Finnish mental hospital Study

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Finnish Mental Hospital Study(soy oil replacing dairy fat in habitual diet)

Published as two separate papers:

Turpeinen O et al. Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study. Int J

Epidemiol. 1979 Jun;8(2):99-118.

Page 1

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.

WOMEN

MEN



http://www.ncbi.nlm.nih.gov/pubmed/393644


Page 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?

Miettinen M et al. 1983 & Turpeinen O et al. 1979 http://www.facebook.com/pronutritionist

http://www.ajcn.org/content/91/3/535.full

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=229002&Ausgabe=250361&ProduktNr=223977&filename=229002.pdf


http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000252


http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002137.pub2/abstract





Methods (schematic)

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Miettinen M et al. 1983 & Turpeinen O et al. 1979

Randomization of the order of which hospital to start with the active treatment (SCL diet)

Soy oil (SCL) diet in Hospital N (Nikkilä)

Dairy fat (NORM) diet in Hospital K (Kellokoski)

Dairy fat (NORM) diet in Hospital N

Soy oil (SCL) diet in Hospital K

“reverse of diets”, ie. hospital

kitchens changed roles

6 years 6 years

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

y. 1959 y. 1971





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







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

*) Serum Cholesterol Lowering Diet Page 5 http://www.facebook.com/pron

utritionist






Methods (patient journeys, 5 eligible examples)



A) Patient staying in hospital N for the both periods (12 years)

C) Patient staying in hospital K for 4,5 years

B) Patient staying in hospital N for the NORM period but just 3,1 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)





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


Miettinen M et al. 1983




Results (Women 2/5)



Soy oil (SCL) diet in Hospital N

Dairy fat (NORM) diet in Hospital K



2.88 years 4.06 years


Mean periods of

observation

Presence of patients at hospitals




Results (Women 3/5)



SCL diet (soy oil diet)

NORM diet (dairy fat diet)

Δ during SCL 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

Dietary changes




Results (Women 4/5)



Total cholesterol (covering 384 patients ie. 65 % of all subjects)

Total cholesterol(mean of two hospitals)


SCL Diet 6.1 mmol/L(240 mg/dl)

-12,8 % lower during SCL soy oil diet

NORM DIET 7.1 mmol/L(275 mg/dl)




Results (Women 5/5)



Coronary death and composite coronary end point (incidence/ 1000 person years) /Intrahospital (mean)

NS

P=0.07*

*) adjusted with weight. Without weight adjustment p =0.04

Δ - 37 %




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


Turpeinen O et al. 1979




Results (Men 2/5)



Soy oil (SCL) diet in Hospital N

Dairy fat (NORM) diet in Hospital K





Mean periods of

observation

Presence of patients at hospitals




Results (Men 3/5)



SCL diet (soy oil diet)

NORM diet (dairy fat 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

Dietary changes (same for both sexes!?)




Results (Men 4/5)



Total cholesterol (covering 384 patients ie. 65 % of all subjects)

Total cholesterol(mean of two hospitals)


SCL Diet 5.8 mmol/L(226 mg/dl)

-15,5 % lower during SCL soy oil diet

NORM DIET 6.8 mmol/L(267 mg/dl)




Results (Men 5/5)



Coronary death and composite coronary end point (incidence/ 1000 person years) /Intrahospital (mean)

NS

P=0.008

Δ - 44 %




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)








Pronutritionist’s discussion (2/4)Weaknesses

Stated (actual) CommentDrop out rate Up to 55 % / 6 year

(no intention to treat analysis)Max 20 % is acceptable (Dumville 2006)

Mix of parallel and cross over design

1/3 of patients within Cross Over2/3 of patients only in Paralell set up

Mixture of designs is not scientifically sound even is researchers highlighted interhospital analyses

“Carry on” effect of SFA in interhospital analysis

Not discussed Bias in SCD diet during second period

Intermittent hospitalization Only mean presence reported:3-4 years / 6 years

Subjects ate food at home 2-3 years / each 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. Cluster 1: Hospital KCluster 2: Hospital N

Each hospital served its own geographic population. Patients were drawn to hospitals without randomization



http://www.bmj.com/content/332/7547/969.extract





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.



http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(73)91009-X/fulltext



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



Read also about Oslo Diet Heart Study

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Reijo Laatikainen, Authorized Nutritionist, MBA

Health & Medicine

Finnish mental hospital Study