Sunday, March 25, 2012

Good Fats, Bad Fats: Separating Fact from Fiction

Good Fats, Bad Fats: Separating Fact from Fiction

Written by Chris Masterjohn    March 24 2012
Few driving factors have had such a profound influence on the transition from traditional to modern industrial diets as the campaign against animal fats and tropical oils. We have responded to this campaign not only by depriving ourselves of the nutrient-dense animal foods so important to human health, but also by replacing these traditional fats with processed foods laden with refined vegetable oil, flour, and sugar.

Since its inception, this campaign has been based on a series of myths. These include the myths that saturated fat is the “bad fat” while polyunsaturated fat is the “good fat,” that arachidonic acid is the “bad fat,” and that so-called “solid fats” are empty calories with no nutritional value. We will consider each of these myths in the pages that follow.


The myth that saturated fatty acids are “bad fat” while polyunsaturated fatty acids (PUFA) are “good fat” emerged in the 1950s as the dietheart hypothesis. This hypothesis stated that the saturated fat found in animal fats and tropical oils would contribute to heart disease by raising blood cholesterol levels while the PUFA found in vegetable oils would do just the opposite.

If the nutritional and medical establishments had taken the approach of Weston Price and endeavored to begin unraveling the causes of heart disease by studying the diets and lifestyles of populations that were immune to the disease, it is unlikely the diet-heart hypothesis would ever have emerged. The traditional diets of Pacific islanders free of heart disease, for example, vary widely in their proportions of fat and carbohydrate, but as can be seen in Figure 1, they are all rich in saturated fat and low in PUFA when compared to the standard American diet.1,2,3 Each of these traditional diets is based primarily on starches, fruits, coconut and fish, so the PUFA comes mostly from fish rather than from vegetable oils.

The foundation of the establishment’s approach to the riddle of heart disease featured no such investigation of traditional diets, and the result of this negligence was the diet-heart hypothesis. Advocates of this hypothesis supported it in the early 1950s with two key pieces of evidence. The first was that blood cholesterol levels were statistically associated with heart disease risk.4 The second was that, in highly controlled laboratory experiments, replacing saturated fats like butter, lard or coconut oil with polyunsaturated oils like corn or safflower oil would lower blood cholesterol levels.5,6 Playing a game of connect the dots, they argued that substituting vegetable oils for traditional animal fats and tropical oils would lower the risk of heart disease.

In 1957, the American Heart Association called the hypothesis “highly speculative,” and concluded that “the evidence at present does not convey any specific implications for drastic dietary changes, specifically in the quantity or type of fat in the diet of the general population, on the premise that such changes will definitely lessen the incidence of coronary or cerebral artery disease.”7 Four years later, the state of the evidence remained the same but three members of the committee were dropped and replaced by four new members, including Ancel Keys, a leading proponent of the hypothesis. The updated report recommended that men who are overweight, have high blood pressure or high cholesterol, lead “sedentary lives of relentless frustration,” or have a strong family history of heart disease should replace part of the saturated fat in their diets with PUFA.8

The hypothesis nevertheless remained controversial in the scientific community for decades. The tide turned in 1984 when the Coronary Primary Prevention Trial showed that cholestyramine could prevent heart attacks.9 Cholestyramine is a drug that binds bile acids in the intestine and causes their excretion in the feces. As a result, the liver takes cholesterol in from the blood in order to make more bile acids and the concentration of cholesterol in the blood falls. Time magazine hailed the trial as a vindication of the American Heart Association’s twenty-three-year-old stance against animal fats. Butter, eggs, and bacon were all conspicuously absent from the treatment protocol of this trial, but Time nevertheless ran a cover story entitled “Hold the Eggs and Butter,” which artfully featured a frowning face with eyes of sunnyside up eggs and a downturned mouth of a slice of fried bacon. The article declared, “cholesterol is proved deadly, and our diet may never be the same.”10
In our own day, the American Heart Association continues to promote the hypothesis with vigor. In 2009, it updated its official stance, recommending at least 5 to 10 percent of calories as omega-6 PUFA with additional PUFA coming from omega-3 sources, and concluded that intakes even higher than this “appear to be safe and may be even more beneficial (as part of a low-saturated fat, low-cholesterol diet).”11 It was one thing to promote this hypothesis in 1961 when it had never been tested, but to throw a PUFA party in 2009 and suggest we all wash away our cardiovascular concerns with swigs of soybean oil is to ignore with callow abandon all the lessons we have learned from clinical trials published in the intervening decades.

Six randomized, controlled trials specifically testing the effect of the substitution of polyunsaturated vegetable oils for animal fats on heart disease have been published.12-17 These trials were all published between 1965 and 1989. Two of them found that vegetable oils increased the risk of heart disease,12, 14 although one of these creatively concluded from this that “men who have had myocardial infarction are not a good choice for testing the lipid hypothesis.”14 Two of them reported no effect of vegetable oil.13, 15 The authors of one of these two trials, however, only reported the results half-way through the study.15 In the final report, they pooled the two groups together and compared them to a new control group that had not received any dietary advice at all.18 As a result, we have no way of knowing the true effect of vegetable oil in that study. Two of the six trials were double-blind, and deserve special attention.16, 17 These are the Minnesota Coronary Survey and the Los Angeles Veterans Administration Hospital Study.

The Minnesota Coronary Survey tested the effect of substituting vegetable oils for animal fats in hospital patients who were on the diets for an average duration of only one year.16 As shown in Figure 2, vegetable oil had no effect on cardiovascular disease. While its effect on total mortality was not statistically significant, however, total survival was nevertheless better in the group eating saturated fat. We naturally must wonder what would have happened to total mortality had the subjects been on the diets for longer than one year.

The Los Angeles Veterans Administration Hospital Study lasted over eight years, and most of the subjects were enrolled for at least six years.17 It is the only one of these six studies where the mean age of the subjects was greater than sixty, so it allows us to better see the effect of vegetable oils on the risk of cancer, if such an effect exists.

Subjects eating the diet rich in vegetable oils had a lower risk of cardiovascular mortality, but a higher risk of mortality from other causes. As a result, diet had no effect on total mortality. This is clearly shown in Figure 3. As shown in Figure 4, deaths from cancer began to increase in the vegetable oil group after two years, and the increase became much larger after five years.19 As shown in Figure 5, the difference in the incidence of all deaths from non-cardiovascular causes began to increase in the vegetable oil group only after four years and remained extremely small until seven years.17 After seven years, non-cardiovascular mortality began to increase rapidly. The disturbing possibility that the true harms of vegetable oils take years to emerge did not escape the authors, and they concluded that “future clinical trials of diets rich in unsaturated fat must be planned for periods well in excess of eight years, rather than for the five-year periods that have been the usual goal.” Such longer trials have never been conducted.

Although a superficial analysis of this study would suggest that vegetable oils decrease the risk of heart disease while increasing the risk of cancer and other diseases, this may not be the case. Even though the investigators randomly allocated the subjects to each group, the randomization failed to equally balance rates of smoking between the two groups. There were twice as many heavy smokers and 60 percent more moderate smokers in the group consuming traditional animal fats, while there were more light smokers and non-smokers in the group consuming vegetable oils.17 The diet rich in animal fats, moreover, was deficient in vitamin E. Animal experiments suggest that we should obtain 0.6 milligrams of vitamin E for every gram of PUFA we consume. The vegetable oil diet came close to this requirement, supplying a ratio of over 0.5, but the animal fat diet fell miserably short of it, supplying a ratio of less than 0.2.20

Animal fats are not intrinsically deficient in vitamin E, however. The average store-bought butter, for example, easily meets the vitamin E requirement, and a high-quality pastured butter can provide more than double this requirement. 21,22 It is thus unclear why the animal fat diet was so deficient in the vitamin, but this deficiency in combination with the higher rate of smoking may have contributed to the greater risk of cardiovascular disease in the animal fat group.

It appears from these studies, then, that vegetable oils promote cancer while animal fats protect against it even in the presence of smoking and vitamin E deficiency. Vegetable oils may promote heart disease as occurred in two studies,12, 14 but the results of the LA Veterans Administration Hospital Study make this unclear. The authors of this study themselves concluded as follows: “. . . we consider our own trial, with or without the support of other published data, to have fallen short of providing a definitive and final answer concerning dietary prevention of heart disease.”

These studies leave many questions to be answered. Are the effects of vegetable oils with different proportions of omega-6 and omega-3 fatty acids different from one another? What is the effect of vegetable oils over a lifetime, beginning in youth? Are there certain dietary contexts that make vegetable oils harmful, and others that make them safe? The larger question, however, is whether, given all this uncertainty, we should make ourselves guinea pigs for these newfangled foods. No one has yet offered a better summary of the issue than that offered by the late endocrinologist Broda Barnes in his 1976 book, Solved: The Riddle of Heart Attacks:
Everyone should have the privilege of playing Russian Roulette if it is desired, but it is only fair to have the warning that with the use of polyunsaturated fats the gun probably contains live ammunition.23


The second myth is that animal fats promote inflammation because they contain a small amount of the omega-6 PUFA arachidonic acid, found primarily in liver and egg yolks with smaller amounts in butter and meat fats. This hypothesis emerged in the scientific literature in the 1980s and 1990s as researchers began attributing the low rate of heart disease among traditional Inuit to their consumption of large amounts of omega-3 fatty acids from marine oils.24 Researchers argued that these omega-3 fatty acids were protective precisely because they counteracted the inflammatory effects of arachidonic acid. Barry Sears popularized this idea in his best-selling 1995 book The Zone Diet.25 Therein, he proclaimed excess arachidonic acid “your worst biological nightmare.” Not only is it inflammatory, he wrote, but it “is so potent and so dangerous that when you inject it into the bloodstream of rabbits the animals die within three minutes.”

Despite these sensational claims, arachidonic acid is not inherently inflammatory. Its deficiency, in fact, produces a number of inflammatory symptoms, including dandruff, hair loss, infertility and irritated, red, sore, swollen, and scaly skin.26,27 Inhibiting supposedly “inflammatory” products made from arachidonic acid such as prostaglandin E2 using over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) can produce a number of inflammatory outcomes. These drugs induce intestinal pathologies that closely resemble celiac disease in laboratory animals in response to gluten or even egg white,28,29 and they interfere with the resolution of autoimmune conditions.30

Although it is true that our bodies use arachidonic acid to initiate inflammation—a vital process if we want to survive to adulthood without being wiped out by pathogenic microbes —our bodies also use this fatty acid to suppress inflammation or to resolve inflammation once it has run its course. We use arachidonic acid to make cell-to-cell junctions that form physical barriers against toxins and pathogens,31-33 to create a unique environment in the gut that causes our immune system to react to food proteins with tolerance instead of intolerance,34 and to make important molecules called lipoxins that help resolve existing inflammation.30,35 We even use arachidonic acid to signal the conversion of omega-3 fatty acids to resolvins, another class of molecules that help resolve inflammation.30 It makes little sense to characterize this fatty acid as singularly inflammatory in nature when it has so many anti-inflammatory functions, and when it is present in so many traditional foods consumed by populations free of inflammatory diseases.


The third myth, that “solid fats” are empty calories with no nutritional value, has emerged more recently with the latest revision of the USDA’s Dietary Guidelines for Americans. This document defines a “nutrient-dense” food as one whose “nutrients and other beneficial substances . . . have not been 'diluted' by the addition of calories from added solid fats, added sugars, or added refined starches, or by the solid fats naturally present in the food.”36 This peculiar definition of “nutrient-dense” allows the addition of liquid oils but requires the removal of natural solid fats. “Solid fats” are defined as “fats with a high content of saturated and/or trans fatty acids, which are usually solid at room temperature.” Using this definition, one could ostensibly make milk more “nutrient-dense” by replacing its natural butterfat with corn oil.

The natural fats present in foods carry all of their fat-soluble vitamins, and added fats further increase their bioavailability. Human trials, for example, have clearly shown that butterfat increases the absorption of vitamin E,37 and that canola oil increases the absorption of carotenoids from salad.38 The more fat one adds, according to these studies, the greater the absorption of fatsoluble nutrients. This can hardly be considered a decrease in nutrient density!

Animal experiments, moreover, suggest that fats and oils low in PUFA provide the best absorption of fat-soluble nutrients. When compared to corn oil, for example, olive oil roughly doubles the absorption of lycopene and astaxanthin in rats.39 If the lower absorption seen with corn oil is a result of its higher PUFA content, then socalled “solid fats” might prove superior even to olive oil, and certainly to canola oil.


Clinical trials have failed miserably to support the hypothesis that replacing saturated animal fats with polyunsaturated vegetable oils would prevent heart disease. They have shown instead that vegetable oils likely promote cancer and perhaps even heart disease. Arachidonic acid in animal fat is not "deadly," but is necessary for our bodies to initiate, suppress, or resolve inflammation as needed. These are all vital processes that allow us to respond appropriately to our environment. “Solid fats” do not “dilute” the nutrient density of our food. On the contrary, they carry fat-soluble nutrients and provide for their absorption.

When we observe the ease with which these myths arise and the vigor with which they are promulgated to the public, it is important for us not to create our own equal and opposite myths. We should keep in mind that traditional diets varied widely in their fat and carbohydrate contents. Nutritional needs vary from person to person, and from one stage of life to another. Any health-promoting component of the diet, including animal fat, can become harmful if it displaces other health-promoting components. It is thus entirely plausible that some people under some circumstances may benefit by reducing their intakes of animal fat and increasing their intakes of other traditional foods. We should thus beware of promoting any “correct” amount of animal fat to consume. We should instead look upon the earth’s menu of natural, traditional foods without fear, and choose those foods we need and enjoy in freedom.

1. Lindeberg S, et al. Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava study. Am J Clin Nutr. 1997;66(4):845-52.
2. Prior IA, et al. Cholesterol, coconuts, and diet on Polynesian atolls: a natural experiment: the Pukapuka and Tokelau island studies. Am J Clin Nutr. 1981;34(8):1552-61.
3. USDA Agricultural Research Service.What We Eat in America, NHANES 2007-2008. Table 5. Energy Intakes: Percentages of Energy from Protein, Carbohydrate, Fat, and Alcohol, by Gender and Age, in the United States, 2007- 2008 http://www.ars.usda.gov/SP2UserFiles/Place/12355000/pdf/0708/Table_5_EIN_GEN_07.pdf Accessed December 29, 2011.
4. Keys A. Atherosclerosis: a problem in newer public health. J Mt Sinai Hosp NY. 1953;20(2):118-39.
5. Kinsell LW, et al. Dietary modification of serum cholesterol and phospholipid levels. J Clin Endocrinol. Metab. 1952;12(7):909-13.
6. Ahrens EH Jr., et al..Effect on human serum lipids of substituting plant for animal fat in diet. Proc Soc Exp Biol Med. 1954;86(4):872-8.
7. Page IH, et al. Atherosclerosis and the Fat Content of the Diet. Circulation. 1957;16:163-178.
8. Dietary fat and its relation to heart attacks and strokes: report by the Central Committee for Medical and Community Program of the AHA. 1961;23:133-6.
9. The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of coronary heart disease to cholesterol lowering. JAMA. 1984;251(3):365-74.
10. Wallis C, Crook C, Delaney P, Gribben S. Hold the Eggs and Butter. Time magazine. March 26, 1984.
11. Harris WS, et al. Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the AHA Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation. 2009;119(6):902- 7.
12. Rose GA, et al. Corn oil in treatment of ischaemic heart disease. Br Med J. Jun 12 1965;1(5449):1531- 1533.
13. Controlled trial of soya-bean oil in myocardial infarction. Lancet. Sep 28 1968;2(7570):693-699.
14. Woodhill JM, et al. Low fat, low cholesterol diet in secondary prevention of CHD. Adv Exp Med Biol. 1978;109:317-330.
15. Bierenbaum ML, et al. Modified-fat dietary management of the young male with CD. A five-year report. JAMA. Dec 25 1967;202(13):1119-1123.
16. Frantz ID, Jr., et al. Test of effect of lipid lowering by diet on cardiovascular risk. Minnesota Coronary Survey. Arteriosclerosis. Jan-Feb 1989;9(1):129-135.
17. Dayton S, et al. A Controlled Clinical Trial of a Diet High in Unsaturated Fat in Preventing Complications of Atherosclerosis. Circulation. 1969;150(1 Suppl 2):II-1-II-2.
18. Bierenbaum ML, et al. Ten-year experience of modified-fat diets on younger men with coronary heartdisease. Lancet. 1973;1(7817):1404-7.
19. Pearce ML and Dayton S.Incidence of Cancer in Men on a Diet High in Polyunsaturated Fat. Lancet. 1971;297(7697):464-467.
20. Dayton S, et al. Vitamin E Status of Humans During Prolonged Feeding of Unsaturated Fats. J Lab Clin Med. 1965;65:739-47.
21. NutritionData: know what you eat. Butter, without salt. http://www.nutritiondata.com/facts/dairy-andegg- products/133/2 Accessed April 21, 2009.
22. Searles SK, et al. Vitamin E, Vitamin A, and Carotene Contents of Alberta Butter. J Dairy Sci. 1970;53(2):150-5.
23. Barnes BO, Solved: The Riddle of Heart Attacks. Fries Communications, 1976.
24. Mann NJ, et al. Arachidonic Acid Content of the Australian Diet Is Lower than Previously Estimated. J Nutr. 1995;125:2528-35.
25. Sears B. The Zone Diet. HarperCollins, 1995.
26. Burr GO, Burr MM. A New Deficiency Disease Produced by the Rigid Exclusion of Fat From the Diet. J Biol Chem. 1929;LXXXII(2):345-67.
27. Turpeinen O. Further Studies on the Unsaturated Fatty Acids Essential in Nutrition. J Nutr. 1938;15(4):351-66.
28. Newberry RD, Stenson WF, Lorenz RG. Cyclooxygenase-2-dependent arachidonic acid metabolites are essential modulators of the intestinal immune response to dietary antigen. Nat Med. 1999;5(8):900-6
29. D'Arienzo R, Stefanile R, Maurano F, Luongo D, Bergamo P, Mazzarella G, Troncone R, Auricchio S, David C, Rossi M. A deregulated immune response to gliadin causes a decreased villus height in DQ8 transgenic mice. Eur J Immunol. 2009;39(12):3552-61.
30. Chan MM, Moore AR. Resolution of Inflammation in Murine Autoimmune Arthritis Is Disrupted by Cyclooxygenase-2 Inhibition and Restored by Prostaglandin E2-Mediated Lipoxin A4 Production. J Immunol. 2010;184(11):6418-6426.
31. Agrawal R, Daniel EE. Control of gap junction formation in canine trachea by arachidonic acid metabolites. Am J Physiol. Mar 1986;250(3 Pt 1):C495-505.
32. Civitelli R, Ziambaras K, Warlow PM, et al. Regulation of connexin43 expression and function by prostaglandin E2 (PGE2) and parathyroid hormone (PTH) in osteoblastic cells. J Cell Biochem. Jan 1 1998;68(1):8-21.
33. Blikslager AT, Roberts MC, Rhoads JM, Argenzio RA. Prostaglandins I2 and E2 have a synergistic role in rescuing epithelial barrier function in porcine ileum. J Clin Invest. Oct 15 1997;100(8):1928-1933
34. du Pre MF, Samson JN. Adaptive T-cell responses regulating oral tolerance to protein antigen. Allergy. 2011;66(4):478-90.
35. Banneberg G, Serhan CN. Specialized pro-resolving lipid mediators in the inflammatory response: An update. Biochim Biopys Acta. 2010; 1801(12):1260-73.
36. U.S. Department of Agriculture, U.S. Department of Health and Human Services. Dietary Guidelines for Americans 2010. www.dietaryguidelines.gov. Accessed December 30, 2012.
37. Bruno RS, Leonard SW, Park SI, Zhao Y, Traber MG. Human vitamin E requirements assessed with the use of apples fortified with deuterium-labeled alpha-tocopheryl acetate. Am J Clin Nutr. 2006;83(2):299- 304.
38. Brown MJ, Ferruzzi MG, Nguyen ML, Cooper DA, Eldridge AL, Schwartz SJ, White WS. Carotenoid bioavailability is higher from salads ingested with full-fat than with fat-reduced salad dressings as measured with electrochemical detection. Am J Clin Nutr. 2004;80(2):396-403.
39. Clark RM, Yao L, She L, Furr HC. A comparison of lycopene and astaxanthin absorption from corn oil and olive oil emulsions. Lipids. 2000;35(7):803-6.
This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly magazine of the Weston A. Price Foundation, Spring 2012.
Read the full article here.

Friday, March 23, 2012

Tom Naughton's talk to Office of Research Integrity

From 's blog watch this 20 minute presentation by Tom Naughton. Tom hits another bull's Eye! And, "Yes he does mention heart disease!"

Tom says     "Doctors, nutritionists, researchers, medical industry trade groups, government agencies and other established authorities handing out dietary advice that flat-out doesn’t work very well for an awful lot of people."

Dr John Briffa says....

Tom recently gave a 20-minute talk in Washington DC in which he gives a (I think) great summary of the dunderheaded dietary advice given to us by government agencies, health groups and most health professionals. He also highlights the fact that people are increasingly looking for help on-line, and finding it in the form of blogs and within social media. He makes the point that getting information this way can be better and more useful than taking, say, one piece of advice from a so-called ‘expert’ who just so happens to have it all wrong. He’s right.

Tom’s presentation gives us cause for optimism. He seems to be rightly aware that people appear to be turning away from conventional sources of information in their droves, and that people are increasingly looking for genuinely helpful dietary advice in all the right places. If I had 20 minutes to say what I feel is wrong with conventional dietetic advice and where people would be better off looking for useful (and science-based) information and advice, I hope it would come out a lot like Tom’s talk.

See Tom's own site here.

I have high cholesterol, and I don’t care

I have high cholesterol, and I don’t care

May 31, 2010 in Heart DiseaseMyths & Truths

Still think saturated fat is bad for you?

Still think eating eggs raises cholesterol?

Still think high cholesterol causes heart disease?

If you answered yes to any of those questions, you really need to watch these videos. (But hey, you might learn something even if you answered “no”.)

In this presentation I:
  • debunk the myth that eating saturated fat and cholesterol causes heart disease.
  • explain why LDL and total cholesterol are not useful markers for heart disease.
  • present three markers that are useful markers for heart disease.
  • demonstrate that low-fat, high carb diets promote – rather than protect against – heart disease.
  • show you how eating saturated fat and cholesterol can prevent heart attacks
  • tell you how to order a test that more accurately predicts your risk of heart disease
http://www.sott.net/article/223262-I-have-high-cholesterol-and-I-dont-care ==================================================================
Please visit CHRIS KRESSER's site and watch his informative video's here.

Thursday, March 22, 2012

5 reasons not to worry about your cholesterol numbers

5 reasons not to worry about your cholesterol numbers

I do a lot of public speaking. As you might suspect, regardless of the specific topic I’m presenting the dietary recommendations I make are always essentially the same: high-fat, nutrient-dense and low in toxins. Since omega-6 vegetable oils are toxins, when I say high fat I’m talking about saturated and monounsaturated fat. You know this.

But a lot of people I speak to don’t. They fully steeped in 50 years of mainstream propaganda perpetuating the idea that saturated fats cause heart disease – primarily by raising blood cholesterol. So, inevitably, when I stand up in front of a group of people and tell them all to eat lots of saturated fat, I get a question that goes something like this:
But won’t that raise my cholesterol? And won’t high cholesterol give me a heart attack?
I haven’t yet perfected an answer that can dismantle a half century of cultural brainwashing about fat and cholesterol in less than 3 minutes. But I’m working on it.

In the meantime, I usually explain some variation of the following:

Point #1: Eating saturated fat doesn’t raise cholesterol levels in the blood

There’s no convincing evidence that eating saturated fat raises blood cholesterol. Stephan Guyenet spanked that old yarn to the curb in this recent blog post. In short, of all of the studies examining the relationship between saturated fat intake and serum cholesterol, only one found a clear relationship between the two and even that association was weak. The rest found no association at all.

Point #2: Eating cholesterol doesn’t (usually) raise cholesterol levels in the blood

Nor is there evidence that eating cholesterol in the diet raises cholesterol levels in your blood. A recent review of the scientific literature published in Current Opinion in Clinical Nutrition and Metabolic Care clearly indicates that egg consumption has no discernible impact on blood cholesterol levels in 70% of the population. In the other 30% of the population (termed “hyperresponders”), eggs do increase both circulating LDL and HDL cholesterol.

An increase of HDL is a good thing. And as it turns out, so is a boost of the type of LDL that eating saturated fat and cholesterol increases. We now know there are two different types of LDL: small, dense LDL, and large, buoyant LDL. Small, dense LDL is a significant risk factor for heart disease because it’s more likely to oxidize and cause inflammation. Large, buoyant LDL is not a risk factor for heart disease. And guess what? Eating eggs not only increases the benign large, buoyant LDL, but it also decreases the harmful small, dense LDL by 20%. I’ve written more about this here and here, and you can also watch some videos on this topic here.

Point #3: Even if eating saturated fat and cholesterol did raise cholesterol levels in your blood, it wouldn’t matter because “high cholesterol” isn’t a strong risk factor for heart disease.

This is the one that really spins people out. Even if they follow me on the first two points, their eyes tend to glaze over when I mention this one. As Mark Twain used to say:
The history of our race, and each individual’s experience, are sown thick with evidence that a truth is not hard to kill and that a lie told well is immortal.
Nowhere is that more true than with the lie that high cholesterol causes heart disease. It’s so deeply ingrained in our collective consciousness that it’s become an almost unassailable article of faith. That’s why people are so surprised to learn that there’s very little evidence to support the idea.

This point is the current bottleneck in my “3-minute” explanation, because it takes a while to explain why it’s not true. I’ve written about it extensively here, here and here. For the purposes of this brief article, we’ll have to leave it at this: both total and LDL cholesterol – which are the numbers your doctor, the media and everyone else seems to be concerned with – are only weakly associated with heart disease.

If “high cholesterol” were the cause of heart disease, you’d expect it to be a risk factor in:
  1. All populations around the world.
  2. In both men and women.
  3. In people of all ages.
And you’d also expect that lowering cholesterol should prevent heart disease.
Makes sense, right?

Unfortunately for the lipophobes, the cholesterol hypothesis fails on all fronts.
  1. High cholesterol is not a risk factor in all populations. The French have among the highest cholesterol levels in the world, and among the lowest rates of heart disease of any industrialized nation. The Austrians and other European nations are similar.
  2. Women on average have 300% lower rates of heart disease than men, despite higher average cholesterol levels.
  3. The rate of heart disease in 65 year-old men is 10 times that of 45-year old men. Yet high cholesterol is not a risk factor in men over 65. (In fact, men over 65 with low cholesterol (<150 mg/dL) are twice as likely to die from heart disease as those with normal or even "high" cholesterol.)
Finally, more than 40 trials have been performed to see if lowering cholesterol prevents heart disease. In some trials more people got heart disease, in others fewer. But when all the results were taken together, just as many people died in the treatment groups (those who took cholesterol-lowering drugs) as the control groups (those who did not).

Point #4: If you want to worry about your cholesterol numbers, forget about total cholesterol and LDL and pay attention to the ratio of triglycerides to HDL.

In general I’m not a fan of people worrying about their lipid panel numbers at all. Like Dr. Kurt Harris, I think this compulsive testing and re-testing of lipids that has become common in the Paleo community not only isn’t necessary, but may even be harmful. There’s still a lot we don’t know about how these numbers change on a day-to-day basis. What’s more, it’s not always easy to distinguish between cause and effect. Researchers made the mistake of assuming high cholesterol was the cause of heart disease, when in reality it’s much more likely that high cholesterol is a consequence of it.

But for crying out loud, if you’re going to get your lipds tested at least pay attention to the right numbers. And the most important number on a conventional lipid panel is the relationship between triglycerides and HDL. (Divide triglyercids by HDL to get it.) If that number is less than 2, this suggests you have mostly large, buoyant LDL – which is not a risk factor for heart disease. If that number is higher than 3, it suggests you have mostly small, dense LDL – which most certainly is a risk factor for heart disease.

Point #5: Eat good food and don’t worry about the numbers.

But in the end, even that ratio doesn’t matter so much. Why? Because the treatment is always the same! If your TG:HDL ratio is high (bad), what should you do? Eat a high-fat (saturated, of course) diet. This will reduce your triglycerides and small, dense LDL, and increase your HDL. Triple win. And if your TG:HDL ratio is low (good), what should you do? The exact same thing: eat a high-fat diet.

Conversely, replacing saturated fat with carbs, as we’ve been told to do for 50 years to protect ourselves from heart disease, actually contributes to it in three ways: it increases triglycerides and small, dense LDL, and decreases HDL.

Finally, I often get emails from people who’ve switched to a high-fat / Paleo-type diet expressing concern that their LDL and total cholesterol levels have gone up. My response usually has three parts: 1) don’t worry about it, because high total and LDL cholesterol do not cause heart disease; 2) the increase is usually temporary, and may be the result of the body curing itself of fatty liver (a good thing!); 3) don’t worry about it. Doesn’t hurt to remind them.

**Note: if your total cholesterol levels are very high (i.e. above 300 mg/dL), this may be an indicator of a metabolic abnormality or inflammatory process that needs to be addressed. Cholesterol is a repair substance in the body, and persistent elevations beyond a certain threshold may point to an underlying problem that hasn’t been identified.

Is Red Meat Killing Us?

“For the greatest enemy of truth is very often not the lie — deliberate, contrived and dishonest — but the myth — persistent, persuasive, and unrealistic. Too often we hold fast to the clichés of our forebears. We subject all facts to a prefabricated set of interpretations. We enjoy the comfort of opinion without the discomfort of thought.

- John F. Kennedy, Yale University commencement address (June 11, 1962)
This is one of my favorite quotes. Unfortunately, it’s a little bit too appropriate for the field of nutrition science.

As I alluded to last week, I’m going to devote this post to a discussion on what I like to call the Scientific Weapons of Mass Destruction: observational epidemiology, at least for nutrition science. I hope some of you have “prepared” for this post, as I had recommended, by reading this article written by Gary Taubes in 2007. It really is required reading to get the most out of what I’m going to talk about in this post.

I had always planned to write about this most important topic soon enough, but the recent study out of Harvard’s School of Public Health generated more than enough stories like this one such that I figured it was worth putting some of my other ideas on the back-burner, at least for a week. If you’ve been reading this blog at all you’ve hopefully figured out that I’m not writing it to get rich. What I’m trying to do is help people understand how to think about what they eat and why. I have my own ideas, shared by some, of what is “good” and what is “bad,” and you’ve probably noticed that I don’t eat like most people.

However, that’s not the real point I want to make. I want to help you all become thinkers not followers. And that includes not being mindless followers of me or my ideas! Being a critical thinker doesn’t mean you reject everything out there for the sake of being contrarian. It means you question everything out there. I failed to do this in medical school and residency. I mindlessly accepted what I was taught about nutrition without ever looking at the data myself. Shame on me.

Too often we cling to nice stories because they make us feel good, but we don’t ask the hard questions. You’ve had great success improving your health on a vegan diet? No animals have died at your expense. Great! But, why do you think it is you’ve improved your health on this diet? Is it because you stopped eating animal products? Perhaps. What else did you stop eating? How can we figure this out? If we don’t ask these questions, we end up making incorrect linkages between cause and effect. This is the sine qua non of bad science.

The reason Gary Taubes and I founded the Nutrition Science Initiative (NuSI), which we hope to launch this summer, is not to advance a low-carb agenda (contrary to what some might think) – it’s to help the field of nutrition science join the other scientific fields. Most disciplines of science — such as physics, chemistry, and biology — use something called the Scientific Method to answer questions.

A simple figure of this approach is shown below:
Scientific Method
The figure is pretty self-explanatory, so let me get to the part where nutrition science is making the biggest mistakes: “Conduct an experiment.” There is no shortage of observations, questions, or hypotheses in the nutrition science world – so we’re doing well on that front. It’s that pesky experiment part we’re getting hung up on. Without doing controlled experiments it is not possible to distinguish the relationship between cause and effect. [Just a heads up – this is going to be a recurring theme this week.]

What is an experiment?

There are several types of experiments and they are not all equally effective at determining the cause and effect relationship. Climate scientists and social economists (like one of my favorites, Steven Levitt, whom I’ve been fortunate enough to spend a day with), for example, often carry out natural experiments. Why? Because the “laboratory” they study can’t actually be manipulated in a controlled setting. For example, when Levitt and his colleagues tried to figure out if swimming pools or guns were more dangerous to children – i.e., Was a child more likely to drown in a house with a swimming pool or be shot by a gun in a home with a gun? – they could only look at historical, or observational, data. They could not design an experiment to study this question prospectively and in a controlled manner.

How would one design such an experiment? In a “dream” world you would find, say, 100,000 families and you would split them into two groups – group 1 and group 2. Group 1 and 2 would be statistically identical in every way once divided. Because of the size of the population, any differences between them would cancel out (e.g., socioeconomic status, number of kids, parenting styles, geography). The 50,000 group 1 families would then have a swimming pool installed in their backyard and the 50,000 group 2 families would be given a gun to keep in their house.
For a period of time, say 5 years, the scientists would observe the differences in child death rates from these two causes (accidental drownings and gunshot wounds). At the conclusion, provided the study was powered appropriately, the scientists would know which was more hazardous to the life of a child, a home swimming pool or a home gun.

Unfortunately questions like this (and the other questions studied by folks like Levitt) can’t be studied in a controlled way. Such studies are just impractical, if not impossible, to do.

Similarly, to rigorously study the anthropogenic CO2 – climate change hypothesis, for example, we would need another planet earth with the same number of humans, cows, lakes, oceans, and kittens that did NOT burn fossil fuels for 50 years. But, since these scenarios are never going to happen the folks that carry out natural experiments do the best they can to statistically manipulate data to separate as many confounding factors as possible in every effort to identify the relationship between cause and effect. Cause and effect. Say it with me one more time…cause and effect.

Enter the holy grail of experiments: the controlled experiment. In a controlled experiment, as the name suggests, the scientists have control over all variables between the groups (typically what we call a “control” group and a “treatment” group). Furthermore, they study subjects prospectively (rather than backwards looking, or retrospectively) while only changing one variable at a time. Even a well-designed experiment, if it changes too many variables (for example), prevents the investigator from making the important link: cause and effect. Remember my silly example from this post a few weeks back?
Imagine a clinical experiment for patients with colon cancer. One group gets randomized to no treatment (“control group”). The other group gets randomized to a cocktail of 14 different chemotherapy drugs, plus radiation, plus surgery, plus hypnosis treatments, plus daily massages, plus daily ice cream sandwiches, plus daily visits from kittens (“treatment group”). A year later the treatment group has outlived the control group, and therefore the treatment has worked. But how do we know EXACTLY what led to the survival benefit? Was it 3 of the 14 drugs? The surgery? The kittens? We cannot know from this experiment. The only way to know for certain if a treatment works is to isolate it from all other variables and test it in a randomized prospective fashion.
As you can see, even doing a prospective controlled experiment is not enough, like the one above, if you fail to design the trial correctly. Technically, the fictitious experiment I describe above is not “wrong,” unless someone – for example, the scientist who carried out the trial or the newspapers who report on it – misrepresented it.

If the New York Times and CNN reported the following: New study proves that kittens cure cancer!, would it be accurate? Not even close. Sadly, most folks would never read the actual study to understand why this bumper-sticker conclusion is categorically false. Sure, it is possible, based on this study, that kittens can cure cancer. But the scientists in this hypothetical study have wasted a lot of time and money if their goal was to determine if kittens could cure cancer. The best thing this study did was to reiterate a hypothesis. Nothing more. In other words, this experiment (even assuming it was done perfectly well from a technical standpoint) learned nothing other than the combination of 20 interventions was better than none because of an experimental design problem.

So what does all of this have to do with eating red meat?

In effect, I’ve already told you everything you need to know. I’m not actually going to spend any time dissecting the actual study published last week that led to the screaming headlines about how red meat eaters are at greater risk of death from all causes (yes, “all causes,” according to this study) because it’s already been done a number of times by others this week alone. Three critical posts on this specific paper can be found here, here, and here.

I can’t suggest strongly enough that you read them all if you really want to understand the countless limitations of this particular study, and why its conclusion should be completely disregarded. If you want bonus points, read the paper first, see if you can understand the failures of it, then check your “answer” against these post. As silly as this sounds, it’s actually the best way to know if you’ve really internalized what I’m describing.

Now, I know what you might be thinking: Oh, come on Peter, you’re just upset because this study says something completely opposite to what you say!

Not so. In fact, I have the same criticism of similarly conducted studies that “find” conclusions I agree with. For example, on the exact same day the red meat study was published online (March 12, 2012) in the journal Archives of Internal Medicine, the same group of authors from Harvard’s School of Public Health published another paper in the journal Circulation. This second paper reported on the link between sweetened beverage consumption and heart disease, which “showed” that consumption of sugar-sweetened beverages increased the risk of heart disease in men. [On another day I will give you my thoughts on why the media chose to report on the red meat study rather than the sugar study, despite them both coming out on the same day, by the same authors, from the same prestigious university.]

I agree that sugar-sweetened beverages increase the risk of heart disease (not just in men, of course, but in women, too) along with a whole host of other diseases like cancer, diabetes, and Alzheimer’s disease. But, the point remains that this study does nothing to add to the body of evidence implicating sugar because it was not a controlled experiment. This was a waste of time and money reiterating an already strong hypothesis. That effort should have been spent on a controlled experiment.

This problem is actually rampant in nutrition

We’ve got studies “proving” that eating more grains protect men from colon cancer, that light-to-moderate alcohol consumption reduces the risk of stroke in women, and that low levels of polyunsaturated fats, including omega-6 fats, increase the risk of hip fractures in women. Are we to believe these studies? They sure sound authoritative, and the way the press reports on them it’s hard to argue, right?

How are these studies typically done?
Let’s talk nuts and bolts for a moment. I know some of you might already be zoning out with the detail, but if you want to understand why and how you’re being misled, you actually need to “double-click” (i.e., get one layer deeper) a bit. What the researchers do in these studies is follow a cohort of several tens of thousands of people — nurses, health care professionals, AARP members, etcetera — and they ask them what they eat with a food frequency questionnaire (FFQ) that is known to be almost fatally flawed in terms of its ability to accurately acquire data about what people really eat. Next, the researchers correlate disease states, morbidity, and maybe even mortality with food consumption, or at least reported food consumption (which is NOT the same thing). So, the end products are correlations — eating food X is associated with a gain of Y pounds, for example. Or eating red meat three-times a week is associated with a 50% increase in the risk of death from falling pianos or heart attacks or cancer.

The catch, of course, is that correlations hold no (i.e., ZERO) causal information. Just because two events occur in step does not mean you can conclude one causes the other. Often in these articles you’ll hear people give the obligatory, “correlation doesn’t necessarily imply causality.” But saying that suggests a slight disconnect from the real issue. A more accurate statement is “correlation does not imply causality” or “correlations contain no causal information.”

So what explains the findings of studies like this (and virtually every single one of these studies coming out of massive health databases like Harvard’s)?

For starters, the foods associated with weight gain (or whichever disease they are studying) are also the foods associated with “bad” eating habits in the United States — french fries, sweets, red meat, processed meat, etc. Foods associated with weight loss are those associated with “good” eating habits –fruit, low-fat products, vegetables, etc. But, that’s not because these foods cause weight gain or loss, it’s because they are markers for who the people who eat a certain way and live a certain way.
Think about who eats a lot of french fries (or a lot of processed meats). They are people who eat at fast food restaurants regularly (or in the case of processed meats, people who are more likely to be economically disadvantaged). So, eating lots of french fries, hamburgers, or processed meats is generally a marker for people with poor eating habits, which is often the case when people are less economically advantaged and less educated than people who buy their food fresh at the local farmer’s market or at Whole Foods (or Whole Paycheck as I like to call it). Furthermore, people eating more french fries and red meat are less health conscious in general (or they wouldn’t be eating french fries and red meat – remember, those of us who do eat red meat regularly are in the slim minority of health conscious folks). These studies are rife with methodological flaws, and I could devote an entire Ph.D. thesis to this topic alone.

What should we do about this?

I’m guessing most of you – and most physicians and policy makers in the United States for that matter – are not actually browsing the American Journal of Epidemiology (where one can find studies like this all day long). But occasionally, like last week, the New York Times, Wall Street Journal, Washington Post, CBS, ABC, CNN, and everyone else gets wind of a study like the now-famous red meat study and comments in a misleading fashion. Health policy in the United States – and by extension much of the world – is driven by this. It’s not a conspiracy theory, by the way. It’s incompetence. Big difference. Keep Hanlon’s razor in mind – Never attribute to malice that which is adequately explained by stupidity.

This behavior, in my opinion, is unethical and the journalists who report on it (along with the scientists who stand by not correcting them) are doing humanity no favors.

I do not dispute that observational epidemiology has played a role in helping to elucidate “simple” linkages in health sciences (e.g., a great example is that of contaminated water and cholera or the linkage between scrotal cancer and chimney sweeps). However, multifaceted or highly complex pathways (e.g., cancer, heart disease) rarely pan out, unless the disease is virtually unheard of without the implicated cause. A great example of this is the elucidation of the linkage between small-cell lung cancer and smoking – we didn’t need a controlled experiment to link smoking to this particular variant of lung cancer because nothing else has ever been shown to even approach the rate of this type of lung cancer the way smoking has (by a factor of over 100). As a result of this unique fact, Richard Doll and Austin Bradford Hill were able to design a clever observational analysis to correctly identify the cause and effect linkage between tobacco and lung cancer. But this sort of example is actually the exception and not the rule when it comes to epidemiology.
I trust by now you have a better understanding of why the “science” of nutrition is so bankrupt. It is based on almost a complete reliance on these observational studies. Virtually every piece of nutritional dogma we suffer from today stems from – you guessed it – an observational study.

Whether it’s Ancel Keys’ observations and correlations of saturated fat intake and heart disease in his famous Seven Countries Study, which “proved” saturated fat is harmful or Denis Burkitt’s observation that people in Africa ate more fiber than people in England and had less colon cancer “proving” that eating fiber is the key to preventing colon cancer, virtually all of the nutritional dogma we are exposed to has not actually been scientifically tested. Perhaps the most influential current example of observational epidemiology is the work of T. Colin Campbell, lead author of The China Study, which claims, “the science is clear” and “the results are unmistakable.” Really? Not if you define science the way scientists do. This doesn’t mean Colin Campbell is wrong (though I wholeheartedly believe he is wrong on about 75% of what he says based on current data). It means he has not done any real science to advance the discussion and hypotheses he espouses. If you want to read the most remarkable and detailed critiques of this work, please look no further than here (Denise Minger) and here (Michael Eades).

I can only imagine the contribution to mankind Dr. Campbell could have given had he spent the same amount of time and money doing actual scientific experiments to elucidate the impact of dietary intake and chronic disease. [For example, Campbell would have designed a prospective study following subjects randomized to one of two different types of diets for 10 years: plant-based and animal-based, but with all other factors controlled for.] This is one irony of enormous observational epidemiology studies. Not only are they of little value, in a world of finite resources, they actually detracts from real science being done.

It’s time to start doing real science. We do actually have the luxury of doing controlled experiments (in fact, several have been done, they just tend to get ignored), in contrast to climate scientists and social economists. Isn’t it time we stop guessing and find out what foods really increase our risk of dying prematurely? That’s exactly our intent with NuSI, but more on that another day…
Read the complete article here.

Wednesday, March 21, 2012

Looks like the same U-shaped curves of mortality vs total cholesterol applies to half a million Korean men, too. Look at how cancer goes up at the lower TC levels, and how low CHD is compared to all the other causes of death. A full-text pdf file is available.


Which Cholesterol Level Is Related to the Lowest Mortality in Population with Low Mean Cholesterol Level: A 6.4-Year Follow-up Study of 482,472 Korean Men

Yun-Mi Song1, Joohon Sung2 and Joung Soon Kim3

1 Department of Family Medicine, SungKyunKwan University School of Medicine Suwon, Korea
2 Department of Preventive Medicine, College of Medicine, Seoul National University Seoul Korea
3 Department of Epidemiology, Graduate School of Public Health, Seoul National University Seoul, Korea

Received June 1, 1998.
Accepted December 16, 1998.


To evaluate the relation between low cholesterol level and mortality, the authors followed 482,472 Korean men aged 30–65 years from 1990 to 1996 after a baseline health examination. The mean cholesterol level of the men was 189.1 mg/100 ml at the baseline measurement. There were 7,894 deaths during the follow-up period. A low cholesterol level (>165 mg/100 ml) was associated with increased risk of total mortality, even after eliminating deaths that occurred in the first 5 years of follow-up. The risk of death from coronary heart disease increased significantly in men with the highest cholesterol level (≥252 mg/100 ml). There were various relations between cholesterol level and cancer mortality by site. Mortality from liver and colon cancer was significantly associated with a very low cholesterol level (>135 mg/100 ml) without any evidence of a preclinical cholesterol-lowering effect. With lengthening follow-up, the significant relation between a very low cholesterol level (>135 mg/100 ml) and mortality from stomach and esophageal cancer disappeared. The cholesterol level related with the lowest mortality ranged from 211 to 251 mg/100 ml, which was higher than the mean cholesterol level of study subjects. Am J Epidemiol 2000; 151:739–47.
emphasis added by bd

Read the full article here.

the Norwegian HUNT 2 study

Rationale, aims and objectives
Many clinical guidelines for cardiovascular disease

(CVD) prevention contain risk estimation charts/calculators. These have shown a tendency

to overestimate risk, which indicates that there might be theoretical flaws in the algorithms.

Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate

that the predictive properties of cholesterol might not be as straightforward as widely

assumed. Our aim was to document the strength and validity of total cholesterol as a risk

factor for mortality in a well-defined, general Norwegian population without known CVD

at baseline.

Our study provides an updated epidemiological indication of possible errors

in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable,

clinical and public health recommendations regarding the ‘dangers’ of cholesterol should

be revised. This is especially true for women, for whom moderately elevated cholesterol

(by current standards) may prove to be not only harmless but even beneficial.
We assessed the association of

Read the complete article here.


Tuesday, March 20, 2012

Effects of n-3 fatty acids on major cardiovascular events in statin users

These statistics seem to show that omega-3 are better at secondary prevention than statins.

Effects of n-3 fatty acids on major cardiovascular events in statin users and non-users with a history of myocardial infarction


Aims Recent secondary prevention trials have failed to demonstrate a beneficial effect of n-3 fatty acids on cardiovascular outcomes, which may be due to the growing use of statins since the mid-1990s. The aim of the present study was to assess whether statins modify the effects of n-3 fatty acids on major adverse cardiovascular events in patients with a history of myocardial infarction (MI).
Methods and results Patients who participated in the Alpha Omega Trial were divided into consistent statin users (n = 3740) and consistent statin non-users (n = 413). In these two groups of patients, the effects of an additional daily amount of 400 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA), 2 g α-linolenic acid (ALA), or both on major cardiovascular events were evaluated. Multivariable Cox's proportional hazard models were used to calculate adjusted hazard rate ratios (HRadj). Among the statin users 495 (13%) and among the statin non-users 62 (15%) developed a major cardiovascular event. In statin users, an additional amount of n-3 fatty acids did not reduce cardiovascular events [HRadj 1.02; 95% confidence interval (CI): 0.80, 1.31; P = 0.88]. In statin non-users, however, only 9% of those who received EPA–DHA plus ALA experienced an event compared with 18% in the placebo group (HRadj 0.46; 95% CI: 0.21, 1.01; P= 0.051).
Conclusion In patients with a history of MI who are not treated with statins, low-dose supplementation with n-3 fatty acids may reduce major cardiovascular events. This study suggests that statin treatment modifies the effects of n-3 fatty acids on the incidence of major cardiovascular events.
ClinicalTrials.gov number: NCT00127452.

Key words

Noncardiac Benefits of Statins Found Lacking

Noncardiac Benefits of Statins Found Lacking

On the other hand, they found that statins were associated with an increased risk of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataracts.

Cox and Coupland also calculated numbers needed to treat to see a benefit for cardiovascular disease, and to harm for other outcomes.

They found that for women at high risk of heart disease, the number needed to treat to prevent one case over five years was 37. For men, it was 33.

With regard to esophageal cancer, the number needed to treat to prevent one cancer case was substantially higher -- at 1,266 among women and 1,082 among men.

For adverse outcomes among women, the number needed to harm for an additional case of acute renal failure over five years was 434, 259 for myopathy, 136 for liver dysfunction, and 33 for cataract.

Those numbers were similar among men, except for myopathy, which was significantly lower at 91.
Statins are among the most widely prescribed medicines, and researchers say their use is likely to continue to increase. For example, in February, the FDA approved rosuvastatin (Crestor) for primary prevention of cardiovascular disease. (See FDA Okays Statin for Primary Prevention)
Other studies have investigated potential benefits of statins in a variety of conditions, including multiple sclerosis and colorectal cancer.

Still, the literature remains unclear as to the full range of risks and benefits of the drugs, Cox and Coupland wrote.

To quantify unintended effects of statins, the researchers conducted a prospective open cohort study involving 368 general practices in England and Wales that participate in the QResearch database.
A total of 2,004,692 patients ages 30 to 84 were involved in the cohort, and about 11% were new users of statins -- 70.7% were prescribed simvastatin, 22.3% atorvastatin, 3.6% pravastatin, 1.9% rosuvastatin, and 1.4% fluvastatin.

The primary outcome was the first recorded occurrence of any malady -- including cardiovascular disease, liver dysfunction, renal failure, venous thromboembolism, Parkinson's disease, dementia, rheumatoid arthritis, cataract, osteoporotic fracture, gastric cancer, esophageal cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer.

Besides the lack of relationship with all but esophageal cancer, the researchers found no association between statins and risk for Parkinson's disease, rheumatoid arthritis, venous thromboembolism, dementia, or osteoporotic fracture.

Risks for liver and kidney problems,  myopathy, and cataracts were generally similar across statin types, except for liver dysfunction, in which risk was highest for fluvastatin. In women, risk of liver dysfunction was increased 2.53-fold with that statin (95% CI 1.84 to 3.47) and in men it was 1.97-fold higher (95% CI 1.43 to 2.72).

There was generally a dose-response effect for both renal failure and liver dysfunction.

The good news, the researchers found, was that after stopping statin therapy, the risk of developing cataracts returned to normal within a year, and the risk of acute renal failure and liver dysfunction did so within one to three years.

The researchers said that further study is needed in order to confirm the associations and to understand which patients are at the highest risk of adverse effects so that they can be monitored safely.

Overall, they said, the findings "would tend to support a policy of using lower doses of statins in people at high risk of the adverse event."

In an accompanying editorial, Alawi A. Alsheikh-Ali, MD, of Sheikh Khalifa Medical City in Abu Dhabi in the United Arab Emirates, and Richard H. Karas, MD, of Tufts University in Boston, said the findings are "reassuring" in that they didn't find an association between statins and a host of diseases.

"Statin use is not associated with cancer, severe muscle toxicity is rare, and liver abnormalities seem to be reversible, which is consistent with analyses of trial data," they wrote.

Still, they cautioned that physicians "should not overstate the benefits of statins."

"It would be wise to interpret the present observations in the context of the confirmed cardioprotective effects of statins," they wrote, "and remind ourselves and our patients that these drugs, although considered safe, are, like any intervention in medicine, not entirely free of adverse events."