All diets succeed at first, and eventually fail

It is not very hard to find studies supporting one diet or another. Gardner and colleagues, for example, conducted a study in which the Atkins diet came out on top when compared with the Zone, Ornish, and LEARN diets (). In Dansinger and colleagues’ study (), on the other hand, following the Atkins diet led to relatively poor results compared with the Ornish, Weight Watchers, and Zone diets.

Often the diets compared have different macronutrient ratios, which end up becoming the focus of the comparison. Many consider Sacks and colleagues’ conclusion, based on yet another diet comparison study (), to be the most consistent with the body of evidence as a whole: “Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize”.

I think there is a different conclusion that is even more consistent with the body of evidence out there. This conclusion is highlighted by the findings of almost all diet studies where participants were followed for more than 1 year. But the relevant findings are typically buried in the papers that summarize the studies, and are almost never mentioned in the abstracts. Take for example the study by Toubro and Astrup (); Figure 3 below is used by the authors to highlight the study’s main reported finding: “Ad lib, low fat, high carbohydrate diet was superior to fixed energy intake for maintaining weight after a major weight loss”.

But what does the figure above really tell us? It tells us, quite simply, that both diets succeeded at first, and then eventually failed. One failed slightly less miserably than the other, in this study. The percentage of subjects that maintained a weight loss above 25 kg (about 55 lbs) approached zero after 12 months, in both diets. This leads us to the conclusion below, which is always missing in diet studies even when the evidence is staring back at us. This is arguably the conclusion that is the most consistent with the body of evidence out there.

All diets succeed at first, and eventually fail.

In using the terms “succeed” and “fail” I am referring to the diets’ effects on the majority of the participants. This is in fact better demonstrated by the figure below, from the same study by Toubro and Astrup; it is labeled as Figure 2 there. Most of the participants at a certain weight, lose a lot of weight within a period of 1 year or so, and after 2 years (see the two points at the far right) are at the same original weight again. What is the average time to regain back the weight? From what I’ve seen in the literature, all the weight and some tends to be regained after 2-3 years.

The regained weight is not at all lean body mass. It is primarily, if not entirely, body fat. In fact, many studies suggest that those who diet tend to have a higher percentage of body fat when they regain their original weight; proportionally to how fast they regain the weight lost. Since the extra body fat tends to cause additional problems, which are compounded by the dieting process’ toll on the body, those dieters would have been slightly better off not having dieted in the first place.

Guyenet and Schwartz have recently authored an article that summarizes quite nicely what tends to happen with both obese and lean dieters (). Take a look at Figure 2 of the article below. The obese need to lose body fat to improve health markers, and avoid a number of downstream complications, such as type 2 diabetes and cancer (). Yet, with very few exceptions, the obese (and even the overweight) remain obese (or overweight) after dieting; regardless of the diet.

So what about those exceptions, what do they do to lose significant amounts of body fat and keep it off? Well, I rarely use myself as an example for anything in this blog, but this is something with which I unfortunately/fortunately have personal experience. I was obese, lost about 60 lbs of weight, and kept it off for quite a while already (). Like most of the formerly obese, I can very easily gain body fat back.

But I don’t seem to be gaining back the formerly lost body fat, and the reason is consistent with some of the studies based on data from the National Weight Control Registry, which stores information about adults who lost 30 lbs or more of weight and kept it off for at least 1 year (). I systematically measure my weight, body fat percentage, and a number of other variables; probably even more than the average National Weight Control Registry member. Based on those measurements, I try to understand how my body responds in the short and long term to stimuli such as different exercise, types of food, calorie restriction, sleep patterns etc.

And I act accordingly to keep any body fat gain from happening; by, for example, varying calorie intake, increasing exercise intensity, varying the types of food I eat etc. With a few exceptions (e.g., avoiding industrial seed oils), there is no generic formula. Customization based on individual responses and cyclical patterns seems to be a must.

Looking back, it was relatively easy for me to lose all that fat. This is consistent with the studies summarized in this post; all diets that rely on caloric reduction work marvelously at first for most people. The really difficult part is to keep the body fat off. I believe that this is especially true as the initial years go by, and becomes easier after that. This has something to do with initial inertia, which I will discuss soon in a post on metabolic rates and their relationship with overall body mass.

For people living in the wild, I can see one thing working in their favor. And that is not regular starvation; sapiens is too smart for that. It is laziness. Hunger has to reach a certain threshold for people to want to do some work to get their food; this acts as a natural body composition regulator, something that I intend to discuss in one of my next posts. It seems that people almost never become obese in the wild, without access to industrial foods.

As for living in the wild, in spite of the romantic portrayals of it, the experience is not as appealing after you really try it. The book Yanomamo: The Fierce People () is a solid, if not somewhat shocking, reminder of that. I had the opportunity to meet and talk at length with its author, the great anthropologist Nap Chagnon, at one of the Human Behavior and Evolution Society conferences. The man is a real-life Indiana Jones ().

In the formerly obese, the body seems to resort to “guerrilla warfare”, employing all kinds of physiological and psychological mechanisms, some more subtle than others, to make sure that the lost fat is recovered. Why? I have some ideas, which I have discussed indirectly in posts throughout this blog, but I still need to understand the whole process a bit better. My ideas build on the notion of compensatory adaptation ().

You might have heard some very smart people say that you do not need to measure anything to lose body fat and keep it off. Many of those people have never been obese. Those who have been obese often had not cleared the 2-3 year “danger zone” by the time they made those statements.

There are many obese or overweight public figures (TV show hosts, actors, even health bloggers) who embark on a diet and lose a dramatic amount of body fat. They talk and/or write for a year or so about their success, and then either “disappear” or start complaining about health issues. Those health issues are often part of the “guerrilla warfare” I mentioned above.

A few persistent public figures will gain the fat back, in part or fully, and do the process all over again. It makes for interesting drama, and at least keeps those folks in the limelight.

What is a good low carbohydrate diet? It is a low calorie one

My interview with Jimmy Moore should be up on the day that this post becomes available. (I usually write my posts on weekends and schedule them for release at the beginning of the following weeks.) So the time is opportune for me to try to aswer this question: What is a good low carbohydrate diet?

For me, and many people I know, the answer is: a low calorie one. What this means, in simple terms, is that a good low carbohydrate diet is one with plenty of seafood and organ meats in it, and also plenty of veggies. These are low carbohydrate foods that are also naturally low in calories. Conversely, a low carbohydrate diet of mostly beef and eggs would be a high calorie one.

Seafood and organ meats provide essential fatty acids and are typically packed with nutrients. Because of that, they tend to be satiating. In fact, certain organ meats, such as beef liver, are so packed with nutrients that it is a good idea to limit their consumption. I suggest eating beef liver once or twice a week only. As for seafood, it seems like a good idea to me to get half of one’s protein from them.

Does this mean that the calories-in-calories-out idea is correct? No, and there is no need to resort to complicated and somewhat questionable feedback-loop arguments to prove that calories-in-calories-out is wrong. Just consider this hypothetical scenario; a thought experiment. Take two men, one 25 years of age and the other 65, both with the same weight. Put them on the same exact diet, on the same exact weight training regime, and keep everything else the same.

What will happen? Typically the 65-year-old will put on more body fat than the 25-year-old, and the latter will put on more lean body mass. This will happen in spite of the same exact calories-in-calories-out profile. Why? Because their hormonal mixes are different. The 65-year-old will typically have lower levels of circulating growth hormone and testosterone, both of which significantly affect body composition.

As you can see, it is not all about insulin, as has been argued many times before. In fact, average and/or fasting insulin may be the same for the 65- and 25-year-old men. And, still, the 65-year-old will have trouble keeping his body fat low and gaining muscle. There are other hormones involved, such as leptin and adiponectin, and probably several that we don’t know about yet.

A low carbohydrate diet appears to be ideal for many people, whether that is due to a particular health condition (e.g., diabetes) or simply due to a genetic makeup that favors this type of diet. By adopting a low carbohydrate diet with plenty of seafood, organ meats, and veggies, you will make it a low calorie diet. If that leads to a calorie deficit that is too large, you can always add a bit more of fat to it. For example, by cooking fish with butter and adding bacon to beef liver.

One scenario where I don’t see the above working well is if you are a competitive athlete who depletes a significant amount of muscle glycogen on a daily basis – e.g., 250 g or more. In this case, it will be very difficult to replenish glycogen only with protein, so the person will need more carbohydrates. He or she would need a protein intake in excess of 500 g per day for replenishing 250 g of glycogen only with protein.

Ketones and Ketosis: Physiological and pathological forms

Ketones are compounds that have a specific chemical structure. The figure below (from: Wikipedia) shows the chemical structure of various types of ketones. As you can see, all ketones share a carbonyl group; that is the “O=” part of their chemical structure. A carbonyl group is an oxygen atom double-bonded to a carbon atom.

Technically speaking, many substances can be classified as ketones. Not all of these are involved in the same metabolic processes in humans. For example, fructose is technically a ketone, but it is not one of the three main ketones produced by humans from dietary macronutrients (discussed below), and is not metabolized in the same way as are those three main ketones.

Humans, as well as most other vertebrates, produce three main ketones (also known as ketone bodies) from dietary macronutrients. These are acetone, acetoacetate and beta-hydroxybutyrate. Low carbohydrate diets tend to promote glycogen depletion, which in turn leads to increased production of these ketones. Glycogen is stored in the liver and muscles. Liver glycogen is used by the body to maintain blood glucose levels within a narrow range in the fasted state. Examples of diets that tend to promote glycogen depletion are the Atkins Diet and Kwaśniewski’s Optimal Diet.

A search for articles on ketosis in scientific databases usually returns a large number of articles dealing with ketosis in cows. Why? The reason is that ketosis reduces milk production, by both reducing the amount of fat and glucose available for milk synthesis. In fact, ketosis is referred to as a “disease” in cows.

In humans, most articles on ketosis refer to pathological ketosis (a.k.a. ketoacidosis), especially in the context of uncontrolled diabetes. One notable exception is an article by Williamson (2005), from which the table below was taken. The table shows ketone concentrations in the blood under various circumstances, in mmol/l.

As you can see, relatively high concentrations of ketones occur in newborn babies (neonate), in adults post-exercise, and in adults fed a high fat diet. Generally speaking, a high fat diet is a low carbohydrate diet, and a high carbohydrate diet is a low fat diet. (One occasionally sees diets that are high in both carbohydrates and fat; which seem excellent at increasing body fat and thus reducing life span. This diet is apparently popular among sumo wrestlers, where genetics and vigorous exercise usually counter the negative diet effects.)

Situations in which ketosis occurs in newborn babies (neonate), in adults post-exercise, and in adults fed a high fat diet are all examples of physiological, or benign, ketosis. Ketones are also found in low concentrations in adults fed a standard American diet.

Ketones are found in very high concentrations in adults with untreated diabetes. This is an example of pathological ketosis, even though ketones are produced as part of a protective compensatory mechanism to spare glucose for the brain and red blood cells (which need glucose to function properly). Pathological ketosis leads to serum ketone levels that can be as much as 80 times (or more) those found in physiological ketosis.

Serum ketone concentrations increase proportionally to decreases in stored glycogen and, when glycogen is low or absent, correlate strongly (and inversely) with blood glucose levels. In some individuals glycogen is practically absent due to a genetic condition that leads to hepatic glycogen synthase deficiency. This is a deficiency of the enzyme that promotes glycogen synthesis by the liver. The figure below (also from Williamson, 2005) shows the variations in glucose and ketone levels in a child with glycogen synthase deficiency.

What happened with this child? Williamson answers this question: “It is of interest that this particular child suffered no ill effects from the daily exposure to high concentrations of ketone bodies, underlining their role as normal substrates for the brain when available.”

Unlike glucose and lipoprotein-bound fats (in VLDL, for example), unused ketones cannot be converted back to substances that can be stored by the body. Thus excess ketones are eliminated in the urine; leading to their detection by various tests, e.g., Ketostix tests. This elimination of unused ketones in the urine is one of the reasons why low carbohydrate diets are believed to lead to enhanced body fat loss.

In summary, ketones are present in the blood most of the time, in most people, whether they are on a ketogenic diet or not. If they do not show up in the urine, it does not mean that they are not present in the blood; although it usually means that their concentration in the blood is not that high. Like glucose, ketones are soluble in water, and thus circulate in the blood without the need for carriers (e.g., albumin, which is needed for the transport of free fatty acids; and VLDL, needed for the transport of triglycerides). Like glucose, they are used as sources of energy by the brain and by muscle tissues.

It has been speculated that ketosis leads to accelerated aging, through the formation of advanced glycation endproducts (AGEs), a speculation that seems to be largely unfounded (see this post). It is difficult to believe that a metabolic process that is universally found in babies and adults post-exercise would have been favored by evolution if it led to accelerated aging.

References:

Williamson, D.H. (2005). Ketosis. Encyclopedia of Human Nutrition, 91-98.

Long-term adherence to Dr. Kwaśniewski’s Optimal Diet: Healthy with high LDL cholesterol

This is a study (Grieb, P. et al., 2008; full reference at the end of this post) that I read a few years ago, right after it came out, and at the time I recall thinking about the apparent contradiction between the positive effects of the Optimal Diet and the very elevated LDL cholesterol levels among the participants. I say “contradiction” because of the established and misguided dogma among medical doctors, particularly general practitioners, that decreasing LDL cholesterol levels is the best strategy to avoid cardiovascular disease.

The Optimal Diet is one of the best examples of a healthy diet where LDL cholesterol levels are generally high, in fact much higher than most people are willing to accept as healthy today. (In this study, LDL cholesterol levels were calculated based on the Friedewald equation.)

It is not uncommon to see people concerned about their high LDL cholesterol levels after adopting a low carbohydrate diet. (A low carbohydrate diet is, generally speaking, a high fat diet.) This study shows that this is a rather common thing, and also that it is not something that those who experience it should be too concerned about. To be convinced of this, one can always do a VAP test (see this post for a link to a sample VAP test report) and check his or her LDL particle pattern.

The study presents the Optimal Diet as the Polish equivalent to the Atkins diet. It states that the Diet’s main characteristic is maintaining the proportion of proteins:fat:carbs. in the range of 1:2.5-3.5:0.5, with no restriction on the amount of food consumed. In fact, as you will see in this post, more than 70 percent of the calories consumed by the study participants came from fat.

Easily digestible carbohydrate-rich foods are not part of the Optimal Diet. More specifically, the following foods were listed as not being allowed in the Optimal Diet: sucrose, sweets, honey, jam, white rice, bread, starches in general, beans, potatoes (only in small amounts), and sweetened drinks. Also, the Optimal Diet is definitely a low carbohydrate diet, but not what is often referred to as a "very low carbohydrate diet". In this study, the typical carbohydrate intake per day was around 60 g.

Thirty-one healthy people participated in the study, 17 women and 14 men. The average age was 51.7 (standard deviation: 16.6). They had self-reportedly adhered to the Optimal Diet for at least 1 year prior to the study; the average period of adherence was 4.1 years (standard deviation: 1.9). So, the vast majority had been on the diet for more than 2.2 years, about half for 4.1 years or more, and about one-sixth for more than 6 years. (Check this post if you want to know how these figures can be calculated based on the average period of adherence and the standard deviation.)

The table below (click on it to enlarge) shows anthropometric and physiologic characteristics of the participants. Note that longer adherence to the Optimal Diet (right end of the table) was associated with lower systolic and diastolic blood pressure, as well as lower body mass index (BMI). (It was also associated with lower height and BMR, so I am guessing that more women tended to be long-term adherers than men.) Most of the participants had BMIs in the normal range, with only one in the obese category. That was a 43-year-old man who followed the diet for 1.5 years; he had a BMI of 34.1.

The macronutrient distribution of the Optimal Diet is shown on the table below (click on it to enlarge), as followed by the participants. As you can see, protein intake was not that high; about 53.9 g per day on average for men, a bit less for women. Note the percentage of calories from fat: more than 77 percent for men and 72 percent for women. Given the BMIs just discussed, one can safely say based on this that eating a lot of fat did not make the participants fat.

The table below (click on it to enlarge) has some interesting health markers. Note that free fatty acids (FFAs) were elevated. This is to be expected, as these folks were burning fat for energy most of the time, and not as much glucose. The FFAs are not really “free”, but bound to a protein called albumin, which is abundant in human blood. FFAs yield large quantities of adenosine triphosphate (ATP), the main energy “currency” used by the body.

These levels of FFAs are also usually associated with mild ketosis, where ketones are produced by the body and used for energy. Unlike albumin-bound FFAs, ketones are soluble in water, and thus circulate freely through the blood. The mild ketosis experienced by the participants was possibly to the point where ketones showed in the urine. The article mentions this, and provides a measure of beta-HB (beta-hydroxybutyrate, a ketone body), which is elevated as expected, but does not provide urine or other blood ketone measures (e.g., blood acetone levels). Also note the fairly healthy fasting glucose levels, slightly higher in men than in women, but fairly low overall. Fairly healthy insulin levels as well; at the high end of what Stephan at Whole Health Source would recommend, but still significantly lower than the average insulin level in the U.S. at the time of the article's publication.

Finally, the table below (click on it to enlarge) shows lipids and a few other measures. Total cholesterol was on average a bit more than 278 mg/dL. LDL cholesterol was a bit higher than 188 mg/dL on average; high enough to make most doctors cringe today. Based on the means and standard deviations provided, we can estimate that about 16 percent of the participants had LDL cholesterol levels higher than 228.1 mg/dL. About 2.5 percent of the participants had LDL cholesterol levels higher than 268 mg/dL. And this is all after adhering to the diet for a relatively long period of time; even higher LDL cholesterol levels might have occurred right after adoption.

Yet average HDL cholesterol was a very high and protective 71.6 mg/dL. This high HDL and the relatively low triglycerides suggest a large-buoyant non-atherogenic LDL particle pattern.

Average HOMA(IR), a measure of insulin resistance, was a low 1.35 mU/mmol; strongly indicating, together with the relatively low fasting glucose levels, that the participants were far from being pre-diabetic, let alone diabetic.

Diabetes is a strong risk factor for cardiovascular disease, and many other health complications; much more so than elevated LDL cholesterol.

The Optimal Diet does not seem to be a diet for bodybuilders, but I would say that, overall, Peter at Hyperlipid has chosen a diet that makes some sense.

Reference:

Grieb, P. et al. (2008). Long-term consumption of a carbohydrate-restricted diet does not induce deleterious metabolic effects. Nutrition Research, 28(12), 825-833.

Ketosis, methylglyoxal, and accelerated aging: Probably more fiction than fact

This is a follow up on this post. Just to recap, an interesting hypothesis has been around for quite some time about a possible negative effect of ketosis. This hypothesis argues that ketosis leads to the production of an organic compound called methylglyoxal, which is believed to be a powerful agent in the formation of advanced glycation endproducts (AGEs).

In vitro research, and research with animals (e.g., mice and cows), indeed suggests negative short-term effects of increased ketosis-induced methylglyoxal production. These studies typically deal with what appears to be severe ketosis, not the mild type induced in healthy people by very low carbohydrate diets.

However, the bulk of methylglyoxal is produced via glycolysis, a multi-step metabolic process that uses sugar to produce the body’s main energy currency – adenosine triphosphate (ATP). Ketosis is a state whereby ketones are used as a source of energy instead of glucose.

(Ketones also provide an energy source that is distinct from lipoprotein-bound fatty acids and albumin-bound free fat acids. Those fatty acids appear to be preferred vehicles for the use of dietary or body fat as a source of energy. Yet it seems that small amounts of ketones are almost always present in the blood, even if they do not show up in the urine.)

Thus it follows that ketosis is associated with reduced glycolysis and, consequently, reduced methylglyoxal production, since the bulk of this substance (i.e., methylglyoxal) is produced through glycolysis.

So, how can one argue that ketosis is “a recipe for accelerated AGEing”?

One guess is that ketosis is being confused with ketoacidosis, a pathological condition in which the level of circulating ketones can be as much as 40 to 80 times that found in ketosis. De Grey (2007) refers to “diabetic patients” when he talks about this possibility (i.e., the connection with accelerated AGEing), and ketoacidosis is an unfortunately common condition among those with uncontrolled diabetes.

A gentle body massage is relaxing, and thus health-promoting. Add 40 times to the pressure, and the massage will become a form of physical torture; certainly unhealthy. That does not mean that a gentle body massage is unhealthy.

Interestingly, ketoacidosis often happens together with hyperglycemia, so at least part of the damage associated with ketoacidosis is likely to be caused by high blood sugar levels. Ketosis, on the other hand, is not associated with hyperglycemia.

Finally, if ketosis led to accelerated AGEing to the same extent as, or worse than, chronic hyperglycemia does, where is the long-term evidence?

Since the late 1800s people have been experimenting with ketosis-inducing diets, and documenting the results. The Inuit and other groups have adopted ketosis-inducing diets for much longer, although evolution via selection might have played a role in these cases.

No one seems to have lived to be 150 years of age, but where are the reports of conditions akin to those caused by chronic hyperglycemia among the many that went “banting” in a more strict way since the late 1800s?

The arctic explorer Vilhjalmur Stefansson, who is reported to have lived much of his adult life in ketosis, died in 1962, in his early 80s. After reading about his life, few would disagree that he lived a rough life, with long periods without access to medical care. I doubt that Stefansson would have lived that long if he had suffered from untreated diabetes.

Severe ketosis, to the point of large amounts of ketones being present in the urine, may not be a natural state in which our Paleolithic ancestors lived most of the time. In modern humans, even a 24 h water fast, during an already low carbohydrate diet, may not induce ketosis of this type. Milder ketosis states, with slightly elevated concentrations of ketones showing up in blood tests, can be achieved much more easily.

In conclusion, the notion that ketosis causes accelerated aging to the same extent as chronic hyperglycemia seems more like fiction than fact.

Reference:

De Grey, A. (2007). Ending aging: The rejuvenation breakthroughs that could reverse human aging in our lifetime. New York: NY: St. Martin’s Press.

Want to improve your cholesterol profile? Replace refined carbs and sugars with saturated fat and cholesterol in your diet

An interesting study by Clifton and colleagues (1998; full reference and link at the end of this post) looked at whether LDL cholesterol particle size distribution at baseline (i.e., beginning of the study) for various people was a determinant of lipid profile changes in each of two diets – one low and the other high in fat. This study highlights a few interesting points made in a previous post, which are largely unrelated to the main goal or findings of the study, but that are supported by side findings:

- As one increases dietary cholesterol and fat consumption, particularly saturated fat, circulating HDL cholesterol increases significantly. This happens whether one is taking niacin or not, although niacin seems to help, possibly as an independent (not moderating) factor. Increasing serum vitamin D levels, which can be done through sunlight exposure and supplementation, are also known to increase circulating HDL cholesterol.

- As one increases dietary cholesterol and fat consumption, particularly saturated fat, triglycerides in the fasting state (i.e., measured after a 8-hour fast) decrease significantly, particularly on a low carbohydrate diet. Triglycerides in the fasting state are negatively correlated with HDL cholesterol; they go down as HDL cholesterol goes up. This happens whether one is taking niacin or supplementing omega 3 fats or not, although these seem to help, possibly as independent factors.

- If one increases dietary fat intake, without also decreasing carbohydrate intake (particularly in the form of refined grains and sugars), LDL cholesterol will increase. Even so, LDL particle sizes will shift to more benign forms, which are the larger forms. Not all LDL particles change to benign forms, and there seem to be some genetic factors that influence this. LDL particles larger than 26 nm in diameter simply cannot pass through the gaps in the endothelium, which is a thin layer of cells lining the interior surface of arteries, and thus do not induce plaque formation.

The study by Clifton and colleagues (1998) involved 54 men and 51 women with a wide range of lipid profiles. They first underwent a 2-week low fat period, after which they were given two liquid supplements in addition to their low fat diet, for a period of 3 weeks. One of the liquid supplements contained 31 to 40 g of fat, and 650 to 845 mg of cholesterol. The other was fat and cholesterol free.

Studies that adopt a particular diet at baseline have the advantage of departing from a uniform diet across conditions. They also typically have one common characteristic: the baseline diet reflects the beliefs of the authors about what an ideal diet is. That is not always the case, of course. If this was indeed the case here, we have a particularly interesting study, because in that case the side findings discussed below contradicted the authors’ beliefs.

The table below shows the following measures for the participants in the study: age, body mass index (BMI), waist-to-hip ratio (WHR), total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and three subtypes of high-density lipoprotein (HDL) cholesterol. LDL cholesterol is the colloquially known as the “bad” type, and “HDL” as the good one (which is an oversimplification). In short, the participants were overweight, middle-aged men and women, with relatively poor lipid profiles.

At the bottom of the table is the note “P < 0.001”, following a small “a”. This essentially means that on the rows indicated by an “a”, like the “WHR” row, the difference in the averages (e.g., 0.81 for women, and 0.93 for men, in the WHR row) was significantly different from what one would expect it to be due to chance alone. More precisely, the likelihood that the difference was due to chance was lower than 0.001, or 0.1 percent, in the case of a P < 0.001. Usually a difference between averages (a.k.a. means) associated with a P < 0.05 will be considered statistically significant.

Since the LDL cholesterol concentrations (as well as other lipoprotein concentrations) are listed on the table in mmol/L, and many people receive those measures in mg/dL in blood lipid profile test reports, below is a conversion table for LDL cholesterol (from: Wikipedia).

The table below shows the dietary intake in the low and high fat diets. Note that in the high fat diet, not only is the fat intake higher, but so is the cholesterol intake. The latter is significantly higher, more than 4 times the intake in the low fat diet, and about 2.5 times the recommended daily value by the U.S. Food and Drug Administration. The total calorie intake is reported as slightly lower in the high fat diet than in the low fat diet.

Note that the largest increase was in saturated fat, followed by an almost equally large increase in monounsaturated fat. This, together with the increase in cholesterol, mimics a move to a diet where fatty meat and organs are consumed in higher quantities, with a corresponding reduction in the intake of refined carbohydrates (e.g., bread, pasta, sugar, potatoes) and lean meats.

Finally, the table below shows the changes in lipid profiles in the low and high fat diets. Note that all subtypes of HDL (or "good") cholesterol concentrations were significantly higher in the high fat diet, which is very telling, because HDL cholesterol concentrations are much better predictors of cardiovascular disease than LDL or total cholesterol concentrations. The higher the HDL cholesterol, the lower the risk of cardiovascular disease.

In the table above, we also see that triglycerides are significantly lower in the high fat diet, which is also good, because high fasting triglyceride concentrations are associated with cardiovascular disease and also insulin resistance (which is associated with diabetes).

However, the total and LDL cholesterol were also significantly higher in the high fat compared to the low fat diet. Is this as bad as it sounds? Not when we look at other factors that are not clear from the tables in the article.

One of those factors is the likely change in LDL particle size. LDL particle sizes almost always increase with significant increases in HDL; frequently going up in diameter beyond 26 nm, and thus passing the threshold beyond which an LDL particle can penetrate the endothelium and help form a plaque.

Another important factor to take into consideration is the somewhat strange decision by the authors to use the Friedewald equation to estimate the LDL concentrations in the low and high fat diets. Through the Friedewald equation, LDL is calculated as follows (where TC is total cholesterol):

    LDL = TC – HDL – Triglycerides / 5

Here is one of the problems with the Friedewald equation. Let us assume that an individual has the following lipid profile numbers: TC = 200, HDL = 50, and trigs. = 150. The calculated LDL will be 120. Let us assume that this same individual reduces trigs. to 50, from the previous 150, keeping all of the other measures constant. This is a major improvement. Yet, the calculated LDL will now be 140, and a doctor will tell this person to consider taking statins!

By the way, most people who do a blood test and get their lipid profile report also get their LDL calculated through the Friedewald equation. Usually this is indicated through a "CALC" note next to the description of the test or the calculated LDL number.

Finally, total cholesterol is not a very useful measure, because an elevated total cholesterol may be primarily reflecting an elevated HDL, which is healthy. Also, a slightly elevated total cholesterol seems to be protective, as it is associated with reduced overall mortality and also reduced mortality from cardiovascular disease, according to U-curve regression studies comparing mortality and total cholesterol levels in different countries.

We do not know for sure that the participants in this study were consuming a lot of refined carbohydrates and/or sugars at baseline. But it is a safe bet that they were, since they were consuming 214 g of carbohydrates per day. It is difficult, although not impossible, to eat that many carbohydrates per day by eating only vegetables and fruits, which are mostly water.

This is why when one goes on a paleo diet, he or she reduces significantly the amount of dietary carbohydrates; even more so on a targeted low carbohydrate diet, such as the Atkins diet. Richard K. Bernstein, who is a type 1 diabetic and has been adopting a strict low carbohydrate diet during most of his adult life, had the following lipid profile at 72 years of age: HDL = 118, LDL = 53, trigs. = 45. His fasting blood sugar was reportedly 83 mg/dl. Click here to listen to an interview with Dr. Bernstein on the The Livin' La Vida Low-Carb Show.

The lipid profile improvement observed (e.g., a 14 percent increase in HDL from baseline for men, and about half that for women, in only 3 weeks) was very likely due to an increase in dietary saturated fat and cholesterol combined with a decrease in refined carbohydrates and sugars. The improvement would probably have been even more impressive with a higher increase in saturated fat, as long as it was accompanied by the elimination of refined carbohydrates and sugars from the participants’ diets.

Reference:

Clifton, P. M., M. Noakes, and P. J. Nestel (1998). LDL particle size and LDL and HDL cholesterol changes with dietary fat and cholesterol in healthy subjects. J. Lipid. Res. 39: 1799–1804.

Half-hearted Atkins diet and cardiovascular disease

I would like to comment on a recent article comparing the Atkins, Ornish and South Beach diets (Miller et al., 2009; full reference at the end of this posting), which has been causing quite a lot of commotion among bloggers recently. Especially low carb. bloggers.

An excellent post by Michael Eades clarifies a number of issues with the study, including what one could argue is the study's main flaw. Apparently the study compared a half-hearted Atkins diet, with probably equally half-hearted Ornish and South Beach diets.

I refer to the study's Atkins diet as half-hearted because it seems to rely on a daily consumption of between 120 and 180 grams of carbohydrates. This is unlikely to lead to ketosis, the cornerstone of the Atkins diet, where the body uses ketone bodies (made from dietary as well as body fat) as a source of energy.

As I see it, the main findings of the study were that the participants in the half-hearted Atkins diet, after a period of 4 weeks on the diet, and when compared with the participants in the other diets, had: (a) greater levels of total cholesterol and LDL cholesterol, with only a small improvement in their HDL cholesterol and triglycerides levels; and (b) greater levels of markers for inflammation (e.g., C-reactive protein).

The participants were young and healthy. Their average age was 30.6 years, and their average body mass index was 22.6. On average, their total cholesterol was 184.9 mg/dL, triglycerides were 78.1 mg/dL, LDL cholesterol was 107.2 mg/dL, and HDL cholesterol was 62.2 mg/dL. These are arguably fairly healthy numbers; although quite a few doctors might want to put most of these folks preventively on statins because of their LDL being greater than 100.

What I find interesting about this study, and consistent with both my own experience and also a theory that I have, is that it suggests that a low carb. diet has to really be low carb. in order to bring about the benefits that one normally sees as a result of a diet that induces ketosis. A diet with, say, > 150 g of refined grains per day, is not really a low carb. diet.

Again, in my experience, and that of many other people, a truly low carb. diet (very low in, if not devoid of, refined carbs and sugars), will lead to an impressive increase in HDL cholesterol (especially for those who have low HDL to start with), an equally impressive decrease in triglycerides, increased insulin sensitivity, and possibly a decrease in LDL.

However, a half-hearted Atkins diet may actually lead to elevated LDL (of the small-dense type), and more inflammation, just like this study suggests it does, without the benefits regarding HDL and trigs. The reason is that the still relatively high level of carbohydrate intake, especially if it comes in the form of refined carbs. and sugars, will lead to higher levels of insulin being secreted into the bloodstream. This will promote increased body fat deposition. The extra saturated fat being consumed will be turned into body fat, and not used as energy, starving the cells and leading to increased hunger.

A diet rich in saturated fat may indeed be bad when it is also a diet even moderately rich in insulin-boosting, easily digestible carbs. This may be one of the main reasons why there have been so many studies in the past showing a correlation between saturated fat consumption and heart disease; studies that typically did not control for carbohydrate consumption.

In a recent interview on the Livin' La Vida Low-Carb Blog, Dr. John Salerno goes into more detail regarding this issue, recommending a much more rigid adoption of the Atkins diet than many think is okay. (In fact, I often talk to people who think that if they cut a very high carb. intake in half - e.g., from 400 to 200 grams per day - replacing the carbs with fat, they will be halfway into a full blown Atkins diet.) Dr. Salerno has worked in the past with Dr. Atkins. He calls his diet the Silver Cloud Diet. I am not sure I agree with all that Dr. Salerno had to say, but his argument in favor of a diet very low in carbs. does make sense to me.

Finally, I think that it is dangerous to extrapolate the results of any study, no matter how comprehensive, to the population in general. Each individual is unique in terms of his or her genetic makeup and life history; the latter also influences metabolic patterns. (Even identical twins raised together may display different metabolic patterns, because of their different life histories.)  So, while a low carb. diet may work well for a lot of people, it may have very negative effects on a few. Increases in inflammation markers and adverse effects on LDL cholesterol (especially when LDL is measured directly, accounting for particle numbers and sizes) are warning signs that any low carb. dieter should pay attention to.

Reference:

Miller, M. et al. (2009). Comparative effects of three popular diets on lipids, endothelial function, and c-reactive protein during weight maintenance. Journal of the American Dietetic Association, 109, 713-717.