Foods-Fortified-with-Soybean-or-Palm-Oil-Show-No-Effect-on-In_2026_Current-D.pdf

Nutritional biochemistry and physiologic mechanisms
Foods Fortified with Soybean or Palm Oil Show No Effect on 
Inflammation or Oxidized Low-Density Lipoprotein in Adults with 
Overweight or Obesity: a Secondary Analysis of a Randomized 
Placebo-Controlled Crossover Trial
Cheng-Tse Yang 1 , Rachel M Cole 1 , Eric Colombo 2 , Austin Angelotti 3 , Andy Ni 4 ,
Martha A Belury 1,*
1 Department of Food Science and Technology, The Ohio State University, Columbus, OH, United States; 2 Department of Nutrition Services, The 
Ohio State University Wexner Medical Center, The Ohio State University, Columbus, OH, United States; 3 Heart and Vascular Institute, Department 
of Medicine, College of Medicine, Penn State University, Hershey, PA, United States; 4 Division of Biostatistics, College of Public Health, The Ohio 
State University, Columbus, OH, United States
A B S T R A C T
Background: Popular and social media outlets have recent posts claiming that vegetable and seed oils high in linoleic acid (LA) cause 
inflammation and oxidative stress. However, substantial evidence in the scientific literature shows LA biomarkers are associated with lower 
risks for type 2 diabetes, cardiovascular disease, and systemic inflammation.
Objectives: The primary aim of this study is to evaluate the impact of dietary fortification with soybean oil (high in LA) compared with 
palm oil on markers of systemic inflammation and oxidized low-density lipoprotein (oxLDL) in healthy overweight adult participants. 
Methods: This double-masked crossover clinical trial consisted of 2 diet periods where adults with overweight or obesity were randomly 
assigned to receive 3 study foods delivering 30 g oil/d of either soybean or palm oil for 4-wk periods. During a 2-wk wash-out period, 
participants refrained from consuming study foods. Erythrocyte and plasma fatty acid composition, blood biomarkers of systemic 
inflammation and oxLDL, desaturase indices, and body weights were measured at each study visit.
Results: After 4 wk of consuming 30 g/d of soybean or palm oil snacks, most inflammatory markers and oxLDL remained unchanged. 
However, interleukin-6 showed a trend toward reduction in the soybean oil group (P = 0.09). Fatty acid analysis revealed that C20:4n–6 
(arachidonic acid) significantly decreased in erythrocytes after soybean oil intake (P = 0.0234), suggesting altered n–6 fatty acid meta-
bolism through δ-6 and δ-5 desaturases. There were no lingering treatment effects during the 2-week washout period between diet periods
1 and 2.
Conclusions: Incorporating study foods containing 30 g oil/d of soybean or palm oil had no significant impact on inflammatory markers, 
suggesting that higher LA intake is not proinflammatory as is stated in popular media outlets. In addition, a two week washout period may 
be sufficient for dietary oil interventions in crossover study designs.
This trial was registered at clinicaltrials.gov as NCT04975763.
Keywords: linoleic acid, soybean oil, inflammation, omega-6 fatty acids, seed oils, oxidized LDL, IL-6, arachidonic acid
Abbreviations: AA, arachidonic acid; ALA, α-linolenic acid; CRP, C-reactive protein; D5D, δ-5 desaturase; D6D, δ-6-desaturase; DBS, dried blood spots; LA, linoleic 
acid; LBP, LPS-binding protein; oxLDL, oxidized LDL; PBMC, peripheral blood mononuclear cells; RBC, red blood cells; SCD1, stearoyl-CoA desaturase-1; sCD14, 
soluble CD14.
* Corresponding author. E-mail address: belury.1@osu.edu (M.A. Belury).
journal homepage: https://cdn.nutrition.org/
https://doi.org/10.1016/j.cdnut.2025.107635
Received 2 September 2025; Received in revised form 19 December 2025; Accepted 30 December 2025; Available online 7 January 2026
2475-2991/© 2026 The Author(s). Published by Elsevier Inc. on behalf of American Society for Nutrition. This is an open access article under the CC BY-NC-ND 
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Current Developments in Nutrition 10 (2026) 107635
(arachidonic acid) dramatically decreased in erythrocytes after soybean oil intake (P 0.0234), suggesting altered fatty acid meta-
Introduction
Linoleic acid [LA; 18:2n–6], an essential fatty acid, is pri-
marily obtained from plant oils (such as sunflower, safflower, 
soybean, and corn) and nuts, and is recommended for health in 
most dietary guidelines [1,2]. LA plays essential roles in main-
taining skin barrier integrity, regulating inflammation, sup-
porting cardiometabolic health, and potentially influencing 
brain function [3]. LA intake is inversely associated with coro-
nary artery disease risk: higher dietary LA intake is related to 
reduced heart disease [2,4]. In addition, LA intake promotes 
insulin sensitivity and reduces the risk of hypertension [2]. 
Currently, the United States Adequate Intakes (AIs) for LA in 
adults are set at 11 to 12 g/d for females and 14 to 17 g/d for 
males, which corresponds to ~6% of daily energy intake [5]. 
However, many oils that were once high in LA have been 
replaced with oleic acid-rich alternatives, indicating that LA 
intake in the United States may be gradually declining [6]. 
Therefore, incorporating LA through sources like snack foods 
may be necessary to help maintain AI.
The metabolism of LA is well characterized and highly 
controlled through enzymatic regulation. LA is converted to 
γ-LA (GLA) by δ-6 desaturase (D6D), then elongated to dihomo-
GLA, and subsequently converted to arachidonic acid (AA) by 
δ-5 desaturase (D5D) [7]. AA serves as a precursor for various 
proinflammatory and anti-inflammatory and thrombogenic 
metabolites, including prostaglandins, thromboxanes, leukotri-
enes, and lipoxins, which act as signaling molecules to initiate 
and resolve the inflammatory process by modulating the pro-
duction of cytokines such as IL-6 [8,9]. Although AA plays a 
central role in inflammation, the conversion rate of LA to AA in 
plasma is extremely low, estimated at only ~0.2% [10]. 
Nevertheless, it is often claimed, without evidence, LA is directly 
converted into AA and thereby promotes inflammation [11]. 
Moreover, omega (ω)-6 fatty acids, particularly LA, have been 
hypothesized to play a role in initiating the formation of 
oxidized LDL (oxLDL) [12]. Therefore, some edible vegetable 
and seed oils rich in LA have recently come under public scru-
tiny, largely due to unsubstantiated claims circulating in print, 
televised, and social media regarding purported negative health 
effects. However, inflammation and oxidative stress have not 
been shown to increase with higher LA intake in clinical trials 
[13,14]. The primary objective of this study was to evaluate 
whether delivering 30 g/d of LA-rich soybean oil through snack 
foods influences biomarkers of inflammation and oxLDL. On the 
basis of prior randomized controlled trials [13,15], we hypoth-
esized that LA-enriched snacks using 30 g soybean oil/d would 
not promote inflammation.
Methods
Experimental design
This is a secondary study leveraging samples and data from 
our previous pilot study [16], which was a double-masked, 
randomized, placebo-controlled crossover trial involving 10 
adult participants. The study protocol was approved by the Ohio 
State University Institutional Review Board (IRB #2021H0232) 
and registered on clinicaltrials.gov (NCT04975763). Each 
participant was assigned to the 2 groups in random order in
blocks of 2 or 4 using a randomization scheme that was gener-
ated by a person outside of the study team. Participants were 
provided with study foods delivering 30 g/d of either soybean 
oil or palm oil. Palm oil was selected as a comparator because it 
is rich in SFA and MUFA and contains relatively little PUFA, in 
contrast to the PUFA-rich profile of soybean oil [17,18]. This 
distinction allows us to differentiate the effects of PUFA from 
those of saturated and monounsaturated fats. In addition, the 
mixed fatty acid profile of palm oil aligns with that of the typical 
United States adult diet [19]. Study visits were conducted at the 
beginning and end of each diet period. At the first study visit of 
each diet period, participants received their assigned study 
foods and then returned any uneaten portions at the ensuing 
visit. The detailed adherence results are reported in the primary 
manuscript [16]. A registered dietitian nutritionist met with 
participants at the study visit preceding each diet period to 
strategize how study foods could be incorporated into their 
habitual daily intake as parts of meals or snacks composed of 
similar foods. The goal of working with the dietitian was to 
minimize or prevent weight gain during the diet periods.
After completing a 2-wk run-in period, each diet period 
consisted of 4 wk interrupted by a 2-wk wash-out period. Blood 
samples were collected at each visit to analyze dried blood spots 
(DBS), peripheral blood mononuclear cells (PBMC), plasma, and 
red blood cells (RBC) fatty acid profile. In addition, the primary 
markers of this study were systemic inflammatory markers, 
including soluble CD14 (sCD14), IL-6, C-reactive protein (CRP), 
LPS-binding protein (LBP), and oxLDL, which were measured 
from these blood samples. Additional assessments, such as 
anthropometric measurements, were measured in every visit. 
Figure 1 illustrates the study design flowchart; Figure 2 presents 
the participant recruitment flowchart.
Participant characteristics
Eligible participants included males and females with over-
weight or obesity, and a BMI ranging from 25 to 55 kg/m 2 be-
tween ages 25 and 80 y. All participants were nonsmokers and 
were screened by self-report to exclude individuals with a cur-
rent or history of cardiovascular or renal disease, diabetes, and 
some hepatic and autoimmune diseases and current gastroin-
testinal diseases, cancer diagnosis, and food allergies, or those 
who were pregnant or lactating. Participants were instructed to 
abstain from the use of weight-loss supplements, medications 
contraindicated with the study foods (such as weight-loss drugs 
like Orlistat and Alli that may affect fat absorption), supple-
ments high in LA, and the consumption of alcohol or recrea-
tional drugs throughout the study period. The study included 10 
participants (4 males and 6 females), with a mean age of 47.0 ± 
17.3 y and a mean BMI of 33.4 ± 4.5 kg/m 2 . Detailed participant 
characteristics are provided in the primary manuscript [16].
Study foods consumption and dietary intake
Dietary intake was assessed using 24-h recalls via the ASA24 
tool, and physical activity via ACT24 and dietary recalls with 
daily intake >1000 kcal were included in the analysis. Study 
foods were prepared at 2 locations: a classroom kitchen in The 
Ohio State University campus and the Original Goodie Shop 
bakery. Participants selected from a variety of food items based 
on personal preference, including garlic spread, brownies, 
chocolate cookies, spice cookies, quick bread muffins, and yeast
C.-T. Yang et al.
Current Developments in Nutrition 10 (2026) 107635
2
bread rolls. Each serving of test foods contained 10 g of either 
soybean or palm oil, so that consuming 3 servings/d amounted 
to a total daily intake of 30 g of the designated oil. The fortifi-
cation goals for each diet period are shown in Table 1, which 
indicates that participants were provided 30 g/d of soybean oil, 
consisting of 16 g of additional LA, an amount comparable to 
that used in previous studies demonstrating significant biolog-
ical effects [17,18,20]. The 4-wk duration was chosen to align 
with previous clinical trials that replenished dietary oils at 4-wk 
intervals [13,21]. The objective of the primary study was to 
evaluate acceptability and adherence to consuming 3 study 
foods daily, and this timeframe supported that aim while 
matching the planned replenishment schedule for future longer
studies [16]. The nutrient composition of oil and study foods 
was calculated using the Nutrition Data System for Research 
software, version 2020, developed by the Nutrition Coordi-
nating Center at the University of Minnesota, Minneapolis, MN. 
Detailed nutrient composition of the study foods is provided in 
the primary research paper [16].
Fatty acid profiling and desaturase activity 
estimation
Procedures for analyzing fatty acids in DBS [22,23], eryth-
rocytes [24], plasma [25,26], and PBMC [25] were conducted as 
previously described. All samples were analyzed using gas 
chromatography equipped with a 30-m Omegawax 320 fused
FIGURE 1. Study design flowchart.
FIGURE 2. Participant recruitment flowchart. SO, soybean oil; PO, palm oil.
C.-T. Yang et al. 
Current Developments in Nutrition 10 (2026) 107635
3
silica capillary column (Supelco) and flame ionization detector 
with conditions as previously described [26,27]. Fatty acid 
methyl ester retention times were compared against reference 
standards obtained from Matreya, LLC, and Nu-Check Prep Inc. 
Desaturase enzyme activities were inferred by calculating the 
ratios of specific fatty acid products to their precursors in DBS, 
erythrocytes, plasma, and PBMC. Specifically, stearoyl-CoA 
desaturase-1 (SCD1) activity was estimated using the ratios 
C16:1n–7/C16:0 and C18:1n–9/C18:0, referred to as SCD16 and 
SCD18, respectively. D6D indices were assessed using the ratio 
C18:3n–6/C18:2n–6, whereas D5D indices were estimated using 
the ratio C20:4n–6/C20:3n–6 [28], as described in previous 
research [29].
Blood sample analysis
Serum IL-6 and CRP and plasma LBP were analyzed using the 
MesoScale Diagnostics MSD kit. Plasma sCD14 and oxLDL were 
measured with ELISA kits (R&D Systems Inc. and Mercodia).
Statistics
Statistical analysis was performed using STATA Versions 18 
(StataCorp LLC). Mixed-effects linear regression with 
participant-level random intercepts was used to assess the 
lingering effects of the intervention across multiple biomarkers, 
accounting for repeated measures and interaction terms. Within-
participant changes in fatty acids and biochemical markers 
within each diet period were compared with 0 using the Wil-
coxon Signed Rank Test. Within-participant differences in 
changes between diet periods were also tested using the Wil-
coxon Signed Rank Test.
Results
Lingering effect
The study employed a crossover design, and potential 
carryover effects were evaluated using mixed-effects linear 
regression. Results showed that all parameters were nonsignif-
icant, indicating no evidence of a crossover effect.
Impact of palm and soybean oil snacks on markers 
of inflammation and oxLDL concentrations
Table 2 illustrates the changes in the primary outcomes, 
which include inflammatory markers and ox-LDL over the 
course of the diet period for both the palm oil and the soybean 
oil groups. Among the markers assessed, IL-6 showed a trend for
a decrease in the soybean oil group (P = 0.09). In contrast, IL-6 
concentrations in the palm oil group remained relatively stable 
throughout the diet period. Other inflammatory markers, 
including CRP, sCD14, LBP, and oxLDL, did not exhibit signifi-
cant changes in either group. In summary, most inflammatory 
markers remained relatively stable during the intervention, 
whereas the soybean oil group demonstrated a trend of reduc-
tion in IL-6 concentrations.
Impact of palm and soybean oil snacks on n–6 and 
n–3 fatty acids
Concentrations of LA and LA-derived n–6 fatty acids in 
plasma and RBC are presented in Table 3; data from DBS and 
PBMC are shown in Supplementary Tables 1 and 2. Overall, 
other than LA, n–6 fatty acids concentrations remained un-
changed in the palm oil or the soybean oil groups. However, in 
RBC, a trend toward increased concentrations of C22:5n–6 was 
observed in the soybean oil group (P = 0.0547). In addition, AA 
concentrations in RBC significantly decreased in the soybean oil 
group (P = 0.0234). These findings suggest that although most 
LA-derived n–6 fatty acids are unaffected by palm or soybean oil 
consumption, AA decreased in response to soybean oil intake in 
erythrocytes.
Concentrations of α-linolenic acid (ALA) and ALA-derived 
n–3 fatty acid in plasma and RBC are presented in Table 3, 
whereas data from DBS and PBMC are shown in Supplementary 
Tables 1 and 2. Overall, other than ALA, most n–3 fatty acid 
concentrations remained stable in either palm oil or the soybean 
oil group. A significant decrease in C22:6n–3 (DHA) was 
observed in RBC in the soybean oil group (P = 0.0078),
TABLE 1
Fatty acid fortification goals for each diet period
Fatty acid
Palm oil 
diet group
Soybean oil 
diet group
Palmitic acid 1 (C16:0) 
13.8
3
Stearic acid 1 (C18:0)
1.5
1.5
Oleic acid 1 (C18:1n–9) 
11.7
7.2
Linoleic acid 1 (C18:2n–6) 
3
16.2
α-Linolenic acid 1 (C18:3n–3)
0
2.1
Fatty acid analysis was performed using Nutrition Data System for 
Research software version 2020, Nutrition Coordinating Center, Uni-
versity of Minnesota.
1 g/day.
TABLE 2
Markers of inflammation and oxLDL concentrations
Biomarkers
Group
Week
0 mean 
(SD)
Week 4 
mean 
(SD)
P
value
Between
group
IL-6 1 
(pg/mL)
Palm oil 
1.73 ±
0.70
1.46 ±
0.49
0.3125
0.2500
Soybean
oil
1.60 ±
0.66
1.43 ±
0.58
0.0938
CRP 1 
(mg/mL)
Palm oil 
1.33 ±
1.16
2.76 ±
3.79
0.6406
1.0000
Soybean 
oil 
2.33 ± 
2.77
1.54 ±
2.65
0.2188
sCD14 1 
(μg/mL)
Palm oil 
1.44 ±
0.27
1.50 ±
0.35
0.6250
0.2969
Soybean 
oil 
1.41 ± 
0.28
1.49 ±
0.29
0.5781
LBP 1 
(pg/mL)
Palm oil
4.54
±1.78 
3.97 ±
2.22
0.9219
0.6875
Soybean 
oil 
3.52 ±
2.35
3.35 ±
2.66
1.0000
oxLDL 1 
(U/L)
Palm oil 
61.43 ± 
14.11
60.20 ±
10.22
0.6406
0.3750
Soybean 
oil
57.75 ± 
12.85
57.64 ±
15.64
0.2969
Abbreviations: CRP, C-reactive protein; sCD14, soluble CD14; LBP, 
LPS-binding protein; oxLDL, oxidized LDL; PO, palm oil group; SO, 
soybean oil group.
1 Planned sample sizes were PO (n = 10) and SO (n = 9); however, 
due to limited blood availability, actual sample sizes varied: IL-6 and 
CRP (PO: n = 8, SO: n = 6), sCD14 and LBP (PO: n = 10, SO: n = 7), 
oxLDL (PO: n = 8, SO: n = 7).
C.-T. Yang et al.
Current Developments in Nutrition 10 (2026) 107635
4
TABLE 3
Fatty acid profile and desaturase indices of plasma and red blood cells
Fatty acid
Group
Week 0 
Mean (SD)
Week 4 
Mean (SD)
P value
Between group
SFA in plasma
C16:0
Palm oil 
20.97 ± 1.16
22.44 ± 1.28
0.0039
0.0273
Soybean oil 
21.01 ± 0.75
20.85 ± 0.83
0.4258
C18:0
Palm oil 
1.43 ± 0.42
1.28 ± 0.47
0.6953
1.0000
Soybean oil 
7.07 ± 0.77
7.01 ± 0.42
0.7344
MUFA in plasma
C16:1n–7
Palm oil 
1.51 ± 0.55
1.48 ± 0.43
0.6953
0.4258
Soybean oil 
6.86 ± 0.54
6.99 ± 1.20
0.3594
C18:1n–9
Palm oil 
18.22 ± 2.14
18.56 ± 1.76
0.4316
0.0391
Soybean oil 
18.38 ±2.78 
16.70 ± 2.41
0.1289
LA-derived PUFA in plasma 
C18:2n–6
Palm oil 
33.62 ± 3.97
32.02 ± 3.70
0.0371
0.0117
Soybean oil 
33.40 ± 3.72
35.75 ± 3.70
0.0742
C18:3n–6
Palm oil 
0.47 ± 0.17
0.47 ± 0.19
1.0000
0.9102
Soybean oil 
0.42 ± 0.13
0.45 ± 0.21
0.7344
C20:3n–6
Palm oil 
1.41 ± 0.34
1.47 ± 0.41
0.9219
0.7344
Soybean oil 
1.36 ± 0.28
1.35 ± 0.24
0.5703
C20:4n–6
Palm oil 
8.13 ± 1.32
7.87 ± 1.72
0.4316
0.4961
Soybean oil 
7.97 ± 1.79
7.93 ± 1.89
1.0000
C22:4n–6
Palm oil 
0.22 ± 0.07
0.20 ± 0.07
0.5566
0.2031
Soybean oil 
0.21 ± 0.06
0.22 ± 0.06
0.3008
C22:5n–6
Palm oil 
0.19 ± 0.07
0.20 ± 0.09
0.6953
0.6523
Soybean oil 
0.19 ± 0.09
0.18 ± 0.06
0.7344
ALA-derived PUFA in plasma 
C18:3n–3
Palm oil 
0.61 ± 0.20
0.53 ± 0.17
0.2324
0.4961
Soybean oil 
0.75 ± 0.32
0.76 ± 0.22
0.7344
C20:5n–3
Palm oil 
0.44 ± 0.17
0.48 ± 0.24
0.8457
0.8203
Soybean oil 
0.37 ± 0.08
0.42 ± 0.23
0.7344
C22:5n–3
Palm oil 
0.36 ± 0.07
0.37 ± 0.10
0.6953
0.5703
Soybean oil 
0.34 ± 0.06
0.39 ± 0.08
0.3008
C22:6n–3
Palm oil 
1.26 ± 0.25
1.33 ± 0.37
0.3750
0.4961
Soybean oil 
1.24 ± 0.17
1.23 ± 0.25
0.7344
Desaturase indices in plasma 
SCD16
Palm oil 
0.07 ± 0.02
0.07 ± 0.02
0.4316
0.4961
Soybean oil 
0.07 ± 0.02
0.06 ± 0.02
0.4258
SCD18
Palm oil 
2.78 ± 0.55
2.68 ± 0.24
1.0000
0.1641
Soybean oil 
2.61 ± 0.51
2.38 ± 0.30
0.0547
D5D
Palm oil 
0.02 ± 0.01
0.02 ± 0.01
0.3223
0.3594
Soybean oil 
0.013 ± 0.005
0.01 ± 0.01
1.0000
D6D
Palm oil 
5.97 ± 1.78
5.74 ± 1.93
0.8457
0.8203
Soybean oil 
6.20 ± 1.81
6.12 ± 2.08
0.6523
SFA in RBC
C16:0
Palm oil 
24.62 ± 1.16
24.97 ± 1.15
0.3750
0.8438
Soybean 1 oil 
24.00 ± 1.01
24.56 ± 1.02
0.0547
C18:0
Palm oil 
0.31 ± 0.12
0.31 ± 0.11
0.0195
0.0156
Soybean 1 oil 
19.52 ± 0.59
19.86 ± 0.87
0.1953
MUFA in RBC
C16:1n–7
Palm oil 
0.32 ± 0.12
0.33 ± 0.09
0.4316
0.9453
Soybean 1 oil 
20.35 ± 0.74
19.70 ± 0.66
0.7422
C18:1n–9
Palm oil 
12.97 ± 0.77
13.22 ± 0.68
0.0840
0.0078
Soybean 1 oil 
13.12 ± 0.73
12.53 ± 0.54
0.0078
LA-derived PUFA in RBC 
C18:2n–6
Palm oil 
12.76 ± 1.71
12.98 ± 1.85
0.7695
0.0781
Soybean 1 oil 
13.68 ± 1.80
14.77 ± 2.11
0.0547
C20:3n–6
Palm oil 
1.43 ± 0.28
1.48 ± 0.35
0.5566
0.6406
Soybean 1 oil 
1.50 ± 0.30
1.48 ± 0.30
0.7422
C20:4n–6
Palm oil 
15.38 ± 1.27
15.22 ± 0.99
0.8457
0.1484
Soybean 1 oil 
15.65 ± 1.31
14.82 ± 1.23
0.0234
C22:4n–6
Palm oil 
4.15 ± 0.77
4.07 ± 0.77
0.4922
0.1484
Soybean 1 oil 
4.08 ± 0.72
3.87 ± 0.68
0.1484
C22:5n–6
Palm oil 
0.57 ± 0.19
0.58 ± 0.17
0.6250
0.3125
Soybean 1 oil 
0.57 ± 0.23
0.58 ± 0.15
0.8438
ALA-derived PUFA in RBC 
C18:3n–3
Palm oil 
0.17 ± 0.08
0.17 ± 0.06
1.0000
0.5469
Soybean 1 oil 
0.21 ± 0.08
0.24 ± 0.07
0.5469
C20:5n–3
Palm oil 
0.29 ± 0.18
0.36 ± 0.23
0.6250
0.1484
Soybean 1 oil 
0.34 ± 0.12
0.31 ± 0.12
0.1953
C22:5n–3
Palm oil 
2.19 ± 0.49
2.23 ± 0.29
0.3750
1.0000
Soybean 1 oil 
2.09 ± 0.32
2.13 ± 0.36
0.9453
C22:6n–3
Palm oil 
3.07 ± 0.58
3.08 ± 0.60
0.6250
0.0234
Soybean 1 oil 
3.33 ± 0.62
3.02 ± 0.55
0.0078
Desaturase indices in RBC
SCD16
Palm oil 
0.013 ± 0.005
0.013 ± 0.004
0.3750
0.9453
Soybean 1 oil 
0.013 ± 0.005
0.013 ± 0.004
0.9453
SCD18
Palm oil
0.65 ± 0.06
0.67 ± 0.04
0.0195
0.0078
(continued on next page)
C.-T. Yang et al.
Current Developments in Nutrition 10 (2026) 107635
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accompanied by a significant between-group difference (P = 
0.0234). These findings suggest that although the majority of 
n–3 fatty acid profiles are unaffected by these diet periods, DHA 
concentrations in RBC are negatively affected by soybean oil 
intake.
Effect of palm and soybean oil snacks on SCD16, 
SCD18, D6D, and D5D indices in plasma and RBC
Concentrations of C16:1n–7 (palmitoleic acid) and C18:0 
(stearic acid) are shown in Table 3. The only significant change 
observed was decreased C18:0 in the palm oil group (P = 
0.0195) with a significant difference between groups (P = 
0.0156). Fatty acid desaturation indices: SCD16, SCD18, D6D, 
and D5D for plasma and RBC are in Table 3; indices for DBS and 
PBMC are presented in Supplementary Tables 1 and 2. There are 
no significant differences in D5D and D6D in any samples in 
either group. A decrease in SCD18 was observed in the soybean 
oil group across DBS (P = 0.0195), plasma (P = 0.0547), and 
RBC (P = 0.0156). In addition, SCD18 significantly increased in 
the palm oil group in RBC (P = 0.0195), with a significant dif-
ference between groups (P = 0.0078). Our findings show that 
soybean oil and palm oil intake differentially affect desaturase 
activity, with significant changes in SCD18 but no effect on D5D 
or D6D.
Discussion
The primary outcomes of this study were differences between 
dietary oils for changes in systemic inflammatory markers and 
oxLDL concentrations; none showed a change in response to 30 g 
of soybean oil or palm oil consumption. IL-6 and CRP are 
commonly used as markers of systemic inflammation because 
they are strongly associated with inflammatory processes and 
chronic disease [30]. In addition, both LBP and sCD14 are 
acute-phase inflammatory proteins whose blood concentrations 
are positively associated with BMI and markers of insulin 
resistance [31–35]. OxLDL, a modified form of LDL, is 
commonly used as a surrogate marker of systemic oxidative 
stress and vascular inflammation in clinical trials [36]. Elevated 
IL-6, CRP, LBP, and sCD14 are widely recognized as proin-
flammatory markers linked to cardiometabolic risk and sub-
clinical vascular changes [34,37]. Findings from this study are
consistent with our previous supplementation study, where 
supplementation with 6.9 g LA/d for 16 wk did not affect oxLDL 
or CRP concentrations [13]. Furthermore, a systematic review of 
randomized controlled trials found no evidence that dietary LA 
increases inflammatory marker concentrations [38]. These 
findings indicate that LA intake, at a dose of ~16 g LA/d, does 
not increase inflammation as theoretically expected and may 
decrease risk of cardiovascular disease (CVD), type 2 diabetes, 
and other cardiometabolic conditions [39,40].
We observed a trend toward reduced IL-6 concentrations 
after the soybean oil diet period in our current study, consistent 
with our previous observational findings where erythrocyte LA 
concentrations were inversely associated with serum IL-6 [27]. 
In another prior study, we observed a reduction in CRP in the 
LA-rich safflower oil group in females with type 2 diabetes [15]. 
In a large population-based cross-sectional study, serum con-
centrations of n–6 PUFA were not linked to increased systemic 
inflammation in males; instead, LA was strongly associated with 
lower concentrations of CRP [14]. In agreement, previous 
research has shown that individuals with the lowest plasma n–6 
PUFA concentrations had the highest concentrations of proin-
flammatory markers, including TNF-α, IL-6, and CRP, and the 
lowest concentrations of anti-inflammatory markers (trans-
forming growth factor-beta, TGF-β) [41]. The observed reduc-
tion in IL-6, alongside the unchanged CRP concentrations after 
soybean oil intake, may be explained by the role of IL-6 as an 
upstream inflammatory cytokine that drives CRP production. As 
such, IL-6 may respond more rapidly to dietary interventions, 
whereas downstream markers like CRP may require exposure 
that is longer than the 4-wk diet period here [42]. In contrast, 
sCD14 and LBP reflect microbial translocation and chronic 
low-grade inflammation, which typically respond more slowly 
and may require extended or targeted interventions to improve 
[43]. Collectively, these findings reinforce the evidence that LA 
supplementation does not promote systemic inflammation or 
LDL oxidation but may in fact, reduce markers of inflammation 
and oxidation.
Whether LA consumption promotes inflammation and 
oxidative stress has long been debated in the popular press and 
in scientific circles [44]. Although some studies suggest that LA 
may enhance inflammatory responses or oxidative stress, many 
of these findings are based on in vitro models in cell cultures 
using excessively high concentrations of LA, ranging from 75 to
TABLE 3 (continued )
Fatty acid
Group
Week 0 
Mean (SD)
Week 4 
Mean (SD)
P value
Between group
Soybean 1 oil 
0.67 ± 0.05
0.64 ± 0.03
0.0156
D5D
Palm oil 
11.09 ± 2.59
10.85 ± 2.71
0.2754
0.9453
Soybean 1 oil
10.96 ± 2.78
10.55 ± 2.72
0.3125
Fatty acid values are expressed as percentages of total fatty acids.
C16:1n–7 (palmitoleic acid); C18:0 (stearic acid); C18:3n–6 (γ-linolenic acid, GLA); C20:3n–6 (dihomo-γ-linolenic acid, DGLA); C20:4n–6 
(arachidonic acid, AA); C22:4n–6 (adrenic acid); C22:5n–6 (DHA n–6); C20:3n–6 (dihomo-γ-linolenic acid, DGLA); C20:4n–6 (arachidonic acid, 
AA); C22:4n–6 (adrenic acid); C22:5n–6 (DHA n–6); C20:5n–3 (EPA); C22:5n–3 (DHA n–3); C22:6n–3 (DHA); RBC, red blood cells; SCD1, stearoyl-
CoA desaturase-1; SCD16 = C16:1n–7/C16:0, SCD18 = C18:1n–9/C18:0, D5D (δ-5 desaturase) = C18:3n–6/C18:2n–6, D6D (δ-6-desaturase) = 
C20:4n–6/C20:3n–6. Details of C16:0 (palmitic acid), C18:1 n9 (oleic acid), C18:2n–6 (linoleic acid, LA), and C18:3n–3 (α-LA, ALA) are provided 
in our primary manuscript [16]. C18:3n–6 (γ-linolenic acid, GLA) in RBC is below the detectable range. D6D activity could not be presented in RBC 
due to the undetectable concentrations of GLA.
1 n = 8, 1 subject is unable to get enough blood to isolate RBC.
C.-T. Yang et al.
Current Developments in Nutrition 10 (2026) 107635
6
600 μM, which may not be achievable as a circulating LA con-
centration in human [45,46]. Although in vitro studies offer 
mechanistic insights, they lack the systemic complexity of whole 
organisms, limiting the applicability of their results to practical 
dietary settings. In addition, AA is often mischaracterized as 
proinflammatory [47]. Although AA can be converted into 
proinflammatory mediators such as leukotrienes, prostaglan-
dins, and thromboxanes, AA also serves as a precursor to 
anti-inflammatory compounds like lipoxins (e.g., LXA4), which 
are essential for resolving inflammation [47]. This highlights a 
dual role of AA in both initiating and resolving inflammatory 
responses.
Fatty acid composition
We measured the impact of soybean compared with palm oils 
on fatty acid profiles of plasma, RBC, PBMC, and DBS because 
each blood fraction provides complementary insights into di-
etary fatty acid effects on biomarkers. Each blood fraction may 
offer practical alternatives to tissue sampling, which is not 
feasible in clinical trials. These blood compartments may serve 
as accessible indicators of dietary fatty acid intake and may 
reflect organ fatty acid composition [48]. Plasma reflects 
short-term intake due to rapid turnover [49], whereas RBC 
membranes may serve as long-term markers of fat quality intake 
given 120-d lifespan of erythrocyte [48]. PBMC, with a turnover 
of 3 to 10 d, offer functional relevance by linking lipid remod-
eling to immune and cardiometabolic processes [25]. Although 
RBC and PBMC may be better indicators of chronic fat quality 
intake, a drawback of RBC and PBMC is the requirement for 
laboratory processing with immediate storage of samples in − 80 
freezers [50]. The DBS provides an integrated measure of short-
and long-term changes and practical advantages for large-scale 
studies [50] and can be collected by the participants without 
assistance from remote locations. After 4 wk of palm oil or 
soybean oil snack consumption at 30 g oil/d, most n–6 and n–3 
fatty acid profiles in DBS, PBMC, plasma, and RBC remain un-
changed. However, soybean oil snack intake was associated with 
reductions in AA and DHA concentrations in erythrocytes, sug-
gesting a potential impact on fatty acid profile in RBC. Although 
it is often claimed that higher dietary LA intake elevates AA 
concentrations, our findings support previous studies that do not 
show dietary LA increases plasma AA [10,51,52]. A systematic 
review found that increasing dietary LA does not raise plasma 
AA concentrations in adults, with most studies reporting only 
minimal and statistically insignificant changes [51]. With 
higher dietary intake of LA, plasma AA concentrations remained 
unchanged or were inversely associated with LA [52], suggest-
ing that increased LA does not promote AA synthesis in healthy 
adults and that factors beyond n–6 fatty acid intake play a sig-
nificant role in regulating plasma AA concentrations. In a study 
using stable isotope [ 13 C], increasing dietary intake of LA does 
not significantly raise concentrations of LA or AA in plasma, as 
the conversion of LA to AA is extremely low, ~0.2% [10]. 
Collectively, these findings support our results, where 16 g LA/d 
does not increase, and may even reduce, AA concentrations in 
erythrocytes.
Interestingly, we observed a trend toward increased 
C22:5n–6 concentrations in DBS in the soybean oil group (P = 
0.0547). Although the biological significance of this finding is 
unclear, and no prior studies have reported similar results, it
may reflect alterations in elongation or desaturation pathways 
in response to increased dietary LA. Given that this trend did not 
reach statistical significance and was not observed in RBC, 
further research is needed to confirm and elucidate the under-
lying mechanisms.
We observed a significant decrease in DHA concentrations in 
RBC in the soybean oil group. Although the underlying mecha-
nism remains unclear, 1 previous study reported that higher 
RBC LA concentrations are inversely associated with concen-
trations of AA, EPA, and DHA in Canadian pregnant females; in 
this prior study, the authors speculated that the lower AA, EPA, 
and DHA were due to competition for incorporation into mem-
brane lipids [53]. DHA can be elongated into tetracosahex-
aenoic acid (THA; 24:6n–3), a C24 fatty acid that may serve 
additional physiological functions [54]. Unfortunately, we did 
not measure THA in our study. Given our findings, further 
research is needed to better understand the mechanisms un-
derlying the reduction of DHA in RBC after soybean oil 
consumption.
Desaturase indices
Several studies have shown that desaturase indices derived 
from blood-based fatty acid profiles, such as those in plasma and 
RBC, can serve as reliable surrogate markers of hepatic enzyme 
activity, making them useful in clinical research settings 
[55–57]. SCD16 and SCD18 are rate-limiting lipogenic enzymes 
anchored in the endoplasmic reticulum membrane, both 
contributing to the synthesis of MUFA [58]. Specifically, the 
SCD16 ratio reflects the conversion of C16:0 (palmitic acid) to 
C16:1n–7 (palmitoleic acid), whereas the SCD18 ratio reflects 
the conversion of C18:0 (stearic acid) to C18:1n–9 (oleic acid) 
[28]. In our study, a decrease in SCD18 activity was observed in 
the soybean oil group across DBS, plasma, and RBC samples. In a 
previous study, rats fed a purified diet supplemented with corn 
oil, which contained ~60% LA by weight of its fatty acids and 
was adjusted to maintain 410 to 415 kcal/100g, showed reduced 
hepatic SCD activity, likely due to downregulation of SCD gene 
expression [59]. Conversely, SCD18 activity was significantly 
increased in the palm oil group in RBC, with a notable difference 
between groups. This finding aligns with previous research 
reporting that palm oil consumption enhances SCD activity in 
rats, particularly in the phospholipid and free fatty acid fractions 
of liver tissue, an effect potentially driven by oleic acid derived 
from palm oil [60]. Supporting this, we also observed a signif-
icant reduction in C18:0 concentrations in the palm oil group, 
which is consistent with elevated SCD18 activity, as a decrease 
in the substrate (C18:0) corresponds with an increased desa-
turase index. Overall, our findings suggest that dietary fatty acid 
composition can modulate SCD activity, with different oils 
exerting distinct effects on desaturase indices across lipid 
fractions.
In addition to SCDs, D6D, and D5D are involved in the 
biosynthesis of PUFA [29]. D6D is the rate-limiting enzyme for 
essential PUFA conversion, along with D5D, as the main de-
terminants of PUFA concentrations [61]. PUFA ratios are 
commonly used to estimate desaturase activities in human 
studies because enzymes reside and are primarily active in the 
liver [62,63]. There has been speculation that a diet high in n–6 
fatty acids may lead to elevated desaturase activity, thereby 
increasing the bioavailability of AA and promoting the synthesis
C.-T. Yang et al.
Current Developments in Nutrition 10 (2026) 107635
7
RBC and PBMC may be worse indicators of chronic fat quality contributing to the synthesis of MUFA [58]. Specifically, the
of AA-derived proinflammatory eicosanoids [64]. However, our 
study failed to show significant changes in D5D or D6D in either 
the soybean oil or the palm oil groups. To the best of our 
knowledge, this is the first human clinical trial to directly 
compare the effects of soybean oil compared with palm oil 
intake on D5D and D6D indices. Others have reported a negative 
correlation between dietary LA intake and the expression of D5D 
mRNA and D6D mRNA in PBMC [65]. In addition, mechanistic 
evidence indicates that PUFA-derived products regulate D5D 
and D6D expression through transcriptional feedback mecha-
nisms [66]. Our findings suggest that increased LA intake does 
not enhance the activity of these rate-limiting enzymes to pro-
mote AA production, as previously theorized.
Limitations
This study offers valuable insights; however, there are a few 
limitations. The health status of participants was based on self-
reported medical history without confirmation through serum 
biochemistry or blood pressure measurements. CRP values were 
within normal ranges, suggesting that the participants with 
overweight or obesity in this cohort were generally healthy. A 
notable constraint is our limited analyses of downstream LA and 
ALA-derived fatty acid, which may hinder a comprehensive 
understanding of the metabolic pathways involved. We focused 
on several commonly observed fatty acids that are players in 
cellular and physiological processes associated with purported 
inflammation associated with vegetable oils (e.g., “seed oils” in 
popular press). This investigation was designed as a pilot study 
to inform and guide future research directions and, therefore, 
has a small sample size; thus, it is inappropriate to generalize 
our findings to a broader adult population. Even with these 
limitations, we believe these findings substantiate a plethora of 
evidence that dietary intake of n–6 PUFAs does not increase 
systemic inflammation in healthy overweight adults. In addi-
tion, this study sets a foundational framework for evaluating the 
potential health benefits of LA-fortified snacks in larger cohort 
studies.
In summary, consumption of snack foods containing either 
soybean oil or palm oil at 30 g/d for 4 wk did not significantly 
alter most biomarkers of essential fatty acid metabolism or 
systemic inflammation. Soybean oil intake notably reduced 
erythrocyte AA concentrations and demonstrated a trend to-
ward lower circulating IL-6 concentrations. These results sug-
gest that dietary soybean oil does not increase proinflammatory 
biomarkers and may support favorable shifts in fatty acid 
metabolism, countering widespread social media claims that ω-6 
fatty acids are inherently proinflammatory.
Acknowledgments
We extend our gratitude to Stephan Zarich for his critical 
evaluation of the data and manuscript.
Author contributions
The authors’ responsibilities were as follows – RMC, MAB: 
designed research; RMC, EC, AA: conducted research; C-TY, 
RMC, AN: analyzed data; MAB: had primary responsibility for 
final content; and all authors: wrote the paper, read and 
approved the final manuscript.
Declaration of generative AI and AI-assisted 
technologies in the writing process
No generative AI or AI-assisted technologies were used in the 
preparation or writing of this manuscript.
Conflict of interest
MAB serves on the board of trustees for the American Society 
for Nutrition Foundation and has received travel reimbursement 
from the United Soybean Board for a scientific session. The other 
authors declare that they have no known competing financial 
interests or personal relationships that could have appeared to 
influence the work reported in this paper.
Funding
This research was funded by the United Soybean Board 
(2411-108-0101), Soy Nutrition Institute Global, the Ohio 
Agriculture 335 Research and Development Center, and the 
National Center for Advancing Translational Sciences, Grant 
336 UM1TR004548. Soybean oil was donated by Cargill, 
Incorporated. The sponsors had no role in the design or conduct 
of the study, the data analysis, or the decision to publish.
Data availability
Data described in the manuscript, code book, and analytic 
code will be made available upon request, pending application 
and approval.
Appendix A. Supplementary data
Supplementary data to this article can be found online at 
https://doi.org/10.1016/j.cdnut.2025.107635.
References
[1] S.M. Mousavi, Y. Jalilpiran, E. Karimi, D. Aune, B. Larijani,
D. Mozaffarian, et al., Dietary intake of linoleic acid, its concentrations, 
and the risk of type 2 diabetes: a systematic review and dose-response 
meta-analysis of prospective cohort studies, Diabetes Care. 44 (9) 
(2021) 2173–2181, https://doi.org/10.2337/dc21-0438.
[2] M.S. Farvid, M. Ding, A. Pan, Q. Sun, S.E. Chiuve, L.M. Steffen, et al., 
Dietary linoleic acid and risk of coronary heart disease: a systematic 
review and meta-analysis of prospective cohort studies, Circulation. 
130 (18) (2014) 1568–1578, https://doi.org/10.1161/ 
CIRCULATIONAHA.114.010236.
[3] I. Djuricic, P.C. Calder, Beneficial outcomes of omega-6 and omega-3 
polyunsaturated fatty acids on human health: an update for 2021, 
Nutrients. 13 (7) (2021) 2421, https://doi.org/10.3390/nu13072421.
[4] D.A. Wood, R.A. Riemersma, S. Butler, M. Thomson, C. Macintyre, R. 
A. Elton, et al., Linoleic and eicosapentaenoic acids in adipose tissue 
and platelets and risk of coronary heart disease, Lancet. 1 (8526) 
(1987) 177–183, https://doi.org/10.1016/s0140-6736(87)90001-8.
[5] S.K. Raatz, Z. Conrad, L. Jahns, Trends in linoleic acid intake in the 
United States adult population: NHANES 1999-2014, Prostaglandins 
Leukot. Essent. Fatty Acids. 133 (2018) 23–28, https://doi.org/ 
10.1016/j.plefa.2018.04.006.
[6] S.K. Raatz, Z. Conrad, L. Jahns, M.A. Belury, M.J. Picklo, Modeled 
replacement of traditional soybean and canola oil with high-oleic 
varieties increases monounsaturated fatty acid and reduces both 
saturated fatty acid and polyunsaturated fatty acid intake in the US 
adult population, Am. J. Clin. Nutr. 108 (3) (2018) 594–602, https:// 
doi.org/10.1093/ajcn/nqy127.
[7] S. Sergeant, E. Rahbar, F.H. Chilton, Gamma-linolenic acid, dihommo-
gamma linolenic, eicosanoids and inflammatory processes, Eur. J. 
Pharmacol. 785 (2016) 77–86, https://doi.org/10.1016/j. 
ejphar.2016.04.020.
[8] Y. Zhou, H. Khan, J. Xiao, W.S. Cheang, Effects of arachidonic
acid metabolites on cardiovascular health and disease, Int. J. Mol.
C.-T. Yang et al.
Current Developments in Nutrition 10 (2026) 107635
8
This study offers valuable insights; however, there are a many
Sci. 22 (21) (2021) 12029, https://doi.org/10.3390/ 
ijms222112029.
[9] J.K. Innes, P.C. Calder, Omega-6 fatty acids and inflammation,
Prostaglandins Leukot, Essent. Fatty Acids. 132 (2018) 41–48, https:// 
doi.org/10.1016/j.plefa.2018.03.004.
[10] N. Hussein, E. Ah-Sing, P. Wilkinson, C. Leach, B.A. Griffin, D.
J. Millward, Long-chain conversion of [ 13 C] linoleic acid and alpha-
linolenic acid in response to marked changes in their dietary intake in 
men, J. Lipid Res. 46 (2) (2005) 269–280, https://doi.org/10.1194/jlr. 
M400225-JLR200.
[11] J.L. Burns, M.T. Nakamura, D.W.L. Ma, Differentiating the biological 
effects of linoleic acid from arachidonic acid in health and disease, 
Prostaglandins Leukot. Essent. Fatty Acids. 135 (2018) 1–4, https:// 
doi.org/10.1016/j.plefa.2018.05.004.
[12] J.J. DiNicolantonio, J.H. O'Keefe, Omega-6 vegetable oils as a driver of 
coronary heart disease: the oxidized linoleic acid hypothesis, Open 
Heart. 5 (2) (2018) e000898, https://doi.org/10.1136/openhrt-2018-
000898.
[13] R.M. Cole, S. Puchala, J.-Y. Ke, M. Abdel-Rasoul, K. Harlow,
B. O’Donnell, et al., Linoleic acid–rich oil supplementation increases 
total and high-molecular-weight adiponectin and alters plasma 
oxylipins in postmenopausal women with metabolic syndrome, Curr. 
Dev. Nutr. 4 (9) (2020) nzaa136, https://doi.org/10.1093/cdn/ 
nzaa136.
[14] J.K. Virtanen, J. Mursu, S. Voutilainen, T.P. Tuomainen, The 
associations of serum n-6 polyunsaturated fatty acids with serum C-
reactive protein in men: the Kuopio ischaemic heart disease risk factor 
study, Eur. J. Clin. Nutr. 72 (3) (2018) 342–348, https://doi.org/ 
10.1038/s41430-017-0009-6.
[15] M.L. Asp, A.L. Collene, L.E. Norris, R.M. Cole, M.B. Stout, S.Y. Tang, et 
al., Time-dependent effects of safflower oil to improve glycemia, 
inflammation and blood lipids in obese, post-menopausal women with 
type 2 diabetes: a randomized, double-masked, crossover study, Clin. 
Nutr. 30 (4) (2011) 443–449, https://doi.org/10.1016/j. 
clnu.2011.01.001.
[16] R.M. Cole, E. Colombo, A. Angelotti, G.C. Sparagna, R.E. Choriego,
R. Jimenez-Flores, Feasibility study of soybean oil-fortified foods to 
alter blood content of linoleic acid and body weight: A randomized 
double-masked placebo-controlled crossover trial, J Nutr (2025) 
101288, https://doi.org/10.1016/j.tjnut.2025.101288.
[17] F. Rosqvist, D. Iggman, J. Kullberg, J. Cedernaes, H.E. Johansson,
A. Larsson, et al., Overfeeding polyunsaturated and saturated fat causes 
distinct effects on liver and visceral fat accumulation in humans, 
Diabetes. 63 (7) (2014) 2356–2368, https://doi.org/10.2337/db13-
1622.
[18] W. Stonehouse, D. Sergi, B. Benassi-Evans, G. James-Martin,
N. Johnson, C.H. Thompson, et al., Eucaloric diets enriched in palm 
olein, cocoa butter, and soybean oil did not differentially affect liver fat 
concentration in healthy participants: a 16-week randomized 
controlled trial, Am. J. Clin. Nutr. 113 (2) (2021) 324–337, https://doi. 
org/10.1093/ajcn/nqaa347.
[19] D.B. Snoke, A. Angelotti, K. Borkowski, R.M. Cole, J.W. Newman, M.
A. Belury, Linoleate-rich safflower oil diet increases linoleate-derived 
bioactive lipid mediators in plasma, and brown and white adipose 
depots of healthy mice, Metabolites. 12 (8) (2022) 743, https://doi. 
org/10.3390/metabo12080743.
[20] H. Bjermo, D. Iggman, J. Kullberg, I. Dahlman, L. Johansson,
L. Persson, et al., Effects of n-6 PUFAs compared with SFAs on liver fat, 
lipoproteins, and inflammation in abdominal obesity: a randomized 
controlled trial, Am. J. Clin. Nutr. 95 (5) (2012) 1003–1012, https:// 
doi.org/10.3945/ajcn.111.030114.
[21] L.E. Norris, A.L. Collene, M.L. Asp, J.C. Hsu, L.F. Liu, J.R. Richardson, 
et al., Comparison of dietary conjugated linoleic acid with safflower oil 
on body composition in obese postmenopausal women with type 2 
diabetes mellitus, Am. J. Clin. Nutr. 90 (3) (2009) 468–476, https:// 
doi.org/10.3945/ajcn.2008.27371.
[22] T. Jumbe, S.S. Comstock, S.L. Hahn, W.S. Harris, J. Kinabo, J.I. Fenton, 
Whole blood levels of the n-6 essential fatty acid linoleic acid are 
inversely associated with stunting in 2-to-6 year old Tanzanian 
children: a cross-sectional study, PLOS ONE. 11 (5) (2016) e0154715, 
https://doi.org/10.1371/journal.pone.0154715.
[23] T. Jumbe, S.S. Comstock, W.S. Harris, J. Kinabo, M.B. Pontifex, J.
I. Fenton, Whole-blood fatty acids are associated with executive 
function in Tanzanian children aged 4-6 years: a cross-sectional study, 
Br. J. Nutr. 116 (9) (2016) 1537–1545, https://doi.org/10.1017/ 
S0007114516003494.
[24] W.S. Harris, S.L. Lemke, S.N. Hansen, D.A. Goldstein, M.A. DiRienzo,
H. Su, et al., Stearidonic acid-enriched soybean oil increased the 
omega-3 index, an emerging cardiovascular risk marker, Lipids. 43 (9) 
(2008) 805–811, https://doi.org/10.1007/s11745-008-3215-0.
[25] R.M. Cole, A. Angelotti, G.C. Sparagna, A. Ni, M.A. Belury, Linoleic 
acid-rich oil alters circulating cardiolipin species and fatty acid 
composition in adults: a randomized controlled trial, Mol. Nutr. Food 
Res. 66 (15) (2022) e2101132, https://doi.org/10.1002/ 
mnfr.202101132.
[26] L.E. Arnold, A.S. Young, M.A. Belury, R.M. Cole, B. Gracious, A.
M. Seidenfeld, et al., Omega-3 fatty acid plasma levels before and after 
supplementation: correlations with mood and clinical outcomes in the 
omega-3 and therapy studies, J. Child Adolesc. Psychopharmacol. 27 
(3) (2017) 223–233, https://doi.org/10.1089/cap.2016.0123.
[27] M.A. Belury, R.M. Cole, B.E. Bailey, J.Y. Ke, R.R. Andridge, J.
K. Kiecolt-Glaser, Erythrocyte linoleic acid, but not oleic acid, is 
associated with improvements in body composition in men and 
women, Mol. Nutr. Food Res. 60 (5) (2016) 1206–1212, https://doi. 
org/10.1002/mnfr.201500744.
[28] E. Saito, T. Okada, Y. Abe, M. Odaka, Y. Kuromori, F. Iwata, et al., 
Abdominal adiposity is associated with fatty acid desaturase activity in 
boys: implications for C-reactive protein and insulin resistance, 
Prostaglandins Leukot. Essent. Fatty Acids. 88 (4) (2013) 307–311, 
https://doi.org/10.1016/j.plefa.2013.01.005.
[29] K. Svendsen, T. Olsen, T.C. Nordstrand Rusvik, S.M. Ulven, K.
B. Holven, K. Retterstøl, et al., Fatty acid profile and estimated 
desaturase activities in whole blood are associated with metabolic 
health, Lipids Health Dis. 19 (1) (2020) 102, https://doi.org/10.1186/ 
s12944-020-01282-y.
[30] M. Del Giudice, S.W. Gangestad, Rethinking IL-6 and CRP: why they 
are more than inflammatory biomarkers, and why it matters, Brain 
Behav. Immun. 70 (2018) 61–75, https://doi.org/10.1016/j. 
bbi.2018.02.013.
[31] R.R. Schumann, S.R. Leong, G.W. Flaggs, P.W. Gray, S.D. Wright, J.
C. Mathison, et al., Structure and function of lipopolysaccharide 
binding protein, Science. 249 (4975) (1990) 1429–1431.
[32] T. Sakura, T. Morioka, A. Shioi, Y. Kakutani, Y. Miki, Y. Yamazaki, et 
al., Lipopolysaccharide-binding protein is associated with arterial 
stiffness in patients with type 2 diabetes: a cross-sectional study, 
Cardiovasc. Diabetol. 16 (1) (2017) 62, https://doi.org/10.1186/ 
s12933-017-0545-3.
[33] S. Bas, B.R. Gauthier, U. Spenato, S. Stingelin, C. Gabay, CD14 is an 
acute-phase protein, J. Immunol. 172 (7) (2004) 4470–4479, https:// 
doi.org/10.4049/jimmunol.172.7.4470.
[34] A.P. Reiner, E.M. Lange, N.S. Jenny, P.H. Chaves, J. Ellis, J. Li, et al., 
Soluble CD14: genomewide association analysis and relationship to 
cardiovascular risk and mortality in older adults, Arterioscler. Thromb. 
Vasc. Biol. 33 (1) (2013) 158–164, https://doi.org/10.1161/ 
atvbaha.112.300421.
[35] J.M. Fernandez-Real, M. Broch, C. Richart, J. Vendrell, A. Lopez-
Bermejo, W. Ricart, CD14 monocyte receptor, involved in the 
inflammatory cascade, and insulin sensitivity, J. Clin. Endocrinol. 
Metab. 88 (4) (2003) 1780–1784, https://doi.org/10.1210/jc.2002-
020173.
[36] J. Valaitien_ 
e, A. Laucyt_ 
e-Cibulskien_ 
e, Oxidative stress and its 
biomarkers in cardiovascular diseases, Artery Res. 30 (1) (2024) 18.
[37] C.N. Metz, M. Brines, X. Xue, P.K. Chatterjee, R.P. Adelson, J. Roth, et 
al., Increased plasma lipopolysaccharide-binding protein and altered 
inflammatory mediators reveal a pro-inflammatory state in overweight 
women, BMC Womens Health. 25 (1) (2025) 57, https://doi.org/ 
10.1186/s12905-025-03588-4.
[38] G.H. Johnson, K. Fritsche, Effect of dietary linoleic acid on markers of 
inflammation in healthy persons: a systematic review of randomized 
controlled trials, J. Acad. Nutr. Diet. 112 (7) (2012) 1029, https://doi. 
org/10.1016/j.jand.2012.03.029, 41.e15.
[39] K.H. Jackson, W.S. Harris, M.A. Belury, P.M. Kris-Etherton, P.C. Calder, 
Beneficial effects of linoleic acid on cardiometabolic health: an update, 
Lipids Health Dis. 23 (1) (2024) 296, https://doi.org/10.1186/s12944-
024-02246-2.
[40] M.A. Belury, Linoleic acid, an omega-6 fatty acid that reduces risk for 
cardiometabolic diseases: premise, promise and practical implications, 
Curr. Opin. Clin. Nutr. Metab. Care. 26 (3) (2023) 288–292.
[41] L. Ferrucci, A. Cherubini, S. Bandinelli, B. Bartali, A. Corsi,
F. Lauretani, et al., Relationship of plasma polyunsaturated fatty acids 
to circulating inflammatory markers, J. Clin. Endocr. Metab. 91 (2) 
(2006) 439–446, https://doi.org/10.1210/jc.2005-1303.
C.-T. Yang et al.
Current Developments in Nutrition 10 (2026) 107635
9
[42] Y. Ma, J.R. Hebert, W. Li, E.R. Bertone-Johnson, B. Olendzki, S.
L. Pagoto, et al., Association between dietary fiber and markers of 
systemic inflammation in the women’s health initiative observational 
study, Nutrition. 24 (10) (2008) 941–949, https://doi.org/10.1016/j. 
nut.2008.04.005.
[43] J.R. Stehle Jr., X. Leng, D.W. Kitzman, B.J. Nicklas, S.B. Kritchevsky, K. 
P. High, Lipopolysaccharide-binding protein, a surrogate marker of 
microbial translocation, is associated with physical function in healthy 
older adults, J. Gerontol. A Biol. Sci. Med. Sci. 67 (11) (2012) 
1212–1218, https://doi.org/10.1093/gerona/gls178.
[44] K.L. Fritsche, Too much linoleic acid promotes inflammation—doesn’t 
it? Prostaglandins Leukot, Essent. Fatty Acids. 79 (3) (2008) 173–175, 
https://doi.org/10.1016/j.plefa.2008.09.019.
[45] X. Cao, H. Guo, Y. Dai, G. Jiang, W. Liu, X. Li, et al., Excessive linoleic 
acid induces muscle oxidative stress through 5-lipoxygenase-dependent 
peroxidation, Redox Biol. 71 (2024) 103096, https://doi.org/10.1016/ 
j.redox.2024.103096.
[46] W. Zhang, F. Wu, Linoleic acid induces human ovarian granulosa cell 
inflammation and apoptosis through the ER-FOXO1-ROS-NFκB 
pathway, Sci. Rep. 14 (1) (2024) 6392.
[47] B. Wang, L. Wu, J. Chen, L. Dong, C. Chen, Z. Wen, et al., Metabolism 
pathways of arachidonic acids: mechanisms and potential therapeutic 
targets, Signal Transduct. Target Ther. 6 (1) (2021) 94, https://doi. 
org/10.1038/s41392-020-00443-w.
[48] C. Ferreri, A. Sansone, A. Ferocino, I. Tueros, S.A. Martinez, Fatty acid 
profile of red blood cells as markers in dietary regimes and beyond. 
Biomarkers in Nutrition, Springer Nature Switzerland AG, Cham, 
Switzerland, 2022, pp. 1–25. https://doi.org/10.1007/978-3-030-
81304-8_26-1.
[49] P. Rise, S. Eligini, S. Ghezzi, S. Colli, C. Galli, Fatty acid composition of 
plasma, blood cells and whole blood: relevance for the assessment of 
the fatty acid status in humans, Prostaglandins Leukot. Essent. Fatty 
Acids. 76 (6) (2007) 363–369, https://doi.org/10.1016/j. 
plefa.2007.05.003.
[50] A.H. Metherel, K.D. Stark, The stability of blood fatty acids during 
storage and potential mechanisms of degradation: a review, 
Prostaglandins Leukot, Essent. Fatty Acids. 104 (2016) 33–43, https:// 
doi.org/10.1016/j.plefa.2015.12.003.
[51] B.S. Rett, J. Whelan, Increasing dietary linoleic acid does not increase 
tissue arachidonic acid content in adults consuming Western-type 
diets: a systematic review, Nutr. Metab. (Lond). 8 (2011) 36, https:// 
doi.org/10.1186/1743-7075-8-36.
[52] Y. Angela Liou, S.M. Innis, Dietary linoleic acid has no effect on 
arachidonic acid, but increases n-6 eicosadienoic acid, and lowers 
dihomo-γ-linolenic and eicosapentaenoic acid in plasma of adult men, 
Prostaglandins Leukot. Essent. Fatty Acids. 80 (4) (2009) 201–206, 
https://doi.org/10.1016/j.plefa.2009.02.003.
[53] R.W. Friesen, S.M. Innis, Linoleic acid is associated with lower long-
chain n–6 and n–3 fatty acids in red blood cell lipids of Canadian 
pregnant women, Am. J. Clin. Nutr. 91 (1) (2010) 23–31, https://doi. 
org/10.3945/ajcn.2009.28206.
[54] A.H. Metherel, R.P. Bazinet, Updates to the n-3 polyunsaturated fatty 
acid biosynthesis pathway: DHA synthesis rates, tetracosahexaenoic
acid and (minimal) retroconversion, Prog. Lipid Res. 76 (2019) 
101008, https://doi.org/10.1016/j.plipres.2019.101008.
[55] P. Bispo, P.O. Rodrigues, N.M. Bandarra, Dietary oleic acid and SCD16 
and ELOVL6 estimated activities can modify erythrocyte membrane n-
3 and n-6 HUFA partition: a pilot study, Curr. Issues Mol. Biol. 47 (2) 
(2025) 81, https://doi.org/10.3390/cimb47020081.
[56] M.C. Hua, H.M. Su, T.C. Yao, M.L. Kuo, M.W. Lai, M.H. Tsai, et al., 
Alternation of plasma fatty acids composition and desaturase activities 
in children with liver steatosis, PLOS ONE 12 (7) (2017) e0182277, 
https://doi.org/10.1371/journal.pone.0182277.
[57] E. Warensj€ 
o, M. Rosell, M.L. Hellenius, B. Vessby, U. De Faire,
U. Riserus, Associations between estimated fatty acid desaturase 
activities in serum lipids and adipose tissue in humans: links to obesity 
and insulin resistance, Lipids Health Dis. 8 (2009) 37, https://doi.org/ 
10.1186/1476-511x-8-37.
[58] A.L. AM, D.N. Syed, J.M. Ntambi, Insights into Stearoyl-CoA 
desaturase-1 regulation of systemic metabolism, Trends Endocrinol. 
Metab. 28 (12) (2017) 831–842, https://doi.org/10.1016/j. 
tem.2017.10.003.
[59] J.M. Ntambi, Regulation of stearoyl-CoA desaturase by 
polyunsaturated fatty acids and cholesterol, J. Lipid Res. 40 (9) (1999) 
1549–1558, https://doi.org/10.1016/S0022-2275(20)
33401-5.
[60] A. Levitsky, A. Markov, V. Velichko, I. Selivanskaya, A. Lapinskaya, 
Effect of an antidisbiotic agent on the biosynthesis of fatty acids of liver 
lipids of rats which received palm oil on the background of dysbiosis, 
J. Educ. Health Sport. 12 (5) (2022) 292–303.
[61] F. Tosi, F. Sartori, P. Guarini, O. Olivieri, N. Martinelli, Delta-5 and 
delta-6 desaturases: crucial enzymes in polyunsaturated fatty acid-
related pathways with pleiotropic influences in health and disease, 
Adv. Exp. Med. Biol. 824 (2014) 61–81, https://doi.org/10.1007/978-
3-319-07320-0_7.
[62] W.S. Harris, J. Luo, J.V. Pottala, K.L. Margolis, M.A. Espeland, J.
G. Robinson, Red blood cell fatty acids and incident diabetes mellitus 
in the Women’s Health Initiative Memory Study, PLOS ONE. 11 (2) 
(2016) e0147894, https://doi.org/10.1371/journal.pone.
0147894.
[63] N. Martinelli, D. Girelli, G. Malerba, P. Guarini, T. Illig, E. Trabetti, et 
al., FADS genotypes and desaturase activity estimated by the ratio of 
arachidonic acid to linoleic acid are associated with inflammation and 
coronary artery disease, Am. J. Clin. Nutr. 88 (4) (2008) 941–949, 
https://doi.org/10.1093/ajcn/88.4.941.
[64] N. Martinelli, L. Consoli, O. Olivieri, A ‘desaturase hypothesis’ for 
atherosclerosis: Janus-faced enzymes in omega-6 and omega-3 
polyunsaturated fatty acid metabolism, J. Nutrigenet. Nutrigenomics. 2 
(3) (2009) 129–139, https://doi.org/10.1159/000238177.
[65] M. Xiang, M. Rahman, H. Ai, X. Li, L. Harbige, Diet and gene 
expression: delta-5 and delta-6 desaturases in healthy Chinese and 
European subjects, Ann. Nutr. Metab 50 (6) (2007) 492–498.
[66] M.T. Nakamura, T.Y. Nara, Structure, function, and dietary regulation 
of Δ6, Δ5, and Δ9 desaturases, Annu. Rev. Nutr. 24 (1) (2004) 
345–376.
C.-T. Yang et al.
Current Developments in Nutrition 10 (2026) 107635
10