Dietary Polyunsaturated to Saturated Fatty Acid Ratio as an Indicator for LDL Cholesterol Response: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Open accessAbstract
Background Dietary guidelines recommend limiting saturated fat (SFA) intake by replacing SFA with polyunsaturated fats (PUFA). PUFA and SFA have opposing effects on LDL-cholesterol (LDL-C) and therefore the dietary ratio of PUFA to SFA (P:S) may be a better indicator of LDL-C response than SFA alone. Objectives A systematic review and meta-analysis of randomized clinical trials was conducted to examine LDL-C responses to higher P:S ratio diets compared to isoenergetic, total fat-matched diets with lower P:S ratios in healthy adults. Methods A systematic search of PubMed, Cochrane Central, and Web of Science was conducted. Randomized complete feeding trials lasting ≥3 weeks including two test diets with P:S ratios differing by >0.3 that were matched for energy, fiber, and total fat were included. Random effects meta-analysis was used to evaluate the mean difference (MD) in LDL-C with higher P:S ratio diets compared to lower P:S ratio diets. Heterogeneity in the effect of the P:S ratio by SFA content of the test diets was also evaluated. Results In total, 1001 publications were identified, and 24 publications reporting 24 trials (n=1011) were eligible. Higher P:S ratio diets (median P:S ratio 1.2; PUFA 10.6%kcal; SFA 8.0%kcal; MUFA 12.6%kcal) lowered LDL-C (MD −9.84 mg/dL; 95%CI −13.65, −6.04; I 2 =79%) compared to lower P:S ratio diets (median P:S ratio 0.4; PUFA 4.4%kcal; SFA 12.5%kcal; MUFA 14.6%kcal). Heterogeneity in the P:S ratio effect was observed by the test diet SFA content (p<0.001). Higher versus lower P:S ratio diets lowered LDL-C (MD −15.72 mg/dL; 95%CI −20.51, −10.92; I 2 =68%) when the test diets differed in SFA (≥2%kcal), but not when diets were SFA matched (MD −3.45 mg/dL; 95%CI −7.88, 0.98; I 2 =70%). Conclusion Compared to lower P:S ratio diets, higher P:S ratio diets were associated with greater LDL-C reductions in generally healthy adults, and this effect was stronger when PUFA replaced SFA. Registry Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42023452550
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Written from the paper’s full text.
TL;DR
This systematic review and meta-analysis of 24 randomized controlled feeding trials (n = 1011) found that higher dietary P:S ratio diets lowered LDL cholesterol compared with lower P:S ratio diets. The effect was driven by SFA replacement with PUFA, with little LDL cholesterol difference when test diets were SFA-matched.
Key findings
- Higher P:S ratio diets (median P:S 1.2; PUFA 10.6% kcal; SFA 8.0% kcal) lowered LDL cholesterol versus lower P:S ratio diets (median P:S 0.4; PUFA 4.4% kcal; SFA 12.5% kcal): WMD −9.83 mg/dL (95% CI: −13.63, −6.04; I² = 79%).
- When test diets differed in SFA (≥2% kcal), higher P:S ratio diets lowered LDL cholesterol by WMD −15.72 mg/dL (95% CI: −20.51, −10.92; I² = 68%); when diets were SFA-matched, WMD was −3.45 mg/dL (95% CI: −7.88, 0.98; I² = 70%) (heterogeneity P < 0.001).
- Greater LDL cholesterol lowering occurred when the higher P:S diet had <10% kcal from SFA and the lower P:S diet had ≥10% kcal from SFA (WMD −16.70 mg/dL; 95% CI: −22.10, −11.30; I² = 75%); no between-diet difference was observed when both diets had ≥10% kcal from SFA (WMD −1.32 mg/dL; 95% CI: −7.75, 5.10; I² = 63%).
- No heterogeneity was observed by mean baseline BMI (P = 0.80) or mean baseline LDL cholesterol (P = 0.49); certainty of evidence was rated moderate.
Methods
- Systematic review and meta-analysis registered as PROSPERO CRD42023452550; PubMed, Cochrane Central, and Web of Science were searched, yielding 1001 publications after duplicate removal, with 24 publications reporting 24 trials (n = 1011) eligible.
- Included randomized complete feeding trials lasting ≥3 wk in generally healthy adults ≥18 y, with 2 test diets differing in P:S ratio by >0.3 and matched for energy, fiber, and total fat; 23 trials were crossover and 1 was parallel, with median duration 28 d (range: 21–42 d).
- Random-effects DerSimonian–Laird meta-analysis evaluated mean difference in LDL cholesterol for higher versus lower P:S ratio diets, with subgroup analyses by SFA match, baseline BMI, baseline LDL cholesterol, and SFA guideline categories; crossover SDs were imputed using a correlation coefficient of 0.5.
Limitations
- The paper states that fatty acid profiles were chemically analyzed in only 7 studies and estimated from nutrition databases in 17; the crossover SD correlation coefficient was assumed to be 0.5; half of trials took place in North America, limiting diversity; and phytosterol composition was reported for only a few trials.
- The paper also states substantial heterogeneity (I² ≥50%) across analyses, inability to assess SFA type because it was inconsistently reported, baseline LDL cholesterol varied from 94–184 mg/dL, and study-level subgroup analyses are prone to ecologic bias.
- Evident from the text: 17 trials had some concerns in ≥1 risk-of-bias domain and 1 trial had high risk of bias; certainty was downgraded for risk of bias, inconsistency, and publication bias, and some included trials enrolled adults with hypercholesterolemia, hyperlipidemia, or CVD risk factors, which may limit generalizability to all generally healthy adults.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
13 of 35 cited sources checked · 8 supported · 0 flagged · accuracy not yet measured
- Premisecitation
SFA raises LDL cholesterol by reducing hepatic LDL receptor activity.
“SFA raises LDL cholesterol by reducing hepatic LDL receptor activity”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [6] Fernandez M.L. West K.L. Mechanisms by which dietary fatty acids modulate plasma lipids J. Nutr. 135 9 2005 2075 2078 16140878 source
- cites [7] Bennett A.J. Billett M.A. Salter A.M. Mangiapane E.H. Bruce J.S. Anderton K.L. Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and triolein Biochem. J. 311 Pt 1 1995 167 173 Pt 1 7575449 PMC1136134 source
The Discussion reports that trimyristin and tripalmitin lowered hepatic LDL receptor mRNA in hamsters and suggests that reduced receptor synthesis might explain their higher LDL cholesterol. It did not measure receptor activity in this study or establish that mechanism as causal. The Introduction also notes that saturated fatty acids differ in their effects, so the claim is too broad for SFA as a whole. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
PUFA lowers LDL cholesterol by increasing hepatic LDL receptor activity via decreased receptor turnover and increased receptor synthesis.
“PUFA lowers LDL cholesterol by increasing hepatic LDL receptor activity via decreased receptor turnover and increased receptor synthesis [6,7].”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [6] Fernandez M.L. West K.L. Mechanisms by which dietary fatty acids modulate plasma lipids J. Nutr. 135 9 2005 2075 2078 16140878 source
The “Fat saturation and cholesterol synthesis” section says PUFA-associated LDL-C lowering is likely due in part to LDL-receptor upregulation. “Fat saturation and LDL receptors” reports increased receptor levels and mRNA with PUFA intake and suggests an effect on receptor synthesis, but does not establish increased synthesis as the mechanism or mention decreased receptor turnover. Page numbers are unavailable in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [7] Bennett A.J. Billett M.A. Salter A.M. Mangiapane E.H. Bruce J.S. Anderton K.L. Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and triolein Biochem. J. 311 Pt 1 1995 167 173 Pt 1 7575449 PMC1136134 source
The Introduction (page unavailable) says LDL cholesterol is higher with certain saturated-fat diets than with unsaturated-fat diets. The Discussion (page unavailable) links the higher LDL in hamsters fed trimyristin or tripalmitin to potentially decreased LDL receptor synthesis. It does not establish that PUFA lowers LDL through increased receptor synthesis or decreased receptor turnover. (LLM, conf=0.76)
Experimental — accuracy not yet measured
- Premisecitation
Lipids and lipoproteins stabilize within 3 weeks.
“For inclusion, trials had to have an intervention period of ≥3 wk because lipids/lipoproteins stabilize within this time period [20].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [20] Kris-Etherton P.M. Dietschy J. Design criteria for studies examining individual fatty acid effects on cardiovascular disease risk factors: human and animal studies Am. J. Clin, Nutr. 65 5 Suppl 1997 1590s 1596s 9129499 source
- Premisecitation
PUFA and SFA have opposing actions on hepatic LDL receptors and therefore on LDL cholesterol.
“PUFA and SFA have opposing actions on hepatic LDL receptors and, therefore, LDL cholesterol [6,7].”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [6] Fernandez M.L. West K.L. Mechanisms by which dietary fatty acids modulate plasma lipids J. Nutr. 135 9 2005 2075 2078 16140878 source
- cites [7] Bennett A.J. Billett M.A. Salter A.M. Mangiapane E.H. Bruce J.S. Anderton K.L. Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and triolein Biochem. J. 311 Pt 1 1995 167 173 Pt 1 7575449 PMC1136134 source
The Results and Discussion (page unavailable) report that, in hamsters, trimyristin and tripalmitin lowered hepatic LDL-receptor mRNA relative to triolein and raised LDL cholesterol. The paper does not test PUFA effects on hepatic LDL receptors: triolein supplies oleate, a monounsaturated fatty acid. It therefore supports the SFA finding, but not the claimed opposing receptor actions of PUFA and SFA. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Premisecitation
Replacement of 5% of energy from SFA with PUFA is associated with a 25% lower risk of coronary artery disease.
“Replacement of 5% of energy from SFA with PUFA is associated with a 25% lower risk of coronary artery disease [10].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [10] Li Y. Hruby A. Bernstein A.M. Ley S.H. Wang D.D. Chiuve S.E. Saturated fats compared with unsaturated fats and sources of carbohydrates in relation to risk of coronary heart disease: a prospective cohort study J. Am. Coll. Cardiol. 66 14 2015 1538 1548 26429077 PMC4593072 source
- Premisecitation
Adults with elevated cholesterol exhibit larger cholesterol reductions in response to targeted dietary intervention.
“Evidence supports that adults with elevated cholesterol exhibit larger cholesterol reductions in response to targeted dietary intervention [51,52].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [51] Ros E. Health benefits of nut consumption Nutrients 2 7 2010 652 682 22254047 PMC3257681 source
Section 4.1 reports that cholesterol lowering from nut consumption was greater among participants with higher initial LDL-cholesterol. This supports the baseline-cholesterol comparison, but the evidence concerns nut feeding specifically, not targeted dietary interventions generally. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [52] Sabaté J. Oda K. Ros E. Nut consumption and blood lipid levels: a pooled analysis of 25 intervention trials Arch. Intern. Med. 170 9 2010 821 827 20458092 source
- Findingown data
The lower P:S ratio diets had a median P:S ratio of 0.4 (total fat 34.5%; PUFA 4.4% kcal; SFA 12.5% kcal; MUFA 14.6%; carbohydrates 50.0% kcal; and protein 15.5% kcal).
“and the lower P:S ratio diets had a median P:S ratio of 0.4 (total fat 34.5%; PUFA 4.4% kcal; SFA 12.5% kcal; MUFA 14.6%; carbohydrates 50.0% kcal; and protein 15.5% kcal).”
Quote in the paperNot a substantial claim - Findingown data
Heterogeneity in the P:S ratio effect was not observed by mean baseline LDL cholesterol (P = 0.49).
“nor by mean baseline LDL cholesterol (P = 0.49) (Supplemental Figure 4).”
Quote in the paperNot a substantial claim - Findingown data
Heterogeneity (I2 = 86.6%, P = 0.0006) in the effect of the P:S ratio on LDL cholesterol was observed according to whether the intervention and comparator diets met the dietary guidelines for limiting SFA intake (<10% of kcal).
“However, heterogeneity (I2 = 86.6%, P = 0.0006) in the effect of the P:S ratio on LDL cholesterol was observed according to whether the intervention and comparator diets met the dietary guidelines for limiting SFA intake (<10% of kcal) (Figure 4).”
Quote in the paperSubstantial claim - Findingown data
Twenty-four publications reporting 24 trials (n = 1011) were eligible.
“In total, 1001 publications were identified, and 24 publications reporting 24 trials (n = 1011) were eligible.”
Quote in the paperSubstantial claim - Findingown data
When test diets were SFA-matched, higher compared to lower P:S ratio diets did not lower LDL cholesterol (MD −3.45 mg/dL; 95% CI: −7.88, 0.98; I2 = 70%).
“but not when diets were SFA-matched (MD −3.45 mg/dL; 95% CI: −7.88, 0.98; I2 = 70%).”
Quote in the paperSubstantial claim - Findingown data
In subgroup analysis, diets that differed in SFA (≥2% of kcal; k = 14; WMD, −15.72 mg/dL; 95% CI: −20.51, −10.92; I2 = 68%) had greater LDL cholesterol lowering than trials in which the diets were matched for SFA (k = 10; WMD, −3.45 mg/dL; 95% CI: −7.88, 0.98; I2 = 70%) (P < 0.001).
“Subgroup analysis showed that when comparing diets with a higher to lower P:S ratio, diets that differed in SFA (≥2% of kcal; k = 14; WMD, −15.72 mg/dL; 95% CI: −20.51, −10.92; I2 = 68%) had greater LDL cholesterol lowering compared with trials in which the diets were matched for SFA (k = 10; WMD, −3.45 mg/dL; 95% CI: −7.88, 0.98; I2 = 70%) (P < 0.001) (Figure 3).”
- Also stated in: § Discussion · plain
“A higher dietary P:S ratio was associated with a greater reduction in LDL cholesterol when the test diets differed in SFA compared with when the test diets were matched for SFA.”
- Also stated in: § Discussion · plain
“In contrast, when the diets were matched for SFA and differed in PUFA and MUFA, no difference in LDL cholesterol was observed between diets with a higher compared to lower P:S ratio.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The phytosterol composition of the test diets did not differ between diets.
- Also stated in: § Discussion · plain
- Findingown data
The higher P:S ratio diets had a median P:S ratio of 1.2 (total fat 34.5% kcal; PUFA 10.6% kcal; SFA 8.0% kcal; MUFA 12.6% kcal; carbohydrates 50.2% kcal; and protein 15.6% kcal).
“The higher P:S ratio diets had a median P:S ratio of 1.2 (total fat 34.5% kcal; PUFA 10.6% kcal; SFA 8.0% kcal; MUFA 12.6% kcal; carbohydrates 50.2% kcal; and protein 15.6% kcal)”
Quote in the paperNot a substantial claim - Findingown data
When test diets differed in SFA (≥2% kcal), higher compared to lower P:S ratio diets lowered LDL cholesterol (MD −15.72 mg/dL; 95% CI: −20.51, −10.92; I2 = 68%).
“Higher compared to lower P:S ratio diets lowered LDL cholesterol (MD −15.72 mg/dL; 95% CI: −20.51, −10.92; I2 = 68%) when the test diets differed in SFA (≥2% kcal)”
Quote in the paperSubstantial claim - Findingown data
Heterogeneity in the P:S ratio effect on LDL cholesterol was observed by the test diet SFA content (P < 0.001).
“Heterogeneity in the P:S ratio effect was observed by the test diet SFA content (P < 0.001).”
Quote in the paperSubstantial claim - Findingown data
Consumption of diets with a higher P:S ratio lowered LDL cholesterol concentration compared with diets with a lower P:S ratio in generally healthy adults (WMD, −9.83 mg/dL; 95% CI: −13.63, −6.04; I2 = 79%).
“Consumption of diets with a higher P:S ratio lowered LDL cholesterol concentration (WMD, −9.83 mg/dL; 95% CI: −13.63, −6.04; I2 = 79%) compared with diets with a lower P:S ratio (Figure 2).”
- Also stated in: § Discussion · plain
“This systematic review and meta-analysis of 24 controlled feeding trials (n =1011) showed that a higher dietary P:S ratio lowered LDL cholesterol concentrations to a greater extent than a lower dietary P:S ratio in generally healthy adults.”
- Also stated in: § Discussion · plain
“In conclusion, this systematic review and meta-analysis of 24 randomized controlled trials provides moderate quality evidence that diets with a higher P:S ratio lower LDL cholesterol to a greater extent than diets with a lower P:S ratio in generally healthy adults.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The phytosterol composition of the test diets did not differ between diets.
- Also stated in: § Discussion · plain
- Findingown data
Heterogeneity in the P:S ratio effect was not observed by mean baseline BMI of participants in the included trials (P = 0.80).
“Heterogeneity in the P:S ratio effect was not observed by mean baseline BMI of participants in the included trials (P = 0.80) (Supplemental Figure 3)”
Quote in the paperNot a substantial claim - Findingcitation
Across all analyses conducted, substantial heterogeneity (I2 = ≥50%) was observed.
“Across all analyses conducted, substantial heterogeneity (I2 = ≥50%) was observed and therefore the results should be interpreted with caution [50].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [50] Higgins J.P. Thompson S.G. Quantifying heterogeneity in a meta-analysis Stat. Med. 21 11 2002 1539 1558 12111919 source
- Findingown data
When the higher P:S ratio diet had <10% of kcal from SFA and the lower P:S ratio diet had ≥10% of kcal from SFA, greater LDL cholesterol lowering was observed (k = 11; WMD, −16.70 mg/dL; 95% CI: −22.10, −11.30; I2 = 75%) compared with when both higher and lower P:S ratio diets had <10% of kcal from SFA (k = 6; WMD, −6.31 mg/dL; 95% CI: −10.03, −2.59; I2 = 28%).
“When the higher P:S ratio diet had <10% of kcal from SFA and the lower P:S ratio diet had ≥10% of kcal from SFA greater LDL cholesterol lowering (k = 11; WMD, −16.70 mg/dL; 95% CI: −22.10, −11.30; I2 = 75%) was observed compared with when both higher and lower P:S ratio diets had <10% of kcal from SFA (k = 6; WMD, −6.31 mg/dL; 95% CI: −10.03, −2.59; I2 = 28%).”
- Also stated in: § Discussion · plain
“Findings showed that greater LDL cholesterol-lowering occurred when diets had a higher P:S ratio and an SFA content <10% kcal compared with a lower P:S ratio and an SFA content ≥10%.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The phytosterol composition of the test diets did not differ between diets.
- Also stated in: § Discussion · plain
- Findingown data
There was no between-diet difference in LDL cholesterol for trials where both the higher and lower P:S ratio diets had ≥10% of kcal from SFA (k = 7; WMD, −1.32 mg/dL; 95% CI: −7.75, 5.10; I2 = 63%).
“However, there was no between-diet difference in LDL cholesterol for trials where both the higher and lower P:S ratio diets had ≥10% of kcal from SFA (k = 7; WMD, –1.32 mg/dL; 95% CI: −7.75, 5.10; I2 = 63%).”
- Also stated in: § Discussion · plain
“Furthermore, when both diets had ≥10% kcal from SFA, no difference in LDL cholesterol was observed between diets with a higher compared to lower dietary P:S ratio.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The phytosterol composition of the test diets did not differ between diets.
- Also stated in: § Discussion · plain
- Findingown data
When both higher and lower P:S ratio diets had <10% of kcal from SFA, greater LDL cholesterol lowering was observed with the higher compared with the lower P:S ratio diet (k = 6; WMD, −6.31 mg/dL; 95% CI: −10.03, −2.59; I2 = 28%).
“when both higher and lower P:S ratio diets had <10% of kcal from SFA (k = 6; WMD, −6.31 mg/dL; 95% CI: −10.03, −2.59; I2 = 28%).”
- Also stated in: § Discussion · plain
“Interestingly, when both diets had <10% kcal from SFA and an approximately matched SFA content, greater LDL cholesterol lowering was observed with a higher compared with lower dietary P:S ratio.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The phytosterol composition of the test diets did not differ between diets.
- Also stated in: § Discussion · plain
- Study design and conductown data
For all trials, risk of bias from outcome assessment methods was low.
“for all trials, there was a low risk of bias from outcome assessment methods.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The dietary ratio of PUFA to SFA (P:S) may be a better indicator of LDL cholesterol concentration than SFA intake alone.
“Therefore, the dietary ratio of PUFA to SFA (P:S) may be a better indicator of LDL cholesterol concentration than SFA intake alone.”
Quote in the paperSubstantial claim - Interpretationreasoning
The P:S ratio may assist in predicting or estimating diet-induced LDL cholesterol responses, in addition to dietary fatty acid composition.
“Use of the P:S ratio in addition to dietary fatty acid composition may assist in predicting diet-induced LDL cholesterol responses.”
- Also stated in: § Conclusions · hedged
“Thus, the P:S ratio may assist in estimating the effect of dietary intake on LDL cholesterol.”
Quote in the paperSubstantial claim - Also stated in: § Conclusions · hedged
- Premisecitation
PUFA improves cell membrane fluidity to enhance the binding capacity of LDL to receptors.
“Additionally, PUFA improves cell membrane fluidity to enhance the binding capacity of LDL to receptors [8].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8] Feingold K.R. Feingold K. Ahmed S. Anawalt B. The effect of diet on cardiovascular disease and lipid and lipoprotein levels 2000 MDText.com, Inc. South Dartmouth (MA) [Updated 2024 Mar 31] 33945244
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
Replacing 1% of energy from SFA with PUFA lowers LDL cholesterol by 2.1 mg/dL.
“replacing 1% of energy from SFA with PUFA lowers LDL cholesterol by 2.1 mg/dL”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Mensink R.P. Effects of saturated fatty acids on serum lipids and lipoproteins: a systematic review and regression analysis. [Internet] 2016 [cited XXX]. Available from
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationcitation
The effect of SFA on LDL cholesterol is twice as potent as PUFA.
“This suggests that the effect of SFA on LDL cholesterol is twice as potent as PUFA.”
Quote in the paperSubstantial claim - Study design and conductown data
Leave-one-out analyses showed that the WMD estimates from the primary analysis were unaffected after individual removal of each trial.
“Leave-one-out analyses showed that the WMD estimates from the primary analysis were unaffected after individual removal of each trial (Supplemental Table 3).”
Quote in the paperNot a substantial claim - Premisecitation
Replacing 1% of energy from PUFA with SFA increases LDL cholesterol by 2.2 mg/dL.
“replacing 1% of energy from PUFA with SFA increases LDL cholesterol by 2.2 mg/dL [11].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Mensink R.P. Effects of saturated fatty acids on serum lipids and lipoproteins: a systematic review and regression analysis. [Internet] 2016 [cited XXX]. Available from
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationown data
The effect of higher P:S ratio diets on LDL cholesterol was stronger when PUFA replaced SFA.
“Compared with lower P:S ratio diets, higher P:S ratio diets were associated with greater LDL cholesterol reductions in generally healthy adults, and this effect was stronger when PUFA replaced SFA.”
Quote in the paperSubstantial claim - Premisecitation
Predictive regression equations generally include regression coefficients showing that SFA increases LDL cholesterol twice as much as PUFA reduces LDL cholesterol.
“These equations generally include regression coefficients that show SFA increases LDL cholesterol twice as much as PUFA reduces LDL cholesterol [[12], [13], [14]].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [12] Yu S. Derr J. Etherton T.D. Kris-Etherton P.M. Plasma cholesterol-predictive equations demonstrate that stearic acid is neutral and monounsaturated fatty acids are hypocholesterolemic Am. J. Clin. Nutr. 61 5 1995 1129 1139 7733039 source
- cites [13] Hegsted D.M. Ausman L.M. Johnson J.A. Dallal G.E. Dietary fat and serum lipids: an evaluation of the experimental data Am. J. Clin. Nutr. 57 6 1993 875 883 8503356 source
- cites [14] Mensink R.P. Katan M.B. Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials Arterioscler. Thromb 12 8 1992 911 919 1386252 source
- Study design and conductnone given
For all crossover trials, risk of bias from carryover effects was low.
“For all the crossover trials, there was low risk of bias from carryover effects”
Quote in the paperNot a substantial claim - Interpretationreasoning
These findings support use of the P:S ratio in conjunction with dietary fatty acid composition as an indicator for diet-induced LDL cholesterol responses.
“These findings support use of the P:S ratio in conjunction with the dietary fatty acid composition as an indicator for diet-induced LDL cholesterol responses.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The phytosterol composition of the test diets did not differ between diets.
- Interpretationown data
The finding of greater LDL cholesterol lowering when both diets had <10% kcal from SFA does not align with the subgroup analysis showing the P:S ratio does not predict LDL cholesterol response when SFA is matched.
“This finding does not align with results from the subgroup analysis showing the P:S ratio does not predict LDL cholesterol response when SFA is matched.”
Quote in the paperNot a substantial claim- Rests on an assumption: Study-level subgroup analyses are prone to ecologic bias.
- Interpretationown data
The dietary P:S ratio is only a predictor of LDL cholesterol response under conditions where SFA is replaced by PUFA.
“This suggests that the dietary P:S ratio is only a predictor of LDL cholesterol response under conditions where SFA is replaced by PUFA.”
- Also stated in: § Discussion · hedged
“However, the capacity for the dietary P:S ratio to predict LDL cholesterol responses appears to be driven by the extent to which the P:S ratio difference between 2 test diets reflects SFA replacement with PUFA.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The phytosterol composition of the test diets did not differ between diets.
- Also stated in: § Discussion · hedged
- Premisecitation
PUFA and SFA exert opposing effects on LDL cholesterol.
“given that PUFA and SFA exert opposing effects on LDL cholesterol [11].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Mensink R.P. Effects of saturated fatty acids on serum lipids and lipoproteins: a systematic review and regression analysis. [Internet] 2016 [cited XXX]. Available from
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationown data
The P:S ratio had the greatest utility when the higher P:S ratio diets were lower in SFA and higher in PUFA than the lower P:S ratio diets.
“Specifically, findings from our subgroup analysis showed that the P:S ratio had the greatest utility when the higher P:S ratio diets were lower in SFA and higher in PUFA than the lower P:S ratio diets.”
Quote in the paperSubstantial claim - Premisecitation
Substitution of MUFA for PUFA has minimal effect on LDL cholesterol.
“Although limited research has investigated substitution of MUFA for PUFA, available data suggest minimal effect on LDL cholesterol [48,49,].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [48,49,]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning
In the 24 included trials, the types of SFAs included in the test diets varied, likely contributing to between-trial variation in LDL cholesterol responses.
“In the 24 included trials, the types of SFAs included in the test diets varied, likely contributing to between-trial variation in LDL cholesterol responses.”
Quote in the paperSubstantial claim - Premisecitation
Replacement of SFA with PUFA lowers LDL cholesterol.
“This aligns with prior research showing that replacement of SFA with PUFA lowers LDL cholesterol [11].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Mensink R.P. Effects of saturated fatty acids on serum lipids and lipoproteins: a systematic review and regression analysis. [Internet] 2016 [cited XXX]. Available from
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Study design and conductown data
A limitation of this meta-analysis is that the fatty acid profile of the test diets was chemically analyzed in only 7 studies and was estimated from various nutrition databases in 17 studies, which may introduce variability and estimation error.
“A limitation of this meta-analysis is that the fatty acid profile of the test diets was chemically analyzed in only 7 studies and was estimated from various nutrition databases in 17 studies, which may introduce variability and estimation error.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Consideration of the P:S ratio in addition to dietary fatty acid composition may assist in predicting diet-induced LDL cholesterol responses.
“These findings suggest that consideration of the P:S ratio in addition to dietary fatty acid composition may assist in predicting diet-induced LDL cholesterol responses.”
Quote in the paperSubstantial claim - Interpretationown data
The magnitude of LDL cholesterol lowering observed in response to a higher dietary P:S ratio is driven by the extent to which SFA is replaced with PUFA.
“The results of this meta-analysis support our hypothesis but also highlight that the magnitude of LDL cholesterol lowering observed in response to a higher dietary P:S ratio is driven by the extent to which SFA is replaced with PUFA.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The phytosterol composition of the test diets did not differ between diets.
- May combine two claims. 17
- Classified as probably not a substantial claim. 19
- The quote only partly states this claim. 1
May combine two claims.
FindingcitationAmong the 24 included trials, only 6 trials required participants to have an elevated LDL cholesterol; the remaining 18 trials included participants with normal and elevated LDL cholesterol.
“Among the 24 included trials, only 6 trials required participants to have an elevated LDL cholesterol [25,30,33,37,39,47]; the remaining 18 trials included participants with normal and elevated LDL cholesterol.”
Quote in the paperNot a substantial claim2 of 6 sources checked- cites [25] Binkoski A.E. Kris-Etherton P.M. Wilson T.A. Mountain M.L. Nicolosi R.J. Balance of unsaturated fatty acids is important to a cholesterol-lowering diet: comparison of mid-oleic sunflower oil and olive oil on cardiovascular disease risk factors J. Am. Diet. Assoc. 105 7 2005 1080 1086 15983524 source
- cites [30] Gillingham L.G. Gustafson J.A. Han S.Y. Jassal D.S. Jones P.J. High-oleic rapeseed (canola) and flaxseed oils modulate serum lipids and inflammatory biomarkers in hypercholesterolaemic subjects Br. J. Nutr. 105 3 2011 417 427 20875216 source
- cites [33] Howard B.V. Hannah J.S. Heiser C.C. Jablonski K.A. Paidi M.C. Alarif L. Polyunsaturated fatty acids result in greater cholesterol lowering and less triacylglycerol elevation than do monounsaturated fatty acids in a dose-response comparison in a multiracial study group Am. J. Clin. Nutr. 62 2 1995 392 402 7625348 source
- cites [37] Lichtenstein A.H. Matthan N.R. Jalbert S.M. Resteghini N.A. Schaefer E.J. Ausman L.M. Novel soybean oils with different fatty acid profiles alter cardiovascular disease risk factors in moderately hyperlipidemic subjects Am. J. Clin. Nutr. 84 3 2006 497 504 16960162 source
- cites [39] Meng H. Matthan N.R. Wu D. Li L. Rodríguez-Morató J. Cohen R. Comparison of diets enriched in stearic, oleic, and palmitic acids on inflammation, immune response, cardiometabolic risk factors, and fecal bile acid concentrations in mildly hypercholesterolemic postmenopausal women-randomized crossover trial Am. J. Clin. Nutr. 110 2 2019 305 315 31179489 source
- cites [47] Vega-Lopez S. Ausman L.M. Jalbert S.M. Erkkila A.T. Lichtenstein A.H. Palm and partially hydrogenated soybean oils adversely alter lipoprotein profiles compared with soybean and canola oils in moderately hyperlipidemic subjects Am. J. Clin. Nutr. 84 1 2006 54 62 16825681 source
May combine two claims.
PremisecitationLauric, myristic, and palmitic acids raise LDL cholesterol, while stearic acid has a neutral effect.
“Although lauric, myristic, and palmitic acids raise LDL cholesterol, stearic acid has a neutral effect [9].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [9] Sacks F.M. Lichtenstein A.H. Wu J.H.Y. Appel L.J. Creager M.A. Kris-Etherton P.M. Dietary fats and cardiovascular disease: a presidential advisory from the American Heart Association Circulation 136 3 2017 e1 e23 28620111 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSFAs exert different effects on LDL cholesterol based on their fatty acid chain length.
“SFAs exert different effects on LDL cholesterol based on their fatty acid chain length [9].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [9] Sacks F.M. Lichtenstein A.H. Wu J.H.Y. Appel L.J. Creager M.A. Kris-Etherton P.M. Dietary fats and cardiovascular disease: a presidential advisory from the American Heart Association Circulation 136 3 2017 e1 e23 28620111 source
May combine two claims.
Findingown dataOverall, 23 crossover randomized clinical trials and 1 parallel randomized clinical trial were included, with a median study duration of 28 d (range: 21-42 d).
“Overall, 23 crossover randomized clinical trials and 1 parallel randomized clinical trial were included with a median study duration of 28 d (range: 21–42 d).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataThe 24 included papers were published between 1985 and 2024 and reported on 24 clinical trials.
“The 24 papers were published between 1985 and 2024 and reported on 24 clinical trials (Table 2)”
Quote in the paperNot a substantial claimThe quote only partly states this claim.
Findingown dataHigher P:S ratio diets lowered LDL cholesterol compared with lower P:S ratio diets in generally healthy adults (MD −9.83 mg/dL; 95% CI: −13.63, −6.04; I2 = 79%).
“Higher P:S ratio diets (median P:S ratio 1.2; PUFA 10.6% kcal; SFA 8.0% kcal; and MUFA 12.6% kcal) lowered LDL cholesterol [MD −9.83 mg/dL; 95% confidence interval (CI): −13.63, −6.04; I2 = 79%] compared with lower P:S ratio diets”
- Also stated in: § Conclusions · plain
“A higher dietary P:S ratio lowers LDL cholesterol compared to a lower dietary P:S ratio.”
Quote in the paperSubstantial claim- Also stated in: § Conclusions · plain
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataA total of 1011 participants were included, with median percent males 47% (range: 0-100%) and median age 44 y.
“A total of 1011 participants (median percent males: 47%; range: 0–100%) were included in the trials with a median age of 44 y.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataThe search strategy identified 1017 publications, of which 1001 were eligible for title and abstract screening after removal of duplicates.
“The search strategy identified a total of 1017 publications, of which 1001 were eligible for title and abstract screening after removal of duplicates (Figure 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe certainty of evidence for the effect of the P:S ratio on LDL cholesterol was rated moderate because of serious concerns for risk of bias, inconsistency, and publication bias, with no serious concerns for imprecision and indirectness, and was upgraded for detecting a moderate effect size.
“The certainty of evidence of the effect of the P:S ratio on LDL cholesterol concentration was rated as moderate because of serious concerns for risk of bias, inconsistency, and presence of publication bias (Supplemental Figure 1); however, there were no serious concerns with imprecision and indirectness, and the evidence rating was upgraded for detecting a moderate effect size (Supplemental Table”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataIn 6 trials, risk of bias due to deviations from the intended intervention was unclear, in 1 trial it was high, and in 17 trials it was low.
“In 6 trials, the risk of bias because of deviations from the intended intervention was unclear, in 1 trial it was high, and in 17 trials it was low.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataA sensitivity analysis using a correlation coefficient of 0.6 to calculate the SD of the WMD for crossover studies showed a similar effect to the primary analysis.
“A sensitivity analysis using a correlation coefficient of 0.6 to calculate the SD of the WMD for crossover studies showed a similar effect (Supplemental Figure 2).”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationSFA decreases the formation of cholesterol esters, increasing free cholesterol, thus inhibiting activation of sterol receptor binding protein, which is necessary to increase LDL receptor expression.
“SFA decreases the formation of cholesterol esters, increasing free cholesterol, thus inhibiting the activation of sterol receptor binding protein, which is necessary to increase LDL receptor expression [8].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Feingold K.R. Feingold K. Ahmed S. Anawalt B. The effect of diet on cardiovascular disease and lipid and lipoprotein levels 2000 MDText.com, Inc. South Dartmouth (MA) [Updated 2024 Mar 31] 33945244
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataIn 2 trials, risk of bias from missing outcome data was unclear, and in the remaining 22 trials it was low.
“In 2 trials, the risk of bias from missing outcome data was unclear, and in the remaining 22 trials, it was low.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationThe systematic review and meta-analysis were conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions.
“A systematic review and meta-analysis were conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions [19] to examine LDL cholesterol responses to diets with a higher P:S ratio compared to isoenergetic, total fat-matched diets with a lower P:S ratio in generally healthy adults, who were free of chronic disease.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions Chichester, UK: Cochrane Training; 2024 [Available from: https://training.cochrane.org/handbook/current] accessed 13 December 2024.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
PremisecitationPUFA increases cholesterol ester formation, reducing free cholesterol and upregulating LDL receptor expression.
“Conversely, PUFA increases cholesterol ester formation, reducing free cholesterol and upregulating LDL receptor expression [8].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Feingold K.R. Feingold K. Ahmed S. Anawalt B. The effect of diet on cardiovascular disease and lipid and lipoprotein levels 2000 MDText.com, Inc. South Dartmouth (MA) [Updated 2024 Mar 31] 33945244
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Classified as probably not a substantial claim.
Study design and conductcitationRisk of bias was independently assessed by at least two authors using the Cochrane Risk of Bias Tool for each publication.
“Risk of bias was independently assessed by ≥2 authors (TLH, ZSD, KET, FJ, and JJD) using the Cochrane Risk of Bias Tool for each publication [19].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions Chichester, UK: Cochrane Training; 2024 [Available from: https://training.cochrane.org/handbook/current] accessed 13 December 2024.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Classified as probably not a substantial claim.
Study design and conductcitationThe GRADE tool was used to investigate the certainty of evidence of the effect of the P:S ratio on LDL cholesterol concentration.
“The Grading of Recommendations Assessment, Development and Evaluation tool [22] was used to investigate the certainty of evidence of the effect of the P:S ratio on LDL cholesterol concentration.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] Guyatt G. Oxman A.D. Akl E.A. Kunz R. Vist G. Brozek J. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables J. Clin. Epidemiol. 64 4 2011 383 394 21195583 source
May combine two claims.
Study design and conductown dataAmong the 24 included trials, 6 had low overall risk of bias, 17 had some concerns in at least one domain, and 1 had high risk of bias.
“Six of the 24 trials had low risk of bias, 17 trials had some concerns in ≥1 domain, and 1 trial had high risk of bias (Figure 2).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe systematic review was prospectively registered at PROSPERO (CRD42023452550).
“This systematic review was prospectively registered at the Prospective Register of Systematic Reviews (PROSPERO ID: CRD42023452550).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataIn 1 trial, risk of bias from selection of the reported results was unclear, and for 23 trials it was low.
“In 1 trial, the risk of bias from selection of the reported results was unclear, and for 23 trials, it was low.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataIn 12 trials, risk of bias from the randomization process was unclear, and in the remaining 12 trials it was low.
“In 12 trials, the risk of bias from the randomization process was unclear, and in the remaining 12 trials, it was low.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe correlation coefficient used to calculate the standard deviation of the WMD for crossover trials was assumed to be 0.5.
“the correlation coefficient used to calculate the standard deviation of the WMD for crossover trials was assumed to be 0.5”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoningA strength of this systematic review and meta-analysis was the inclusion of only controlled feeding randomized clinical trials, which ensures that participants received diets with the target macronutrient profile.
“A strength of this systematic review and meta-analysis was the inclusion of only controlled feeding randomized clinical trials, which ensures that participants received diets with the target macronutrient profile.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationThe 2020-2025 Dietary Guidelines for Americans recommend limiting intake of SFA to <10% kcal.
“based on whether the test diets met the 2020–2025 Dietary Guidelines for Americans recommendation to limit intake of SFA to <10% kcal [5].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] U.S. Department of Agriculture and U.S. Department of Health and Human Services Dietary guidelines for americans 2020-2025
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Study design and conductown dataHalf of the included trials took place in North America, limiting diversity.
“half of the included trials took place in North America, limiting diversity.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningOther likely sources that contributed to high heterogeneity include baseline LDL cholesterol and the type of dietary SFA.
“Other likely sources that contributed to high heterogeneity include baseline LDL cholesterol and the type of dietary SFA.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataLDL cholesterol concentration varied substantially within included trials (means ranged from 94-184 mg/dL), which may have reduced the ability to detect baseline LDL cholesterol related effect modification.
“However, LDL cholesterol concentration varied substantially within included trials (means ranged from 94–184 mg/dL), which may have reduced our ability to detect baseline LDL cholesterol related effect modification.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe phytosterol composition of the test diets was only reported for a few trials.
“Lastly, the phytosterol composition of the test diets was only reported for a few trials.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe authors were unable to assess whether the type of SFAs included in the test diets contributed to the observed heterogeneity because this information was not consistently reported in the included publications.
“We were unable to assess whether the type of SFAs included in the test diets contributed to the observed heterogeneity because this information was not consistently reported in the included publications.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
InterpretationcitationOur findings are consistent with current dietary recommendations to reduce SFA and replace SFA with PUFA.
“Our findings are consistent with current dietary recommendations to reduce SFA and replace SFA with PUFA [5] and support the use of the P:S ratio as an indicator for LDL cholesterol responses when SFA is replaced with PUFA.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] U.S. Department of Agriculture and U.S. Department of Health and Human Services Dietary guidelines for americans 2020-2025
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
The paper relies on this without support.
No recent research has evaluated the dietary P:S ratio as an indicator for LDL cholesterol response.
“However, no recent research has evaluated the dietary P:S ratio as an indicator for LDL cholesterol response.”
The authors state this as an assumption.
The correlation between LDL cholesterol following higher and lower P:S ratio diets is 0.5 for crossover studies.
“Therefore, the SD of the MD was calculated using a correlation coefficient of 0.5.”
The authors state this as an assumption.
The phytosterol composition of the test diets did not differ between diets.
“Although we do not expect that the phytosterol composition differed between diets, any differences may confound the LDL cholesterol response.”
The paper relies on this without support.
Study-level subgroup analyses are prone to ecologic bias.
“However, cautious interpretation is warranted given that study-level subgroup analyses are prone to ecologic bias.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Howard trial's reported LDL change does not match its endpoints
MinorFor the higher-P:S diet, an endpoint of 15 mg/dL minus a baseline of 164 mg/dL gives −149 mg/dL, not the reported −8 mg/dL.
Reported -8 · recomputed -149
“Howard 1995 [33] | CO | Adults with LDL cholesterol 132–190 mg/dL n = 63M: 47.6%Age: 46 ± 10 yBMI: 26 ± 4 kg/m2 | 42 | CHO: 56 Protein: 17 Fat: 27 | SFA: 8.5 MUFA: 14.8 PUFA: 3.2 | 0.38 | 164 ± 27.1 | 160 ± 29.0 | −4 | CHO: 56 Protein: 17 Fat: 27 | SFA: 9.9 MUFA: 5.9 PUFA: 13.0 | 1.31 | 164 ± 27.1 | 15 ± 24.0 | −8 |”
Atherosclerosis trial conflicts with the stated exclusion criterion
MinorThe eligibility criteria exclude adults with chronic diseases such as CVD, but Table 2 includes a trial described as enrolling adults with atherosclerosis.
“Trials including adults with chronic diseases that may affect lipoprotein metabolism were excluded (e.g., diabetes, CVD, and kidney disease).”
“Gustafsson 1985 [32] | CO | Adults with hyperlipidemia, atherosclerosis, or both n = 14M: 43%Age: 50–65 yBMI: NR”
Two different counts of publications identified
MinorThe abstract says 1001 publications were identified, whereas the Results say 1017 were identified and 1001 remained after duplicates were removed.
“In total, 1001 publications were identified, and 24 publications reporting 24 trials (n = 1011) were eligible.”
“The search strategy identified a total of 1017 publications, of which 1001 were eligible for title and abstract screening after removal of duplicates (Figure 1).”
Claim of substantial heterogeneity across all analyses conflicts with a subgroup result
MinorThe Discussion says I2 was at least 50% across all analyses, but the subgroup where both diets had less than 10% of kcal from SFA reports I2 = 28%.
“Across all analyses conducted, substantial heterogeneity (I2 = ≥50%) was observed and therefore the results should be interpreted with caution [50].”
“both higher and lower P:S ratio diets had <10% of kcal from SFA (k = 6; WMD, −6.31 mg/dL; 95% CI: −10.03, −2.59; I2 = 28%).”
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“The 24 papers were published between 1985 and 2024 and reported on 24 clinical trials (Table 2) [ 25 –”
Forsythe, C. E., Phinney, S. D., Feinman, R. D., Volk, B. M., Freidenreich, D. J., Quann, E. E., Ballard, K. D., Puglisi, M. J., Maresh, C. M., Kraemer, W. J., et al. (2010) · Lipids · doi:10.1007/s11745-010-3467-3 · Cited by 90 · see citing works
Howard, B., Hannah, J., Heiser, C., Jablonski, K., Paidi, M., Alarif, L., Robbins, D., & Howard, W. (1995) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/62.2.392 · Cited by 86 · cited 1× · see citing works
“Among the 24 included trials, only 6 trials required participants to have an elevated LDL cholesterol [25,30,33,37, 39,47]; the remaining 18 trials included participants with normal and elevated LDL cholesterol.”
Iggman, D., Gustafsson, I., Berglund, L., Vessby, B., Marckmann, P., & Risérus, U. (2011) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2011.02383.x · Cited by 82 · see citing works
Bowen, K. J., Kris‐Etherton, P. M., West, S. G., Fleming, J. A., Connelly, P. W., Lamarche, B., Couture, P., Jenkins, D. J. A., Taylor, C. G., Zahradka, P. C., et al. (2018) · Journal of Nutrition · doi:10.1093/jn/nxy307 · Cited by 76 · see citing works
Meng, H., Matthan, N. R., Wu, D., Li, L., Rodríguez-Morató, J., Cohen, R., Galluccio, J. M., Dolnikowski, G. G., & Lichtenstein, A. H. (2019) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz095 · Cited by 75 · cited 1× · see citing works
“Among the 24 included trials, only 6 trials required participants to have an elevated LDL cholesterol [25,30,33,37, 39,47]; the remaining 18 trials included participants with normal and elevated LDL cholesterol.”
Wahrburg, U., Martin, H., Sandkamp, M., Schulte, H., & Assmann, G. (1992) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/56.4.678 · Cited by 73 · see citing works
Maki, K. C., Lawless, A. L., Kelley, K., Kaden, V. N., Geiger, C. J., & Dicklin, M. R. (2014) · Journal of clinical lipidology · doi:10.1016/j.jacl.2014.10.006 · Cited by 63 · see citing works
The Effect of Dietary Fat on LDL Size Is Influenced by Apolipoprotein E Genotype in Healthy Subjects
Moreno, J. A., Pérez‐Jiménez, F., Marı́n, C., Gómez, P., Pérez‐Martínez, P., Moreno‐Luna, R., Bellido, C., Fuentes, F. J., & López‐Miranda, J. (2004) · Journal of Nutrition · doi:10.1093/jn/134.10.2517 · Cited by 57 · see citing works
Bennett, A. J., Billett, M. A., Salter, A. M., Mangiapane, E. H., Bruce, J. S., Anderton, K. L., Marenah, C. B., Lawson, N., & White, D. A. (1995) · Biochemical Journal · doi:10.1042/bj3110167 · Cited by 46 · cited 2× · see citing works
“SFA raises LDL cholesterol by reducing hepatic LDL receptor activity, whereas PUFA lowers LDL cholesterol by increasing hepatic LDL receptor activity via decreased receptor turnover and increased receptor synthesis [6,7].”
Goyens, P. L. L., & Mensink, R. P. (2005) · Journal of Nutrition · doi:10.1093/jn/135.12.2799 · Cited by 41 · see citing works
The Effect of Diet on Cardiovascular Disease and Lipid and Lipoprotein Levels
Feingold, K. R. (2021) · Europe PMC (PubMed Central) · Cited by 30 · see citing works
Poli, A., Catapano, A. L., Corsini, A., Manzato, E., Werba, J. P., Catena, G., Cetin, I., Cicero, A. F. G., Cignarella, A., Colivicchi, F., et al. (2022) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2022.10.001 · Cited by 27 · see citing works
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Desjardins, L.-C., Brière, F., Tremblay, A. J., Rancourt-Bouchard, M., Drouin‐Chartier, J., Corbeil, J., Lemelin, V., Charest, A., Schaefer, E. J., Lamarche, B., et al. (2024) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2024.03.015 · Cited by 15 · see citing works
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Some Thoughts Regarding the P:S Ratio Concept
Kinsell, L. W. (1963) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/12.3.228 · Cited by 9 · cited 1× · see citing works
“The dietary P:S ratio was commonly used from the 1960s to the early 2000s [15 – 18].”
Kinlay, S., Elliott, H., & Heller, R. F. (1997) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1997.136142000.x · Cited by 3 · see citing works
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Lange, E., & Pałkowska-Goździk, E. (2025) · Nutrients · doi:10.3390/nu17233789 · Cited by 3 · see citing works
“…a meta-analysis of 24 randomized trials (1011 participants) showed that a diet with a higher ratio of polyunsaturated to saturated fatty acids (median P:S ratio of 1.2) significantly lowered LDL cholesterol ( − 9.8 mg/dL) compared to a diet with a lower P:S ratio (median P:S ratio of 0.4) [18].”
InfluentialMuñoz, A. M., Anticona, M., Casimiro, S., et al. (2025) · Discover Food · doi:10.1007/s44187-025-00662-6 · Cited by 1 · see citing works
“A higher PUFA/SFA ratio is generally associated with beneficial effects, such as lower LDL cholesterol and a reduced risk of heart disease [51].”
Lim, C. J., Wong, J. Y., Leow, W. S. K., et al. (2025) · Journal of Animal Science · doi:10.1093/jas/skaf426 · Cited by 1 · see citing works
Influence of Season on Milk Lipid Indices in Simmental and Montbéliarde Cows in Bulgaria
Penev, T. G., Stancheva, E., Bachevska, G., et al. (2026) · Ruminants · doi:10.3390/ruminants6010008 · Cited by 1 · see citing works
“Higher UFA/SFA, PUFA/SFA, and MUFA/SFA ratios are considered beneficial for human health, as they reflect a greater proportion of unsaturated fatty acids relative to saturated fatty acids and are associated with improved lipid metabolism and a reduced risk of cardiovascular diseases [19].”
Pedersen, J., Sjælland, A., Kramme, F., Halkjær, J., Olsen, A., Dahm, C., Holven, K. B., Schmidt, E., Venø, S. K., & Bork, C. (2026) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2026.120685
Varzaru, I., Untea, A. E., Vlaicu, P. A., Oancea, A. G., & Turcu, R. P. (2026) · Antioxidants · doi:10.3390/antiox15030349
“Regarding the fatty acid composition of the analyzed fruits, data have shown that the PUFA/SFA ratio was significantly higher in rowanberry fruits (3.69) than in hawthorn fruits (2.91), indicating a more favorable lipid profile from a cardiovascular health perspective [41].”
InfluentialDiet Quality, Physical Activity, and Epigenetic Aging in the Finnish Working-Age Population
Ida, A., Aino, S., Marttila, S., Raitoharju, E., Mishra, P. P., Pahkala, K., Satu, M., Mononen, N., Kähönen, M. A. P., Fogelholm, M., et al. (2026) · Journal of Nutrition · doi:10.1016/j.tjnut.2026.101540
“Finally, the ratio of PUFAs to SFAs (P/S) can be considered a crucial dietary marker for cardiovascular and metabolic risks [59].”
Iordanishvili, S., Chiradze, N., Agladze, D., Kikvidze, M., Solomonia, R. O., & Lagani, V. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48060591
“The APOE -related findings are compatible with APOE ’s central role in lipoprotein clearance and with prior evidence that dietary fatty acid composition can influence LDL metabolism [37,38].”
Comparative Characterization of Ancient Wheat Cultivars Through Fatty Acid and Phytosterol Profiling
Crescente, G., Famiglietti, M., Siano, F., et al. (2026) · Foods · doi:10.3390/foods15122151
“In human nutrition, a PUFA/SFA ratio of at least 0.4 is commonly recommended, with values around 1.0–1.5 considered favourable for reducing cardiovascular risk, and higher PUFA/SFA ratios are associated with greater reductions in LDL cholesterol [27,28].”
InfluentialChemical and Functional Characterization of a Novel European Black Soybean Variety
Zdaniewicz, M., Lekowski, S., Mickowska, B., Kowalski, S., & Makarewicz, M. (2026) · Molecules · doi:10.3390/molecules31142417
“The lipid fraction is also nutritionally relevant because fats provide dietary energy, supply fatty acids, support the absorption of fat-soluble vitamins, and differ in their health effects depending on the proportions of saturated, monounsaturated, polyunsaturated, and trans fatty acids [15–19].”
Liikonen, V., Cera, S., Blontrock, E., Lu, J., Immonen, M., Partanen, R., Zehnder-Wyss, O., Courtin, C. M., Gómez-Gallego, C., Kaartinen, N. E., et al. (2026) · Clinical Nutrition · doi:10.1016/j.clnu.2026.106744
Aomori, M., & Maeda, H. (2026) · HIV Medicine · doi:10.1111/hiv.70298
Kapranova, L. L., Dikareva, J. D., Ryabushko, V. I., Kapranov, S. V., Kozintsev, A. F., Velyaev, Y. O., Kuznetsova, T. V., & Barinova, S. S. (2026) · Comparative Biochemistry and Physiology Part D Genomics and Proteomics · doi:10.1016/j.cbd.2026.102009
Odabaşıoğlu, M. İ., Çakır, A., Sanyürek, N. K., et al. (2026) · Molecules · doi:10.3390/molecules31183168
Laokuldilok, T., Klangpetch, W., Osiriphun, S., Kanha, N., Rakariyatham, K., Braspaiboon, S., & Jaisan, C. (2026) · Foods · doi:10.3390/foods15193444
“The PUFA/SFA ratio reflects the balance between fatty acids generally considered beneficial for cardiovascular health and those less desirable when consumed in excess [32].”
Plant-Based Fat Substitutes: From Structural Design to Application-Specific Performance
Men, S.-D., Xu, Y.-H., Liu, J.-W., Wang, Y., Yang, H., Zeng, X.-B., & Yu, H.-S. (2026) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2026.106123
- Authors
- Hart, T. L., Damani, J. J., DiMattia, Z. S., Tate, K. E., Jafari, F., & Petersen, K. S.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Petersen, Kristina S
- ORCID
- Venue
- Advances in Nutrition
- Publisher
- Elsevier BV
- Published
- 2025-10
- Volume
- 16
- Issue
- 10
- Pages
- 100502
- ISSN
- 2156-5376 (ISSN-L)
- 2161-8313
- PMC
- PMC12483678
- OpenAlex
- W4413801842
- Semantic Scholar
- a82a4778c8515ee119d603ab4500e3a99350f060
- Cited by
- 16
- References
- 46
- Citations by year
- 2026: 13 · 2025: 3
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Advances in Nutrition (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion, cc-by-nc-nd)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- National Heart Lung and Blood Institute (R01HL157535)
- Pennsylvania State University
- National Institutes of Health (1U01HL072510)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- polyunsaturated to saturated fatty acid ratio, LDL cholesterol, saturated fat, polyunsaturated fatty acids, dietary fat composition, isocaloric diet, monounsaturated fatty acids, dietary intervention
- MeSH terms
- Adult, Diet, Dietary Fats, Fatty Acids, Fatty Acids, Unsaturated, Female, Humans, Cholesterol, LDL, Male, Middle Aged, Randomized Controlled Trials as Topic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-19.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-19.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
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