Thursday, 19 June 2014

Siri-Tarino et al, Forests & Trees and "Eureka!" moments.

Here's Fig. 2 from Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease:-
Risk ratios and 95% CIs for fully adjusted random-effects models examining associations between saturated fat intake in relation to coronary heart disease and stroke.

The above "Forest" plot has a subtotal RR of 1.07 (95% CI 0.96 1.19). The overall conclusion is that there's no association between saturated fat intake and the RR for CHD. Hmmm.

I looked at the data in Table 3. Of the 16 studies contributing to the CHD results, only 3 of them specify high sat fat intakes over a wide range. The results from these 3 studies are as follows:-

Pietinen et al: RR=0.93 (95% CI 0.6, 1.44).
Mann et al: RR=2.77 (95% CI 1.25, 6.13).
Boniface et al: Pooled RR = 1.37 (95% CI 1.17, 1.65).

The results from Pietinen et al are statistically-insignificant (95% CI values are way above & below 1) with an overall slight protective effect. The results from Mann et al have a RR >> 1 with both 95% CI's >1 and the results from Boniface et al have a RR >1 with both 95% CI's >1.

Other studies either have sat fat intakes varying from very low to low, or specify mean/median sat fat intakes without values for highest & lowest tertiles/quartiles/quintiles etc. Other studies have results that are statistically-insignificant.

However, there are some studies that show a slight protective effect of small amounts of sat fats. How come?

Thanks to George Henderson, I had a "Eureka!" moment. He posted a link to Dietary intake of saturated fat by food source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis.

Here's Fig. 1 from that study.
HRs and 95% CI's of CVD risk according to quintiles of energy-adjusted SF from different sources (n = 5209).

The Meat SF plot has a net positive slope (bad news, but the range of intake is very small), the Butter & Plant SF plots are random, but the Dairy SF plot has a net negative slope (good news). Dairy saturated fats in amounts of up to 10g/day are protective against CHD. As the Dairy sat fat intake is too small to have a significant effect on lipids, what's the mechanism? I think that it's Vitamin K2. See Chowdhury et al, More forests & more trees and more "Eureka!" moments with cheese.

When you average out the results from all studies, the result is null. This is data dilution statistics.

EDIT: See also Study: Saturated Fat as Bad as Sugar!


George said...

Yes, this difference is striking; the vitamin K2 link is good. Retinol too, maybe.
I thought of some other ways to explain it - saturated fats in meat are associated with more PUFA than dairy fats, and this total fat is subjected to more heating and more intense processing. (the MESA meat SFA correlation was minimised by eliminating processed meats). Thus dairy fat is a) mainly a raw fat, b) where not, more heat stable.
The parallel is with nuts; nut epidemiology is highly protective, linoleic acid not so much, one is the least refined and least heated source of the other.
When you have weak associations with SFA and CHD these may be - I would say are - due to associations between SFA and other factors which have not been adjusted for. You can't adjust for everything. Also, values for confounders change with time (sugar will be given more weight today) but no-one rewrites the old papers to take this into account.

George said...

The Mann et al. study is quite curious:

The study differs from

previous prospective studies of diet and IHD in

that the volunteers were individuals whose self

selected diet resembled, in nutrient content,

current dietary recommendations rather than

the relatively high saturated fat diet typical of

most affluent societies. The findings may not

only help to explain which attributes of a

vegetarian diet protect against IHD but also

which foods and nutrients are important in the

aetiology of IHD in populations who modify

their diets along the lines of present guidelines.

In other words, a high-carbohydrate wholegrain diet? Deserves more investigation. Included many more vegetarians than the other studies, hence the high OR, but what did the vegetarians die of?

billy the k said...

Great posting Nige, and great comments George. Led me to dig up the superlative article by Chris Masterjohn on vitamin K2 ["On the Trail of the Elusive X-Factor: a 62-Year-Old Mystery Finally Solved." In: Sally Fallon's "Wise Traditions; Spring 2007, p14-32.] Chris included a very helpful table [Figure 4]: Vitamin K2 Contents of Selected Foods: The Vitamin K2 Content in mcg/100g food; also--the percentage of Vitamin K2 present as MK-4 represents that synthesized by animal tissues, while the remainder represents that synthesized by bacteria during fermentation.


Natto 1103.4 (0% MK-4)
Goose Liver Paste 369.0 (100%MK-4)
Hard Cheeses 76.3 (6% MK-4)
Soft Cheeses 56.5 (6.5% MK-4)
Egg Yolk (Netherlands) 32.1 (98% MK-4)
Goose Leg 31.0 (100% MK-4)
Curd Cheeses 24.8 (1.6% MK-4)
Egg Yolk (United States) 15.5 (100% MK-4)
Butter 15.0 (100% MK-4)
Chicken Liver 14.1 (100% MK-4)
Salami 9.0 (100% MK-4)
Chicken Breast 8.9 (100% MK-4)
Chicken Leg 8.5 (100% MK-4)
Bacon 5.6 (100% MK-4)
Calf Liver 5.0 (100% MK-4)
Sauerkraut 4.8 (8% MK-4)
Whole Milk 1.0 (100% MK-4)
2% Milk 0.5 (100% MK-4)
Salmon 0.5 (100% MK-4)
Mackerel 0.4 (100% MK-4)
Egg White 0.4 (100% MK-4)
Skim Milk 0.0
Fat-Free Meats 0.0

George said...

I'll add to that - spirulina 11mcg per g.
The Bonniface study is interesting too - no effect for men, all weight is IHD mortality in women, with this twist - The result for the Keys statistic indicates that a higher level of saturated fat can be compensated by a lower level of polyunsaturated fat, in the ratio 2:1.
There is a definite sweet spot for Key's difference in the second quintile, but not enough data to tell what this is.
There's no data about total mortality there that I can see.

Nigel Kinbrum said...

Thanks. is why I currently supplement with 5mg/day of MK-4.
"Risk of incident CHD, however, was strongly and significantly reduced in
upper tertile of menaquinone intake (RR =
0.59), as were risk of CHD mortality (RR = 0.43) and all-cause mortality
(RR = 0.74)." Also,
"Calcified plaques are more prone to rupture,
which will elicit a thrombotic response, thereby increasing the risk of a coronary event (29)."
The lower and upper tertiles of dietary menaquinone were <21.6μg/d & >32.7μg/d, respectively.

Nigel Kinbrum said...

Just as there are carbs, carbs, carbs, carbs & carbs, it would appear that there are sat fats, sat fats, sat fats, sat fats & sat fats.

Salient points of this post:-
1) It's not safe to state that there is no association between sat fat intake & RR for CHD at any level of intake.
2) Sat fats from different sources have different effects, for a variety of reasons. Some sources are protective, some are benign & some are damaging.
3) Meta-studies that include studies with widely-varying populations are likely to give RR ~1 (95% CI <1, >1).

George said...

There is no total mortality in Bonniface et al, but in Mann et al., SFA association with IHD is also a protective association against all other causes of death, of which cancer seems to be main one.
In Bonniface CHD harm association with SFA and meat is not seen when all the respondents with pre-existing medical conditions are included in analysis. Yet if SFA and meat are harmful, surely these are most vulnerable people.The CHD association is only seen in healthy women. What does that mean?

Nigel Kinbrum said...

I have no idea.

Nigel Kinbrum said...

I'm familiar with (I linked to it in my blog post on Coconuts), though that wasn't one of the studies in Siri-Tarino et al.

I gather from the above study that the Tokelauans had a very natural diet, until they migrated to NZ and started eating "the displacing foods of modern civilisation", which worsened their lipid profiles.

George said...

It's frustrating that the data from both these studies has only been analysed in one way, but I guess it is hard enough to do that, and once you've produced the paper most people would be too exhausted to then go on to answer other questions that were raised. In some of the bigger studies with lots of data that's been kept in some easily accessible format different groups of researchers go through the same evidence at different times to produce different conclusions, a la groundhog day.

billy the k said...

Paul Jaminet [of "Perfect Health Diet"] thinks so:

"Cereal grains...are rich in toxins that poison humans. They are the most dangerous foods...Grazing animals have evolved defenses for these toxins--for instance...rumens that allow the brunt of the toxins to be taken in by bacteria. Humans, lacking such organs, are comparatively defenseless...we can detoxify grains the way cows do: by replacing rumens with vats and fermenting grains into alcohol. In medieval Europe, alcoholic beverages such as mead and ale often made up nearly half of calories. We would never recommend obtaining half your calories from alcoholic beverages, but it may be more healthful than eating bread!'
[Paul Jaminet. Perfect Health Diet (2012) p196-198]

Nigel Kinbrum said...

Cereal grains are toxic & dangerous foods? Is he including white rice (that presumably forms/formed a substantial part of his wife's diet)?

This requires a graphic!

Nigel Kinbrum said...

That's another good point. The abstract of the TNT (Treating to New Targets) statin study proudly announced that 80mg/day of Atorvastatin significantly reduced CHD mortality (by about 25 out of 5,000 subjects, whoop-de-do!) compared to 10mg/day.

The abstract conveniently forgot to mention that total mortality increased by a statistically-insignificant amount (6 extra deaths) in the 80mg/day group, compared to the 10mg/day group.

billy the k said...

Nige's lightning-quick Bull***t-Detector strikes again!

Jaminet claims that "the antinutrition factors in the rice grain...including phytin (phytate), trypsin inhibitor, oryzacystatin and haemaggluinin-lectin...All the antinutrition factors are proteins and all except phytin (phytate) are subject to heat denaturation.
We recommend avoiding brown rice because of the phytin...No antibodies to rice proteins have ever been identified..." [p 233].

So he concluded that, along with taro and cassava, white rice was another starchy plant that could be rendered safe [and lucky thing it was--to preserve marital harmony with Shou-Ching!]

Nigel Kinbrum said...

Phew, that was too close!

I hope things don't "kick-off" here, as I'm going to be busy later.

George said...

Uffe Ravnskov puts it like this - "is there some other way you'd like to die?". For someone who has the disease of CHD, it makes sense to follow these clues, eat more nuts, fish less meat, and so on. For the average person to eat a convenient diet that has been designed around CHD risk factors is just to invite in a host of other diseases that they may well be susceptible to, in ways they were never susceptible to CHD. And it's questionable whether such a diet really imitates the patterns associated with lower CHD risk anyway.

Nigel Kinbrum said...

"is there some other way you'd like to die?"
Yes. Fatal shooting after being caught in Flagrante wossname with a nubile 18 year-old! ;-D