Sea food consumption for improving cardiac and cerebral manifestations of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes
Letter to the Editor

Sea food consumption for improving cardiac and cerebral manifestations of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes

Fulvio A. Scorza1, Josef Finsterer2

1Disciplina de Neurociência, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM/UNIFESP), São Paulo, Brazil; 2Krankenanstalt Rudolfstiftung, Vienna, Austria

Correspondence to: Josef Finsterer, MD, PhD. Postfach 20, 1180 Vienna, Austria. Email: fifigs1@yahoo.de.

Submitted Jun 12, 2017. Accepted for publication Jun 29, 2017.

doi: 10.21037/atm.2017.07.02


Since the initial description >30 y ago, therapeutic options for mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, the most well-known of the mitochondrial disorders (MIDs), remain limited due to the complexity of its genetic background and its clinical manifestations (1,2). MELAS is a maternally inherited, progressive MID, usually affecting people <40 y of age, with a prevalence ranging from 18.4 to 236/100,000 individuals (1-6). Clinically, MELAS manifests with cerebral, psychiatric, muscular, cardiac, renal, gastrointestinal, endocrine, auditory, dermatological, or visual abnormalities (2,3,7). Cardiac and neurological involvement has the strongest impact on the prognosis and outcome of these patients. One of the cerebral manifestations of MELAS is epilepsy, which may be linked or unlinked to stroke-like episodes. Cardiac involvement includes cardiomyopathy, pulmonary hypertension, conduction defects, or arrhythmias, possibly complicated by sudden cardiac death (SCD). Treatment of epilepsy and cardiac disease in MIDs is challenging. Whether intake of omega-3 highly unsaturated fatty acids (O3-HUFAs) has a beneficial effect on epilepsy or cardiac disease in MELAS or MIDs in general is unknown but this letter is dedicated to considerations about the usefulness of O3-HUFAs in the treatment of mitochondrial epilepsy and cardiac disease.

MELAS may be associated with partial or generalized seizures, including convulsive or non-convulsive status epilepticus (3,8). The pharmacological treatment of epilepsy in MIDs is usually not at variance from therapy of epilepsy due to other causes (8). However, mitochondrion-toxic AEDs such as valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), or barbiturates should be avoided if possible (8-10). Treatment of epilepsy in MIDs relies on classical AEDs, the ketogenic diet, L-arginine, pyruvate, or ketamine (8,11-13). Death from epilepsy in MIDs has been only rarely reported (8) and sudden unexpected death in epilepsy (SUDEP), the most common cause of death in people with intractable epilepsy (14), is unreported in MELAS.

Cardiac dysfunction represents an important cause of disability in MELAS patients and MIDs in general (15-17). Cardiac involvement in MIDs, including MELAS, needs to be recognized by comprehensive cardiovascular screening protocols and needs to be carefully monitored and adequately treated, to reduce the risk of morbidity and mortality (17). Currently, there is a lack of clinical and experimental studies evaluating cardiac complications and preventive and curative strategies in MELAS (17,18). Though cardiac abnormalities can be a major problem in MELAS patients, our understanding of the best way to prevent cardiac compromise is still unknown. Accordingly, MELAS patients live with a chronic intractable disorder, which reduces the quality of life with a subsequent burden on the caregiver, the family, and the society (19).

About 10 years ago a debate about the dietary management with O3-HUFA supplementation for epilepsy, SUDEP, and cardiovascular disease evolved (20-22). It was proposed to develop new methods or actions, other than classical medical therapies, to prevent or treat it. Already the Old Testament book of Tobias proclaimed the benefits of consuming O3-HUFAs as a possible type of medical therapy (“Then the angel said to him: Take out the entrails of the fish, and lay up his heart, and his gall, and his liver for thee; for these are necessary for useful medicines”) (23,24). Since Bang and Dyerberg reported in 1972 that Greenland Eskimos on a diet rich in O3-HUFAs have a lower incidence of cardiovascular disease, a series of translational studies were conducted in order to evaluate the beneficial effects promoted by O3-HUFAs on human diseases and health systems in general (25,26).

O3-HUFAs have been shown to be effective in preventing stroke and myocardial infarction. Particularly in individuals with high cardiovascular risk, moderate-to-high consumption of fish lowered the prevalence of chronic diseases associated with obesity, diabetes, and some types of cancer and displayed neuroprotective properties and exerted beneficial effects on neurological and psychiatric disease (20-22,27-34). In a meta-analysis of patients with arterial hypertension O3-HUFAs reduced high blood pressure values (35). There are also indications that O3-HUFAs have an anti-arrhythmic effect and positively influence atrial fibrillation (36). In a study of 205 patients with chronic heart failure, intake of O3-HUFAs significantly improved left ventricular diastolic dysfunction and reduced proBNP levels (37). The beneficial effect of O3-HUFA on heart failure was also confirmed by other studies (38). In a study of pediatric patients with dilated cardiomyopathy, O3-HUFA supplementation during 6 months resulted in improvement of various echocardiographic parameters (39). O3-HUFA may also cause adverse reactions. In animals but not in humans O3-HUFA has been shown to reduce insulin-resistance. However, intake of O3-HUFA appears to carry an increased risk for developing diabetes (40).

O3-HUFAs, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential fatty acids (41,42), which exert their beneficial effect via anti-inflammatory, anti-oxidative, or anti-fibrotic mechanisms. Since the human body cannot synthesize O3-HUFAs, an appropriate diet represents an important source of these essential fatty acids (25,43,44). Evaluating these considerations, advantages and nutritional benefits of a diet rich in fish or other seafood are particularly due to the content of high-quality protein and high concentrations of EPA and DHA in various marine species (45-47). The most appropriate fish choices for consumption, particularly with regard to the amount of O3-HUFAs, the predatory characteristics, and the concentrations of contaminants (e.g., methylmercury, polychlorinated biphenyls and dioxins), are anchovies, atlantic herring, salmon, trout, and sardines (27,45-48). For subjects who prefer a diet with safe concentrations of contaminants and would like to enjoy the benefits of O3-HUFAs, fish oil supplements or intake of foods such as walnuts or oils from flax, canola, or soybean, can be alternatively given (49,50). According to national and international guidelines containing recommendations for the general population on the prevention of chronic diseases, consumption of at least 250 mg/day of long-chain O3-HUFAs or at least 2 servings/week of oily fish is recommended (51).

Overall, MELAS is a currently incurable genetic disorder with cardiac and cerebral involvement and although our proposal is speculative, there is a strong need that thought is given to new considerations and that studies are carried out if O3-HUFAs are effective regarding the cardiovascular and CNS compromise in MELAS or other MIDs. Until new therapeutic options are available, MID patients should undergo comprehensive diagnostic work-up and monitoring, particularly of neurological and cardiac abnormalities, not to miss application of effective treatment and prophylaxis. Regular intake of O3-HUFA-rich fish is a good option, because it is healthy and relatively inexpensive. Moreover, prescribing non-contaminated fish to MID and MELAS patients is recommendable since it has no adverse effects and may exhibit a beneficial effect on epilepsy and cardiac complications in these patients.


Acknowledgements

Our studies are supported by the following grants: FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo); CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), CEPID/FAPESP; and FAPESP/CNPq/MCT (Instituto Nacional de Neurociência Translacional).


Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.


References

  1. Pavlakis SG, Phillips PC, DiMauro S, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol 1984;16:481-8. [Crossref] [PubMed]
  2. Sproule DM, Kaufmann P. Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci 2008;1142:133-58. [Crossref] [PubMed]
  3. Kaufman KR, Zuber N, Rueda-Lara MA, et al. MELAS with recurrent complex partial seizures, nonconvulsive status epilepticus, psychosis, and behavioral disturbances: case analysis with literature review. Epilepsy Behav 2010;18:494-7. [Crossref] [PubMed]
  4. Uusimaa J, Moilanen JS, Vainionpää L, et al. Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children. Ann Neurol 2007;62:278-87. [Crossref] [PubMed]
  5. Manwaring N, Jones MM, Wang JJ, et al. Population prevalence of the MELAS A3243G mutation. Mitochondrion 2007;7:230-3. [Crossref] [PubMed]
  6. Malhotra K, Liebeskind DS. Imaging of MELAS. Curr Pain Headache Rep 2016;20:54. [Crossref] [PubMed]
  7. Bhuvaneswar CG, Goetz JL, Stern TA. Multiple neurologic, psychiatric, and endocrine complaints in a young woman: a case discussion and review of the clinical features and management of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke. Prim Care Companion J Clin Psychiatry 2008;10:237-44. [Crossref] [PubMed]
  8. Finsterer J, Zarrouk Mahjoub S. Epilepsy in mitochondrial disorders. Seizure 2012;21:316-21. [Crossref] [PubMed]
  9. Pronicka E, Weglewska-Jurkiewicz A, Pronicki M, et al. Drug-resistant epilepsia and fulminant valproate liver toxicity. Alpers-Huttenlocher syndrome in two children confirmed post mortem by identification of p.W748S mutation in POLG gene. Med Sci Monit 2011;17:CR203-9. [Crossref] [PubMed]
  10. Saneto RP, Lee IC, Koenig MK, et al. POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders. Seizure 2010;19:140-6. [Crossref] [PubMed]
  11. Toribe Y, Tominaga K, Ogawa K, et al. Usefulness of L-arginine infusion for status epilepticus in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. No To Hattatsu 2007;39:38-43. [PubMed]
  12. Koga Y, Povalko N, Katayama K, et al. Beneficial effect of pyruvate therapy on Leigh syndrome due to a novel mutation in PDH E1α gene. Brain Dev 2012;34:87-91. [Crossref] [PubMed]
  13. Prüss H, Holtkamp M. Ketamine successfully terminates malignant status epilepticus. Epilepsy Res 2008;82:219-22. [Crossref] [PubMed]
  14. Scorza FA, Cavalheiro EA, Costa JC. Sudden cardiac death in epilepsy disappoints, but epileptologists keep faith. Arq Neuropsiquiatr 2016;74:570-3. [Crossref] [PubMed]
  15. Taniguchi A, Kitagawa T, Kuzuhara S. MELAS sudden death due to paroxysmal arrhythmia. Nihon Rinsho 2002;60 Suppl 4:606-9. [PubMed]
  16. Thomas T, Craigen WJ, Moore R, et al. Arrhythmia as a cardiac manifestation in MELAS syndrome. Mol Genet Metab Rep 2015;4:9-10. [Crossref] [PubMed]
  17. Finsterer J, Zarrouk-Mahjoub S. Arrhythmias in MELAS syndrome. Mol Genet Metab Rep 2016;7:54. [Crossref] [PubMed]
  18. Finsterer J, Zarrouk-Mahjoub S. In the heart of MELAS syndrome. Int J Cardiol 2016;214:157-8. [Crossref] [PubMed]
  19. Sofou K. Mitochondrial disease: a challenge for the caregiver, the family, and society. J Child Neurol 2013;28:663-7. [Crossref] [PubMed]
  20. Scorza FA, Cysneiros RM, Arida RM, et al. The other side of the coin: Beneficiary effect of omega-3 fatty acids in sudden unexpected death in epilepsy. Epilepsy Behav 2008;13:279-83. [Crossref] [PubMed]
  21. Scorza FA, Cysneiros RM, Arida RM, et al. Fish consumption, contaminants and sudden unexpected death in epilepsy: many more benefits than risks. Braz J Biol 2010;70:665-70. [Crossref] [PubMed]
  22. DeGiorgio CM, Taha AY. Omega-3 fatty acids (ῳ-3 fatty acids) in epilepsy: animal models and human clinical trials. Expert Rev Neurother 2016;16:1141-5. [Crossref] [PubMed]
  23. Anglicans Articles of Religion. Available online: http://anglicansonline.org/
  24. Superko HR, Superko AR, Lundberg GP, et al. Omega-3 Fatty Acid Blood Levels Clinical Significance Update. Curr Cardiovasc Risk Rep 2014;8:407. [Crossref] [PubMed]
  25. Davidson MH. Omega-3 fatty acids: new insights into the pharmacology and biology of docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid. Curr Opin Lipidol 2013;24:467-74. [Crossref] [PubMed]
  26. Bang HO, Dyerberg J. Plasma lipids and lipoproteins in Greenlandic west coast Eskimos. Acta Med Scand 1972;192:85-94. [Crossref] [PubMed]
  27. Gil A, Gil F. Fish, a Mediterranean source of n-3 PUFA: benefits do not justify limiting consumption. Br J Nutr 2015;113 Suppl 2:S58-67. [Crossref] [PubMed]
  28. Delgado-Lista J, Perez-Martinez P, Lopez-Miranda J, et al. Long chain omega-3 fatty acids and cardiovascular disease: a systematic review. Br J Nutr 2012;107 Suppl 2:S201-13. [Crossref] [PubMed]
  29. FAO. Fats and fatty acids in human nutrition. Report of an expert consultation. FAO Food Nutr Pap 2010;91:1-166. [PubMed]
  30. Oehlenschläger J. Seafood: nutritional benefits and risk aspects. Int J Vitam Nutr Res 2012;82:168-76. [Crossref] [PubMed]
  31. Lund EK. Health benefits of seafood; is it just the fatty acids? Food Chem 2013;140:413-20. [Crossref] [PubMed]
  32. Mazza M, Pomponi M, Janiri L, et al. Omega-3 fatty acids and antioxidants in neurological and psychiatric diseases: an overview. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:12-26. [Crossref] [PubMed]
  33. Scorza FA, Cysneiros RM, Terra VC, et al. Omega-3 consumption and sudden cardiac death in schizophrenia. Prostaglandins Leukot Essent Fatty Acids 2009;81:241-5. [Crossref] [PubMed]
  34. Dangour AD, Andreeva VA, Sydenham E, et al. Omega 3 fatty acids and cognitive health in older people. Br J Nutr 2012;107 Suppl 2:S152-8. [Crossref] [PubMed]
  35. Colussi G, Catena C, Novello M, et al. Impact of omega-3 polyunsaturated fatty acids on vascular function and blood pressure: Relevance for cardiovascular outcomes. Nutr Metab Cardiovasc Dis 2017;27:191-200. [Crossref] [PubMed]
  36. Christou GA, Christou KA, Korantzopoulos P, et al. The Current Role of Omega-3 Fatty Acids in the Management of Atrial Fibrillation. Int J Mol Sci 2015;16:22870-87. [Crossref] [PubMed]
  37. Chrysohoou C, Metallinos G, Georgiopoulos G, et al. Short term omega-3 polyunsaturated fatty acid supplementation induces favorable changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; A randomized clinical trial. Vascul Pharmacol 2016;79:43-50. [Crossref] [PubMed]
  38. Kohashi K, Nakagomi A, Saiki Y, et al. Effects of eicosapentaenoic acid on the levels of inflammatory markers, cardiac function and long-term prognosis in chronic heart failure patients with dyslipidemia. J Atheroscler Thromb 2014;21:712-29. [Crossref] [PubMed]
  39. Firuzi O, Shakibazad N, Amoozgar H, et al. Effects of omega-3 polyunsaturated Fatty acids on heart function and oxidative stress biomarkers in pediatric patients with dilated cardiomyopathy. Int Cardiovasc Res J 2013;7:8-14. [PubMed]
  40. Djoussé L, Gaziano JM, Buring JE, et al. Dietary omega-3 fatty acids and fish consumption and risk of type 2 diabetes. Am J Clin Nutr 2011;93:143-50. [Crossref] [PubMed]
  41. Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol 2013;75:645-62. [Crossref] [PubMed]
  42. Yates CM, Calder PC, Ed Rainger G. Pharmacology and therapeutics of omega-3 polyunsaturated fatty acids in chronic inflammatory disease. Pharmacol Ther 2014;141:272-82. [Crossref] [PubMed]
  43. Ghasemifard S, Turchini GM, Sinclair AJ. Omega-3 long chain fatty acid "bioavailability": a review of evidence and methodological considerations. Prog Lipid Res 2014;56:92-108. [Crossref] [PubMed]
  44. Leaf A, Kang JX, Xiao YF. Fish oil fatty acids as cardiovascular drugs. Curr Vasc Pharmacol 2008;6:1-12. [Crossref] [PubMed]
  45. Castro-González MI, Méndez-Armenta M. Heavy metals: Implications associated to fish consumption. Environ Toxicol Pharmacol 2008;26:263-71. [Crossref] [PubMed]
  46. Clarkson TW. The three modern faces of mercury. Environ Health Perspect 2002;110 Suppl 1:11-23. [Crossref] [PubMed]
  47. Domingo JL, Bocio A, Falcó G, et al. Benefits and risks of fish consumption Part I. A quantitative analysis of the intake of omega-3 fatty acids and chemical contaminants. Toxicology 2007;230:219-26. [Crossref] [PubMed]
  48. Scorza CA, Cavalheiro EA, Calderazzo L, et al. Chew on this: sardines are still a healthy choice against SUDEP. Epilepsy Behav 2014;41:21-2. [Crossref] [PubMed]
  49. Jeejeebhoy KN. Benefits and risks of a fish diet--should we be eating more or less? Nat Clin Pract Gastroenterol Hepatol 2008;5:178-9. [Crossref] [PubMed]
  50. Domingo JL. Omega-3 fatty acids and the benefits of fish consumption: is all that glitters gold? Environ Int 2007;33:993-8. [Crossref] [PubMed]
  51. Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 2011;58:2047-67. [Crossref] [PubMed]
Cite this article as: Scorza FA, Finsterer J. Sea food consumption for improving cardiac and cerebral manifestations of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes. Ann Transl Med 2017;5(17):369. doi: 10.21037/atm.2017.07.02

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