Do increased levels of Arachidonic Acid in one’s diet increase your risk of inflammation and angiogenesis in one’s body and lead to angiogenesis-based diseases?

I think it does!

But there is a good deal of controversy among those who are involved in diet plans and overall medical health.

I will commend on this further but would like by starting to compile a list of references in favor of this theory.

I do think a profile of each of the following factos of a particular food need to be considered when eating. Let us call it the “Global Index of Food Therapy” or the “GIFT of GAFC”

-Glycemic Index per 100mg
-Arachidonic Acid Level per 100mg
-Fat Content per 100mg
-Calories per per 100mg

GAFC

Each molecule we put in our mouth has a potential positive and potential negative effect on our body. We need to find out the particular GAFC of each molecule and then see which of these 4 key components is most important in controlling inflammation in one’s body and controlling inflammation based diseases such as diabetes.

Some foods have high glycemic indices and very low arachidonic levels such as popcorn. Too much of this is also not good for your body.

The goal is moderation in all things, but I for one would like to see each food out there labelled under a standard measure of “per 100mg or 1000mg” with GAFC calculations separately calculated and globally.

Here begins some recent references that hint to the answer to my question above being YES!

[As a note to self in Meibomian Gland Probing:
Also, it will be very interesting to see a head to head trial of the following:
-injection into the meibomian glands steroid versus EPA+DHA (omega-3 PUFAs results in a rapid increase of EPA and DHA in plasma PC and of EPA in erythrocytes, suggesting that infusion of omega-3 PUFAs could be used to induce a rapid effect especially in targeting inflammation)

Used below: each 100 ml of Lipidem® will typically contain about 1.25 g EPA plus DHA (0.74 g EPA and 0.51 g DHA).]

Lipids Health Dis. 2013; 12: 64.
Published online 2013 May 7. doi:  10.1186/1476-511X-12-64
PMCID: PMC3659039

Changes in plasma and erythrocyte omega-6 and omega-3 fatty acids in response to intravenous supply of omega-3 fatty acids in patients with hepatic colorectal metastases

Omer Al-Taan,1 James A Stephenson,1 Laura Spencer,1 Cristina Pollard,1 Annette L West,2 Philip C Calder,corresponding author2,3Matthew Metcalfe,1 and Ashley R Dennison1
Author information ► Article notes ► Copyright and License information ►

Abstract

Background

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are functionally the most important omega-3 polyunsaturated fatty acids (PUFAs). Oral supply of these fatty acids increases their levels in plasma and cell membranes, often at the expense of the omega-6 PUFAs arachidonic acid (ARA) and linoleic acid. This results in an altered pattern of lipid mediator production to one which is less pro-inflammatory. We investigated whether short term intravenous supply of omega-3 PUFAs could change the levels of EPA, DHA, ARA and linoleic acid in plasma and erythrocytes in patients with hepatic colorectal metastases.

Methods

Twenty patients were randomised to receive a 72 hour infusion of total parenteral nutrition with (treatment group) or without (control group) omega-3 PUFAs. EPA, DHA, ARA and linoleic acid were measured in plasma phosphatidylcholine (PC) and erythrocytes at several times points up to the end of infusion and 5 to 12 days (mean 9 days) after stopping the infusion.

Results

The treatment group showed increases in plasma PC EPA and DHA and erythrocyte EPA and decreases in plasma PC and erythrocyte linoleic acid, with effects most evident late in the infusion period. Plasma PC and erythrocyte EPA and linoleic acid all returned to baseline levels after the 5–12 day washout. Plasma PC DHA remained elevated above baseline after washout.

Conclusions

Intravenous supply of omega-3 PUFAs results in a rapid increase of EPA and DHA in plasma PC and of EPA in erythrocytes. These findings suggest that infusion of omega-3 PUFAs could be used to induce a rapid effect especially in targeting inflammation.

Trial registration

http://www.clinicaltrials.gov identifier NCT00942292
Keywords: Parenteral nutrition, Fish oil, Omega-3 fatty acids, Eicosapentaenoic acid, Docosahexaenoic acid, Arachidonic acid, Liver metastases

Background

Polyunsaturated fatty acids (PUFAs) have important roles in membrane structure and function, cell signalling and regulation of gene expression, and as substrates for synthesis of lipid mediators involved in inflammation, immunity, coagulation, smooth muscle contraction and many other physiological responses [
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Destroy user interface control]. The two main families of PUFAs are the omega-6 and omega-3 families. The main dietary omega-6 PUFA is linoleic acid [

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Destroy user interface control] and its derivative, arachidonic acid (ARA), is important with regard to all of the roles mentioned above [

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Destroy user interface control]. The main dietary omega-3 PUFA is α-linolenic acid [

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Destroy user interface control]. Its derivatives, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are again involved in the roles mentioned above [

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Destroy user interface control–

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Destroy user interface control], although it is important to note that conversion of α-linolenic acid to EPA, and especially to DHA, appears to be limited in humans [

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Destroy user interface control]. Omega-6 and omega-3 PUFAs frequently compete with one another for metabolism and often act in an opposing manner to one another [

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Destroy user interface control–

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Destroy user interface control]. This is especially so for ARA and EPA with regard to inflammatory processes [

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Destroy user interface control]. Hence achieving the correct “balance” between specific members of the omega-6 and omega-3 PUFA families is likely to be important for good health and for improved patient outcomes. Conversely a disturbed balance may be associated with poorer health and poorer patient outcome. Because of the high dietary abundance of omega-6 PUFAs [

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Destroy user interface control] and the relatively poor abundance of omega-3 PUFAs, omega-6 fatty acids predominate over omega-3 in blood lipids, blood cells and most tissues [

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Destroy user interface control–

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Destroy user interface control]. However, increased oral intake of EPA and DHA results in an increase in their abundance in blood lipids [

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Destroy user interface control], in blood cells [

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Destroy user interface control], and in tissues [

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Destroy user interface control]. Likewise, intravenous supply of EPA and DHA increases the content of those fatty acids in blood lipids [

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Destroy user interface control] and in blood cells [

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Patients who undergo major surgery have a risk of infectious complications and these may increase morbidity, length of hospital stay and mortality. It is possible that the risk of infection, of further complications and of being unable to recover from the complications is increased by a high status of omega-6 fatty acids and/or a low status of omega-3 fatty acids, especially EPA and DHA [
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Destroy user interface control]. Therefore, providing EPA and DHA in advance of a surgical insult might reduce the risk of adverse consequences [

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Destroy user interface control]. Intravenous administration of EPA and DHA, in the form of a lipid emulsion containing some fish oil, is a strategy to easily and rapidly increase omega-3 PUFA supply and status [

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Destroy user interface control]. The impact of intravenous fish oil has been explored in some surgical settings, mainly related to colorectal cancer resection [

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Destroy user interface control], but not in the context of removal of liver metastases. The aim of the present study was to examine the fatty acid composition of plasma phosphatidylcholine (PC), the major phospholipid in the circulation, and erythrocytes during and after short term intravenous administration of a lipid emulsion that includes fish oil in patients awaiting surgery for removal of liver colorectal metastases.

Methods

Study design

This study was part of a double blind randomised controlled trial examining the effect of fish oil on human colorectal metastases. Ethical approval was obtained from the Leicestershire, Northamptonshire and Rutland Research Ethics Committee (REC number 06/Q2501/16) and approval for the study was obtained from the Medicines and Healthcare Products Regulatory Agency (EudraCT number: 2006-000044-71). The trial is registered at http://www.clinicaltrials.gov with identifier NCT00942292. Patients gave written informed consent.

Patient selection and lipid administration

Patients who had hepatic colorectal metastases larger than 3 cm in diameter were identified from the University Hospitals of Leicester Hepatobiliary Cancer Multi-Disciplinary Team meetings. Patients where the lesion was deemed amenable for curative resection were invited to enrol in the study. To be eligible for inclusion, patients had to have normal liver function tests and normal plasma lipid concentrations. Twenty patients were enrolled in the trial. Patients were aged 44 to 80 years and there were 9 men and 11 women. Patients received total parenteral nutrition for 72 hr continuously at a rate of 1.5 ml per kilogram body weight per hr via a peripherally inserted central catheter and only drank water by mouth. The parenteral nutrition was in the form of 2000 ml Nutriflex basal® (B Braun, Melsungen, Germany) compounded with 500 ml Lipidem® 20% (B Braun) in the treatment group or with 500 ml Lipofundin® MCT 20% (B Braun) in the control group. Lipidem® (also known as Lipoplus®) is a 50:40:10 (vol/vol/vol) mix of medium-chain triglycerides, soybean oil and fish oil; each 100 ml of Lipidem® will typically contain about 1.25 g EPA plus DHA (0.74 g EPA and 0.51 g DHA). Lipofundin® MCT is a 50:50 (vol/vol) mix of medium-chain triglycerides and soybean oil. Median age (69 years in the control group and 63 years in the treatment groups) and the balance of men and women (5:6 in the control group and 4:5 in the treatment group) did not differ between the two groups.

Blood sampling and processing

Blood samples were taken immediately before the infusion and 1, 3, 6, 20, 44, 68 and 72 hr after starting the infusion. On finishing the infusion, patients were discharged home and re-admitted within 2 weeks (5 to 12 days; mean 9 days) to have resection of the liver lesion; at this stage one further blood sample was taken. Blood was collected into heparin as anti-coagulant. Blood was centrifuged to obtain plasma and an erythrocyte pellet. These were separated and stored at −80°C until analysis.

Fatty acid composition of plasma phosphatidylcholine and erythrocytes

Total lipid was extracted from plasma or erythrocytes using chloroform/methanol (2:1 vol/vol). PC was separated from other plasma lipids by solid phase extraction on Bond Elut cartridges (Varian, Palo Alto, CA, USA). Plasma PC and erythrocyte lipids were saponified and fatty acid methyl esters formed by heating at 50°C for 2 hr in the presence of sulphuric acid containing 2% methanol. Fatty acid methyl esters were extracted into hexane and concentrated by evaporation under nitrogen. Fatty acid methyl esters were separated by gas chromatography on a Hewlett Packard 6890 gas chromatograph (Hewlett Packard, CA, USA) fitted with a BPX70 column (SGE Europe, Milton Keynes, Bucks, UK). Running conditions were as described elsewhere [
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Destroy user interface control]. Fatty acids were identified by comparison of retention times with those of authentic standards. Data are expressed as percentage contribution to the total fatty acid pool. The main focus of the data shown in this paper is on EPA, DHA, ARA and linoleic acid.

Statistical analysis

Data are shown as mean + SEM. Data were first analysed using two-factor ANOVA (factors: time and group) for repeated measures. This was followed by analysis of effects within a group and by pairwise comparisons between groups as appropriate. Statistical analysis was performed using GraphPad Prism for windows (GraphPad Software Inc., CA, USA). Differences were considered significant at P < 0.05.

Results

The control group (n = 11) received total parenteral nutrition for 72 hr with the lipid component being in the form of a 50:50 (vol/vol) mixture of medium-chain triglycerides and soybean oil. The treatment group (n = 9) received a 50:40:10 (vol/vol/vol) mixture of medium-chain triglycerides, soybean oil and fish oil. Blood samples were taken immediately before infusion and 1, 3, 6, 20, 44, 68 and 72 hr after starting the infusion. A further sample was collected 5 to 12 days (mean 9 days) after the end of the infusion period. The fatty acid compositions of plasma PC and erythrocytes were determined. These did not differ between groups at baseline (i.e. prior to infusion).

Plasma phosphatidylcholine fatty acids

There was a significant effect of time (P < 0.001) and group (P < 0.001) and a significant time x group interaction (P < 0.001) for plasma PC EPA. Plasma PC EPA showed a small, but significant, decrease in the control group (P = 0.004), with the decrease apparent after 20 (P = 0.010 vs baseline), 44 (P = 0.019), 68 (P = 0.002) and 72 (P = 0.003) hr of infusion (Figure 1). Plasma PC EPA showed a marked and significant increase in the treatment group (P < 0.001), with the increase apparent after 20 (P = 0.066 vs baseline), 44 (P < 0.001), 68 (P < 0.001) and 72 (P < 0.001) hr of infusion (Figure 1). Plasma PC EPA was higher in the treatment group than in the control group at 20, 44, 68 and 72 hr (all P < 0.001). Plasma PC EPA returned to baseline values in both control and treatment groups after the 5 to 12 day washout period (Figure 1).
Figure 1

Plasma PC eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid and linoleic acid before (baseline), during (1 hr to 72 hr) and 5–12 days after stopping infusion of a mixture of medium-chain triglycerides and soybean oil (control: …
There was a significant effect of time (P < 0.001) and a significant time x group interaction (P < 0.001) for plasma PC DHA. Plasma PC DHA did not change significantly in the control group (P > 0.05; Figure 1). Plasma PC DHA increased in the treatment group (P < 0.001), with the increase apparent at 44 (P = 0.031 vs baseline), 68 (P = 0.008) and 72 (P = 0.011) hr (Figure 1). Plasma PC DHA was higher in the treatment group than in the control group at 68 (P = 0.007) and 72 (P = 0.067) hr. Plasma PC DHA remained elevated above baseline levels (P = 0.050) in the treatment group after the 5 to 12 day washout period (Figure 1).
There was a significant effect of time (P < 0.001) and a strong trend toward a significant time x group interaction (P = 0.062) for plasma PC ARA. Plasma PC ARA tended to decrease in the both groups (Figure 1). However, there were no significant differences from baseline in either group and there were no differences between groups at any timepoint.
There was a significant effect of time (P < 0.001) and a significant time x group interaction (P < 0.001) for plasma PC linoleic acid. Plasma PC linoleic acid did not change in the control group (P > 0.05; Figure 1). Plasma PC linoleic acid decreased in the treatment group (P < 0.001). In the treatment group plasma PC linoleic acid was lower than baseline at 44 (P = 0.019), 68 (P = 0.008) and 72 (P = 0.004) hr. Plasma PC linoleic acid differed between the control and treatment groups at 68 (P = 0.038) and 72 (P = 0.009) hr. Plasma PC linoleic acid returned to baseline values after the 5 to 12 day washout period (Figure 1).
As a result of these changes in EPA, DHA and linoleic acid content of plasma PC the omega-6 to omega-3 ratio was significantly decreased late in the infusion period in the treatment group (at 20, 44, 68 and 72 hr). There was no difference in the proportion of any other fatty acid in plasma PC between the two groups or over time.

Erythrocyte fatty acids

There was a strong trend toward a significant time x group interaction for erythrocyte EPA (P = 0.054). Erythrocyte EPA did not change significantly in the control group (Figure 2), but increased in the treatment group late in the infusion period (P < 0.005) (Figure 2). However, further analysis did not show any significant differences compared to baseline erythrocyte EPA or compared with the control group. Erythrocyte EPA returned to baseline values in the treatment group after the 5 to 12 day washout period (Figure 2). Erythrocyte DHA and ARA did not change significantly in either group and the groups did not differ at any timepoint (Figure 2). There was a significant effect of time (P = 0.011) and a significant time x group interaction (P = 0.012) for erythrocyte linoleic acid. Erythrocyte linoleic acid did not change in the control group but decreased in the treatment group late in the infusion period before returning to baseline levels at the 5 to 12 day washout (Figure 2). However, further analysis did not show any significant differences compared to baseline erythrocyte linoleic acid or compared with the control group. There was no difference in the proportion of any other fatty acid in erythrocytes between the two groups or over time.
Figure 2

Erythrocyte eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid and linoleic acid before (baseline), during (1 hr to 72 hr) and 5–12 days after stopping infusion of a mixture of medium-chain triglycerides and soybean oil …

Discussion

This current study shows that intravenous infusion of omega-3 PUFAs in the form of Lipidem® (B. Braun, Melsungen, Germany) induces a fairly rapid and marked increase in EPA and DHA in plasma PC and a small increase of EPA in erythrocytes. Amongst these changes, the elevation of EPA in plasma PC occurred the earliest. Interestingly in the control group not receiving fish oil-type omega-3 PUFAs there was a small decline in plasma PC EPA. The effect of the infusion of omega-3 PUFAs on plasma PC and erythrocyte EPA was reversed when the infusion was stopped. In contrast, elevated DHA was retained in plasma PC beyond the end of the infusion period. The retention of DHA in plasma PC was more marked in some individuals that others. Overall these data indicate that infused omega-3 PUFAs, especially EPA, are rapidly incorporated into plasma PC and also into erythrocytes and that turnover of EPA and DHA in plasma PC is different so that there is retention of DHA after supply is terminated even when EPA has returned to its starting level. Thus, this study provides further evidence that EPA and DHA may be handled differently in the body. The preferential retention of DHA has been demonstrated in plasma phospholipids [
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Destroy user interface control], platelets [

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Destroy user interface control], white blood cells [

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Destroy user interface control] and erythrocytes [

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Destroy user interface control,

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Destroy user interface control] after oral dosing of omega-3 PUFAs. These observations might indicate a special functional significance or importance of DHA over EPA

The rapid appearance of EPA and DHA with intravenous infusion is an advantage over oral supply where appearance of these fatty acids is slower [
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Destroy user interface control]. This is most likely because oral intake of omega-3 PUFAs must be followed by the processes of digestion and absorption before the fatty acids can be incorporated into plasma lipids and of further processing before they can be incorporated into cellular lipids. These processes all take time and depend on other factors such as the fat content and macronutrient composition of the meal. In contrast, intravenous infusion provides the fatty acids directly into the bloodstream introducing them into blood lipids, like PC, and directly exposing cells very quickly. A second aspect of intravenous infusion that will favour incorporation of EPA and DHA is the dose that can be administered. Studies of oral dosing typically use 1 to 4 g EPA + DHA per day, although higher doses have been used in some studies. In contrast, intravenous administration can easily provide more than 10 g of EPA + DHA on a daily basis. The higher dose will promote quicker incorporation and also a higher level of incorporation than is possible with oral supply. It is important to note that this high level of intravenous omega-3 PUFAs was well tolerated in all patients and there were no adverse reactions shown by study participants. Again this is an advantage over oral supply where moderate to high doses of fish oil can be associated with adverse gastrointestinal reactions.

The increase in EPA and DHA, which was mirrored by a decrease in the omega-6 fatty acid linoleic acid, resulting in decrease in the omega-6 to omega-3 PUFA ratio could be functionally important especially with regard to inflammation [
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Destroy user interface control] and perhaps also immune function [

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Destroy user interface control] and blood coagulation [

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Destroy user interface control]. The infusion of EPA + DHA promotes an anti-inflammatory and anti-coagulatory environment that would be an advantage in many patient groups including acute severe pancreatitis, sepsis, head trauma and even in advance of major gastrointestinal or hepatic surgery. In the current study the functional implications of the fatty acid changes described were not investigated.

Erythrocytes from patients receiving intravenous fish oil did not show an elevation of DHA, despite the small elevation of EPA. This suggests a slower rate of incorporation of DHA than EPA into erythrocytes and that the period of infusion (72 hr) was insufficient for net DHA incorporation to occur. Browning et al. [
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Destroy user interface control] demonstrated slower appearance of DHA than EPA into erythrocytes of healthy subjects consuming oral supplements containing EPA and DHA. Once again these observations indicate a slower turnover of DHA than EPA in cells.

The control group received a mixture of soybean oil and medium-chain triglycerides. This mix is fairly rich in linoleic acid, although less so than traditional soybean oil lipid emulsions [
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Destroy user interface control]. One interesting observation is that plasma PC EPA decreased slightly but significantly in the control group. Given the role of EPA in limiting inflammation and preventing coagulation, the decline seen in the control group suggests an undesirable effect of infusing lipid that does not contain preformed EPA.

In the clinical setting, the overall aim of the infusion protocol used here would be to enrich cells and tissues with biologically active omega-3 PUFAs in order to slow or reduce tumour growth and to promote a favourable response to a subsequent insult such surgery. Such a favourable response might involve prevention of excessive inflammation and reducing the likelihood of immune paralysis. Here, erythrocyte fatty acids were measured as a surrogate for those in tissue. At the end of the infusion period EPA had increased in erythrocytes of those patients receiving the intravenous fish oil. However, the infusion period was stopped some days before surgery and this resulted in a reversal of the infusion-induced fatty acid composition change in erythrocytes. This may also have occurred in tissues including the liver. It will be important in future studies to prolong the infusion period up to the time of surgery, in order to maximise the likelihood of establishing a beneficial impact of omega-3 fatty acids on the response to surgery, and to sample liver tissue in order to confirm that its fatty acid composition is modified. Furthermore, it will be important to link changes in plasma, blood cell and tissue fatty acid composition to biological effects such as the concentrations of lipid mediators and cytokines and to clinical outcomes.

Conclusions

Intravenous supply of omega-3 PUFAs results in a rapid increase of EPA and DHA in plasma PC and of EPA in erythrocytes, suggesting that infusion of omega-3 PUFAs could be used to induce a rapid effect especially in targeting inflammation.

Abbreviations

ARA: Arachidonic acid; DHA: Docosahexaenoic acid; EPA: Eicosapentaenoic acid; PC: Phosphatidylcholine; PUFA: Polyunsaturated fatty acid.

Competing interests

ARD, MSM, JS, OAT and CP have received educational travelling grants from B. Braun. PCC has received speaking fees from B. Braun, Fresenius Kabi, Baxter Healthcare, Abbott Nutrition, and Nestle and has received research funding from B. Braun and Abbott Nutrition.

Authors’ contributions

MM and ARD designed the study, obtained ethical approval and identified suitable patients for recruitment. OAT, JAS, LS and CP recruited the patients. OAT, JAS and LS supervised the infusions, collected blood samples and isolated the plasma and erythrocytes. OAT, JS, and ALW performed the gas chromatography under the supervision of PCC. OAT, JS and PCC analysed the data and wrote the paper. All authors read and approved the paper.

Acknowledgements

The study was part funded by an educational grant for research from B. Braun, Melsungen, Germany.

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  • Wachtler P, Konig W, Senkal M, Kemen M, Koller M. Influence of a total parenteral nutrition enriched with ω-3 fatty acids on leukotriene synthesis of peripheral leukocytes and systemic cytokine levels in patients with major surgery. J Trauma. 1997;12:191–198. doi: 10.1097/00005373-199702000-00004. [PubMed] [Cross Ref]
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  • Calder PC. Lipids for intravenous nutrition in hospitalised adult patients: a multiple choice of options. Proc Nutr Soc. in press. [PubMed]
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  • Versleijen MW, Roelofs HM, Rombouts C, Hermans PW, Noakes PS, Calder PC, Wanten GJ. Short-term infusion of a fish oil-based lipid emulsion modulates fatty acid status, but not immune function or (anti)oxidant balance: a randomized crossover study. Eur J Clin Invest. 2012;12:290–302. doi: 10.1111/j.1365-2362.2011.02582.x. [PubMed] [Cross Ref]
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  • Simoens CM, Deckelbaum RJ, Massaut JJ, Carpentier YA. Inclusion of 10% fish oil in mixed medium-chain triacylglycerol longchain triacylglycerol emulsions increases plasma triacylglycerol clearance and induces rapid eicosapentaenoic acid (20:5n-3) incorporation into blood cell phospholipids. Am J Clin Nutr. 2008;12:282–288. [PubMed]
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  • Popp-Snijders C, Schouten JA, van Blitterswijk WJ, van der Veen EA. Changes in membrane lipid composition of human erythrocytes after dietary supplementation of (n-3) polyunsaturated fatty acids – Maintenance of membrane fluidity. Biochim Biophys Acta. 1986;12:31–37. doi: 10.1016/0005-2736(86)90061-1. [PubMed] [Cross Ref]
  • Faber J, Berkhout M, Vos AP, Sijben JW, Calder PC, Garssen J, van Helvoort A. Supplementation with a fish oil-enriched, high-protein medical food leads to rapid incorporation of EPA into white blood cells and modulates immune responses within one week in healthy men and women. J Nutr.2011;12:964–970. doi: 10.3945/jn.110.132985. [PubMed] [Cross Ref]
  • Yaqoob P, Calder PC. Fatty acids and immune function: new insights into mechanisms. Brit J Nutr. 2007;12:S41–S45. [PubMed]
  • Marcus AJ, Safier LB, Broekman MJ, Islam N, Fliessbach JH, Hajjar KA, Kaminski WE, Jendraschak E, Silverstein RL, von Schacky C. Thrombosis and inflammation as multicellular processes: significance of cell-cell interactions. Thromb Haemost. 1995;12:213–217. [PubMed]
  • Calder PC, Jensen GL, Koletzko BV, Singer P, Wanten GJ. Lipid emulsions in parenteral nutrition of intensive care patients: current thinking and future directions. Intens Care Med. 2010;12:735–749. doi: 10.1007/s00134-009-1744-5. [PMC free article] [PubMed] [Cross Ref]

 2013 May 16. [Epub ahead of print]

Omega-6 and Omega-3 Polyunsaturated Fatty Acids And Allergic Diseases In Infancy And Childhood.

Miles EA, Calder PC.

Source

Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, IDS Building, MP887 Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom. pcc@soton.ac.uk.

Abstract

There may be a causal relationship between intake of n-6 polyunsaturated fatty acids (PUFAs) and childhood allergic diseases. This can be explained by plausible biological mechanisms involving eicosanoid mediators produced from the n-6 PUFA arachidonic acid. Long chain n-3 PUFAs are found in fish and fish oils. These fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will lower the risk of developing allergic diseases. In support of this, protective associations have been reported between maternal fish intake during pregnancy and allergic outcomes in infants and children from those pregnancies. However, studies of fish intake during infancy and childhood and allergic outcomes in those infants or children are inconsistent, although some reported a protective association. Supplementing pregnant women with fish oil can induce immunologic changes in cord blood. This supplementation has been reported in some studies to decrease sensitisation to common food allergens and to lower the prevalence and severity of atopic dermatitis in the first year of life. The protective effect of maternal n-3 PUFAs may last until adolescence of the offspring. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, although this benefit may not persist. Whether fish oil is a useful therapy in children with asthma receiving standard therapy is not clear from studies performed to date and this requires further exploration.

 2013 Apr 25;14(5):9005-17. doi: 10.3390/ijms14059005.

The influence of polyunsaturated Fatty acids on the phospholipase d isoforms trafficking and activity in mast cells.

Basiouni S, Fuhrmann H, Schumann J.

Source

Institute of Physiological Chemistry, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, An den Tierkliniken 1, 04103 Leipzig, Germany. julia.schumann@vmf.uni-leipzig.de.

Abstract

The impact of polyunsaturated fatty acid (PUFA) supplementation on phospholipase D (PLD) trafficking and activity in mast cells was investigated. The enrichment of mast cells with different PUFA including α-linolenic acid (LNA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid(LA) or arachidonic acid (AA) revealed a PUFA-mediated modulation of the mastoparan-stimulated PLD trafficking and activity. All PUFA examined, except AA, prevented the migration of the PLD1 to the plasma membrane. For PLD2 no PUFA effects on trafficking could be observed. Moreover, PUFA supplementation resulted in an increase of mastoparan-stimulated total PLD activity, which correlated with the number of double bonds of the supplemented fatty acids. To investigate, which PLD isoform was affected by PUFA, stimulated mast cells were supplemented with DHA or AA in the presence of specific PLD-isoform inhibitors. It was found that both DHA and AA diminished the inhibition of PLD activity in the presence of a PLD1 inhibitor. By contrast, only AA diminished the inhibition of PLD activity in the presence of a PLD2 inhibitor. Thus, PUFA modulate the trafficking and activity of PLD isoforms in mast cells differently. This may, in part, account for the immunomodulatory effect of unsaturated fatty acids and contributes to our understanding of the modulation of mast cell activity by PUFA.
 2013 May 16. pii: S1357-2725(13)00146-5. doi: 10.1016/j.biocel.2013.05.009. [Epub ahead of print]

Role of arachidonic acid metabolites on the control of non-differentiated intestinal epithelial cell growth.

Cabral M, Martín-Venegas R, Moreno JJ.

Source

Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Avda Joan XXIII s/n, 08028 Barcelona, Spain.

Abstract

Increasingly evidence indicates that enzymes, receptors and metabolites of the arachidonic acid (AA) cascade play a role in intestinal epithelial cell proliferation and colorectal tumorigenesis. However, the information available does not provide a complete picture and contains a number of discrepancies. For this reason it might be appropriate a thorough study into the impacts of the AA cascade on intestinal epithelial cell growth. Our data show that non-differentiated Caco-2 cells cultured with 10% fetal bovine serum (FBS) synthesize appreciable amounts of prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and 5-, 12 and 15-hydroxyeicosatetraenoic acid (HETE) but not LTD4, 20-HETE and epoxyeicosatrienoic acids. We also found that inhibitors of PGE2, LTB4 and 5-, 12-, 15-HETE synthesis as well as receptor antagonists of PGE2 and LTB4 blocked Caco-2 cell growth and DNA synthesis induced by 10% FBS without cytotoxic or apoptotic activity. Interestingly, PGE2, LTB4 and 5-, 12- and 15-HETE at concentrations reached in 10% FBS Caco-2 cultures (1-10nM) were able to induce Caco-2 cell growth and DNA synthesis. This was due to the interaction of PGE2 with EP1 and EP4 receptors and LTB4 and HETEs with BLT1 and BLT2 receptors. Moreover, we provide evidence that PGE2 stimulates several cell signaling pathways such as ERK, P38α, CREB and GSKβ/β-catenin involved in the regulation of Caco-2 growth. Finally, we provide evidence that the mitogenic effects of LTB4 and HETEs can be dependent, at least in part, on PGE2 synthesis.
 2013 May 10;12(1):71. [Epub ahead of print]

Effects of polyunsaturated fatty acids on the growth of gastric cancer cells in vitro.

Dai J, Shen J, Pan W, Shen S, Das UN.

Abstract

Polyunsaturated fatty acids (PUFAs) have tumoricidal action, though the exact mechanism of their action is not clear. The results of the present study showed that of all the fatty acids tested, linoleic acid (LA) and alpha-linolenic acid (ALA) were the most effective in suppressing the growth of normal gastric cells (GES1) at 180 and 200 muM, while gastric carcinoma cells (MGC and SGC) were inhibited at 200 muM. Arachidonic acid (AA) suppressed the growth of GES1, MGC and SGC cells and lower concentrations (120 and 160 muM) of AA were more effective against gastric carcinoma (MGC and SGC) cells compared to normal gastric cells (GES1). Paradoxically, both eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids though are more unsaturated than AA, were less effective compared with LA, ALA and AA in suppressing the growth of both normal and cancer cells. At the concentration used, methotrexate showed much less growth suppressive action compared to all the fatty acids tested. PUFAs-treated cells showed accumulation of lipid droplets. A close association was noted between apoptosis and lipid peroxides formed compared to the ability of normal and tumor cells to generate ROS (reactive oxygen species) and induce SOD (superoxide dismutase activity) in response to fatty acids tested and methotrexate. Both normal and tumor cells generated lipoxin A4 (LXA4) in response to supplementation of fatty acids and methotrexate though no significant correlation was noted between their ability to induce apoptosis and LXA4 formed. These results suggest that PUFAs induced apoptosis of normal gastric and gastric carcinoma cells could, partly, be attributed to lipid peroxidation process.
 2013 May 10. [Epub ahead of print]

Analysis of esterified and nonesterified fatty acids in serum from obese individuals after intake of breakfasts prepared with oils heated at frying temperature.

Orozco-Solano MI, Priego-Capote F, Luque de Castro MD.

Source

Department of Analytical Chemistry, Annex Marie Curie Building, Campus of Rabanales, University of Córdoba, 14071, Córdoba, Spain.

Abstract

In this study, levels of esterified and nonesterified fatty acids (EFAs and NEFAs, respectively) were compared in obese individuals (body mass index between 30 and 47 kg m-2) in basal state and after intake of four different breakfasts prepared with oils heated at frying temperature. The target oils were three sunflower oils-pure, enriched with dimethylsiloxane (400 μg mL-1) as lipophilic oxidation inhibitor, and enriched with phenolic compounds (400 μg mL-1) as hydrophilic oxidation inhibitors-and virgin olive oil with a natural content of phenolic compounds of 400 μg mL-1. The intake of breakfasts was randomized to avoid trends associated to this variability source. EFAs and NEFAs were subjected to a sequential derivatization step for independent gas chromatography-mass spectrometry analysis of both fractions of metabolites in human serum. Derivatization was assisted by ultrasonic energy to accelerate the reaction kinetics, as required for high-throughput analysis. Statistical analysis supported on univariate (multifactor ANOVA) and multivariate approaches (principal component analysis and partial least squares-discriminant analysis) allowed identification of the main variability sources and also discriminating between individuals after intake of each breakfast. Individuals’ samples after intake of breakfasts prepared with virgin olive oil were clearly separated from those who ingested the remaining breakfasts. The main compounds contributing to discrimination were omega-3 and omega-6 EFAs with special emphasis on arachidonic acid and eicosapentaenoic acid. These two polyunsaturated fatty acids are the precursors of eicosanoid metabolites, which are of vital importance as they play important roles in inflammation and in the pathogenesis of vascular and malignant diseases as cancer.
 2013 May 4. doi: 10.1002/dneu.22088. [Epub ahead of print]

Arachidonic acid closes innexin/pannexin channels and thereby inhibits microglia cell movement to a nerve injury.

Samuels SE, Lipitz JB, Wang J, Dahl G, Muller KJ.

Source

Neuroscience Program, University of Miami, Miami, FL, 33136, USA; Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, FL, 33136, USA.

Abstract

Pannexons are membrane channels formed by pannexins and are permeable to ATP. They have been implicated in various physiological and pathophysiological processes. Innexins, the invertebrate homologues of the pannexins, form innexons. Nerve injury induces calcium waves in glial cells, releasing ATP through glial pannexon/innexon channels. The ATP then activates microglia. More slowly, injury releases arachidonic acid (ArA). The present experiments show that ArA itself reduced the macroscopic membrane currents of innexin- and of pannexin-injected oocytes; ArA also blocked K+ -induced release of ATP. In leeches, whose large glial cells have been favorable for studying control of microglia migration, ArA blocked glial dye-release and, evidently, ATP-release. A physiological consequence in the leech was block of microglial migration to nerve injuries. Exogenous ATP (100 µM) reversed the effect, for ATP causes activation and movement of microglia after nerve injury, but nitric oxide directs microglia to the lesion. It was not excluded that metabolites of ArA may also inhibit the channels. But for all these effects, ArA and its non-metabolizable analogue eicosatetraynoic acid (ETYA) were indistinguishable. Therefore, ArA itself is an endogenous regulator of pannexons and innexons. ArA thus blocks release of ATP from glia after nerve injury and thereby, at least in leeches, stops microglia at lesions. © 2013 Wiley Periodicals, Inc. Develop Neurobiol, 2013.
 2013 May 9;12(1):69. [Epub ahead of print]

Chicken meat nutritional value when feeding red palm oil, palm oil or rendered animal fat in combinations with linseed oil, rapeseed oil and two levels of selenium.

Nyquist NF, Rødbotten R, Thomassen M, Haug A.

Abstract

Chicken meat nutritional value with regard to fatty acid composition and selenium content depends on the choice of dietary oil and selenium level used in the chickens’ feed. The objective of this study was to investigate the effect of replacing commonly used rendered animal fat as a dietary source of saturated fatty acids and soybean oil as a source of unsaturated fatty acids, with palm oil and red palm oil in combinations with rapeseed oil, linseed oil and two levels of selenium enriched yeast on chicken breast meat nutritional value. The study also wished to see whether red palm oil had a cholesterol lowering effect on chicken plasma.204 male, newly hatched broiler chickens were randomly divided into twelve dietary treatment groups, and individually fed one out of six dietary fat combinations combined with either low (0.1 mg Se /kg feed) or high (1 mg Se/kg feed) dietary selenium levels. Linseed oil, independent of accompanying dietary fat source, lead to increased levels of the n-3 EPA, DPA and DHA and reduced levels of the n-6 arachidonic acid (AA). The ratio between AA/EPA was reduced from 19/1 in the soybean oil dietary groups to 1.7/1 in the linseed oil dietary groups. Dietary red palm oil reduced total chicken plasma cholesterol levels. There were no differences between the dietary groups with regard to measured meat antioxidant capacity or sensory evaluation. Chicken meat selenium levels were clearly influenced by dietary selenium levels, but were not influenced by feed fatty acid composition. High dietary selenium level lead to marginally increased n-3 EPA and higher meat fat % in breast muscle but did not influence the other LC PUFA levels. Chicken breast meat nutritional value from the soybean oil and low selenium dietary groups may be regarded as less beneficial compared to the breast meat from the linseed oil and high selenium dietary groups. Replacing rendered animal fat with palm oil and red palm oil had no negative effects on chicken muscle nutritional value with regard to fatty acid composition. Red palm oil decreased total chicken plasma cholesterol, confirming the cholesterol reducing effect of this dietary oil.

———-

This diet below seems to go a bit against the idea that foods high in arachidonic acid are not as important as a balanced diet. While this is partly likely true, I think this is why Dr. Atkins died of cardiovascular disease: he underestimated the risk of arachidonic acid and fat causing inflammation and free radicals that cause cellular damage.

http://www.marksdailyapple.com/arachidonic-acid/#axzz2Up49GbFu

Dear Mark: Arachidonic Acid

steakeggs 1I spend a lot of time highlighting the importance of omega-3 fatty acids and downplaying their poly cohorts, omega-6s. Of course, I do this for good reason. Western dietary patterns and modern agricultural practices have made omega-3s harder to come by and blown any semblance of omega-3/omega-6 dietary balance out of the water. As maligned as omega-6s are these days, however, they’re still essential fatty acids. Our bodies need them and can’t produce them on their own – straight and simple. The problem comes when we mistake emphasizing the omega imbalance in modern diets with disparaging omega-6 entirely. Although the Primal Blueprint promotes a healthy fatty acid balance – one that parallels that of our hunter-gatherer ancestors – I still get questions about omega-6s, particularly reservations about the role arachidonic acid (part of the omega-6 fatty acid family) plays in the PB.
Dear Mark,
While I totally agree with the importance and value of meat/eggs and vegetables, minus all grains and added sugars…my question is about the arachidonic acid (AA) found mostly in meat and egg yolks. It has been demonized by many, Barry Sears, etc., as the cause of all inflammation in the body. Is that a concern for us on the PB plan?
Arachidonic acid is both a product of the body’s natural linoleic acid conversion and, as the question notes, an existing (but modest) component of animal-based foods like egg yolk and meat – as well as human breastmilk. The particular beef with arachidonic acid revolves around its common conversion to omega-6 derived, “pro-inflammatory” eicosanoids, compounds (e.g. prostaglandins, prostacyclins, thromboxanes, leukotrienes, etc.) that play a role in the intercellular signaling that directs, among other key activities, neurological function and immune response – including inflammatory response. (Eicosanoids are also derived from EPA in the omega-3 family. These are considered anti-inflammatory.) Your proportion of omega-3 derived to omega-6 derived eicosanoids correlate for the most part with your dietary intake of omega-3s and 6s.
Already this correspondence shows that your omega-3 to omega-6 ratio has the most significant impact on your level of omega-6 derived eicosanoids and their inflammatory effects on your system. Consider that the average American has an omega ratio of 20:1, and that’s the ball game. Studies emphasizing the detrimental effects of AA generally focus on the isolated supplementation of AA rather than the impact of supplement when balanced with a correspondingly high intake of omega-3. Research that does gauge the impact of AA supplementation with a high omega-3 intake shows no significant cardiovascular impact. Invited analysis and commentary for the British Journal of Nutrition (which published the original study), citing a number of studies that show little to no appreciable effect of AA on many cardiovascular health and immune function markers, concluded (PDF) that “moderately increased arachidonic acid intake [designated as up to 1.5 grams or 1500 milligrams] is probably harmless in healthy adults.” Just for comparison sake, the average intake of dietary AA in the Western diet is estimated at 50-300 milligrams a day.
But there’s more reason for reassurance. Much of people’s AA content is likely determined by (and derived from) their high linoleic acid intake (in the forms of corn, soy and vegetable oils). Cut those out of your diet as the PB suggests, and you’re already ahead. As for direct AA dietary sources, chicken eggs weigh in at about 390 mg and 100 gram meat servings generally between 35-100 mg dependent in part on fat content (organ meat reach into the 150 mg range). In the context of a healthy omega ratio, the Primal Blueprint’s modest increase in direct dietary arachidonic acid doesn’t present a novel dietary risk as some (like Sears) would have your believe. Next, consider that grass-fed beef is lower in AA than feedlot beef (PDF). (Remember, it’s not just what you eat but what the cow/pig/chicken/duck/game animal/etc. on your plate ate before it got there. Stuff animals with omega-6 loaded feed and you’ll get meat loaded with forms of omega-6.) Add to this the protective (antioxidant, anti-cancer, pro-cardiovascular health) effects of conjugated linoleic acid (CLA) present in grass fed meats and dairy – up to five times the CLA as you’ll find in grain-fed animals.
Next, there are the other mitigating factors of a Primal Blueprint diet. A healthy, nutrient-rich diet also has some effect on the prevalence of AA from linoleic acid conversion. Linoleic acid, the “parent” omega-6 compound, is broken down by the body into gamma-linoleic acid (GLA). From there, the conversion leads toward either arachidonic acid or dihomogamma-linolenic acid (DGLA), which is actually anti-inflammatory. Minerals like magnesium and zinc and vitamins like C, B3 and B6 appear to encourage the body to redirect GLA conversion toward DGLA instead of AA. Research shows it’s a more complicated picture – inflammatory and anti-inflammatory.
And if you’re a tea drinker, know that all the steeping and sipping curbs the metabolism of arachidonic acid.
Finally, as I mentioned before, it’s important to keep in mind that arachidonic acid isn’t the bogeyman that it’s made out to be. It comprises a necessary component of cellular membrane structure and supports everything from dermal integrity to muscular growth and repair. It’s no accident that arachidonic acid is present in breast milk. AA plays a critical role in brain development, and a whole host of research comparing AA-supplemented formula with non-supplemented formula underscores this connection. Likewise, AA supports continuing role in neurological health as demonstrated in studies involving older adults. When it comes to arachidonic acid, the general principle holds: it’s all about overall balance and healthfulness.
Thanks as always for the great questions and comments, and keep ‘em coming!



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