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Sunday, 22 June 2014

Epidemiology can be Interesting



      Hat tip to Nigel Kinburn for pulling up two studies from Siri-Tarino et al.’s 2010 saturated fat meta-analysis that did show correlations with heart disease. These were also the studies with the widest range of intakes. So what can they tell us?
      The first is by Jim Mann and colleagues from 1993, and straight up I am surprised that this has been included in any meta-analysis, because it uses a self-selected vegetarian cohort, with friends and family standing in for the rest of the population.
      “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.”
      It’s odd that such high-bias methodology isn’t excluded from meta-analysis, and makes me wonder what else is included.
      What does Mann et al. tell us?
“Results—IHD mortality was less than half that expected from the experience reported for all of England and Wales. An increase in mortality for IHD was observed with increasing intakes of total and saturated animal fat and dietary cholesterol—death rate ratios in the third tertile compared with the first tertile: 3.29, 95% confidence interval (CI) 1.50 to 7.21; 2.77, 95% CI 1.25 to 6.13; 3.53, 95% CI 1.57 to 7.96, respectively. No protective effects were observed for dietary fibre, fish or alcohol. Within the study, death rate ratios were increased among those in the upper half of the normal BMI range (22.5 to under 25) and those who were overweight (BMI over 25) compared with those with BMI 20 to under 22.5.
(Relative risk figures have been converted from 100 to 1.0)

      IHD was significantly associated with higher consumption of eggs, cholesterol, animal fat, and saturated fat.
      But, here’s the surprising finding; none of those dietary factors was associated with any increase in total mortality, significant or non-significant. People who avoided dying of IHD by following the healthy eating guidelines were dying at the same rate – the same ages - as their less health-conscious friends and family. This wasn’t pinned down to any particular cause of death.

      The fact that BMI under 20 was associated with as much increased risk of overall mortality as BMI over 25 (“total mortality was significantly higher in those with an initial BMI under 20, and a similar though not statistically significant trend is apparent for IHD mortality.”) wasn’t mentioned in the abstract, and is underplayed in the text (if it can be explained by undiagnosed pre-existing disease, so can the correlation with higher BMI). A bit like this dodgy AHF BMI calculator. Set this to BMI 7 (maximum height, minimum weight) and you still look healthy; muscular or curvy depending on gender. Results in real life may vary.

      The main dietary finding pertaining to all-cause mortality in Mann et al.;
“all cause mortality for all subjects was significantly lower in the middle and highest intakes of green vegetables (0.62, 95% CI 0.46–0.83; and 0.74, 95% CI 0.56–0.99) and among those consuming the highest intake of nuts (0.76, 95% CI 0.60–0.97) compared with the lowest intakes of these foods.”


     The second paper is by Bonniface et al., and unfortunately doesn’t supply all-cause mortality data.
      “Not consuming alcohol, smoking, not exercising and being socially disadvantaged were related to high saturated fat intake and CHD death. Cox survival analyses adjusting for these factors found that a level of saturated fat 100 g per week higher corresponded to a relative risk for CHD death for men of 1.00 (0.86-1.18) and 1.40 (1.09-1.79) for women. This difference between the effects of saturated fat in men and women was statistically significant (P=0.019).”

     Mean intakes of SFA in Bonniface et al. - Men: 47.0 g/d Women: 34.4 g/d. A respectable ~20%E (similar to the consumption by Indians eating food prepared with ghee in Raheja et al. 1995).
“The cut-off points for the quintiles of saturated fat in grams per week were 220, 276, 337 and 427 for men and 159, 202, 252 and 319 for women. There was a clear trend to higher CHD death rates associated with higher total and saturated fats and Keys' fat difference in women.”

      Keys' fat difference? This is the ratio between SFA and PUFA.
      “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.”
      PUFA by itself showed no correlations, but the Keys difference did. In fact, the correlation between Keys' difference and CHD in table 3 is pretty striking.

     Both populations were in Britain. Perhaps the take-home is, that in Britain, at least at a certain point in time, you could choose how you wanted to die to some extent by choosing your diet around heart guidelines. Or by watching your Keys' ratio if you were female (women today, with vegetable oil diets, would not have ideal Keys' ratios by these tables). But living longer than those around you by restricting saturated fat is not a prediction supported by this epidemiology, or by any meta-analysis, as was discussed by Simon Thornley, Grant Schofield and I in our letter to the NZMJ.

     Diet epidemiology is interesting stuff. It’s incredibly hard to do well, and the things we can take away from it are sometimes unexpected. The papers that go into meta-analyses, even for something like SFA, are wildly heterogeneous in design and in quality. Jim Mann et al.’s 1993 paper told me just about everything I wanted to know that it was possible to tell from the data collected. Bonniface et al. were more obscure; critical data points for the Keys' difference were not included. What use are quintiles without means or cut-offs?
      I was surprised, as I said, that the Mann et al. paper, good though it is, is being included in meta-analysis, because of the self-selection bias (so, self-selection in Paleo or LCHF diet studies shouldn't be a barrier to being taken seriously either). That it was included speaks to the impartiality of meta-studies like Siri-Tarino et al. 2010 that exculpate saturated fat. Meta-studies give the overall truth that is relevant for public health planning, but miss the finer details of what is happening in specific communities at specific times. For example:
      In Mann et al., nuts are protective. This is a common finding, e.g. in Hu et al. 1998. In Bonniface et al. PUFA is not associated with harm, but the Keys' difference is. In Britain at the time of this study, among the mainly middle and upper classes, perhaps vegetable oils were not in common use. Perhaps nuts were a major source of linoleic acid, enough to attenuate its relationship with disease. And in Bonniface et al., with its more working class catchment (and this being Britain, class distinctions do matter), perhaps the ideal Keys' difference of 2:1 is what you get closer to eating nuts and fish with meat and dairy fat, and the adverse lower and higher ratios are what you get either not eating nuts and fish, or using vegetable oils and spreads instead of animal fats.
(the mean PUFA intake of 63.1g/week for women is ~4%E).
     Because it may turn out that when diet-heart epidemiologists one day separate PUFA in nuts and fish from PUFA in oils they will get very different values, as these AMD researchers did.

     Take home: For someone who has the disease of CHD, especially someone following a moderate fat, higher carbohydrate diet like most of the population (the dietary pattern at the heart of all epidemiology) it makes sense to follow these clues, as well as recognising the modern risk factors of sugar and refined flour; eat some nuts, fish, don’t eat red meat every day, eat only a few eggs per week, eat some full-fat dairy, and so on.
      On the other hand, for the average person to eat a pleasurable diet that has been designed around avoiding CHD risk factors from animal foods risks inviting in a host of other diseases that they may be susceptible to in ways they were never susceptible to CHD. Advice to the general population should be limited to recommending those protective factors for CHD that a) supply micronutrients, and b) are also protective factors in a wider sense (nuts, fish, fruit and vegetables, and full fat dairy), instead of messing with Keys' difference based on theories about blood lipids, as opposed to consistent findings based on real food inputs and hard endpoints.

13 comments:

Nigel Kinbrum said...

Nigel Kilburn? Never heard of him! :-D

garymar said...

Nigel Kilburn was the guy who posted a video of "Boys Boys Boys" by Sabrina.

Well, the song was titled "Boys Boys Boys", but the video should have been named "Nips Nips Nips".

john said...

These sorts of things themselves have so little application that I just find it silly for one to actually reference one as a piece of evidence. I am 5'9 185 but am a weightlifter and have little body fat; I don't know my BMI, but it's probably high. Some days I eat 200-300 grams of fat. These statisticians/"scientists" sure do try hard to make saturated fat look bad.

George Henderson said...

What strikes me now is the position of class, caste and gender in these studies. Education, European race, ancestors who usually had enough to eat, when combined with an interest in vegetarianism, are associated with fewer heart attack deaths, but more deaths from other causes so no net change in mortality.
And as a result of this finding, the whole world is told to follow suit.
The Mann study is good and doesn't need statistics to make its point, but it's a self-selected group, volunteers. Vegetarians that weren't doing so well would have been more inclined to stay away, you would get the more motivated ones, the people with a sense of purpose.
Under the circumstances, the fact that people avoiding the risk factors didn't have lower mortality is odd - I would have expected them to be healthier all round. You are always going to get show-offs volunteering.

raphi said...

Your analysis is pretty spot-on George.

Meta-analysis sound so definite, authoritative & their conclusions nearly sacred to laymen & scientists alike.

In fact, taking a page from computer scientists and physicists, we're forced to recognize that "garbage in = garbage out".

The concept of a double-edged sword comes to mind...

Andrew said...

"You are always going to get show offs volunteering". Tell me about it!! I'm analyzing some surveys from distance runners who volunteered. Bejebbus. Fortunately I'm also interviewing them. Whew.

FredT said...

also these do not speak of age. BMI typically increase with age to a point. So higher BMI suggest older. Something seems wrong with a study that ignores age - death relationship

George Henderson said...

We have to assume that mortality is age-adjusted, or that groups have equal age spreads, or else it would be meaningless. Mann describes the age calculations thus:
The data presented are based on 10 802 subjects (4102 men, 6700 women). Subjects were censored on reaching the age of 80 years. Person- years of observation and deaths in nine age groups (16–39 years and 5 year age groups 40–79 years) and three calendar periods (1980–84, 1985–89, 1990–95) were calculated using the person-years (PYRS) computer program. To describe the mortality of the cohort as a whole we also calculated standardised mortality ratios (SMRs) for men and women for all major causes of death using national mortality data for England and Wales; 95% confidence intervals (CI) for the SMRs were calculated assuming that the observed number of deaths followed a Poisson distribution.

I understand none of this but think Mann far too experienced not to have made best allowance for age. I don't doubt the results are accurate, but the study was designed to exaggerate them. You have a bunch of people making a stand against the 80's British diet, so no doubt they ate much less processed and deep fried food and fewer sweets than their mates. The lack of stats for sugar, deep fried meals, and baked deserts is probably the biggest unanswered question (but possibly this data exists in another paper somewhere).
Also, consider stress - are people who feel able to opt out and choose their own eating patterns overall less affected by stress?

George Henderson said...

Nice - Denise Minger's presentation of the Keys studies as revised by Yerushalmy and Hilleboe matches the findings from Mann et al.; Dietary factors that have +ve associations with CHD have -ve association with non-CHD deaths
http://rawfoodsos.com/2011/12/22/the-truth-about-ancel-keys-weve-all-got-it-wrong/

Galina L. said...

Dear guys,
I have a relative who is dealing with a lymphoma for a while,and who is about to re-start a chimo, but her another issue - zero immunity due to the chemo. You have been reading my LC comments for a while, so you could guess I recommended her to do fasting before chemo and couple times a week, cutting all sugars, bread,and other things which would be better to skip. I am bringing with me D3, astragalus and magnesium to Moscow. Some of the supplements will go to another relative with fibromialgia.
Do you mind to tell me something I may not know?
Probably, I should ask people on Wooo's blog too, but she is mostly on twitter nowadays, as a rumor says.

raphi said...

Hi Galina L.,

I'm sorry to hear you have a sick relative.

1) Circadian rhythm entrainment will aid in recovery & fatigue managment ==> $10 Blue-blocker glasses http://www.amazon.com/Uvex-S1933X-Eyewear-SCT-Orange-Anti-Fog/dp/B000USRG90

2) See Dr.Rhonda Patrick for details (http://www.foundmyfitness.com/wp-content/uploads/2014/02/VitaminsAreBadREBUTTAL-v5.pdf)...but try to make sure your relatives' folate intake isn't any higher than it needs to be. Folate 'protects' against cancer for for those without & becomes an undesirable cellular replicator for people who are already afflicted by cancer.

3) Medically, quality marijuana is a no-brainer. It is safe & highly effective for pain, nausea, inflammation (& so on). I'm guessing this isn't a very realistic option - especially not in Moscow.

Good luck with everything!

Galina L. said...

Thank you, raphi.

George Henderson said...

Perfect Health Diet has some specific posts on surviving chemo; so does the Life Extension website oncology page.
Non-hodgkins lymphoma is a a gluten-associated cancer; Russia seems to have some good probiotics which I would use.