A landmark trial from 1960's with many methdological issues. However, delivered robust results when dairy fat was replaced with soy oil

1. Finnish Mental Hospital Study
(soy oil replacing dairy fat in habitual diet)
Published as two separate papers:
WOMEN
Miettinen M et al. Dietary prevention of coronary heart
disease in women: the Finnish mental hospital study. Int J
Epidemiol.1983 Mar;12(1):17-25.
MEN
Turpeinen O et al. Dietary prevention of coronary heart
disease: the Finnish Mental Hospital Study. Int J
Epidemiol. 1979 Jun;8(2):99-118.
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2. Pronutritionist’s background
• In recent meta-analyses, saturated fat intake was not linked to coronary
heart disease (CHD) incidence (Siri-Tarino et al. 2010, Skeaff & Miller J
. 2009 and Mente et al. 2009)
• Another meta-analysis based on the randomized outcome trials,
demonstrated a lower incidence of CHD if saturated fat was replaced by
polyunsaturated fat (Mozaffarian et al. 2010)
• The results of Mozaffarian’s meta-analysis were heavily driven by two
outlier studies: a) Finnish Mental Hospital Study (FMHS) and b) Oslo
Diet-Heart
• Validity of the findings in Finnish Mental Hospital study has been
questioned by Ramsden et al. 2010. Also, a recent Cochrane meta-
analysis excluded FMHS from the analysis due to “non-randomization” (
Hooper et al. 2011)
• Finnish Mental Hospital is still a landmark trial in Diet Heart hypothesis,
but how does it stand the test of time?
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3. Methods (schematic)
Randomization of the order of
which hospital to start with the
active treatment (SCL diet)
Soy oil (SCL) diet in Dairy fat (NORM) diet in
Hospital N (Nikkilä) Hospital N
“reverse of diets”,
y. 1959 6 years ie. hospital 6 years y. 1971
kitchens changed
roles
Dairy fat (NORM) diet in Soy oil (SCL) diet in
Hospital K (Kellokoski) Hospital K
SCL = Serum Cholesterol Lowering Diet with soy oil filled skim milk and “soft margine”
NORM= Whole milk, butter and “ordinary margarine”
Patient admission to hospitals was not randomized
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4. Methods (patients)
• A cluster –”randomized” controlled clinical trial. Non blinded
• Only 2 Clusters: hospital K and hospital N
• Cross-over design with NO wash out period in between
• Primary prevention (CHD was excluded in these analyses).
• Primary outcomes: CHD and serum total cholesterol
• Hospitalized mental patients. The hospitalization was not covering the whole six
year period for the most
• A hospitalization period per arm could vary from 6 months to 6 years (“In the final
assessment subjects whose period of the hospitalization was less than six months
were excluded”), and discontinuous stay was allowed as far as the patients “were
present minimum 50 % of the time interval between their first admission and the
last discharge”
• Some subjects were discharged and were free to eat anything they wanted after
discharge, ie. during the home stay
• Age at the outset: 34-64 men and 44-64 for women
• Length: 6 years per arm (ie. 12 years alltogether)
• Era: 1959-1971
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5. Methods (diet)
• Feeding study, all food during hospital stay was provided
• Discontinuous stay was allowed, but no food instructions were given for
periods after discharge, ie. for home stay
• Analysis of diet: direct measure of the food provided (not the food consumed)
and fatty acid composition of adipose tissue (fat sample covering 13 % of
females and 34-40 % of males)
• Primary changes in diet:
– Control (NORM): Continued use of whole milk as drink, butter and
“ordinary margarine”
– Active (SCL*): Skim milk blended with soy oil (“filled milk”) and “soft
margarine” in stead of “ordinary margarine” and butter
– No other changes were too be done, ie. Total fat content was not be
changed
• Aim: to replace dairy fat as far as possible by PUFA containing soy oil
*) Serum Cholesterol Lowering
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6. Methods
(patient journeys, 5 eligible examples)
A) Patient staying in hospital N for the both periods (12 years)
B) Patient staying in hospital N for the NORM period but just 3,1 years
C) Patient staying in hospital K for 4,5 years
D) Patient staying in hospital N for 5,5 years
E) Patient staying in hospital N for 3 years and in K for 3,5 years as shorter periods (say
7 months minimum) in discontinuous manner (and having home stay for 5,5 years)
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7. Results (Women 1/5)
• Totally 591 subjects were accepted into the analysis
• Results are mixture of cross over design (31 % of
patients) and parallel design (69 % of patients)
• 45 % of subjects remained in the study for either six year
period, ie. drop out rate is 55 % for a single six year
period
• High drop out was partly due to intended “rejuvenation of
cohorts” at time of reversal of diets (discharging oldest
patients and admitting younger patients)
• 31 % of subjects were present during both six year
periods
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8. Results (Women 2/5)
Presence of patients at hospitals
Soy oil (SCL) diet in Dairy fat (NORM) diet in
Hospital N Hospital N
2.88 years 4.06 years
Mean
periods of
observation
4.02 years 3.77 years
Dairy fat (NORM) diet in Soy oil (SCL) diet in
Hospital K Hospital K
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9. Results (Women 3/5)
Dietary changes
SCL diet NORM diet Δ during SCL
(soy oil diet) (dairy fat diet) diet (%)
Total fat 110 g 107 g +3%
SFA 27.3 g 54.7 g -50 %
MUFA 36.8 g 33.3 g +11 %
PUFA 40.5 g 13.6 g +197 %
Cholesterol 282 mg 480 mg -41 %
Trans fat N/A N/A N/A
Carbohydrates N/A N/A N/A
Protein N/A N/A N/A
Fiber N/A N/A N/A
Other nutrients N/A N/A N/A
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10. Results (Women 4/5)
Total cholesterol (covering 384 patients
ie. 65 % of all subjects)
Total cholesterol Δ during SCL diet (%)
(mean of two
hospitals)
SCL Diet 6.1 mmol/L -12,8 % lower during
(240 mg/dl) SCL soy oil diet
NORM DIET 7.1 mmol/L
(275 mg/dl)
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11. Results (Women 5/5)
Coronary death and composite coronary end point
(incidence/ 1000 person years) /Intrahospital (mean)
P=0.07*
Δ - 37 %
NS
*) adjusted with weight. Without weight adjustment p =0.04
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12. Results (Men 1/5)
• Totally 676 subjects were accepted into the analysis
• Results are mixture of cross over design (36 % of
patients) and parallel design (64 % of patients)
• 53 % of subjects remained in the study for either six year
period, ie. drop out rate is 47 % for a single six year
period
• High drop out was partly due to intended “rejuvenation of
cohorts” at time of reversal of diets (discharging oldest
patients and admitting younger patients)
• 36 % of subjects were present during both six year
periods
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13. Results (Men 2/5)
Presence of patients at hospitals
Soy oil (SCL) diet in Dairy fat (NORM) diet in
Hospital N Hospital N
4.39 years 4.42 years
Mean
periods of
observation
4.38 years 4.11 years
Dairy fat (NORM) diet in Soy oil (SCL) diet in
Hospital K Hospital K
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14. Results (Men 3/5)
Dietary changes (same for both sexes!?)
SCL diet NORM diet Δ during SCL
(soy oil diet) (dairy fat diet) diet (%)
Total fat 110 g 107 g +3%
SFA 27.3 g 54.7 g -50 %
MUFA 36.8 g 33.3 g +11 %
PUFA 40.5 g 13.6 g +197 %
Cholesterol 282 mg 480 mg -41 %
Trans fat N/A N/A N/A
Carbohydrates 372 g 379 g -2%
Protein 110 g 107 g +3%
Fiber N/A N/A N/A
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15. Results (Men 4/5)
Total cholesterol (covering 384 patients
ie. 65 % of all subjects)
Total cholesterol Δ during SCL diet (%)
(mean of two
hospitals)
SCL Diet 5.8 mmol/L -15,5 % lower during
(226 mg/dl) SCL soy oil diet
NORM DIET 6.8 mmol/L
(267 mg/dl)
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16. Results (Men 5/5)
Coronary death and composite coronary end point
(incidence/ 1000 person years) /Intrahospital (mean)
P=0.008
Δ - 44 %
NS
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17. Pronutritionist’s discussion (1/4)
• Finnish Mental Hospital was the second study to show that replacing
saturated fat with polyunsaturated fat would decrease the incidence of
coronary heart disease among men by 44 % while lowering serum total
cholesterol by 16 %.
• The same effects were not demonstrated among women even if the trend
was in line with the results among men (p = 0,07 for weight corrected).
Total cholesterol was lowered by 13 % among women during the soy oil
diet
• The results may not be applicable to modern era for many reasons:
– During the soy oil diet PUFA intake was near to current intake at population level in
Finland, ie. 22 grams for women and 31 grams for men. It is impossible to further
decrease saturated fat intake in modern diet by 27 grams as it was done in the study.
Thus re-production of the results seems impossible with current background diet. In
contrast, increasing SFA intake by 30 g from the current level might increase CHD
occurrence
– Soy oil is currently abandoned as cooking oil and replaced by canola and olive oil
– Trans fat content of diets was not calculated even if harder “ordinary margarine” was
replaced by a “softer margarine” during SCD diet (soy oil) diet
– Use of old fashioned and pro-arrhythmic psychotropic drugs was unevenly distributed
and may cause bias (Ramsden et al. 2010)
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18. Pronutritionist’s discussion (2/4)
Weaknesses
Stated (actual) Comment
Drop out rate Up to 55 % / 6 year Max 20 % is acceptable
(no intention to treat analysis) (Dumville 2006)
Mix of parallel and cross over 1/3 of patients within Cross Over Mixture of designs is not scientifically sound
design 2/3 of patients only in Paralell set even is researchers highlighted interhospital
up analyses
“Carry on” effect of SFA in Not discussed Bias in SCD diet during second period
interhospital analysis
Intermittent hospitalization Only mean presence reported: Subjects ate food at home 2-3 years / each
3-4 years / 6 years 6 year period of study
Home food was not controlled Not discussed Subject ate whatever they wanted when
discharged
Trans fat effect unknown Not discussed Ramsden et el. 2011 argue the “soft
margarine” induced a big decrease in
industrial trans fat intake in Hosp N during
1st period
No real randomization Cluster randomization. Each hospital served its own geographic
Cluster 1: Hospital K population. Patients were drawn to hospitals
Cluster 2: Hospital N without randomization
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19. Pronutritionist’s discussion (3/4)
Strengths of FMHS
• Pure fat modification trial (no changes in milk proteins,
meat, fish, fiber, vegetable/fruit intake)
• Primary prevention study
• Meals were provided when patients stayed in hospital and
a substantial change took place in SFA intake (decrease of
27 grams, circa 10 E % during soy oil diet)
• For men (only) comparisons were done both intrahospital
and interhospital and also for the first and second 6 year
period separately giving congruent results
• Mortality results were published as an additional (3rd) paper
in Lancet (Miettinen et al. 1972). Mortality was decreased
among males but not among females. Mortality decreased
– 53 % among males.
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20. Pronutritionist’s discussion (4/4)
Conclusion
• FMHS delivered robust results among men but with serious
inherent methodological issues
– Mean study period per arm 3-4 years, ie. 2-3 years shorter than
intention
– Drop out rate (attrition) unacceptably high (up to 55 %)
– Not genuinely randomized
– Many subjects were discharged and re-hospitalized several times (and
had whatever food they wanted at home)
– Change in trans fat intake was not taken into consideration (hard
“ordinary margarine” was switched to soft margarine during SCL Diet
only)
• Background diet and use oils has changed since 1960s
• The study is clearly a ”outlier” in the context of other similar
trials and the results must be interpreted with extreme
caution due to methodological problems
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utritionist

21. Read also about
Oslo Diet Heart Study
Click for slides here
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Reijo Laatikainen, Authorized Nutritionist, MBA
22 19/02/13