Sunday, August 30, 2009

Control of Overeating

For many of those who have just started low-carbing, one of the best aspects of the diet is a new-found freedom from the constant need to eat. A low-carber can consume a reasonable portion of food, feel full, and not have to eat again until his or her next scheduled meal.

At least, that's true for many low-carbers. However, some low-carbers find that they still overeat, or that they continue to crave carbohydrates. What then?

One of the more interesting solutions to the overeating problem has been described by diabetes expert Dr. Richard K. Bernstein. He has observed that in some patients, Byetta (generic name, exenatide) is able to curb overeating and carbohydrate cravings. Byetta is an injectable drug that works very much like the natural gut hormone glucagon-like peptide-1 or GLP-1.

GLP-1 is one of the incretin hormones. Whenever food is eaten, GLP-1 is secreted by the L cells in the intestinal mucosa. GLP-1 has several actions:
  1. It stimulates the release of insulin.
  2. It inhibits the release of glucagon.
  3. It slows stomach emptying.
  4. It increases satiety.

When GLP-1 is given in an intravenous infusion to patients with type 2 diabetes, it is able to reduce blood glucose even in severe diabetes. Unfortunately, because GLP-1 has a half-life of about two minutes, it cannot be taken in the form of single injections. The drug Byetta is called an incretin mimetic because it is able to activate the same receptors used by GLP-1. Byetta's advantage is that, because it has a slightly different structure than GLP-1, Byetta has a half-life of about 2.4 hours.

In the treatment of diabetes, Byetta is typically given by injection twice a day, an hour before a meal is eaten. However, because of the 2.4 hour half-life, this means that Byetta cannot provide complete 24-hour control of blood glucose. For that reason, Byetta needs to be taken in combination with other oral hypoglycemic agents such as metformin and the thiazolidinediones. It is able to perform functions #1 and #2 of GLP-1, but it does not do them very well.

However, in its use for functions #3 and #4 (delay of stomach emptying and promotion of satiety), Byetta is much more promising. During a three-year open-label study of Byetta, an unexpected result was noticed. Investigators found that participants lost an average of 12 pounds over the three years, with one in four of these losing an average of almost 29 pounds.

Because of these observations, Dr. Bernstein began using Byetta to help treat overeating in patients who were in the early stages of diabetes. In Dr. Bernstein's Diabetes Solution, he says that he advises his patients to inject 5-10 micrograms of Byetta about one hour before the times when snacking or overeating typically occur. The maximum daily dosage of Byetta is 20 micrograms per day, permitting as many as four injections daily.

Patient reports indicate that Byetta reduces appetite and/or carb cravings for many people but not for all of them. There is no way to predict beforehand who will or will not respond, but it takes only about a month to determine whether a particular person is in the group that can benefit from the weight-loss aspects of the drug. If it does work, it gives the patient the opportunity to train himself or herself in the habit of eating healthy low-carb foods in moderate portions. In that way Byetta is somewhat similar to weight-loss surgery. It is able to give the patient a period of time to adapt to eating less food and making better food choices, but the use of Byetta also allows the patient to avoid the dangers of anesthesia, surgical wound healing and impaired absorption of vital nutrients.

Sunday, August 23, 2009

The Ketogenic Diet and Epilepsy

The logo in the picture above belongs to the Charlie Foundation. "Charlie" is Charlie Abrahams, the son of a Hollywood producer named Jim Abrahams. In 1993, at 20 months of age, Charlie had been having up to 100 epileptic seizures a day. Although he was on several powerful anti-seizure medications, and had even had brain surgery, Charlie's seizures continued. His parents tried everything they could think of to help him. Finally they learned of an old treatment for epilepsy called the ketogenic diet. It consisted of approximately 90% fat, with adequate protein for growth and a very small amount of carbohydrate.

The ketogenic diet had originally been invented in the 1920's. Early in that decade, a physician named Hugh Conklin began to treat children with epilepsy by having them consume only water for 10 to 25 days. Amazingly, when the children resumed normal eating, many of them were found to be seizure-free for long periods of time. Although enforced fasting was a difficult treatment for these children, at that time it was considered a reasonable alternative to a lifetime of constant seizures. Eventually investigators discovered that seizure reduction could also be achieved with a diet that produced many of the effects of starvation while providing sufficient calories for survival and growth. The key was that the diet was very high in fat and very low in carbohydrate and, like starvation, it produced a large amount of ketone bodies including acetoacetate and beta hydroxybutyrate.

Low-carbers know that on a standard American diet, the tissues of the brain use glucose as their primary fuel. They also know that on a low-carb diet, after a period of metabolic adjustment, most of the tissues in the brain are able to use ketone bodies for fuel. For low-carbers, this is just an interesting fact. However, for children in the 1920's with epilepsy, it had profound implications. By maintaining a high level of ketones and a low availability of gluocose for their brains to use as fuel, many children were able to reduce or avoid epileptic seizures altogether.

Then in 1938, a new drug called Dilantin (phenytoin) was introduced. Dilantin proved to be such an effective anticonvulsant that physicians began to turn their attention to pharmaceutical interventions for epilepsy, and the dietary approach to the treatment of epilepsy was all but forgotten. By the 1990's, Johns Hopkins Hospital was one of the few places that treated epileptic children with a ketogenic diet, and even they initiated treatment on only about ten patients per year.

That's where Charlie Abrahams entered the picture. After two days on the Johns Hopkins ketogenic diet, Charlie was seizure-free. (Remember, he had been having up to 100 seizures per day.) After a month, he was off all of his seizure medication. Understandably, his parents were impressed. They used their resources and contacts to establish the Charlie Foundation in order to help other parents whose children were not responding well to standard epileptic treatments.

Fifteen years later, Charlie Abrahams himself is still doing well and can be seen to be a normal teenager in a video filmed in 2008. Because of the resurgence of interest in the ketogenic diet, in 2007 the American Academy of Pediatrics published a review article called The Ketogenic Diet: One Decade Later. The article discusses the dramatic increase in the use of the ketogenic diet for the treatment of epilepsy. Although the mechanism by which the diet reduces seizures is still a matter of speculation, the diet appears to be effective in children of different ages and can be used to treat both generalized and partial seizure disorders. About half of the children who initiate the diet are not able to follow it long-term, but among the rest, about 10%–15% of are seizure-free one year later, while another 30% experience a 90% reduction in seizures. For those who cannot follow the strict ketogenic diet, a small study using a diet that approximated Atkins Induction found that 65% of patients had a 50% reduction in seizures and 35% had a 90% reduction.

The review article as well as the website for the Charlie Foundation make fascinating reading. If you have epilepsy or if you have a child who has epilepsy, it is important to contact experienced professionals before attempting to do the ketogenic diet. It turns out to be much more complicated than just picking up a copy of Dr. Atkins' Diet Revolution and forging ahead on your own. But there appears to be lots of help available for those who would like to consider using a ketogenic diet an an additional approach to the management of difficult-to-control epilepsy.

Sunday, August 16, 2009

Natural Chemicals

My training is in chemistry. Because of that, I tend to see the world as an array of chemicals, from the the cotton in my clothes to the gasoline in my car. But a comment on last week's post reminded me that in recent decades we have been trained to see chemicals in two different classifications--natural and man-made. We have been taught that natural things are by definition good and man-made things may very well be bad and could hurt us in the long run. For those of us who are interested in healthy eating, the distinctions have particular significance. In the world of low-carbing, are natural foods the safest foods? Not necessarily.

One of the natural foods we have been discussing lately is fructose. It's found in high-fructose corn syrup, of course, but it is also found in fruits and honey. Regardless of where it's found, fructose is fructose. The molecule stays the same. And the molecule fructose, when eaten in large quantities, is able to produce a fatty liver, protein glycation, and even gout.

Another natural food is potatoes. Potatoes are not recommended on low-carb diets, but some of us can't keep away from the french fries and chips. Potatoes are in the nightshade family of vegetables and contain the glycoalkaloids solanine and chaconine. These chemicals are acetyl cholinesterase inhibitors and are used to protect the potato from attack by fungus and insects. Unfortunately, they also have a negative effect on some people. They can produce joint pain and symptoms of digestive inflammation, and even mental confusion in a few cases. Cooking destroys some but not all of the glycoalkaloids in potatoes.

Whole wheat is beloved of those who promote a natural lifestyle. Wheat contains proteins called lectins, which act as a primitive immune system for a plant. When wheat is eaten by bacteria, insects, rodents or humans, the ingested lectins are able to bind to cell walls and membranes and cause the clumping of cells, as well as inappropriate cell division and hormone reactions. These effects can cause inflammation and damage to the lining of the small intestine, as well as possible autoimmune reactions if the lectins are absorbed into the circulation. Cooking or baking is able to break down some lectins but not all of them. It is interesting to note that early agriculturalists knew how to decrease lectin content by sprouting and fermenting the wheat they harvested.

Corn oil is another all-natural product that is used both in cooking and in the manufacture of margarine. Corn oil is high in total polyunsaturated fatty acids as well as omega-6 polyunsaturated fatty acids. A recent study in Sweden has shown an association between omega-6 fatty acid intake and breast cancer. A 2006 study showed that the addition of omega-6 fatty acids to prostate tumor cells doubled their growth rate in culture. Another study showed a similar result in a strain of mice that was bred to be susceptible to prostate cancer.

What does all of this mean? Is anything safe to eat? Probably not, but there are obvious risks to fasting indefinitely.

What these examples imply is that a description of "natural" is not a guarantee of safety. Not only that, it wouldn't matter if the foods described above were grown in an organic way on local farms or in the conventional way on huge industrial farms. The natural chemicals (fructose, glycoalkaloids, lectins, omega-6 fatty acids) would be there whether or not organic farming methods were followed.

Fortunately for us, experience has shown that humans are well able to tolerate small amounts of toxic substances. However, for those who are interested in following a maximally healthy lifestyle, each food needs to be considered on its own. Animals defend themselves with horns and hooves. Plants defend themselves with chemicals. Some of these chemicals are beneficial, but some are not, and it pays to be aware of the differences.

Sunday, August 9, 2009

Diet Drinks, Ups and Downs

Diet drinks are one of the mainstays of the low-carb community. Diet Coke, Diet Pepsi, Diet Rite and many more provide fairly palatable carb-free alternatives to sugar-laden soda pop.

Some low-carbers drink all sorts of diet drinks and claim they have no problems with them. Others state that diet drinks cause them to gain weight or cause them to stall in their weight-loss programs, almost as if they were drinking the full-sugar equivalents. One of the ways to look at this phenomenon is to see if diet drinks cause the release of insulin.

One possibility is that the sweet taste of the diet drinks causes a cephalic or first-phase insulin response. Two 1995 studies by Teff, Devine and Engelman had normal-weight men sip and spit solutions that contained either water, aspartame, saccharin, or sucrose. Blood was drawn before and at two-minute intervals after the solutions were tasted. They found no significant increase in plasma insulin, even though the men had tasted the sweetened solutions for as long as three minutes.

Another possibility is that the presence of a sweet taste in the gut causes the release of peptides, and these in turn increase the secretion of insulin as part of a second-phase insulin response. It has recently been found that there is a TR2+T1R3 sweet taste receptor in the intestinal endocrine cells of the gut. In 2007, Margolskee et al. demonstrated that sucralose (brand name, Splenda) could activate this receptor in dishes of intestinal endocrine cells and cause the release of two incretin hormones, GLP-1 and GIP. In a whole organism, the incretin hormones would be expected to promote the release of insulin.

In 2009, Jin Ma et al. tested this hypothesis by infusing 500 ml of various solutions into the stomachs of seven healthy humans. (Putting a solution directly into the stomach bypassed any possible cephalic insulin response.) The first solution contained 50 grams of sucrose in water. The remaining solutions were: normal saline, 80 mg of sucralose in normal saline, and 800 mg of sucralose in normal saline. Of the four solutions, only the sucrose solution caused an increase in blood glucose. And contrary to the findings expected from the intestinal endrocrine cell study, only the sucrose caused an increase in GLP-1, GIP and insulin. The saline and sucralose solutions had no effect. Fujita et al. saw similar results when diabetic Zucker rats were given gastric boluses of solutions of glucose, sucralose, saccharin, acesulfame potassium, and stevia. Only the glucose solution affected the blood glucose, and only the glucose solution
increased the plasma GLP-1 and GIP levels. The artifically-sweetened solutions had no effect.

To drink or not to drink? A recent review of the literature in the American Journal of Clinical Nutrition noted that the use of nonnutritive sweeteners has increased along with the increase in Body Mass Index (BMI) in the United States. However, the authors found that if this is a cause-and-effect relationship, most of the mechanisms by which it is postulated to occur cannot be supported by current evidence. As we can see from the studies cited above, it appears that increased first-phase or second-phase insulin secretion is probably not a good explanation for any gain in weight as a result of diet drinks. As always, research is ongoing, but for now it looks as if diet drinks can be consumed without undue worry about their effect on insulin secretion and an insulin-associated gain in weight.

Sunday, August 2, 2009

Blood Glucose, Cancer, and Coronary Heart Disease

Elevated blood glucose is most often associated with the symptoms of diabetes, such as retinal damage, kidney failure and peripheral neuropathy. However, the consequences of hyperglycemia are not confined to diabetics. As blood glucose values rise in nondiabetics, it is possible for them to experience an increased relative risk of cancer and of coronary heart disease as well.

In 2007, Par Stattin and colleagues published a prospective study that investigated a possible relationship between hyperglycemia and the risk of various forms of cancer. More than sixty thousand Swedish men and women with no previous history of diabetes were studied over a 13-year period. During that time approximately 2,500 cases of cancer were identified in the study group. The investigators looked at the relationship between fasting glucose levels and the risk of cancer in this nondiabetic population. Among the participants who had elevated fasting blood glucose, there were small but statistically significant increases in the relative risk for several specific types of cancer. These included pancreatic cancer, cancer of the urinary tract and malignant melanoma. In women there was an increased risk of endometrial cancer. Among women less than 49 years of age, there was an increased risk of breast cancer. On the other hand, in men there was actually a decrease in the risk of prostatic cancer as fasting blood glucose levels rose.

Nondiabetics were also shown to have an association between glycemic control and the risk of coronary heart disease in a 2005 study published in the Archives of Internal Medicine. In a prospective study, investigators followed 1321 nondiabetic adults to assess a possible relationship between the level of hemoglobin A1c (HbA1c) and the incidence of coronary heart disease.

Hemoglobin A1c measures the percentage of glycated hemoglobin in a patient's red blood cells. The HbA1c value provides a picture of a person's average blood glucose control for the previous 2 to 3 months. The normal range for HbA1c in people without diabetes is
4% to 6%. For diabetics, the American Diabetes Association recommends that the HbA1c be maintained at 7.0% or less.

The nondiabetic patients in the coronary heart disease study were followed for 8 to 10 years. In order to remove possibly confounding variables, when the data was analyzed, it was adjusted for age, race, sex, BMI, blood pressure, LDL cholesterol, HDL cholesterol, triglycerides and smoking status. The adjustments for these risk factors allowed the investigators to examine whether hyperglycemia might provide an independent risk factor for coronary heart disease. They found that when HbA1c was below 4.6%, the adjusted data showed no apparent relationship between glycemic control and an increased risk of coronary heart disease. However, as the HbA1c rose above 4.6%, the adjusted data showed that not only did the risk of coronary heart disease rise, but it did so at an ever-increasing rate. The study found that the risk of coronary heart disease in nondiabetics rose 2.4-fold with every 1% increase in HbA1c above 4.6%.

Findings similar to those seen in both of these studies have also been reported by other investigators, and references can be found within each paper. However, it is important to remember that correlation does not equal causation. The relationship between increased blood glucose in nondiabetics and the incidence of cancer or the incidence of coronary heart disease may rest upon variables that are not as yet defined. However, it is worth noting that it may be important even for nondiabetics to keep an eye on their fasting blood glucose and their HbA1c.