Omega 3 & 6 <br />Effects on CF and PA<br />Ayesha Paul & Hannah Hulsey<br />Roena Kulynych Center<br /> for Memory and Co...
Clinical Case<br />76 y.o. woman with concern about her memory <br />Hypertension<br />Hyperlipidemia<br />Mild OA<br />Me...
Omega-3 <br />Nutritionally-essential fatty acids:<br />Docosahexanoic acid (DHA)<br />Eicosapentaenoic acid (EPA)<br />Al...
Omega-3<br />Health benefits:<br />Reduces risk of cardiovascular disease through the ability to lower inflammation, blood...
Omega 6<br />Essential Fatty Acid (EFA)<br />Linoleic Acid (LA)<br />Sunflower seeds<br />γ-Linoleic Acid (GLA)<br />Peanu...
Omega 6-Essential Health Benefits<br />Health Benefits<br />Maintenance of heart health<br />LA & AA give rise to anti-inf...
Omega-3 and Brain Function<br />Needed in the brain to maintain normal nerve-cell function<br />Makes cell membranes more ...
Omega-3 Fatty Acid Treatment in 174 patients with Mild to Moderate Alzheimer Disease: OmegAD Study<br />Overview: <br />Ra...
Results: <br />No significant 12 month difference overall between the omega-3 supplemented and placebo groups on the cogni...
An n-3 Fatty Acid Deficient Diet Affects Mouse Spatial Learning in the Barnes Circular Maze<br />Overview:<br />Observed t...
Results:<br />Omega-3 deficient mice had between 47-51% lower DHA content in their brains<br />Omega-3 deficient mice had ...
DHA Dietary Supplementation Enhances The Effects Of Exercise On Synaptic Plasticity And Cognition<br />Overview<br />Tests...
DHA Dietary Supplementation Enhances The Effects Of Exercise On Synaptic Plasticity And Cognition<br />Results<br />Exerci...
DHA Clinical Trial<br />Overview:<br />Does regular DHA supplementation slow<br />the progression of cognitive and<br />fu...
DHA study: Criteria for participation<br />Probable Alzheimer’s Disease<br />MMSE=14-26<br />Baseline DHA intake ≤ 200 mg/...
Intervention<br />Randomized, double blind, placebo controlled trial of 2 grams DHA vs. placebo<br />400 subjects<br />60%...
Study drug: Martek’s DHA<br />Vegetarian source (from algae, not fish)<br />Advantage over fish or fish oil: No ocean-born...
Sub-studies: MRI and CSF <br />MRI at baseline and 18 months in half (200) subjects<br />Cerebro-spinal fluid (CSF) collec...
Design Summary<br />Rationale for DHA trial is strong<br />Design of the DHA study will permit:<br />determination of effe...
28% early <br />Termination;<br />5.8% due <br />to AE<br />24% early <br />Termination;<br />6.1% due <br />to AE<br />
Baseline status: DHA vs placebo<br />
Compliance-plasma DHA<br />
Compliance-CSF DHA<br />p<0.001<br />n=44 @ 18 months (15 placebo, 29 DHA)<br />
Co-Primary outcome: ADAS-cog<br />p=0.407<br />(Means and 95%<br /> confidence <br />intervals)<br />worsening<br />Modest...
Secondary outcome: ADCS-ADL<br />p=0.377<br />(Means and 95%<br /> confidence <br />intervals)<br />worsening<br />There w...
Pre-specified sub-group analyses: ADAS result in ApoE4 positive and negative<br />p=0.028*<br />p=0.659<br />E4 positive (...
Conclusions<br />Omega-3 and omega-6 fatty acids are nutritionally essential and must be derived from diet<br />Omega-3 do...
Recommendation to our patient/daughter<br />Omega-3 possibly benefits patients with normal cognitive function (daughter)<b...
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Internship - Omega 3 & 6 Effects on CF and PA

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Effects on CF and PA

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Internship - Omega 3 & 6 Effects on CF and PA

  1. 1. Omega 3 & 6 <br />Effects on CF and PA<br />Ayesha Paul & Hannah Hulsey<br />Roena Kulynych Center<br /> for Memory and Cognition Research <br />J. Paul Sticht Center on Aging <br />Wake Forest University School of Medicine<br />
  2. 2. Clinical Case<br />76 y.o. woman with concern about her memory <br />Hypertension<br />Hyperlipidemia<br />Mild OA<br />Meds: HCTZ, atorvastatin<br />Parent and one sibling with alzheimer’s disease <br />MMSE 28/30 (last year 30/30 <br />Exam otherwise not remarkable<br />“Doctor, should I be taking fish oil supplement for my memory?”<br />Daughter: “Should I take it too?” <br />
  3. 3. Omega-3 <br />Nutritionally-essential fatty acids:<br />Docosahexanoic acid (DHA)<br />Eicosapentaenoic acid (EPA)<br />Alpha- linolenic acid (ALA)<br />Cannot be manufactured in body, must be derived from diet<br />ALA must be converted to DHA in body<br />Dietary Sources: <br />DHA and EPA<br />Fish oil<br />ALA<br />Flaxseed, walnuts, and soy beans<br />
  4. 4. Omega-3<br />Health benefits:<br />Reduces risk of cardiovascular disease through the ability to lower inflammation, blood pressure, triglycerides and cholesterol in body<br />Stimulates blood circulation and improves blood flow <br />Reduces symptoms of psychological disorders<br />Helps repair any damage by promoting growth in neurons<br />Improves brain function and may slow cognitive decline<br />
  5. 5. Omega 6<br />Essential Fatty Acid (EFA)<br />Linoleic Acid (LA)<br />Sunflower seeds<br />γ-Linoleic Acid (GLA)<br />Peanuts<br />Arachidonic Acid (AA)<br />Red meats<br />Egg yolks<br />Dietary sources<br />Pumpkin seeds<br />Peanuts<br />Soybeans<br />Walnuts<br />Sunflower seeds<br />Almonds<br />
  6. 6. Omega 6-Essential Health Benefits<br />Health Benefits<br />Maintenance of heart health<br />LA & AA give rise to anti-inflammatory molecules<br />Suppress the production of adhesion molecules, chemokines, & interleukins<br />Replacement of saturated fats with PUFA will lower risk of heart disease<br />Mediation of immune response<br />Regulation of smooth muscles and autonomic reflexes<br />Regulation of cell division<br />Maintenance of fluid and rigidness of cellular membranes<br />Regulation of nerve transmission and communication<br />
  7. 7. Omega-3 and Brain Function<br />Needed in the brain to maintain normal nerve-cell function<br />Makes cell membranes more fluid, improving communication between brain cells<br />More elastic cell membranes allow ion channels to change shape easier as quicker transmission between neurons<br />
  8. 8. Omega-3 Fatty Acid Treatment in 174 patients with Mild to Moderate Alzheimer Disease: OmegAD Study<br />Overview: <br />Randomized double-blind trial to test the effects of DHA and EPA on patients with AD<br />Methods: <br />204 patients with mild to moderate AD (MMSE score of 15 pts or more); only 174 fulfilled the trial<br />All subjects were randomized to daily receive 1.7g of DHA and 0.6 g of EPA or a placebo for a course of 6 months <br />Freund-Levi, et.al. J Arch Neuro 2006<br />
  9. 9. Results: <br />No significant 12 month difference overall between the omega-3 supplemented and placebo groups on the cognitive tests<br />Participants with the mildest impairment experienced a slower cognitive decline with the omega-3 supplements<br />Recommended further research on omega-3 fatty acids and memory loss <br />Freund-Levi, et.al. J Arch Neuro 2006<br />
  10. 10. An n-3 Fatty Acid Deficient Diet Affects Mouse Spatial Learning in the Barnes Circular Maze<br />Overview:<br />Observed the effects on the amount of DHA in the brain of mice on performance in the Barnes Circular Maze<br />Methods:<br />3 groups of mice reared from second day of life<br />Mice given n-3 deficient milk<br />Mice given n-3 adequate milk<br />Mice reared with diet in dams<br />Spatial performance in the Barnes Circular Maze was analyzed as well as reference<br /> and working memory <br />Fedorova, et.al. 2007<br />
  11. 11. Results:<br />Omega-3 deficient mice had between 47-51% lower DHA content in their brains<br />Omega-3 deficient mice had decreased spatial performance compared to the other groups in the reference memory test<br />Speed of learning in n-3 deficient mice was decreased, no difference in working memory<br />Fedorova, et.al. 2007<br />
  12. 12. DHA Dietary Supplementation Enhances The Effects Of Exercise On Synaptic Plasticity And Cognition<br />Overview<br />Tests effects of DHA enriched diet plus exercise on cognition and BDNF related plasticity<br />Methods<br />2 groups of mice: DHA enriched diet vs. normal diet<br />Mice maintained on diet for 1 week then divided into 4 groups<br />RD sedentary<br />RD exercise<br />DHA sedentary<br />DHA exercise<br />After 1st week mice were tested in Morris water maze w/ 2 consecutive trials/day for 5 days<br />Fresh tissues and hippocampus were dissected<br />Ying, et.al J . Neuroscience 2008<br />
  13. 13. DHA Dietary Supplementation Enhances The Effects Of Exercise On Synaptic Plasticity And Cognition<br />Results<br />Exercise increased levels of synapsin I (neurotransmitter release, axonal elongation, & maintenance of synaptic concepts) <br />DHA enriched diet enhanced effects of exercise on<br /> synaptic plasticity <br />overall cognition <br />Possible mechanisms: DHA increased<br /> Activity of Akt in the hippocampus<br />activated BDNF <br />Ying, et.al J . Neuroscience 2008<br />
  14. 14. DHA Clinical Trial<br />Overview:<br />Does regular DHA supplementation slow<br />the progression of cognitive and<br />functional decline over 18 months in<br />mild to moderate Alzheimer’s Disease<br />(AD), as indicated by change in scores on<br />cognitive tests?<br />
  15. 15. DHA study: Criteria for participation<br />Probable Alzheimer’s Disease<br />MMSE=14-26<br />Baseline DHA intake ≤ 200 mg/day<br />fatty fish once a week OK, twice a week probably exclusionary<br />Average American DHA intake = 70 mg/day<br />Cholinesterase inhibitors and memantine OK<br />Psychotropic medications limited<br />No other significant exclusions<br />
  16. 16. Intervention<br />Randomized, double blind, placebo controlled trial of 2 grams DHA vs. placebo<br />400 subjects<br />60% randomized to treatment group, 40% to placebo group<br />Treatment for 18 months<br />Clinic visits every 3 months<br />
  17. 17. Study drug: Martek’s DHA<br />Vegetarian source (from algae, not fish)<br />Advantage over fish or fish oil: No ocean-borne contaminants (e.g., mercury)<br />FDA – DHA generally recognized as safe <br />Supplied by Martek<br />
  18. 18. Sub-studies: MRI and CSF <br />MRI at baseline and 18 months in half (200) subjects<br />Cerebro-spinal fluid (CSF) collection in 60 subjects at baseline and 18 months<br />
  19. 19. Design Summary<br />Rationale for DHA trial is strong<br />Design of the DHA study will permit:<br />determination of effect of DHA on progression of mild-moderate AD<br />determination of mechanism of effect, if present<br />collection of biomarker data for the design of future trials, regardless of whether DHA shows a therapeutic effect <br />
  20. 20. 28% early <br />Termination;<br />5.8% due <br />to AE<br />24% early <br />Termination;<br />6.1% due <br />to AE<br />
  21. 21. Baseline status: DHA vs placebo<br />
  22. 22. Compliance-plasma DHA<br />
  23. 23. Compliance-CSF DHA<br />p<0.001<br />n=44 @ 18 months (15 placebo, 29 DHA)<br />
  24. 24. Co-Primary outcome: ADAS-cog<br />p=0.407<br />(Means and 95%<br /> confidence <br />intervals)<br />worsening<br />Modest difference in 12 month change in ADAS scores (Wilcoxon rank p=0.027), but no significant difference between DHA and placebo groups using LME model. Also no difference in sensitivity analysis (GEE) and per protocol analyses.<br />
  25. 25. Secondary outcome: ADCS-ADL<br />p=0.377<br />(Means and 95%<br /> confidence <br />intervals)<br />worsening<br />There was no significant difference between DHA and placebo groups using LME model or GEE on<br />ITT or per protocol populations, with adjustment for MMSE and gender. <br />
  26. 26. Pre-specified sub-group analyses: ADAS result in ApoE4 positive and negative<br />p=0.028*<br />p=0.659<br />E4 positive (57.7%) <br />n=137 DHA; n= 95 placebo <br />E4 negative (42.3%) <br />n=91 DHA; n=67 placebo <br />*not corrected for multiple comparisons<br />
  27. 27. Conclusions<br />Omega-3 and omega-6 fatty acids are nutritionally essential and must be derived from diet<br />Omega-3 does not reverse symptoms of memory loss once already present<br />Recent (7-09) industry study showed Omega-3 maintained memory in people with normal CF<br />Studies needed:<br />on interaction of physical activity and effects of omega fatty acids on cognition<br />On genetic-based effectiveness of omega fatty acids<br />
  28. 28. Recommendation to our patient/daughter<br />Omega-3 possibly benefits patients with normal cognitive function (daughter)<br />Not found beneficial for patients diagnosed with AD or dementia overall<br />Important to eat well balanced diet including plenty of fruits, vegetables, high fiber whole grains, and lean meat<br />Further study needed but exercise remains an important feature of preserving memory in persons with and without dementia<br />

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