Category Archives: Saturated Fat

High-Fat Diet, Especially High Saturated Fat, Increases Risk For Breast Cancer In Large Multicountry Study

Something That’s Red Is Invisible Against A Red Background

When most of the participants in a study are consuming fat above a threshold that promotes disease, it will look like fat is not disease-promoting.

I often say that in studies comparing one group to another, you won’t detect a harmful effect of _____ if both groups are exposed to a level of ______ that is risk-producing. I said this recently about that saturated fat study (meta-analysis) that got so much attention in the media, and that spurred proclamations such as “Eat Butter” and “Saturated Fat Vindicated”:

“One way you can arrive at all your groups showing similar risk, which this study found, is when there isn’t much difference in consumption among your comparison groups. … Or when most of your participants are consuming saturated fat above a threshold where risk for CVD increases.”

As Jeff Novick pointed out:

“One major problem with this study is they did not look at any studies where the saturated fat intake was less than 7%, which is the level recommended by the [American Heart Association]. … Most of the diets had saturated fat intakes in the range of 10-15% (or more).”

I also said this in reference to the PREDIMED study. That was a big trial studying effects of the Mediterranean diet. It had three groups: “low-fat,” olive oil, and nuts. All the groups ate high-fat, even the “low-fat” group which ate 37% of their calories from fat! Not even the American Heart Association considers that low-fat. For perspective, a whole-food plant-based diet gets less than 15% of its calories from fat. The PREDIMED study found eating lots of olive oil was similar in CVD risk to eating “low-fat.” All groups suffered heart attacks at similar rates. All groups were exposed to a level of fat that was risk-producing.

I just saw a video that Dr. Greger posted about a month ago where he says essentially the same thing:

He cited this study:

Sick Individuals And Sick Populations, International Journal of Epidemiology, 2001

“If everyone smoked 20 cigarettes a day, then clinical, case-control and cohort studies alike would lead us to conclude that lung cancer was a genetic disease; and in one sense that would be true, since if everyone is exposed to the necessary agent, then the distribution of cases is wholly determined by individual susceptibility.”

Within a population, that is, within a group with similar characteristics, you may not see a big range of exposure to something, e.g. in the US, most people eat around 30-35% fat, not a big range. But when you compare populations with different characteristics…

But at the level of populations it is a different story: it has proved easy to show strong associations between population mean values for saturated fat intake versus serum cholesterol level and coronary heart disease incidence, sodium intake versus blood pressure, or energy intake versus overweight.

The reason we know that smoking increases the risk for lung cancer is because:

In the case of cigarettes and lung cancer it so happened that the study populations contained about equal numbers of smokers and non-smokers, and in such a situation case/control and cohort studies were able to identify what was also the main determinant of population differences and time trends.

In sum:

But to identify the causal agent by the traditional case-control and cohort methods will be unsuccessful if there are not sufficient differences in exposure within the study population at the time of the study.

There are some real gems in this paper…

Grateful patients are few in preventive medicine, where success is marked by a non-event.

That’s so true! You don’t really know if your behaviors are adding years to your life.

And this. I can’t believe he said this:

Harder to overcome than any of these, however, is the enormous difficulty for medical personnel to see health as a population issue and not merely as a problem for individuals.

Just about 100% of the people I know, even those in the public health community, harp on about individual behavior. You will never, ever be successful in disease prevention if you only intervene at the individual level. Social norms, peer pressure, environmental pollutants, occupational hazards, there are just too many things an individual is up against, and doesn’t control. You have to change the environment in addition to, perhaps more than, changing individuals’ behavior.

Greger is right when he says:

This is one of the most famous papers ever written in preventive medicine. It should be required reading for all medical students.

Back to the point I was making at the beginning of this post… If you want to know if something is harmful – smoking cigarettes, eating saturated fat, watching television – make sure you have a comparison group that isn’t doing it, or isn’t doing very much of it. Something that’s red is invisible against a red background.

National Dairy Council’s And Unilever’s Involvement In Saturated Fat Study

Dr. Vogel: “Olive Oil Depresses Endothial Function”

Time Magazine: “Eat Butter”

8 Replies

The cover of Time Magazine’s next issue is going to say “Eat Butter.” The associated cover story by Bryan Walsh is entitled “Ending The War On Fat.” I haven’t read the article, so I don’t know what he bases his claims on. But I have read thousands of studies in my lifetime, and “eat butter” is not my conclusion. My cover story would read “Don’t Eat Butter.”

Here’s the video that accompanied Time’s story. It’s emceed by Walsh. It’s going to tell you that everything you’ve been led to believe about fat is wrong. It’s wrong.
http://c.brightcove.com/services/viewer/federated_f9?isVid=1&isUI=1

Dr. McDougall addressed Time’s upcoming story here. Marion Nestle addressed it here. (Nestle says saturated fat consumption is down, and so are deaths from heart disease.)

There is an abundance of research that implicates consumption of saturated fat in the development of heart disease. I am curious how Walsh will present this. McDougall says that one particular study, paid for by the National Dairy Council, is often cited to justify the “eat butter” proclamation:

Meta-Analysis Of Prospective Cohort Studies Evaluating The Association Of Saturated Fat With Cardiovascular Disease, American Journal of Clinical Nutrition, March 2010

However, that study was taken to task, not least of which by the renowned Dr. Stamler, in the very same issue where the study was published:

Diet-Heart: A Problematic Revisit, Jeremiah Stamler, American Journal of Clinical Nutrition, March 2010

Stamler infers that the authors’ intent was not to clarify the association between fat and heart disease, but to inject doubt.

“… the authors seem to be dissociating themselves from prevailing national and international dietary recommendations to the general population for primordial, primary, and secondary prevention of CHD/CVD and the established major metabolic risk factors. But they are not explicit. Is that their intent?“

What are those prevailing recommendations?

“Specifically, do they disagree with the merits of heart-healthy fare on the basis of DASH-, OmniHeart-, Mediterranean-, East Asian–type eating patterns, which emphasize vegetables, fruit, whole grains, legumes/seeds/nuts, fat-free/low-fat dairy products, fish/shellfish, lean poultry, egg whites, seed oils in moderation, alcohol (if desired) in moderation, and portion size/calorie controlled and deemphasize red and processed meats, cheeses, ice cream, egg yolks, cookies/pastries/pies/cakes/other sweets/sweetened beverages, snacks, and salt/commercial foods with added salt. Estimated nutrient composition of this fare is as follows: total fat ≈20–25% of kcal, SFA 6–7%, MUFA 7–9%, PUFA 7–9%, cholesterol <100 mg/1000 kcal, total protein 18–25%, vegetable protein 9–12%, carbohydrate 55–60% (mostly complex), fiber 30–35 g/d, 50–65 mmol Na/d (2900–3770 mg NaCl/d), mineral/vitamin intake high (6). A vast array of concordant multidisciplinary research evidence is the sound foundation for these recommendations.”

Nothing has changed. Don’t eat butter.

Proposed Warning Label For Meat: “Eating Meat Contributes To Insulin Resistance And Diabetes”

2 Replies

The California Senate just passed a bill requiring warning labels on sugar-sweetened beverages:

“Drinking beverages with added sugar(s) contributes to obesity, diabetes, and tooth decay.”

It’s a shame that sweetened beverages are being singled out. I would like to see a similar label on meat:

“Eating meat contributes to insulin resistance and diabetes.”

Why? Because meat-eating is a risk factor for developing diabetes:
Meat Consumption As A Risk Factor For Type 2 Diabetes, Nutrients, February 2014

Researchers evaluated studies that examined different amounts and types of meat consumption and the risk for developing diabetes. They found that meat-eaters had a significantly higher risk of developing diabetes compared with non-meat-eaters. Here’s a chart summarizing the results of one of the included studies, Type of Vegetarian Diet, Body Weight, and Prevalence of Type 2 Diabetes, Diabetes Care, 2009:

Mechanisms for meat’s effect on diabetes risk:

Effect on body weight – “Nearly all observational studies comparing meat-eaters with those who avoid meat show higher body weights among the former group, a finding mirrored in the results of intervention studies using meatless diets.”
Effect on visceral fat (fat around organs in abdominal area) – “Visceral adipose tissue is associated with insulin resistance as a result of increased proinflamatory cytokines.”
Effect on intracellular lipid (fat inside cells) – Impairs insulin action. This would involve, in part, the glucose transporter (GLUT4), which I discussed here.
Effect on iron balance – “Meat provides a substantial quantity of heme iron … a prooxidant that encourages the production of reactive oxygen species, which may damage body tissues, including insulin-producing pancreatic cells.” Even moderately elevated iron stores are associated with insulin resistance and type 2 diabetes.
Nitrates in processed meats – Nitrites and sodium are both linked to elevated diabetes risk.
Systemic inflammation – “A 2014 Harvard study reported that as total red meat consumption increased, so did biomarkers of inflammation.”
One they didn’t mention was presence of persistent organic pollutants (POPs): Animal Fat Is A Natural Reservoir For Environmental Pollutants. “There is now solid evidence demonstrating the contribution of POPs at environmental levels, to metabolic disorders … such as obesity and type 2 diabetes.”

Do you think a meat label could come to pass? There certainly is enough justification for it.

New Study: How High-Fat Diet Promotes Insulin Resistance

1 Reply

Diagram from the study showing: A high-fat diet leads to low oxygen in the fat cell, initiating an inflammatory response, resulting in insulin resistance and increased glucose output from the liver.

Since I was just talking about this (Mechanism By Which Dietary Fat Can Raise Blood Glucose And Insulin) I thought I’d post this study that appeared in my inbox this morning:

Increased Adipocyte O2 Consumption Triggers HIF-1α, Causing Inflammation And Insulin Resistance In Obesity, Cell, 5 June 2014

Here’s the press release:
The Connection Between Oxygen and Diabetes, A Lack Of O2 In Fat Cells Triggers Inflammation And Insulin Resistance In Obesity, University of California, San Diego School of Medicine, 5 June 2014

It’s known that dietary fat, both the quantity and the degree of saturation, promotes an inflammatory response. That inflammation promotes insulin resistance. These researchers say that fat-induced inflammation may be caused by increased oxygen consumption in mitochondria.

Researchers at the University of California, San Diego School of Medicine have, for the first time, described the sequence of early cellular responses to a high-fat diet, one that can result in obesity-induced insulin resistance and diabetes.

In today’s Cell paper, the scientists describe the earliest stages of [the development of systemic insulin resistance and diabetes], which begins even before obesity becomes manifest.

They observed that the abundant saturated fatty acids in the diet activated adenine nucleotide translocase 2 (ANT2) … [which] caused increased oxygen consumption, which meant less was available for the rest of the cell. The result was a relative state of hypoxia or inadequate oxygen supply, one that subsequently induced production of a protective transcription factor in fat cells called HIF-1alpha. In turn, HIF-1alpha triggered release of chemokines, proteins that signal cellular distress, launching the immune system’s inflammatory response. A sustained high-fat diet ensured that the process continued unabated, leading to obesity, chronic low-grade tissue inflammation and eventually, insulin resistance in the mice.

Mechanism By Which Dietary Fat Can Raise Blood Glucose And Insulin

5 Replies

Back in 2008, I began writing about the effect of dietary fat on insulin sensitivity, and blood levels of glucose and insulin. Here’s one of the studies:

Effects Of Isoenergetic High-Carbohydrate Compared With High-Fat Diets On Human Cholesterol Synthesis And Expression Of Key Regulatory Genes Of Cholesterol Metabolism, American Journal of Clinical Nutrition, 2001

It was a small randomized crossover study on healthy subjects that compared:

High-fat diet (40% carbohydrate, 45% fat)
High-carb diet (55% carbohydrate, 30% fat)

“During the oral-glucose-tolerance test, both glucose and insulin rose to higher concentrations after the high-fat diet than after the high-carb diet, showing lower glucose tolerance and insulin sensitivity with the high-fat diet.”

Over the years I learned that saturated fat decreased insulin sensitivity more than other fats, e.g. the KANWU Study.

One mechanism by which dietary fat decreases insulin sensitivity, raising blood glucose and insulin levels is through reduced action of the glucose transporter GLUT4. There seems to be both a reduced expression of the GLUT4 gene, and a reduced translocation or movement of GLUT4 to the cell membrane in the presence of a high-fat, especially high-saturated fat diet. (GLUT4 is one of the glucose transport proteins that move glucose from the bloodstream into muscle and fat cells. Its insertion into the membrane is controlled by insulin. See diagram.)

When glucose cannot enter cells, blood glucose levels rise. When normal amounts of insulin fail to clear blood of glucose, the pancreas responds by releasing more. The result is impaired glucose tolerance, hyperinsulinemia, and eventual development of type 2 diabetes. Over time, compensatory insulin output from beta cells in the pancreas diminishes and a person with type 2 diabetes may find themselves injecting insulin instead of just taking oral meds.

Here are some studies and reviews that address this:

1. A High Fat Diet Impairs Stimulation of Glucose Transport in Muscle, The Journal of Biological Chemistry, October 1998

Rats fed a high (50% of calories) fat diet for 8 weeks showed 50% decreases in insulin-stimulated glucose transport.

“Our findings provide evidence that … impaired GLUT4 translocation to the cell surface plays a major role in the decrease in stimulated glucose transport.”

2. Insulin Resistance in Morbid Obesity: Reversal With Intramyocellular Fat Depletion, Diabetes, January 2002

Subjects were deprived of dietary fat (via gastric surgery that decreases predominantly fat absorption). After 6 months “insulin resistance was fully reversed and GLUT4 expression was restored.”

“We conclude that lipid deprivation selectively depletes intramyocellular lipid stores and induces a normal metabolic state (in terms of insulin-mediated whole-body glucose disposal, intracellular insulin signaling, and circulating leptin levels) despite a persistent excess of total body fat mass.”

3. Transcriptional Regulation Of The Insulin-Responsive Glucose Transporter GLUT4 Gene: From Physiology To Pathology, American Journal of Physiology, Endocrinology and Metabolism, July 2008

“Regulation of gene expression by dietary fats has a significant impact on the development of insulin resistance and its related pathophysiologies. … FFAs also attenuate insulin signaling and GLUT4 translocation through activation of the IκB kinase (IKK) pathway. … Low-fat diet improves glycemic control.” (He cited Barnard’s study.)

4. Dietary Fat Differentially Modulate The mRNA Expression Levels Of Oxidative Mitochondrial Genes In Skeletal Muscle Of Healthy Subjects, Nutrition, Metabolism, and Cardiovascular Diseases, December 2013

“[A meal high in saturated fat] was associated with a marked reduction in the expression of GLUT4 genes.”

5. Moderate GLUT4 Overexpression Improves Insulin Sensitivity And Fasting Triglyceridemia In High-Fat Diet–Fed Transgenic Mice, Diabetes, July 2013

Mice that were fed a high-fat diet and that became obese were protected against insulin resistance and the high glucose and insulin levels of their counterparts when they were bred to have more GLUT4.

6. A Comprehensive Review On Metabolic Syndrome, Cardiology Research and Practice, March 2014

A good description of the pathogenesis of insulin resistance. It adds to what I said above with discussion of intracellular response to insulin binding:

“Binding of insulin results in a tyrosine phosphorylation of downstream substrates and activation of two parallel pathways: the phosphoinositide 3-kinase (PI3K) pathway and the mitogen activated protein (MAP) kinase pathway. The PI3K-Akt pathway is affected, while, the MAP kinase pathway functions normally in insulin resistance. This leads to a change in the balance between these two parallel pathways. Inhibition of the PI3K-Akt pathway leads to a reduction in endothelial NO production, resulting in an endothelial dysfunction, and a reduction in GLUT4 translocation, leading to a decreased skeletal muscle and fat glucose uptake.”

That reduction in endothelial NO (NO is nitric oxide) production contributes to high blood pressure.

There are multiple mechanisms by which a diet high in fat can lead to insulin resistance. (See also: Fatty acid-induced NLRP3-PYCARD inflammasome activation interferes with insulin signaling, Nature Immunology, May 2011.) There is an acute effect of fat in a meal which is distinct from and may be additive to the effect of diets that are chronically high in fat (details of each are still being sussed). Also, the fat we eat can change the composition of lipid in cell membranes. A diet high in saturated fat has been shown to make membranes less fluid and may impair GLUT4 insertion.

These are just a few I have time to post about. There really is abundant research on the role of dietary fat in the development of insulin resistance, a condition which manifests as elevated glucose, elevated insulin, and the development of type 2 diabetes.