Tuesday, December 19, 2006

Trans fats: The evidence

It is easy to see why the medical profession is generally critical of dietary trans fats. The medical gurus are nearly as critical of trans fats as they once were of dietary cholesterol. If you give people a heap of trans fats to eat in some form and then check their blood chemistry a couple of hours later, the changes observed are indeed in the direction associated with heart disease. For many in the medical profession, that is all the evidence you need to condemn trans fats in the diet. Old hands however are aware that there is no end of medical studies based on short term observations of some factor in isolation (also usually associated with atypically high doses of something) which generate either panics or enthusiasms but which later find no support when one looks at long term or overall effects in epidemiology or in better conducted studies.

And intellectual fashions have an alarming tendency to be self-reinforcing. The only kind of study which could settle the question of long term overall ill-effects from trans fats is of course a double-blind prospective study -- where normal, average healthy people are divided into two groups and over a long period fed diets that differ only in trans fat content. You then see how many die in each group in the given period. Drug evaluation research routinely uses such studies but in the case of trans fats, such research has recently been declared "unethical" (See D. Mozaffarian, M. B. Katan, A. Ascherio, M. J. Stampfer, and W. C. Willett. "Trans Fatty Acids and Cardiovascular Disease" N.Engl.J.Med., 2006, 354:1601-1613) and nobody seems to be doing it. It must be comforting to rule out in advance research that could prove you wrong. It is at least dogmatic and arrogant (though parading as compassionate, of course).

It is perhaps because of the lack of proper prospective studies and the need for the prevailing religion to be reinforced that the medical literature is replete with review articles that stress the evils of trans fats. And each new review quotes a lot from previous reviews. The image it all calls to my mind is of one turtle clinging to the back of another turtle who is clinging to the back of another turtle who is clinging to the back of another turtle. One can only hope that the bottom turtles (research reports) are standing on something solid. Knowing how often medical journal articles overlook important confounding variables like social class I doubt it of course. As a humble retired psychologist who comes to this field out of an interest in the sociology of knowledge, I have neither the time nor the ease of access to look at the multitude of bottom turtles concerned but I do notice something about the reviews: It is notable that the most recent reviews are the most definite and mention fewer "non-conforming" research results.

I thought it might be interesting therefore to reproduce below the epidemiology section of an older (1999) review so that readers can see that there are many studies which do not show ill effects of such fats and which mention many doubts about those studies which do show ill effects (Quote: "Interpretation of comparisons among populations with widely different lifestyles is hazardous"). The authors still come to the conclusion that theory and short-term observations would suggest but it is of course the long-term and overall effect of trans fat ingestion that is the issue -- hence the interest of epidemiological studies. The source article for the excerpt below is: Ascherio A, Katan MB, Zock PL, Stampfer MJ, Willett WC. "Trans fatty acids and coronary heart disease". N Engl J Med 1999;340:1994-1998. It is from a prestigious journal and has often been cited

"Epidemiologic Studies

The strong correlation between the level of intake of saturated fatty acids and the rates of coronary heart disease among the 16 populations examined in the Seven Countries Study19 is often quoted as evidence that the consumption of saturated fat increases the risk of coronary heart disease. A subsequent biochemical analysis of food composites representing the average intake of each cohort at base line20 not only confirmed that the intake of saturated fatty acids was strongly correlated with the risk of death from coronary heart disease (r=0.88, P<0.001) but also showed that the intake of trans fatty acids was correlated with the risk of death from coronary heart disease (r=0.78, P<0.001). Interpretation of comparisons among populations with widely different lifestyles is hazardous, but these data leave room for a potentially substantial effect of trans fatty acids on the risk of coronary heart disease.

Several case–control or cross-sectional studies have also been conducted. In a case–control study of subjects in the Boston area, we found a strong and significant positive association between the intake of trans fatty acids, assessed with the use of dietary questionnaires, and the risk of acute myocardial infarction.21 The relative risk of acute myocardial infarction for the quintile with the highest intake of trans fatty acids as compared with the quintile with the lowest intake was 2.4 (P for trend <0.001); this association was entirely explained by the intake of these fats from hydrogenated vegetable oil. Bolton-Smith et al. performed a cross-sectional analysis of the association between the intake of trans fatty acids and the presence of previously undiagnosed coronary heart disease among participants in the Scottish Heart Study.22 The intake of trans fatty acids was positively correlated with the ratio of LDL plus very-low-density lipoprotein cholesterol to HDL cholesterol. The odds ratios for coronary heart disease in the quintile with the highest intake as compared with the quintile with the lowest intake were elevated but not significantly so (1.26 in women and 1.08 in men).

Studies in which the composition of fatty acids in tissue or plasma was used as a marker of trans-fatty-acid intake have yielded conflicting results. With one exception, however, these studies have been too small to detect an association reliably. The results of the only large study,23 which included 671 men with acute myocardial infarction from eight European countries, were inconclusive. The overall analyses revealed no association between the intake of trans fatty acids and the risk of myocardial infarction. However, in contrast to the centers studied in other countries, the two centers studied in Spain, where the rates of coronary heart disease are very low, reported extremely low levels of trans-fatty-acid intake and little variation between subjects and thus provided little information. After the exclusion of these data, the odds ratios for the third and fourth quartiles of intake, as compared with the lowest, were 1.53 and 1.44, respectively. The interpretation of the results of this study has caused controversy,24 but in any case they do not provide strong evidence against the hypothesis that the consumption of trans fatty acids increases the risk of coronary heart disease.

The strongest epidemiologic evidence relating dietary factors to the risk of coronary heart disease has been provided by three large prospective studies: the Health Professionals Follow-up Study,25 the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study,26 and the Nurses' Health Study.27 Those studies assessed the intake of trans fatty acids using detailed food-frequency questionnaires whose results were validated by comparison with the composition of adipose tissue or food diaries. Each of these studies reported an adverse effect of trans fatty acids. The relative risk of coronary heart disease associated with an absolute increase of 2 percent in the intake of trans fatty acids was 1.36 (95 percent confidence interval, 1.03 to 1.81) in the Health Professionals Follow-up Study, 1.14 (95 percent confidence interval, 0.96 to 1.35) in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, and 1.93 (95 percent confidence interval, 1.43 to 2.61) in the Nurses' Health Study. The higher relative risk in the Nurses' Health Study may have resulted from the fact that there were four dietary measurements during the follow-up period, thereby reducing the degree of error in assessing trans-fatty-acid consumption. In these three cohorts, the relative risks were higher than those for saturated-fat consumption. For example, in the Nurses' Health Study, replacing 5 percent of energy intake from saturated fat with unsaturated fat was associated with a 42 percent decrease in the risk of coronary heart disease, whereas replacing 2 percent of energy intake from trans fatty acids with cis fatty acids was associated with a 53 percent decrease in the risk.

These studies have been criticized on the grounds that measurements of the intake of trans fatty acids were unreliable4; however, random errors in measuring the intake would only have led to an underestimation of the association with the risk of coronary heart disease. It has also been suggested that the observed associations resulted from a shift from the use of butter to the use of margarine among high-risk subjects. If so, the association between the intake of trans fatty acids and the risk of coronary heart disease should have been weaker among subjects with stable margarine consumption and stronger during the first few years of follow-up. However, in the Nurses' Health Study,28 the exclusion of women who changed their diet before the beginning of the study strengthened the association. Moreover, consumption of foods high in trans fatty acids such as cookies, which are hardly perceived as healthy, was also positively associated with the risk of coronary heart disease.

Confounding as a result of unmeasured or poorly measured risk factors is a potential problem in any observational study, but these associations were adjusted for many risk factors related to diet and lifestyle, and no credible confounding factor has been identified. Adjustment for the intake of dietary fiber attenuated the relation of trans-fatty-acid intake to the risk of coronary heart disease in the Health Professionals Follow-up Study,25 but not in the other two studies26 (and Hu FB: personal communication). Thus, prospective studies provide consistent evidence that the consumption of trans fatty acids increases the risk of coronary heart disease. The observed relative risks of coronary heart disease were larger than one might predict from the effects of trans fatty acids on LDL and HDL cholesterol levels alone. The increases in triglyceride and Lp(a) lipoprotein levels account for only a small increase in risk; therefore, other mechanisms may be involved."

Note also that the most recent review article reports only two studies of sudden death from heart disease (which is what most people would be worried about) in which trans fats were examined. In one there was no effect and in the other a weak effect was found only by examining extreme groups. See the excerpt below from D. Mozaffarian, M. B. Katan, A. Ascherio, M. J. Stampfer, and W. C. Willett. "Trans Fatty Acids and Cardiovascular Disease" N.Engl.J.Med., 2006, 354:1601-1613:

"Sudden Death from Cardiac Causes

Some data suggest that trans fatty acids may increase the risk of sudden death from cardiac causes. In a study that compared adipose tissue obtained at autopsy from 66 patients with sudden death from cardiac causes with that obtained from 286 healthy age- and sex-matched controls, levels of trans fat were not found to be associated with sudden death from cardiac causes. In contrast, in a larger, community-based case-control study (179 cases), levels of trans fatty acids in erythrocyte membranes were associated with an increase in the risk of sudden cardiac death (odds ratio for interquintile range, 1.47; 95 percent confidence interval, 1.01 to 2.13), after adjustment for other risk factors."

Note also the general comments at the foot of today's posts

Gene therapy for impotence

Doctors have developed a gene therapy treatment that could cure millions of men who suffer from impotence. This comes after researchers were able to identify a gene that is responsible for the condition that affects as many as 60 per cent of men over the age of 55 and around three million men in total in the UK. Tests of the therapy have already started in humans, and the first small trial using the gene has proved that it is safe and works. Men suffering from impotence would need just two injections a year to be able to enjoy a normal sex life.

Although drugs like Viagra have revolutionised the treatment of men with erectile dysfunction, many still claim there is a lack of spontaneity, as love-making has to be planned in advance by taking a pill.

Doctors who discovered the gene say that - for the first time - it will give men with impotence problems total control over their love lives. Around 30 per cent of impotence cases have psychological reasons, but the remaining 70 per cent are physical. Heart disease and diabetes are two of the biggest causes in the middle-aged and elderly.

The gene breakthrough has been made by a team at the Albert Einstein College of Medicine in New York, who say the treatment could become available in less than five years. Lead researcher Professor Arnold Melman says: "Our initial research proves that this is a safe method of treatment for male impotence that works very effectively. "The initial trial was in 11 impotent men - two of whom were able to have intercourse for six months after having their gene therapy jab. "It would have worked for all 11 patients, but initially we had to give a combination of low doses and high doses because this was a phase one safety trial, principally looking at the safety of the therapy. "The two men for whom it worked had the highest doses of the drug. "One of the attractions of the drug is that men have just two injections a year and do not have to worry about taking pills - they can just forget they have a problem. The existing impotence drugs can have side effects, such as making men feel dizzy, but so far we have found none with gene therapy." Professor Melman - a urologist - and fellow researcher Dr George Christ will now give high doses of the jab, called Maxi K, to almost 200 men in a trial starting in the New Year.

The gene used in the treatment has been artificially created in the laboratory and is an exact copy of a gene found in human "smooth muscle" tissue, the type of muscle found in the penis. Dr Melman points out that the gene is entirely safe and has been developed without having to use a human virus - such as the common cold virus -to "carry it" to the part of the body where it is needed. "One of the concerns with gene therapy has been the use of viruses and how they can affect the immune system," he says. "We have got round that by developing a gene that does the job without needing assistance."

The gene works in a similar way to impotence drugs like Viagra - except it lasts longer because it stays in the body for months, rather than just a few hours. The gene jab enables extra potassium to be produced, which acts to relax the smooth muscle in the penis, allowing an increased flow of blood into the blood vessels. For it to work properly, it has to be injected into the penis, but Dr Melman says modern techniques mean this is relatively painless. He says: "For many men, the mind might be willing -they desire their partner - but the chemical and mechanical reaction to make things happen is not strong enough. What this gene does is to boost the existing cells so love-making becomes possible."

Dr Richard Petty, medical director of the London Wellman Clinic, approves of the gene breakthrough. "This is fantastic news, because impotence pills like Viagra work for only about 60 per cent of men, and there are many who can't take these pills because of conditions such as heart disease. "Men don't like being reminded they have a problem, but that's what happens every time they pop a pill. The fact they can have a jab that restores their sexuality for six months will be a big boost for men."



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter? It is just about pure fat. Surely it should be treated as contraband in kids' lunchboxes! [/sarcasm].

Trans fats:

For one summary of the weak science behind the "trans-fat" hysteria, see here. Trans fats have only a temporary effect on blood chemistry and the evidence of lasting harm from them is dubious. By taking extreme groups in trans fats intake, some weak association with coronary heart disease has at times been shown in some sub-populations but extreme group studies are inherently at risk of confounding with other factors and are intrinsically of little interest to the average person.

The use of extreme quintiles to examine effects is in fact so common as to be almost universal but suggests to the experienced observer that the differences between the mean scores of the experimental and control groups were not statistically significant -- thus making the article concerned little more than an exercise in deception


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