. 2024 Sep 5;75:102807. doi: 10.1016/j.eclinm.2024.102807

Table 1.

GRADE assessment of direct, indirect and network estimates for the main fatty acid networks (5% isocaloric energy substitution).

Network 2 fatty acid expanded network (n = 1,102,268 participants; n = 224,319 mortality events)
		Direct evidence			Indirect evidence		Network Meta-Analysis
Comparison	N studies	Proportion direct evidence	HR (95% CI)	Certainty of evidence	HR (95% CI)	Certainty of evidence	HR (95% CI)	Certainty of evidence
↑ PUFA
↓ MUFA	10	88	0.92 [0.86, 0.99]	⨁⨁⨁◯^a	1.11 [0.92, 1.35]	⨁⨁◯◯	0.94 [0.88, 1.01]	⨁⨁◯◯^d
↓ SFA	12	90	0.86 [0.80, 0.92]	⨁⨁⨁◯^a	0.84 [0.69; 1.03]	⨁⨁◯◯	0.86 [0.81, 0.91]	⨁⨁⨁◯
↓ TFA	5	68	0.64 [0.56, 0.73]	⨁⨁⨁◯^a	1.07 [0.88, 1.30]	⨁⨁◯◯	0.75 [0.67, 0.84]	⨁⨁⨁◯
↓ CHO	12	88	0.90 [0.84, 0.96]	⨁⨁◯◯^a^,^c	0.88 [0.74, 1.05]	⨁⨁⨁◯	0.90 [0.84, 0.95]	⨁⨁⨁◯
↓ PRO	2	54	0.99 [0.86, 1.14]	⨁⨁◯◯^b	0.82 [0.70; 0.95]	⨁⨁◯◯	0.91 [0.82, 1.01]	⨁◯◯◯^d
↑ MUFA
↓ SFA	11	88	0.91 [0.86, 0.97]	⨁⨁⨁◯^a	0.90 [0.75; 1.08]	⨁⨁⨁◯	0.91 [0.86, 0.97]	⨁⨁⨁◯
↓ TFA	5	70	0.74 [0.65, 0.84]	⨁⨁⨁◯^a	0.95 [0.78, 1.16]	⨁⨁◯◯	0.80 [0.72, 0.89]	⨁⨁⨁◯
↓ CHO	11	86	0.94 [0.88, 1.01]	⨁⨁⨁◯^a	1.01 [0.86, 1.19]	⨁⨁⨁◯	0.95 [0.90, 1.01]	⨁⨁◯◯^d
↓ PRO	2	51	0.95 [0.82, 1.09]	⨁◯◯◯^b^,^c	0.98 [0.85; 1.14]	⨁⨁◯◯	0.96 [0.87, 1.07]	⨁◯◯◯^d
↑ SFA
↓ TFA	5	68	0.85 [0.75, 0.97]	⨁⨁⨁◯^a	0.92 [0.76, 1.12]	⨁⨁◯◯	0.87 [0.78, 0.97]	⨁⨁⨁◯
↓ CHO	12	86	1.06 [1.00, 1.13]	⨁⨁⨁◯^a	0.95 [0.82; 1.11]	⨁⨁◯◯	1.04 [0.99, 1.11]	⨁⨁◯◯^d
↓ PRO	4	77	1.01 [0.91, 1.13]	⨁⨁◯◯^a^,^c	1.23 [1.01, 1.51]	⨁⨁◯◯	1.06 [0.96, 1.16]	⨁◯◯◯^d
↑ TFA
↓ CHO	6	86	1.18 [1.05, 1.32]	⨁⨁◯◯^a^,^c	1.30 [0.98, 1.72]	⨁⨁⨁◯	1.20 [1.08, 1.33]	⨁⨁⨁◯
↓ PRO	1	6	1.04 [0.60, 1.82]	⨁⨁◯◯^b	1.22 [1.06; 1.41]	⨁⨁◯◯	1.21 [1.05, 1.39]	⨁⨁◯◯

Network 3: MUFA-origin network (n = 628,803 participants; n = 151,006 mortality events)
		Direct evidence			Indirect evidence		Network Meta-Analysis
Comparison	N studies	Proportion direct evidence	HR (95% CI)	Certainty of evidence	HR (95% CI)	Certainty of evidence	HR (95% CI)	Certainty of evidence
↑ Plant-MUFA
↓ Animal-MUFA	4	100	0.81 [0.76, 0.85]	⨁⨁⨁◯^a	NA	NA	0.81 [0.76, 0.85]	⨁⨁⨁◯
↓ SFA	4	97	0.85 [0.80, 0.90]	⨁⨁⨁◯^a	0.88 [0.64, 1.22]	⨁⨁⨁◯	0.85 [0.80, 0.90]	⨁⨁⨁◯
↓ TFA	2	96	0.78 [0.66, 0.92]	⨁⨁⨁◯^a	1.25 [0.57, 2.74]	⨁⨁⨁◯	0.79 [0.67, 0.94]	⨁⨁⨁◯
↓ CHO	4	99	0.90 [0.85, 0.95]	⨁⨁⨁◯^a	1.11 [0.53, 2.34]	⨁⨁⨁◯	0.90 [0.85, 0.95]	⨁⨁⨁◯
↑ Animal-MUFA
↓ SFA	4	96	1.05 [0.98, 1.12]	⨁⨁⨁◯^a	1.20 [0.86, 1.68]	⨁⨁⨁◯	1.05 [0.99, 1.12]	⨁⨁◯◯^d
↓ TFA	2	92	1.01 [0.85, 1.20]	⨁⨁⨁◯^a	0.75 [0.42, 1.34]	⨁⨁⨁◯	0.99 [0.84, 1.16]	⨁⨁◯◯^d
↓ CHO	4	99	1.12 [1.05, 1.19]	⨁⨁⨁◯^a	1.07 [0.55, 2.12]	⨁⨁⨁◯	1.12 [1.05, 1.18]	⨁⨁⨁◯

Network 4: PUFA-origin network (n = 884,003 participants; n = 179,859 mortality events)
		Direct evidence			Indirect evidence		Network Meta-Analysis
Comparison	N studies	Proportion direct evidence	HR (95% CI)	Certainty of evidence	HR (95% CI)	Certainty of evidence	HR (95% CI)	Certainty of evidence
↑ n-3 PUFA
↓ n-6 PUFA	4	79	0.92 [0.74, 1.13]	⨁⨁⨁◯^a	0.60 [0.40, 0.90]	⨁⨁⨁◯	0.84 [0.70, 1.01]	⨁⨁◯◯^d
↓ MUFA	1	52	0.81 [0.57, 1.15]	⨁⨁◯◯^b	0.70 [0.49, 1.01]	⨁⨁◯◯	0.75 [0.58, 0.97]	⨁⨁◯◯
↓ SFA	3	88	0.70 [0.58, 0.86]	⨁⨁⨁◯^a	0.59 [0.35, 0.99]	⨁⨁⨁◯	0.69 [0.57, 0.83]	⨁⨁⨁◯
↓ TFA	1	86	0.83 [0.43, 1.58]	⨁⨁◯◯^b	0.51 [0.10, 2.51]	⨁⨁◯◯	0.77 [0.42, 1.41]	⨁◯◯◯^e
↓ CHO	5	83	0.82 [0.66, 1.01]	⨁⨁⨁◯^a	0.38 [0.24, 0.59]	⨁⨁⨁◯	0.72 [0.59, 0.86]	⨁⨁⨁◯
↓ PRO	1	48	0.83 [0.59, 1.17]	⨁⨁◯◯^b	0.73 [0.53, 1.01]	⨁⨁◯◯	0.78 [0.61, 0.98]	⨁⨁◯◯
↑ n-6 PUFA
↓ MUFA	1	78	0.96 [0.76, 1.21]	⨁⨁◯◯^b	0.70 [0.45, 1.08]	⨁⨁◯◯	0.90 [0.73, 1.10]	⨁◯◯◯^d
↓ SFA	3	90	0.86 [0.77, 0.97]	⨁⨁⨁◯^a	0.55 [0.39, 0.78]	⨁⨁⨁◯	0.82 [0.74, 0.92]	⨁⨁⨁◯
↓ TFA	1	97	0.98 [0.54, 1.78]	⨁⨁◯◯^b	0.12 [0.005, 2.95]	⨁⨁◯◯	0.92 [0.51, 1.64]	⨁◯◯◯^e
↓ CHO	4	95	0.85 [0.77, 0.94]	⨁⨁⨁◯^a	0.89 [0.55, 1.42]	⨁⨁⨁◯	0.85 [0.77, 0.94]	⨁⨁⨁◯
↓ PRO	1	74	0.99 [0.81, 1.22]	⨁⨁◯◯^b	0.76 [0.54, 1.08]	⨁⨁◯◯	0.93 [0.77, 1.11]	⨁◯◯◯^d

⨁⨁⨁⨁ High; ⨁⨁⨁◯ Moderate; ⨁⨁◯◯ Low; ⨁◯◯◯ Very low.

95% CI 95% confidence interval; animal-MUFA monounsaturated fatty acids of animal origin; CHO carbohydrates; GRADE Grading of Recommendations Assessment, Development and Evaluations; HR hazard ratio; MUFA monounsaturated fatty acids; n-3 PUFA n-3 polyunsaturated fatty acids; n-6 PUFA n-6 polyunsaturated fatty acids; NA not applicable (the proportion of evidence was 100% for the direct estimate); plant-MUFA monounsaturated fatty acids of plant origin; PRO protein, RoB risk of bias, SFA saturated fatty acids; TFA trans-fatty acids.

Downgraded by 1 level for RoB: less than 2/3 of the studies (and their contributing weight) were rated with a low RoB, and less than 2/3 of the studies were rated with a high RoB, OR more than 2/3 of the studies (and their contributing weight) were rated with a high RoB, but the effect estimate in the subgroup analysis, excluding studies with a high RoB, was robust.

Downgraded by 2 levels for RoB: More than 2/3 of the studies (and their contributing weight) were rated with a high RoB. No subgroup analysis for RoB could be conducted to test to robustness of the effect estimates.

Downgraded by 1 level for inconsistency: The point estimates differ substantially between primary studies, and the corresponding 95% CI overlap only minimally or not at all. We found no clinical or methodological explanation for this inconsistency.

Downgraded by 1 level for imprecision: The 95% CI includes a RR/HR of 1 and the 95% CI is not narrow (maximal width of 0.05).

Downgraded by 2 levels for imprecision: The 95% CI includes a RR/HR of 1 and the ratio of the upper to the lower CI bound is > 3.