Anhang zum Beitrag Fette und Öle

Transkript

Anhang zum Beitrag «Fette und Öle zur Gesundheitsförderung empfehlen?» aus Ars Medici 24/2018

Tabelle 1: Zusammenhang zwischen Konsum von Nahrungsfetten und kardiovaskulären Erkrankungen sowie Schlaganfall (Metaanalysen 2012–2017)

Abbreviations: CHO, Carbohydrates, CHD, coronary heart disease CVD, cardiovascular disease; DHA, docosahexaen acid; DM, diabetes mellitus; T2D; Diabetes mellitus Typ2, EPA, Eisosapentaen acid; HOMA-IR = Homoeostasis Model Assessment of Insulin Resistance, LOE: level of evidence, MUFA, unsaturated fatty acids; n.s., not specified, PC, prospective cohort study; PUFA, polyunsaturated fatty acids; RCT, randomized controlled trial; RR, relative risk; SD, Standard Deviation SFA, saturated fatty acids, S-RR das Summary Relative Risk, SRRE, Summary Relative Risk Estimate

Source

Study category

Disease

Harcombe Z, Meta-

2017 [21]

analysis of

PCs

CHD

Micha R 2017 (PLoS1) [22]
Micha R 2017 (JAMA) [23]

Metaanalysis and systematic review of metaanalyses of PCs & RCTs
Data from NHANES & metaanalyses of PCs & RCTs

CVD & diabetes
CVD & diabetes

Alexander D. et al. 2017 [24]

Metaanalysis of PCs &
RCTs

CHD

End point Mortality

Main nutritional theme
Total fat and SFA intake

No. of included studies
6 PCs

No. of subjects
89'801

Subject group
Adults without CHD

Disease risk 10 foods & 7 23 meta-

nutrients

analyses

(including PUFA

& trans)

140'000– 820'000

Adults

Mortality

10 dietary

not

factors

stated

(including PUFA

& seafood

omega-3 fats)

not stated Adults

Risk & mortality

EPA &DHA from foods or supplements

18 RCTs 93,000 & 16 PCs (RCT trials)
& 732,000
in PC studies

Adults with and without
CHD

Duration RR (95%CI)

Limitations

Conclusions

LOE

6-20 yrs. Not stated
years 5–40 yrs.

The RR 1.04 (0.98-1.1) for total fat, and 1.08 (0.94–1.25) for SFA
Refers to individual meta-analyses
CHD: PUFA, % energy replacing carbohydrates or saturated fats per 5% energy/d (age 50): RR 0.88 (0.83– 0.94); Seafood omega 3 per 100 mg/d: RR0.82 (0.075-0.90)
Among RCTs, risk reduction (CHD) with EPA&DHA (SRRE=0.94; 95% CI, 0.85–1.05) was n.s. Subgroup analyses indicated a significant CHD risk reduction with EPA&DHA in higher-risk populations (e.g. with elevated TG levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated LDL-c (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of PCs resulted in a significant SRRE of 0.82 (95% CI,

Lack of generalisability, dietary recalls are unreliable
Possible bias by clustering of dietary patterns which could still cause unmeasured confounding, e.g., from clustering of healthful factors.
Dietary habits were based on self-reported 24hour recalls, which have known measurement errors for individual people
Large heterogeneity of studies

Epidemiological evidence to date found no significant association between CHD mortality and total fat or saturated fat intake
There was evidence for protective cardiometabolic effects of seafood omega-3s, polyunsaturated fats, and adverse effects of trans-fats. Optimal mean population intake of PUFA replacing SAFA or CHO: 11% E [of 2000 kcal]
Most cardiometabolic deaths in USA were estimated to be related to excess sodium intake, insufficient intake of nuts/seeds, high intake of processed meats, and low intake of seafood omega-3 fats
EPA&DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs

II a
Ia& II a
Ia& II a
Ia& II a

Pimpin 2016 [25]

Meta-
analysis of PCs

CVD, Mortality

Risk & Mortality

Butter

15 PCs 636'151

de Souza RJ, Meta-

2015 [26]

analysis of

PCs

CVD, stroke, diabetes

Risk & mortality

SFA & trans

12 PCs

fats (industrial &

ruminant)

90'500339'000

Hooper L.
2015 (Cochrane) [27]

Meta-
analysis of RCTs

CVD

Morbidity, mortality

Replacing SFA
with CHO, PUFA or other nutrients

15 RCTs 59'000

Farvid M.S. 2014 [28]

Metaanalysis of PCs

CHD

Risk & death

Dietary linoleic 13 PCs 310'602 acid

Wen YT, 2014 [29]

Metaanalysis of RCTs

CV events & mortality

Omega 3 PUFA 14 RCTs 16'338 supplements

Adults Adults
Adults Adults
Patients with CHD

0.74-0.92) for higher intakes of EPA&DHA

10–22 yrs.

Butter consumption (14 g/d) was
weakly associated with mortality; RR = 1.01, 95%CI = 1.00, 1.03, P =0.045) but not with any CVD (RR = 1.00,
95%CI = 0.98, 1.02; P = 0.704), CHD (RR = 0.99, 95%CI = 0.96,1.03; P = 0.537), or stroke (N = 3; RR = 1.01,
95%CI = 0.98, 1.03; P = 0.737)

Not stated RR SFA 0.99 (0.91-1.09) for total mortality, 0.95 (0.88-1.03) for CVD mortality, 1.02 (0.9-1.15) for stroke,
0.95 (0.88-1.03) for DM. Industrial, but not ruminant, trans fats were associated with CHD mortality (1.18
(1.04 to 1.33) v 1.01 (0.71 to 1.43)) and CHD (1.42 (1.05–1.92) v 0.93 (0.73–1.18))

No evidence for heterogeneity nor publication bias
Evidence is heterogeneous; methodological limitations

>2 yrs.

Reducing dietary saturated fat reduced The studies

the risk of cardiovascular events by

provide mode-

17% (risk ratio (RR) 0.83; 95%

rate-quality evi-

confidence interval (CI) 0.72–0.96,

dence that redu-

mainly when saturated fat calories

cing SFA and

replaced polyunsaturated fat

replacing it with

PUFA reduces

our risk of CVD

5.3-30 yrs.

Highest vs lowest category of LA intake resulted in a 15% lower risk of CHD events (pooled RR, 0.85; 95% CI
0.78–0.92; I2=35.5%), and a 21% lower risk of CHD deaths (pooled RR, 0.79; 95% CI 0.71–0.89; I2=0.0%). A
5% of energy increment in LA intake replacing SFA was associated with a 9% lower risk of CHD events (RR,
0.91; 95% CI, 0.87–0.96) and a 13% lower risk of CHD deaths (RR, 0.87; 95% CI, 0.82–0.94)

No evidence of publication bias for either CHD
events or death.

3 mo.- 4.6 yrs.

Omega-3 PUFAs did not demonstrate satisfactory improvements of major cardiovascular events (OR, 0.93; 95%
CI, 0.86–1.01; P Z 0.08; I2 Z 46%). By contrast, omega3 PUFAs reduced risks of death from cardiac causes and
death from all causes (OR, 0.88; 95% CI, 0.80 to 0.96; P= 0.003; OR, 0.86; 95% CI, 0.76 to 0.98; P= 0.03; and OR, 0.92; 95% CI, 0.85 to 0.99; P=
0.02)

No evidence of publication bias for either CHD
events or death

There were relatively small or II a
neutral overall associations of butter with mortality & CVD

SFA are not associated with all-cause mortality, CVD, CHD, ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with methodological limitations. Trans fats are associated with allcause mortality, total CHD, and CHD mortality, probably because of higher levels of intake of industrial than ruminant trans fat
A small but potentially important reduction in cardiovascular risk on reduction of saturated fat intake is observed when replacing SFA with PUFA

II a Ia

In prospective observational studies, dietary LA intake is inversely associated with
CHD risk in a dose– response manner. These data provide support for current
recommendations to replace saturated fat with polyunsaturated fat for
primary prevention of CHD

II a

Supplement of Omega-3 PUFAs in patients with CHD does not prevent major
cardiovascular events, but reduces death from cardiac causes, and death from all
causes. Whether dietary supplementation with Omega3 PUFAs should be still considered in patients with
CHD is currently debated

Schwings-
hackl L, 2014 [BMJ open] [30]

Meta-
analysis of RCTs

CHD

Chowdhury R, 2014 [31]

Systematic review &
metaanalysis of observa-
tional studies & of RCTs

CHD

de Goede J, 2013 [32]

Meta-
Analysis of 2 cohort studies

CHD

Risk & death

Fat reduction;
replacing SFA with PUFA or other nutrients

12 RCTs 7'150

Risk

Dietary & circulating fatty
acids

32 observa-
tional studies, 27 RCTs

up to 512‘000

Mortality

Associations
with plasma fatty acid cholesteryl
esters

2
observational cohorts

558

Patients with CHD
Adults, with and without CHD
Dutch adults

1–6 yrs.
5–23 yrs. in PCs, 18 yrs. in RCTs
8-19 yrs.

When comparing modified fat diets
versus control diets no significant risk reduction could be observed considering all-cause mortality (RR
0.92, p=0.60; I2=59%) and cardiovascular mortality (RR 0.96, p=0.84; I2=69%), combined
cardiovascular events (RR 0.85, p=0.30; I2=75%) and myocardial infarction (RR 0.76, p=0.13; I2=55%).
Sensitivity analyses did not reveal a significant risk reduction for any outcome parameter when
polyunsaturated fat was increased in exchange for saturated fat

Some studies
were >50 yrs. old. Substantial heterogeneity for
several outcomes

Recommending higher
intakes of PUFA in replacement of SFA was not associated with risk reduction
in patients with CHD

In observational studies, relative risks Potential biases Current evidence from RCTs

for CHD were 1.03 (95% CI, 0.98–

from preferential does not clearly support

1.07) for SFA, 1.00 (CI, 0.91–1.10) for publication and cardiovascular guidelines that

MUFA, 0.87 (CI, 0.78 to 0.97) for LC n- selective reporting encourage high consumption

3 PUFA, 0.98 (CI, 0.90 to 1.06) for n-6

of polyunsaturated fatty acids

PUFA, and 1.16 (CI, 1.06–1.27) for

and low consumption of total

trans fatty acids when the top and

saturated fats

bottom thirds of baseline dietary fatty

acid intake were compared. In RCTs,

relative risks for CHD were 0.97 (CI,

0.69 to 1.36) for ALA, 0.94 (CI, 0.86–

1.03) for LC n-3 PUFA, and 0.86 (CI,

0.69– 1.07) for n-6 PUFA

supplementations

After adjustment for confounders, the Blood samples

OR (95%CI) for fatal CHD per SD

were stored >10

increase in plasma linoleic acid was yrs. Data of

0.89 (0.74–1.06). The ORs (95%CI) for plasma n-3 FA

fatal CHD for an SD increase in n-3 esters were

PUFA were 0.92 (0.74–1.15) for alpha- possibly

linolenic acid and 1.06 (0.88–1.27) for unreliable

EPA-DHA. In the meta-analysis, a 5%

higher linoleic acid level was

associated with a 9% lower risk

(relative risk: 0.91; 95% CI: 0.84–0.98)

of CHD

Linoleic acid in plasma
cholesteryl is inversely associated with CHD. There was no such relation with n-3
PUFA cholesteryl esters

Ia
Ia& II a
II a

Ramsden

RCT

CE, 2013 [33] (Sydney

Diet Heart

Study) &

meta-

Analysis of

RCTs

Pan A, 2012 [34]

Metaanalysis of
cohorts

CHD CVD

Mortality

Dietary linoleic 1 (+2+4) 458

acid (LA)

RCTs

Risk

Dietary -

251'049

linolenic acid cohorts

(ALA)

(pro-&

retrospec

tive)

Kotwal S, 2012 [35]

Metaanalysis of
RCTs

CVD

Risk & death

Omega 3 PUFA supplements
(fish oil) or intervention

20 RCTs

>60'000

Hooper L.
2012 (Cochrane) [36]

Meta-
analysis of RCTs

CVD

Risk & death

Fat intake,
replacement of fat with other macronutrients

48 RCTs >80'000

Schwings- Metahackl L, 2014 analysis of
[Lipids Health PCs Dis] [37]

CVD & stroke

CV events Monounsaturate 32 PCs & mortality, d fatty acids,
stroke risk olive oil

841'211

Men with recent CHD
Adults
Mostly patients with CHD
Adults, with and without CHD
Adults, most of them without CVD at baseline

12 mo. 5–33.7 yrs. 0.6–7 yrs.
>6 mo.
4.6–30 yrs.

Replacement of dietary SFA with omega 6 LA (intervention) had higher
rates of death than controls (all cause 17.6% v 11.8%, HR 1.62 (95% CI 1.00 to 2.64), P=0.05; CVD 17.2% v 11.0%,
1.70 (1.03–2.80), P=0.04; CHD 6.3% v 10.1%, 1.74 (1.04–2.92), P=0.04)

Results of borderline
significance. Small trial

-Linoleic acid intervention trials showed no evidence of
cardiovascular benefit

The overall pooled RR was 0.86 (95% CI: 0.77, 0.97; I2 = 71.3%). The
association was n.s. with biomarkers of ALA

High unexplained heterogeneity

Higher ALA exposure is associated with a moderately
lower risk of CVD. The results were generally consistent for dietary studies but were not
statistically significant for biomarker studies

There was no overall effect of ω-3 FA Significant on composite cardiovascular events heterogeneity
(RR=0.96; 95% CI, 0.90–1.03; P=0.24) between the trials or on total mortality (RR=0.95; 95% CI, 0.86–1.04; P=0.28). ω-3 FA did protect
against vascular death (RR=0.86; 95% CI, 0.75–0.99; P=0.03) but not coronary events (RR=0.86; 95% CI,
0.67–1.11; P=0.24)

Omega 3 fatty acids did not protect against composite
cardiovascular events but showed some protection against CV death. There is no
clear effect on total mortality, sudden death, stroke, or arrhythmia. The beneficial
effects of omega 3 fatty acids are not as large as previously implied

Reducing SFA by reducing and/or
modifying dietary fat reduced the risk of CV events by 14% (RR 0.86, 95%CI 0.77 to 0.96, 24 comparisons, 65'508
participants of whom 7% had a cardiovascular event). Subgrouping suggested that this reduction was
observed only in studies of at least two years duration and in men (not of women). Dietary fat
reduction/modification had no effect on total and on CV mortality

Uncertainty over
allocation concealment, lack of blinding and
presence of systematic differences- but
scale and consistency of evidence makes
findings relatively robust

Modifying fat in our food
(replacing some SFA with plant oils and unsaturated spreads) may reduce risk of
heart and vascular disease, but it is not clear whether MUFA or PUFA are more
beneficial. There were no clear effects of dietary fat changes on total and
cardiovascular mortality

The comparison of the top versus bottom third of the distribution of a
combination of MUFA (of both plant and animal origin) showed reduced allcause mortality (RR: 0.89, 95% CI
0.83, 0.96, p = 0.001; I2 = 64%), CV mortality (RR: 0.88, 95% CI 0.80,0.96, p = 0.004; I2 = 50%), CV events (RR:
0.91, 95% CI 0.86, 0.96, p = 0.001; I2 = 58%), and stroke (RR: 0.83,95% CI 0.71, 0.97, p = 0.02).

Potential publiccation bias for
combined CV events (p = 0.018) & total mortality (p
= 0.041). No evidence of publication bias
for risk of CHD (p = 0.28) and stroke (p = 0.28)

There was an overall risk reduction of stroke (17%)
when comparing the top versus bottom third of MUFA, olive oil, oleic acid, and
MUFA: SFA ratio. Only olive oil seems to be associated with reduced risk

Ia II a Ia
Ia
II a

Cheng P, 2016 [38]

Metaanalysis of
cohorts

Stroke

Risk & death

Cheng P 2015 [39]

Meta-
analysis of cohorts

Stroke

Risk & death

MartínezGonzález MA
2014 [40]

Metaanalysis of
cohorts; 1 RCT

Stroke

Risk

Larssen SC 2012 [41]

Metaanalysis of PCs

Stroke

Risk

Chowdhury R, 2012 [42]

Metaanalysis of PC & RCTs

Stroke (cerebrovascular disease)

Risk & mortality

SFA
Long-chain n-3 PUFA
Olive Oil consumption
Long-chain n-3 PUFA
Long-chain n-3 PUFA

15 PCs 476'569
14 PCs 514'483 2 PCs, 1 Ca. 40’000 RCT 8 PCs 242'076
26 PC2 & 794'000 12 RCTs

Adults

7.6–18 yrs.

Adults

4–21.2 yrs.

Adults

years

Adults

4–28 yrs.

Adult with 3- 15.1 & without yrs. CVD

Higher SFA intake was associated with reduced stroke risks for East-Asians
[RR = 0.79 (95 % CI 0.69–0.90)], for dose <25 g/day [RR = 0.81 (95 % CI 0.71–0.92)], for males [RR = 0.85 (95 % CI 0.75–0.96)], and for individuals with body mass index (BMI) <24 [RR = 0.75 (95 % CI 0.65–0.87)], but not for non-East- Asians, females, and individuals with dose >25 g/day and BMI >24

Possible threshold effect of
SFA consumption

Higher consumption of SFA was associated with
decreased stroke risk (morbidity, mortality) in certain groups of subjects (not in
Non-East-Asians)

II a

Higher long chain n-3 PUFA intake
was associated with reduced overall stroke risk [relative risk (RR) = 0.87; 95% confidence interval (CI), 0.79–
0.95

Significant
heterogeneity between the trials

Higher long chain n-3 PUFA
intake is inversely associated with risk of stroke morbidity and mortality

II a

The combined RR of stroke for an increment of 25 g olive oil consumed
per d was 0·76 (95% CI 0·67, 0·86; P,0·001), with a negligible change after including the PREDIMED trial
(Referenz?)

Relatively few trials

Higher olive oil intake is

Ia&

inversely associated with risk II b

of stroke incidence

The combined RR of total stroke was 0.90 (95 % CI, 0.81–1.01) for the highest versus lowest category of long-
chain omega-3 PUFA intake, without heterogeneity among studies (P = 0.32)

No association between

II a

stroke risk & n-3 PUFA intake

The RR for cerebrovascular disease comparing the top thirds of baseline LC omega 3 fatty acids with the bottom thirds for circulating biomarkers was
1.04 (0.90–1.20) and for dietary exposures was 0.90 (0.80–1.01). In the RCTs the RR for cerebrovascular
disease in the LC omega 3 supplement compared with the control group in primary prevention trials was
0.98 (0.89–1.08) and in secondary prevention trials 1.17 (0.99–1.38)

There were moderate, inverse I a & associations of fish consump- II a tion and LC omega 3 fatty acids with cerebrovascular
risk. LC omega 3 fatty acids in RCTs with supplements had no significant effect

Tabelle 2: Zusammenhang zwischen Konsum von Nahrungsfetten und Risiko für Diabetes mellitus-Typ 2 und Adipositas (Metaanalysen 2012–2017)

Source Jovanovski E 2017 [43] Wu J.H.Y 2017 [44]
Schwingshackl L 2017 [45]
Lin N 2016 [46]

Study category Disease End point

Systematic review & metaanalysis of RCTs
Systematic review & metaanalysis of PCs

Diabetes T2 Glycaemic control, insulin sensitivity
Diabetes T2 New diabetes risk

Systematic review & metaanalysis of PCs

Diabetes T2 Diabetes T2 risk & glycaemic control

Systematic review & meta-
analysis of RCTs

Diabetes T2 CRP, other markers of
inflammation

Main nutritional theme
-linolenic acid

No. of included studies
8 RCTs

Omega-6 fatty 20 PCs acid biomarkers

Olive oil

4 PCs, 29 RCTs

n-3 PUFA,

8 RCTs

mostly fish oil

No. of subjects 212 39'740
15’784 DM T2
955

Subject group

Duration

Adults with 3 months DM T2

Adults

mean 8 yrs.

Adults with 5- 22 yrs.

and without for PCs, 2

DM T2

wks.- 4

yrs. for

RCTs

Adults with 6–12

DM T2

weeks

RR (95%CI)

Limitations

n.s. for: HbA1c, IR (HOMA), FBG

Considerable
unexplained heterogeneity

Higher proportions of linoleic acid biomarkers as % of total fatty acid were associated with a lower risk of type 2
diabetes [RR per interquintile range 0∙65, 95% CI 0∙60–0∙72, p<0.0001). Levels of arachidonic acid were n.s. Linoleic acid biomarkers reflect dietary intake but are not identical to dietary intake The highest olive oil intake category There was showed a 16% reduced risk of T2D (RR: evidence for a 0.84; 95% CI: 0.77, 0.92) compared with nonlinear the lowest. In T2D patients olive oil relationship supplementation resulted in a significantly more pronounced reduction in HbA1c (MD: − 0.27%; 95% CI: − 0.37, − 0.17) and fasting plasma glucose (MD: − 0.44 mmol/; 95% CI − 0.66, − 0.22) as compared with the control groups N-3 PUFAs significantly reduced CRP concentration compared with control [SMD 95 % CI, 1.90 (0.64, 3.16), Z = 2.96, P = 0.003, random effect model Small trials, short duration Conclusions LOE -linolenic acidenriched diets did not affect HbA1c, FBG, or FBI. Linoleic acid has long-term benefits for the prevention of type 2 DM and that arachidonic acid is not harmful Olive oil could be beneficial for the prevention and management of T2D Ia II a II a N-3 PUFAs decrease CRP concentration in type-2 DM mellitus Ia Pimpin 2016 [25] Meta-analysis Diabetes of PCs Risk Butter 11 PCs 23‘954 incident DM Qian F 2016 [47] Systematic review & metaanalysis of RCTs Diabetes T2 Glycaemic (T2D) control, blood pressure lipids MUFA compared to CHO & PUFA 24 RCTs 1'504 comparing with CHO, 4 RCTs with PUFA Adults Adults with DM T2 10–22 yrs. 2–48 weeks Butter consumption (14 g/d) was inversely associated with incidence of diabetes (N = 11; RR = 0.96, 95%CI = 0.93, 0.99; P = 0.021) High-MUFA compared to high-CHO diets reduced fasting plasma glucose (WMD -0.57mmol/L [95%CI -0.76,0.39]), triglycerides (-0.31 mmol/L [0.44, -0.18]), body weight (-1.56 kg [2.89,-0.23]), and systolic blood pressure (-2.31 mm Hg), &-increased HDL cholesterol (0.06 mmol/L [0.02, 0.10]). High-MUFA diets compared with highPUFA diets reduced fasting plasma glucose (-0.87 mmol/L [-1.67, -0.07]) No evidence for heterogeneity nor publication bias Low to medium levels of heterogeneity There was a II a relatively small association of butter with diminished risk of DM Evidence that consuming diets high in MUFA can improve metabolic risk factors among patients with T2D Ia 6 Imamura F 2016 [48] Systematic review & meta- analysis of RCTs Diabetes T2, metabolic syndrome Glucoseinsulin homeostasis (HOMA model) SFA, PUFA, MUFA, and carbohydrate 102 RCTs 4'220 Abbott KA 2016 Systematic [49] review & meta- analysis of RCTs Diabetes T2, metabolic syndrome Insulin resistance (IR), in men and women n-3 PUFA, 26 RCTs 1'848 mostly fish oil Chen C 2015 [50] Meta-analysis of RCTs Diabetes T2 Glucose n-3 PUFA, 20 RCTs control, lipids, mostly fish oil BMI 1'209 Souza RJ 2015 [26] Systematic review & meta- analysis of PCs & RCTs Diabetes T2 Diabetes T2 risk SFA & trans 12 PCs fats (industrial & ruminant) 90000339000 Aronis KN 2012 Meta-analysis Diabetes T2 Glucose, Trans fats [51] of RCTs insulin & lipids (TFA) 7 RCTs 208 Adults with 3–168 Replacing 5% energy from carbohydrate Small number In comparison to I a and without days with SFA had no significant effect on of trials for carbohydrate, SFA, DM T2 fasting glucose; replacing carbohydrate some out- or MUFA, most with MUFA lowered HbA1c (-0.09%; - comes and consistent 0.12, -0.05; n = 23), 2 h post-challenge potential issues favourable effects insulin (-20.3 pmol/L; -32.2, -8.4; n = 11), and HOMA-IR (-2.4%; -4.6, -0.3; n = 30). Replacing carbohydrate with of blinding, were seen with compliance, PUFA, which were generalisability, linked to improved PUFA significantly lowered HbA1c (- heterogeneity glycaemia, 0.11%; -0.17, -0.05) and fasting insulin due to unmea- diminished insulin (-1.6 pmol/L; -2.8, -0.4). Replacing SFA sured factors, resistance, and with PUFA significantly lowered and public- improved insulin glucose, HbA1c, C-peptide, and HOMA cation bias secretion capacity Adults with 1–6 and without months With all studies pooled, there was no There was effect of n–3 PUFA on IR at the group significant Improvement of insulin resistance Ia DM T2 level (SMD: 0.089; 95% CI: 20.105, heterogeneity with LC-n-3-PUFA 0.283; P = 0.367). In trials of >6 wks., a between groups in women but not in

significant improvement in IR was seen and a limited men

in women (SMD: 20.266; 95% CI:

number of trials

20.524, 20.007; P =0.045) but not in

in men and

men (SMD: 0.619; 95% CI: 20.583,

women

1.820; P = 0.313

separately

Adults with mostly <12 Triglyceride (TG) levels were Relatively small Suggestion that a I a DM T2 weeks significantly decreased by 0.24 mmol/L studies high EPA/DHA ratio by n-3 PUFAs. No significant change of total cholesterol (TC), HbA1c, fasting plasma glucose, postprandial plasma affects glucose control favourably glucose, BMI or body weight was observed. High ratio of EPA/DHA contributed to a greater decreasing tendency in plasma insulin, HbAc1, TC, TG, and BMI measures, although no statistical significance was identified (except TG). Adults 1–32 yrs. SFA intake was not associated with type The evidence is SFA are not asso- I a & 2 diabetes (0.95, 0.88 to 1.03). heterogeneous ciated with risk of II a Ruminant trans-palmitoleic acid was with method- type 2 DM; ruminant inversely associated with type 2 logical trans fats appear to diabetes (0.58, 0.46 to 0.74) limitations be associated with protection Adults, nondiabetic 4–16 wks. Increased TFA intake did not result in significant changes in glucose or insulin concentrations. Increased TFA intake led to a significant increase in total and LDL-cholesterol (ES [95% CI]: 0.28 [0.04, 0.51] and 0.36 [0.13, 0.60], respectively) and a significant decrease in HDL-cholesterol concentrations (ES [95% CI]: 20.25 [20.48, 20.01]) No publication bias TFA affect LDL-C & HDL-C but not glucose-insulin homeostasis Ia 7 Zheng J-S, 2012 [52] Systematic Diabetes T2 Relative Risk n-3 PUFA, 24 PCs review & meta- of diabetes T2 mostly fish oil, analysis of PCs and fish >500'000 Adults

Zhou Y, 2012 [53]

Systematic

Diabetes T2 Relative Risk n-3 PUFA,

13 PCs

review & meta-

of diabetes T2 mostly fish oil, (mostly

analysis of PCs

and fish

Western)

>100'000

Adults

Wu J.H.Y 2012 Systematic

Diabetes T2 Diabetes T2

[54] review & meta-

incidence

analysis of PCs

n-3 PUFA,

18 PCs

ALA & mostly

fish oil

540'184

Adults

Wallin A 2012 [55]

Systematic

Diabetes T2 Diabetes T2

review & meta-

incidence

analysis of PCs

n-3 PUFA,

16 PCs

mostly fish oil,

and fish

527'441

Adults

4–18 yrs. 6–15 yrs. 4–17 yrs.
6–19 yrs.

The RR of T2D for the highest vs lowest categories of total fish, marine n-3 PUFA and alpha-linolenic acid intake was 1.07 (95% CI: 0.91, 1.25), 1.07 (95% CI: 0.95, 1.20) and 0.93 (95% CI: 0.81, 1.07), respectively. For Asian populations the RR (highest vs lowest category) of T2D for fish and marine n-3 PUFA intake was 0.89 (95% CI: 0.81, 0.98) and 0.87 (95% CI: 0.79, 0.96); for Western populations the RR was 1.20 (95% CI: 1.01, 1.44) and 1.16 (95% CI: 1.04, 1.28)
Comparing the highest v. lowest categories, the pooled RR of T2DM for intake of fish and n-3 fatty acid was 1·146 (95% CI 0·975, 1·346) and 1·076 (95% CI 0·955, 1·213), respectively. In the linear dose–response relationship, the pooled RR for an increment of one time (about 105 g)/week of fish intake (four times/month) and of 0·1 g/d of n-3 fatty acid intake was 1·042 (95% CI 1·026, 1·058) and 1·057 (95% CI 1·042, 1·073), respectively
Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100 g/d = 1·12, 95% CI = 0·94, 1·34); nor were consumption of EPA &DHA (n= 16 cohorts; RR per 250 mg/d= 1·04, 95% CI= 0·97, 1·10) nor circulating levels of EPA &DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids = 0·94, 95% CI= 0·75, 1·17). Both dietary ALA (n=7 studies; RR per 0·5 g/d = 0·93, 95% CI = 0·83, 1·04) and circulating ALA biomarker levels (n=6 studies; RR per 0·1% of total fatty acid = 0·90, 95% CI = 0·80, 1·00, P=0·06) were associated with non-significant trend towards lower risk of DM
For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02–1.09), 1.03 (0.96–1.11), and 0.98 (0.97–1.00) combining U.S., European, and Asian/Australian studies, respectively

Classifications of fish and n-3 PUFA intake amounts were inconsistent; observational studies could not avoid residual confounders
Potential biases and confounders could not be ruled out completely
No publication bias, but substantial heterogeneity between fish oil studies
Heterogeneous results due to geographical differences

Marine n-3 PUFA have beneficial effects on the prevention of T2DM in Asian populations
Both fish oil and other n-3 fatty acids might be weakly positively associated with the T2DM risk (mostly Western populations)
The findings do not support either major harms or benefits of fish/seafood or EPA&DHA on development of DM. ALA consumption showed a n.s. trend towards diminished risk.
There were differences of risk of DM between geographical regions with observed associations of fish consumption and dietary intake of LC n-3 FA.

II a II a II a
II a

Alhazmi A 2012 Systematic

Diabetes T2 Relative Risk Macronutrient 22 PCs

[56] review & meta-

of diabetes T2 intake

analysis of PCs

>500'000

Mansoor N 2016 [57]

Meta-analysis of RCTs

Obesity &
CV risk factors

Weight loss, lipids

Low fat versus 11 RCTs 1'369 low carb

Tobias DK 2015 [58]

Meta-analysis Obesity of RCTs

Weight loss, serum triglycerides

Low fat versus 53 RCTs other dietary interventions

68128

SacknerBernstein J,
2015 [59]

Meta-analysis Obesity of RCTs

Weight loss, CV risk
factors

Low fat versus 17 RCTs low carb

1'797

Hooper L 2015 Meta-analysis
(Cochrane) [60] of RCTs & of PCs

Weight gain Change of
body weight, Lipids

Total fat intake

32 RCTs, 54'000 25 PCs (RCTs)

Adults

4.6–20 yrs.

Adults,

6 months

overweight

-obese

Adults, overweight -obese,
formerly obese

>1 yr.

Adults,

8 wks.–2

overweight yrs.

-obese

Adults, not Median: 5
aiming to yrs. lose weight

High intake of dietary carbohydrate was associated with an increased type 2 diabetes risk (RR= 1.11, 95% CI: 1.01 to 1.22, p=0.035); however, this effect was not observed in an analysis stratified by gender. Intake of total fat, SFA, MUFA & PUFA was not associated with diabetes risk Participants on LoFat diets compared to LoCarb diets lost more weight (WMD – 2·17 kg; 95% CI –3·36, –0·99) and triglycerides (WMD –0·26 mmol/l; 95% CI –0·37, –0·15), but had a greater increase in HDL-cholesterol (WMD 0·14 mmol/l; 95% CI 0·09, 0·19) and LDLcholesterol (WMD 0·16mmol/l; 95% CI 0·003, 0·33 fehlen da Kommata oder Punkte?)
In weight loss trials, low-carbohydrate interventions led to significantly greater weight loss than did low-fat interventions (18 comparisons; WMD 1.15 kg [95% CI] 0.52–1.79
Compared with low fat diet, low carbohydrate was associated with significantly greater reduction in weight (Δ = -2.0 kg, 95% CI: -3.1, -0.9) and significantly lower predicted risk of atherosclerotic cardiovascular disease events (p<0.03) Eating less fat (compared with usual diet) resulted in a mean weight reduction of 1.5 kg (95% CI -2.0 to -1.1 kg), but greater weight loss results from greater fat reductions. The size of the effect on weight does not alter over time and is mirrored by reductions in body mass index (BMI) (-0.5 kg/m2, 95% CI 0.7 to -0.3) and waist circumference (0.3 cm, 95% CI -0.6 to -0.02) No studies fulfilled all requirements for a highquality study free of bias Heterogeneity was moderate to high for all variables Incomplete outcome data was a high potential source of bias for 39 trials because of drop-out and loss-to-followup rates exceeding 5% No patient-level data; frequent loss of follow-up There was a high risk of performance bias due to lack of blinding; most RCTs were at unclear risk of reporting bias; some trials had high attrition rates Fat and individual fatty acid intake was not associated with DM T2 risk The beneficial changes of LoCarb diets must be weighed against the possible detrimental effects of increased LDL-cholesterol Higher-fat, lowcarbohydrate dietary interventions led to a slight but significant, greater long-term weight loss than did low-fat interventions LoCarb diet appears to achieve greater weight loss and reduction in predicted risk of ASCVD events compared with LoFat diet Lowering the proportion of fat in food leads to a small but noticeable decrease in body weight, body mass index and waist circumference in both, adults and children. The effect did not change over time II a Ia Ia Ia Ia& II a 9 Tabelle 3: Zusammenhang zwischen Konsum von Nahrungsfetten und Risiko für das Auftreten bestimmter Krebsformen (Metaanalysen 2012–2017) Source Study category Disease Brennan SF 2017 [61] Systematic review & meta-analysis of PCs Breast cancer End point Survival from breast cancer Main nutritional theme Dietary fat, SFA No. of included studies 15 PCs No. of subjects 29241 Subject group Women with breast cancer Zhao J 2016 [62] Systematic review & meta-analysis of PCs or case control studies Endometrial cancer Risk of new cancer Dietary fat, SFA, MUFA, PUFA 7 PCs & 14 case controls approx. 15'000 Women Cao Y 2016 [63] Systematic review & meta-analysis of PCs Breast cancer Xia H, 2015 [64] Systematic review & meta-analysis of PCs or case control studies Breast cancer Han J 2015 [65] Meta-analysis of observational studies Gastric cancer Risk of new Dietary fat, 24 PCs cancer SFA, PUFA, MUFA 38262 & 1.4 Women Mio controls Risk of new Dietary SFA 24 PCs & 35651 BC, cancer 28 case 1.8 Mio controls controls Women Risk of new Dietary fat cancer 22 studies approx. 8500 cases & 500'000 controls Adults Duration RR (95%CI) Limitations Conclusions LOE 16 yrs. There was no difference in risk of breast-cancer- Heterogeneity Saturated fat intake II a specific death or all-cause death in the highest between was negatively versus lowest category of total fat intake. Breast- studies; small associated with breast cancer-specific death (n=4; HR=1.51; 95% CI: sample size cancer survival 1.09, 2.09; p < 0.01) was higher for women in the highest versus lowest category of saturated fat intake 1 mo.–10 Endometrial cancer risk was significantly Measurement High intake of total fat II a yrs. increased by 5% per 10% kilocalories from total error linked to and SFA was fat intake (P=0.02) and by 17% per 10g/1000 kcal the nature of associated with of saturated fat intake (P<0.001). 3 cohort studies food frequen- increased endometrial showed significant inverse association between cy question- cancer risk. In MUFA & cancer risk (odds ratio=0.84, 95% naire addition, dietary MUFA confidence interval= 0.73–0.98). No significant was associated with associations were found for PUFAs decreased risk in cohort studies 2–25 yrs. No association was observed between animal fat, No subgroups Dietary total fat and II a vegetable fat, SAFA, MUFA, PUFA, n-3 PUFA, n- of cancer fatty acids might be 6 PUFA and risk of breast cancer types. FFQ not associated with are subject to risk of breast cancer error. Not stated The associations between dietary SFA intake and Possible bias A relationship was II a risk of BC were 1.18 for case-control studies (high in case found between SFA vs low intake, 95% confidence interval [CI]=.03– control intake and incidence of 1.34) and 1.04 for cohort studies (95% CI=0.97– studies BC in case–control 1.11) (selection & studies, and of recall) postmenopausal BC risk in case–control but not in cohort studies Not stated The S-RR was 1.18 with highest intake versus Case control Intake of total fat is II a lowest intake of total fat (95% CI: 0.999–1.39; n = studies may potentially positively 28; P< 0.001). There were positive associations introduce associated with gastric between SAFA intake (SRR = 1.31; 95% CI: 1.09– recall and cancer risk, and 1.58; n = 18; P<0.001), and inverse association selection bias, specific subtypes of between PUFA intake (SRR = 0.77; 95% CI: FFQ, fats account for 0.65–0.92; n = 16; P = 0.003) measurement different effects errors etc. 10 Tabelle 4: Zusammenhang zwischen Konsum von Nahrungsfetten und Risiko für andere Endpunkte (neurologische, psychiatrische); (Metaanalysen 2012–2017) Source Study category Grosso G 2016 [66] Review & meta-analysis of observational studies Zhang y, 2016 [67] Meta-analysis of PCs Appleton KM, 2015 (Cochrane) [68] Meta-analysis of RCTs Cooper RE, Meta-analysis 2015 [69] of RCTs Disease Depression Dementia, Parkinson disease Depression Cognitive Impairment End point Main nutritional theme Risk of new n-3 PUFA & disease fish No. of included studies No. of subjects 31 255’076 sub- observational jects, 20’000 studies cases with depression Risk of new n-3 PUFA & 21 PCs disease fish 18‘1580 subjects, 4438 with cognitive impairment Risk of new n-3 PUFA & 25 RCTs disease fish 1’438 Symptoms Omega-3 PUFA 24 RCTs Subject group Duration RR (95%CI) Limitations Conclusion LOE Adults Elderly adults, mostly >65 yrs.
Adults
Adults & children (with ADHD & related disorders)

Not stated
2.1–21 yrs.
wks.– months

Pooled risk estimates of depression for extreme categories of both total n-3 PUFA and fish-de-
rived n-3 PUFA [EPA&DHA] resulted in decreased risk for the highest compared with the low-
est intake (RR=0.78, 95% CI:0.67, 0.92and RR=0.82, 95% CI:0.73, 0.92, respectively.
A 1-serving/wk. increment of dietary fish was associated with lower risks of dementia (RR:
0.95; 95% CI: 0.90, 0.99; P = 0.042, I2 = 63.4%) and Alzheimer D. (RR: 0.93; 95% CI: 0.90,
0.95; P = 0.003, I2 = 74.8%). Pooled RRs of Mild Cognitive Impairment and Parkinson
Disease were 0.71 (95% CI: 0.59, 0.82; P = 0.733, I2 = 0%) and 0.90 (95% CI: 0.80, 0.99; P
= 0.221), respectively, for an 8g/d increment of PUFA intake. A 0.1-g/d increment of dietary DHA
intake was associated with lower risks of dementia (RR: 0.86; 95% CI: 0.76, 0.96; P=0.001).
For the placebo comparison, n-3 PUFA supplementation results in a small to modest benefit for de-
pressive symptomology, compared to placebo: standardised mean difference (SMD) -0.30
(95% confidence interval (CI) 0.10 to -0.50
n-3 PUFA supplementation, in
the whole sample and the TD and ADHD+RD subgroup, did not show improvements in any of
the cognitive performance measures. In those with low n-3 PUFA status, supplementation
improved short-term memory.

Design of the studies included was confounding due to lack adjustment for certain variables
Vitamin E intake appeared as the mostfrequent confounding factor
The quality of the evidence for all outcomes was judged as low to very low.

Dietary n-3 PUFA intake is associated with lower risk of depression
Marine-derived DHA was associated with lower risk of dementia and Alzheimer disease but without a linear dose-response relation
Possible benefit in severe depression (not in mild symptomatology)
There is some evidence that n-3 PUFA supplementation improves cognition in those who are n-3 PUFA deficient, but not in those who were sufficient.

II a II a
Ia Ia

Meta-Analysen zum Zusammenhang zwischen Konsum von Nahrungsfetten und kardiovaskulären Erkrankungen sowie Schlaganfall (2012 bis 2017)
Tabelle 1: Die Publikationen zeigen, dass der Konsum von Gesamtfett und gesättigtem Fett (in % der Energieaufnahme) nicht signifikant mit kardiovaskulärer Morbidität und Mortalität assoziiert war. Ein kleiner, aber potentiell wichtiger Vorteil hinsichtlich des kardiovaskulären Risikos ergab sich aus der Reduktion von gesättigtem Fett, wenn es durch Öle mit reichlich mehrfach ungesättigten Fettsäuren ersetzt wurde. Dieser Vorteil wurde bei Patienten mit bestehender kardiovaskulärer Erkrankung nicht beobachtet. Der Konsum der PUFA Linolsäure wurde mit einer verminderten kardiovaskulären Morbidität und Mortalität in Verbindung gebracht; Es gibt jedoch keine ausreichenden Beweise, um eine bestimmte Art von ungesättigtem Fett als Ersatz für gesättigte Fette zu priorisieren. Von Fischen abgeleitete PUFA (n-3) -Zusätze verringerten nachweislich Herzkreislaufkomplikationen und Sterblichkeit bei kardiovaskulären Hochrisikopatienten. Der Verzehr von industriellen Transfettsäuren ging mit einer erhöhten kardiovaskulären Morbidität und Mortalität und Gesamtmortalität einher. Hinsichtlich des Schlaganfallrisikos wurde ein höherer Konsum von MUFA (insbesondere Olivenöl) mit einem verringerten Risiko assoziiert. Es gibt Belege aus Kohortenstudien, dass der Konsum von langkettigen n-3-PUFAs das Schlaganfallrisiko vermindert, Randomisierte kontrollierte Studien mit langkettigen n-3-PUFAs haben jedoch diesbezüglich keine eindeutigen Resultate ergeben.
Tabelle 2: Die Artikel zeigen, dass der Konsum von Gesamtfett oder gesättigtem Fett nicht signifikant mit dem Risiko für Diabetes Typ 2- in Zusammenhang gebracht werden kann. Erhöhter Konsum von MUFA, Olivenöl und in einigen Fällen von n-6-PUFA ging mit einem verminderten Risiko für neu auftretenden Diabetes einher. Bei Patienten mit etabliertem Diabetes verbesserte sich die Stoffwechselkontrolle, wenn kohlenhydratreiche Nahrungsmittel mit MUFA- haltigen ersetzt werden. In Bezug auf einen hohen oder niedrigen Konsum von pflanzlichen n-3PUFA wurde in einigen Studien ein verringertes Risiko für die Entwicklung von Typ-2-Diabetes und eine verminderte Insulinresistenz beobachtet, die Ergebnisse waren jedoch nicht konsistent.
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Von Fischen stammende langkettige n-3-PUFA reduzierten das Diabetes-Typ-2-Risiko in asiatischen Studien, nicht aber in solchen bei westlichen Populationen. Bei Übergewicht und Adipositas führte die Senkung des Fettanteils in der Ernährung zu einer zwar geringen, aber signifikanten Abnahme des Körpergewichts. Wenn eine Fettreduktion mit einer Kohlenhydratreduktion verglichen wurde, war die letztere etwas wirksamer zur Senkung des Gewichts. Tabelle 3: Diese Studien zeigen, dass eine hohe Aufnahme von Gesamtfett und von gesättigten Fettsäuren in einigen, aber nicht allen Kohortenstudien mit einem erhöhten Risiko für Brust-, Endometrium- und Magenkrebs in Verbindung gebracht wurde. Der Zusammenhang war jedoch nicht stark. Tabelle 4: Die Hauptergebnisse von Kohortenstudien ergeben Hinweise dafür, dass die erhöhte Aufnahme von langkettigen n-3-Fettsäuren mit einer verminderten Inzidenz von kognitiver Beeinträchtigung bei älteren Menschen, einem verringerten Demenzrisiko und einem verringerten Risiko für schwere Depressionen einhergeht. Randomisierte kontrollierte Studien liessen jedoch eine Verbesserung der Kognition nur bei Patienten, die n3 PUFA-defizient waren, nachweisen.
13