Wednesday, February 24, 2010

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.

Tuesday, February 16, 2010

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.

Tuesday, February 9, 2010

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.

Monday, February 1, 2010

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.