Low-Fat Diets
In 2000, the International Journal of Obesity published a nice review article of low-fat diet trials. It included data from 16 controlled trials lasting from 2-12 months and enrolling 1,910 participants (1). What sets this review apart is it only covered studies that did not include instructions to restrict calorie intake (ad libitum diets). On average, low-fat dieters reduced their fat intake from 37.7 to 27.5 percent of calories. Here's what they found:
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Clarifications About Carbohydrate and Insulin
My statements about carbohydrate and insulin in the previous post seem to have kicked up some dust! Some people are even suggesting I've gone low-fat! I'm going to take this opportunity to be more specific about my positions.
I do not think that post-meal insulin spikes contribute to obesity, and they may even oppose it. I'm not aware of anyone who researches metabolism for a living who thinks post-meal insulin spikes contribute to obesity, and after having looked into it, I understand why. It's not a controversial issue in my field as far as I can tell. Elevated fasting insulin is a separate issue-- that's a marker of insulin resistance. It's important not to confuse the two. Does insulin resistance contribute to obesity? I don't know, but it's hypothetically possible since insulin acts like leptin's kid brother in some ways. As far as I can tell, starch per se and post-meal insulin spikes do not lead to insulin resistance.
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I do not think that post-meal insulin spikes contribute to obesity, and they may even oppose it. I'm not aware of anyone who researches metabolism for a living who thinks post-meal insulin spikes contribute to obesity, and after having looked into it, I understand why. It's not a controversial issue in my field as far as I can tell. Elevated fasting insulin is a separate issue-- that's a marker of insulin resistance. It's important not to confuse the two. Does insulin resistance contribute to obesity? I don't know, but it's hypothetically possible since insulin acts like leptin's kid brother in some ways. As far as I can tell, starch per se and post-meal insulin spikes do not lead to insulin resistance.
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Healthy Skeptic Podcast and Reader Questions
Chris Kresser, Danny Roddy and I just finished recording the podcast that will be released on May 24th. It went really well, and we think you'll find it informative and maybe even practical!
Unfortunately, we only got around to answering three of the questions I had selected:
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Unfortunately, we only got around to answering three of the questions I had selected:
- How does one lose fat?
- What do I (Stephan) eat?
- Why do many people gain fat with age, especially postmenopausal women?
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Dairy Fat and Diabetes
Introduction
Having access to embargoed news from the Annals of Internal Medicine is really fun. I get to report on important studies at the same time as the news media. But this week, I got my hands on a study that I'm not sure will be widely reported (Mozaffarian et al. Trans-palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in US Adults. Ann Internal Med. 2010). Why? Because it suggests that dairy fat may protect against diabetes.
The lead author is Dr. Dariush Mozaffarian, whose meta-analysis of diet-heart controlled trials I recently criticized (1). I think this is a good opportunity for me to acknowledge that Dr. Mozaffarian and his colleagues have published some brave papers in the past that challenged conventional wisdom. For example, in a 2005 study, they found that postmenopausal women who ate the most saturated fat had the slowest rate of narrowing of their coronary arteries over time (2). It wasn't a popular finding but he has defended it. His colleague Dr. Walter Willett thinks dietary fat is fine (although he favors corn oil), whole eggs can be part of a healthy diet, and there are worse things than eating coconut from time to time. Dr. Willett is also a strong advocate of unrefined foods and home cooking, which I believe are two of the main pillars of healthy eating.
Let's hit the data
Investigators collected two measures of dairy fat intake in 3,736 Americans:
Even though certain blood fatty acids partially represent food intake, they can also represent metabolic conditions. For example, people on their way to type II diabetes tend to have more saturated blood lipids, independent of diet (3, 4)*. So it's reassuring to see that dietary trans-palmitoleate intake was closely related to the serum level. The investigators also noted that "greater whole-fat dairy consumption was associated with lower risk for diabetes," which increases my confidence that serum trans-palmitoleate is actually measuring dairy fat intake to some degree. However, in the end, I think the striking association they observed was partially due to dairy fat intake, but mostly due to metabolic factors that had nothing to do with dairy fat**.
Here's a nice quote:
*Probably due to uncontrolled de novo lipogenesis because of insulin resistance. Many studies find that serum saturated fatty acids are higher in those with metabolic dysfunction, independent of diet. They sometimes interpret that as showing that people are lying about their diet, rather than that serum saturated fatty acids don't reflect diet very well. For example, in one study I cited, investigators found no relationship between dietary saturated fat and diabetes risk, but they did find a relationship between serum saturated fatty acids and diabetes risk (5). They then proceeded to refer to the serum measurements as "objective measurements" that can tease apart "important associations with diabetes incidence that may be missed when assessed by [food questionnaires]." They go on to say that serum fatty acids are "useful as biomarkers for fatty acid intake," which is true for some fatty acids but not remotely for most of the saturated ones, according to their own study. Basically, they try to insinuate that dietary saturated fat is the culprit, and the only reason they couldn't measure that association directly is that people who went on to develop diabetes inaccurately reported their diets! A more likely explanation is that elevated serum saturated fatty acids are simply a marker of insulin resistance (and thus uncontrolled de novo lipogenesis), and had nothing to do with diet.
**Why do I say that? Because mathematically adjusting for dairy and meat fat intake did not substantially weaken the association between phospholipid trans-palmitoleate and reduced diabetes risk (Table 4). In other words, if you believe their math, dairy/meat fat intake only accounted for a small part of the protective association. That implies that healthy people maintain a higher serum phospholipid trans-palmitoleate level than unhealthy people, even if both groups eat the same amount of trans-palmitoleate. If they hadn't mentioned that full-fat dairy fat intake was directly associated with a lower risk of diabetes, I would not find the study very interesting because I'd have my doubts that it was relevant to diet.
***I find it highly doubtful that trans-palmitoleate entirely mediates the positive health outcomes associated with dairy fat intake. I think it's more likely to simply be a marker of milk fat, which contains a number of potentially protective substances such as CLA, vitamin K2, butyric acid, and the natural trans fats including trans-palmitoleate. In addition, dairy fat is low in omega-6 polyunsaturated fat. I find it unlikely that their fancy math was able to tease those factors apart, because those substances all travel together in dairy fat. trans-palmitoleate pills are not going to replace butter.
****That's a joke. I think butter can be part of healthy diet, but that doesn't mean gorging on it is a good idea. This study does not prove that dairy fat prevents diabetes, it simply suggests that it may.
Having access to embargoed news from the Annals of Internal Medicine is really fun. I get to report on important studies at the same time as the news media. But this week, I got my hands on a study that I'm not sure will be widely reported (Mozaffarian et al. Trans-palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in US Adults. Ann Internal Med. 2010). Why? Because it suggests that dairy fat may protect against diabetes.
The lead author is Dr. Dariush Mozaffarian, whose meta-analysis of diet-heart controlled trials I recently criticized (1). I think this is a good opportunity for me to acknowledge that Dr. Mozaffarian and his colleagues have published some brave papers in the past that challenged conventional wisdom. For example, in a 2005 study, they found that postmenopausal women who ate the most saturated fat had the slowest rate of narrowing of their coronary arteries over time (2). It wasn't a popular finding but he has defended it. His colleague Dr. Walter Willett thinks dietary fat is fine (although he favors corn oil), whole eggs can be part of a healthy diet, and there are worse things than eating coconut from time to time. Dr. Willett is also a strong advocate of unrefined foods and home cooking, which I believe are two of the main pillars of healthy eating.
Let's hit the data
Investigators collected two measures of dairy fat intake in 3,736 Americans:
- 24 hour dietary recall questionnaires, six times. This records volunteers' food intake at the beginning of the study.
- Blood (plasma phospholipid) content of trans-palmitoleate. Dairy fat and red meat fat are virtually the only sources of this fatty acid, so it reflects the intake of these foods. Most of the trans-palmitoleate came from dairy in this study, although red meat was also a significant source.
Even though certain blood fatty acids partially represent food intake, they can also represent metabolic conditions. For example, people on their way to type II diabetes tend to have more saturated blood lipids, independent of diet (3, 4)*. So it's reassuring to see that dietary trans-palmitoleate intake was closely related to the serum level. The investigators also noted that "greater whole-fat dairy consumption was associated with lower risk for diabetes," which increases my confidence that serum trans-palmitoleate is actually measuring dairy fat intake to some degree. However, in the end, I think the striking association they observed was partially due to dairy fat intake, but mostly due to metabolic factors that had nothing to do with dairy fat**.
Here's a nice quote:
Our findings support potential metabolic benefits of dairy consumption and suggest that trans-palmitoleate may mediate these effects***. They also suggest that efforts to promote exclusive consumption of low-fat and nonfat dairy products, which would lower population exposure to trans-palmitoleate, may be premature until the mediators of the health effects of dairy consumption are better established.Never thought I'd see the day! Not bad, but I can do better:
Our findings support eating as much butter as possible****. Don't waste your money on low-fat cream, either (half-n-half). We're sorry that public health authorities have spent 30 years telling you to eat low-fat dairy when most studies are actually more consistent with the idea that dairy fat reduces the risk obesity and chronic disease.What are these studies suggesting that dairy fat may be protective, you ask? That will be the topic of another post, my friends.
*Probably due to uncontrolled de novo lipogenesis because of insulin resistance. Many studies find that serum saturated fatty acids are higher in those with metabolic dysfunction, independent of diet. They sometimes interpret that as showing that people are lying about their diet, rather than that serum saturated fatty acids don't reflect diet very well. For example, in one study I cited, investigators found no relationship between dietary saturated fat and diabetes risk, but they did find a relationship between serum saturated fatty acids and diabetes risk (5). They then proceeded to refer to the serum measurements as "objective measurements" that can tease apart "important associations with diabetes incidence that may be missed when assessed by [food questionnaires]." They go on to say that serum fatty acids are "useful as biomarkers for fatty acid intake," which is true for some fatty acids but not remotely for most of the saturated ones, according to their own study. Basically, they try to insinuate that dietary saturated fat is the culprit, and the only reason they couldn't measure that association directly is that people who went on to develop diabetes inaccurately reported their diets! A more likely explanation is that elevated serum saturated fatty acids are simply a marker of insulin resistance (and thus uncontrolled de novo lipogenesis), and had nothing to do with diet.
**Why do I say that? Because mathematically adjusting for dairy and meat fat intake did not substantially weaken the association between phospholipid trans-palmitoleate and reduced diabetes risk (Table 4). In other words, if you believe their math, dairy/meat fat intake only accounted for a small part of the protective association. That implies that healthy people maintain a higher serum phospholipid trans-palmitoleate level than unhealthy people, even if both groups eat the same amount of trans-palmitoleate. If they hadn't mentioned that full-fat dairy fat intake was directly associated with a lower risk of diabetes, I would not find the study very interesting because I'd have my doubts that it was relevant to diet.
***I find it highly doubtful that trans-palmitoleate entirely mediates the positive health outcomes associated with dairy fat intake. I think it's more likely to simply be a marker of milk fat, which contains a number of potentially protective substances such as CLA, vitamin K2, butyric acid, and the natural trans fats including trans-palmitoleate. In addition, dairy fat is low in omega-6 polyunsaturated fat. I find it unlikely that their fancy math was able to tease those factors apart, because those substances all travel together in dairy fat. trans-palmitoleate pills are not going to replace butter.
****That's a joke. I think butter can be part of healthy diet, but that doesn't mean gorging on it is a good idea. This study does not prove that dairy fat prevents diabetes, it simply suggests that it may.
Can a Statin Neutralize the Cardiovascular Risk of Unhealthy Dietary Choices?
The title of this post is the exact title of a recent editorial in the American Journal of Cardiology (1). Investigators calculated the "risk for cardiovascular disease associated with the total fat and trans fat content of fast foods", and compared it to the "risk decrease provided by daily statin consumption". Here's what they found:
I can't be sure, but I think there's a pretty good chance the authors were being facetious in this editorial, in which case I think a) it's hilarious, b) most people aren't going to get the joke. If they are joking, the editorial is designed to shine a light on the sad state of mainstream preventive healthcare. Rather than trying to educate people and change the deadly industrial food system, which is at the root of a constellation of health problems, many people think it's acceptable to partially correct one health risk by tinkering with the human metabolism using drugs. To be fair, most people aren't willing to change their diet and lifestyle habits (and perhaps for some it's even too late), so frustrated physicians prescribe drugs to mitigate the risk. I accept that. But if our society is really committed to its own health and well-being, we'll remove the artificial incentives that favor industrial food, and educate children from a young age on how to eat well.
I think one of the main challenges we face is that our current system is immensely lucrative for powerful financial interests. Industrial agriculture lines the pockets of a few large farmers and executives (while smaller farmers go broke and get bought out), industrial food processing concentrates profit among a handful of mega-manufacturers, and then people who are made ill by the resulting food spend an exorbitant amount of money on increasingly sophisticated (and expensive) healthcare. It's a system that effectively milks US citizens for a huge amount of money, and keeps the economy rolling at the expense of the average person's well-being. All of these groups have powerful lobbies that ensure the continuity of the current system. Litigation isn't the main reason our healthcare is so expensive in the US; high levels of chronic disease, expensive new technology, a "kitchen sink" treatment approach, and inefficient private companies are the real reasons.
If the editorial is serious, there are so many things wrong with it I don't even know where to begin. Here are a few problems:
The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder®) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices.Wow. Later in the editorial, they recommend "a new and protective packet, “MacStatin,” which could be sprinkled onto a Quarter Pounder or into a milkshake." I'm not making this up!
Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.
I can't be sure, but I think there's a pretty good chance the authors were being facetious in this editorial, in which case I think a) it's hilarious, b) most people aren't going to get the joke. If they are joking, the editorial is designed to shine a light on the sad state of mainstream preventive healthcare. Rather than trying to educate people and change the deadly industrial food system, which is at the root of a constellation of health problems, many people think it's acceptable to partially correct one health risk by tinkering with the human metabolism using drugs. To be fair, most people aren't willing to change their diet and lifestyle habits (and perhaps for some it's even too late), so frustrated physicians prescribe drugs to mitigate the risk. I accept that. But if our society is really committed to its own health and well-being, we'll remove the artificial incentives that favor industrial food, and educate children from a young age on how to eat well.
I think one of the main challenges we face is that our current system is immensely lucrative for powerful financial interests. Industrial agriculture lines the pockets of a few large farmers and executives (while smaller farmers go broke and get bought out), industrial food processing concentrates profit among a handful of mega-manufacturers, and then people who are made ill by the resulting food spend an exorbitant amount of money on increasingly sophisticated (and expensive) healthcare. It's a system that effectively milks US citizens for a huge amount of money, and keeps the economy rolling at the expense of the average person's well-being. All of these groups have powerful lobbies that ensure the continuity of the current system. Litigation isn't the main reason our healthcare is so expensive in the US; high levels of chronic disease, expensive new technology, a "kitchen sink" treatment approach, and inefficient private companies are the real reasons.
If the editorial is serious, there are so many things wrong with it I don't even know where to begin. Here are a few problems:
- They assume the risk of heart attack conveyed by eating fast food is due to its total and trans fat content, which is simplistic. To support that supposition, they cite one study: the Health Professionals Follow-up Study (2). This is one of the best diet-health observational studies conducted to date. The authors of the editorial appear not to have read the study carefully, because it found no association between total or saturated fat intake and heart attack risk, when adjusted for confounding variables. The number they quoted (relative risk = 1.23) was before adjustment for fiber intake (relative risk = 1.02 after adjustment), and in any case, it was not statistically significant even before adjustment. How did that get past peer review? Answer: reviewers aren't critical of hypotheses they like.
- Statins mostly work in middle-aged men, and reduce the risk of heart attack by about one quarter. The authors excluded several recent unsupportive trials from their analysis. Dr. Michel de Lorgeril reviewed these trials recently (3). For these reasons, adding a statin to fast food would probably have a negligible effect on the heart attack risk of the general population.
- "Statins rarely cause negative side effects." BS. Of the half dozen people I know who have gone on statins, all of them have had some kind of negative side effect, two of them unpleasant enough that they discontinued treatment against their doctor's wishes. Several of them who remained on statins are unlikely to benefit because of their demographic, yet they remain on statins on their doctors' advice.
- Industrial food is probably the main contributor to heart attack risk. Cultures that don't eat industrial food are almost totally free of heart attacks, as demonstrated by a variety of high-quality studies (4, 5, 6, 7, 8, 9). No drug can replicate that, not even close.
Saturated Fat Consumption Still isn't Associated with Cardiovascular Disease
The American Journal of Clinical Nutrition just published the results of a major Japanese study on saturated fat intake and cardiovascular disease (1). Investigators measured dietary habits, then followed 58,453 men and women for 14.1 years. They found that people who ate the most saturated fat had the same heart attack risk as those who ate the least*. Furthermore, people who ate the most saturated fat had a lower risk of stroke than those who ate the least. It's notable that stroke is a larger public health threat in Japan than heart attacks.
This is broadly consistent with the rest of the observational studies examining saturated fat intake and cardiovascular disease risk. A recent review paper by Dr. Ronald Krauss's group summed up what is obvious to any unbiased person who is familiar with the literature, that saturated fat consumption doesn't associate with heart attack risk (2). In a series of editorials, some of his colleagues attempted to discredit and intimidate him after its publication (3, 4). No meta-analysis is perfect, but their criticisms were largely unfounded (5, 6).
*Actually, people who ate the most saturated fat had a lower risk but it wasn't statistically significant.
This is broadly consistent with the rest of the observational studies examining saturated fat intake and cardiovascular disease risk. A recent review paper by Dr. Ronald Krauss's group summed up what is obvious to any unbiased person who is familiar with the literature, that saturated fat consumption doesn't associate with heart attack risk (2). In a series of editorials, some of his colleagues attempted to discredit and intimidate him after its publication (3, 4). No meta-analysis is perfect, but their criticisms were largely unfounded (5, 6).
*Actually, people who ate the most saturated fat had a lower risk but it wasn't statistically significant.
Saturated Fat and Insulin Sensitivity, Again
A new study was recently published exploring the effect of diet composition on insulin sensitivity and other factors in humans (1). 29 men with metabolic syndrome-- including abdominal obesity, low HDL, high blood pressure, high triglycerides, and high fasting glucose-- were fed one of four diets for 12 weeks:
The paper that's typically cited by people who wish to defend the idea that saturated fat impairs insulin sensitivity is the KANWU study (3). In this study, investigators found no significant difference in insulin sensitivity between volunteers fed primarily SFA or MUFA for 12 weeks. You wouldn't realize this from the abstract however; you have to look very closely at the p-values in table 4.
One of the questions one could legitimately ask, however, is whether SFA have a different effect on people with metabolic syndrome. Maybe the inflammation and metabolic problems they already have make them more sensitive to the hypothetical damaging effects of SFA? That's the question the first study addressed, and it appears that SFA are not uniquely harmful to insulin signaling in those with metabolic syndrome on the timescale tested.
It also showed that the different diets did not alter the proportion of blood fats being burned in muscle, as opposed to being stored in fat tissue. The human body is a remarkably adaptable biological machine that can make the best of a variety of nutrient inputs, at least over the course of 12 weeks. Metabolic damage takes decades to accumulate, and in my opinion is more dependent on food quality than macronutrient composition. Once metabolic dysfunction is established, some people may benefit from carbohydrate restriction, however.
- A diet containing 38% fat: 16% saturated (SFA), 12% monounsaturated (MUFA) and 6% polyunsaturated (PUFA)
- A diet containing 38% fat: 8% SFA, 20% MUFA and 6% PUFA
- A diet high in unrefined carbohydrate, containing 28% fat (8% SFA, 11% MUFA and 6% PUFA)
- A diet high in unrefined carbohydrate, containing 28% fat (8% SFA, 11% MUFA and 6% PUFA) and an omega-3 supplement (1.24 g/day EPA and DHA)
The paper that's typically cited by people who wish to defend the idea that saturated fat impairs insulin sensitivity is the KANWU study (3). In this study, investigators found no significant difference in insulin sensitivity between volunteers fed primarily SFA or MUFA for 12 weeks. You wouldn't realize this from the abstract however; you have to look very closely at the p-values in table 4.
One of the questions one could legitimately ask, however, is whether SFA have a different effect on people with metabolic syndrome. Maybe the inflammation and metabolic problems they already have make them more sensitive to the hypothetical damaging effects of SFA? That's the question the first study addressed, and it appears that SFA are not uniquely harmful to insulin signaling in those with metabolic syndrome on the timescale tested.
It also showed that the different diets did not alter the proportion of blood fats being burned in muscle, as opposed to being stored in fat tissue. The human body is a remarkably adaptable biological machine that can make the best of a variety of nutrient inputs, at least over the course of 12 weeks. Metabolic damage takes decades to accumulate, and in my opinion is more dependent on food quality than macronutrient composition. Once metabolic dysfunction is established, some people may benefit from carbohydrate restriction, however.
Have Seed Oils Caused a Multi-Generational Obesity Epidemic?
In 2006, Drs. Gerard Ailhaud and Philippe Guesnet hypothesized that industrial seed oils such as corn, soybean, safflower, sunflower and cottonseed oil are at least partially responsible for the current obesity epidemic (1). These oils were not a significant part of the human diet until very recently, yet they have been promoted due to their supposed ability to prevent cardiovascular disease. The Western world has been living a massive uncontrolled experiment ever since.
Linoleic acid is an omega-6 polyunsaturated fatty acid (PUFA) that makes up a large proportion of seed oils. It's a very bioactive molecule, in part because it's the precursor of two classes of signaling molecules (eicosanoids and endocannabinoids), some of which influence the development of fat tissue and regulate appetite.
Linoleic acid is an omega-6 polyunsaturated fatty acid (PUFA) that makes up a large proportion of seed oils. It's a very bioactive molecule, in part because it's the precursor of two classes of signaling molecules (eicosanoids and endocannabinoids), some of which influence the development of fat tissue and regulate appetite.
Dr. Ailhaud and his colleagues pointed out that not only are people eating far more linoleic acid than ever before; that very same linoleic acid is accumulating in our fat tissue and showing up in breast milk. Here are a few graphs to illustrate the point. The first graph is of PUFA consumption in the US over the last century, primarily reflecting seed oil intake (based on USDA food disappearance records):
Here's a graph of added fat intake based on USDA data. Added animal fats such as butter and lard have remained stable since 1970 (although total animal fat intake has declined), while seed oil consumption has gone from high to higher:
The following graph shows linoleic acid accumulation in human body fat over the last few decades in Western nations (mostly the US). I put this together based on two references (2, 3). I didn't find any data from the US past 1986. Linoleic acid, unlike most other fatty acids, accumulates disproportionately in body fat (4):
And finally, linoleic acid in the breast milk of US mothers, from Dr. Ailhaud's 2006 paper (the black dots):
In 2009, Dr. Ingeborg Hanbauer published a paper showing that when mice are fed a diet with a poor omega-6:3 balance (77:1), after three generations they develop adult obesity (5). Mice fed the same diet with a better omega-6:3 balance (9.5:1) did not develop obesity, and remained smaller overall. This shows that PUFA imbalance can cause multi-generational effects resulting in obesity and excessive tissue growth. Cmdr. Joseph Hibbeln, a collaborator of Dr. Bill Lands, was an author. The thing I don't like about this paper is they didn't quantify the obesity by measuring fat mass, so we have to take the authors' word that they had more fat.
This week, Dr. Florence Massiera and collaborators published a similar paper titled “A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations” (6). Drs. Ailhaud and Guesnet were both on this paper. They showed that a 35% fat diet with an omega-6:3 ratio of 28 caused obesity that progressively increased over four generations of mice. Although this study was more detailed than the study by Dr. Hanbauer and colleagues, it lacked a comparison group with a more favorable omega-6:3 balance to show that the obesity was specifically the result of omega-6:3 imbalance, rather than the fact that the diet was higher in fat overall or some other aspect of its composition.
If this is true in humans, it would be a straightforward explanation for the obesity epidemic that has plagued the Western world in recent decades. It would explain why the epidemic began in children around 1970, but didn’t show up in adults until about 1980. It would explain why the epidemic is less severe in Europe, and even less so in Asia. And of course, it correlates well with trends in seed oil consumption. This graph is based on US NHANES survey data:
We already know that a number of prenatal factors can have an effect on adult body fat levels in rodents, and observational studies have suggested that the same may apply to humans. If a mother’s body fat is full of linoleic acid, she will pass it on to the fetus as it grows, and after birth in breast milk, influencing its development.
As long-time followers of Whole Health Source know, I suspect industrial seed oils contribute to many of our modern ills. I can’t say for sure that seed oils are responsible for the current obesity epidemic, but the evidence certainly gives me pause. In any case, seed oils are an unnatural part of the human diet and it won’t hurt anyone to avoid them. The half-life of linoleic acid in fat tissue is about two years, so reducing it is a long-term prospect.
Omega-3 Eggs
Eggs are an exceptionally nutritious food, as are all foods destined to nourish a growing animal. However, one concern lies in eggs' high concentration of arachidonic acid (AA), a long-chain omega-6 fat that is the precursor to many eicosanoids. Omega-6 derived eicosanoids are essential molecules that are involved in healing, development and defense. Some of them are inflammatory mediators that can contribute to disease when present in excess. Eggs are one of the main sources of AA in the modern diet.
The percent long-chain omega-6 fats (including AA) in red blood cell membranes associates quite well with heart attack risk. You can see the relationship in this graph compiled by Dr. Bill Lands. However, egg consumption has never been convincingly linked to heart attack risk or any other disorder I'm aware of, despite dire warnings about eggs' cholesterol content. Nevertheless, conventionally raised eggs are unnaturally rich in AA, and unnaturally low in omega-3, due to the hens' diet of grains and soybeans.
The ideal egg is one that comes from a hen raised outdoors (often on pasture), in a place where she can eat a variety of green plants and insects. Hens raised this way typically still eat grain-based feed, but supplemented with a significant amount of foraged food. This dramatically increases the nutritional value of the eggs, as I've noted before. Modern hens lay nearly one egg a day, which is a rate of production that can not be sustained without a large amount of calorie-dense food. They can't eat enough to lay at this rate by foraging.
Not everyone has access to pastured eggs. "Omega-3 eggs" come from hens fed an omega-3 enriched diet*. Not only do they have a much higher omega-3 content than conventional eggs, they also contain less AA. One study found that omega-3 eggs contain 39% less AA than conventional and organic eggs. Omega-3 eggs were also rich in short- and long-chain omega-3 fats. Omega-3 eggs are certainly not nutritionally equivalent to pastured eggs, but they're a step in the right direction.
I don't really know if the AA content of eggs is a concern. Eicosanoid biology is complex and it doesn't like to fit into simple models. I'll look forward to seeing more research on the matter. In the meantime, I'll be eating pastured eggs, and when they're not available I'll eat omega-3 eggs.
*Typically from flax seeds, but some operations also use seaweed. The hens in the paper I cited were fed flax. The hens managed to convert a substantial portion of the alpha-linolenic acid into the important animal fat DHA, and presumably EPA although it was not measured.
The percent long-chain omega-6 fats (including AA) in red blood cell membranes associates quite well with heart attack risk. You can see the relationship in this graph compiled by Dr. Bill Lands. However, egg consumption has never been convincingly linked to heart attack risk or any other disorder I'm aware of, despite dire warnings about eggs' cholesterol content. Nevertheless, conventionally raised eggs are unnaturally rich in AA, and unnaturally low in omega-3, due to the hens' diet of grains and soybeans.
The ideal egg is one that comes from a hen raised outdoors (often on pasture), in a place where she can eat a variety of green plants and insects. Hens raised this way typically still eat grain-based feed, but supplemented with a significant amount of foraged food. This dramatically increases the nutritional value of the eggs, as I've noted before. Modern hens lay nearly one egg a day, which is a rate of production that can not be sustained without a large amount of calorie-dense food. They can't eat enough to lay at this rate by foraging.
Not everyone has access to pastured eggs. "Omega-3 eggs" come from hens fed an omega-3 enriched diet*. Not only do they have a much higher omega-3 content than conventional eggs, they also contain less AA. One study found that omega-3 eggs contain 39% less AA than conventional and organic eggs. Omega-3 eggs were also rich in short- and long-chain omega-3 fats. Omega-3 eggs are certainly not nutritionally equivalent to pastured eggs, but they're a step in the right direction.
I don't really know if the AA content of eggs is a concern. Eicosanoid biology is complex and it doesn't like to fit into simple models. I'll look forward to seeing more research on the matter. In the meantime, I'll be eating pastured eggs, and when they're not available I'll eat omega-3 eggs.
*Typically from flax seeds, but some operations also use seaweed. The hens in the paper I cited were fed flax. The hens managed to convert a substantial portion of the alpha-linolenic acid into the important animal fat DHA, and presumably EPA although it was not measured.
Heart Attack Risk Reduction: The Low-Hanging Fruit
Dr. Yongsoon Park and colleagues recently published a great article in the British Journal of Nutrition titled "Erythrocyte fatty acid profiles can predict acute non-fatal myocardial infarction". Stated simply, the title says that the fat in your red blood cell membranes, which reflects dietary fat composition, can predict your likelihood of having a heart attack*. More accurately than standard measures of heart attack risk such as blood cholesterol.
Let's cut to the data. The investigators examined the fat composition of red blood cells in people who had suffered a heart attack, versus an equal number who had not. Participants who had heart attacks had less omega-3, more long-chain omega-6, and particularly higher trans fat in their red blood cells. In fact, 96% of the heart attack patients had elevated trans fat levels, compared to 34% of those without heart attacks. This is consistent with a number of other studies showing a strong association between blood levels of trans fat and heart attack risk (ref).
92% of heart attack patients were in the lowest category of EPA in their red blood cells, as opposed to 32% of those without heart attacks. EPA is an omega-3 fat that comes from fish, and is also made by the body if there's enough omega-3 alpha-linolenic acid (think flax and greens) around and not too much linoleic acid (industrial vegetable oil) to inhibit its production. 96% of heart attack patients were in the lowest category for alpha-linolenic acid, compared to 34% of the comparison group. 0% of the heart attack patients were in the highest category for alpha-linolenic acid.
62% of heart attack patients were in the highest category of arachidonic acid (AA), compared to 34% of the comparison group. AA is made from linoleic acid, and is also found in animal foods such as eggs and liver. Animal foods from pasture-raised animals are lower in AA than their conventionally-raised counterparts, and also contain more omega-3 fats to balance it.
The investigators found that low omega-3, high AA and high trans fats in red blood cells associate with heart attack risk far better than the Framingham risk score, a traditional and widely-used measure that incorporates age, sex, smoking status, total cholesterol, HDL, hypertension and diabetes.
If the associations in this study represent cause-and-effect, which I believe they do based on their consistency with other observational studies and controlled trials, they imply that we can have a very powerful effect on heart attack risk by taking a few simple steps:
In the future, I hope that most doctors will measure blood fatty acids to predict heart attack risk, with more success than current approaches. Instead of measuring cholesterol and prescribing a statin drug, doctors will prescribe fish oil and easy-to-follow diet advice**. Fortunately, some doctors are beginning to measure red blood cell fatty acid levels in their patients. The forward-thinking cardiologist Dr. William Davis has discussed this on his blog here. Take a good look at the graphs he posted if you get the chance.
*The title of the study is misleading because it implies a prospective design, in which blood fatty acids would be measured and volunteers followed to see who develops heart disease at a later time point. This study was cross-sectional (also called case-control), meaning they found people who had just had a heart attack and measured their blood fatty acids retrospectively. The other study I referenced above was prospective, which is a nice confirmation of the principle.
**"Eat butter on your toast. Ditch the margarine."
Let's cut to the data. The investigators examined the fat composition of red blood cells in people who had suffered a heart attack, versus an equal number who had not. Participants who had heart attacks had less omega-3, more long-chain omega-6, and particularly higher trans fat in their red blood cells. In fact, 96% of the heart attack patients had elevated trans fat levels, compared to 34% of those without heart attacks. This is consistent with a number of other studies showing a strong association between blood levels of trans fat and heart attack risk (ref).
92% of heart attack patients were in the lowest category of EPA in their red blood cells, as opposed to 32% of those without heart attacks. EPA is an omega-3 fat that comes from fish, and is also made by the body if there's enough omega-3 alpha-linolenic acid (think flax and greens) around and not too much linoleic acid (industrial vegetable oil) to inhibit its production. 96% of heart attack patients were in the lowest category for alpha-linolenic acid, compared to 34% of the comparison group. 0% of the heart attack patients were in the highest category for alpha-linolenic acid.
62% of heart attack patients were in the highest category of arachidonic acid (AA), compared to 34% of the comparison group. AA is made from linoleic acid, and is also found in animal foods such as eggs and liver. Animal foods from pasture-raised animals are lower in AA than their conventionally-raised counterparts, and also contain more omega-3 fats to balance it.
The investigators found that low omega-3, high AA and high trans fats in red blood cells associate with heart attack risk far better than the Framingham risk score, a traditional and widely-used measure that incorporates age, sex, smoking status, total cholesterol, HDL, hypertension and diabetes.
If the associations in this study represent cause-and-effect, which I believe they do based on their consistency with other observational studies and controlled trials, they imply that we can have a very powerful effect on heart attack risk by taking a few simple steps:
- Avoid trans fat. It's found in margarine, shortening, refined soy and canola oils, many deep fried foods and processed foods in general.
- Avoid industrial vegetable oils and other sources of excess omega-6. Eating pastured or omega-3 eggs, rather than conventional eggs, can help reduce dietary AA as well.
- Ensure a regular intake of omega-3 fats from seafood, or small doses of high-vitamin cod liver oil or fish oil. Flax oil is also helpful, but it's an inferior substitute for fish oil.
In the future, I hope that most doctors will measure blood fatty acids to predict heart attack risk, with more success than current approaches. Instead of measuring cholesterol and prescribing a statin drug, doctors will prescribe fish oil and easy-to-follow diet advice**. Fortunately, some doctors are beginning to measure red blood cell fatty acid levels in their patients. The forward-thinking cardiologist Dr. William Davis has discussed this on his blog here. Take a good look at the graphs he posted if you get the chance.
*The title of the study is misleading because it implies a prospective design, in which blood fatty acids would be measured and volunteers followed to see who develops heart disease at a later time point. This study was cross-sectional (also called case-control), meaning they found people who had just had a heart attack and measured their blood fatty acids retrospectively. The other study I referenced above was prospective, which is a nice confirmation of the principle.
**"Eat butter on your toast. Ditch the margarine."
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:
* 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
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 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 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 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.
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.
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.
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.
The Diet-Heart Hypothesis: Stuck at the Starting Gate
The diet-heart hypothesis is the idea that (1) dietary saturated fat, and in some versions, dietary cholesterol, raise blood cholesterol in humans and (2) therefore contribute to the risk of heart attack.
I'm not going to spend a lot of time on the theory in relation to dietary cholesterol because there really isn't much evidence to debunk in humans. As far as I can tell, most diet-health researchers don't take this theory seriously anymore because the evidence has simply failed to materialize. Dr. Walter Willett doesn't believe it, and even Dr. Ancel Keys didn't believe it. Here's a graph from the Framingham Heart study (via the book Prevention of Coronary Heart Disease, by Dr. Harumi Okuyama et al.) to drive home the point. Eggs are the most concentrated source of cholesterol in the American diet. In this graph, the "low" group ate 0-2 eggs per week, the "medium" group ate 3-7, and the "high" group ate 7-14 (click for larger image):
The distribution of blood cholesterol levels between the three groups was virtually identical. The study also found no association between egg consumption and heart attack risk. Dietary cholesterol does not raise serum cholesterol in the long term, because humans are adapted to eating cholesterol. We simply adjust our own cholesterol metabolism to compensate when the amount in the diet increases, like dogs. Rabbits don't have that feedback mechanism because their natural diet doesn't include cholesterol, so feeding them dietary cholesterol increases blood cholesterol and causes vascular pathology.
The first half of the diet-heart hypothesis states that eating saturated fat raises blood cholesterol. This has been accepted without much challenge by mainstream diet-health authorities for nearly half a century. In 1957, Dr. Ancel Keys proposed a formula (Lancet 2:1959. 1957) to predict changes in total cholesterol based on the amount of saturated and polyunsaturated fat in the diet. This formula, based primarily on short-term trials from the 1950s, stated that saturated fat is the primary dietary influence on blood cholesterol.
According to Keys' interpretation of the trials, saturated fat raised, and to a lesser extent polyunsaturated fat lowered, blood cholesterol. But there were serious flaws in the data from the very beginning, which were pointed out in this searing 1973 literature review in the American Journal of Clinical Nutrition (free full text).
The main problem is that the controlled trials typically compared saturated fats to omega-6 linoleic acid (LA)-rich vegetable oils, and when serum cholesterol was higher in the saturated fat group, this was most often attributed to the saturated fat raising blood cholesterol rather than the LA lowering it. When a diet high in saturated fat was compared to the basal diet without changing LA, often no significant increase in blood cholesterol was observed. Studies claiming to show a cholesterol-raising effect of saturated fat often introduced it after an induction period rich in LA. Thus, the effect may have more to do with LA lowering blood cholesterol than saturated fat raising it. This is not at all what I was expecting to find when I began looking through the short-term trials.
I recently read a 2003 study that addresses this point directly. Muller et al. (free full text) compared the effects of three controlled diets on the blood cholesterol of 25 healthy women. The diets were:
Reading through the short-term controlled trials, I was struck by the variability and lack of agreement between them. Some of this was probably due to a lack of control over variables and poor study design. But if saturated fat has a dominant effect on serum cholesterol in the short term, it should be readily and repeatably demonstrable. It clearly is not, so I'm left wondering why diet-health authorities are so certain of themselves on this point.
The long-term data are also not kind to the diet-heart hypothesis. Reducing saturated fat while greatly increasing LA does lower blood cholesterol substantially. This was the finding in the well-controlled Minnesota Coronary Survey trial, for example (14% reduction). But in other cases where LA intake changed less, such as MRFIT, the Women's Health Initiative Diet Modification trial and the Lyon Diet-Heart trial, reducing saturated fat intake had little or no effect on total cholesterol or LDL (0-3% reduction). This generally dumbfounded the investigators. The small changes that did occur could easily have been due to other factors, such as increased fiber and phytosterols, since these were multiple-factor interventions.
Another blow to the idea that saturated fat raises cholesterol in the long term comes from observational studies. Here's a graph of data from the Health Professionals Follow-up study, which followed 43,757 health professionals for 6 years (via the book Prevention of Coronary Heart Disease by Dr. Harumi Okuyama et al.):
What this graph shows is that at a relatively constant LA intake, neither saturated fat intake nor the ratio of LA to saturated fat were related to blood cholesterol in freely living subjects. This was true across a wide range of saturated fat intakes (7-15%). If we can't even find a consistent association between dietary saturated fat and blood cholesterol in observational studies, how can we claim that saturated fat is a dominant influence on blood cholesterol?
There's more. If saturated fat were important in determining the amount of blood cholesterol in the long term, you'd expect populations who eat the most saturated fat to have high blood cholesterol levels. But that's not at all the case. The Masai traditionally get almost 2/3 of their calories from milk fat, half of which is saturated. In 1964, Dr. George V. Mann published a paper showing that traditional Masai warriors eating nothing but very fatty milk, blood and meat had an average cholesterol of 115 mg/dL in the 20-24 year age group. For comparison, he published values for American men in the same age range: 198 mg/dL (J. Atherosclerosis Res. 4:289. 1964). Apparently, eating three times the saturated animal fat and several times the cholesterol of the average American wasn't enough to elevate their blood cholesterol. What does elevate the cholesterol of a Masai man? Junk food.
Now let's swim over to the island of Tokelau, where the traditional diet includes nearly 50% of calories from saturated fat from coconut. This is the highest saturated fat intake of any population I'm aware of. How's their cholesterol? Men in the age group 20-24 had a concentration of 168 mg/dL in 1976, which was lower than Americans in the same age group despite a four-fold higher saturated fat intake. Tokelauans who migrated to New Zealand, eating half the saturated fat of their island relatives, had a total cholesterol of 191 mg/dL in the same age group and time period, and substantially higher LDL (J. Chron. Dis. 34:45. 1981). Sucrose consumption was 2% on Tokelau and 13% in New Zealand. I think fructose (which makes up 50% of sucrose-- or table sugar-- and 55% of high-fructose corn syrup) is a more logical explanation for the high serum cholesterol and LDL of modern affluent societies, particularly considering the results of this study.
The inevitable conclusion is that if saturated fat influences total cholesterol or LDL concentration at all, the effect is modest and is dwarfed by other factors.
I'm not going to spend a lot of time on the theory in relation to dietary cholesterol because there really isn't much evidence to debunk in humans. As far as I can tell, most diet-health researchers don't take this theory seriously anymore because the evidence has simply failed to materialize. Dr. Walter Willett doesn't believe it, and even Dr. Ancel Keys didn't believe it. Here's a graph from the Framingham Heart study (via the book Prevention of Coronary Heart Disease, by Dr. Harumi Okuyama et al.) to drive home the point. Eggs are the most concentrated source of cholesterol in the American diet. In this graph, the "low" group ate 0-2 eggs per week, the "medium" group ate 3-7, and the "high" group ate 7-14 (click for larger image):
The distribution of blood cholesterol levels between the three groups was virtually identical. The study also found no association between egg consumption and heart attack risk. Dietary cholesterol does not raise serum cholesterol in the long term, because humans are adapted to eating cholesterol. We simply adjust our own cholesterol metabolism to compensate when the amount in the diet increases, like dogs. Rabbits don't have that feedback mechanism because their natural diet doesn't include cholesterol, so feeding them dietary cholesterol increases blood cholesterol and causes vascular pathology. The first half of the diet-heart hypothesis states that eating saturated fat raises blood cholesterol. This has been accepted without much challenge by mainstream diet-health authorities for nearly half a century. In 1957, Dr. Ancel Keys proposed a formula (Lancet 2:1959. 1957) to predict changes in total cholesterol based on the amount of saturated and polyunsaturated fat in the diet. This formula, based primarily on short-term trials from the 1950s, stated that saturated fat is the primary dietary influence on blood cholesterol.
According to Keys' interpretation of the trials, saturated fat raised, and to a lesser extent polyunsaturated fat lowered, blood cholesterol. But there were serious flaws in the data from the very beginning, which were pointed out in this searing 1973 literature review in the American Journal of Clinical Nutrition (free full text).
The main problem is that the controlled trials typically compared saturated fats to omega-6 linoleic acid (LA)-rich vegetable oils, and when serum cholesterol was higher in the saturated fat group, this was most often attributed to the saturated fat raising blood cholesterol rather than the LA lowering it. When a diet high in saturated fat was compared to the basal diet without changing LA, often no significant increase in blood cholesterol was observed. Studies claiming to show a cholesterol-raising effect of saturated fat often introduced it after an induction period rich in LA. Thus, the effect may have more to do with LA lowering blood cholesterol than saturated fat raising it. This is not at all what I was expecting to find when I began looking through the short-term trials.
I recently read a 2003 study that addresses this point directly. Muller et al. (free full text) compared the effects of three controlled diets on the blood cholesterol of 25 healthy women. The diets were:
- High in saturated fat from coconut, low in LA
- Same as #1, with half the saturated fat replaced by carbohydrate
- Low in saturated fat, high in LA, with the same total fat as in #1
The most important finding of this study was that lowering total saturated fat in the form of coconut oil, from 22.7 to 10.5 E% without change in the P/S ratio [polyunsaturated to saturated ratio], did not lower total or LDL cholesterol, but significantly reduced HDL cholesterol.Among the heaps of poorly conducted studies, I was able to find one apparently well-controlled counterexample: Arterioscler. Thromb. Vasc. Biol. 18:441. 1988. In this 8-week study, increasing saturated fat (at the expense of carbohydrate and with LA constant) increased total cholesterol and LDL, while also increasing HDL, and decreasing Lp(a) and triglycerides. Decreasing saturated fat from 15% to 6% of calories (drastic), reduced total cholesterol by 9% and LDL by 11% (calculated by the Friedewald equation). The variation between trials may have to do with the specific saturated fatty acids used in each trial, their duration, or some other unknown confounder.
Reading through the short-term controlled trials, I was struck by the variability and lack of agreement between them. Some of this was probably due to a lack of control over variables and poor study design. But if saturated fat has a dominant effect on serum cholesterol in the short term, it should be readily and repeatably demonstrable. It clearly is not, so I'm left wondering why diet-health authorities are so certain of themselves on this point.
The long-term data are also not kind to the diet-heart hypothesis. Reducing saturated fat while greatly increasing LA does lower blood cholesterol substantially. This was the finding in the well-controlled Minnesota Coronary Survey trial, for example (14% reduction). But in other cases where LA intake changed less, such as MRFIT, the Women's Health Initiative Diet Modification trial and the Lyon Diet-Heart trial, reducing saturated fat intake had little or no effect on total cholesterol or LDL (0-3% reduction). This generally dumbfounded the investigators. The small changes that did occur could easily have been due to other factors, such as increased fiber and phytosterols, since these were multiple-factor interventions.
Another blow to the idea that saturated fat raises cholesterol in the long term comes from observational studies. Here's a graph of data from the Health Professionals Follow-up study, which followed 43,757 health professionals for 6 years (via the book Prevention of Coronary Heart Disease by Dr. Harumi Okuyama et al.):
What this graph shows is that at a relatively constant LA intake, neither saturated fat intake nor the ratio of LA to saturated fat were related to blood cholesterol in freely living subjects. This was true across a wide range of saturated fat intakes (7-15%). If we can't even find a consistent association between dietary saturated fat and blood cholesterol in observational studies, how can we claim that saturated fat is a dominant influence on blood cholesterol? There's more. If saturated fat were important in determining the amount of blood cholesterol in the long term, you'd expect populations who eat the most saturated fat to have high blood cholesterol levels. But that's not at all the case. The Masai traditionally get almost 2/3 of their calories from milk fat, half of which is saturated. In 1964, Dr. George V. Mann published a paper showing that traditional Masai warriors eating nothing but very fatty milk, blood and meat had an average cholesterol of 115 mg/dL in the 20-24 year age group. For comparison, he published values for American men in the same age range: 198 mg/dL (J. Atherosclerosis Res. 4:289. 1964). Apparently, eating three times the saturated animal fat and several times the cholesterol of the average American wasn't enough to elevate their blood cholesterol. What does elevate the cholesterol of a Masai man? Junk food.
Now let's swim over to the island of Tokelau, where the traditional diet includes nearly 50% of calories from saturated fat from coconut. This is the highest saturated fat intake of any population I'm aware of. How's their cholesterol? Men in the age group 20-24 had a concentration of 168 mg/dL in 1976, which was lower than Americans in the same age group despite a four-fold higher saturated fat intake. Tokelauans who migrated to New Zealand, eating half the saturated fat of their island relatives, had a total cholesterol of 191 mg/dL in the same age group and time period, and substantially higher LDL (J. Chron. Dis. 34:45. 1981). Sucrose consumption was 2% on Tokelau and 13% in New Zealand. I think fructose (which makes up 50% of sucrose-- or table sugar-- and 55% of high-fructose corn syrup) is a more logical explanation for the high serum cholesterol and LDL of modern affluent societies, particularly considering the results of this study.
The inevitable conclusion is that if saturated fat influences total cholesterol or LDL concentration at all, the effect is modest and is dwarfed by other factors.
Diet Modification Trials: Notes on Study Design
The other day, my internet meanderings brought me back to a review of fat modification trials conducted by the Cochrane collaboration. This is a not-for-profit group known for its rigorous meta-analyses.
They selected 27 studies that reduced saturated fat or total fat (in some cases along with increased PUFA), and fit several inclusion criteria. The results:
I'll be the first to admit the meta-analysis isn't perfect. They cast too wide a net, not allowing them to distinguish the effect of reducing total fat from the effect of reducing saturated fat. They lumped both together, which from a practical standpoint isn't actually a problem because both sets of studies show essentially the same thing: zilch. But it's still not the best way to conduct a meta-analysis. They also omitted the Sydney Diet-Heart study for mysterious reasons, which was a five year randomized trial that found an increase in mortality in volunteers substituting vegetable oils for animal fat. Then there's the conclusion, which boggles the mind:
In any case, this brings me to my main point. There are two types of outcomes you can measure in these trials: "hard endpoints" and "soft endpoints". Hard endpoints are not subjective. The hardest endpoint is death. Either you're dead or you aren't; there's no room for interpretation there. A bit less hard is death from a particular cause, such as heart attack. In that case, you're definitely dead, but the physician has to guess what you died of. That involves some judgment on the part of the physician and can introduce bias, depending on the study design. The softest endpoints are non-fatal events like angina, bypasses and stents. These depend on the judgment of both the physician and the patient, and are the most susceptible to bias.
The gold standard for controlled trials is a design known as "double-blind", where neither the participant nor the physician knows which group the participant is in. This design eliminates bias from both the participant and the physician side, allowing correction for the placebo effect and subtle bias in diagnosis. This is easy to do for drug trials, where placebo pills look just like the drug. But it's more difficult to pull off in a diet trial, where the patient knows what foods he's eating. Still, it can be done by giving participants similar-looking margarines containing either saturated or polyunsaturated fats, or sometimes by controlling diets in an institutionalized setting.
There have been three double-blind trials comparing the incidence of heart attack and/or mortality in volunteers eating either saturated animal fat or polyunsaturated vegetable fat: the 1968 National Diet-Heart trial (2 years), the 1969 Los Angeles Veterans' Administration trial (8 years), and the 1989 Minnesota Coronary Survey trial (4.5 years). The two studies that reported total mortality found no significant difference between groups. Two out of three found no difference in heart attack deaths. Of the two that reported on non-fatal cardiovascular endpoints, one found a significant difference. The V.A. trial was the only one to find a significant difference in heart attack deaths (18% decrease) and non-fatal events. There were significantly more heavy smokers in the animal fat arm of the V.A. trial, which was an unfortunate consequence of the participant randomization process. So that result is difficult to interpret.
The three double-blind diet trials, with the least potential for bias, really give no support to the idea that saturated/animal fat contributes to cardiovascular disease. As the participants were already eating a diet high in omega-6 to begin with, there is also no detectable effect of increasing omega-6 on cardiovascular health.
Many of the trials of this nature have been "single-blinded", where the participant knows which group he's in, but the physician doesn't. In this case, all endpoints involving death will be unbiased, because the physician deciding the diagnosis is not influenced by knowing what group the patient is in. However, soft, non-fatal events such as angina are still highly susceptible to the placebo effect. This is because they depend on the subjective judgment of the patient, who knows which group he's in.
I think it's interesting to note that very few dietary fat modification trials have found reductions in total mortality, which is the hardest endpoint and the least susceptible to bias. This is reflected in the Cochrane collaboration's findings. However, a number of the non-blinded and single-blinded studies have found differences in non-fatal cardiovascular events, sometimes creating absurd results. For example, in the 1966 Anti-Coronary Club trial, participants in the vegetable oil group had a significant reduction in non-fatal cardiovascular events, but a massive increase in cardiovascular deaths and total mortality. The former result could result from a placebo effect, due to the non-blinded nature of the trial.
The fact that the Cochrane review found statistically significant benefits of fat modification in soft, non-fatal endpoints (for a portion of the data set), but not endpoints involving death, suggests to me that what we're seeing may actually be a placebo effect resulting from the fact that patients were not blinded in the majority of these trials.
The only "fat modification" intervention that consistently reduces total and cardiovascular mortality is omega-3 fat supplementation, ideally in combination with omega-6 restriction. This is supported by the results of the DART trial, the Lyon Diet-Heart trial, the ISIS trial and the the GISSI-prevenzione trial.
They selected 27 studies that reduced saturated fat or total fat (in some cases along with increased PUFA), and fit several inclusion criteria. The results:
There was no significant effect on total mortality (rate ratio 0.98, 95% CI 0.86 to 1.12), a trend towards protection form cardiovascular mortality (rate ratio 0.91, 95% CI 0.77 to 1.07), and significant protection from cardiovascular events (rate ratio 0.84, 95% CI 0.72 to 0.99). The latter became non-significant on sensitivity analysis."Sensitivity analysis" is a statistical method that allows investigators to take into account the limitations of their model, in this case, the way in which they aggregated the studies' data. Another way of putting their findings is that they found no significant effect of fat modification on mortality or cardiovascular mortality, and they found a reduction in non-fatal "cardiovascular events" (more on this phrase later) only in a subset of the data.
Trials where participants were involved for more than 2 years showed significant reductions in the rate of cardiovascular events and a suggestion of protection from total mortality ["suggestion" = not statistically significant]. The degree of protection from cardiovascular events appeared similar in high and low risk groups, but was statistically significant only in the former.
I'll be the first to admit the meta-analysis isn't perfect. They cast too wide a net, not allowing them to distinguish the effect of reducing total fat from the effect of reducing saturated fat. They lumped both together, which from a practical standpoint isn't actually a problem because both sets of studies show essentially the same thing: zilch. But it's still not the best way to conduct a meta-analysis. They also omitted the Sydney Diet-Heart study for mysterious reasons, which was a five year randomized trial that found an increase in mortality in volunteers substituting vegetable oils for animal fat. Then there's the conclusion, which boggles the mind:
Lifestyle advice to all those at high risk of cardiovascular disease (especially where statins are unavailable or rationed), and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates.Are these the same people who wrote the results section? I don't understand how they arrived at that conclusion from their own results.
In any case, this brings me to my main point. There are two types of outcomes you can measure in these trials: "hard endpoints" and "soft endpoints". Hard endpoints are not subjective. The hardest endpoint is death. Either you're dead or you aren't; there's no room for interpretation there. A bit less hard is death from a particular cause, such as heart attack. In that case, you're definitely dead, but the physician has to guess what you died of. That involves some judgment on the part of the physician and can introduce bias, depending on the study design. The softest endpoints are non-fatal events like angina, bypasses and stents. These depend on the judgment of both the physician and the patient, and are the most susceptible to bias.
The gold standard for controlled trials is a design known as "double-blind", where neither the participant nor the physician knows which group the participant is in. This design eliminates bias from both the participant and the physician side, allowing correction for the placebo effect and subtle bias in diagnosis. This is easy to do for drug trials, where placebo pills look just like the drug. But it's more difficult to pull off in a diet trial, where the patient knows what foods he's eating. Still, it can be done by giving participants similar-looking margarines containing either saturated or polyunsaturated fats, or sometimes by controlling diets in an institutionalized setting.
There have been three double-blind trials comparing the incidence of heart attack and/or mortality in volunteers eating either saturated animal fat or polyunsaturated vegetable fat: the 1968 National Diet-Heart trial (2 years), the 1969 Los Angeles Veterans' Administration trial (8 years), and the 1989 Minnesota Coronary Survey trial (4.5 years). The two studies that reported total mortality found no significant difference between groups. Two out of three found no difference in heart attack deaths. Of the two that reported on non-fatal cardiovascular endpoints, one found a significant difference. The V.A. trial was the only one to find a significant difference in heart attack deaths (18% decrease) and non-fatal events. There were significantly more heavy smokers in the animal fat arm of the V.A. trial, which was an unfortunate consequence of the participant randomization process. So that result is difficult to interpret.
The three double-blind diet trials, with the least potential for bias, really give no support to the idea that saturated/animal fat contributes to cardiovascular disease. As the participants were already eating a diet high in omega-6 to begin with, there is also no detectable effect of increasing omega-6 on cardiovascular health.
Many of the trials of this nature have been "single-blinded", where the participant knows which group he's in, but the physician doesn't. In this case, all endpoints involving death will be unbiased, because the physician deciding the diagnosis is not influenced by knowing what group the patient is in. However, soft, non-fatal events such as angina are still highly susceptible to the placebo effect. This is because they depend on the subjective judgment of the patient, who knows which group he's in.
I think it's interesting to note that very few dietary fat modification trials have found reductions in total mortality, which is the hardest endpoint and the least susceptible to bias. This is reflected in the Cochrane collaboration's findings. However, a number of the non-blinded and single-blinded studies have found differences in non-fatal cardiovascular events, sometimes creating absurd results. For example, in the 1966 Anti-Coronary Club trial, participants in the vegetable oil group had a significant reduction in non-fatal cardiovascular events, but a massive increase in cardiovascular deaths and total mortality. The former result could result from a placebo effect, due to the non-blinded nature of the trial.
The fact that the Cochrane review found statistically significant benefits of fat modification in soft, non-fatal endpoints (for a portion of the data set), but not endpoints involving death, suggests to me that what we're seeing may actually be a placebo effect resulting from the fact that patients were not blinded in the majority of these trials.
The only "fat modification" intervention that consistently reduces total and cardiovascular mortality is omega-3 fat supplementation, ideally in combination with omega-6 restriction. This is supported by the results of the DART trial, the Lyon Diet-Heart trial, the ISIS trial and the the GISSI-prevenzione trial.
The Finnish Mental Hospital Trial
This diet trial was conducted between 1959 and 1971 in two psychiatric hospitals near Helsinki, Finland. One hospital served typical fare, including full-fat milk and butter, while the other served "filled milk", margarine and polyunsaturated vegetable oils. Filled milk has had its fat removed and replaced by an emulsion of vegetable oil. As a result, the diet of the patients in the latter hospital was low in saturated fat and cholesterol, and high in polyunsaturated fat compared to the former hospital. At the end of six years, the hospitals switched diets. This is known as a "crossover" design.
The results were originally published in 1972 in the Lancet (ref), and a subset of the data were re-published in 1979 in the International Journal of Epidemiology (ref). They found that during the periods that patients were eating the diet low in saturated fat and cholesterol, and high in vegetable oil, male participants (but not females) had roughly half the incidence of heart attack deaths. There were no significant differences in total mortality in either men or women. The female data were omitted in the 1979 report.
This study is often cited as support for the idea that saturated fat increases the risk of heart attack. The reason it's cited so often is it's one of a minority of trials that came to that conclusion. The only other controlled trial I'm aware of that replaced animal fat with polyunsaturated vegetable oil (without changing other variables at the same time) and found a statistically significant decrease in cardiovascular deaths was the Los Angeles Veterans' Administration study. However, there was no difference in total mortality, and there were significantly more heavy smokers in the control group. The difference in heart attack deaths in the V.A. trial was 18%, far less than the difference seen in the Finnish trial.
I can cite three controlled trials that came to the opposite conclusion, that switching saturated fat for vegetable oil increases cardiovascular mortality and/or total mortality: the Anti-Coronary Club Trial (4 years), the Rose et al. corn oil trial (2 years), and the Sydney Diet-Heart trial (5 years). Other controlled trials found no difference in total mortality or heart attack mortality from this intervention, including the National Diet-Heart Study (2 years) and the Medical Research Council study (7 years). Thus, the Finnish trial is an outlier whose findings have never been replicated by better-conducted trials.
I have three main bones to pick with the Finnish trial. The first two are pretty bad, but the third is simply fatal to its use as support for the idea that saturated fat contributes to cardiovascular risk:
1) A "crossover" study design is not an appropriate way to study a disease with a long incubation period. How do you know that the heart attacks you're observing came from the present diet and not the one the patients were eating for the six years before that? The Finnish trial was the only trial of its nature ever to use a crossover design.
2) The study wasn't blinded. When one wants to eliminate bias in diagnosis for these types of studies, one designs the study so that the physician doesn't know which group the patients came from. That way he can't influence the results, consciously or unconsciously. Obviously there was no way to blind the physicians in this study, because they knew what the patients in each hospital were eating. I think it's interesting that the only outcome not susceptible to diagnostic bias, total mortality, showed no significant changes in either men or women.
3) The Finnish Mental Hospital trial was not actually a controlled trial. In an editorial in the November 1972 issue of the Lancet, Drs. John Rivers and John Yudkin pointed out, among other things, that the amount of sugar varied by almost 50% between diet periods. In the December 30th issue, the lead author of the study responded:
I could continue listing other problems with the study, such as the fact that the hospital population included in the analysis had a high turnover rate (variable, but as high as 40%), and patients were included in the analysis even if they were at the hospital for as little as 50% of the time between first admission and final discharge (i.e., they came and went). But what's the use in beating a dead horse?
The Finnish trial is still very useful, however. I use it as a litmus test to determine which papers are solid and which are desperate for data that confirm their biases. Any author who cites the Finnish trial in support of the idea that saturated fat causes heart attacks either isn't familiar with it, or is not objective.
The results were originally published in 1972 in the Lancet (ref), and a subset of the data were re-published in 1979 in the International Journal of Epidemiology (ref). They found that during the periods that patients were eating the diet low in saturated fat and cholesterol, and high in vegetable oil, male participants (but not females) had roughly half the incidence of heart attack deaths. There were no significant differences in total mortality in either men or women. The female data were omitted in the 1979 report.
This study is often cited as support for the idea that saturated fat increases the risk of heart attack. The reason it's cited so often is it's one of a minority of trials that came to that conclusion. The only other controlled trial I'm aware of that replaced animal fat with polyunsaturated vegetable oil (without changing other variables at the same time) and found a statistically significant decrease in cardiovascular deaths was the Los Angeles Veterans' Administration study. However, there was no difference in total mortality, and there were significantly more heavy smokers in the control group. The difference in heart attack deaths in the V.A. trial was 18%, far less than the difference seen in the Finnish trial.
I can cite three controlled trials that came to the opposite conclusion, that switching saturated fat for vegetable oil increases cardiovascular mortality and/or total mortality: the Anti-Coronary Club Trial (4 years), the Rose et al. corn oil trial (2 years), and the Sydney Diet-Heart trial (5 years). Other controlled trials found no difference in total mortality or heart attack mortality from this intervention, including the National Diet-Heart Study (2 years) and the Medical Research Council study (7 years). Thus, the Finnish trial is an outlier whose findings have never been replicated by better-conducted trials.
I have three main bones to pick with the Finnish trial. The first two are pretty bad, but the third is simply fatal to its use as support for the idea that saturated fat contributes to cardiovascular risk:
1) A "crossover" study design is not an appropriate way to study a disease with a long incubation period. How do you know that the heart attacks you're observing came from the present diet and not the one the patients were eating for the six years before that? The Finnish trial was the only trial of its nature ever to use a crossover design.
2) The study wasn't blinded. When one wants to eliminate bias in diagnosis for these types of studies, one designs the study so that the physician doesn't know which group the patients came from. That way he can't influence the results, consciously or unconsciously. Obviously there was no way to blind the physicians in this study, because they knew what the patients in each hospital were eating. I think it's interesting that the only outcome not susceptible to diagnostic bias, total mortality, showed no significant changes in either men or women.
3) The Finnish Mental Hospital trial was not actually a controlled trial. In an editorial in the November 1972 issue of the Lancet, Drs. John Rivers and John Yudkin pointed out, among other things, that the amount of sugar varied by almost 50% between diet periods. In the December 30th issue, the lead author of the study responded:
In view of the design of the experiment the variations in sugar intake were, of course, regrettable. They were due to the fact that, aside from the fatty-acid composition and the cholesterol content of the diets, the hospitals, for practical reasons, had to be granted certain freedom in dietary matters.In other words, the diets of the two hospitals differed significantly in ways other than their fat composition. Sugar was one difference. Carbohydrate intake varied by as much as 17% and total fat intake by as much as 26% between diet periods (on average, carbohydrate was lower and total fat was higher in the polyunsaturated fat group). The definition of a controlled trial is an experiment in which all variables are kept constant except the one being evaluated. Therefore, the Finnish trial cannot rightfully be called a controlled trial. This places it in the same category as other observational studies, in which variables are not controlled and one can only guess what factors caused the difference in disease incidence. The fact that the result has never been replicated casts further doubt on the study.
I could continue listing other problems with the study, such as the fact that the hospital population included in the analysis had a high turnover rate (variable, but as high as 40%), and patients were included in the analysis even if they were at the hospital for as little as 50% of the time between first admission and final discharge (i.e., they came and went). But what's the use in beating a dead horse?
The Finnish trial is still very useful, however. I use it as a litmus test to determine which papers are solid and which are desperate for data that confirm their biases. Any author who cites the Finnish trial in support of the idea that saturated fat causes heart attacks either isn't familiar with it, or is not objective.
The Coronary Heart Disease Epidemic: Possible Culprits Part II
In the last post, I reviewed some of the factors that I believe could have contributed to the epidemic of heart attacks that began in the 1920s and 1930s in the U.S. and U.K., and continues today. I ended on smoking, which appears to be a major player. But even smoking is clearly trumped by another factor or combination of factors, judging by the unusually low incidence of heart attacks in France, Japan and on Kitava.
One of the major changes in diet that I didn't mention in the last post was the rise of industrial liquid vegetable oils over the course of the 20th century. In the U.S. in 1900, the primary cooking fats were lard, beef tallow and butter. The following data only include cooking fats and spreads, because the USDA does not track the fats that naturally occur in milk and meat (source):
Animal fat is off the hook. This is the type of information that makes mainstream nutrition advice ring hollow. Let's see what happened to industrial vegetable oils in the early 1900s:
I do believe we're getting warmer. Now let's consider the composition of traditional American animal fats and industrial vegetable oils:
It's not hard to see that the two classes of fats (animal and industrial vegetable) are quite different. Animal fats are more saturated (blue). However, the biggest difference is that industrial vegetable oils contain a massive amount of omega-6 (yellow), far more than animal fats. If you accept that humans evolved eating primarily animal fats, which is well supported by the archaeological and anthropological literature, then you can begin to see the nature of the problem.
Omega-6 and omega-3 fats are polyunsaturated fatty acids that are precursors to a very important class of signaling molecules called eicosanoids, which have a hand in virtually every bodily process. Omega-6 and omega-3 fats compete with one another for the enzymes (desaturases and elongases) that convert them into eicosanoid precursors. Omega-6-derived eicosanoids and omega-3-derived eicosanoids have different functions. Therefore, the balance of omega-6 to omega-3 fats in the diet influences the function of the body on virtually every level. Omega-6 eicosanoids tend to be more inflammatory, although the eicosanoid system is extraordinarily complex and poorly understood.
What's better understood is the fact that our current omega-6 consumption is well outside of our ecological niche. In other words, we evolved in an environment that did not provide large amounts of omega-6 all year round. Industrial vegetable oils are a product of food processing techniques that have been widespread for about 100 years, not enough time for even the slightest genetic adaptation. Our current level of omega-6 intake, and our current balance between omega-6 and omega-3, are therefore unnatural.
The ideal ratio is probably very roughly 2:1 omega-6:omega-3. Leaf lard is 6.8, beef tallow is 2.4, good quality butter is 1.4, corn oil is 45, cottonseed oil is 260. It's clear that a large qualitative change in our fat consumption occurred over the course of the 20th century.
I believe this was a major factor in the rise of heart attacks from an obscure condition to the primary cause of death. I'll be reviewing the data that convinced me in the next few posts.
The Coronary Heart Disease Epidemic
The Coronary Heart Disease Epidemic: Possible Culprits Part I
The Omega Ratio
A Practical Approach to Omega Fats
Polyunsaturated Fat Intake: Effects on the Heart and Brain
Polyunsaturated Fat Intake: What About Humans?
Vegetable Oil and Homicide
One of the major changes in diet that I didn't mention in the last post was the rise of industrial liquid vegetable oils over the course of the 20th century. In the U.S. in 1900, the primary cooking fats were lard, beef tallow and butter. The following data only include cooking fats and spreads, because the USDA does not track the fats that naturally occur in milk and meat (source):
Animal fat is off the hook. This is the type of information that makes mainstream nutrition advice ring hollow. Let's see what happened to industrial vegetable oils in the early 1900s:
I do believe we're getting warmer. Now let's consider the composition of traditional American animal fats and industrial vegetable oils:
It's not hard to see that the two classes of fats (animal and industrial vegetable) are quite different. Animal fats are more saturated (blue). However, the biggest difference is that industrial vegetable oils contain a massive amount of omega-6 (yellow), far more than animal fats. If you accept that humans evolved eating primarily animal fats, which is well supported by the archaeological and anthropological literature, then you can begin to see the nature of the problem.Omega-6 and omega-3 fats are polyunsaturated fatty acids that are precursors to a very important class of signaling molecules called eicosanoids, which have a hand in virtually every bodily process. Omega-6 and omega-3 fats compete with one another for the enzymes (desaturases and elongases) that convert them into eicosanoid precursors. Omega-6-derived eicosanoids and omega-3-derived eicosanoids have different functions. Therefore, the balance of omega-6 to omega-3 fats in the diet influences the function of the body on virtually every level. Omega-6 eicosanoids tend to be more inflammatory, although the eicosanoid system is extraordinarily complex and poorly understood.
What's better understood is the fact that our current omega-6 consumption is well outside of our ecological niche. In other words, we evolved in an environment that did not provide large amounts of omega-6 all year round. Industrial vegetable oils are a product of food processing techniques that have been widespread for about 100 years, not enough time for even the slightest genetic adaptation. Our current level of omega-6 intake, and our current balance between omega-6 and omega-3, are therefore unnatural.
The ideal ratio is probably very roughly 2:1 omega-6:omega-3. Leaf lard is 6.8, beef tallow is 2.4, good quality butter is 1.4, corn oil is 45, cottonseed oil is 260. It's clear that a large qualitative change in our fat consumption occurred over the course of the 20th century. I believe this was a major factor in the rise of heart attacks from an obscure condition to the primary cause of death. I'll be reviewing the data that convinced me in the next few posts.
The Coronary Heart Disease Epidemic
The Coronary Heart Disease Epidemic: Possible Culprits Part I
The Omega Ratio
A Practical Approach to Omega Fats
Polyunsaturated Fat Intake: Effects on the Heart and Brain
Polyunsaturated Fat Intake: What About Humans?
Vegetable Oil and Homicide
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