion, it is possible to get mediocre research published. You can present a preliminary poster of your findings at a scientific meeting and it will appear in a volume summarizing all the posters from that meeting. You can submit your manuscript to a journal that will simply print it for you without any pesky review by your scientific peers.

But if you want credibility for your work, you send it to a respected journal where two or more qualified scientists will analyze it, tear it apart and ask you many questions about how you can back up your claims. The more respected the journal, the more likely that your submission will not pass muster and will be returned to you for submission elsewhere. In the scientific world, it's not just "publish or perish." The quality of the journals in which you publish is also extremely important.

For that reason, it is very significant that on July 17, 2008, the New England Journal of Medicine published an article entitled Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet. The study enrolled 322 Israelis (men and women, average age 52, diabetic and non-diabetic) who worked at a nuclear research facility and were moderately obese. They were divided into three groups.

The Low-Fat group adhered to the guidelines of the American Heart Association (AHA). They ate 30% fat, and were permitted very little saturated fat and cholesterol. Men were limited to 1800 calories per day and women were limited to 1500 calories per day.

The Mediterranean Diet group ate 35% fat, mostly in the form of olive oil. They ate lots of vegetables and were instructed to get their protein from chicken and fish. Men were limited to 1800 calories per day and women were limited to 1500 calories per day.

The Low-Carbohydrate group ate 20 grams of carbohydrates per day for two months, followed by a gradual increase to a maximum of 120 grams of carbs per day. Participants were told to choose vegetarian sources of fat and protein. Daily calories were not limited.

The results were not unequivocally in favor of the Low-Carb group. They had the poorest long-term adherence rate to their diet (78%). Their fasting plasma glucose levels did not improve. Their blood pressure, LDL cholesterol, insulin and leptin levels and high molecular weight adiponectin all improved, but there was no significant difference in the degree of improvement among the three diet groups.

Compared with the other two groups, the Low-Carb group did see a significant drop in their weight, in their glycosylated hemoglobin, and in their ratio of total cholesterol to HDL cholesterol. In several other markers, the Low-Carb and the Mediterranean diet groups were not different from each other, but showed significant improvement over the group following the AHA-recommended Low-Fat diet.

One of the criticisms made against the low-carb diet is that it might not be safe or effective in the long term when compared with the standard American Heart Association low-fat diet. This study specifically addressed that question. It is notable that in the Discussion, the authors of this article state, "In this 2-year dietary-intervention study, we found that the Mediterranean and low-carbohydrate diets are effective alternatives to the low-fat diet for weight loss and appear to be just as safe as the low-fat diet." The wobble you just felt was the tide turning.

This study has received wide publicity in print and on television. It is possible that, at long last, the medical community and the media are beginning to question the dogma that the only healthy diet is a low-fat diet.

Fructose II

Sucrose, also known as table sugar, is a disaccharide. In the gut, it is split into its constituent monosaccharides--glucose and fructose. Sucrose is frequently replaced by high fructose corn syrup (HFCS) in commercially prepared foods and soft drinks. High fructose corn syrup is a mixture of about 45% glucose and 55% fructose. You probably knew all of that already.

The important thing about sucrose and HFCS is that they are the main sources of fructose in the American diet. As we saw in the previous post, when fructose is metabolized in the liver, it is most likely to be broken down into glycerol 3-phosphate and acyl-coA, which are then assembled into triglycerides, i.e., fat.

Eat fructose, create fat. But that's not the end of the story. Fructose increases glucose metabolism in the liver by mobilizing an enzyme called glucokinase. The liver takes up more glucose than it normally would, and the excess glucose is also synthesized into fat.

In addition to fructose-induced lipogenesis, other long-term effects of fructose have been observed in experimental animals and in humans. Although fructose produces a very small insulin response, long-term use of fructose nevertheless induces insulin resistance, which eventually results in fructose-induced hypertension. Somewhat surprisingly, the low concentration of insulin released after fructose ingestion also means that there is a low satiety response to fructose. It is possible to consume a great deal of fructose without feeling full. Finally, fructose is 10-17 times more effective than glucose in producing Advanced Glycation Endproducts--the crosslinked matrix of proteins and sugars that accumulates in our tissues and stiffens them.

In 1960, the average American consumed approximately 110 pounds of sweeteners per year, mostly in the form of cane and beet sugar. Since then, the use of table sugar has declined, but the use of high fructose corn syrup has more than replaced it. Americans now consume an average of over 140 pounds of sweeteners per year. Because half of those sweeteners by weight is composed of fructose, the potential negative health effects are worth serious consideration.

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If you're interested in learning more about fructose metabolism:
Medbio
Hyperlipid

Fructose--Not as healthy as it appears to be

What if there was a food that could easily be converted to fat in your body? You would think that that food would be on the list of substances to avoid among those who are weight-conscious. You would be wrong.

Fructose is the sugar is found in most fruits. Like glucose, it is a simple sugar, but our bodies handle fructose in a special way. Look at the diagram below, which appears in Fructose, weight gain, and the insulin resistance syndrome by Sharon Elliot and coauthors.

The metabolic pathways for glucose are on the right side of the diagram. Note that there are many steps between glucose and the final product in this figure--acyl glycerols (triglycerides) which are packaged into VLDL (Very Low Density Lipoproteins) and sent out into the body for storage as fat. Depending on the body's needs, glucose can be used for energy via glycolysis and the citric acid cycle, and it can be stored as glycogen. If glucose is present in excess, it can be converted to triglycerides in the liver, but that is only one of many options.

For fructose, there are fewer choices. Fructose by itself does not stimulate insulin release. If insulin is low and glucagon is high, fructose can enter the gluconeogenesis pathway and be turned into glucose. But we seldom eat pure fructose. If we eat fructose with other carbohydrates, or if we eat it in the form of table sugar, the more likely situation is that insulin will be high and glucagon will be low. This will direct the fructose to be converted into the intermediates for fatty acid synthesis, and then into triglycerides. The result will be a phenomenon called fructose-induced lipogenesis.

Photo of apples: FreeDigitalPhotos.net

Reversing Insulin Resistance

It is commonly thought that weight loss is required to reverse insulin resistance. A small study of obese type 2 diabetics indicates that this may not be the case. Ten diabetic patients, seven of whom were on diabetes medications, checked into a hospital with an average weight of 252 pounds. For seven days they acted as their own Control group. They ate their normal diets, averaging 3111 calories and 309 grams of carbohydrate a day. On day 7 their blood glucose and blood inuslin levels were measured over a 24 hour period. The time course of glucose and insulin is represented by the black circles in the graphs below.

On day 8 the patients remained in the hospital and became the Low-carbohydrate diet group. They were switched to a low-carbohydrate diet which included 21 daily grams of carbohydrate, plus as much fat and protein as they desired. Adherence to the low-carbohydrate diet was confirmed by measurement of urinary ketones. After two weeks on this diet, blood glucose and blood insulin levels were again measured over a 24 hour period. The time course of glucose and insulin after two weeks of eating low-carb is represented by the blue circles in the graphs above. (For the sake of reference, the 6mmol/L Glucose Level is roughly equivalent to a glucometer reading of 100 and the 8 mmol/L Glucose Level is roughly equivalent to a reading of 150.)

There were no set mealtimes, so all of the curves are fairly flat. Nevertheless, it is easy to see that a diet of 309 grams of carbohydrate a day produced high glucose levels around the clock and high insulin levels during waking hours. By contrast, just two weeks of eating 21 grams of carbohydrate a day brought blood glucose levels to a normal range and kept insulin levels low both during waking hours and at night.

Other measures of insulin resistance reflected the values shown in the graphs. In just two weeks on the low-carbohydrate regimen, glycosylated hemoglobin fell from 7.3% to 6.8%. Insulin sensitivity improved by approximately 75%, while plasma triglycerides decreased by 35% and cholesterol levels decreased by 10%.

During the last two weeks of the study, patient weights also decreased by an average of 1.8%. Although it might be possible to attribute the large improvement in lab values to this small decrement in weight, it seems more likely that both the weight loss and the rapid improvement in insulin resistance was attributable to the patients' adherence to a low-carbohydrate diet.

Low-Carb at the Movies

Analyst Maxwell Smart is briefing agents at the secret U.S. government spy agency CONTROL. What does it mean, he asks rhetorically, that agents at the enemy terrorist organization KAOS have been overheard discussing muffins?

His answer: "Muffins are comfort food. Why would they eat comfort food unless they were nervous about something?"

Hmmm. Where did that come from? In this summer's theater version of the old TV series, "Get Smart," we learn that that the handsome and heroic secret agent Maxwell Smart was once very fat. When his partner, Agent 99, tells him that she used to look like her mom, Max responds, "I used to look like two of my moms, put together."

Flashbacks show us that, in order to advance from analyst to agent, Smart had to lose 150 pounds. And how did he do it? By low-carbing. References to low-carbing and to the fact that big people have feelings, too, abound throughout the movie.

Would-you-believe that low-carbing has again reached the mainstream? Probably not, but seeing it discussed in a serious way on the big screen is certainly is an encouraging development.

Metabolic Syndrome

In several recent posts we've mentioned something called "metabolic syndrome." What is metabolic syndrome?

Metabolic syndrome is not a disease, but rather a set of symptoms that frequently appear together in patients as they grow older. Typically these symptoms include obesity, low HDL cholesterol levels, high triglyceride levels, high glucose and insulin levels, and high blood pressure. As these symptoms worsen, patients with metabolic syndrome frequently progress to type 2 diabetes and cardiovascular disease. If we could somehow prevent or reverse the symptoms of metabolic syndrome, it seems logical that we could correspondingly decrease the incidence of type 2 diabetes and cardiovascular disease.

Obesity is one of the characteristics of metabolic syndrome. Because obesity is easy to observe, it is commonly assumed that metabolic syndrome is caused by obesity. However, a careful inspection of the markers associated with metabolic syndrome reveals that they are all related to insulin resistance.

While weight loss will relieve some of the symptoms of metabolic syndrome, weight loss is notoriously difficult to accomplish and even harder to maintain. The good news is that carbohydrate restriction, even in the absence of dramatic weight loss, is effective in alleviating all of the aspects of metabolic syndrome.


In a study published in the New England Journal of Medicine, 63 obese patients were assigned to a low-carb/high-fat/high-protein diet or to a high-carb/low-fat/low-calorie conventional diet. They were given little follow-up to mimic typical dieting conditions. The graph above summarizes the findings. Light blue bars represent low-carbers at 6 months and dark blue bars represent low-carbers at 12 months. Light red bars represent high-carbers at 6 months and dark red bars represent high-carbers at 12 months.

Although the low-carb group lost more weight than the high-carb group, at 12 months the difference was not significant. The low-carb group experienced a slight decline in systolic blood pressure while the high-carb group experienced a slight increase. HDL cholesterol was significantly higher and triglycerides were significantly lower and in the low-carb group at 12 months. Finally, there was less insulin released in the low-carb group at 6 months, though the difference was no longer significant at 12 months.

Jeff Volek and Richard Feinman have compiled a review of over 30 dietary studies, tabulating the effects of carbohydrate restriction on the markers associated with metabolic syndrome. As we might expect, some studies show great differences and other show little or none. However, taken together, the studies show that while both low-carb diets and conventional diets are associated with an overall decrease in weight, low-carb diets also typically produce the following

• an increase in HDL cholesterol
  
• a decrease in triglycerides
  
• a decrease in glucose levels
  
• a decrease in insulin levels
  
• a decrease in blood pressure

In other words, a review of the scientific literature shows that dietary carbohydrate restriction is a reproducible way to improve the features of metabolic syndrome.

Roots and Branches

What are the diseases of civilization? Measles? Whooping cough? AIDS?

No--you can get all of those diseases without being civilized!

The diseases of civilization are conditions that appear in indigenous populations within about 20 years of significant contact with Western culture. They include dental caries, ulcers, gallstones, appendicitis, diverticulitis, constipation, obesity, asthma, varicose veins, diabetes, high blood pressure, cardiovascular disease, stroke and cancer. Early twentieth century missionaries from Albert Schweitzer in Africa to Samuel Hutton in Labrador noticed that prior to Western contact, these populations experienced such diseases rarely if at all. However, as decades passed and the local people began to adopt Western culture, inevitably Western diseases would gradually appear and eventually become prevalent.

Western civilization brought modern medicine and good public health practices. Why should it also bring poor health? It is possible that an increase in smoking, a decrease in physical activity, high fat consumption and resultant obesity explain why local populations became progressively less healthy over time. However, another explanation is that arriving Westerners brought with them foods that would not spoil over long ocean voyages. White flour, white rice and sugar do not provide much in the way of vitamins and minerals, but they keep well, are fairly cheap, contain necessary calories, and taste very good. They are also rich in easily digestible carbohydrates.

(Illustration inspired by Dave Hatch of Green Bay, Wisconsin)
Look at the tree above. In the branches are many of the diseases of Western civilization. Conventional wisdom says that obesity is at the root of the tree, and that obesity results from too much food and too little exercise. In the tree above, however, we see refined carbohydrates as the root cause. Too much carbohydrate leads to too much insulin release and too much insulin leads to a host of symptoms which eventually manifest themselves as the diseases of civilization. What is the root cause of these diseases--obesity or an excessive intake of carbohydrates? A lot depends on which answer is the correct one.

Weight Regain

You've worked hard. You've lost all that weight on a low-carb lifestyle, and now you're going to gain it all back, right? Not necessarily.

A couple of studies indicate that those who stick to a low-carb lifestyle have a reasonable chance of maintaining at least part of their weight loss. The National Weight Control Registry (NWCR) tracks over 5,000 individuals who have lost significant amounts of weight and kept it off for long periods of time. Most of these people have lost weight on low-calorie diets, but some have lost it on low-carb. In 2007 the NWCR reported a comparison of 96 low-carbers with 795 others, all of whom had lost at least 30 pounds and had maintained a weight loss for a year. At three years the low-carbers regained an average of 15.4 pounds and the others had regained 12.5 pounds, which was not a significant difference.

In 2005, AV Nielson and colleagues compared the efficacy of a low-carb versus a high-carb diet in the control of body weight in diabetic patients. At six months the low-carb group had lost an average of 25 pounds and the low-calorie group had lost an average of 4 pounds. In a followup paper published in 2006, Nielson reported that 7 of the 16 original low-carb patients retained the same bodyweight from 6 to 22 months or reduced it further, and all but one of the sixteen had lower weight at 22 months than at their entry into the study, even though they were not being closely monitored after the initial study was completed. For people who have lost weight successfully on low-carb, that's a very encouraging result.

Low-Carb Is Also Good for Weight Loss

People who follow the low-carb lifestyle report that they feel better when they are doing low-carb. But do they also lose weight?

A study published in March 2007 in the Journal of the American Medical Association says that they do. The A to Z Weight Loss Study, where "A" represents Atkins and "Z" represents Zone, compared those two diets as well as the standard American diet (called LEARN) and the Ornish diet. 311 free-living, overweight/obese (body mass index, 27-40) nondiabetic, premenopausal women were randomized into the four diets and were followed for a year.

The graph above shows clearly that the group doing the Atkins low-carb diet had significantly greater weight loss at 6 months and 12 months than all of the other three groups.

Two other items are interesting. The first is that at 12 months, the Atkins low-carb group had lower systolic and diastolic blood pressures, lower blood glucose, lower triglycerides and higher HDL (good) cholesterol than the other groups, although the differences did not always reach statistical significance. To see a table of the actual numbers, look here.

The second interesting item is that 88% of the women who did the Atkins low-carb diet completed the study. By contrast, the 12-month retention rate among each of the other three groups was about 77%. One of the commonly-used objections to low-carb dieting is that people won't stick with it. In the A-Z Study, over the course of a year, the Atkins low-carb group retained more of its subjects than the groups following the Zone diet, the LEARN diet or the Ornish diet.

Why Should We Low-Carb?

This post is not about science. It's about anecdotes. But occasionally anecdotes can give us valuable insights.

Many of us think that low-carb eating is primarily a way of losing weight. Anybody who has tried a low-fat low-calorie diet is aware of how hard it is to stay on such a diet. We get hungry, we lose energy, and very often we don't lose much weight.

By contrast, in most cases a dedicated low-carber can lose significant amounts of weight without a great deal of hunger. However, the sad truth is that no matter how we may have lost our weight, statistically we are almost sure to regain it. If that's true, why should we bother with a low-carb diet at all?

I'm a member of an Atkins-related board on Yahoo. Over the years I have noticed that most of the members of this board have lost some weight by doing Atkins, but very few of them have actually reached and maintained their goal weights. When I asked the members of the board why they continue to do low-carb I received these answers.

• One woman said that she had lost 70 pounds. She is still 30 pounds from her goal weight, but she has maintained the 70 pound loss for 5 years. Her back problems and reflux have vanished, and she doesn't get sick all the time. She says she has energy and has never been this healthy.
  
  
• Another said that she has lots of hormonal problems, and by doing low-carb, she is at least not gaining weight.
  
  
• A third woman said, "I am no longer considered a diabetic (no more meds for it either!) I no longer have high blood pressure (no more meds for that either), I no longer have any signs of sleep apnea (no more c-pap), I CAN (don't like it) do some exercising... I will never be a runner- I don't want to, don't like it and that is my choice so I will never run in a marathon. :) But I do walk - a lot, which I couldn't do before."
  
  
• Almost everybody said that they feel better when they do low-carb.

Next I went to a bulletin board called Low Carb Friends. They saw similar benefits from following the low-carb lifestyle, and added a few more to the list.

• Lowered cholesterol, triglycerides and blood pressure
  
• Stabilized blood sugar
  
• Better skin, hair and nails
  
• Fewer aches and pains
  
• No heartburn
  
• No acid reflux
  
• Fewer colds
  
• No more sleepy feeling in the afternoon
  
• Better sleep at night
  
• Better stamina

Are these results guaranteed for everybody? No. But there are definitely more benefits to the low-carb lifestyle than simple weight loss.

More on Tim Russert

Since Tim Russert's untimely death on June 13, 2008, more information about his medical history has come to light.

According to Tim's physician, Dr. Michael Newman, we know that Tim had these findings:

Fasting blood glucose=104 (Normal is 70-100)
Hemoglobin A1c=5.7 (Normal is 4-6)
HDL (the "good cholesterol")=37 (Normal is greater than 40)
LDL (the "bad cholesterol)=68 (Normal is less than 130)
Elevated triglycerides
Increased waist circumference
High blood pressure, controlled by medication
Heart scan=210 in 1998 (The score should be zero)

Tim did not have diabetes, but his fasting blood sugar was elevated. His HDL was low and his triglycerides were high. This indicates that he ate a relatively high percentage of carbohydrates in his diet. He was overweight and had high blood pressure. Taken together, these findings suggest that Tim Russert was starting to experience metabolic syndrome, a condition which includes elevated fasting blood glucose and insulin resistance.


The picture above illustrates some of the damage discussed in the previous post, describing what elevated blood glucose and insulin do to the interior of our arteries. They produce fat and cholesterol deposits, promote smooth muscle thickening, cause oxidative damage and make the arteries stiffer because of AGE (Advanced Glycation Endproduct)-related damage. If the carbohydrate hypothesis of heart disease is correct, Tim Russert was a prime candidate for a heart attack, not a person whose sudden death from cardiac arrest should have come as a surprise to his physician.

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In case you're interested, several other bloggers have written about the issues raised by Tim Russert's untimely death:
Jackie Eberstein, R.N.
Jimmy Moore
William Davis, M.D.

What Causes Coronary Artery Disease?

In January 1961 a physiologist named Ancel Keys was featured on the cover of Time magazine. His appearance marked the victory of the idea that heart disease is caused by high blood cholesterol. Beginning in the 1940's, Dr. Keys had noted correlations between dietary fat intake and heart disease. He believed that high dietary fat produced high blood cholesterol, which in turn produced coronary artery disease. When the data Dr. Keys used is examined more carefully, the causal relationships between dietary fat, blood cholesterol and heart disease are less persuasive. In spite of that, by December 1960, the American Heart Association was willing to state that cholesterol is the leading risk factor for heart disease and that Americans should reduce their intake of fat, particularly of saturated fat.

However, there is an alternative hypothesis for the cause of coronary artery disease. As we have seen, insulin is a storage hormone. When insulin is released, it promotes the storage of fat in our adipose tissue. It also promotes the storage of cholesterol and fat in our arterial walls. Not only that, insulin promotes the synthesis of cholesterol and fat in the lining of our arteries. Although we haven't discussed this, another role of insulin is as a growth factor--it causes an increase in the number of smooth muscle cells lining our arteries, which in turn causes the artery walls to thicken.

Insulin is released in response to elevated glucose in the blood. When blood sugar is high, cells will preferentially burn glucose for fuel. In certain tissues, the burning of glucose produces reactive oxygen species, which include oxygen ions, free radicals, and peroxides. If the body does not have sufficient antioxidant protection, the reactive oxygen species will interact with cells and cause cellular breakdown. Another cause of breakdown was discussed in a previous post. Advanced Glycation Endproducts (AGEs) are produced when sugar molecules attach to proteins and crosslink them, eventually making our tissues, including our arteries, stiff and inelastic.

The two hypotheses for the cause of coronary artery disease suggest two very different lines of treatment. The cholesterol-lipid hypothesis implies that we should cut back on dietary cholesterol and fat, taking cholesterol-lowering medication if necessary, which will reduce cholesterol deposits, which will produce fewer heart attacks. The carbohydrate hypothesis implies that we should cut back on carbohydrates, which will lower blood glucose and blood insulin, which will cause less damage to arterial walls, which will produce fewer heart attacks. It appears that Tim Russert's physician believed the cholesterol-lipid hypothesis, and Tim Russert followed his advice. At age 58, Tim Russert died of sudden caradiac arrest. Tim was only one man, and his medical history might not be representative of the American population as a whole. On the other hand, Tim's unexpected death might signal that it is time for us to reconsider our approach to heart disease. It might be time for the medical community to do some long-range studies to see if the cholesterol-lipid hypothesis or the carbohydrate hypothesis produces better outcomes in the prevention and treatment of coronary artery disease.

Tim Russert and Sudden Cardiac Arrest

Tim Russert, for many years the host of NBC's Meet the Press Sunday morning show, died suddenly on June 13, 2008. Michael Newman, Tim Russert's physician, said in an interview that the 58 year old newsman had died of coronary artery disease. This was surprising because his blood pressure was well controlled and his cholesterol fractions were optimal. Dr. Newman said that Tim had shown a high level of stamina on his stress test on April 29th, worked out regularly, and had done so on the morning of his death.

According to Dr. Newman, the postmortem on Tim Russert showed that, although Tim had been asymptomatic, he had significant heart disease, particularly in the left anterior descending coronary artery. Tim had a sudden rupture of a cholesterol plaque in the wall of that coronary artery. This produced a large clot which lodged in his heart, caused ventricular arrhythmia and took his life.

Could this have been avoided? Tim Russert had the best of medical care and tried to follow good health practices. The American medical community recommends regular exercise and keeping blood cholesterol low by eating sparingly of fat- and cholesterol-containing foods and by taking cholesterol-lowering medications if dietary measures are not sufficient. Americans have, in fact, been following these recommendations, and there has not been a large decline in the incidence of heart disease. There has actually been a slight increase in the incidence of heart disease, despite the fact that more and more Americans are also giving up smoking.

We cannot know if Tim Russert's health choices were the proper ones for him. Indeed, they might have enabled him to live longer than he would have lived without them. However, it is important to consider that there is an alternative to the cholesterol-lipid hypothesis for the incidence of heart disease. We'll look at that in the next post.

Glycosylation and Glycation

Two more big words.

When proteins are assembled in our cells, sometimes specific sugar molecules are attached to them in carefully-defined ways. This is called "glycosylation." Enzymes add the sugar molecules to help proteins fold properly and to route proteins to various places inside and outside the cell. Glycosylation patterns also help our bodies to distinguish proteins that are "self" versus "not-self" and are useful in immune responses. Glycosylation results from controlled reactions and is important for our biochemical wellbeing.

When we have glucose in our blood (and if we're alive, we do), sugar molecules are also added to proteins in a random fashion. The random addition of sugar molecules to proteins is called "glycation." If only single glucose molecules have been added to a protein, when the blood sugar level drops, the glucose can detach and the protein will again be normal. But if blood glucose remains high, more sugars will be added. These will rearrange and crosslink, eventually producing something called an Advanced Glycation Endproduct or AGE. One example of an AGE is hemoglobin A1c, the form of hemoglobin found elevated amounts in the red blood cells of poorly-controlled diabetics. Evidence suggests that many other proteins in our bodies are also converted into Advanced Glycation Endproducts by elevated blood sugar. Glucose and fructose in the blood interact with and crosslink these other proteins in our bodies, forming AGEs that accumulate in our eyes, kidneys, arteries, nerve endings, joints and skin.

Although our bodies have mechanisms to cope with the identification and disposal of AGEs, the AGEs gradually accumulate and stiffen our tissues. The elasticity of youth is slowly replaced by the physical degeneration of old age. In other words, crosslinked AGE proteins produce in us the symptoms we associate with old age. This happens in all people, but the process is made worse and happens more quickly in the presence of high blood sugar.

(The illustration is taken from the cover of the journal Science, March 23, 2001.)

Glycemic Index

What happens if a large percentage of your diet consists of bread, potatoes, gravy, corn, sugary soft drinks and desserts? How could that contribute to obesity and type II diabetes?

The key to this question comes from understanding the Glycemic Index or GI.

The glycemic index of a food is measured by having a person eat a certain amount of that food and measuring how much of the carbohydrate in the food is converted into glucose in the blood within two hours. If a food has a high glycemic index, it will raise blood glucose very rapidly. If it has a low glycemic index, it will raise it slowly. In general, the higher the glycemic index, the more insulin your pancreas will have to secrete in order to bring your blood glucose reading back into the safe and normal range.

If pure glucose has a glycemic index of 100, a baked potato has a glycemic index of 111. Kellogg's Corn Flakes have a glycemic index of 92. Wonder Bread has a glycemic index of 73. Coca Cola has a glycemic index of 58. Beef, chicken and fish have a glycemic index close to zero.

It used to be thought that simple carbohydrates (like the high fructose corn syrup in Coca Cola) raised blood sugar quickly and complex carbohydrates (like the starch in potatoes) raised it slowly. From studying the glycemic index of various foods, we now know this isn't true. If you want to raise your blood sugar rapidly and release a large amount of insulin in response, eating significant quantities of any carbohydrate will do it for you. That's fine as long as your muscles and liver remain insulin responsive. But when they start to become insulin resistant, your blood sugar will go higher than it should and will stay elevated for longer than it should. Your pancreas will have to secrete more insulin to keep your blood sugar levels under good control. As we have seen, hyperinsulinemia is hard on our bodies. Hyperglycemia is hard on our bodies, too. Unfortunately, it's a Catch-22.

Obesity Can Fool You

When you look at a fat person, what do you see? Somebody who eats too much? Somebody who exercises too little? Do you ever think that you might be looking at a person who is suffering from internal starvation?

We live in a society where the tastiest, cheapest, easiest-to-obtain calories come from carbohydrates. If you look around, the poorest among us are also the fattest. They eat breaded meats, casseroles, potatoes, gravy, rolls, corn, sugary soft drinks and desserts. Because they are poor, they often work jobs that require manual labor, but the extra exercise does not seem to keep them from becoming obese. They suffer from increased rates of heart disease, high blood pressure and Type II diabetes. Is it possible that it is not their lifestyle, nor the amount of food they are eating, but the type of food they are eating that is putting them at risk? Is it possible that they are giving their bodies empty calories (delicious calories, but empty calories nonetheless) and in exchange are becoming both obese and unhealthy?

(The illustration is made of screen captures from http://www.youtube.com/watch?v=Cs3ZNLQhe40 by Svegen.)

Internal Starvation

We've learned in the previous two posts that insulin is necessary to maintain life. Insulin is your friend. We've also learned that some of us develop a condition called insulin resistance. In insulin resistance, the food we eat is not stored properly. Our pancreas responds by producing more insulin, and the food does get stored. In the case of fat, there is a complication. The food is stored properly, but the additional insulin makes it very difficult to get the fat back out of storage. Our bodies are not able to use all of the calories in the food we eat. As insulin levels rise, a percentage of what we eat is stored in our fat cells and stays there. Calories in no longer equal calories out and we begin to put on weight. Insulin is becoming our enemy. We are starting to experience internal starvation.

Imagine that a penny equals a calorie. Imagine that the only grocery store in town is your body. If you took $20.00 (2000 calories) to the grocery store every day to buy food, you would expect to receive $20.00 (2000 calories) worth of groceries. But what if the stockers in the store became "resistant" to managment and decided to change the rules? What if they decided that you would only get $18.00 (1800 calories) worth of food to use for yourself? The stockers would keep the other $2.00 (200 calories) worth of groceries stacked in the corner, but they wouldn't let you get to it. Eventually you would grow angry because you would see all that unavailable food stacked in the corner.

You might decide to cut back your budget and spend $10.00 (1000 calories) a day on groceries instead. The store would keep $1.00 (100 calories) worth of groceries and would allow you to have $9.00 worth of food. Groceries would still stack up in the corner, but at a slower rate, and you would find that you're getting hungry. Say you get tired of that and decide to spend $25.00 (2500 calories) a day on groceries for a while. You aren't hungry any more, but now the store keeps $2.50 (250 calories) worth of your groceries and the stack in the corner grows even faster.


You have figured out by now that the stack of food in the corner represents fat deposits. If you are experiencing insulin resistance, you can eat a little or eat a lot, and the fat deposits grow slowly or they grow quickly, but in the long run they always grow. With insulin resistance, even if you have iron willpower and eat exactly as many calories as you should for your height, weight and metabolic level, you will experience internal starvation. You end up looking fat on the outside, but at the same time your cells are starving for proper nutrition on the inside. You are experiencing internal starvation.