Elevated Free Fatty Acids (FFA) Are Associated With Cancer, Stroke, Cardiovascular Mortality

Limon9

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A high serum-free fatty acid level is associated with cancer.
J Cancer Res Clin Oncol. 2020 Mar;146(3):705-710. Zhang L, Han L, He J, Lv J, Pan R, Lv T.
". . . serum FFAs were collected from 2206 patients. Overall, 1168 patients (53%) were male and had a median age of 50 years. Patients were divided into two groups: a cancer group and a noncancer group. The main baseline characteristics of the patients are summarized in Table 1. The cancer patients were older than the noncancer patients (52.62 vs 47.85 years, P < 0.001), and the proportion of males in cancer patients was lower than that in noncancer patients (43% vs 62% male, P < 0.001). The BMI in the cancer group was 24.29 kg/m2, which was lower than that in the noncancer group (24.94 kg/m2, P < 0.001). Compared with the noncancer group, the cancer group had a higher FFA level (0.45 vs 0.41 mmol/L, P < 0.001) and a higher albumin level (42.41 vs 40.56 mmol/L, P < 0.001). As shown in Table 2, the univariate analysis revealed that old age, female sex, a low BMI, and high FFA and albumin levels were associated with an increased risk of cancer. After adjusting for age, sex, BMI, and albumin, each unit of the ln-transformed FFA values generated a 35.8% risk of cancer [OR (95% CI): 1.358 (1.126, 1.638), P < 0.001]."
"In the present study, we investigated whether the FFA level was meaningful between cancer and noncancer patients and found that the FFA level was higher in cancer patients than in noncancer patients. These findings indicate that the FFA level is pathogenically involved in cancer, which was clearly demonstrated in several studies in related fields. Recent advances in proteomics and metabolomics have deepened our understanding of the role of fatty acid metabolism in determining the fate of cancer cells"
"FFAs may be affected in a number of pathological conditions, such as insulin resistance, type 2 diabetes, obesity, severe liver dysfunction, hyperthyroidism, and so on(Rui 2014; Tseng et al. 2015). It is also affected by dietary and insulin fluctuations (Xin et al. 2019). Elevated FFA levels can lead to insulin resistance and other metabolic disorders (Arner 2002; Boden 2003). According to the multivariate analysis, there is an increased risk of cancer associated with a high FFA level after adjusting for other confounders. The results suggested that an elevated FFA level is an independent risk factor for cancer, especially lung cancer, gastric cancer, thyroid cancer, rectal cancer, colon cancer, and ovarian cancer. The results also showed that there was a significant positive correlation between the FFA level and BMI in noncancer patients [but I thought niacinamide makes you fat?] and breast cancer patients, while in the other cancer group, there was no significant correlation."

High free fatty acid level is associated with recurrent stroke in cardioembolic stroke [CE] patients.
Neurology. 2014 Apr 1;82(13):1142-8. Choi J, Kim J, Kim JH, Oh K, Koh S, Seo W.
"From January 2008 to May 2010, we recruited patients within 7 days of the onset of acute ischemic stroke using the prospectively collected hospital-based stroke registry . . . During the study period, a total of 864 patients with acute ischemic stroke and appropriate radiologic findings were recruited. Of these patients, 20 died at initial admission, 79 had no measurement of their baseline FFA level, and 96 were lost to follow-up. Finally, 669 patients were analyzed (figure). Clinical and laboratory parameters including hypertension, diabetes, lipid profiles, smoking, and body mass index were assessed as in previous studies.13"
"In this study, plasma FFA concentration was associated with stroke caused by CE. The baseline level of FFA in CE stroke patients was approximately 1.5-fold higher than that of non-CE stroke patients. Furthermore, we showed that plasma FFA concentration was independently associated with recurrent stroke only in the CE stroke group. Moreover, we found that FFA may potentially play different roles in stroke recurrence depending on the underlying cause of the stroke."
"Several possible explanations exist for the association found between plasma FFA concentration and CE stroke in this study.17 First, FFA may generate arrhythmia. Previously, we demonstrated that the association between FFA and CE stroke might result from the association between FFA and AF.13 Numerous experimental studies have also suggested the arrhythmogenicity of FFA. Studies using rats showed that if the molar ratio of FFA to albumin was sufficiently high, FFA could be directly arrhythmogenic in the absence of ischemia.18"
"The arrhythmogenicity of FFA may have been confirmed recently in a population-based prospective cohort study using 4,175 men, in which an increased risk of AF [atrial fibrillation] in subjects with higher FFA concentration was shown at a 10-year follow-up.12"

Cerebrospinal Fluid Free Fatty Acid Levels Are Associated with Stroke Subtypes and Severity in Chinese Patients with Acute Ischemic Stroke
World Neurosurg. 2015 Nov;84(5):1299-304. Sun G, Ding S, Ling W, Wang F, Yang X.
"In our study, from a total of 213 eligible patients, CSF was collected after admission for a standardized measurement of FFA and Hs-CRP in 119 patients; these measurements could not be performed in 94 patients (Four patients died, 56 were discharged to another institution before the standardized CSF sampling could be performed, 12 were omitted by mistake and 26 refused to participate)."
"The CSF levels of FFA at different time-points after admission were tested. We found that a two-fold increase of FFA compared with the baseline values has shown to begin 12 h after admission, reaching peak values at 24 h and returning to admission values by 48h (Figure 1a and table 1). The results indicated that the CSF FFA levels were significantly (P<0.0001) higher in AIS as compared to controls (0.22; IQR, 0.11-0.31mmol/L and 0.11; IQR, 0.06-0.14mmol/L, respectively; Figure 1b.). The CSF FFA levels increased with the increasing severity of stroke as defined by the NIHSS score. There were positive correlations that linked the levels of FFA to the NIHSS (r=0.424, P<0.0001; Figure 2a.) and Hs-CRP levels (r=0.208, P=0.006). There was still a significant positive trend between FFA levels and NIHSS score (P=0.002) using ordered logistic regression after multivariate adjustments for above possible confounders."
"In our study, we reported that CSF FFA levels were significantly higher in stroke than in controls and displayed many similarities to data obtained in experiments in humans (19) and rats (20). Our main findings were that FFA levels were in correlation with stroke subtypes and could be seen as an indicator for the diagnosis of CE stroke. In this process, the positive predictive value was 84.0% and the negative predictive value was 89.6%. The baseline level of FFA in CE stroke patients was approximately 2.5-fold higher than that of non-CE stroke patients, which was supported by Choi et al. (5). Furthermore, we found that the FFA levels increased as the severity of stroke increased, which was defined by the NIHSS score and infarct volume. Those positive trends still existed even after correcting for possible confounding factors. "
". . . elevated FFA might have thrombogecity in CE stroke patients (23). Consistent with this, animal studies have demonstrated a systemic thromboembolism after FFA infusion (6), with activation of factor XII by stearic acids postulated as a possible mechanism(9). Third, an increase of plasma FFA in stroke patients may reflect a metabolic state of CE strokes attributed to AF. An elevated plasma FFA concentration could be associated with hyper-triglyceridemia, obesity, insulin resistance, and cardiovascular disease (12). Finally, the effects of free fatty acids on brain inflammation have been evaluated (14). Dasu et al. (7) concluded that FFA exacerbates HG-induced TLR expression and activity in monocytic cells with excess superoxide release, enhanced NF-κB activity, and induced pro-inflammatory factor release."

Nonesterified fatty acids and cardiovascular mortality in elderly men with CKD.
Clin J Am Soc Nephrol . 2015 Apr 7;10(4):584-91. Xiong Z et al.
"During this examination, participants were aged 70–71 years (examinations performed during 1991–1995; n=1221). A total of 632 individuals were identified as having CKD on the basis of cystatin C eGFR<60 ml/min per 1.73 m2 (n=537) or urine albumin excretion rate (UAER) ≥20 µg/min (16) (n=86), or both of these conditions (n=125). NEFA measurements were available in 623 (98.6%) of those patients included in the analysis. . . . Follow-up for mortality was done from examination date until death or December 31, 2007, with no loss to follow-up. The Swedish National Registry recording for date and cause of death was used to define end points. The primary outcome considered was death attributed to CVD (ICD-9 codes 390–459 or ICD-10 codes I00–I99). We included death due to IHD (ICD-9 codes 410–414 or ICD-10 codes I20–I25) or acute myocardial infarction (AMI) (ICD-9 code 410, ICD-10 code I21) as secondary outcomes. Other CVD causes were lumped together, including cerebrovascular events (ICD-9 codes 430–438 or ICD-10 codes I60–I69), acute rheumatic fever (ICD-9 codes 390–392 or ICD-10 codes I00–I02), chronic rheumatic heart diseases (ICD-9 codes 393–398, ICD-10 codes I05–I09), hypertensive diseases (ICD-9 codes 401–405, ICD-10 codes I10–I15), pulmonary circulation diseases (ICD-9 codes 415–417, ICD-10 codes I26–I28), and other forms of heart diseases (ICD-9 codes 420–429, ICD-10 codes I30–I32)."
"Across increasing NEFA tertiles, participants with CKD had a higher BMI, and a trend toward higher prevalence of diabetes, hypertension and hyperlipidemia (higher triglycerides), fasting glucose, and insulin, as well as lower insulin sensitivity among nonpatients with diabetes."
"Kaplan–Meier curves show an association between NEFA and CVD mortality (log rank× 2=8.83, P=0.01; Figure 1). Table 3 presents analyses of the association between NEFA as a continuous variable and outcomes. Despite multivariable adjustment, every log2 mg/dl higher in NEFA (thus, every doubling in NEFA concentration) associated with higher hazards for mortality, and more strongly for CVD mortality. The magnitude of the hazards increased when addressing the secondary outcomes of IHD and AMI mortality. A spline curve analysis based on hazard ratios of the fully adjusted model for CVD mortality associated with serum NEFA showed a significant association of NEFA levels with mortality risk (Figure 2)."
"To our knowledge, this is the first prospective cohort study to address serum NEFA concentrations in relation to CVD mortality in individuals with CKD. We show that NEFAs are independent predictors for mortality, but more specifically so for CVD mortality, including IHD and AMI mortality as secondary outcomes."
"Here we show that NEFA levels predict fatal cardiovascular events in a moderately large population of elderly patients with CKD. This is in line with previous case-control studies in individuals with diabetes (33), linking NEFA concentrations with IHD risk. In another study of patients with IHD, increased NEFA concentrations predicted all-cause and CVD mortality (6). Finally, at a community level, NEFA associated with AMI incidence (5,10) and the risk of sudden cardiac death (7–9)."
"In conclusion, serum NEFA was associated with CVD mortality in elderly men with CKD. These findings, if confirmed in subsequent studies, offer interesting perspectives regarding therapeutic strategies focusing on improved myocardial metabolism via decreased NEFA levels (26)."
 

exile

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Does anyone know what ideal ffa levels are? I measured mine recently (fatty acids non ester) and my fasting results were .9 meq/l (range was .1-.9). Just curious others results if you’ve done one. Only quotes I’m seeing from Ray is that the ffa levels should be low and “Keep the free fatty acids low in relation to albumin, they will largely be carried bound to the albumin to the liver.” What dietary changes lower ffa? Seeing contradicting info whether lower fat makes a difference.
 

Regina

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A high serum-free fatty acid level is associated with cancer.
J Cancer Res Clin Oncol. 2020 Mar;146(3):705-710. Zhang L, Han L, He J, Lv J, Pan R, Lv T.




High free fatty acid level is associated with recurrent stroke in cardioembolic stroke [CE] patients.
Neurology. 2014 Apr 1;82(13):1142-8. Choi J, Kim J, Kim JH, Oh K, Koh S, Seo W.





Cerebrospinal Fluid Free Fatty Acid Levels Are Associated with Stroke Subtypes and Severity in Chinese Patients with Acute Ischemic Stroke
World Neurosurg. 2015 Nov;84(5):1299-304. Sun G, Ding S, Ling W, Wang F, Yang X.





Nonesterified fatty acids and cardiovascular mortality in elderly men with CKD.
Clin J Am Soc Nephrol . 2015 Apr 7;10(4):584-91. Xiong Z et al.
Thanks for posting these!
 

Apple

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Is it possible to gain healthy subcutaneous fat without elevated fatty acids ?
 
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