Fun with Graphs

For the next few weeks, I will be on an overseas vacation. In the meantime, I've been searching on Google and have come up with a set of graphs that should be interesting to look at and consider in the context of low-carbing. Most, but not all, of the data comes from the United States. These graphs are provided without any context to describe how the data was collected or how valid it might be. They just provide something to think about. If you want to enlarge any graph, just click on it, and it will open in a larger version.

One of the more interesting graphs shows that there is not much of a relationship between average cholesterol and rates of death from heart disease. Ancel Keys used seven carefully selected countries to "prove" the opposite, but the countries used for this graph tell another story.



Here's a graph that should be completely unsurprising to a low-carber. It shows a steadily increasing consumption of sugar in the United Kingdom and the United States and, beginning about 1900, a dramatic increase in rates of obesity.



Starting in about 1970, people in the United States began substituting high fructose corn syrup (HFCS) for table sugar. Interestingly, there was also an increase in the incidence of diabetic end stage renal disease during that time. Correlation is not causation, but the values do increase in a similar manner.



End stage renal disease is one of the complications of diabetes, which has also been increasing in the United States.



Sugar consumption, and in recent years HFCS consumption, has been increasing. Has anything else been increasing? Yes, we have been using more wheat flour per capita in the United States.



We are also eating more carbohydrates as a percentage of our total calories.



Not only are we eating a higher percentage of carbs, we are also eating more total calories per person every day.



All of these observations are consistent with (but do not prove) the hypothesis that eating refined carbohydrates can result in the diseases of civilization. However, other factors may also contribute to the increase in metabolic diseases during the past century, and here are some more graphs to consider in that regard.

It is possible that insufficient fiber can be blamed for an increase in health problems. I couldn't find a graph that described fiber consumption over time, but did find one on vegetable consumption. It appears that we are eating more vegetables (and presumably more fiber) than we used to.



It's possible that products that are subject to "sin taxes" could contribute to health problems. Although the introduction of cigarette smoking could be associated with the arrival of Western civilization and its diseases, it is interesting to note that the per capita consumption of cigarettes has actually declined since 1977.



Total alcohol consumption has decreased, too.



As discussed in a previous post, a high intake of omega-6 fats promotes the formation of inflammatory intermediates. Another possible explanation for the increased incidence of the diseases of Western civilization is the increased use of omega-6 rich vegetable oils in place of animal fats. As usual, correlation is not causation, but as shown in the graph below, the production of soybean oil for food consumption went from close to zero in 1935 to 25 pounds person per year in 1999.



Consumption of canola oil has also increased dramatically, from zero in 1984 to seven pounds per person per year in 2004, while the consumption of olive oil went to about two pounds per person per year and the consumption of butter declined.



What do all of these graphs prove? Not a thing. Although they show associations, they cannot prove causation. But I present them for your consideration because they do give us some things to think about as we enjoy a low-carb summer. Have a happy, healthy June!

Cortisol Versus Insulin

The man in the picture has insulin resistance and what the Heart Scan Blog" calls "wheat belly," right? Wrong. He has a hormone problem, but in this case the hormone isn't insulin, it's cortisol.

Insulin, which we discuss frequently on this blog, is a storage hormone. In response to ingestion of carbohydrates, and to a lesser degree of amino acids, the pancreas releases insulin. As a result, within minutes to hours, carbohydrates, amino acids and fats are stored after each meal.

Cortisol is a glucocorticoid hormone that is released from the adrenal glands in response to stress. The stress can be physical or emotional. The effects of cortisol in the body occur over hours to days and include suppression of the immune system, suppression of inflammation and an increase in blood glucose. When people survived by hunting, or when they were involved in combat, elevated cortisol would allow a person to ignore pain and illness in order to concentrate on the task at hand. It would also provide excess glucose in the blood, allowing the person additional energy to fuel the brain and muscles in extreme situations.

Both insulin and cortisol are powerful hormones. Too much insulin for too long will eventually result in insulin resistance, a condition in which more and more insulin must be secreted to produce normal insulin responses in tissues such as muscle, brain and liver. Too much cortisol for too long produces an increased risk of infection, reduced bone density, increased muscle weakness and excess glucose in the blood. Cushing's syndrome is the result of having excessively high cortisol for several years. Take another look at the picture at the beginning of this post. The patient looks like a person with metabolic syndrome, doesn't he? But this person actually has Cushing's syndrome.

Cushing's syndrome can be caused by an adrenal or pituitary tumor, or it may be the result of taking high doses of glucocorticoids for a long period of time. People who do not have these tumors and who do not take exogenous glucocorticoids do not have to worry about Cushing's syndrome, but the man in the picture does illustrate the point that there may be metabolic side effects from stress-induced hypercortisolism.

In a May 2010 review in the American Journal of Physiology-Endocrinology and Metabolism, Dake Qi and Brian Rodrigues described the effects of glucocorticoids on insulin-responsive tissues. Many of the studies in the review used dexamethasone, a synthetic glucocorticoid that is about 50 times as potent as cortisol and produces robust reactions in a short period of time. However, clinical experience with excess cortisol secretion supports these observations. At any rate, excess glucocorticoids will produce:

• Decreased glucose uptake and utilization in muscle and adipose tissue.
  
• Increased gluconeogenesis and glucose output by the liver.
  
• Increased triglyceride storage in the liver.
  
• Increased fatty acid uptake, fat synthesis and fat storage in adipose cells.

Readers of the previous post will recognize that these symptoms are consistent with insulin resistance. What makes it complicated is that there are many different molecules involved in insulin signaling, and each of these can be regulated on several levels. Any of the signaling intermediates can be synthesized more slowly or more rapidly, degraded more slowly or more rapidly, and activated or inactivated through phosphorylation or dephosphorylation by various kinases or phosphatases at numerous sites. These multiple levels of regulation mean that insulin resistance can be achieved through one mechanism when excess cortisol is involved and through another mechanism when excess insulin is involved. Consequently it is possible that both hormones working together can achieve more damage to insulin signaling pathways than one hormone acting alone.

Stress is able to produce a ten-fold increase in cortisol secretion. If the stress is chronic, it is possible that this alone could result in insulin resistance and eventually in the symptoms of the metabolic syndrome. This has been postulated by Anagnostis et al. in The Pathogenetic Role of Cortisol in the Metabolic Syndrome: A Hypothesis.

As we have noted, when primitive cultures adopt Western lifestyles, within about twenty years they can expect to begin experiencing the chronic diseases of Western civilization. While the carbohydrate hypothesis postulates that a diet of refined carbohydrates is the chief cause of insulin resistance and ultimately of the metabolic syndrome, it is also possible that the stress associated with the Western lifestyle is a contributor to insulin resistance. Stress and cortisol secretion are unavoidable, but in the absence of mammoth hunts and hand-to-hand warfare, those of us who wish to avoid the symptoms of insulin resistance would do well to avoid stress while also minimizing our intake of refined carbohydrates.

Insulin Resistance and the Metabolic Syndrome

The metabolic syndrome is a symptom set that includes the following: increased truncal obesity, high blood pressure, high blood glucose, low HDL cholesterol and high triglycerides. As anyone who has observed adults and even children in Western countries can confirm, the metabolic syndrome is becoming more and more prevalent. In Good Calories Bad Calories, Gary Taubes uses several lines of argument to show that one unifying explanation for the development of the metabolic syndrome is the prior development of insulin resistance.

Interestingly, one of the arguments Taubes does not use for his hypothesis is something called the "knockout mouse." The knockout mouse is not a small pugilist with boxing gloves. Instead, it is a genetically engineered mouse in which one or more genes have been turned off (knocked out) through targeted deletions. If we want to know what the effect of insulin is on a particular tissue, one approach is to delete the expression of the insulin receptor in that tissue.

The first attempt at an insulin receptor knockout mouse was to remove insulin receptor expression from the entire mouse. These mice were smaller than normal but were born alive at term. Shortly after birth they developed diabetic ketoacidosis and died. This was not helpful to the investigation of the relationship of insulin receptor signaling to various metabolic conditions, and the investigators moved on.

Because muscle insulin resistance is thought to be important in the development of type 2 diabetes, the next group of knockout studies involved mice that lacked insulin receptors specifically on muscle tissue. These mice had normal levels of blood glucose and plasma insulin. However, they had a 74% decrease in insulin-stimulated glucose transport into their muscle tissue. This caused blood glucose to be preferentially taken up by adipose tissue. Although these mice did not develop overt symptoms of diabetes, they demonstrated two of the features of the metabolic syndrome: increased fat mass and high triglycerides.

Another tissue targeted for insulin receptor deletion was the liver. By two months of age, the mice lacking liver insulin receptors had high levels of serum insulin but were were hyperglycemic in the fed state. To a great extent this was found to be attributable to the fact that insulin was unable to suppress the production of glucose by the liver. This suggests that hepatic insulin resistance is necessary for the onset of overt diabetes.

Because insulin receptors are widely distributed in the brain, investigators also developed a neural insulin receptor knockout mouse. The brains of these mice were normally developed, but the mice showed increased food intake and moderate diet-dependent obesity. It is known that the brain is able to regulate hepatic glucose production. When these neural-knockout mice were given exogenous insulin, they were only about half as effective as normal mice at suppressing hepatic glucose output.

Finally, the insulin receptor was uniquely deleted in the pancreatic beta cells of another group of mice. The investigators were expecting the pancreas to sense glucose concentrations directly rather than to use insulin signaling as an intermediary. To their surprise, mice that lacked pancreatic beta cell insulin receptors showed both a decreased ability to sense glucose and an insufficient secretion of insulin in response to glucose. Some, but not all, of the mice developed diabetes.

For those who would like to read more about these experiments, additional information can be found here and here. The use of insulin receptor knockout mice is a rather blunt instrument to determine whether insulin resistance can be implicated as the cause of the development of the metabolic syndrome. And mice are not people. Nonetheless, it is interesting to note that the deletion of insulin signaling in various tissues can produce obesity, high triglycerides, poor suppression of glucose output by the liver and both impaired pancreatic production of insulin and insufficient release of insulin in response to glucose.

The Fiber Hypothesis

Today's question is: What if you know that the dietary-saturated-fat-and-cholesterol hypothesis doesn't work very well to explain heart disease, but at the same time you don't want to admit that eating too many refined carbohydrates might be the cause?

Answer: You put the blame on fiber. Or rather on not eating enough fiber.

In 1972, Peter Cleave tried to explain to a U.S. Senate Select Committee that when primitive cultures adopted Western eating patterns, they also began to experience the diseases of Western civilization, including diabetes, heart disease and hypertension. Cleave pointed out that the fat and cholesterol hypothesis of heart disease did not explain this transition, but that the adoption of a diet rich in refined carbohydrates did account for it rather elegantly. The Senators reached the only logical conclusion. They refused to believe Dr. Cleave. Dr. Ancel Keys had so completely won the argument that dietary fat was the cause of heart disease, that any alternative hypothesis had to be rejected out of hand.

The Senators were left with the problem of how to explain the increased incidence of heart disease in transitioning cultures. Enter a famous medical missionary, Denis Burkitt. While working in Uganda, Dr. Burkitt had noticed that Africans produced several times more feces than people in Western countries. He hypothesized that the presence of dietary fiber produced the absence of the diseases of Western civilization. Burkitt collected over 800 anectodal reports showing that primitive peoples ate high fiber foods, while Westernized cultures tended to eat foods that were nutritionally dense and low in bulk, not providing enough volume to allow the intestines to remain healthy. This idea made sense to the granola-eating counterculturalists of the time. More importantly, it did not contradict Ancel Keys' diet-heart hypothesis.

Forty years later, the need for high fiber in the diet has become received wisdom. Some studies show that eating more dietary fiber is associated with lower all-cause mortality, for example Dietary fiber intake in relation to coronary heart disease and all-cause mortality over 40 y: the Zutphen Study. Other studies show no relationship between fiber intake and all-cause mortality, including this one, The long-term effect of dietary advice in men with coronary disease: follow-up of the Diet and Reinfarction trial (DART).

For the purposes of low-carbers, several of the studies on the relationship of glycemic load with the risk of type 2 diabetes may be instructive. The glycemic load is the glycemic index of each food eaten, multiplied by the number of carbohydrate grams of that food eaten, summed for all items consumed during a day. In two studies (here in women and here in men), Salmerón et al. showed that the combination of a high glycemic load and a low cereal fiber intake increased the risk of type 2 diabetes when compared with a low glycemic load and high cereal fiber intake. The figure below is taken from the women's study.Looking at the X axis, at all levels of intake of cereal fiber, the relative risk of diabetes decreases as the glycemic load goes from high to medium to low. On the Z axis, at all levels of glycemic load the relative risk of diabetes decreases as the cereal fiber intake goes from low to medium to high.

Let's say that two low-carbers eat an identical number of carbs. One eats high-glycemic foods and has a high glycemic load. The other eats low-glycemic foods and has a low glycemic load. Both of them will need to release insulin to dispose of the carbs, but the first low-carber will have to release insulin in spikes to counteract the rapid rise of his blood glucose, while the second low-carber will be able to get by with a more gradual release of insulin. As Sullivan et al. have shown here, there is reason to believe that insulin spikes contribute to the development of insulin resistance.

How does fiber fit into the equation? The traditional explanation is that fiber fills us up. However, experiments done with caloric dilution show that when low-calorie foods are subsituted for higher-calorie ones, humans are well able to adjust their consumption of food to maintain their customary caloric intake. Another function of fiber is that it slows the absorption of nutrients from food. In other words, the addition of fiber can be expected to lower the effective glycemic index of high-, medium- and low-glycemic index carbohydrates. The relationship of the total amount of fiber to the total number of carbs to the glycemic index is probably quite complex, which may explain why many of the fiber-health studies do not show clearcut relationships between fiber intake and outcomes such as heart disease, type 2 diabetes, obesity and cancer.

In other words, if low-carb is good and low-glycemic index carb is good, the addition of fiber to all of that might be better. Low-glycemic-index foods like broccoli and nuts do tend to contain more fiber, so perhaps the point is moot for low-carbers who are careful about the type of carbs they consume. In any case, there is good evidence that lowering carbohydrate intake and lowering the glycemic index of those carbs is protective against the diseases of Western civilization. The data on the benefits of fiber intake is not overwhelming, so use your own judgment to decide what level of fiber intake might be right for you.

Food Nazis?

When low-carbers begin following the low-carb lifestyle, they start to feel free. Free of the hunger that forces them to eat every few hours even though they are morbidly obese. Free of enslavement to particular foods that they have never been able to resist. And after a while, free of many, many pounds of fat that they have been hauling around everywhere, all the time.

Low-carbing is an odd way to eat, but the freedom makes it worth the trouble of figuring out a new way to shop and a new way to eat out in restaurants. There are many low-carb bulletin boards and blogs for support. There is more and more scientific evidence demonstrating the superiority of low-carbing in the control of diabetes and heart disease and its efficacy in weight loss as well. The recent appearance of the paleolithic approach to low-carbing has given a common-sense aspect to the low-carb lifestyle. When observers object to low-carb food choices, low-carbers can point out that this is the way humans have eaten for millennia. It's only recently that humans began to eat lots of refined carbohydrates, and with that change in diet, perhaps not coincidentally, humans also began to experience the diseases of Western civilization.

So far, so good. But as I look back on my recent blogposts and those of other bloggers, I have started to notice a more rigid, regimented (shall we say Nazi-like?) aspect to the world of low-carbing. Some examples:

• It's good to eat fat, but be sure the fat has the right omega-3 to omega-6 ratio.
  
• It's good to eat nonstarchy vegetables, but remember that broccoli has goitrogens and tomatoes are nightshades. And wheat, even whole wheat, contains many compounds that can damage the human digestive tract.
  
• It's good to eat meat, but it should be grass fed, not grain fed.
  
• It's good to eat eggs and chicken, but they need to be free range.
  
• It's good to eat seafood, but watch out for the mercury.
  
• It's good to avoid sugar, but it's better to avoid artificial sweeteners as well.

The list could go on and on.

In the last couple of days I've noticed one low-carber who seems to be on the edge of dropping out because of the difficulty of following all the extra rules all at once. Another works 60 hours a week and is not sure he has the time required to be sure all his food meets the higher standards for healthy low-carb eating. A third concern is that, although low-carb foods tend to cost more than the Standard American Diet, the more strict versions of low-carbing become prohibitively expensive for people on a limited budget.

Low-carbing is literally a lifesaver for people who are on their way to diabetes, heart disease, and morbid obesity. Some people have additional health issues, and it is fine to refine the low-carb lifestyle to help address those needs.

However, it's important for low-carbers to remember that we don't need to sacrifice the good for the sake of the perfect. For those who are new to the low-carb lifestyle, or for those who don't have the concentration, the time or the money to pursue all the ins and outs of healthy eating, can I make a plea for mercy?

Let's not become low-carb food Nazis. Low-carbing is a gift. Please let people enjoy the freedom it provides. If they want to add additional aspects to it, fine. If not, we can rejoice that they are at least doing something that will significantly improve the quality of their lives. With that knowledge, we can follow our own set of dietary rules while giving other low-carbers the freedom to choose what additional modifications they will or will not follow.

Is Diabetes Caused by Refined Carbohydrates?

Last week we criticized Good Calories Bad Calories. This week we shall praise it. In chapter 6 of GCBC, Gary Taubes discusses Captain Thomas Latimore Cleave, a physician who believed that the common chronic diseases of Western civilization could be linked to the consumption of refined carbohydrates. Cleave had observed that non-Western societies tended to remain healthy even if they ate relatively large amounts of low glycemic index carbohydrates such as brown rice, wholemeal flour, non-starchy vegetables and nuts. But when a cultural group switched from traditional foods to white rice, white flour and sugar, the chronic diseases of civilization would begin to appear. To illustrate this, Cleave prepared the chart at the top of this post, which has been scanned from page 116 of GCBC. The dashed line shows per capita sugar consumption in England and Wales from just before 1905 to just after 1945. Sugar consumption increased during prosperous times and decreased during periods of wartime rationing. If diabetes had no relation to sugar intake, one would expect that deaths from diabetes (diabetic mortality) would gradually decrease as (1) injectable insulin was introduced and (2) medical treatments in general improved. Instead, until 1945 the index of diabetic mortality increased and declined in parallel with the consumption of sugar. Correlation is not causation, but the close relationship between sugar consumption and deaths from diabetes bears serious consideration.

Since 1945, the use of antibiotics to treat infection, the widespread use of home blood glucose monitors and the advent of new drugs to treat diabetes has dramatically reduced the death rate from diabetes. Nevertheless, there seems to be a steadily-increasing incidence of diabetes, particularly of type 2 diabetes. A recent article in Science Daily describes a study showing that type 2 diabetes has reached epidemic proportions in China. The scientists estimated that 9.7% of adult Chinese have diabetes and 15.5% have prediabetes. The prevalence of both conditions is higher in urban areas. Possible causes may include longer lifespans, increased smoking, decreased physical activity, increased air pollution, increased food consumption and decreased food quality.

Along the lines of Dr. Cleave's hypothesis about the relationship of refined carbohydrates and diabetes, in 2007 the Archives of Internal Medicine published an article suggesting one possible cause for the increase of diabetes in China. Its title was "Prospective Study of Dietary Carbohydrates, Glycemic Index, Glycemic Load, and Incidence of Type 2 Diabetes Mellitus in Middle-aged Chinese Women".

The study spent 4.6 years observing a cohort of about 64000 Chinese women with no history of diabetes or other chronic disease at baseline. These women were between 40 and 70 years old and lived in seven communities in urban Shanghai. They were divided into sets of quintiles according to several measures of carbohydrate intake. Adjustments were made for possible confounding factors including age, education, income, occupation, smoking status, alcohol consumption, total daily energy intake, physical activity, body mass index, waist-to-hip ratio and presence or absence of hypertension.

When confounding factors were eliminated, it was found that in middle-aged Chinese women, the percentage of carbohydrate in the diet was positively associated with the risk of developing type 2 diabetes. When glycemic index was considered, the higher the glycemic index of the food eaten, the more likely the women were to develop type 2 diabetes. In Shanghai, rice is a main staple food, contributing 73.9% of dietary glucose load (calculated by multiplying the total carbohydrate of a food by the glycemic index of the food and summing the values for all foods over a day). When women were stratified according to the amount of rice they ate, the group eating the most rice (over three cups of cooked rice per day) had a relative risk of 1.78 of developing diabetes as compared with those eating the least rice (less than two cups of rice per day).

For this group of Chinese women living in an urban area, carbohydrate intake averaged between about 260 and 340 grams per day. The largest part of their diet consisted of rice, which has a glycemic index of 55 (glucose=100). In this population, when adjusted for other factors predisposing to diabetes, a diet high in carbohydrates with a high glycemic index was associated with a higher risk of type 2 diabetes. Does this mean that diabetes is caused by refined carbohydrates? No, but once again, the close association between a higher intake of refined carbohydrates and a higher incidence of type 2 diabetes is worth serious consideration.

Good Calories Bad Calories Is Not Necessarily Infallible

When Good Calories Bad Calories (abbreviated here as GCBC) was published in 2007, the low-carb community was ecstatic. Dr. Robert Atkins and the Doctors Eades had discussed the scientific basis for the low-carb lifestyle, but their writings were usually presented in the context of clinical observations. With GCBC, Gary Taubes gave low-carbers 460 pages of tightly reasoned discussion and another 113 pages listing many specific citations from the scientific literature.

For a layperson, the book was not easy to read, but with effort it was comprehensible. At last low-carbers had access to information that cast doubt on the hypothesis that excessive consumption of fat raises cholesterol levels, which in turn causes heart disease and early death. Taubes presented plausible evidence for an alternative hypothesis--that excessive carbohydrate consumption, not fat consumption, is the cause of diabetes, heart disease, hypertension and even cancer.

Since the publication of GCBC, two interesting things have happened. (A) GCBC has moved into the position of holy writ in the eyes of many low-carbers and (B) several low-carb blogs and forums have arisen to discuss the scientific and practical aspects of low-carbing.

A rereading of GCBC in 2010 shows that many of its ideas have been supported by the subsequent publication of prospective dietary studies, including Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet, published in the New England Journal of Medicine. However, recent discussions in the blogosphere show that some statements in GCBC may need to be reconsidered.

Specifically, on page 394 of the hardbound edition of GCBC, Taubes states, "By the mid-1960s, four facts had been established beyond reasonable doubt: (1) carbohydrates are singularly responsible for prompting insulin secretion; (2) insulin is singularly responsible for inducing fat accumulation; (3) dietary carbohydrates are required for excess fat accumulation; and (4) both Type 2 diabetics and the obese have abnormally elevated levels of circulating insulin and a 'greatly exaggerated' insulin response to carbohydrates in the diet..."

Let's address these statements in order.

1. Although consumption of carbohydrates does prompt insulin secretion, it is a well-known physiological fact that consumption of proteins also prompts insulin secretion. The amount of insulin released in response to protein is about a third of that released in response to carbohydrate on a gram-for-gram basis, but the increase is still measurable. Dr. Mike Eades has an illustration of this on page 37 of the paperback edition of Protein Power. Scientific articles measuring the insulin release in response to protein can be found here and here. Insulin response to various foods in terms of 120 minute area under the curve can be found in Table 4 here.

2. Insulin release does promote the storage of fat in adipocytes, but it is not the only signaling protein that produces fat storage. Acylation Stimulating Protein (ASP) is secreted by fat cells and allows fat to be removed from chylomicrons and stored in fat cells. Acylation Stimulating Protein permits the body to store fat in the absence of insulin. The process is discussed here by Dave Dixon and here by Petro Dobromylskyj (Hyperlipid).

3. While it is difficult to accumulate excess fat in the absence of dietary carbohydrates, it is not impossible. On various discussion boards, a few zero-carbers have related anecdotal evidence that they gained weight while eating large amounts of protein and fat. From a theoretical perspecive, on pages 388-392 of GCBC Taubes goes into great detail about the necessity of glycerol phosphate for the storage of fat in adipose tissue. (Glycerol phosphate is the precursor to the molecule used as the backbone of a triglyceride, the storage form of fat.) On page 392 Taubes says, "Dietary glucose is the primary source of glycerol phosphate. The more carbohydrates consumed, the more glycerol phosphate available, and so the more fat can accumulate. For this reason alone, it may be impossible to store excess body fat without at least some carbohydrates in the diet and without the ongoing metabolism of these dietary carbohydrates to produce glucose and the necessary glycerol phosphate." This sounds logical. However, biochemists know that glycerol phosphate can readily be produced from protein via glyceroneogenesis. The absence of dietary carbohydrate in no way prevents the synthesis of triglycerides from a high-protein or even a high-fat diet.

(4) It is true that high insulin is often associated with type 2 diabetes, but it is important to remember that type 2 diabetics do not always have an excess of circulating insulin. Instead they have insulin resistance. If their body tries to control high blood glucose levels with excess insulin production by the pancreas, this can result in beta cell burnout and a patient who actually has less endogenous insulin production than a person without diabetes.

As described here the scientific method is an ongoing process. Good Calories Bad Calories is an excellent book and provides many good arguments for the low-carb lifestyle. But the scientific method requires that we keep testing and evaluating our hypotheses, and it is important to realize that not everything we read in GCBC will necessarily stand the test of time.

Eat Fat for Weight Loss

As most low-carbers already know, eating fat produces satiety. But in some cases, eating fat also helps a dieter lose weight.

It turns out that the chain length of the fatty acids in the triglyceride is an important factor in choosing a fat that promotes weight loss. Most of the fats found in a normal diet will contain long-chain fatty acids. That is, most of the triglycerides we eat will have fatty acids that contain between 13 and 22 carbons. These long-chain fatty acids are digested in the gut, where they are packaged into chylomicrons. The chylomicrons are moved into the lymphatic system and eventually enter the blood at the left subclavian vein in the upper chest. (A review of the process can be found here.)

When the chylomicrons reach the blood, the long-chain fatty acids in them can be absorbed by any cell, including fat cells, that contain lipoprotein lipase. Once these fatty acids are absorbed into a fat cell, they are still available for later mobilization into the blood via hormone-sensitive lipase. But in insulin-resistant individuals, the activity of hormone-sensitive lipase is down-regulated by high insulin levels. In those people, stored fat tends to remain in storage.

Medium-chain fatty acids contain from 6 to 12 carbons. (In a normal diet, the most common source is probably butter, which contains about 10% medium-chain fatty acids. For those who shop the health food aisles, another source is coconut oil, containing about 66% medium chain fatty acids.) Medium-chain fatty acids are processed differently in the gut. Because they are more water-soluble, they tend not to be packaged into chylomicrons. Instead, they are absorbed from the gut directly into the blood as free fatty acids. Medium-chain fatty acids are bound to serum albumin in the blood, and in that form they travel to the liver where they are used primarily for energy production. Some are converted to ketones that are in turn used for energy by many of the cells of the body.

A 1996 review article by Bach et al. discussed the fact that, compared with long-chain triglycerides, medium-chain triglycerides have more rapid delivery to the liver, higher oxidation rates, poorer rates of incorporation into fat cells, and greater control of satiety. However, there were some counteracting factors that suggested that eating medium-chain fatty acids might not produce the expected reduction in body weight.

After that review article was published, Marie-Pierre St-Onge and her colleagues began studying the effect of human diets that were either rich in medium-chain triglycerides or rich in long-chain triglycerides. The medium-chain triglyceride oil contained primarily caprylic (8 carbons, saturated) and capric (10 carbons, saturated) fatty acids. The long-chain triglyceride oil was olive oil, which contains primarily oleic acid (18 carbons, monounsaturated).


In a randomized crossover controlled feeding trial published in 2003, energy expenditure was measured before and up to 5.5 hours after eating a breakfast meal. Although both groups saw increases in fat oxidation and energy expenditure following the meal, the medium-chain triglyceride group saw larger increases at some though not all of the timepoints after the breakfast meal. The medium-chain triglyceride group also saw a trend toward lower energy intake at the subsequent lunch meal. Not surprisingly, over the four-week duration of the study, the medium-chain triglyceride group saw a significant loss of total adipose tissue of about 1.8 pounds. The reduction in adipose of the olive oil group did not reach significance.

In 2008 Dr. St-Onge and colleagues performed a 16-week double-blind non-crossover weight loss study in overweight men and women. Once again, the groups were divided according to diets containing either medium-chain triglycerides or olive oil. Women consumed 1500 calories per day and men consumed 1800 calories per day, with about 12% of these calories as the prescribed study oil. At the end of the study, those who consumed medium-chain triglyceride oil had lost about 3.7 more pounds of body weight than those in the olive oil group. The loss of total fat mass was also about 3.2 pounds greater in the medium-chain triglyceride group compared with the olive oil group.

These findings are consistent with those of other investigators, both for animal models of obesity and for humans. In 2007 a group in China performed a pilot study to see if other health parameters are affected with the ingestion of medium-chain triglycerides. For ninety days, forty moderately overweight type 2 diabetic patients were given either 18 grams per day of medium-chain triglycerides or 18 grams per day of corn oil. The medium-chain triglyceride group showed a reduction in body weight, a reduction in waist circumference, a decline in serum cholesterol, an increase in serum C-peptide and a reduction of insulin resistance.

The studies discussed in this blogpost are not definitive, and much more research will be necessary to see if medium-chain triglycerides are an effective tool for reducing obesity. Nevertheless, it is encouraging to see that, at least in an experimental setting, these fats are able to decrease fat mass in both overweight men and women over time.

To Eat Saturates or Not to Eat Saturates?

As we discussed in the previous post, saturated fats are not fats that are saturated with calories or saturated with cholesterol. "Saturated" is a chemical term that can be thought of as a measure of the stability of a particular fat in the presence of heat, light and oxygen. Saturated fats are more stable than monounsaturated fats and much more stable than polyunsaturated fats. Saturated fats are generally solid at room temperature. The richest sources are from animals (lard, butter, tallow) or from tropical plants (coconut oil, palm oil).

When heart disease began to become prevalent in the 20th century, scientists looked for a cause and decided that saturated fats were a good candidate. By the end of the 20th century most people thought that the science was settled--eating saturated fats causes heart disease. But studies are starting to accumulate that suggest that this isn't necessarily so.

Two articles (abstracts here and here) by Ronald Krauss and colleagues were recently published in the American Journal of Clinical Nutrition. They did an analysis of twenty one prospective cohort studies (i.e., these were actual clinical studies, not just correlational number crunching) and examined the relationship between intake of saturated fat and the risk of coronary heart disease, stroke and cardiovascular disease. This type of analysis depends on the integrity of the authors in selecting the studies to be analyzed, especially if the authors have a bias toward a particular outcome. With that caveat, it is noteworthy that the authors concluded that "there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD [coronary heart disease] or CVD [coronary vascular disease]." (There was also no significant association with stroke, and the authors stated that results were not affected by age, sex or the quality of a particular study.)

The authors noted that when studies replaced saturated fat with a higher carbohydrate intake, this resulted in increased triglycerides, smaller LDL particles and reduced HDL cholesterol. In the studies that replaced saturated fat with mono- or polyunsaturated fat, patients saw a reduction in their LDL cholesterol, but they also reduced their "good" HDL cholesterol.

But these were the only studies that showed no relationship between saturated fat and cardiovascular disease, right? Not exactly.

In his blog, Dr. Michael Eades describes a group of 264 men who entered a study after experiencing their first heart attack. From 1957 to 1963 the treatment group ate a diet with about 13.5% saturated fat. The control group continued to eat their normal diet, which probably contained about 25% saturated fat according to Dr. Eades' ballpark estimate. After six years, both groups had the same heart attack relapse rate and the same death rate.

Eades also describes a study in which patients with ischemic heart disease ate either a high-saturated fat diet, a diet in which most of the fat was olive oil or a diet in which most of the fat was corn oil. After two years, 75% of the high-saturated fat group was alive and free from a second heart attack. Fifty seven percent of the olive oil group was alive and heart attack free at the completion of the study. And the corn oil group had only 52% alive and heart attack free at the end of two years.

Finally, a 2004 study by Mozaffarian et al. examined the progression of coronary atherosclerosis in postmenopausal women with established coronary heart disease. Comparing the intake of saturated fatty acid among these women over three years, they found that the intake of saturated fat was inversely related to the rate of progression of coronary atherosclerosis, and was unrelated both to unstable angina and to death from myocardial infarction. Unexpectedly, investigators saw a positive association between polyunsaturated fat intake and the rate of narrowing of the coronary arteries. This was particularly true in women with diabetes, lower HDL cholesterol, a lower protein intake and a higher carbohydrate intake. (It is important to note that this was a correlational study and the outcome could be affected by confounding factors that were not identified.)

To eat or not to eat saturated fat? It appears that it is up to the individual. Some studies have shown a slightly increased risk of heart disease with consumption of saturated fats, but many studies show no correlation at all. On the other hand, the increased consumption of carbohydrates, particularly refined carbohydrates, is associated with increased triglycerides, decreased LDL particle size, and decreased HDL cholesterol, all of which are associated with increased risk of cardiovascular disease. If we have to choose between fat and carbohydrate for heart health, it appears that fat may be the better choice.

Saturated Fats/Unsaturated Fats

Since Dr. Ancel Keys and his colleagues formulated and promulgated the diet-heart hypothesis in the 1960's, the idea of eating saturated fat has become anathema in most nutritional circles. When Americans were told that that consumption of saturated fat was positively correlated with the incidence of heart disease, they began to eat more of the "heart-healthy" mono- and polyunsaturated fats and fewer of the saturated ones. In spite of that, the number of hospital discharges with cardiovascular disease as the first listed diagnosis has continued to increase in the U.S. This is especially surprising in light of the fact that the percentage of U.S. adults who smoke has declined from over 40% in 1965 to about 20% in 2007. Is it possible that saturated fats are not as evil as they have been portrayed?

To begin the discussion, it is important to understand that a saturated fat is not saturated with calories or with cholesterol. In this case, "saturated" is a chemical term, and it means that the molecule in question is saturated with hydrogens--that is, it contains the maximum number of hydrogens it can hold. Here are two fatty acids, one saturated and the other unsaturated:


In the fatty acid at the top, the carbon-carbon bond between the two green C's is a single bond. Each green carbon holds two hydrogens, and they are saturated with hydrogen. In the fatty acid at the bottom, there is a double bond between the two green C's. Each of those carbons holds one hydrogen. The carbons do not hold as many hydrogens as they possibly could and they are therefore unsaturated. This particular fatty acid has only one unsaturated carbon-carbon bond, so it is monounsaturated. If it had two or more unsaturated bonds, it would be polyunsaturated.

The important thing about unsaturated fatty acids is that the presence of a double bond weakens the carbon-hydrogen bonds on the carbons next to the double bond. In the picture above, those carbon-hydrogen bonds are marked with green asterisks. That doesn't sound particularly interesting until we understand what happens when those hydrogens are removed by something like oxygen, heat or metal ions. As soon as we remove one of the vulnerable hydrogens, our heart-healthy unsaturated fatty acid becomes a free radical. In other words, it contains an unpaired electron and it becomes extremely chemically reactive.

Once the first free radical is formed, the generation of free radicals from unsaturated fatty acids happens in a self-propagating manner. One free radical can interact with other unsaturated fatty acids to produce more free radicals, which in turn produce even more free radicals, and so on. Besides damaging the fatty acids, these free radicals can also destroy other molecules, including vitamins and proteins. In addition, the free radicals are able to react with oxygen to produce hydroperoxides. These eventually break down into aldehydes, which produce the odors and flavors associated with rancidity.

The reactivity of fatty acids increases with the number of double bonds they contain. Stearic acid is an 18-carbon saturated fatty acid. If we add one double bond, it becomes one hundred times more likely to form a free radical. If we add three double bonds, it becomes 2500 times more likely to form a free radical. The health effects of saturated versus unsaturated fatty acids won't be addressed until the next blogpost, but it is certain that saturated fatty acids are far more stable than their unsaturated counterparts.

There are several ways to decrease the likelihood of free radical formation and rancidification in fatty acids. One is to be sure that heat is not used to extract the fatty acid from its source. In the case of unrendered animal fats, this is not a problem. In the case of vegetable fats, cold pressing ensures (at least it does in the EU) that the oil will not be heated above about 80 degrees Fahrenheit. Unfortunately the U.S. definition of cold pressed is not particularly rigorous, so it may be necessary to check websites or make telephone calls to the manufacturer to determine the temperature a particular brand of oil reaches as it is extracted. When fat is used for cooking, it is important to realize that the higher it is heated and the longer it is heated, the more likely it will be to form free radicals.

Another strategy to avoid free radical formation and rancidification in fats and oils is to be sure that they are kept away from light, particularly UV light. It is also helpful to keep fats and oils away from oxygen. They should not be stored for long periods, and once a container is opened, it should be used up as quickly as possible.

As we have already seen, some polyunsaturated fats are necessary for growth and for optimal health. However it pays to know which fats are which and to be careful with respect to the amounts and types of dietary fats we consume. In closing, here is a table that presents the approximate composition of some common fats, arranged from the lowest to the highest percentage of polyunsaturated fatty acids.

Deadline

I have a project and a deadline in the real world, so I probably won't be able to blog for a while longer. Questions and comments on previous blogposts are still welcomed, however. (Be sure to include in the comment which specific post you're commenting on. Blogger doesn't provide that information and sometimes I can't find the comments after I've accepted them.)

In the meantime, I know you'll keep moving forward on your journey into good health.

More on Omega-3 and Omega-6

Omega-3 and omega-6 fatty acids are long-chain polyunsaturated fatty acids. They cannot be synthesized by the human body, but are important for growth, for cardiovascular health and for immune function. They may also be involved in a variety of other health-related issues including the prevention of cancer and of central nervous system disorders. Their effects are somewhat non-specific, but because the omega-3s in particular have shown positive effects in many controlled double-blind prospective scientific studies, people who are interested in nutrition are also interested in the omega-3 and omega-6 fatty acids. This blogpost, and the previous one, attempt to explain a few principles that may make it easier for readers to evaluate their own use of these essential fatty acids.

The omega-3 and omega-6 fatty acids are unbranched molecules ranging from 16 to 24 carbons in length and carrying from two to six unsaturated bonds. The most common forms are illustrated above. When they are ingested in the diet, these polyunsaturated fatty acids gradually become incorporated into the phospholipid bilayers that form the cell walls of most of the cells in our bodies. As phospholipids, the omega-3 and omega-6 fatty acids affect the flexibility and permeability of the membrane surrounding each cell. They also exist in equilibrium with the unsaturated free fatty acids that circulate in our blood. It is this pool of free fatty acids that is used by the body as precursors for the eicosanoid signaling molecules, i.e., the prostaglandins, thromboxanes, leukotrienes and prostacyclins.

From a survey of the omega-3 literature, it appears that the longer the molecule, the more biologically potent it is. (An example is found here.) The body is able to convert one form of omega-3 fatty acid to another, but it is not particularly efficient at it. For instance, although flax seed oil is rich in alpha-linolenic acid (ALA), ALA (18 carbons) is converted into EPA (20 carbons) at an efficiency of about 5-10% and into DHA (22 carbons) at an efficiency of about 2-5%. Recent studies indicate that in some individuals the conversion rates may be less than 1%. By contrast, EPA and DHA can be obtained directly from fish oil and require no modification to provide maximum protection against conditions such as coronary artery disease. Vegetarians and those who are allergic to fish will be able to eat extra ALA to compensate for the poor conversion rate to EPA and DHA, but they must bear in mind that not all omega-3s are created equal.

Another consideration in omega-3 and -6 fatty acid intake is the interchangeability of the omega-3 and omega-6 fatty acids in the eicosanoid synthesis pathways. Take a look at the figure above. EPA (eicosapentaenoic acid) is an omega-3 fatty acid with 20 carbons and five double bonds. AA (arachidonic acid) is an omega-6 fatty acid with 20 carbons and four double bonds. Superficially, they look very similar. These molecules also look similar to the enzymes involved in eicosanoid synthesis and, as such, they compete with one another. Metabolites of omega-6 fatty acids, particularly metabolites of arachidonic acid (20 carbons), are significantly more inflammatory than those of omega-3 fatty acids. This becomes important because the Westernized diet has a fatty acid ratio of omega-6 to omega-3 that falls between 10:1 and 30:1. If our dietary raw material is almost all omega-6 fatty acids, the metabolites will be predominately pro-inflammatory. For some interesting lists of omega-6 sources, see here. I can't vouch for the accuracy of the lists, but in general they provide some surprising insights.

One way to decrease the omega-6-derived inflammatory intermediates is simply to replace omega-6 polyunsaturated fats with saturated and monounsaturated fats. (A recent journal article suggests that eating saturated fat is not as dangerous as previously thought.) Saturated and monounsaturated fats provide energy, but they cannot be converted into eicosanoid signaling molecules. Another strategy is to take advantage of the metabolic competition between omega-3 and omega-6 fatty acids by replacing the intake of omega-6s with omega-3s. Although the omega-3 fatty acids can be pro-inflammatory when eaten to excess (probably more than three grams per day), in general they will form less-inflammatory signaling intermediates and will also decrease the omega-6-stimulated production of small pro-inflammatory proteins called cytokines.

A review article on omega-3 fatty acids suggests setting a goal of an omega-6 to omega-3 ratio between 1:1 to 1:4, though it gives no rationale for these numbers other than speculation that that was the ratio consumed by our ancestors. The article also recommends consuming fatty fish three times per week. Unfortunately the oceans are no longer pristine, and fish tend to contain pollutants such as mercury, PCBs and dioxin. For those who prefer not to take the risk, purified fish oil supplements are available from manufacturers who use high-vacuum, low-temperature molecular distillation to purify their fish oils. Another source of EPA and DHA is krill oil, which comes from animals that are low on the food chain and therefore low in pollutants. Krill oil is quite expensive, however. Meat, eggs and plant sources also contain omega-3s in varying amounts. For the obsessive-compulsive, here is a list of the total omega-3 content of 200 calories' worth of various foods.

Omega-3 and omega-6 fatty acids are essential for life. They also affect the quality of life in positive and negative ways. Because they are stored in the phospholipid bilayers of our cell membranes, they take a long time to act. They must build up, reach an equilibrium with their free fatty acid form in the blood and then be converted to intermediates. For that reason, it may take weeks or months before a negative effect starts to decline or a positive effect is noticed. However, there are many scientific articles that indicate that it may be worth the time, effort and expense of attending to our intake of these essential fatty acids.

Essential Fatty Acids (Omega-3 and Omega-6)

Certain dietary deficiency diseases are quite straightforward. For instance, if we don't consume enough vitamin C for a long period of time, we will develop scurvy. Children who don't get enough vitamin D and/or calcium, will suffer from rickets. Adults with a persistent deficiency of vitamin D and/or calcium will eventually experience osteopenia and perhaps osteoporosis.

Other dietary deficiencies produce less obvious symptoms. As early as the 1920's, it was noted that a complete dietary deficiency of fatty acids produced impaired growth in animals. When this was investigated farther, it was found that the omega-3 and omega-6 fatty acids were particularly important for growth and development.

Now a detour to explain some nomenclature. Fatty acids are the carbon chains that are attached to glycerol backbones to form triglycerides. Illustrated above are three such fatty acids, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The zig zag lines are a form of shorthand that circumvents the necessity of writing out all the carbons and hydrogens found in these molecules. Each inflection of the zig zag (plus the right end of the zig zag) represents a carbon atom. Count these points on ALA, and you will find 18 carbon atoms. On DHA there are 22. The straight lines between the points represent covalent bonds. A single straight line between two carbons is a single bond, also called a saturated bond. A double line between two carbons is a double bond, also called an unsaturated bond. You can see that all three of these fatty acids contain several unsaturated bonds, which is why they are called polyunsaturated fatty acids.

On the left of each fatty acid molecule is a carboxyl group, which is used to join the fatty acid to the glycerol backbone. On the extreme right is the omega (or final) carbon. In each of the fatty acids shown above, at carbon #3, there is a double bond. The presence of that bond means that these are omega-3 fatty acids. Fatty acids that have a double bond at carbon #6, but not at carbon #3 are called omega-6 fatty acids.

Back to the dietary deficiency story. In a review article, William Lands describes how further research showed that omega-3 and omega-6 fatty acids are somewhat interchangeable, but that omega-6 fatty acids are particularly important for maintaining skin integrity, renal function and the process of birth. Omega-3 fatty acids may be more important in the support of visual and neural functions.

As Lands describes it, in 1963 it was discovered that one of the omega-6 fatty acids could be converted to a signaling molecule called a prostaglandin. Prostaglandins act on the vascular system, affect platelet aggregation and regulate inflammation. Further research revealed that omega-3 and omega-6 fatty acids could be converted to a large set of short-lived locally-acting signaling molecules called eicosanoids. Along with the prostaglandins, these include thromboxanes, leukotrienes and prostacyclins. Representative examples are illustrated below. (Both figures in this post are modified from figures found at Wikipedia.)


There are dozens of eicosanoid molecules, and each of them has many actions. Because of this, there is no simple relationship between a deficiency of omega-3 and omega-6 fatty acids and a defined profile of symptoms. When taken in optimal amounts, the eicosanoids promote the health of the cardiovascular system, the central nervous system, and the immune system. For scientific citations, please see the extensive Notes and References section at the end of the Wikipedia article on Omega-3 Fatty Acid. Positive effects have been shown for lowering blood pressure, improving blood lipid profiles, decreasing the risk of stroke and preventing psychotic disorders.

In a practical sense, a Westernized diet provides an abundant supply of omega-6 fatty acids and a relatively poor supply of omega-3 fatty acids. During the past few decades, healthy eating recommendations have caused us to transition from animal fats, rich in omega-3 fatty acids, to corn oil, safflower oil, cottonseed oil, peanut oil and soybean oil, which are all rich in omega-6 fatty acids and poor in omega-3 fatty acids. This is important because, when it comes to omega-6 fatty acids, we cannot say that if a little is good, a lot is better. An excess of omega-6 fatty acids causes these molecules to form inflammatory intermediates which are relevant to processes such as asthma, arthritis and atherosclerosis.

A review article by Artemis Simopoulos describes how these inflammatory intermediates can be counteracted by decreasing our intake of omega-6 fatty acids and increasing our intake of omega-3 fatty acids. Unfortunately, in the modern world, it takes some thought and financial resources to balance our intake of omega-6 and omega-3 fatty acids. That will be the subject of the next blog post.

Caffeine and Weight Loss

In 2004 the Food and Drug Administration banned the sale of dietary supplements containing ephedra in the United States. Although studies had shown a beneficial effect of the combination of ephedra and caffeine for weight loss in trials of six months or less, there were many reports of heart attacks, strokes, seizures and death caused by ephedra. This caused the FDA to discourage and finally to prohibit the sale of dietary supplements containing ephedrine alkaloids.

Caffeine, however, remains readily available in the form of coffee, tea, chocolate and over-the-counter pills. Does caffeine alone have a beneficial effect on weight loss?

It may, but if it does, the effect is slight. By inhibiting an enzyme that degrades intracellular cyclic AMP, caffeine is able to promote thermogenesis and stimulate fat oxidation. However, the long-term effect of these changes is not dramatic. From 1986 to 1998, Lopez-Garcia et al. studied the effect of changes in caffeine intake in a total of 58,000 health care professionals. Caffeine intake was calculated from the self-reported weekly consumption of coffee, tea, soft drinks and chocolate. Participants were divided into quintiles according to the amount that their caffeine intake had varied, from a net decrease to a net increase over the twelve years of the study. Each quintile gained weight during the study, but in the quintile that had increased its caffeine intake the most, less weight was gained. How much less? Slightly under a pound. Over twelve years. It is also important to note that this was a correlational study, and as we have learned, correlation does not equal causation.

One of the interesting aspects of caffeine consumption is that it is associated with an increase in insulin resistance. In this 2005 article in Diabetes Care, Lee et al. show that lean, obese and type 2 diabetic men experienced a 33-37% reduction in insulin sensitivity immediately following ingestion of a capsule containing caffeine equivalent to about 2-3 cups of coffee. The references in the article confirm that other investigators found similar results in single-dose administration of caffeine, but none of these the addressed the effect of chronic caffeine ingestion on insulin resistance.

This is important because in their discussion Lee et al. point out a paradox. The consumption of coffee (as opposed to consumption of pure caffeine) has an inverse relationship with the incidence with type 2 diabetes. Van Dam et al. saw a dose-response relationship between increasing coffee consumption and a declining risk of type 2 diabetes in younger and middle-aged women. This was true both for caffeinated and decaffeinated coffee. Granted, this was another correlational study, but it does raise the interesting possibility that there is a non-caffeine component of coffee that provides a protective effect against type 2 diabetes. Potassium, magnesium, chlorogenic acid, quinic acid, trigonelline and lignan secoisolariciresinol have all been proposed as possible agents for improved glucose metabolism in coffee drinkers, but the association is mostly speculative.


To summarize, from the literature, it appears that caffeine does not provide much help with weight loss, but on the average it does not hinder it either. Caffeine increases insulin resistance in the short term, but it may or may not do so in the long term. For those who get their caffeine fix by drinking coffee, it is possible but by no means certain that the coffee itself contains one or more compounds that have a beneficial effect on glucose metabolism. As of this writing, the use of caffeine on a low-carb diet is up to the dieter. The science is far from settled.

Cinnamon and Blood Glucose

The other day I was at Sam's Club, pushing my cart past the supplement section on the way to the meat counter. As I glanced at the shelves, I noticed something new. There was a bottle containing 500 mg capsules of cinnamon (specifically, ground Cinnamomum cassia bark). On the one hand, I had heard that cinnamon was able to improve blood glucose levels, but I hadn't read any of the papers. On the other hand, my fasting blood glucose levels had been in the 100 mg/dl range for a while, even though I eat less than 10 grams of carbs per day. I had been taking chromium supplements, but they didn't seem to have much of an effect. Since the cinnamon capsules weren't particularly expensive, I decided to take a chance and I bought them.

When I got home, I pulled up some of the scientific papers on cinnamon and saw that a reasonable dose would be about 1.5 grams per day. I took a capsule at breakfast, lunch and bedtime and the next morning my blood glucose was 95. To my amazement, the readings continued near that value throughout the week. I told a prediabetic friend about this, and she decided to try it as well. She too noticed a drop of about 5-10 mg/dl in her blood glucose levels. Next, my husband told one of the people at work about my experience. She has type 2 diabetes and is taking both oral hypoglycemic agents and a bit of insulin. She tried the cinnamon capsules and her blood glucose levels fell by 50 mg/dl.

Alrighty then. I decided it was time to read the scientific papers and see if there was anything to these anecdotal experiences. This blogpost will summarize my findings, such as they are.

In 2003 a paper by Khan et al. appeared in Diabetes Care. It described a group of 60 people who had type 2 diabetes and were being treated with sulfonylurea drugs. They were divided into six groups, with the first three taking 1, 3 or 6 grams of cinnamon daily while the second three were given placebo capsules of 1, 3 or 6 grams of wheat flour. After 40 days of treatment, the placebo groups experienced no change in fasting serum glucose, but the three treatment groups experienced decreases of 25%, 18% and 29%. There did not appear to be a dose-response because all three levels of cinnamon intake produced similar results.

This result was not totally unexpected because cinnamon had been observed to have insulin-enhancing activity in laboratory studies. With that in mind, several groups performed prospective clinical trials with cinnamon in human beings. Five of these studies were reviewed by Baker et al. in 2008. They concluded that the use of cinnamon did not significantly alter hemoglobin A1c or fasting blood glucose in patients with type 1 or type 2 diabetes.

However, other studies showed that there was an improvement in blood glucose with cinnamon. Zeigenfuss et al. used an aqueous cinnamon extract to treat prediabetic subjects and saw no effect at six weeks, but at twelve weeks observed an 8.4% drop in fasting blood glucose. In 2007 Wang et al. studied women with polycystic ovary syndrome (PCOS), a hormone disorder associated with insulin resistance. After eight weeks of treatment with a cinnamon extract, these women experienced significant declines both in fasting blood glucose and in two measures of insulin resistance. In 2009 Paul Crawford studied a heterogenous group of poorly controlled type 2 diabetics in a primary care setting. Their medications and dietary recommendations were left unchanged, but the treatment group received an add-on dose of 1 gram of cinnamon per day in an open-label study. After 90 days, the treatment group had significantly lowered its hemoglobin A1c from 8.47 to 7.64.

A 2008 lecture by Richard A. Anderson gives some insight into the possible mechanisms of cinnamon enhancement of insulin sensitivity. When insulin binds to its receptor, it starts a signaling cascade that begins with the autophosphorylation of the insulin receptor. In the presence of cinnamon extracts, this autophosphorylation is more robust. Not only that, cinnamon inhibits the dephosphorylation of the insulin receptor, which further enhances the signal. Cinnamon also increases the amount of insulin receptor proteins and of other proteins in the insulin signaling pathway. Cinnamon is not a substitute for insulin, but it does make insulin signaling more sensitive to the insulin that is present in the blood.

In summary, it appears that supplementation with cinnamon may provide a small but significant improvement in insulin sensitivity. It appears to have a greater influence in people with poorly controlled blood sugar, especially in those who are taking drugs that enhance insulin secretion by the pancreas. In people who are pre-diabetic, the glucose-lowering effect seems to be less. In fact, when cinnamon is given to normal subjects, it does not decrease their blood glucose, but instead reduces their postprandial serum insulin. Although the anecdotal experiences I related at the beginning would suggest that cinnamon has an immediate effect on blood glucose, from the scientific literature, it appears that it may take up to 12 weeks to exert its actions.

Even though cinnamon is found in practically every kitchen in the Western world, it is important to note that some people are allergic to cinnamon. If you decide to try cinnamon supplementation, be careful to look for rashes, inflammation of the mucous membranes or even trouble with breathing. Be sure to discontinue the cinnamon if any of these symptoms occur.

That said, it appears that supplementation with cinnamon may be helpful as part of a strategy to normalize blood glucose levels.

Induction Flu

Those of us who have done low-carb for years are happy to sing the praises of the low-carb lifestyle--decreased weight and increased energy, plus improvements in blood pressure, triglycerides, HDL and blood glucose numbers. But in much the same way that the joy of having a new baby diminishes our memory of the pain of childbirth, we find it easy to forget that one of the aspects of low-carbing is very hard. It's called Induction flu, or Atkins flu.

On the Standard American Diet (very aptly named the SAD diet) we are used to eating low fat, moderate protein and high carbohydrate. Our body's primary source of energy comes from the burning of hundreds of grams of carbohydrates we consume every day. When we change from a SAD diet to a low-carb diet, we abruptly remove the macronutrient that has provided most of our energy. Eventually our energy will come from the fat we eat, but in the meantime our bodies have a huge transition to make.

Every nucleated cell in our body contains 46 chromosomes with over 3 billion base pairs of DNA. In that DNA is the information needed to make the enzymes required for us to metabolize both carbohydrates and fats into energy. Although the information is there, it is not translated into enzymes unless those enzymes are actually needed. A person eating a SAD diet will have all the enzymes he or she needs to convert carbohydrates into energy, but very few of the enzymes needed to convert fat into energy.

Typically a low-carb diet is begun at a level of 20 to 30 grams of carbohydrate a day. Suddenly the carbohydrate conversion enzymes no longer have a substrate. They initiate Plan B, which is to utilize the glycogen stored in the liver and muscle tissue. Glycogen is converted to glucose, which is converted to energy. After about a day, glycogen is depleted, and the body moves to Plan C. It notices that fat is available in abundance, and it upregulates the machinery to transcribe the necessary codes from the DNA into RNA, and then to translate that into the enzymes that are required to metabolize the fat into energy. Unfortunately this takes a day or two, and in the meantime the new low-carb dieter starts to experience Induction flu.

The symptoms of Induction flu are not those that are normally associated with dieting. Instead of ravening hunger and cravings, there is a headache and nausea. The dieter may be irritable and lack energy and concentration. Chills and fever are not typical symptoms, but other than that, it feels like the flu and will last for about two days.

What to do? First of all, recognize that this is a transitional state and that it will end. Second, pamper yourself. This does not mean that you dive headfirst back into the carbs, but drink plenty of water, sleep, take a hot bath, take NSAIDs or acetaminophen, watch a good video or read a good book. One of the best strategies is to find a supportive friend either on the low-carb boards or in real life to commiserate with. Simply knowing that this stage is coming and planning for it is one of the keys to getting through it.

Sometimes new low-carbers try to change everything all at once. If you're a caffeine addict, you might want to wait until Induction is over before you give up the caffeine. If you are resolved to start an exercise regime along with the low-carb diet, it might be better to wait until you have recovered from the Atkins flu before you hit the pavement or go to the gym. If you are lightheaded or start having muscle cramps, consider taking a potassium supplement or using Lite Salt or a KCl salt supplement on your food. Low-carb diets have a diuretic effect and tend to make the kidneys excrete potassium.

It takes several weeks for the body to become fully keto-adapted, that is, to complete the conversion from from carb utilization to fat utilization for energy. However, the worst of the process should be over by the end of Day 3. At that point the benefits of low-carbing (increased energy, decreased appetite and a sense of freedom from the enslavement to rising and falling insulin) should start to predominate. Low-carbing is a continuous learning process, but once the Induction flu is over, it's a worthwhile journey into good health.