Sunday, May 24, 2015

Don't Displace Useful Advice with Useless Advice

In my opinion, our society has a very depressing narrative on chronic disease, one which is best characterised as hopelessness (blog).  But academics, doctors and people in public health also have their own equally demoralising narrative, which is that people don’t either adopt or stick to healthy lifestyle habits (which is probably a major reason for the emphasis on drugs over diet and lifestyle).  While I can understand and empathise with both points of view, I don’t think either is correct
  
The Risk of Coronary Heart Disease can be Massively Reduced

A review of observational studies found that a ‘healthy lifestyle’ is associated with an approximately 80% reduction in the incidence of first heat attacks (‘primary myocardial infarction’).  The criteria for a ‘healthy lifestyle’ (and the reduction in risk) varies from study to study, but often includes: a healthy diet*, lack of smoking, leisure-time physical activity, moderate alcohol intake, normal body weight, and normal cholesterol and blood pressure [1].  The magnitude of lower risk is consistent with the much lower incidence of CHD in in the industrialised counties at the beginning of the 20th century [2], the reduced risk of CHD in certain multifactorial diet intervention studies (such as the Lyon Diet Heart Study [3]) and the near absence of CHD or CHD risk factors among modern day hunter-gatherers and traditional cultures [4] [5]

* What a ‘healthy diet’ is isn’t defined in this review, though it’s likely to be similar to conventional nutrition recommendations and so may score people on how well they meet the food groups and their intake of SFA, salt and processed foods.  Whether this is the best measure is debatable, but

The Public can make Substantial Changes in Diet and Lifestyle

While only a small number of people tick all the boxes of a ‘healthy lifestyle’ (as defined in the studies cited by [1]), there is evidence that the general public can make substantial changes in their diet and lifestyle.  Smoking is a good example of this, where its prevalence in Australia and the US has decreased substantially (particularly among men*) in the last 50-60 years [6] [7].  Another example is that we reduced our intake of SFA (% of total calories) by about a third in the last ~50-60 years in response to response to dietary recommendations to do so (blog)


* I didn’t appreciate earlier how much of a gender disparity there was in smoking in the mid-20th century.  Perhaps this is what led to people almost exclusively testing the diet heart hypothesis only in men (blog), as much fewer women were smoking and therefore may have had a much lower incidence of CHD.  Also, just by looking at these statistics alone, it’s not surprising that age-adjusted CHD mortality has fallen over the last ~50-60 years

Willpower and Decision Fatigue

Altogether this suggests that one’s risk for CHD can be brought very low through the implementation of a big picture approach to diet and lifestyle that encompasses many elements, and that the general public can make significant changes to their diet and lifestyle, but most have plenty of room for improvement.  In this context, is it wise to promote replacing SFA with PUFA based on speculations regarding cholesterol levels when the evidence from ‘adequately controlled’ clinical trials suggests there’s no benefit of doing so?  Could this (most likely) useless dietary advice displace the delivery of and/or adherence to useful dietary/lifestyle advice?

There isn’t much direct research on how adherence to one aspect of a healthy lifestyle effects adherence to other aspects (the healthy user effect doesn’t count).  One study (experimental) found that withholding from tempting snack food or exerting other forms of self-control led to an increased consumption of ice cream (and in another instance, worse performance on a cognitive task) [8].  This is consistent with the concepts of ego depletion (willpower/self-regulation being a limited resource) [9] and decision fatigue (worse decision making over time) [10] [11].  That study and those concepts would all suggest that adherence to other aspects of a healthy lifestyle is likely to be worse.  Therefore, it should be more productive to initially base lifestyle recommendations on addressing the big picture and to ignore things of questionable clinical relevance (of which I would place replacing SFA with PUFA, as well as a number of other things such as the glycemic index for weight and metabolic health, salt for blood pressure, etc) 

Lastly, on a somewhat related note, some doctors have suggested that statins give people an illusion of protection, leading patients to make unhealthy lifestyle choices because of the thought that the statin will protect them or offset unhealthy decisions [12].  While I didn’t find any research on this (the article doesn’t seem to be based on a peer reviewed paper), it’s quite likely that it happens, at least in some people, and is another reason to not recommend potentially useless advice

Sunday, May 17, 2015

Saturated Fat Intake: Now and Then

National dietary guidelines have been under attack for being associated with the development of the obesity epidemic.  In defence of national dietary guidelines, many have argued that we are fatter simply because we do not follow them.  I agree with that, I don’t think the dietary guidelines made us fat and the dietary guidelines seem to be healthier than what most people currently eat.  Although I think they can be improved, an idea many people surely have, but for different reasons.  Anyway, there has been at least one instance where we have adhered pretty well to the dietary guidelines, and that is that we have reduced our intake of SFA.  Indeed, one of the arguments that gets used in favour of the diet heart hypothesis is that CHD mortality has declined in over the last ~50-60 years and was due in part to reductions in SFA intake.  I have a few objections to this:

·         While SFA has decreased during this period, it seems to have been mostly replaced by refined carbohydrates, which pretty much everyone agrees won’t reduce the risk of CHD based on the total-C:HDL-C ratio [1] and observational studies [2] [3]
·         The evidence even from favourable meta-analyses of observational studies suggests that reducing SFA will only reduce CHD if it is replaced by PUFA [2] [4].  Even though we have modestly increased in PUFA intake during that period [5]* (in absolute terms), the magnitude of the decrease in CHD mortality (from data used by diet heart advocates), far exceeds what is predicted from favourable meta-analyses of observational studies
·         Simply excluding inadequately randomised trials (Finnish Mental Hospital Study) results in the RR for CHD mortality being 0.99 (CI = 0.83-1.20, P = 0.95).  More importantly, the RR for CHD mortality from ‘adequately controlled’ trials excluding the Sydney Diet Heart is 1.04 (CI = 0.85-1.26, P = 0.72) (blog)
·         It ignores other factors such as a dramatic decline in smoking [6], advancements in medical care and environmental toxins [7]

* In that paper, Ramsden, et al estimated PUFA intake from 1909 to 1999.  In summary linoleic acid increased 2.58-fold from 2.79% to 7.21% and alpha-linolenic acid increased 1.85-fold from 0.39% to 0.72%, whereas changes in long chain PUFA were relatively fairly minor [5]


Regarding the decline in SFA intake I wanted to get a rough idea as to how much we have reduced our intake of SFA in the last ~50-60 years, hence the second half of this post:

NHANES

The following tables come from NHANES, which probably is probably the most accurate measure of trends in SFA intake, but unfortunately the surveys didn’t begin until the 1970’s, by which time the general public had received the advice to reduce SFA and cholesterol for many years [8]

Men
1971-1974
1976-1980
1988-1994
1999-2000
Difference
Calories
2450
2439
2666
2618
+6.9%
Fat (%)
36.9
36.8
33.9
32.8
-11.1%
SFA (%)
13.5
13.2
11.3
10.9
-19.3%
Fat (g)
100.5
99.7
100.4
95.4
-5.0%
SFA (g)
36.8
35.8
33.5
31.7
-13.7%

Women
1971-1974
1976-1980
1988-1994
1999-2000
Difference
Calories
1542
1522
1798
1877
+21.7%
Fat (%)
36.1
36
33.4
32.8
-9.1%
SFA (%)
13.0
12.5
11.2
11.0
-15.4%
Fat (g)
61.9
60.9
66.7
68.4
+10.6%
SFA (g)
22.3
21.1
22.4
22.9
+3.0%

USDA Food Supply Data

The USDA’s document Nutrient Content of the U.S. Food Supply, 1909-2000 suggests that SFA intake between 1950-1959 and 1960-1969 was 16.0% and 15.7% respectively, which decreased to a little over 12% at the end of 20th century.  This method overestimates food intake (on average, Americans do not consume 3500-3900 calories and over 20g of fibre) but would be more accurate at measuring nutrients as a percentage of total calories (although this data suggests protein intake was between 10-12% of total calories, whereas it’s probably closer to 15-18%) [9].  (Graph on the left is SFA intake in %, graph on the right is SFA intake in grams)


The Diet Heart Trials

In the diet heart trials the control diet was designed to be very similar to the standard diet served at the institutions or the one that the participants regularly consumed.  So the SFA intake of the participants at baseline and/or of those in the control group may reflect SFA intakes of the time

This is would be especially true of the National Diet Heart Study (NDHS), where the researchers also aimed for their control group (group D) to have an intake of SFA of 16-18% that was similar to the national average and cited research that investigated SFA intake.  Unlike the other trials, they created foods to meet this target, but didn’t achieve it, so I’m using the target intake instead.  At baseline the participants reported a SFA intake of 15.6%, but they were likely more health conscious as a lower proportion of the participants were smokers [10]

Trial
Year
Country
SFA in Control Diet
NDHS
1962-1964
United States
16-18%
LAVAT
1959-1968
United States
16.4%
SDHS
1966-1973
Australia
13.5%*
FMHS
1959-1971
Finland
17.2%
MCS
1968-1973
United States
18.3%
DART
1983-1989
United Kingdom
14.9%
STARS
1987-1990?
United Kingdom
17.1%
* The participants in the control group of SDHS were allowed to use high PUFA margarines/oils if they wished, and many did.  As such, the control group reported a high intake of PUFA (8.9%).  Because the control group in SDHS made some dietary changes, it’s probably more appropriate to look at the participants’ baseline intake of SFA which was 16.4% in the experimental group and 15.9% in the control group.

The Seven Countries Study

In 1958-1964, the ‘US railroad’ cohort in the Seven Countries Study reported consuming 125.9g of fat (49.6% TC), 55.3g of SFA (21.8% TC) and 582 mg cholesterol [11], but whether this N of 30 accurately reflects the US average is quite debatable seeing as it’s a much higher figure than the USDA food supply data and the diet heart trials.

Summary 

It appears that the relative intake of SFA was approximately 16-17% of total calories during the mid-20th century and has declined to a little over 10%, a decrease of approximately one third (absolute intake of SFA (grams/day) have decreased to a lesser extent due to an increase in calories).  However, I think these values underestimate the change in consumer choices/purchases over the last ~50-60 years, as animal fats have been replaced by plant fats, due to large reductions in the intake of butter, full fat dairy, lard, lamb and eggs and an massive increase in vegetable oils [5] [9].  This is because food sources of fat contain a mix of SFA, MUFA and PUFA.  So a hypothetical 50% decrease in foods high in SFA would not decrease SFA intake by as much as 50%

Sunday, May 10, 2015

Proposed Mechanisms and Observational Studies can be Inconsistent with the Results from Randomised Controlled Trials

As risk factors, whether you decide to use total-C, LDL-C or the total-C:HDL-C ratio, all of them would predict that replacing SFA with PUFA would reduce the incidence of CHD*.  In addition, some** meta-analyses of observational studies would also predict that replacing SFA with PUFA would reduce the incidence of CHD.  However, this prediction didn’t come true in the ‘adequately controlled’ clinical trials (blog), and based on limited data the opposite may be the case for women (higher risk of CHD) (blog).

At this point, many conventional dieticians/doctors will claim that the trials are flawed/difficult and appeal to the ‘totality of the evidence’, emphasising the effects of SFA and PUFA on blood lipids and a selection of favourable meta-analyses of observational studies, before recommending that we continue to replace SFA with PUFA.  This is despite meta-analyses of RCTs being the gold standard in medicine.  For example, in the NHMRC evidence hierarchy, meta-analyses of RCTs are at the top (level I), and are followed by RCTs (level II), pseudo-RCTs (level III-1), then cohort studies (level III-2) [1]

We should be cautious of basing recommendations on observational studies and/or proposed mechanisms.  There are some number of examples of things that improve the blood lipid profile and/or are inversely associated with CHD in observational studies, but don’t reduce CHD in RCTs.  Replacing SFA with PUFA is not the first time this has happened and won’t be the last:

·         Hormone therapy (estrogen or estrogen + progesterone) lowers the total-C:HDL-C ratio and is associated with a lower incidence of CVD in postmenopausal women, but a recent Cochrane meta-analysis of RCTs found no benefit for hormone therapy in postmenopausal women [2]
·         CETP increases the total-C:HDL-C ratio, but a recent meta-analysis found that CETP inhibitors do not reduce CHD in RCTs [3]
·         Whole grain consumption and grain fibre is inversely associated with CHD in observational studies [4] [5] and certain types of grain fibre lower LDL-C [4], but DART (the only RCT to test the effect of grain fibre on CHD), found no benefit and instead found a near-significant increase in the risk of CHD events (1.23 (0.97-1.57)) and total mortality (1.27 (0.99-1.65)) (figures are after adjustment for confounders) [6].  In DART, grain fibre did not lower total-C [6]

And here are some other examples that aren’t related to the lipid hypothesis:

·         There are many proposed mechanisms suggesting that lower glycemic index carbohydrates are better for satiety, weight management, insulin resistance and blood lipids compared with higher glycemic index carbohydrates [7], but the evidence from observational studies and RCTs are mixed [8] [9]
·         A high intake of salt is suggested to be a major cause of high blood pressure as due to sodium increasing blood volume, and in ecological studies salt intake is associated with blood pressure, but a Cochrane meta-analysis of RCTs found reducing salt intake had only a very slight effect on blood pressure [10]
·         Carnitine increases TMAO and TMAO is associated with CHD [11], but carnitine supplementation reduces CHD events and total mortality [12] (post)
·         Elevated homocysteine is considered a risk factor for CVD [13], and there are a number of proposed mechanisms [14], but lowering homocysteine with vitamins B6, B9 and/or B12 doesn’t appear to reduce CVD [14]

Observational studies are non-randomised, and therefore there’s a much greater potential for there to be other differences between certain categories of people (for example: those who take a drug/supplement vs. don’t take a drug/supplement; or those who eat a diet low in SFA and high in PUFA vs. those who eat a diet high in SFA and low in PUFA***)****.  These other differences (known as confounding variables) can include other dietary and lifestyle differences, differences in healthcare, etc, may substantially affect the results (known as ‘the healthy user effect’) [15].  While many observational studies attempt to control for a number of confounding variables, this clearly doesn’t work perfectly all the time as evidenced by the examples above, as you can only control for the things you measure

The mechanism by which replacing SFA with PUFA is thought to reduce CHD is by decreasing the total-C:HDL-C ratio.  This proposed mechanism, known as the diet heart hypothesis, is a reasonable hypothesis, but shouldn’t be assumed to be true.  Asserting that replacing SFA with PUFA will reduce CHD based on their effects on cholesterol levels assumes that: replacing SFA with PUFA only affects cholesterol levels and/or that cholesterol levels are the only factor in CHD, a position I doubt anyone would take.  That being said, many people recommend reducing SFA or replacing it with PUFA based on their effects on cholesterol levels.  I don’t think they realise how reductionist those recommendations are, particularly when extended to food, because when discussing nutrients they are ignoring all the other biological effects the nutrient has related CHD, and when extending it food they are also ignoring the combined biological effect of all the other nutrients that is related to CHD*****.  As such, sometimes the mechanism may be correct, but it depends on how it’s targeted.  The salt, blood pressure and mortality connection is a good of example of this.  In meta-analyses of observational studies [16] and RCTs [17] (sometimes they are consistent) the relationship between salt intake and total mortality seems to follow a U-shaped curve, whereby a moderate salt intake is associated with lower mortality compared to low and high salt intakes.  So although reducing salt slightly decreases blood pressure, which would be expected to reduce mortality, it also substantially increases the renin-angiotensin-aldosterone system [10], which has a several very important functions in the body but elevated activation of this pathway has many adverse health effects [18], which is probably the main factor responsible for the higher risk of mortality associated with a lower intake of salt.

* People who decide to use total-C or LDL-C as risk their preferred risk factor (which would predict SFA would be positively associated with CHD) should realise that meta-analyses of observational studies have consistently found no association between SFA and CHD Jakobson, Skeaff, Mente, Siri-Tarino and Chowdhury.  Whereas those who use the total-C:HDL-C ratio or don’t make assumptions don’t experience any cognitive dissonance as SFA doesn’t increase the ratio.  (See below on how replacing carbohydrate with SFA, MUFA or PUFA effects different measures of cholesterol) [19]


SFA
MUFA
PUFA
Total-C
LDL-C
Total-C:HDL-C

** The results from Jakobson and Farvid suggested a benefit in replacing SFA with PUFA, whereas those from Skeaff, Mente and Chowdhury did not

*** Observational studies tend to group people in tertiles, quartiles or quintiles and then compare the highest vs. the lowest groups – in other words comparing the incidence of CHD among the top 20% consumers of SFA vs. the bottom 20% consumers of SFA

**** This can also be seen in inadequately randomised trials like Finnish Mental Hospital Study, which had a substantial difference in cardiotoxic medication use between the groups and hospital stay (blog), as well as many minor differences (in things like age, blood pressure, BMI, etc)

***** Or in other words, how to be a reductionist: focus on everything in blue and ignore everything in green.


****** As risk factors, total-C, LDL-C and the total-C:HDL-C ratio would all predict that replacing SFA with MUFA would decrease the risk of CHD.  Unfortunately, only the Rose Corn Oil Trial tested this, as it had an olive oil group that had a slightly higher incidence of CHD events and mortality (not significant) [20].  In meta-analyses of observational studies, Jakobson, Skeaff and Chowdhury found no association between MUFA and CHD, whereas Mente found an inverse association between MUFA and CHD

Saturday, May 9, 2015

To Err on Which Side of Caution

Diet Heart Dogma and the Totality of the Evidence

When someone publishes a negative meta-analysis of the diet heart trials (e.g. Ramsden and Harcombe) the overwhelming response appeals to the ‘totality of the evidence’, which in this case also includes observational studies (only the favourable ones though) and how SFA and PUFA affect blood lipids.  Essentially this becomes little more than an appeal to authority as the respondent will often say that the AHA/etc has looked at the ‘totality of the evidence’ and recommends replacing SFA with PUFA

·         A new study is published
·         Do the results support your position?
o   If yes: claim the study was well designed and that it supports your position.  Whatever you do, don’t discuss the limitations of the study
o   If no: criticise the study and appeal to the ‘totality of the evidence’

This doesn’t just happen when ‘someone else’ publishes something negative, but also when pro-diet heart hypothesis researches publish a negative paper.  A good example of this comes from the meta-analysis by Skeaff & Miller:

“The evidence from metabolic ward studies clearly shows that diets low in SFA reduce total cholesterol and should therefore reduce the risk of CHD. However, the meta-analysis of results from cohort studies – albeit from a limited number of studies – showed no association between SFA intake and CHD, demonstrating their unreliability. The observational evidence for an association between dietary PUFA and CHD risk is inconsistent and is unreliable.” – Skeaff & Miller (2009)

In addition, the Minnesota Coronary Survey (MCS) was conducted during 1970 to 1973 [1].  The results were presented in 1975 at one of the American Heart Association's Annual Scientific Sessions and the abstracts were published in a supplement of the AHA’s journal ‘Circulation’ in 1975 (the first three studies in my blog post, which don’t exist on the internet, but I was able to access through a university library).  However, the full study was not published until 1989, 14 years later!  In GCBC, Gary Taubes mentions that: “When I asked Frantz in late 2003 why the study went unpublished for sixteen years, he said, “We were just disappointed in the way it came out””

This begs the question: why bother conducting clinical trials or doing a meta-analysis in the first place if you will simply ignore/rationalise unfavourable results.

Nutrition/dietetics is probably among the most dogmatic fields in science and within nutrition/dietetics, the diet heart hypothesis could easily be the worst

So in response to my results that replacing SFA with PUFA doesn’t reduce CHD or mortality, I’m fully expecting that: (1) some people will criticise the trials and suggest that we should instead rely on blood lipids and the (favourable) Jakobsen or Farvid meta-analysis (and not the Skeaff, Mente or Chowdhury meta-analyses, which found no benefit); and (2) some people will talk about moving away from reductionist recommendations while still recommending we reduce SFA, or use certain ‘eating patterns’ to justify themselves (blog)

In the Absence of Perfect Evidence

I agree that the trials aren’t perfect.  That’s why I excluded 4 of them for being ‘inadequately controlled’, described the other 5 as being ‘adequately controlled’ rather than ‘well controlled’ and removed SDHS just in case its negative result was due to a difference in TFA intake.  Most of the participants were middle-aged men with CHD (probably white also), with very few women, people above 70 and without pre-existing CHD.

Ideally a large and long, well designed, randomised controlled trial would be conducted in both men and women to provide a better understanding of whether a valid* and fair** replacement of SFA with PUFA would reduce CHD events, CHD mortality and total mortality (and also how this affects non-CHD events such as gallstones).  However, such a trial is not likely to happen in the near future and even if it began tomorrow there would be period of several years before the results would be in.

So in any event, we still have to decisions about what to eat today.  Should we err on the side of caution of replacing SFA with PUFA, or perhaps we should be cautious about reducing SFA and/or increasing PUFA and should we instead turn our attention elsewhere?

In the next few posts I’m going to argue that we shouldn’t rely on risk factors on observational studies for dietary recommendations; discuss the evidence on whether PUFAs are harmful; and mention reasons not to reduce saturated fat and to instead focus on the bigger picture

* ‘Valid’ = comparing items of food used for similar purposes.  For example: should I put add butter or margarine to my bread/potatoes/etc; and should I cook with butter/coconut oil or vegetable oils? 

** ‘Fair’ = replacing refined/processed sources of SFA (butter, coconut oil, palm oil) with refined/processed sources of PUFA (vegetable oils); or replacing whole food sources of SFA (full fat dairy, fatty meat, coconut) with whole food sources of PUFA (peanuts, nuts and seeds).  No difference in TFA intake, baked goods, fruits and vegetables, etc.  (Another example of a reasonably ‘fair’ comparison is the ‘filled’ meats and milk that were sometimes used in the trials, whereby the fat in meats and milk were taken out and replaced with vegetable oils.  Although it’s debatable as to whether this is a ‘valid’ comparison)

Sunday, April 26, 2015

Testing the Diet Heart Hypothesis in Women

Most of the diet heart trials were only conducted in men probably because CHD is thought to be the ‘fat, middle-aged man’s disease’, but CHD is the leading cause of death in Australian [1] and American [2] women as well.  In Australia, 45.5% of all deaths from CHD occur in women [1].  So while CHD certainly does affect more men than women, this difference seems to be greatly exaggerated.

Despite these statistics, only two of the trials included women (Finnish Mental Hospital Study (FMHS) and Minnesota Coronary Survey (MCS)) and consequently the weighting of events/deaths for women is far below 45.5%


Weighting in ‘Adequately Controlled Trials’
Weighting in All Trials
Men (%)
Women (%)
Men (%)
Women (%)
Major CHD Events (E)
82.6
17.4
86.8
13.2
Major CHD Events (P)
82.5
17.5
86.5
13.5
Total CHD Events (E)
83.8
16.2
83.0
17.0
Total CHD Events (P)
84.1
15.9
83.0
17.0
CHD Mortality
85.0
15.0
79.7
20.3
Total Mortality
77.0
23.0
67.7
32.3

This goes to larger issue in medicine where women are often underrepresented in clinical trials, sometimes even to the extent where women are prescribed a drug which hasn’t even been tested in a single woman in a clinical trial [3].  A lot of small, short term studies are done only using men, as the menstrual cycle may affect the results.  While this is a legitimate concern of small, short term studies, it would have little to no impact in larger, long term studies such as the diet heart trials, particularly if they included mainly postmenopausal women

This is important because certain interventions can affect women differently.  There are a few examples in [3] and [4] and plenty on Suppversity if you do a few searches.  Another example may be statins, as a meta-analysis found that in secondary prevention trials statins don’t significantly reduce total mortality in women, whereas they do with men [5].

Replacing SFA with PUFA may be another example where women respond differently as there was a fairly consistent pattern in MCS and FMHS: when the RRs for men were compared with those for women: men do better than women or women do worse than men (depending on how you look at it).

FMHS
RR for Men
RR for Women
Difference
Major CHD Events
0.330
0.393
+19.1%
Total CHD Events
0.557
0.635
+14.0%
CHD Mortality
0.469
0.659
+40.5%
Total Mortality
0.882
1.064
+20.6%

MCS
RR for Men
RR for Women
Difference
Major CHD Events
0.895
1.317
+47.2%
CHD Mortality
1.102
1.097
-0.5%
Total Mortality
0.992
1.164
+17.3%

Given that women were very underrepresented in the diet heart trials and respond to replacing SFA with PUFA less favourably/worse than men do, I wonder what the results would be if more of the trials included women:

  • Would this pattern persist?  Is this a real effect?
  • Would the pooled result be completely neutral even without excluding inadequately randomised and/or inadequately controlled trials?
  • If there were some repeats of MCS, would health authorities be urging women away from vegetable oils?

The answers to those questions is debatable, simply because we don’t know and I don’t think we can draw too strong a conclusion from two trials (especially because one of them (FMHS) was both inadequately randomised and inadequately controlled).  This is an additional reason to conduct another trial where SFA is replaced with PUFA, one which is randomised, well controlled and includes both men and women.  Conventional dietitians/doctors should be motivated to do so, not only do they have the burden of proof, but also because the current results for women aren't too favourable.