DHA STUDIES
Are fish oil omega-3 long-chain fatty acids and their ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2322958Mar 20, 2008 · These fatty acids act as PPAR agonists that transcript the genes involved in glucose and lipid homeostasis. Present hypothesis suggests that the derivatives of these fatty acids are stronger PPAR agonists than the parent compounds. X-ray structures of PPARs indicate that α or β derivatives of fatty acids would fit into PPARα/γ binding cavity.
Omega-3 Fatty Acids and PPAR γ in Cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526161Aug 27, 2008 · Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator receptor activator (PPAR)γ and, due to the effects of PPARγ on cell proliferation, survival, and differentiation, are potential anticancer agents. Dietary intake of omega-3 PUFAs has been associated with a reduced risk of certain cancers in human populations and in animal …
PPAR Agonists: Definition and Overview -Diabetes Self ...
Jun 15, 2006 · PPAR-gamma is made primarily in fat cells and affects the production of fat cells and the metabolism of lipids and reduces insulin resistance. PPAR-delta is produced in virtually all of the cells throughout the body and may have roles in energy metabolism and reducing inflammation.
What is a PPAR agonist?
PPAR agonists are a family of drugs that activate certain proteins in the body called peroxisome proliferator-activated receptors (PPARs). The PPAR agonists can help to improve blood glucose levels and levels of blood lipids (fats and cholesterol) and may also reduce risks of atherosclerosis because PPARs regulate the expression of genes that affect blood lipid metabolism, the generation of adipocytes (fat cells), and blood glucose control.
Over the years, researchers have come to recognize that a number of risk factors for cardiovascular disease tend to occur together, including insulin resistance, elevated blood glucose levels, Type 2 diabetes, blood lipid abnormalities, and inflammation. Consequently, they are on the lookout for drugs that might address all of these risk factors at once.
Scientists have identified three different forms of PPARs, dubbing them PPAR-alpha, PPAR-gamma, and PPAR-delta (also called PPAR-beta). PPAR-alpha, the first form of PPAR to be identified, is produced primarily in the skeletal muscle and the liver, where it is involved in the body’s breakdown and transport of fatty acids. PPAR-alpha may also play a role in reducing inflammation. PPAR-gamma is made primarily in fat cells and affects the production of fat cells and the metabolism of lipids and reduces insulin resistance. PPAR-delta is produced in virtually all of the cells throughout the body and may have roles in energy metabolism and reducing inflammation. All three forms of PPAR are also made in the endothelial cells lining the blood vessels and in inflammatory cells, suggesting that they may play a role in the development of atherosclerosis. When activated, the PPARs stimulate metabolic pathways that may reduce the risk of atherosclerosis, but some research (mainly in mice) indicates that they may also activate pathways that can promote atherosclerosis.
The currently available PPAR agonists aimed at diabetes are known as thiazolidinediones or “glitazones.” These include pioglitazone (brand name Actos) and rosiglitazone (Avandia). These drugs are known to increase the sensitivity of the body’s tissues to the action of insulin. Researchers now recognize that the thiazolidinediones exert this effect by binding to and activating PPAR-gamma. Furthermore, these drugs may inhibit certain proteins in the blood vessel walls called chemokines, which attract inflammatory cells and thus promote atherosclerosis. Researchers have also come to realize that certain drugs called fibrates may work to lower levels of triglycerides (a blood fat) and raise levels of high-density lipoprotein (HDL, or “good”) cholesterol in part by activating PPAR-alpha.
Recognizing the predominantly beneficial effects of activating the PPARs, scientists have set about to design drugs that activate both PPAR-alpha and PPAR-gamma, which would not only help sensitize the body to insulin but would also have a beneficial effect on lipids. This novel class of Type 2 diabetes medicines, called dual PPAR activators (or PPAR-alpha/gamma agonists or “glitazars”), include the investigational drugs muraglitazar and tesaglitazar.
In preliminary clinical trials presented at the 2005 Annual Meeting of the American Diabetes Association, both drugs significantly improved blood glucose control and lipid profiles in people with Type 2 diabetes. However, in May 2006, the maker of muraglitazar abandoned its development because of concerns about heart safety, and the maker of tesaglitazar halted its development because it didn’t appear to be any more effective than existing diabetes drugs. Other dual PPAR agonists are in various stages of development at other drug companies.
Originally Published June 15, 2006https://www.diabetesselfmanagement.com/diabetes-resources/definitions/ppar-agonists/
What is a PPAR?
It stands for peroxisome proliferator activated receptors, which are activated by ligand transcription factors of nuclear hormone receptor superfamily.
PPAR play a vital role in metabolic functioning of the body as well as in energy homeostasis. PPAR belongs to the family of phylogenetically related protein known as nuclear hormone factor.
Their structure is similar to that of the thyroid hormone receptor and they are stimulated in response to small lipophilic ligands. Peroxisome proliferator activated receptors have the domain structure similar to that of the other members of the nuclear receptor family.
Photo 1: A diagram presentation showing how peroxisome proliferator activated receptors function in the body.
PPAR Alpha
PPAR alpha is a type of protein that has the ability to speed up the breakdown of fat in the liver and other parts of the body. The PPAR alpha function is focused on the metabolism of the body so as to increase the production of energy. It also has the ability to alter the expression of a huge number of genes.
How is PPAR alpha activated? Calorie restriction can trigger the action of PPAR alpha. It is useful in ketogenesis, which is a body’s way of adapting to prolonged fasting. Where can you find PPAR alpha? You can found PPAR alpha in the liver, heart, kidney, and brown fat. A small amount of PPAR alpha can be found in the muscles, adrenal glands, and small and large intestines. (2, 3)
PPAR alpha activation helps in the uptake, utilization, and breakdown of fatty acids. How? It works by increasing the number of genes that act in the transport, binging, activation, and oxidation of fatty acids. It also increases the production of glucose and secretion of bile.
If you are in a fasting stage, the PPAR alpha helps the body cope in the absence of food. Without it, your will be suffering from major metabolic disturbances such as fatty liver disease and hypoglycaemia. (4)
PPAR alpha plays a major role in drugs and toxins detoxification. It also has the ability to inhibit autoimmune disease like multiple sclerosis. It protects the body from possible heart disease by inhibiting the inflammation of macrophage and boosting cholesterol efflux. It is beneficial to people who want to build their muscles because PPAR alpha can significantly increase IGF-1. It facilitates fat loss by increasing UCP-3 (R).
If you want to increase the amount of PPAR alpha in your body, then you have to increase your intake of polyunsaturated fatty acid, omega-6, arachidonic acid, and linoleic acid metabolites. (5, 6)
PPAR Delta/Beta
PPAR Delta or Beta is a nuclear receptor encoded by the PPARD gene. It encodes a member of PPAR family. PPAR delta/beta plays an important role in the production of energy, alleviating pain and inflammation, improving the functions of the heart, improving the body’s endurance, and reducing obesity.
In fact, this nuclear hormone receptor is important in promoting hair growth and preventing heart disease. A high level of PPAR delta increases the energy expenditure of the body. It also increases the fat burning ability of the muscles and fat cells.
On the other hand, a low level of PPAR delta increases the formation of fat cells. There is a study conducted that revealed a high level of PPAR delta in patients with colorectal cancer. (5, 6, 7, 10)
What is a PPAR agonist?
PPAR agonists are classification of drugs that directly acts on the PPAR. They are beneficial in treating metabolic syndrome as they help in lowering the level of blood sugar and triglycerides. There are various types of PPAR agonist.
The PPAR gamma is the primary target of TZDs (thiazolidinediones), which is used in insulin resistance diabetes mellitus. They are also useful in the treatment of hyperlipidemia in patients with atherosclerosis. On the other hand, PPAR delta is the primary target of a chemical GW501516. PPAR delta agonist modifies the body’s preference of fuel, switching from glucose to lipids. (9)
PPAR Supplements
PPAR supplements are created to target the PPAR level in the body. They are a perfect alternative to the pharmaceutical medications. They are safe and effective. One of the highly preferred PPAR supplements is Sesamin. It is a lignan naturally present in the seeds and oil of sesame.
What is a lignan? It is a molecule that binds with a receptor or other entity that acts as activator. It is a highly powerful PPAR alpha agonist. It offers a highly promising result in obese patients as well as patients suffering from diabetes mellitus type 2.
PPAR supplement containing Sesamin can greatly increase the oxidation of fat in the mitochondria. It also increases the oxidation of peroxisomes by increasing the release of enzymes primarily involved in fatty acids beta oxidation. It improves the expression of carnitine palmitoyl transferase (CPT), a mitochondrial enzyme. (5,
European Journal of Pharmacology
15 August 2016
Fatty acids, eicosanoids and PPAR gamma
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) belongs to the family of nuclear nuclear receptors and is mainly expressed in adipose tissue, hematopoietic cells and the large intestine. Contrary to other nuclear receptors that mainly bind a single specific ligand, there are numerous natural PPARγ ligands, in particular fatty acids or their derivatives called eicosanoids. PPARγ have pleiotropic functions: (i) glucose and lipid metabolism regulation, (ii) anti-inflammatory properties, (iii) oxidative stress inhibition, (iv) improvement of endothelial function. Its role has been mainly studied by the use synthetic agonists. In this review, we will focus on the effects of PPARγ mediated through fatty acids and how these have beneficial health properties.
脂肪酸，类花生酸和PPARγ
过氧化物酶体增殖物激活受体γ（PPARγ）属于核受体家族，主要在脂肪组织，造血细胞和大肠和所有血管内皮细胞和炎性细胞中表达。与主要结合单个特异性配体的其他核受体相反，有许多天然的PPARγ配体，特别是脂肪酸或称为类花生酸的衍生物。 PPARγ具有多效功能：（i）葡萄糖和脂质代谢调节，
（ii）抗炎特性，
（iii）抑制氧化应激，
（iv）改善内皮功能。
主要通过使用合成激动剂来研究其作用。OMEGA-3 脂肪酸~亚麻酸、EPA和DHA是天然的PPARγ激动剂，因此具有上述的四大功能。
在这篇综述中，我们将重点研究通过脂肪酸介导的PPARγ的作用，以及它们如何具有有益的健康特性。
https://www.sciencedirect.com/science/article/abs/pii/S0014299915303423
DHA 研究
BY David Tomen Leave a Comment
DHA is an essential brain food that boosts neurotransmission, cognition, memory, learning, reduces brain inflammation, assists in the repair of and helps grow new brain cells.
DHA (docosahexaenoic acid) is an omega-3 fatty acid. DHA is crucial for the healthy structure and function of your brain at all ages.
DHA impacts your brain’s signaling systems, neurotransmitters, memory, learning, focus and attention. It helps reduce and even repair cognitive decline.
The famous Framingham Heart Study followed-up with 899 men and women who were free of dementia. Subjects had a median age of 76 years. And were followed for 9.1 years for the development of dementia and Alzheimer’s Disease.
Results from the study showed 99 new cases of dementia including 71 of Alzheimer’s. The researchers concluded that those with the highest levels of DHA were “associated with a significant 47% reduction in the risk of developing all-cause dementia”.[i]
DHA helps:
BDNF. Brain-derived neurotrophic factor (BDNF) is your brain’s growth hormone. DHA has the ability to turn on your brain’s BDNF.
Neuroplasticity. DHA helps your brain build new neural pathways. Critical for maintaining a healthy brain. And optimizing neural signaling and cognition.
Neuroprotection. DHA acts as an anti-inflammatory by reducing the enzyme COX-2. Inflammation is a key factor in both Alzheimer’s and Parkinson’s Disease. And in every other neurodegenerative disease.
DHA对大脑的保养
脑源性神经营养因子（BDNF）是大脑的生长激素。 DHA可以增加和激活大脑的BDNF。BDNF的好处:
支持现有神经元的存活
通过神经发生促进新神经元和突触的生长和分化
为记忆，学习和思考做出积极贡献
表现出抗抑郁活性
神经可塑性。 DHA可帮助您的大脑建立新的神经通路。对于保持大脑健康至关重要。并优化神经信号和认知。
神经保护。 DHA通过还原酶COX-2起到消炎作用。炎症是阿尔茨海默氏病和帕金森氏病以及其他所有的神经退行性疾病的关键因素。
Table of Contents
Overview
How does DHA Work in the Brain?
DHA vs. EPA: What’s the Difference?
How Things Go Bad:
DHA to the Rescue
How does DHA feel?
The Research
DHA Reduces Hostility and Anger
DHA Restores Neurotransmitters & Memory
DHA Improves Attention & Learning
Dosage Notes
Side Effects
Available Forms
Nootropics Expert Recommendation
Overview
DHA (docosahexaenoic acid) is an omega-3 fatty acid. Your brain is made up of 60% fat. And much of that fat is DHA.
DHA
DHA
Your body does not make DHA on its own. So you must get it from food or a supplement. And if you are a vegan, you are at serious risk of a life-threatening DHA deficiency.
Foods that are rich in DHA include fish, fish oil, Krill and other crustaceans, and algae.
But fish do not make DHA. Fish and other marine predators get it from smaller fish and crustaceans that feed on algae. It’s the algae that have enzymes to produce DHA that we need to remain healthy.
DHA from eggs and some dairy products only supply about 20 mg of DHA per day.
DHA is essential for maintaining brain health, memory and learning functions. DHA reduces brain inflammation, stimulates new nerve cell growth, and assists in brain cell repair.
DHA is critical for brain health
How does DHA Work in the Brain?
Your brain is composed of 60% fat. 15 – 20% of your cerebral cortex is DHA. Even the retina in your eyes is 30 – 60% DHA. Making DHA the most essential nutrient for eye and brain health.
The highest levels of DHA are found in phosphatidylserine (PS) and phosphatidylethanolamine (PE).[ii] Lower levels are found in phosphatidylcholine (PC).
PS makes up about 70% of neuron tissue mass. It helps in the storage, release and activity of neurotransmitters and receptors.
PC also makes up part of the neuron tissue mass. And helps in maintaining cell structure, fat metabolism, neuron signaling and the activation of a number of enzymes.
And PE is part of neuron cell membranes. PE is involved in cellular signaling.
PS, PE and PC are called phospholipids. Together they alter the fluidity of cell membranes. Changing the fluidity of cell membranes alters their permeability and protein activity. And influences cellular signaling.
Made up largely of DHA, these cellular membranes regulate entry into the cell, and control neuroreceptor function. Which facilitates cellular communication between, and within cells.
DHA also reduces inflammation by regulating proteins and enzymes within cells. And boosts the production of anti-inflammatory compounds that protect cells.
DHA maintains the activity of certain enzymes that control electrical signaling between cells. And it regulates the brain cell concentration of PS which is vital for cell survival.
And DHA regulates calcium oscillations, which are involved in neurotransmitter release, mitochondrial function, gene activation, oxidative stress and brain cell development and growth (BDNF).
DHA vs. EPA: What’s the Difference?
Most medical authorities and scientists agree that Omega-3 oils are important for good health. Omega-3’s boost brain function, decrease inflammation, reduce the incidence of fatal heart attacks and strokes, help autoimmune diseases and improve vision.
Omega-3 from fishWe have general agreement about the health benefits of Omega-3 oils. But few appreciate the difference between DHA (docosahexaeonic acid) and EPA (eico-sapentaenoic acid).
The ratio of DHA and EPA varies a lot in commercial Omega-3 supplements. Most have higher concentrations of EPA to DHA. Mainly because it’s cheaper to manufacture, and have less of a fishy odor.
But studies show that most of the brain health benefits of Omega-3’s are derived from DHA rather than EPA.
One study in Chicago followed 815 residents from 1993 – 2000. Study subjects were between 65 and 94 years. 131 study participants developed Alzheimer’s Disease. Those who ate fish at least once a week had a 60% less risk of Alzheimer’s compared to those who didn’t eat fish.
Researchers found that it was the intake of DHA rather than EPA that reduced the risk factor in getting Alzheimer’s. EPA made no difference whatsoever.[iii]
How Things Go Bad:
From reviewing the “How does DHA Work in the Brain” section of this article, you can imagine that when things go bad with DHA – they go really bad.
Fish and marine oil supplements like krill oil are a direct source of DHA and EPA. Plants contain another Omega-3 called alpha-linolenic acid (ALA).
Technically ALA can be converted to DHA and EPA. But most modern humans lack the ability to convert plant sources of Omega-3’s into all the DHA our brain needs.
When we don’t get enough DHA, we experience:
↓ Problems with attention, learning and memory
↑ Depression, anxiety, aggression, anger, suicide risk
↑ Bipolar disorder, Alzheimer’s Disease and Schizophrenia
Not having adequate levels of DHA in the brain cause things to break down. If the inadequate intake of DHA goes on for a while, disease starts to set in. Including neurodegenerative diseases like Alzheimer’s and cancer.
DHA to the Rescue
DHA makes up much of the gray matter in your brain. It’s an integral part of cell membranes and making them function.
Your brain is 60% fat. And a large part of that is DHA.
The good news is; degenerative conditions can not only be prevented by adding DHA to your nootropic stack. It can also be reversed.
DHA for a healthy brain
In one study, researchers worked with 485 elderly subjects with memory problems. They saw significant improvement with those taking 900 mg of DHA per day for 24 weeks compared to the control group.[iv]
In another double-blind, placebo-controlled trial, scientists worked with 49 women aged 60 – 80 years. One group received 800 mg per day of DHA for 4 months.
Researchers found those using DHA had a significant improvement in verbal fluency scores. And an improvement in memory and learning.[v]
How does DHA feel?
Chances are when you start using DHA you won’t feel it. There’s no profound stimulant feeling.
But if you suffer from chronic depression, within a few weeks you should feel the depression lift.
After supplementing with DHA for a while your cognition will be better. You’ll think clearer and quicker. Your memory and ability to learn will improve. And you’ll likely have more energy and motivation.
But it is very likely you won’t think to attribute these improvements to adding DHA to your stack. Something else will get the credit.
The Research
DHA is crucial for an optimally functioning brain. The goal of every neurohacker. DHA impacts your brain’s structure, signaling systems, neurotransmitters, memory, learning, focus and attention.
We have decades of clinical research verifying the importance of DHA in your nootropic stack. And several books have been written on the subject in the last couple of years. Here’s just a snippet of what’s available…
DHA Reduces Hostility and Anger
In a study with 41 university students in Japan, scientists compared a high-DHA diet (1.5 grams/day) with placebo. This was recorded over 3 months to see the effects of hostile responses.
The researchers found a 27% incidence of hostile answers in the placebo group when nothing extraordinary was going on. And hostile responses rose to 92% during final exams.
There was no increase in hostility among those taking a DHA supplement. These guys even found DHA supplementation significantly reduced hostility among university staff.[vi]
DHA Restores Neurotransmitters & Memory
As the brain ages, there is an increase in membrane rigidity. This causes changes in synapses resulting in a decrease in transmitter release. Long-term potentiation is affected which impairs the development of memories.
Several studies have shown that DHA can support healthy levels of these neurotransmitters. In one study with aged rats, researchers restored neurotransmitter release in the hippocampus. And reversed age-related memory problems.
Adding omega-3 fatty acids to the rats feed for 8 weeks raised concentrations of DHA in the rat’s brain. And actually reversed age-related memory impairment.[vii]
DHA Improves Attention & Learning
DHA also has an effect on neurotransmitters serotonin, norepinephrine, acetylcholine, glutamate and dopamine. Deficiencies in DHA have been shown to lower levels of dopamine. Resulting in problems with attention and learning.[viii]
DHA even plays a role in neurotransmitter receptor function. DHA affects brain cell membrane structures including neuroreceptors.[ix]
Some of these receptors communicate inside cells when stimulated by glutamate, serotonin and acetylcholine.[x] The numbers of these receptors can be increased by you, by adding DHA to your nootropic stack.
So if you are using nootropics that affect things like acetylcholine, serotonin, dopamine and serotonin in your brain. It would be wise to add DHA to your nootropic stack. And ensure you get the most bang for your investment in nootropics.
Dosage Notes
Recommended daily dosage of DHA is 1,000 mg.
Fish oil supplements vary in ratios of DHA to EPA. Salmon naturally contain more DHA than EPA. A supplement from algae may contain only DHA.
Krill oil has both DHA and EPA. So read the labels. And whatever supplement you get, make sure you end up with at least 1,000 mg of DHA.DHA-supplement
Most brands of fish oil have been proven safe, and free of mercury. And do not contain unsafe levels of PCB’s (polychlorinated biphenyls).
To further avoid the contaminants in an unrefined supplement, choose a fish oil supplement made from small, oily fish like anchovies, sardines or menhaden. And check the labels carefully for purity.
Ideally, get one of a few supplements now available that are pure, refined DHA only. With no EPA.
Side Effects
Fish oil capsules commonly have both DHA and EPA. Capsules with EPA are not recommended for infants or small children. Because they upset the balance between DHA and EPA during early development. This also applies to pregnant women.
Fish oil could cause minor side effects like loose stools, upset stomach and belching.
Fish oil may lower blood pressure. So if you already take a medication to lower blood pressure, make sure you talk to your doctor first.
If you’re supplement contains EPA, it could interact with blood thinners and increase bleeding. Same is true for aspirin. But this is not true of DHA. DHA-only supplements do not thin the blood.
Fish oil supplements may lower blood sugar levels. So be careful if you’re on diabetes medications.
Omega-3 fatty acids may reduce some of the side effects of cyclosporine which is used to stop rejection after an organ transplant.
Available Forms
DHA is available as a supplement in two forms:
Fish oil capsules. Which usually have both DHA and EPA. Some makers now offer capsules that are pure, refined DHA only.
DHA from algae. Which has no EPA and is vegetarian friendly.
Nootropics Expert Recommendation
DHA (Omega-3) 1,000 mg per day.
Nootropics Expert Tested and ApprovedWe recommend using DHA as a nootropic supplement.
Your body does not make DHA on its own. So you must get it from food. Or take it as a supplement.
DHA is one of the most important nootropics you can add to your stack. Your brain is 60% fat. And much of that fat is DHA.
DHA is critical for brain cell repair and regeneration (neurogenesis). And it is an integral part of neural signaling. Both between neurons as well as inside brain cells.
DHA has an effect on critical neurotransmitters and neuroreceptors. It is a powerful anti-inflammatory. And is involved in neuroplasticity.
Hundreds of studies on Omega-3’s and DHA show benefits in preventing and even reversing neurodegenerative disease.
It’s best if you find a supplement that is pure DHA. And you can safely take 1,000 mg per day.
DHA – Nootropics Expert https://nootropicsexpert.com/dha/
Fatty acids, eicosanoids and PPAR gamma - ScienceDirect
https://www.sciencedirect.com/science/article/pii/S0014299915303423
Aug 15, 2016 · We found that DHA and EPA were the most potent to inhibit IL-6 and IL-8 production through PPARγ as established by agonist/ antagonist experiments (Marion-Letellier et al., 2008). Another aspect of PPARγ role in immunity is macrophage polarization.
Cited by: 67
Publish Year: 2016
Author: Rachel Marion-Letellier, Guillaume Savoye, Subrata Ghosh
Identification of Putative Metabolites of Docosahexaenoic ...
https://www.researchgate.net/publication/8066429_Identification_of_Putative...
Because EPA and DHA are endogenous ligands for PPARs, it is possible that PPARs mediate the insulin sensitizing, lipid lowering, and anti-inflammatory properties of fish oil. Available evidence...
Peroxisome proliferator-activated receptors and their ...
https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-13-17
Feb 14, 2014 · Activation of PPARγ by natural ligands such as PUFAs (mainly docosahexaenoic acid and eicosapentaenoic acid) results in a functional response in the tumor cells. Many studies have provided evidence that DHA inhibits the tumor development through activation of PPARγ (e.g. the growth of human lung cancer cells) [ 53 ].
Omega-3 Fatty Acids and PPAR in Cancer
https://www.hindawi.com/journals/ppar/2008/358052
In contrast, both EPA and DHA were shown to reduce PPRE reporter activity in an HCT-116 colon cancer cells . DHA has recently been shown to reduce the growth of human lung cancer cells in a process that was associated with increased PPARγ protein .
Cited by: 15
Publish Year: 2008
Author: Iris J. Edwards, Joseph T. O'Flaherty
DHA May Prevent Age-Related Dementia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838628
Unlike EPA, DHA is in high concentration in brain and neuronal phospholipids where it may be as high as 35% of phosphatidylethanolamine . AA and DHA compete for esterification into the labile phospholipid SN-2 position, so that releasable SN-2 AA in brain membranes can be reduced by lowering the dietary (n-6):(n-3) PUFA ratio.
Cited by: 137
Publish Year: 2010
Author: Greg M. Cole, Sally A. Frautschy
Microb Pathog. 2016 Oct;99:196-203. doi: 10.1016/j.micpath.2016.08.025. Epub 2016 Aug 24.
Antibacterial and antibiofilm activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against periodontopathic bacteria.
Sun M1, Zhou Z1, Dong J1, Zhang J1, Xia Y1, Shu R2.
1 Department of Periodontology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.
2 Department of Periodontology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China. Electronic address:
Abstract
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are two major omega-3 polyunsaturated fatty acids (n-3 PUFAs) with antimicrobial properties. In this study, we evaluated the potential antibacterial and antibiofilm activities of DHA and EPA against two periodontal pathogens, Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum). MTT assay showed that DHA and EPA still exhibited no cytotoxicity to human oral tissue cells when the concentration came to 100 μM and 200 μM, respectively. Against P. gingivalis, DHA and EPA showed the same minimum inhibitory concentration (MIC) of 12.5 μM, and a respective minimum bactericidal concentration (MBC) of 12.5 μM and 25 μM. However, the MIC and MBC values of DHA or EPA against F. nucleatum were both greater than 100 μM. For early-stage bacteria, DHA or EPA displayed complete inhibition on the planktonic growth and biofilm formation of P. gingivalis from the lowest concentration of 12.5 μM. And the planktonic growth of F. nucleatum was slightly but not completely inhibited by DHA or EPA even at the concentration of 100 μM, however, the biofilm formation of F. nucleatum at 24 h was significantly restrained by 100 μM EPA. For exponential-phase bacteria, 100 μM DHA or EPA completely killed P. gingivalis and significantly decreased the viable counts of F. nucleatum. Meanwhile, the morphology of P. gingivalis was apparently damaged, and the virulence factor gene expression of P. gingivalis and F. nucleatum was strongly downregulated. Besides, the viability and the thickness of mature P. gingivalis biofilm, together with the viability of mature F. nucleatum biofilm were both significantly decreased in the presence of 100 μM DHA or EPA. In conclusion, DHA and EPA possessed antibacterial activities against planktonic and biofilm forms of periodontal pathogens, which suggested that DHA and EPA might be potentially supplementary therapeutic agents for prevention and treatment of periodontal diseases.
KEYWORDS:
Docosahexaenoic acid; Eicosapentaenoic acid; Fusobacterium nucleatum; Porphyromonas gingivalisAntibacterial and antibiofilm activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against periodontopathic bacteria. - PubMed - NCBI
https://www.ncbi.nlm.nih.gov/pubmed/27565090
Cell Mol Neurobiol. 2018 Jan; Roles of Peroxisome Proliferator-Activated Receptor Gamma on Brain and Peripheral Inflammation Peroxisome proliferator-activated receptor gamma (PPARγ) has been implicated in the pathology of numerous diseases involving diabetes, stroke, cancer, or obesity. It is expressed in diverse cell types, including vessels, immune and glial cells, and neurons. PPARγ plays crucial roles in the regulation of cellular differentiation, lipid metabolism, or glucose homeostasis. PPARγ ligands also exert effects on attenuating degenerative processes in the brain, as well as in peripheral systems, and it has been associated with the control of anti-inflammatory mechanisms, oxidative stress, neuronal death, neurogenesis, differentiation, and angiogenesis. This review will highlight key advances in the understanding of the PPARγ-related mechanisms responsible for neuroprotection after brain injuries, both ischemia and traumatic brain injury, and it will also cover the natural and synthetic agonist for PPARγ, angiotensin receptor blockers, and PPARγ antagonists, used in experimental and clinical research. A better understanding of the pleiotropic mechanisms and applications of these drugs to improve the recovery and to repair the acute and chronic induced neuroinflammation after brain injuries will pave the way for more effective therapeutic strategies after brain deficits. Keywords: Agonist; Angiogenesis; Angiotensin receptor blockers; Brain injury; Inflammation; PPAR gamma.
https://pubmed.ncbi.nlm.nih.gov/28975471/
Cancers
Several recent papers supporting more or less the same story – 1. How dietary Omega6 eicosanoids can contribute to cancer progression and 2. how the resolution-phase immune modulators are likely to be useful in prevention of and therapies for cancers. Including:
2014 Involvement of eicosanoids in the pathogenesis of pancreatic cancer: the roles of cyclooxygenase-2 and 5-lipoxygenase. “The interplay between inflammation and cancer progression is a growing area of research. A combination of clinical, epidemiological, and basic science investigations indicate that there is a relationship between inflammatory changes in the pancreas and neoplastic progression. Diets high in ω-6 polyunsaturated fatty acids provide increased substrate for arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) to form eicosanoids. These eicosanoids directly contribute to pancreatic cancer cell proliferation. Both COX-2 and 5-LOX are upregulated in multiple cancer types, including pancreatic cancer. In vitro studies using pancreatic cancer cell lines have demonstrated upregulation of COX-2 and 5-LOX at both the mRNA and protein levels. When COX-2 and 5-LOX are blocked via a variety of mechanisms, cancer cell proliferation is abrogated both in vitro and in vivo.”
