Friday, March 16, 2012

Red meat increases early mortality risk. At least if you live in the USA. Part 1

Background: This week, the news showed us that red meat consumption decreases lifespan (1, 2). But was this effect caused by the red meat, or because meat eaters had a generally unhealthy lifestyle?

The news reports based their conclusion on results from the "Health Professionals Follow up Study" and the "Nurses' Health Study" (3) by Pan et al. 37,698 men and 83,644 women participated in the research. At baseline, participants were asked to complete a food frequency questionnaire. And they were asked to do this again every 4 years. Until now, 8,926 men and 15,000 women died during follow-up (22 years for men and 28 years for women). Men in the highest quintile of red meat consumption had a 37% increased risk of dying within the follow-up period. And risk increased by 24% among women. Both mortality from cardiovascular disease and cancer increased significantly among both men and women. Both processed- and unprocessed red meat increased risk of early mortality.

What did the meat industry think of these results?
Not surprisingly, the American Meat Industry (AMI), criticized the results (4):
The American Meat Institute (AMI) said the study’s main flaw was the fact that it relied on self-reporting to survey participants' diets, but that the method of collecting data was also 'highly inaccurate'.
This conclusion automatically implies that all research on diet is nonsense. All research relies on self-reporting of dietary intakes, unless you are under 24-hour/day surveillance. Who else is going to report what you consume?

The AMI continuous:
According to AMI, the researchers inserted estimated data when actual survey measurement was missing, and stopped updating the dietary information as soon as participants reported a diagnosis.
According to Pan et al, missing values in a follow-up food frequency questionnaire were replaced with the cumulative averages before the missing values.
Additional analysis included updating a participant's diet even after he or she reported a diagnosis of major chronic disease. This can be seen in the online supplemental data (5). Risk of early mortality remained significantly elevated after this update.

According to the AMI:
Red and processed meat continues to be a healthy part of a balanced diet and  nutrition decisions should be based on the total body of evidence, not on single studies that include weak and inconsistent evidence and stand in contrast to other research and to the Dietary Guidelines for Americans, 2010.
No references are given to show that red and processed meat continue to be a healthy part of a balanced diet. No references are given to show that other studies found different results.
The statement is in contradiction to what the Pan et al actually found. Table 2 of the article shows that risk of early mortality increased with every quintile of consumption among both men and women (3). In addition, participants in the 2nd quintile of consumption had a significantly increased risk of dying, compared to participants in the 1st quintile of consumption. Showing that even moderate intakes might decrease lifespan.

Do consumers of red meat die early because of the meat, or because they live unhealthier lives?
Pan et al diminished the chance that possible confounders would influence the relation between red meat and mortality. They adjusted for age, body mass index, alcohol consumption, physical activity, smoking status and other factors. And for dietary variables which may be linked to a healthier lifestyle: whole grains, fruits, and vegetables. Additional adjustment for other foods (fish, poultry, nuts, beans, and dairy products) did not appreciably alter the results.

And according to the researchers:
In addition, the FFQs used in these studies were validated against multiple diet records. However, the measurement errors inherent in dietary assessments were inevitable, including misclassification of ham or cold cuts as unprocessed red meat and inaccurate assessment of red meat content in mixed dishes. Because of the prospective study design, any measurement errors of meat intake are independent of study outcome ascertainment and, therefore, are likely to attenuate the associations toward the null. In the sensitivity analysis accounting for measurement errors, the risk estimates became stronger.
All types of red meat increased risk of early mortality
Pan et al included 6 types of red meat:
-Beef, pork, or lamb as main dishes.
-Beef, pork, or lamb as a sandwich or mix dish.
-Hog dog.
-Other processed red meat.
Mortality rates significantly increased with higher intakes of all 6 types of red meat, among both men and women.

Results from 2 prospective studies show that both unprocessed- and processed red meat may increase risk of early mortality. Risk of death increased with every quintile of increasing consumption.
Evidence for a possible causal relation strengthens when findings are consistent. According to this criterion, red meat did not do well: Early mortality risk increased with all types of red meats examined. And both cardiovascular disease- and cancer mortality risk rose significantly. Findings were similar among men and women.

In Part 2, I will examine if other studies found similar effects.

1) Abcnews. Red meat tied to increased mortality risk. March 12, 2012.
2) Nytimes. Risks: more red meat, more mortality. March 12, 2012.
3) Pan A. Red meat consumption and mortality: results from 2 prospective cohort studies. Arch Intern Med. 2012 Mar 12. [Epub ahead of print].
4) Michel M. Study linking red meat to high mortality under fire. March 13, 2012.
5) Pan A. Red meat consumption and mortality: results from 2 prospective cohort studies. eTables & eFigure.

Tuesday, March 6, 2012

Do trends in fat intake correlate to changes in heart disease?

Background: This is based on an article published in The British Journal of Nutrion by 13 scientists (Pedersen et al.) and 3 published letters to the editor in response to the article. More detailed background information can be found in an article I described earlier (1).

This part describes the evidence for a link between trends in saturated fat consumption and their correlation to changes in CVD.
Pedersen et al (2) state that:

There have been substantial reductions in mortality from CVD (cardiovascular diseases) in North America, Western Europe and Australasia over the last 30 years that reflect successful national public health policies to reduce the intake of SFA (saturated fatty acids), in addition to promoting smoking cessation and controlling blood pressure.

As they state themselves "in addition to promoting smoking cessation and controlling blood pressure". If these changes occur at the same time, how do we know which change "caused" any possible change in CVD?
In addition, no references were given to back up these "claims".

I did find an article providing data about trends in saturated fat intake in America (3). It showed that the energy% from intake of saturated fat sligtly decreased over time, while the absolute intake increased:
A report from the US Department of Agriculture and the US Department of Health and Human Services states that no reductions were found in the intake of SFA in the American diet over the period 1989–1 to 2005–6(4). Indeed, although the intake of SFA as percentage of total energy (en%) was slightly higher over the first time period (12·3), than over the last three time periods (11·2–11·4), the total amount of SFA in g/d increased slightly over this time (25·7–27·8).
And I gave out the following warning:
More importantly, it is not possible to unequivocally associate changes in SFA intake to changes in CHD mortality over time, since many changes in diet, lifestyle, diagnosis and pharmacological treatments have occurred over the last 30 years.
A bit further in the text, the authors state:
That replacement of SFA by a variety of carbohydrate-containing foods also reduces CHD risk may be inferred from ecological studies, e.g. in Finland. CHD was almost non-existent in rural China when mean cholesterol levels were approximately 3.5 mmol/L  with total fat intakes only about 15% of energy and extremely low intakes of SFA. These observations, replicated in many countries, should not be ignored.

This time, 2 references were given (4, 5). Both referred to "The China Study". But no trends in fat intake were examined in the articles referred to. No references were given that correlated saturated fat intake to heart disease in Finland.

How Pedersen et al. responded to my findings, can be found in their response to my letter (6). They concluded that:
Hoenselaar expresses doubt if a reduction in SFA intake has occurred concurrent with the decline in CHD mortality in developed populations. This is illustrated by citing the small relative reduction of SFA intake in the US population during the period 1990-5/6.
This is an incorrect reflection of the trends in SFA intake I mentioned earlier. As I showed before SFA intake increased from 25.7 to 27.8 g/day. The reason why the relative contribution showed a small decline, is that intakes of energy from other nutrients (in this case carbohydrates) increased even more. Therefore, the strongest change is an absolute and relative increase in carbohydrate intake.

Pedersen et al. continue:
During several decades before the turn of the 20th century, SFA intake declined and PUFA intake increased in the USA. There are also reports of declining SFA intake concomitant with the reduction in CHD mortality in several other populations. In all Nordic countries, SFA intake has decreased compared to the levels in the 1960s. The decline has been particularly noticeable in the Finnish population that has experienced the most rapid fall in CHD mortality in the world.

New Zealand may be cited as another example.
This time the authors refer to 5 articles (7-11). No correlations were made between saturated fat intake and heart disease in any of the articles referred to. What these articles actually described were trends in fat intake over different time periods for three different populations. The rest of my comment was as follows:
Two reports described fat intake in the USA. The changes in SFA and PUFA intake were accompanied by a decrease in MUFA intake. Since these three changes were of equal size and took place at the same time, it will take other data to put them in perspective before they can be possibly directly linked to CHD. Two other reports described fat intake in Nordic countries, with an emphasis on Finland. Again, changes in SFA and PUFA intake took place in the same time frame. This time, these changes were accompanied by a decrease in trans-fat (TFA) intake. The New Zealand report is the only article which might suggest a direct link between SFA and CHD. It shows a trend in decreased CHD rates over time, and (in another part of the text) it is mentioned that SFA consumption decreased over time. However, no direct correlation was examined.
I also showed that both heart disease and stroke mortality are highest in countries with low saturated fat consumption. I described this finding in another article on my blog (12).

Conclusion: An international group of scientists states that mortality from cardiovascular diseases has decreased over the past decades. And that this decrease is (partially) caused by a decrease in saturated fat intake. The scientists refer to several articles, none of which examined this correlation. I find it very disturbing that a group of 13 scientists draws firm conclusions, but is not able to find one single study as a base for their findings.
Equally disturbing are their interpretations of simple correlations. If there is a large absolute increase in carbohydrate intakes over the past decades in the USA, the relative contribution of saturated fats will automatically decrease. But this does not mean that saturated fat intakes decreased. In fact, intakes of saturated fats increased from 25.7 to 27.8 g/day! The most obvious conclusion would then be that an increased intake of carbohydrates (or small increase in saturated fat intake) was linked to lower mortality from CVD. Instead, Pedersen et al. suggest that a decrease in saturated fat intake was the cause of lower mortality rates from CVD in the USA.

1) Hoenselaar R. Scientists provide incorrect information (part 1). Natural fats do not negatively influence cholesterol.
2) Pedersen JI et al. (2011). The importance of reducing SFA to limit CHD. Br J Nutr 106, 961-963.
3) US Department of Agriculture and US Department of Health and Human Services (2010) Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans, 2010. 20 September 2011).
4) Campbell TC et al (1998). Diet, lifestyle, and the etiology of coronary artery disease: the Cornell China study. Am J Cardiol. 1998 Nov 26;82(10B):18T-21T.
5) Campbell TC et al (1999). Energy balance: interpretation of data from rural China. Toxicol Sci. 1999 Dec;52(2 Suppl):87-94.
6) Pedersen JI et al (2012). Response to Hoenselaar from Pedersen et al. Br J Nutr 107, 452-454.
7)  Committee on Diet and Health (1989) Dietary intake and nutritional status: trends and assessment. In Diet and Health. Implications for Reducing Chronic Disease Risk, chapter 3, pp. 41–84. Washington, DC: National Research Council, National Academy Press.
8) Stephen et al (1990). Trends in individual consumption of dietary fat in the United States, 1920–1984. Am J Clin Nutr 52, 457–469.
9) The Project Group: Food Consumption in the Nordic Countries (2001) National, Annual Food Balance Sheets (in Swedish) TemaNord 2001:527. Copenhagen: Nordic Council of Ministers.
10) Valsta LM et al (2010). Explaining the 25-year decline of serum cholesterol by dietary changes and use of lipid-lowering medication in Finland. Public Health Nutr 13, 932–938.
11) Ministry of Health and the University of Auckland (2003). Nutrition and the Burden of Disease: NewZealand 1997–2011. Public Health Intelligence Occasional Bulletin No. 17.Wellington: Ministry of Health.
12) Hoenselaar R. Heart disease and stroke mortality are highest in countries with low saturated fat consumption. 

Monday, March 5, 2012

Natural fats do not negatively influence cholesterol

Background: In October 2011, the British Journal of Nutrition published a guest editorial by 13 scientists (Pedersen et al). In this article, they explain the importance of reducing saturated fat intake to limit heart disease risk (1). Because I found that the base of their information was scientifically incorrect, I decided to write a so-called "letter to the editor", which was also published (2). This was followed by a response by Pedersen et al (3) and again, by a response from me (4). All responses got published in the British Journal of Nutrition.

The articles contain a lot of information, so I decided to go for a stepwise analysis of the contents.

Pedersen et al are concerned that saturated fatty acids (SFA) may no longer be considered an important cause of coronary heart disease (CHD):
Uncertainty has recently been expressed as to the role of SFA for the development of atherosclerosis and CHD.
Our main concern, however, is to emphasise the importance of lowering SFA intakes to reduce blood LDL-cholesterol levels at a time when there are tendencies to downplay the importance of SFA.
I was surprised about the 2nd sentence, because the importance of HDL-cholesterol in this association was not mentioned. Two (Katan MB and Mensink RP) of the 13 scientists involved have published an article in the past (5). The conclusions in that article seem completely opposite to their current conclusion. In a meta-analysis of 60 controlled trials they found that replacing carbohydrates by saturated fats will increase both "bad" LDL-cholesterol levels and "good" HDL-cholesterol levels, without changing the ratio total/HDL-cholesterol. Based on this they stated that:
Results suggest that isoenergetic replacement of SFA with carbohydrates does not improve the serum total:HDLcholesterol. All natural fats contain both SFA, which do not  change this ratio, and unsaturated fatty acids, which lower it. As a result, even the replacement of dairy fat and tropical fats with carbohydrates will increase the ratio of total  to HDL-cholesterol.
This can be seen in the following figure they added:

The authors gave us 2 warnings:
Results of prospective observational studies, controlled clinical trials with drugs, mechanistic studies, and genetic 'experiments of nature' all strongly suggest that high concentrations of HDL-cholesterol in the circulation help to prevent coronary artery disease and other CVD. Given these observations, it appears imprudent to ignore the marked effects of diet on HDL-cholesterol.

The effects of dietary fats on total:HDL-cholesterol may differ markedly from their effects on LDL. The effects of fats on these risk markers should not in themselves be considered to reflect changes in risk but should be confirmed by prospective observational studies or clinical trials.
And in 2007, a meta-analysis of 61 prospective studies article was published in the Lancet (6). The authors concluded that including HDL-cholesterol increased the predictive value of non-HDL cholesterol (LDL-cholesterol) for ischemic heart disease (IHD):
Of various simple indices involving HDL cholesterol, the ratio total/HDL cholesterol was the strongest predictor of IHD mortality (40% more informative than non-HDL cholesterol and more than twice as informative as total cholesterol).

Conclusion:  In 2003, Katan MB and Mensink RP concluded that even animal fats will have a positive effect on the ratio total/HDL cholesterol, compared to carbohydrates. They stressed that the effect from dietary fats on HDL-cholesterol should not be ignored and that effects on cholesterol should not in themselves be considered to reflect changes in heart disease risk.
In 2011, the authors completely changed their mind, while they did not reject de results they published earlier. All of a sudden, changes in LDL-cholesterol - and LDL-cholesterol only - are supposed to be the single one predictor of changes in heart disease risk.

1) Pedersen JI et al. (2011) The importance of reducing SFA to limit CHD. Br J Nutr 106, 961-963.
2) Hoenselaar R (2011). The importance of reducing SFA intake to limit CHD risk. Br J Nutr. 2012 Feb;107(3):450-1; author reply 452-4.
3) Pedersen JI et al (2012). Response to Hoenselaar from Pedersen et al. Br J Nutr 107, 452-454.
4) Hoenselaar R (2012). Further response from Hoenselaar. Br J Nutr [Epub ahead of print]
5) Mensink RP et al (2003). Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003 May;77(5):1146-55.
6) Prospective Studies Collaboration (2007) Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 370, 1829-1839.

Thursday, March 1, 2012

Heart disease and stroke mortality are highest in countries with low saturated fat consumption

Background: In 1993, Artaud-Wild et al published an article linking per capita intakes of saturated fat to mortality rates from coronary heart disease (CHD) (1). A global analysis was done including data from 40 countries. Figure 1 shows that a strong positive correlation (R = 0.78) was found between a "cholesterol-saturated fat index" and CHD mortality among men. This correlation was similar for the % of energy from saturated fat intake (R = 0.77).

Figure 1:

Is more recent data available?
No articles about this correlation were published since. But in 2008, the British Heart Foundation published the European Cardiovascular Disease Statistics (2). The report included European mortality rates from both CHD and stroke for 1972 to 2005 for both men and women. In addition, it provided data about European per capita consumption of saturated fat for the year 1998. This data gives us the possibility to link saturated fat intake to mortality rates in 1998. A total of 41 countries had available data about both saturated fat intake and mortality rates for this year. I used a simple Pearson correlation to examine if a significant correlation could be found. The effect can be seen in figure 2.

Figure 2:

Results: unexpectedly, the highest mortality rates from CHD were found in the countries with the lowest intakes of saturated fats. The correlation was significant (2-tailed significant at < 0.01). The R2 for linearity = 0.34.

How can this difference in effect be explained?
  • Artaud-Wild et al used data from the year 1977, I used data from 1998.
  • Artaud-Wild et al used mortality rates that were not adjusted for age. I used age-standardized mortality rates.
  • Artaud-Wild et al used a global analysis including 40 countries. I used a European analysis including 41 countries. Sadly, I could not find data about more countries.
Were results similar looking at women or at stroke mortality?
Pearson correlations showed that higher mortality rates were consistently linked to lower intakes of saturated fat (two-tailed significance = < 0.01 for all). In addition to the correlation shown in figure 2, I also examined 3 other end points. Correlations were slightly stronger than the one seen in figure 2. Results are as follows:
  • Male stroke mortality: R2 = 0.38
  • Female CHD mortality: R2 = 0.43
  • Female stroke mortality: R2 = 0.43
Conclusion: a global analysis including 40 countries showed that higher intakes of saturated fat were linked to higher mortality rates from coronary heart disease among men in 1977. But a European analysis including 41 countries showed that lower intakes of saturated fat were linked to higher mortality rates from both coronary heart disease and stroke in both genders in 1998...............................

1) Artaud-Wild SM et al. Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox. Circulation. 1993 Dec;88(6):2771-9.
2) Allender S et al. European cardiovascular disease statistics 2008 edition.  

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