Replacing saturated fat by unsaturated fat decreases CVD risk. Or maybe not!

Background: Recently, a few systematic reviews were published in which the effect of replacing saturated fats by polyunsaturated fats on coronary heart disease (CHD) was examined (1, 2). Both articles showed that this might lead to a small reduced risk of CHD, but all-cause mortality rates did not change by modifying dietary fats. The authors did not conclude that lowering intakes of saturated fat may reduce CHD risk. And the authors from one of the articles showed that results were strongly biased by potential confounders (2).
Last year another systematic review on this topic was published (3). Based on their results, this was the first time that authors adviced to lower intakes of saturated fat in order to reduce risk of cardiovascular diseases (CVD):

The findings are suggestive of a small but potentially important reduction in cardiovascular risk on modification of dietary fat, but not reduction of total fat, in longer trials. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.

Let's take a look if this advice is valid based on the study results.

Study results:
Table 1/Comparison 1 shows the primary results found by the authors. Effects on total mortality, CVD mortality and CVD events were published. Three types of studies were included:

• Modified fat intake (replacing saturated fat by unsaturated fats).
• Reduced fat intake.
• Both reduced fat intake and modified fat intake.

As stated before, 3 effects were examined. The top effects in table 1 are based on all studies combined. Below that, results can be seen from studies in which effects from fat modification only were examined. When all types of studies were combined, a small significant protective effect (- 14% risk) against CVD risk was found. But fat modification did not lead to a significantly lower risk of CVD: RR = 0.82 (0.66-1.02). No significant effects on CVD mortality, or all-cause mortality were found. Subjects in the fat modification group did not live a day longer than subjects in the control group.

Effects from fat modification on CVD:
Replacing saturated fats by unsaturated fats apparently lead to a non-significant 18% lower risk of CVD events, but effects on CVD mortality were even weaker (- 8%). This suggests that risk of nonfatal CVD events might slightly decrease. But what specific type of events was lowered by fat modification?
If we take a look at other results published by the authors, we see no significant effects on myocardial infarctions (- 9% risk), non-fatal myocardial infarctions (- 14% risk), or stroke (- 30% risk).
It is noteworthy to mention that risk of total, or non-fatal myocardial infarctions did not change by fat modification, since replacing butter by margarine is supposed to lead to a lower risk of this disease.
The authors define cardiovascular events as follows:

Combined cardiovascular events included any of the following data available from a trial: cardiovascular deaths, cardiovascular morbidity (non-fatal myocardial infarction, angina, stroke, heart failure, peripheral vascular events, atrial fibrillation) and unplanned cardiovascular interventions (coronary artery bypass surgery or angioplasty).

So which type of nonfatal CVD was reduced by fat modification? Did the experimental groups have a smaller risk of angina?

The article also shows how the non-significant protective effect against CVD mortality (- 8% risk) was possibly compensated to lead to absolutely no protective effect against all-cause mortality (+ 2% risk): Fat modification lead to a non-significantly increased risk of cancer death (+ 46% risk).

Did the studies included only examine the effect of replacing saturated fat by unsaturated fat?
At least part of the studies should never have been included in the systematic review. In addition to a reduced intake of saturated fats and dietary cholesterol, also the intakes of trans fat were reduced in the experimental groups from the studies included in the review. In some of the studies, the dietary intervention included a complete mediterranean dietary pattern. Bias from other (non)dietary factors is discussed on my other site (4) and in an article of mine that was published recently (5).

Can other types of bias be responsible for the results found by the authors?
The possibility of publication bias was examined by including a socalled "funnel plot". This plot can be seen below. The squares/plots represent the results from the individual studies. The "1" on the x-axis represents zero effect. Plots on the left of the "1" value represent a "protective effect" and plots on the right of the "1" value represent an increased risk of CVD events. The larger trials are plotted higher in the figure. The smaller studies are shown lower in the figure. We see that most larger trials are plotted around the "1"value indicating little or no effect on CVD events. But we can also see that most of the smaller trials are plotted left from the "1" value, showing protective effects. This suggests that small studies showing that the dietary intervention lead to increased risk of CVD events may not have been published. This would indicate that the small protective effect is actually an overestimation of the true effect. The authors conclude the same:

A funnel plot did not suggest severe small study (or publication) bias, but it is likely that a few small studies with more cardiovascular events in the intervention groups may be missing from the review (Figure 4).

Was there a specific effect from saturated fat?
Because intakes of both saturated- and unsatured fats changed in the dietary interventions, it is impossible to assess which change is responsible for the effects found. To examine this, the researchers made an additional analysis, shown in the table below. None of the effects was significant. None of the different types of fat could be held responsible for the effects found.

Conclusion: Dietary interventions in the systematic review by Hooper et al included replacing saturated fat by unsaturated fats, sometimes accompanied by a large amount of other (non)dietary changes which were not mentioned. These interventions may lead to a slightly lower risk of nonfatal CVD events, while risks of fatal CVD and all-cause mortality do not seem to change. It is not clear which types of nonfatal CVD events may be influenced beneficially by these interventions, since risk of non-fatal myocardial infarctions did not significantly change. Saturated fat intake could not be helt responsible for the effects found. It is possible that publication bias lead to an overestimation of the true effects of the dietary interventions on CVD events.


References:
1) Mozaffarian D. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2010 Mar 23;7(3):e1000252. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843598/?tool=pubmed
2) Ramsden CE. n-6 fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials. http://www.ncbi.nlm.nih.gov/pubmed/21118617
3) Hooper L. Reduced or modified dietary fat for preventing cardiovascular disease. http://www.ncbi.nlm.nih.gov/pubmed/22592684
4) Hoenselaar R. Randomized trials substituting polyunsaturated fat for saturated fat and their effect on coronary heart disease (CHD). A closer look. http://canceranddiet.nl/cardiovascular_disease/randomized-saturated-polyunsaturated-fat.html
5) Hoenselaar R. Further response from Hoenselaar. Br J Nutr. 2012 Mar 1:1-4. [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/22377374

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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.
-Hamburger.
-Bacon.
-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.

Conclusion:
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.


References:
1) Abcnews. Red meat tied to increased mortality risk. March 12, 2012.  http://abcnews.go.com/Health/w_DietAndFitness/red-meat-tied-increased-mortality-risk/story?id=15901365#.T2MX-OWoWNY
2) Nytimes. Risks: more red meat, more mortality. March 12, 2012. http://www.nytimes.com/2012/03/13/health/research/red-meat-linked-to-cancer-and-heart-disease.html
3) Pan A. Red meat consumption and mortality: results from 2 prospective cohort studies. Arch Intern Med. 2012 Mar 12. [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/22412075
4) Michel M. Study linking red meat to high mortality under fire. March 13, 2012. http://www.globalmeatnews.com/Industry-Markets/Study-linking-red-meat-to-high-mortality-under-fire
5) Pan A. Red meat consumption and mortality: results from 2 prospective cohort studies. eTables & eFigure. http://archinte.ama-assn.org/cgi/content/full/archinternmed.2011.2287/DC1

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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.


References:
1) Hoenselaar R. Scientists provide incorrect information (part 1). Natural fats do not negatively influence cholesterol. http://dietanddisease.blogspot.com/2012/03/scientists-provide-incorrect.html
2) Pedersen JI et al. (2011). The importance of reducing SFA to limit CHD. Br J Nutr 106, 961-963. http://www.ncbi.nlm.nih.gov/pubmed/21906408
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. http://www.cnpp.usda.gov/DGAs2010-%20DGACReport.htm(accessed 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. http://www.ncbi.nlm.nih.gov/pubmed/9860369
5) Campbell TC et al (1999). Energy balance: interpretation of data from rural China. Toxicol Sci. 1999 Dec;52(2 Suppl):87-94. http://toxsci.oxfordjournals.org/content/52/suppl_1/87.long
6) Pedersen JI et al (2012). Response to Hoenselaar from Pedersen et al. Br J Nutr 107, 452-454. http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8479188
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. http://www.ajcn.org/content/52/3/457.long
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. http://www.ncbi.nlm.nih.gov/pubmed/20513263
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. http://www.maorihealth.govt.nz/moh.nsf/
12) Hoenselaar R. Heart disease and stroke mortality are highest in countries with low saturated fat consumption. http://dietanddisease.blogspot.com/2012/03/heart-disease-and-stroke-mortality-are.html 

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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.



References:
1) Pedersen JI et al. (2011) The importance of reducing SFA to limit CHD. Br J Nutr 106, 961-963. http://www.ncbi.nlm.nih.gov/pubmed/21906408
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. http://www.ncbi.nlm.nih.gov/pubmed/22136957
3) Pedersen JI et al (2012). Response to Hoenselaar from Pedersen et al. Br J Nutr 107, 452-454. http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8479188
4) Hoenselaar R (2012). Further response from Hoenselaar. Br J Nutr [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/22377374
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. http://www.ajcn.org/content/77/5/1146.long
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. http://www.ncbi.nlm.nih.gov/pubmed/18061058

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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...............................


References:
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. http://www.ncbi.nlm.nih.gov/pubmed/8252690
2) Allender S et al. European cardiovascular disease statistics 2008 edition. http://www.bhf.org.uk/idoc.ashx?docid=e4f82fee-58f0-4a51-8099-db9520123e24&version=-1  

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Vegans don't live longer than vegetarians or meat eaters

Background: If we take a look at wikipedia (1), we see that both vegetarians and vegans have lower mortality rates from heart disease, compared to regular meat eaters:

A 1999 meta-analysis of five studies comparing vegetarian and non-vegetarian mortality rates in Western countries found that the mortality rate due to ischemic heart disease was 26 percent lower among vegans compared to regular meat eaters, but 34 percent lower among lacto-ovo vegetarians (vegetarians that eat dairy products and eggs) and pescetarians (those that eat fish but no other meat).

Wikipedia also states that:

No significant difference in mortality was found from other causes.

This line suggests that both vegetarians and vegans may live longer than regular meat eaters. Results from the article referred to (2) can be seen in the following table:

In the table we see that occasional meat eaters, vegetarians and fish eaters had similar risks of mortality from all-causes. These were lower than mortality rates from regular meat eaters. However, vegans had mortality rates identical to those from regular meat eaters.

Conclusion: a meta-analysis of 5 prospective studies showed that both vegetarians and vegans had lower mortality rates from heart disease than regular meat eaters. However, in the case of vegans, this did not lead to lower risk of mortality from all causes.


References:
1) Wikipedia. Veganism. Wikipedia page last modified on 26 February 2012. http://en.wikipedia.org/wiki/Veganism
2) Key TJ et al. Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies. Am J Clin Nutr. 1999 Sep;70(3 Suppl):516S-524S. http://www.ajcn.org/content/70/3/516S.full

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Whole grains may decrease diabetes risk

Background: High calcium intake has been linked to lower risk of diabetes in the past (1), though this association may have been confounded by magnesium intake (2). Likewise, high magnesium intake has also been linked to lower risk of diabetes (3).
Whole grains contain phytic acid which has been linked to decreased absorption of magnesium, calcium and other minerals from the gastrointestinal tract (4). The combination of these factors is sometimes used to prove that whole grains are to increase diabetes risk. However, the theory is very simplistic not taking into account other nutrients in whole grains and not taking into account the complexity of the human body.
If whole grains are to increase diabetes risk, then it would be expected that people with high intakes of whole grains have higher risk of diabetes than people with lower intakes. This association can be examined in human trials.

Methods: A group of scientists searched the scientific databases MEDLINE and EMBASE for prospective cohort studies examining whole grain intake in relation to risk of type 2 diabetes (5). Results from 6 cohorts could be included in the following meta-analysis. The studies included a total of 286,125 participants and 10,944 cases of diabetes type 2.

Table 1:

Results: Table 1 shows results from the 6 individual studies as well as the average (combined) effect. A 21% lower risk of diabetes was found for each 2 serving per day increment in intake of whole grains (RR = 0.79; 95% CI = 0.72-0.87). Table 1 also shows that a protective effect was found in all 6 cohorts. And that protective effects were significant in all cohorts, except for the cohort examined by Montonen et al.

Conclusion: Results from prospective cohort studies consistently show that subjects with higher whole grain consumption have lower risk of diabetes type 2.

References:
1) Pittas AG et al. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis.J Clin Endocrinol Metab. 2007 Jun;92(6):2017-29.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2085234/?tool=pubmed
2) Dong JY et al. Dietary calcium intake and risk of type 2 diabetes: possible confounding by magnesium. Eur J Clin Nutr. 2012 Feb 8. doi: 10.1038/ejcn.2012.5. http://www.ncbi.nlm.nih.gov/pubmed/22318650
3) Dong JY et al. Magnesium intake and risk of type 2 diabetes: meta-analysis of prospective cohort studies. Diabetes Care. 2011 Sep;34(9):2116-22. http://www.ncbi.nlm.nih.gov/pubmed/21868780
4) Zhou JR et al. Phytic acid in health and disease. Crit Rev Food Sci Nutr. 1995 Nov;35(6):495-508. http://www.ncbi.nlm.nih.gov/pubmed/8777015
5) de Munter JS et al. Whole grain, bran, and germ intake and risk of type 2 diabetes: a prospective cohort study and systematic review. PLoS Med. 2007 Aug;4(8):e261. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1952203/?tool=pubmed

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Berries do not decrease cancer risk

Background: berries are said to decrease cancer risk. If we google for "berries cancer" we see that pretty much all titles suggest this to be true. These ideas are based on the assumption that berries include several nutrients thought to be healthy, such as vitamins, minerals and polyphenols. But if we take a closer look at the evidence, we see that articles are consistently based on either:

-Animal research.

-Studies in cell lines.

-Nothing. No references are given to back up the claim.

If berries are to decrease cancer risk in humans, it would be logical that humans with higher intake of berries have lower cancer risk than humans with lower intake of berries.

 

Methods: I searched the Pubmed database for prospective (= cohort) studies relating berry consumption to cancer risk for 7 major types of cancer. Details of the search term and inclusion criteria can be found on my other internetsite (1).

Results.

A) Breast cancer:

Study:	Subjects:	Type of berries:	Effect:
2) Adebamowo CA (2005)	90,630 women	Blueberries	RR = 1.25 (0.86-1.80; P = 0.84)

One study was found. Blueberries did not protect against breast cancer risk.

B) Colorectal cancer:

Study:	Subjects:	Type of berries:	Effect:
3) Michels KB (2000)	88,764 women	Blueberries	No significant association with colon or rectal cancer
3) Michels KB (2000)	47,325 men	Blueberries	No significant association with colon or rectal cancer
4) Lin J (2005)	36,976 women	Blueberries	No significant association with colorectal cancer

Two studies were found, including three cohorts. Blueberries did not protect against colorectal cancer risk. No relative risks were provided in the articles referred to.

C) Lung cancer:

Study:	Subjects:	Type of berries:	Effect:
5) Knekt P (1997)	9,959 men and women	Total berries (lingonberries, blueberries, black currants, raspberries and gooseberries)	RR = 1.80 (1.11-2.93)
6) Cutler GJ (2008)	34,708 women	Total berries (mostly blueberries and strawberries)	No association was found
7) Feskanich D (2000)	77,283 women	Blueberries	No association was found
7) Feskanich D (2000)	47,778 men	Blueberries	No association was found
8) Hirvonen T (2001)	27,110 men	Total berries	A nonsignificant protective effect.

Four studies were found, including five cohorts. Only one study (Knekt P. 1997) provided a relative risk which showed a significant 80% increased risk of lung cancer. No other significant associations were found.

D) Pancreatic cancer risk:

Study:	Subjects:	Type of berries:	Effect:
9) Bobe G (2008)	27,111 men	Total berries	HR = 0.88 (0.63-1.24; P = 0.94)
10) Vrieling A (2009)	478,400 men and women	Total berries (e.g., strawberries and raspberries	HR = 0.90 (0.66-1.23; P = 0.61)

Two studies were found. No associations were found.

E) No prospective studies were found examining berry consumption in relation to esophageal, ovarian, or prostate cancer risk.

Conclusion: prospective cohort studies consistently show that subjects with higher intakes of berries do not have lower cancer risk.

Limitations: results presented here were limited to only 7 types of cancer. However, these include major types of cancer: breast, colorectal, esophageal, lung, ovarian, pancreatic and prostate cancer risk. And no protective effects were found in 2 studies examining total cancer risk (1).

References:

1) Hoenselaar R. Cancer and diet. A systematic review. http://canceranddiet.nl/

2) Adebamowo CA et al. Dietary flavonols and flavonol-rich foods intake and the risk of breast cancer. Int J Cancer. 2005 Apr 20;114(4):628-33. Int J Cancer. 2005 Apr 20;114(4):628-33. http://www.ncbi.nlm.nih.gov/pubmed/15609322

3) Michels KB et al. Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers. J Natl Cancer Inst. 2000 Nov 1;92(21):1740-52.  http://jnci.oxfordjournals.org/content/92/21/1740.full

4) Lin J et al. Dietary intakes of fruit, vegetables, and fiber, and risk of colorectal cancer in a prospective cohort of women (United States). Cancer Causes Control. 2005 Apr;16(3):225-33. http://www.ncbi.nlm.nih.gov/pubmed/15947874

5) Knekt P et al. Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Am J Epidemiol. 1997 Aug 1;146(3):223-30. http://aje.oxfordjournals.org/content/146/3/223.full.pdf

6) Cutler GJ et al. Dietary flavonoid intake and risk of cancer in postmenopausal women: the Iowa Women's Health Study. Int J Cancer. 2008 Aug 1;123(3):664-71. http://www.ncbi.nlm.nih.gov/pubmed/18491403

7) Feskanich D et al. Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. J Natl Cancer Inst. 2000 Nov 15;92(22):1812-23. http://jnci.oxfordjournals.org/content/92/22/1812.full

8) Hirvonen T et al. Flavonol and flavone intake and the risk of cancer in male smokers (Finland). Cancer Causes Control. 2001 Nov;12(9):789-96. http://www.ncbi.nlm.nih.gov/pubmed/11714106

9) Bobe G et al. Flavonoid intake and risk of pancreatic cancer in male smokers (Finland). Cancer Epidemiol Biomarkers Prev. 2008 Mar;17(3):553-62. http://cebp.aacrjournals.org/content/17/3/553.long

10) Vrieling A et al. Fruit and vegetable consumption and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2009 Apr 15;124(8):1926-34. http://www.ncbi.nlm.nih.gov/pubmed/19107929

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Milk does not increase hip fracture risk.

Background: Milk intake has been linked to higher risk of bone fractures. If we google the following combination of search words "milk bone fractures women", we see several titles stating that milk may cause osteoporosis/bone fractures. Or titles with "myths about milk".

Did past studies truly show that milk increases risk of bone fractures?
The links found by google consistently refer to the same scientific article (1). In a 12-year follow-up study, the group of women with the highest intakes of milk, were said to have had a 45% increased risk of hip fracture.

Table 1:

Table 1 shows effects as described in the full text of the article. We see a Relative Risk (RR) of 1.45 (95% CI = 0.87-2.43; P = 0.22) for women consuming 2 or more glasses milk per day. No association was found with risk of forearm fractures.
An effect can be significant in 2 ways:

• The 95% CI of the RR excludes the "1". This is not the case, because the lower boundary = 0.87 and the upper boundary = 2.43.
• The P for trend = < 0.05. This is also not the case. The P for trend = 0.22.

In scientific terms, this means that no significant association was found. Or possibly, that a nonsignificantly increased risk was found.

The nonsignificantly 45% increased risk of hip fractures was found for adult milk consumption. But the article also describes effects from teenage milk consumption (see table 2).

Table 2:

We see that women who drank 3 or more glasses of milk per day, during their teenage years, had a nonsignificantly 47% lower risk of hip fractures (RR = 0.53; 95% CI = 0.25-1.16; P for trend = 0.20).

Women with higher intakes of milk during both their teenage years and their adulthood did not have an increased risk op hip fractures (RR = 0.88; 95% CI = 0.58-1.36; no P-value available).

Newer studies: In 2011, a group of researchers looked at all prospective studies (6 studies for women and 3 studies for men) with available data about the relation between milk intake and hip fracture risk (2). Results from the individual studies were grouped together in a so-called meta-analysis. The pooled results showed no association with risk of hip fractures among women (RR = 0.99; 95% CI = 0.96-1.02 per glass of milk per day), but a nonsignificant protective effect among men (RR = 0.91; 95% CI = 0.81-1.01 per glass of milk per day).

Note: Associations found in the newer studies are based on a small amount of cohorts, including a small amount of hip fractures (3.574 fractures among women and 195 fractures among men). More research is needed before any valid conclusions can be drawn.


References:
1) Feskanich et al. Milk, dietary calcium, and bone fractures in women: a 12-year prospective study. Am J Public Health. 1997 Jun;87(6):992-7. http://www.ncbi.nlm.nih.gov/pubmed/9224182
2) Bischoff-Ferrari HA et al. Milk intake and risk of hip fracture in men and women: a meta-analysis of prospective cohort studies. J Bone Miner Res. 2011 Apr;26(4):833-9. doi: 10.1002/jbmr.279. http://www.ncbi.nlm.nih.gov/pubmed/20949604

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