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PloS One 2016In Tanzania, 35% of all children below five years of age are stunted. Dietary fatty acids (FA) are critical for growth and development. However, whole blood FA levels in...
BACKGROUND
In Tanzania, 35% of all children below five years of age are stunted. Dietary fatty acids (FA) are critical for growth and development. However, whole blood FA levels in Tanzanian children are poorly described.
OBJECTIVE
The objectives of this cross-sectional study were to assess 1) whole blood levels of essential fatty acids and 2) the association between whole blood FA levels and growth parameters in Tanzanian children 2-6 years of age.
METHODS
A drop of blood was collected on an antioxidant treated card and analyzed for FA composition. Weight and height were measured and z-scores calculated. Relationships between FAs and growth parameters were analyzed by linear regression.
RESULTS
Of the 334 children that participated, 30.3% were stunted. The average whole blood level of Mead acid was 0.15%. The anthropometric z-score height-for-age (HAZ) was inversely associated with Mead acid, the Mead acid to arachidonic acid (T/T) ratio, and total n-9 FA. Additionally, HAZ was positively associated with linoleic acid and total n-6 FA. BMI-for-age was positively associated with oleic acid, total n-9 FA and T/T ratio but inversely associated with arachidonic acid and total n-6 FA. Weight-for-height was inversely associated with arachidonic acid and total n-6 FAs and positively associated with oleic acid and total n-9 FA. Weight-for-age was not associated with any FA tested. Total n-3 FAs were not associated with any growth parameters measured.
CONCLUSIONS
The EFA linoleic acid and the markers of FA deficiency were associated with HAZ, an indicator for stunting in 2-6 year old Tanzanian children. Total n-6, total n-9, and a number of individual FAs were associated with growth. Increasing dietary intake of EFA and n-6 FAs may be a strategy to combat stunting in this population.
Topics: Body Height; Body Weight; Child; Child, Preschool; Cross-Sectional Studies; Female; Growth Disorders; Humans; Linoleic Acid; Male; Tanzania
PubMed: 27137223
DOI: 10.1371/journal.pone.0154715 -
Biomedical Reports Jan 2016The effect of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of the development and growth of -methyl--nitrosourea (MNU)-induced mammary cancer in female...
The effect of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of the development and growth of -methyl--nitrosourea (MNU)-induced mammary cancer in female Sprague-Dawley rats was examined. The MA diet (2.4% MA) or control (CTR) diet (0% MA) was started at 6 weeks of age, MNU was injected intraperitoneally at 7 weeks of age, and the rats were maintained on the respective diets for the whole experimental period (until 19 weeks of age). All induced mammary tumors were luminal A subtype carcinomas (estrogen and progesterone receptor positive and HER2/neu negative). The MA diet significantly suppressed the initiation and promotion phases of mammary carcinogenesis; MA suppressed the development (incidence, 61.5 vs. 100%; multiplicity, 2.1 vs. 4.5) and the growth (final tumor weight, 427.1 vs. 1,796.3 mg) of mammary cancers by suppressing cell proliferation, but not by accelerating cell death. There were evident changes in the major fatty acid composition of n-3, n-6, and n-9 fatty acids in the serum of the MA diet group; there was a significant increase in MA and significant decreases in oleic acid (OA), linoleic acid, arachidonic acid and docosahexaenoic acid. In non-tumorous mammary tissue, there was a significant increase in MA and a significant decrease in OA in the MA diet group. The n-6/n-3 ratios in serum and mammary tissue of the MA diet group were significantly decreased. The MA diet suppressed MNU-induced luminal A mammary cancer by lowering cancer cell proliferation. Therefore, MA may be a chemopreventive and chemotherapeutic agent. In addition to hormone therapy, MA supplementation may be a beneficial chemotherapeutic agent for the luminal A subtype of breast cancer.
PubMed: 26870330
DOI: 10.3892/br.2015.530 -
The FEBS Journal Nov 2015An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies...
An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium-chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1 year of supplementation as compared with a control diet. The de novo biosynthesis and elongation of fatty acids, and peroxisomal β-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced de novo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected de novo-synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal β-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing.
Topics: Acyl-CoA Dehydrogenase, Long-Chain; Animals; Congenital Bone Marrow Failure Syndromes; Dietary Fats; Disease Models, Animal; Fatty Acids; Female; Lipid Metabolism, Inborn Errors; Liver; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mitochondrial Diseases; Muscular Diseases; Myocardium; Oxidation-Reduction; Peroxisomes; Triglycerides
PubMed: 26284828
DOI: 10.1111/febs.13418 -
JPEN. Journal of Parenteral and Enteral... Sep 2015The fatty acids, linoleic acid (18:2ω-6) and α-linolenic acid (18:3ω-3), are essential to the human diet. When these essential fatty acids are not provided in... (Review)
Review
The fatty acids, linoleic acid (18:2ω-6) and α-linolenic acid (18:3ω-3), are essential to the human diet. When these essential fatty acids are not provided in sufficient quantities, essential fatty acid deficiency (EFAD) develops. This can be suggested clinically by abnormal liver function tests or biochemically by an elevated Mead acid and reduced linoleic acid and arachidonic acid level, which is manifested as an elevated triene/tetraene ratio of Mead acid/arachidonic acid. Clinical features of EFAD may present later. With the introduction of novel intravenous (IV) lipid emulsions in North America, the proportion of fatty acids provided, particularly the essential fatty acids, varies substantially. We describe a case series of 3 complicated obese patients who were administered parenteral nutrition (PN), primarily using ClinOleic 20%, an olive oil-based lipid emulsion with reduced amounts of the essential fatty acids, linoleic and α-linolenic, compared with more conventional soybean oil emulsions throughout their hospital admission. Essential fatty acid profiles were obtained for each of these patients to investigate EFAD as a potential cause of abnormal liver enzymes. Although the profiles revealed reduced linoleic acid and elevated Mead acid levels, this was not indicative of the development of essential fatty acid deficiency, as reflected in the more definitive measure of triene/tetraene ratio. Instead, although the serum fatty acid panel reflected the markedly lower but still adequate dietary linoleic acid content and greatly increased oleic acid content in the parenteral lipid emulsion, the triene/tetraene ratio remained well below the level, indicating EFAD in each of these patients. The availability and use of new IV lipid emulsions in PN should encourage the clinician to review lipid metabolism based on the quantity of fatty acids provided in specific parenteral lipid emulsions and the expected impact of these lipid emulsions (with quite different fatty acid composition) on measured fatty acid profiles.
Topics: 8,11,14-Eicosatrienoic Acid; Arachidonic Acid; Deficiency Diseases; Dietary Fats, Unsaturated; Fat Emulsions, Intravenous; Fatty Acids, Essential; Humans; Linoleic Acid; Liver; Oleic Acid; Parenteral Nutrition; Plant Oils; Soybean Oil; alpha-Linolenic Acid
PubMed: 26187936
DOI: 10.1177/0148607115595977 -
Journal of Toxicologic Pathology Jan 2015Fatty acids and their derivatives play a role in the response to ocular disease. Our current study investigated the effects of dietary mead acid (MA,...
Fatty acids and their derivatives play a role in the response to ocular disease. Our current study investigated the effects of dietary mead acid (MA, 5,8,11-eicosatrienoic acid) supplementation on N-methyl-N-nitrosourea (MNU)-induced cataract and retinal degeneration in Sprague-Dawley rats. Experiment 1 was designed to inhibit cataract formation, with the dams fed a 2.4% MA or basal (<0.01% MA) diet during lactational periods. On postnatal day 7, male pups received a single intraperitoneal (ip) injection of 50 mg/kg MNU or vehicle. Lens opacity and morphology were examined 7 and 14 days after the MNU injection. Experiment 2 was designed to inhibit retinal degeneration and was performed with female postweaning rats. In this experiment, dams were fed the 2.4% MA or basal diet during the lactational periods. Thereafter, the female pups were continuously fed the same diets during their postweaning periods. On postnatal day 21 (at weaning), pups received a single ip injection of 50 mg/kg MNU. Retinal morphology was examined 7 days after the MNU injection. In experiment 3, six-week-old female rats were fed the 2.4% MA or basal diet starting at one week before the MNU injection and were then continuously fed the same diets until sacrifice. Rats at 7 weeks of age were given a single ip injection of 40 mg/kg MNU, and the retina was then examined morphologically one week after the MNU injection. In experiment 1, mature cataract was found in all of the MNU-treated groups, with or without MA supplementation. In experiments 2 and 3, atrophy of both the peripheral and central outer retina occurred in all rats exposed to MNU, with or without MA supplementation, respectively. The severities of the cataracts and retinal atrophy in the rats were similar regardless of MA supplementation. Dietary mead acid, which is used as a substitute in essential fatty acid deficiency in the body, does not modify MNU-induced cataract and retinal degeneration in rat models.
PubMed: 26023256
DOI: 10.1293/tox.2014-0036 -
Prostaglandins, Leukotrienes, and... May 2015Ossification of the posterior longitudinal ligament (OPLL) involves the replacement of ligamentous tissue with ectopic bone. Although genetics and heritability appear to...
Ossification of the posterior longitudinal ligament (OPLL) involves the replacement of ligamentous tissue with ectopic bone. Although genetics and heritability appear to be involved in the development of OPLL, its pathogenesis remains to be elucidated. Given previous findings that 5,8,11-eicosatrienoic acid [20:3n-9, Mead acid (MA)] has depressive effects on osteoblastic activity and anti-angiogenic effects, and that n-3 polyunsaturated fatty acids (PUFAs) have a preventive effect on heterotopic ossification, we hypothesized that both fatty acids would be involved in OPLL development. To examine the biological significance of these and other fatty acids in OPLL, we conducted this case-control study involving 106 patients with cervical OPLL and 109 age matched controls. Fatty acid composition was determined from plasma samples by gas chromatography. Associations between fatty acid levels and incident OPLL were evaluated by logistic regression. Contrary to our expectations, we found no significant differences between patients and controls in the levels of MA or n-3 PUFAs (e.g., eicosapentaenoic acid and docosahexaenoic acid). Logistic regression analysis did not reveal any associations with OPLL risk for MA or n-3 PUFAs. In conclusion, no potential role was found for MA or n-3 PUFAs in ectopic bone formation in the spinal canal.
Topics: 8,11,14-Eicosatrienoic Acid; Aged; Case-Control Studies; Fatty Acids, Omega-3; Female; Humans; Longitudinal Ligaments; Male; Middle Aged; Ossification, Heterotopic; Risk Factors
PubMed: 25669698
DOI: 10.1016/j.plefa.2015.01.003 -
Lipids in Health and Disease Dec 2014Elevated serum Mead acid as a proportion of total fatty acids is an indirect marker of a deficiency of essential fatty acids (EFA). The aim of the study was to evaluate...
BACKGROUND
Elevated serum Mead acid as a proportion of total fatty acids is an indirect marker of a deficiency of essential fatty acids (EFA). The aim of the study was to evaluate the symptoms and nutrition of food-allergic children with elevated or normal serum Mead acid.
METHODS
Serum fatty acid compositions from 400 children were studied by clinical indications, mostly by suspicion of deficiency of EFA due to inadequate nutrition. A Mead acid level exceeding 0.21% (percentage of total fatty acids) was considered to be a specific sign of an insufficient EFA supply. From a total of 31 children with elevated Mead acid (MEADplus group), 23 (74%) had food allergy. The symptoms and dietary restrictions of this MEADplus group of food allergic children were compared to 54 age-and sex-matched controls with food allergy but normal Mead acid proportions (MEADminus group) before and 6 months after the serum fatty acid determination.
RESULTS
At the beginning of the 6-month follow-up, 44% of the food allergic children in both MEADplus and MEADminus groups were on an elimination diet. These diets did not differ between the two groups and we were not able to document an association between the severity of elimination diet and elevated Mead acid proportion. However, the MEADplus children were on average more symptomatic than MEADminus children. In the MEADplus group, food allergy presented with skin symptoms in 100% (vs. 70% in the MEADminus group, p < 0.001) and with vomiting or diarrhea in 70% (vs. 44% in the MEADminus group, p < 0.05). Clinical suspicion of malnutrition resulted in increase in the use of vegetable oil and milk-free margarine in both groups from <50% to 65-74% during the follow-up. After 6 months, 64% of the MEADplus children with food allergy had been sent to a control serum fatty acid analysis. Of these children, Mead acid had declined to normal level in 69%, and remained elevated in 31%.
CONCLUSIONS
Severe symptoms of food allergy combined with elimination diets in children may lead to insufficient nutrition presenting with elevated serum Mead acid. Adding of supplementary polyunsaturated fat to the diet should be considered in these children.
Topics: 8,11,14-Eicosatrienoic Acid; Case-Control Studies; Child, Preschool; Diet; Fatty Acids, Essential; Female; Food Hypersensitivity; Humans; Infant; Male
PubMed: 25440954
DOI: 10.1186/1476-511X-13-180 -
Oncology Reports Oct 2014The effects of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of breast cancer cell growth and metastasis were examined in vitro and in vivo by using...
The effects of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of breast cancer cell growth and metastasis were examined in vitro and in vivo by using the KPL-1 human breast cancer cell line. MA suppressed KPL-1 cell growth in culture with an IC50 value of 214.2 µM (65.7 µg/ml) for 72 h, and MA significantly suppressed transplanted KPL-1 tumor growth (tumor volume and tumor weight: 872±103 mm3 and 1,000±116 mg vs. 376±66 mm3 and 517±84 mg) and regional (axillary) lymph node metastasis (67%, 10/15 vs. 10%, 1/10) in female athymic mice fed an MA-rich diet for 8 weeks. Tumor suppression was due to the suppression of cell proliferation. In ELISA, although vascular endothelial growth factor (VEGF) levels were unchanged, VEGF receptor (VEGFR)1 and VEGFR2 levels were significantly decreased after treatment with a 214.2-µM dose of MA for 72 h; E-cadherin levels were unchanged. As VEGF, VEGFR1 and VEGFR2 expression was co-localized in KPL-1 cells, the mechanism leading to cell growth suppression was VEGF signaling directly to KPL-1 cells by an autocrine process. In contrast, MA did not influence angiogenesis. The mechanisms of action were through VEGF signaling directly to cancer cells.
Topics: 8,11,14-Eicosatrienoic Acid; Animals; Apoptosis; Breast Neoplasms; Cadherins; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Female; Humans; In Vitro Techniques; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Xenograft Model Antitumor Assays
PubMed: 25109488
DOI: 10.3892/or.2014.3390 -
PloS One 2014Mechanistic data suggest that different types of fatty acids play a role in carcinogenesis and that antioxidants may modulate this relationship but epidemiologic...
Prospective associations between plasma saturated, monounsaturated and polyunsaturated fatty acids and overall and breast cancer risk - modulation by antioxidants: a nested case-control study.
BACKGROUND
Mechanistic data suggest that different types of fatty acids play a role in carcinogenesis and that antioxidants may modulate this relationship but epidemiologic evidence is lacking. Our aim was to investigate the association between plasma saturated, monounsaturated and polyunsaturated fatty acids (SFAs, MUFAs and PUFAs) and overall and breast cancer risk and to evaluate the potential modulatory effect of an antioxidant supplementation on these relationships.
METHODS
A nested case-control study included all first incident cancer cases diagnosed in the SU.VI.MAX study between 1994 and 2002 (n=250 cases, one matched control/case). Participants to the SU.VI.MAX randomized controlled trial received either vitamin/mineral antioxidants or placebo during this intervention period. Baseline fatty acid composition of plasma total lipids was measured by gas chromatography. Conditional logistic regression was performed overall and stratified by intervention group.
RESULTS
Dihomo-γ-linolenic acid (Ptrend=0.002), the dihomo-γ-linolenic/linoleic acids ratio (Ptrend=0.001), mead acid (Ptrend=0.0004), and palmitoleic acid (Ptrend=0.02) were inversely associated with overall cancer risk. The arachidonic/dihomo-γ-linolenic acids ratio (Ptrend=0.02) and linoleic acid (Ptrend=0.02) were directly associated with overall cancer risk. Similar results were observed for breast cancer specifically. In stratified analyses, associations were only observed in the placebo group. Notably, total PUFAs were directly associated with overall (Ptrend=0.02) and breast cancer risk in the placebo group only.
CONCLUSION
Specific SFAs, MUFAs and PUFAs were prospectively differentially associated with cancer risk. In addition, this study suggests that antioxidants may modulate these associations by counteracting the potential effects of these fatty acids on carcinogenesis.
Topics: Antioxidants; Breast Neoplasms; Case-Control Studies; Dietary Supplements; Fatty Acids; Fatty Acids, Unsaturated; Female; Humans; Male; Prospective Studies; Risk
PubMed: 24587366
DOI: 10.1371/journal.pone.0090442 -
Biochimica Et Biophysica Acta Jan 2014In mammals, 5,8,11-eicosatrienoic acid (Mead acid, 20:3n-9) is synthesized from oleic acid during a state of essential fatty acid deficiency (EFAD). Mead acid is thought...
In mammals, 5,8,11-eicosatrienoic acid (Mead acid, 20:3n-9) is synthesized from oleic acid during a state of essential fatty acid deficiency (EFAD). Mead acid is thought to be produced by the same enzymes that synthesize arachidonic acid and eicosapentaenoic acid, but the genes and the pathways involved in the conversion of oleic acid to Mead acid have not been fully elucidated. The levels of polyunsaturated fatty acids in cultured cells are generally very low compared to those in mammalian tissues. In this study, we found that cultured cells, such as NIH3T3 and Hepa1-6 cells, have significant levels of Mead acid, indicating that cells in culture are in an EFAD state under normal culture conditions. We then examined the effect of siRNA-mediated knockdown of fatty acid desaturases and elongases on the level of Mead acid, and found that knockdown of Elovl5, Fads1, or Fads2 decreased the level of Mead acid. This and the measured levels of possible intermediate products for the synthesis of Mead acid such as 18:2n-9, 20:1n-9 and 20:2n-9 in the knocked down cells indicate two pathways for the synthesis of Mead acid: pathway 1) 18:1n-9→(Fads2)→18:2n-9→(Elovl5)→20:2n-9→(Fads1)→20:3n-9 and pathway 2) 18:1n-9→(Elovl5)→20:1n-9→(Fads2)→20:2n-9→(Fads1)→20:3n-9.
Topics: 8,11,14-Eicosatrienoic Acid; Acetyltransferases; Animals; Biomarkers; Fatty Acid Desaturases; Fatty Acid Elongases; Fatty Acids, Essential; Gene Knockdown Techniques; Male; Mice; NIH 3T3 Cells
PubMed: 24184513
DOI: 10.1016/j.bbalip.2013.10.013