Another Fatty Liver Reversal, Part II

A month ago, I wrote about a reader "Steve" who reversed his fatty liver using a change in diet. Non-alcoholic fatty liver disease (NAFLD) is a truly disturbing modern epidemic, rare a few decades ago and now affecting roughly a quarter of the adult population of modern industrialized nations. Researchers cause NAFLD readily in rodents by feeding them industrial vegetable oils or large amounts of sugar.

Steve recently e-mailed me to update me on his condition. He also passed along his liver test results, which I've graphed below. ALT is a liver enzyme that enters the bloodstream following liver damage such as hepatitis or NAFLD. It's below 50 units/L in a healthy person*. AST is another liver enzyme that's below 35 units/L in a healthy person*.

Steve began his new diet in November of 2008 and saw a remarkable and sustained improvement in his ALT and AST levels:

Here's how Steve described his diet change to me:

I totally eliminated sugar, heavy starches, and grains. Started eating more whole, real foods, including things like grass-fed beef and pastured pork and eggs, began supplementing with good fats and omega-3 (pastured butter, coconut oil, cod liver oil). Ate more fruits and vegetables instead of refined carbs. Also completely gave up on the idea that I had to eat only "lean" meats. After my last results, the GI doc said that I wouldn't need the biopsy at all, that things were great, and that if I kept it up I "would live forever."

He did experience some side effects from this diet though:

My triglycerides also went from pre-diet measures of 201 and 147 to post diet 86, 81, and 71.

The added bonus, of course, was that my weight went from 205 pounds to 162 pounds and my body fat percentage from 24% to 12% in the matter of five months--all without the typically excessive cardio I used to try unsuccessfully for weight loss.

The liver is the body's "metabolic grand central station". It's essential for nutrient homeostasis, insulin sensitivity, detoxification, and hormone conversion, among other things. What's bad for the liver is bad for the rest of the body as well. Don't poison your liver with sugar and industrial vegetable oils.


* The cutoff depends on who you ask, but these numbers are commonly used.

How to Fatten Your Liver
Excess Omega-6 Fat Damages Infants' Livers
Health is Multi-Factorial
Fatty Liver Reversal
Another Fatty Liver Reversal

Diabetics on a Low-carbohydrate Diet

Diabetes is a disorder of glucose intolerance. What happens when a diabetic eats a low-carbohydrate diet? Here's a graph of blood glucose over a 24 hour period, in type II diabetics on their usual diet (blue and grey triangles), and after 5 weeks on a 55% carbohydrate (yellow circles) or 20% carbohydrate (blue circles) diet:


The study in question describes these volunteers as having "mild, untreated diabetes." If 270 mg/dL of blood glucose is mild diabetes, I'd hate to see severe diabetes! In any case, the low-carbohydrate, high-fat diet brought blood glucose down to an acceptable level without requiring medication.

It's interesting to note in the graph above that fasting blood glucose (18-24 hours) also fell dramatically. This probably reflects improved insulin sensitivity in the liver. The liver pumps glucose into the bloodstream when it's necessary, and insulin suppresses this. When the liver is insulin resistant, it doesn't respond to the normal signal that there's already sufficient glucose, so it releases more and increases fasting blood glucose. When other tissues are insulin resistant, they don't take up the extra glucose, also contributing to the problem.

Glycated hemoglobin (HbA1c), a measure of average blood glucose concentration over the preceding few weeks, also reflected a profound improvement in blood glucose levels in the low-carbohydrate group:

At 5 weeks, the low-carbohydrate group was still improving and headed toward normal HbA1c, while the high-carbohydrate group remained at a dangerously high level. Total cholesterol, LDL and HDL remained unchanged in both groups, while triglycerides fell dramatically in the low-carbohydrate group.

When glucose is poison, it's better to eat fat.

Graph #1 was reproduced from Volek et al. (2005), which re-plotted data from Gannon et al. (2004). Graph #2 was drawn directly from Gannon et al.

Paleolithic Diet Clinical Trials Part IV

Dr. Staffan Lindeberg has published a new study using the "paleolithic diet" to treat type II diabetics (free full text). Type II diabetes, formerly known as late-onset diabetes until it began appearing in children, is typically thought to develop as a result of insulin resistance (a lowered tissue response to the glucose-clearing function of insulin). This is often followed by a decrease in insulin secretion due to degeneration of the insulin-secreting pancreatic beta cells.

After Dr. Lindeberg's wild success treating patients with type II diabetes or glucose intolerance, in which he normalized the glucose tolerance of all 14 of his volunteers in 12 weeks, he set out to replicate the experiment. This time, he began with 13 men and women who had been diagnosed with type II diabetes for an average of 9 years.

Patients were put on two different diets for 3 months each. The first was a "conventional diabetes diet". I read a previous draft of the paper in which I believe they stated it was based on American Diabetes Association guidelines, but I can't find that statement in the final draft. In any case, here are the guidelines from the methods section:

The information on the Diabetes diet stated that it should aim at evenly distributed meals with increased intake of vegetables, root vegetables, dietary fiber, whole-grain bread and other whole-grain cereal products, fruits and berries, and decreased intake of total fat with more unsaturated fat. The majority of dietary energy should come from carbohydrates from foods naturally rich in carbohydrate and dietary fiber. The concepts of glycemic index and varied meals through meal planning by the Plate Model were explained [18]. Salt intake was recommended to be kept below 6 g per day.

The investigators gave the paleolithic group the following advice:

The information on the Paleolithic diet stated that it should be based on lean meat, fish, fruit, leafy and cruciferous vegetables, root vegetables, eggs and nuts, while excluding dairy products, cereal grains, beans, refined fats, sugar, candy, soft drinks, beer and extra addition of salt. The following items were recommended in limited amounts for the Paleolithic diet: eggs (≤2 per day), nuts (preferentially walnuts), dried fruit, potatoes (≤1 medium-sized per day), rapeseed or olive oil (≤1 tablespoon per day), wine (≤1 glass per day). The intake of other foods was not restricted and no advice was given with regard to proportions of food categories (e.g. animal versus plant foods). The evolutionary rationale for a Paleolithic diet and potential benefits were explained.

Neither diet was restricted in calories. After comparing the effects of the two diets for 3 months, the investigators concluded that the paleolithic diet:

• Reduced HbA1c more than the diabetes diet (a measure of average blood glucose)
• Reduced weight, BMI and waist circumference more than the diabetes diet
• Lowered blood pressure more than the diabetes diet
  
• Reduced triglycerides more than the diabetes diet
• Increased HDL more than the diabetes diet

However, the paleolithic diet was not a cure-all. At the end of the trial, 8 out of 13 patents still had diabetic blood glucose after an oral glucose tolerance test (OGTT). This is compared to 9 out of 13 for the diabetes diet. Still, 5 out of 13 with "normal" OGTT after the paleolithic diet isn't bad. The paleolithic diet also significantly reduced insulin resistance and increased glucose tolerance, although it didn't do so more than the diabetes diet.

As has been reported in other studies, paleolithic dieters ate fewer total calories than the comparison group. This is part of the reason why I believe that something in the modern diet causes hyperphagia, or excessive eating. According to the paleolithic diet studies, this food or combination of foods is neolithic, and probably resides in grains, refined sugar and/or dairy. I have my money on wheat and sugar, with a probable long-term contribution from industrial vegetable oils as well.

Were the improvements on the paleolithic diet simply due to calorie restriction? Maybe, but keep in mind that neither group was told to restrict its caloric intake. The reduction in caloric intake occurred naturally, despite the participants presumably eating to fullness. I suspect that the paleolithic diet reset the dieters' body fat set-point, after which fat began pouring out of their fat tissue. They were supplementing their diets with body fat-- 13 pounds (6 kg) of it over 3 months.

The other notable difference between the two diets, besides food types, was carbohydrate intake. The diabetes diet group ate 56% more carbohydrate than the paleo diet group, with 42% of their calories coming from it. The paleolithic group ate 32% carbohydrate. Could this have been the reason for the better outcome of the paleolithic group? I'd be surprised if it wasn't a factor. Advising a diabetic to eat a high-carbohydrate diet is like asking someone who's allergic to bee stings to fetch you some honey from your bee hive. Diabetes is a disorder of glucose intolerance. Starch is a glucose polymer.

Although to be fair, participants on the diabetes diet did improve in a number of ways. There's something to be said for eating whole foods.

This trial was actually a bit of a disappointment for me. I was hoping for a slam dunk, similar to Lindeberg's previous study that "cured" all 14 patients of glucose intolerance in 3 months. In the current study, the paleolithic diet left 8 out of 13 patients diabetic after 3 months. What was the difference? For one thing, the patients in this study had well-established diabetes with an average duration of 9 years. As Jenny Ruhl explains in her book Blood Sugar 101, type II diabetes often progresses to beta cell loss, after which the pancreas can no longer secrete an adequate amount of insulin.

This may be the critical finding of Dr. Lindeberg's two studies: type II diabetes can be prevented when it's caught at an early stage, such as pre-diabetes, whereas prolonged diabetes may cause damage that cannot be completely reversed though diet. I think this is consistent with the experience of many diabetics who have seen an improvement but not a cure from changes in diet. Please add any relevant experiences to the comments.

Collectively, the evidence from clinical trials on the "paleolithic diet" indicate that it's a very effective treatment for modern metabolic dysfunction, including excess body fat, insulin resistance and glucose intolerance. Another way of saying this is that the modern industrial diet causes metabolic dysfunction.

Paleolithic Diet Clinical Trials
Paleolithic Diet Clinical Trials Part II
One Last Thought
Paleolithic Diet Clinical Trials Part III

Animal Models of Atherosclerosis: Diet-Induced Atherosclerosis

LDL likely plays a role in causing atherosclerosis, with the majority of the damage coming from the oxidized form of LDL. There are at least two ways to increase the concentration of oxidized LDL (oxLDL) in the blood: 1) increase the total concentration of LDL while keeping the proportion of oxLDL the same; 2) increase the proportion of oxLDL. Dietary fats differ in their effects on these two factors, and the net outcome is also dependent on the species eating the fat and the overall dietary context.

The omega-6 polyunsaturated fat, linoleic acid (LA; found abundantly in industrial vegetable oils), is a dominant factor in the susceptibility of LDL to oxidation. LDL is rich in LA regardless of diet, yet the amount of LA in LDL still depends on diet to a certain degree. Thus, on the surface, one would expect a diet high in industrial vegetable oil to promote atherosclerosis. Unfortunately, it's not that simple, because LA also lowers the amount of LDL in the blood of a number of species, including humans.

The amount of atherosclerosis produced by feeding different fats depends both on how much LDL oxidation occurs and on how the fat affects the organism's blood lipid profile. For example, if corn oil lowers LDL by 3-fold relative to lard in a rabbit model, yet increases the proportion of oxLDL by 50%, the rabbit will probably develop more atherosclerosis eating lard than eating corn oil. This is because the total concentration of oxLDL is still higher in the lard group. On the other hand, if corn oil doesn't reduce LDL at all relative to lard in a rhesus monkey, yet the proportion of oxLDL increases by 50%, the corn oil group will probably develop more atherosclerosis, all else being equal.

Then there are other factors that influence atherosclerosis independently of oxLDL, such as the fat-soluble antioxidants, micronutrients and omega-6:3 ratio of the diets. It's also important to keep in mind that atherosclerosis is only one factor that influences the risk of having a heart attack.

In the last post, I argued that feeding excessive cholesterol to herbivorous or nearly herbivorous animals elevates plasma LDL greatly. In many species, saturated fat exacerbates the increase in LDL due to dietary cholesterol overload. However, in the absence of added cholesterol, several commonly used models of atherosclerosis do not show an increase in LDL upon saturated fat feeding. This is similar to the situation in humans.

Rabbits are one of the most commonly used models of diet-induced atherosclerosis. They are very sensitive to dietary cholesterol, due to the fact that their natural adult diet contains virtually none.

I recently found a great study from 1967 titled "Relative Failure of Saturated Fat in the Diet to Produce Atherosclerosis in the Rabbit" (free full text). Investigators fed rabbits cocoa butter, coconut oil and Crisco (hydrogenated cottonseed oil) at 45% of calories. They found that neither cocoa butter nor Crisco increased the rabbits' cholesterol (they didn't measure LDL directly but it typically increases in proportion to total cholesterol in rabbits), while coconut oil caused a transient increase that disappeared by 6 months on the diet. Cocoa butter caused slight atherosclerosis in some of the animals while none was detected in the coconut oil or Crisco groups.

Next, the investigators fed the rabbits cholesterol along with the fats. 0.25% cholesterol with corn oil or Crisco caused a massive (10-fold) increase in blood cholesterol, and produced atherosclerosis. They didn't pair the saturated fats with cholesterol, but the point is still clear: feeding dietary cholesterol, not saturated fat, to an herbivorous species, is the culprit.

However, subsequent studies in rabbits have shown that saturated fats can produce atherosclerosis without added cholesterol. How can this be? It turns out that it only works in the context of a highly refined "synthetic" or "semi-synthetic" diet (ref). So the dietary context plays an important role as well.

The ability of saturated fat to produce atherosclerosis in animal models requires it to cause a large enough increase in serum LDL that it overwhelms saturated fat's natural tendency to reduce LDL oxidation. This process is typically helped along by feeding huge amounts of cholesterol. In the absence of a large increase in LDL, atherosclerosis does not result, all else being equal.

Several studies in primates support this concept. van Jaarsveld and colleagues showed that feeding vervet monkeys 28% of calories from palm oil (SFA-MUFA), sunflower oil (PUFA) or lard (MUFA-SFA) resulted in similar LDL concentrations in the three groups. After more than two years, the palm oil group had the least atherosclerosis and the sunflower oil and lard groups were similar. It's notable that palm oil was the most saturated fat used in this study.

In another telling study by Mott and colleagues, baboons were fed diets containing 40% of calories from a predominantly saturated fat or a predominantly polyunsaturated fat. Each group was further subdivided into two groups: one receiving a small amount of cholesterol in the feed, and one receiving a large amount. Cholesterol feeding increased LDL and atherosclerosis, while the type of fat had a modest effect on LDL and no effect on atherosclerosis both at high and low cholesterol levels. I've noticed that baboons seem to throw a wrench in the gears of the mainstream conception of blood lipid metabolism.

Rudel and colleagues fed african green monkeys and cynomolgus monkeys lard (MUFA-SFA) or safflower oil (PUFA) for 40% of calories, with or without added cholesterol. Without cholesterol, both LDL and the degree of atherosclerosis were low in both monkeys fed both types of fat. Cholesterol feeding raised LDL in both species by 2-3 fold, and caused significant atherosclerosis. Atherosclerosis was more severe in monkeys fed lard plus cholesterol than in monkeys fed safflower oil plus cholesterol, correlating with their considerably higher LDL.

In sum, the ability of a fat to contribute to atherosclerosis depends in part on its ability to increase oxLDL. One way to do this is to massively raise LDL. This can be accomplished by combining dietary cholesterol overload with saturated fat in certain susceptible species. Saturated fat, in the context of a somewhat normal diet, does not appear to raise LDL significantly in most species in the long term. This includes humans.

Animal models of diet-induced atherosclerosis are useful for studying the disease, but they do not support the conclusion that humans should avoid foods containing natural amounts of cholesterol and saturated fat. "Saturated fats" such as lard, palm oil, beef tallow and coconut oil probably have little or no connection to atherosclerosis in humans, or in most species eating a somewhat natural diet.