Prostaglandins, Leukotrienes and Essential Fatty Acids 88 (2013) 251–255

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ISSFAL Society News

It’s an exciting time at ISSFAL, because the Board of Directors hasbeen partially renewed. As usual, I encourage all members to play anactive role in our society and contribute ideas for our growth andwellbeing. One notable example is the first ISSFAL Regional Meeting,which is ready to take off and will surely be successful. Thisexcellent idea can be replicated by other members, who can contactour offices for details.

The sad news is that Dr. Alexander Leaf (one of our FoundingFathers) passed away. We commemorate Dr. Leaf with an obituaryby his close collaborator Dr. George Billman. Also note that PLEFApublished an obituary by Dr. Jing X. Kang (see http://www.sciencedirect.com/science/article/pii/S0952327813000240). Weall remember Dr. Leaf’s verve, good spirits, and humbleness. It’sno coincidence that our most prestigious award is titled after Dr.Leaf and all ISSFAL members will miss him a lot.

As you will read in the View from the Secretary’s Perch, somemembers did not pay their dues as of today. Please remember thatISSFAL wastes time and money by sending reminders, so pleasego online and easily pay your dues via our website. It’s quick andeasy and vital to our welfare.

Final words are for PLEFA, which is going strong, very strongindeed. As always, I encourage members to submit their best work toPLEFA and cite the journal whenever possible. We often hear from newmembers that the way they heard about ISSFAL was precisely throughPLEFA. Therefore, please do remember that PLEFA is our official journaland that we can/should publish high-quality research in it.

As 2013 is the year in which we prepare for our next meeting,once you are finished reading this please go back to the bench andwork through the beautiful experiments whose results you willpresent in Stockholm.

Francesco Visioli, Ph.D.Madrid Institute for Advanced Studies (IMDEA)—Food, Madrid,

Spain.

Methods and biomarkers for omega-3 fatty acid profilingBy Adam Metherel, Ph.D. and Ken Stark, Ph.D., University of

Waterloo, Waterloo, ON, Canada.

L.M. Browning, C.G. Walker, A.P. Mander, A.L. West, J. Madden,J.M. Gambell, S. Young, L. Wang, S.A. Jebb, P.C. Calder.Incorporation of eicosapentaenoic and docosahexaenoic acidsinto lipid pools when given as supplements providing dosesequivalent to typical intakes of oily fish

American Journal of Clinical Nutrition (Oct. 2012), 96:748–58.Numerous blood fractions and biomarkers have previously been

utilized for the assessment of individual and population changes inomega-3 intake. Browning et al. examine changes in eicosapentaenoic

78/$ - see front matter

x.doi.org/10.1016/j.plefa.2013.02.006

(EPA) and docosahexaenoic acid (DHA) in numerous lipids poolsfollowing a 12-month omega-3 capsule intervention study in over200 men. The study is designed to replicate EPA and DHA

intakes achieved with the habitual consumption of oily fish fromthe diet. The comprehensive assessment of blood fractions thatincludes additional buccal cell and adipose tissue measurements iscommendable. Plasma phosphatidylcholine (PC) EPAþDHA appears

to be the most suitable biomarker for acute changes in dietary intake,and platelet and mononuclear cells EPAþDHA are the mostsuitable biomarkers for habitual intakes [1]. This is significant asrecent meta-analyses have determined little to no effect of omega-3advice on cardiovascular disease outcomes. However, these findings

could be attributed to the intention to treat approach utilized thatfails to measure blood changes in omega-3 composition, and subse-quently adherence to study protocols. Determination of bloodbiomarkers for both acute and habitual dietary omega-3 intakes

should be implemented to confirm adherence of study participantswhen dietary change is prescribed.

Red blood cell EPAþDHA compositions have long been con-

sidered a suitable biomarker for habitual intakes, however, due tolarge variability in RBC EPA levels this biomarker was deemed lesssuitable than both platelet and mononuclear cell EPAþDHA. EPAtends to both incorporate into and washout from erythrocytes at amuch faster rate when compared to DHA [2]. These differences in

incorporation and washout between EPA and DHA can be attrib-uted to the preferential incorporation of EPA into PC on the outerRBC membrane and DHA into phsophatidylethanolamine (PE) onthe inner membrane. Fatty acid incorporation into the outer

membrane is a rapid process with very little PC movement toinner membrane via an ATP-independent process. This is comparedto a fast ATP-dependent process for the movement of PE to theinner membrane [3]. Recent meals may increase the availability of

EPA or other fatty acids that could displace EPA from the mem-brane in a short period and result in the increased variabilityreported. This relatively free movement of EPA into and out of theRBC membrane makes the composition of EPA in RBCs a fluid andconstantly changing lipid profile, and could be used to indicate

acute changes in oily fish intake. The findings from this study arefascinating as it may indicate a single blood fraction that can detectboth acute (RBC EPA) and chronic (RBC DHA) oily fish intake, andsimultaneously provide important information on adherence to

dietary intervention protocols.References[1] L.M. Browning, C.G. Walker, A.P. Mander, A.L. West, J.

Madden, J.M. Gambell, S. Young, L. Wang, S.A. Jebb, P.C.Calder, Incorporation of eicosapentaenoic and docosahex-aenoic acids into lipid pools when given as supplements

F. Visioli / Prostaglandins, Leukotrienes and Essential Fatty Acids 88 (2013) 251–255252

providing doses equivalent to typical intakes of oily fish,Am. J. Clin. Nutr. 96 (2012) 748–758.

[2] A.H. Metherel, J.M. Armstrong, A.C. Patterson, K.D. Stark,Assessment of blood measures of n-3 polyunsaturatedfatty acids with acute fish oil supplementation and wash-out in men and women, Prostaglandins Leukot. Essent.Fatty Acids 81 (2009) 23–29.

[3] M. Seigneuret, P.F. Devaux, ATP-dependent asymmetricdistribution of spin-labeled phospholipids in the erythro-cyte membrane: relation to shape changes, Proc. Natl.Acad. Sci. USA. 81 (1984) 3751–3755.

Sex differences in DHA is dependent on DHA intakeBy Alex Kitson, Ph.D. Candidate and Ken Stark, Ph.D., University

of Waterloo, Waterloo, ON, Canada

Szimonetta Lohner, Katalin Fekete, Tamas Marosvolgyi andTamas Desci.

Gender differences in the long-chain polyunsaturated fattyacid status: systematic review of 51 publications

Ann. Nutr. Metab. 2013;62:98–112.This paper by Lohner et al. is a much needed systematic review

of observational studies in humans involving sex differences inhighly unsaturated fatty acid (HUFA) status of blood and adipose[1]. The review, which included 51 studies investigating numer-ous blood fractions and geographic areas, concluded that womenhave significantly higher docosahexaenoic acid (DHA) in plasmatotal lipids, plasma phospholipids, and total erythrocyte mem-brane lipids. No effect of sex was found in DHA of plasmacholesteryl esters, plasma triacylglycerols, erythrocyte phospha-tidyl choline, or adipose tissue, indicating that the higher DHA inwomen is specific to certain lipid pools.

The authors also performed an ecological subgroup analysisexamining whether sex differences in plasma DHA were presentin studies conducted in geographical areas in which DHA intakesare typically high (including Japanese and Inuit individuals) orlow (such as North America and Great Britain). It was found thatwomen had higher plasma DHA only in geographical areasassociated with low n-3 HUFA intakes, indicating that womenhave a metabolic adaptation resulting in higher DHA when n-3HUFA intakes are low. This is consistent with previous studiesshowing that the increased DHA synthesis in women disappearswhen subjects are placed on a high n-3 HUFA diet [2], and thatbaseline sex differences in plasma DHA disappear following an8 g/day fish oil intervention [3]. The mechanism underlying theinteraction between sex and diet on blood DHA status isunclear [4].

It has been proposed that the increased DHA status in womenis an evolutionary adaptation to provide a fetus with DHA duringpregnancy [5]. It appears that the increased female DHA statusonly occurs when DHA intakes are low, suggesting that adapta-tions to ensure DHA status in pregnancy are also dependent onDHA intakes. Future studies examining the effect of dietary DHAon DHA synthesis and metabolism during pregnancy are required.

References[1] S. Lohner, K. Fekete, T. Marosvolgyi, T. Decsi, Gender

differences in the long-chain polyunsaturated fatty acidstatus: systematic review of 51 publications, Ann. Nutr.Metab. 62 (2) (2013) 98–112.

[2] R. Pawlosky, J. Hibbeln, Y. Lin, N. Salem, Jr., n-3 Fatty acidmetabolism in women, Br. J. Nutr. 90 (5) (2003) 993–994.

[3] A.H. Metherel, J.M. Armstrong, A.C. Patterson, K.D. Stark,Assessment of blood measures of n-3 polyunsaturated fattyacids with acute fish oil supplementation and washout in

men and women, Prostaglandins Leukot. Essent. Fatty Acids81 (1) (2009) 23–29.

[4] A.P. Kitson, C.K. Stroud, K.D. Stark, Elevated production ofdocosahexaenoic acid in females: potential molecularmechanisms, Lipids 45 (3) (2010) 209–224.

[5] K.D. Stark, S. Beblo, M. Murthy, M. Buda-Abela, J. Janisse,H. Rockett, J.E. Whitty, S.S. Martier, R.J. Sokol, et al.,Comparison of bloodstream fatty acid composition fromAfrican-American women at gestation, delivery, and post-partum, J. Lipid Res., 46 (3) (2005) 516–525.

Fatty acids and cardiovascular diseaseBy Bill Harris, Director of Research, Health Diagnostic Labora-

tory Inc., USA.

Re-analysis of Sydney heart studyThe role of omega-6 fatty acids, primarily linoleic acid (LA), in

cardiovascular health continues to attract the interest of research-ers. While several expert panels and regulatory bodies haverecommended intakes LA be maintained at approximately 5% to10% of energy for optimal cardiovascular health [1], other scien-tists have argued that LA intakes should be lower to reduce therisk of inflammation-mediated diseases [2–4]. One line of evi-dence used by the American Heart Association (AHA) to supporttheir recommendations was randomized controlled trials inwhich polyunsaturated fatty acids (PUFAs) replaced saturatedfatty acids. Meta-analyses of these trials supported the AHAposition [5], but these conclusions were challenged by Ramdsenet al. who claimed that LA could not be unambiguously creditedsince the oils used in several trials (often soybean oil) alsocontained some alpha-linolenic acid (ALA) [6] which could, intheory, be responsible for the beneficial effects. Most recently,Ramsden and colleagues have focused on a re-analysis of one trialthat has typically been excluded from such meta-analyses, theSydney Diet Heart Study [7]. The Sydney study a single blinded,parallel group, randomized controlled trial conducted in 1966–73in 458 men aged 30–59 years with a recent coronary event. Thestudy was intended to raise LA intakes from the approximately 8%then common in CHD patients in Australia to 15%, with aconcomitant reduction in saturated fatty acids and no additionof ALA. Since only total mortality was originally reported, thequestion of the effects of this intervention of CHD was unclear.Ramsden et al. conducted a more detailed analysis of previouslyunpublished data from the Sydney study and reported evidencefor potentially increased risk for fatal CHD events in men on thehigh PUFA diet, particularly in patients with who smoked ordrank immoderate amounts of alcohol [8]. They went on toinclude the Sydney study results with other randomized trialdata, and concluded that studies in which high levels of omega-6fatty acids were fed with no increase in omega-3 fatty acids led toadverse outcomes, whereas studies with mixed omega-6 andomega-3 were positive. They thus challenge the current recom-mendations that assumed omega-6 fatty acids were ‘‘hearthealthy’’.

This paper certainly contributes to the discussion of the role ofomega-6 in CHD risk reduction, but – as with all studies – thereare caveats. First, two quotations from the original report [7] needto be considered: (1) ‘‘Multivariate analysis revealed that none ofthe dietary factors were significantly related to survival’’; (2)‘‘Clearly what was planned as a test of the lipid hypothesisbecame a multifactorial study. Changes in smoking habit, dietarypattern, body weight, lifestyle and physical activity before andafter entry to the trial may well have had a significant effect onprognosis. On that background, any added effect of further diet

F. Visioli / Prostaglandins, Leukotrienes and Essential Fatty Acids 88 (2013) 251–255 253

change could not be shown.’’ Thus, there are differences ofopinion regarding the interpretation of the study’s findings.Secondly, even if true, there are no organizations currentlyrecommending a diet with 15% en as LA and no omega-3 fattyacids and so the relevance to current dietary guidelines is unclearand these findings do not address the question of the advisabilityof LA intakes in the o5% en range. Finally, the margarines used inthe intervention group were likely major sources of trans fattyacids, particularly transLA (perhaps the worst offenders [9]) and, ifso, the increase in trans intake could have contributed to theadverse outcomes.

Plasma omega-6 fatty acid levels and incident CHD—EPICAlso relevant to the omega-6 question is a new report from the

EPIC study (European Prospective Investigation into Cancer) [10].This nested case-control study examined the associations betweenplasma phospholipid fatty acid composition and subsequent risk forCHD. Fatty acid levels in 2424 patients who developed CHD over theensuing 15 years were compared with levels from 4930 patientswho did not. They observed in fully adjusted models that the onlylong chain omega-3 fatty acid associated (here, inversely) with riskfor CHD was docosapentaenoic acid (C22:5n-3), not EPA or DHA.Higher saturated fatty acid (palmitic and stearic) levels wereassociated with increased risk, whereas higher LA (and evenarachidonicacid) levels were sentinels of decreased risk. The authorsconcluded, ‘‘Early guidelines to prevent CHD recommended reduc-tions in saturated fat but little consistency as to what might besubstituted: other fats, protein, or carbohydrate. Our results add tothe accumulating evidence that substitution of saturated fat by n-6polyunsaturated fat may have more CHD benefits.’’

AnchorOmega-3 fatty acids as ‘‘drugs’’ for dyslipidemia continue to be

developed. One of the largest (n¼702) trials ever to test theeffects of these fatty acids on plasma lipid profiles was publishedby Ballantyne et al. [11]. The ANCHOR study utilized 495% pureEPA ethyl esters [Vascepa, Amarin Corp.; virtually the same asEpadel (Mochida Corp) tested in the JELIS study [12]] in statin-treated patients with triglyceride (TG) levels between 200 and499 mg/dL. Mean baseline TG levels were 262 mg/dL (3 mmol/L)and low density lipoprotein cholesterol (LDL-C) levels of 83 mg/dL(2.2 mmol/L). Patients were randomized to 2 or 4 g/d of Vascepaor placebo (light paraffin oil) for 12 weeks. Focusing on the higherdose groups, TG levels decreased by 18% from baseline and LDL-Cincreased slightly (by 1.5%) from baseline. Interestingly (andcontroversially), the changes from baseline for these two analytesin the placebo group were 6% and 9%, respectively, leading to‘‘placebo-adjusted’’ reductions in TG of 22% and LDL-C of 6.2%.Hence, it was the rises seen in the placebo group that markedlyimpacted the reported effects of Vascepa on these two lipids. Asnoted, this has led to a lively discussion on the appropriateness oflight paraffin oil as a placebo [13] in such trials. With the omega-3pharmaceutical market growing worldwide, and the potentialdifferential effects of EPA vs. DHA on LDL-C levels [14] servingas a (marketing, at least) point of demarcation between agents,interest in defining the physiologic roles of each of the two majoromega-3 fatty acids will intensify.

References[1] W.S. Harris, D. Mozaffarian, E.B. Rimm, P.M. Kris-Etherton,

L.L. Rudel, L.J. Appel, M.M. Engler, M.B. Engler, F.M. Sacks,Omega-6 fatty acids and risk for cardiovascular disease: ascience advisory from the american heart associationnutrition committee, Circulation 119 (2009) 902–907.

[2] B. Lands, A critique of paradoxes in current advice ondietary lipids, Prog. Lipid Res., 47 (2008) 77–106.

[3] A.P. Simopoulos, The importance of the omega-6/omega-3fatty acid ratio in cardiovascular disease and other chronicdiseases, Exp. Biol. Med. (Maywood) 233 (2008) 674–688.

[4] T.L. Blasbalg, J.R. Hibbeln, C.E. Ramsden, S.F. Majchrzak, R.R.Rawlings, Changes in consumption of omega-3 and omega-6 fatty acids in the united states during the 20th century,Am. J. Clin. Nutr. 93 (2011) 950–962.

[5] D. Mozaffarian, R. Micha, S. Wallace, Effects on coronaryheart disease of increasing polyunsaturated fat in place ofsaturated fat: a systematic review and meta-analysis ofrandomized controlled trials, PLoS Med. 7 (2010)e1000252.

[6] C.E. Ramsden, J.R. Hibbeln, S.F. Majchrzak, J.M. Davis. N-6fatty acid-specific and mixed polyunsaturate dietary inter-ventions have different effects on chd risk: a meta-analysisof randomised controlled trials, Br. J. Nutr. 104 (2010)1586–1600.

[7] J.M. Woodhill, A.J. Palmer, B. Leelarthaepin, C. McGilchrist,R.B. Blacket, Low fat, low cholesterol diet in secondaryprevention of coronary heart disease, Adv. Exp. Med. Biol.109 (1978) 317–330.

[8] C.E. Ramsden, D. Zamora, B. Leelarthaepin, S.F. Majchrzak-Hong, K.R. Faurot, C.M. Suchindran, A. Ringel, J.M. Davis, J.R.Hibbeln, Use of dietary linoleic acid for secondary preven-tion of coronary heart disease and death: evaluation ofrecovered data from the sydney diet heart study andupdated meta-analysis. Br. Med. J. 346 (2013) e8707.

[9] R.N. Lemaitre, I.B. King, T.E. Raghunathan, R.M. Pearce, S.Weinmann, R.H. Knopp, M.K. Copass, L.A. Cobb, D.S. Sis-covick, Cell membrane trans-fatty acids and the risk ofprimary cardiac arrest, Circulation 105 (2002) 697–701.

[10] K.T. Khaw, M.D. Friesen, E. Riboli, R Luben, N. Wareham,Plasma phospholipid fatty acid concentration and incidentcoronary heart disease in men and women: the epic-norfolk prospective study, PLoS Med. 9 (2012) e1001255.

[11] C.M. Ballantyne, H.E. Bays, J.J. Kastelein, E. Stein, J.L.Isaacsohn, R.A. Braeckman, P.N. Soni, Efficacy and safetyof eicosapentaenoic acid ethyl ester (amr101) therapy instatin-treated patients with persistent high triglycerides(from the anchor study), Am. J. Cardiol. 110 (2012) 984–992.

[12] M. Yokoyama, H. Origasa, M. Matsuzaki, Y. Matsuzawa, Y.Saito, Y. Ishikawa, S. Oikawa, J. Sasaki, H. Hishida, H.Itakura, T. Kita, A Kitabatake, N. Nakaya, T. Sakata, K.Shimada, K. Shirato, Effects of eicosapentaenoic acid onmajor coronary events in hypercholesterolaemic patients(jelis): a randomised open-label, blinded endpoint analysis.Lancet 369 (2007) 1090–1098.

[13] S.J. Baum, Anchor trial conclusions regarding the effects ofpure eicosapentaenoic acid on low-density lipoproteincholesterol, Am. J. Cardiol. 111 (2013) 454–455.

[14] M.Y. Wei, T.A. Jacobson, Effects of eicosapentaenoic acidversus docosahexaenoic acid on serum lipids: a systematicreview and meta-analysis, Curr. Atheroscler. Rep. 13(2011) 474–483.

In memoriam—Alexander Leaf, MD (1920–2012)By Dr. George E. Billman, Department of Physiology and Cell

Biology, The Ohio State University.

It is with deep sorrow that I announce the recent passing of Dr.Alexander Leaf, one of the founders of ISSFAL and a giant incardio-renal physiology and medicine. After a short illness,Dr. Leaf died peacefully at his home in Concord, Massachusetts

F. Visioli / Prostaglandins, Leukotrienes and Essential Fatty Acids 88 (2013) 251–255254

on December 24, 2012 at the age of 92 years. Those of us whoworked with Alex can personally testify to his sense of humor, hishumility, his enthusiasm for research, and his tireless quest forscientific truth. He was a supportive mentor to literally hundredsof young scientists and physicians—a legacy that will continue tobear fruit for many years to come. Alex had a long and distin-guished career that is difficult to summarize adequately.I encourage all the readers of this brief tribute to read anautobiography that Alex wrote a little over 10 years ago as theintroductory chapter of the 2001 Annual Review of Physiology[11]. His essay provides an excellent overview of his accomplish-ments and clearly conveys his sense of humor and humility. Alexwas the definitive gentleman and scholar.

I shall now attempt to provide the reader with a sense of Alex,the man, as well as a limited summary of his remarkableaccomplishments as a scientist and physician. Alex was born inYokohama, Japan April 10, 1920 where his parents had escapedfrom Czarist Russia shortly before the Bolshevik revolution. Theyleft Japan and settled in Seattle in 1922, where his father opened adental practice. I recall him fondly describing an idyllic boyhood,hiking and exploring the still largely virgin forests of the PacificNorthwest. Alex often claimed that he was not the best studentdue to his very slow reading speed. Later in life, he attempted toremedy this problem by enrolling in a speed reading courseoffered by Harvard University. He related that he succeeded indoubling his reading speed but exactly halved his comprehension.I doubt that Alex was ever as a poor student as he claimed to be.Rather, this I think is an excellent example of his humility andself-deprecating humor. Indeed, prior to completion of his HighSchool education, Alex won a very competitive partial scholarshipto attend Harvard University. However, as it was the height of thedepression, he opted to live at home and complete his under-graduate education at the much more affordable University ofWashington(tuition $30/semester),graduating with a degree inChemistry in 1940. Upon graduation he enrolled in the medicalprogram at the University of Michigan. With the winds of warapproaching gale force, he enlisted in the Army Medical Corpsand, due to an accelerated program, obtained his medical degreein 3 years, graduating in 1943. The army allowed him to completeresidency programs at Massachusetts General Hospital (MGH)and the Mayo Clinic before assuming active duty. Although he hadrequested an overseas assignment, he completed his militaryobligation at Beaumont General Hospital in El Paso, Texas.

After his release from the military in 1946, he returned to theUniversity of Michigan to assist his mentor, Prof. L.H. Newburgh, in

his research. He spent the next two years investigating water andelectrolyte metabolism. As Dr. Newburgh was soon to retire, headvised Alex to accept a position at Massachusetts General. Alexarrived in Boston with a Rockefeller fellowship that allowed him toestablish an independent laboratory. In the 1950s Alex performedseminal studies that established that the higher osmolality of theintracellular environment was maintained not by the active trans-port of water (the prevalent view at the time) but rather due to thepassive redistribution of water secondary to the transport of sodiumand chloride into the extracellular space, thereby regulating cellvolume [9,10,13]). He also completed studies that evaluated neuro-hormonal regulation of water and electrolyte balance [12] and,during a sabbatical leave, completed studies with Hans H. Ussing inCopenhagen and Hans Krebs at Oxford University. Having mastereda new technique, the Ussing chamber [15], to study electrolyte fluxacross the toad urinary bladder, Alex continued to climb theacademicladder, becoming the Jackson Professor of Clinical Medicineand the Chair of the Department of Clinical Medicine at MGH/Harvard in 1966, a position he held until 1981. So far, five studentswho completed their training while Alex was the Chair of ClinicalMedicine have been awarded the Nobel prize, and many more havebecome leading figures in science and medicine both within andoutside of the United States.

Alex indicates in his autobiography, that he became increasinglyfrustrated with what he saw in the clinic. His extensive travels inremote regions of the globe for the World Health Organizationconvinced him that many of the debilitating diseases seen byphysicians in Western society were the result of lifestyle choicesand could be prevented. In his words: ‘‘We physicians waited in ouroffices until a patient came to us with their disease well advanced.There was very little we could do to cure them of these chronicailments. Increasingly we responded with ingenious and expensivetechnology that mostly provided palliative relief, at best’’ [11]. In1981, he resigned as Chief of Clinical Medicine to form and to chairof a new department of preventive medicine and epidemiology, aposition he held until his mandatory retirement at age 70 years in1990. Upon retirement and now freed from administrative burdens,Alex began a new career focusing on the role of diet (and, to a lesserdegree, exercise) in the prevention of disease. As members of ISSFALare well aware, he is widely recognized for this pioneering work onthe cardiovascular effects of omega-3 fatty acids/fish oils in theprevention of cardiovascular disease. I had the great good fortune toparticipate in the studies shortly after Alex’s retirement when hegenerously invited me to evaluate the effects of omega-3 fatty acidsin a canine model of sudden cardiac death [14,1]. We confirmedAlex’s early findings on the salutatory properties on isolatedneonatal rat cardiomyocytes [6] in this conscious animal model.Specifically, we demonstrated that acute intravenous administrationof an emulsion of either fish oil or purified omega-3 fatty acids couldprevent is chemically-induced ventricular fibrillation [3–5]. Workingwith Dr. Jing Kang, Alex built upon these earlier studies, document-ing that these fatty acids reduced myocyte membrane excitabilityvia inhibitory actions on various ion channels (particularly sodiumand L-type calcium channels) [16,7,8,17].

During his illustrious career Alex published in excess of 340 fulllength manuscripts that have been cited nearly 20,000 times. Hewas the recipient of numerous awards and honors including electionas a Fellow to the very prestigious National Academy of Sciences(USA) in 1972 and to the Institute of Medicine, 1978. In 2002, ISSFALestablished the ‘‘Alexander Leaf Distinguished Scientist Award forLife Achievement’’ to honor Alex for his work and his support forthis society. Alex was the first recipient of this award at the 2002congress of the society held in Montreal, Canada. This award is givenat each biannual ISSAFAL congress to recognize and to rewardexcellence in lipid and fatty acid research. This award will continueto serve as memorial to Dr. Leaf for many years to come.

F. Visioli / Prostaglandins, Leukotrienes and Essential Fatty Acids 88 (2013) 251–255 255

Alex is survived by his wife Barbara, whom he married in1943, three daughters (Caroline, Rebecca, and Tamara), and twograndchildren (Alexander and Anna Norregaard). He is alsosurvived by his many students, colleagues, and their students—

his intellectual children and grandchildren. Readers are encour-aged to post their comments and reminiscences.

PS: note that as lightly different version of this memorial hasbeen previously published [2]and is reproduced with permissionof Frontiers Media, SA.

References[1] G.E. Billman, A comprehensive review and analysis of 25

years of data from an in vivo canine model of suddencardiac death: implications for future anti-arrhythmic drugdevelopment, Pharmacol. Ther. 111 (2006) 808–835.

[2] G.E. Billman, Alexander Leaf, MD (1920–2012)—attributeto a life in physiology and medicine, Front. Physiol. 4(2013) 6 (first published online 25.01.13).

[3] G.E. Billman, H. Hallaq, A. Leaf, Prevention of ischemia-induced ventricular fibrillation by omega-3 fatty acid, Proc.Natl. Acad. Sci. USA 91 (1994) 4427–4430.

[4] G.E. Billman, J.X. Kang, A. Leaf, Prevention of ischemia-induced cardiac sudden death by n-3 polyunsaturatedfatty acids in dogs, Lipids 32 (1997) 1161–1168.

[5] G.E. Billman, J.X. Kang, A. Leaf, Prevention of sudden deathby dietary pure n-3 polyunsaturated fatty acids in dogs,Circulation 99 (1999), 2542–2457.

[6] H. Hallaq, A. Sellmayer, T.W. Smith, A. Leaf, Protective effectof eicosapentaenoic acid on ouabain toxicity in neonatal ratcardiac myocytes, Proc. Natl. Acad. Sci. (USA) 87 (1990)7834–7838.

[7] J.X. Kang, Y-.F Xiao, A. Leaf, Free long-chain polyunsatu-rated acids reduce membrane electrical excitability inneonatal rat cardiac myocytes, Proc. Natl. Acad. Sci. (USA)92 (1995) 3997–4001.

[8] J.X. Kang, A. Leaf, Evidence that free polyunsaturated fattyacids modify Naþ channels by directly binding to the channelproteins, Proc. Natl. Acad. Sci. (USA) 93 (1996) 3542–3546.

[9] A. Leaf, On the mechanism of fluid exchange of fluid oftissue in vitro, Biochem. J. 62 (1956) 241–248.

[10] A. Leaf, Maintenance of concentration gradients and regula-tion of cell volume, Ann. NY Acad. Sci. 72 (1959) 396–404.

[11] A. Leaf, Medicine or physiology: my personal mix, Annu.Rev. Physiol. 63 (2001) 1–14.

[12] A. Leaf, F.C. Bartter, R.F. Santos, O. Wrong, Evidence in manthat urinary electrolyte loss induced by pitressin is afunction of water retention, J. Clin. Invest. 33 (1953)1261–1268.

[13] R.H. Maffly, A. Leaf, The potential of water in mammaliantissues, J. Gen. Physiol. 42 (1959) 1257–1275.

[14] P.J. Schwartz, G.E. Billman, H.L. Stone, Autonomic mechan-isms in ventricular fibrillation induced by myocardialischemia during exercise in dogs with healed myocardialinfarctions: an experimental preparation for sudden car-diac death, Circulation 69 (1984) 790–800.

[15] H.H. Ussing, K. Zerhan, Active transport as the source ofcurrent in the short-circuited isolated frog skin, ActaPhysiol. Scand. 23 (1951) 110–127.

[16] Y-.F. Xiao, J.X. Kang, J.P. Morgan, A. Leaf, Blocking effects ofpolyunsaturated fatty acids on Naþ channels of neonatalrat ventricular myocytes, Proc. Natl. Acad. Sci. (USA) 92(1995) 11000–11004.

[17] Y-.F. Xiao, A.M. Gomez, J.P. Morgan, W.J. Lederer, A. Leaf,Suppression of voltage-gated L-type Ca2þ currents bypolyunsaturated fatty acids in adult and neonatal rat

cardiac myocytes, Proc. Natl. Acad. Sci. (USA) 94 (1997)4182–4187.

View from the Secretary’s PerchThe past few months have been busy for the ISSFAL Executive

and Board with elections of new members, the start in earnest of theplanning process for ISSFAL 2014 in Stockholm and the exciting firstISSFAL regional conference coming up in Australia this year.

ISSFAL Board and Executive ElectionsAt the end of March Margaret Craig-Schmidt and Richard

Bazinet are stepping down from the ISSFAL Board; sadly Margaret– having served two terms of office – had to step down and couldnot stand for re-election.

A total of five candidates – all excellent and capable of con-tributing significantly to the Society – contested the two positionsavailable. Following the electronic ballot conducted in February,Richard Bazinet (re-elected) and Barbara Meyer were appointed tothe Board. Congratulations to them both and sincere commisera-tions to the other candidates unsuccessful on this occasion.

At the same time, Seth Baum (Honorary Treasurer) and PeterClough (Honorary Secretary) were appointed unopposed to servesecond terms on the Executive.

Membership feesA plea from the heart – and the wallety individual membership

fees are now overdue and many remain to be paid. We have tried tosimplify the payment process and it is now possible to renew yourmembership on line and to pay via credit card, paypalTM etc. Pleaseif you haven’t paid your 2013 subscription could you do so withoutfurther delay, we would really appreciate it.

Similarly any corporate membership fees that are still unpaid,please could responsible members follow up internally with theiraccounts department to try and expedite payment. On whichsubject, corporate members are essential to our society, we areextremely grateful for their support and we believe they alsoderive considerable benefit from their participation. Buty thenumber of corporate members is declining partly due to economiccircumstances, but primarily to the increasing rationalisation thatis going on throughout the industry. The recent well publicisedacquisitions of Martek and Ocean Nutrition by DSM and Equatecand Pronova by BASF has had the net effect of reducing sixcorporate members to two with a consequent impact on thesociety’s revenues. If you work in industry and your employer isnot a corporate member of ISSFAL please do consider joining, youwould be very welcome and appreciated.

A pack detailing the benefits etc. of corporate membership isavailable on request from me, email mail to: honsecretary@issfal.org.

Forthcoming ISSFAL conferencesYou should have been informed earlier by email of an exciting

regional ISSFAL conference coming up soon in Adelaide Australiaand run in conjunction with the Perinatal Society of Australia andNew Zealand (PSANZ). This meeting will be held on the 17th and18th April, full details and program are available on http://www.psanzcongress.com.au/pages/issfal.php.

Best wishes

Peter Clough

Honorary Secretary