Dr. Ron’s Research Review – September 12, 2018

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This week’s research review focuses on nervonic acid.

Nervonic acid (24:1, n-9) is a fatty acid. It is a monounsaturated analog of lignoceric acid (24:0). It is also known as selacholeic acid and cis-15-tetracosenoic acid.
Nervonic acid is particularly abundant in the white matter of animal brains and in peripheral nervous tissue where nervonyl sphingolipids are enriched in the myelin sheath of nerve fibers.

Demyelinating Disease

An older study of demyelinating disease found decreased levels of nervonic acid, 24:1(n-9), and increased levels of stearic acid, 18:0. (Sargent et al., 1994)

Depression

Plasma nervonic acid is a potential biomarker for major depressive disorder. (Kageyama et al., 2018)

Metabolic Syndrome

A study found that the proportion of nervonic acid in serum lipids was associated with serum plasmalogen levels and metabolic syndrome. (Yamazaki et al., 2014)

Coronary Risk Factors

Oleic acid (OA), linoleic acid (LA), and eicosapentaenoic acid (EPA) were positively related to coronary risk factors (total CRFS = 2, 3, and 4, respectively), while nervonic acid (NA) exerted negative effects on these risk factors (total CRFS = -6 ). NA may have preventive effects on obesity-related metabolic disorders. (Oda et al., 2005)

Dr. Ron

 


Articles

 

Plasma Nervonic Acid Is a Potential Biomarker for Major Depressive Disorder: A Pilot Study.
            (Kageyama et al., 2018) Download
Background:  Diagnostic biomarkers of major depressive disorder, bipolar disorder, and schizophrenia are urgently needed, because none are currently available. Methods:  We performed a comprehensive metabolome analysis of plasma samples from drug-free patients with major depressive disorder (n=9), bipolar disorder (n=6), schizophrenia (n=17), and matched healthy controls (n=19) (cohort 1) using liquid chromatography time-of-flight mass spectrometry. A significant effect of diagnosis was found for 2 metabolites: nervonic acid and cortisone, with nervonic acid being the most significantly altered. The reproducibility of the results and effects of psychotropic medication on nervonic acid were verified in cohort 2, an independent sample set of medicated patients [major depressive disorder (n=45), bipolar disorder (n=71), schizophrenia (n=115)], and controls (n=90) using gas chromatography time-of-flight mass spectrometry. Results:  The increased levels of nervonic acid in patients with major depressive disorder compared with controls and patients with bipolar disorder in cohort 1 were replicated in the independent sample set (cohort 2). In cohort 2, plasma nervonic acid levels were also increased in the patients with major depressive disorder compared with the patients with schizophrenia. In cohort 2, nervonic acid levels were increased in the depressive state in patients with major depressive disorder compared with the levels in the remission state in patients with major depressive disorder and the depressive state in patients with bipolar disorder. Conclusion:  These results suggested that plasma nervonic acid is a good candidate biomarker for the depressive state of major depressive disorder.

Relationships between serum unsaturated fatty acids and coronary risk factors: negative relations between nervonic acid and obesity-related risk factors.
            (Oda et al., 2005) Download
Relative increases in unsaturated fatty acids (USFA) in the diet are considered to exert beneficial effects on coronary risk factors (CRF). However, detailed analysis of the relationships between serum USFA and CRF are scanty and there is no report of the relationship between nervonic acid (NA) and CRF. The objective of the present study was to analyze the relationships between serum USFA and CRF. Body height and weight, blood pressure, fasting serum total cholesterol (TC), triacyl-glycerol (TG), HDL cholesterol (HDLc), fasting blood sugar (FBS), total fatty acid composition, leptin, and high-sensitivity C-reactive protein (CRP) were measured in 31 men (age, 41-78 years) and 11 women (age, 54-77 years). The relationships between serum USFA, and body mass index (BMI), leptin, systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, HDLc, FBS, and CRP were analyzed using multiple regression analysis. The final results were summarized using coronary risk factor scores (CRFS) in order to assess the correlations between USFA with CRF. Oleic acid (OA), linoleic acid (LA), and eicosapentaenoic acid (EPA) were positively related to coronary risk factors (total CRFS = 2, 3, and 4, respectively), while nervonic acid (NA) exerted negative effects on these risk factors (total CRFS = -6 ). It is concluded NA may have preventive effects on obesity-related metabolic disorders.

Nervonic acid and demyelinating disease.
            (Sargent et al., 1994) Download
Demyelination in adrenoleukodystrophy (ALD) is associated with an accumulation of very long chain saturated fatty acids such as 26:0 stemming from a genetic defect in the peroxisomal beta oxidation system responsible for the chain shortening of these fatty acids. Long chain monoenoic acids such as erucic acid, 22:1(n-9), can normalise elevated serum levels of 26:0 in ALD by depressing their biosynthesis from shorter chain saturated fatty acids. Sphingolipids from post mortem ALD brain have decreased levels of nervonic acid, 24:1(n-9), and increased levels of stearic acid, 18:0. Increased levels of 26:0 are accompanied by decreased nervonic acid biosynthesis in skin fibroblasts from ALD patients. Sphingolipids from post mortem MS brain have the same decreased 24:1(n-9) and increased 18:0 seen in post mortem ALD brain. The 24:1(n-9) content of sphingomyelin is depressed in erythrocytes from multiple sclerosis (MS) patients. Defects in the microsomal biosynthesis of very long chain fatty acids including 24:1(n-9) in 'jumpy' and 'quaking' mice are accompanied by impaired myelination. An impairment in the provision of nervonic acid in demyelinating diseases is indicated, suggesting that dietary therapy with oils rich in very long chain monenoic acid fatty acids may be beneficial in such conditions.

Proportion of nervonic acid in serum lipids is associated with serum plasmalogen levels and metabolic syndrome.
            (Yamazaki et al., 2014) Download
An increase in serum plasmalogens (1-O-alk-1-enyl-2-acyl glycerophospholipids), which are endogenous anti-oxidative phospholipids, can potentially prevent age-related diseases such as atherosclerosis and metabolic syndrome (MetS). Very long chain fatty acids (VLCFAs) in plasma may supply the materials for plasmalogen biosynthesis through peroxisomal beta-oxidation. On the other hand, elevated levels of saturated and monounsaturated VLCFAs in plasma appear to be associated with decreased peroxisomal function, and are a symptom of age-related diseases. To reconcile these contradictory findings, we attempted to investigate the relationship between the serum levels of saturated and monounsaturated VLCFAs, clinical and biochemical parameters, and serum levels of plasmalogens in subjects with MetS (n = 117), who were asymptomatic Japanese males over 40 years of age. Fatty acids in serum lipids were quantified using gas chromatography/mass spectrometry (GC/MS). Serum plasmalogen levels were determined by liquid chromatography using radioactive iodine (¹²⁵I-HPLC), and the molecular composition of serum plasmalogens was analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). We found that MetS subjects showed a significant reduction in the proportion of specific saturated and monounsaturated VLCFAs such as behenic acid (C22:0), lignoceric acid (C24:0), and nervonic acid (C24:1) in serum lipids compared to non-MetS subjects. These VLCFAs were positively associated with serum levels of high density lipoprotein cholesterol (HDL-C) as well as plasmalogen-related parameters, and inversely with serum levels of triglyceride (TG) and small dense low density lipoprotein cholesterol (sdLDL-C). In conclusion, the proportion of nervonic acid in serum lipids is associated with serum levels of plasmalogens and with MetS, and probably reflects the peroxisomal dysfunction and enhancement of endoplasmic reticulum (ER) stress seen in common age-related diseases.

 

References

Kageyama, Y, et al. (2018), ‘Plasma Nervonic Acid Is a Potential Biomarker for Major Depressive Disorder: A Pilot Study.’, Int J Neuropsychopharmacol, 21 (3), 207-15. PubMed: 29040586
Oda, E, et al. (2005), ‘Relationships between serum unsaturated fatty acids and coronary risk factors: negative relations between nervonic acid and obesity-related risk factors.’, Int Heart J, 46 (6), 975-85. PubMed: 16394593
Sargent, JR, K Coupland, and R Wilson (1994), ‘Nervonic acid and demyelinating disease.’, Med Hypotheses, 42 (4), 237-42. PubMed: 8072429
Yamazaki, Y, et al. (2014), ‘Proportion of nervonic acid in serum lipids is associated with serum plasmalogen levels and metabolic syndrome.’, J Oleo Sci, 63 (5), 527-37. PubMed: 24770479