Milk Consumption, Calcium Intake, and Decreased Hypertension in Puerto Rico. Puerto Rico Heart Health Program Study

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1 Milk Consumpion, Calcium Inake, and Decreased Hyperension in Puero Rico Puero Rico Hear Healh Program Sudy MARIO R. GARCIA-PALMIERI, M.D., RAUL COSTAS, JR., M.D., MERCEDES CRUZ-VIDAL, M.D., PAUL D. SORLIE, M.S., JEANNE TILLOTSON, M.A., AND RICHARD J. HAVLIK, M.D. SUMMARY The baseline observaions in he Puero Rico Hear Healh Program during involved blood pressure deerminaions, oher measuremens, and a 24-hour dieary recall in 7932 men aged years. This exensive daa base provided an opporuniy o es he hypohesis ha low calcium inake is relaed o increased blood pressure level. Among men wihou baseline coronary hear disease and no aking anihyperensive medicaion, here was an inverse relaionship beween milk consumpion and definie hyperension in urban Puero Rican men and older rural men. When daa from all age and area groups had been averaged, a wofold increase in hyperension was found in subgroups who drank no milk compared o hose who consumed over 1 quar of milk a day. Similar rends were found when an esimae of oal calcium inake from food, principally from milk, was used. Wih mulivariae analysis while known correlaes of blood pressure were simulaneously considered, an independen effec persised beween milk consumpion and blood pressure. These resuls appeared o confirm an inverse associaion beween calcium and hyperension. I was sill no possible o ascribe a causal relaionship beween calcium and blood pressure, however, due o he inricae nework of covarying food inakes, he facors relaed o absorpion or lack of absorpion of calcium, and he possible role ha unmeasured social and culural facors may play in he observed relaions. (Hyperension 6: , 1984) KEY WORDS epidemiology nuriion blood pressure RECENT repors have suggesed ha hyperensive individuals consume less calcium in heir dies, especially in he form of cheese, and have lower ionized serum calcium levels when compared o conrol subjecs. 1-2 Consisen wih such findings is he observaion ha cerain counries wih dies radiionally high in calcium have a low incidence of hyperension wih pregnancy. 3 In addiion, among a From he Deparmen of Medicine, Universiy of Puero Rico Medical School, San Juan, Puero Rico (Garcia-Palmieri, Cosas, and Cruz-Vidal); and he Division of Hear and Vascular Diseases, Naional Hear, Lung, and Blood Insiue, Behesda, Maryland (Sorlie, Tilloson, and Havlik). Suppored in par by Conracs PH and NO 1 HV from he Naional Hear, Lung, and Blood Insiue, Naional Insiues of Healh, U.S. Public Healh Service, o he Universiy of Puero Rico. Address for reprins: Dr. Mario R. Garcia-Palmieri, Direcor, Programa de Salud del Corazon, c/o Deparmen of Medicine, Universiy of Puero Rico, School of Medicine, G.P.O. Box 5067, San Juan, Puero Rico Received February 16, 1983; revision acceped Sepember cohor of 8000 Japanese-American men in Hawaii, milk inake was inversely associaed wih high sysolic and diasolic blood pressure. 4 Analysis of dieary calcium inake and blood pressure in he firs Naional Healh and Nuriion Examinaion Survey 5 revealed a significan inverse correlaion, bu his correlaion was of a low order of magniude. A separae invesigaion 6 of he same daa se found no relaionship beween blood pressure and inake of dairy food, and a posiive relaionship beween oal serum calcium and high blood pressure. Anoher inconsisen repor in Belgium Army personnel involved a posiive relaionship beween 24-hour urinary calcium, oal serum calcium, and blood pressure. 7 In a clinically ill paien, a relaionship has been repored 8 beween hypercalcemia and hyperension, wih reversibiliy of hyperension on lowering of calcium. Because of he availabiliy of exensive dieary and cardiovascular informaion on a large populaion of urban and rural Puero Rican men, i was possible o es he repored hypohesis ha dairy producs or dieary calcium poenially may have a relaionship o hyperension.

2 MILK CONSUMPTION AND BLOOD PRESSURE/Garcia-Palmieri e al. 323 Mehods Populaion and Baseline Characerisics The Puero Rico Hear Healh Program 9 examined men from four rural and hree urban areas during he years Rural areas were defined as enumeraion disrics conaining fewer han 25 dwelling unis in a cluser, and urban areas as enumeraion disrics wih 25 or more dwelling unis in a cluser. A house-o-house census of hese enumeraion disrics was made by he personnel who regularly conduced he decennial census. All men beween 45 and 64 years of age were invied o paricipae in he sudy, and heir ages were verified a he ime of he iniial visi. The response rae was 79.9% in he urban and 82.4% in he rural areas, so ha he proporion of urban/rural populaion in he sudy was approximaely he same as in he general populaion. No oher mehod of selecion was used. Thus, he sudy populaion consised of men aged 45 o 64 years a baseline who were iniially free of coronary hear disease and no aking any anihyperensive medicaion. The firs blood pressure measuremens were made by a physician wih he paien seaed; diasolic pressure was designaed by he Phase V Korokoff sound. Normal blood pressure was defined as a sysolic level lower han 140 mm Hg and a diasolic level lower han 90 mm Hg. Hyperension was defined as a sysolic blood pressure over 160 mm Hg and a diasolic pressure over 95 mm Hg. All oher combinaions of values were considered borderline. Afer requiring subjecs o successfully complee a 24-hour die recall, he sudy had a final populaion of 7932 men, 30% of whom were from he rural area. Relaive weigh was deermined as a raio of he observed weigh a baseline o a sandard weigh for heigh from he Meropolian Life Insurance ables. 10 Educaion level was deermined by highes grade compleed in school and analyzed by grouping ino six caegories. Sandard mehodology for he 24-hour recall was uilized. Mos inerviews were done during one of he regular 5 work days, so ha mos die informaion referred o Sundays hrough Thursdays. However, some inerviews were performed on Saurdays, so here was informaion on Friday dies as well. No inerviews were done on Sundays. In all cases, he day of he week for which he daa were aken was idenified as Monday-hrough-Thursday, Friday, Sunday, or holiday." 12 I was necessary o devise a relaively simple sysem for dieary daa collecion and compuaion ha could be adminisered equally o rural and urban men of varying degrees of sophisicaion and ha also could be processed easily using local resources. For his reason, mos "basic" foods (milk, cheese, eggs, mea, and so forh) repored eaen during he 24-hour recall inerview were allied for enry ino he compuer in erms of sandard porions; nurien inake from hese iems was deermined by compuaion using a nurien daa base appropriae o he area. Mixed dishes (involving recipe calculaion) and less frequenly eaen basic foods were hand-calculaed by he dieiian-inerviewers, and nuriens consumed from hese sources were enered ino he sysem in order o obain each subjec's oal 24-hour nurien inake. Subjecs on special dies were no excluded from analysis. Because of he curren ineres in calcium-conaining foods, he original food composiion able was supplemened for his invesigaion by he addiion of dieary calcium values based on sandard American and Lain American reference sources This allowed an esimae of daily calcium inake o be made for each sudy paricipan. While i was possible o add calcium figures for he basic commonly eaen foods o he original nurien daa base rerospecively, i was no possible o esimae dieary calcium inake from he recipe iems eaen. Alhough approximaely 40% of he die recalls included foods from recipe sources, he amoun of exra food from he sources was small. On he average, only 10% of he oal kilocalories consumed were from recipe foods. Thus, for his repor, calcium inake from hese foods was omied. Saisical Mehods Sraificaion by age and area of residence was mainained during analysis. Relaionships beween blood pressure and baseline characerisics were esimaed by produc momen correlaion coefficiens and muliple linear regression analysis. The saisical analysis sysem (SAS) was used o calculae hese saisics. Resuls The average daily inake of milk for boh urban and rural subjecs was abou 16 oz per day (Table 1). Milk was mos frequenly aken wih coffee (a usual proporion would be 1 oz of Puero Rican coffee o 2 oz of evaporaed milk, equivalen o 4 oz of whole milk). Relaively small inakes of oher dairy producs such as TABLE I. Prevalence Raes ojhyperension by Quaniy o]milk Consumed by Puero Rican Men Milk consumpion: 24-hour recall 28 or 32 oz >32oz Populaion number Average consumpion (oz/day) Rae Rae Rae Rae Daa from Examinaion 1, Puero Rico Hear Healh Program, of men free of coronary hear disease and no aking anihyperensive medicaion. Milk consumpion was recorded in 4 oz unis/day.

3 324 HYPERTENSION VOL 6, No 3, MAY-JUNE 1984 TABLE 2. Correlaion Coefficiens beween Milk Consumpion and Oher Specified Characerisics for a Populaion Free ofchd, No on Anihyperensive Medicaions, and wih Known Values of All Measuremens a Examinaion 1; The Puero Rico Hear Healh Program Characerisics Sysolic BP (mm Hg) Diasolic BP (mm Hg) Proein (g) Fas (g) Carbohydraes (g) Coffee (g) Alcohol (g) Educaion (levels) Blood glucose (mg/dl) Relaive weigh Hear rae (bpm) Cigarees smoked (no./day) Age () Populaion number Minimum correlaion saisically significan a p < ± ± ± ±0.05 Daa from Examinaion 1, Puero Rico Hear Healh Program, of men free of coronary hear disease and no aking anihyperensive medicaion. Milk consumpion was recorded in 4 oz unis/day. cheese and ice cream were repored, wih he lowes inakes repored by rural men. The average calcium inake from whole or evaporaed milk was 587 mg for rural and 573 mg for urban men, wih he nex larges nondairy calcium source being legumes. Individuals who consumed more milk had a lower prevalence of hyperension han hose who consumed less milk. This relaionship was observed in all area and age groups excep in he younger rural group (Table 1). The relaionship was sronges in urban men aged 45 o 54 years, where 20% of hose who consumed no milk were hyperensive and only 4% of hose who consumed more han four glasses a day were hyperensive. The relaionship beween milk consumpion and sysolic blood pressure can be expressed as a correlaion coefficien (Table 2). The magniude of his correlaion ranged from 0.05 o 0.12, depending on age and geographic area. Correlaions wih diasolic blood pressure were similar. Milk consumpion was highly correlaed wih oal proein, fas, and carbohydraes, largely because milk conribued o he overall levels of hese nuriens. Milk consumpion was also posiively correlaed wih coffee drinking since coffee was usually drunk wih milk, and inversely correlaed wih alcohol use. There was a small posiive associaion of milk use wih higher educaion and he greaer number of cigarees smoked. Correlaions beween sysolic blood pressure and hese variables were generally weak excep for he known associaions of blood glucose, relaive weigh, and hear rae. To correc simulaneously for inerrelaionships among milk, oher variables, and blood pressure, mulivariae regression analysis was used (Table 3). A significan inverse relaionship beween milk consumpion and sysolic blood pressure persised in hree of he four subgroups. By using he unsandardized regression coefficiens, i was possible, for example, o esimae ha an incremen of 16 oz of milk would heoreically be equivalen o a 2 mm Hg decrease in sysolic blood pressure. The resuls of he muliple linear regression model in Table 3 show he inabiliy of measured characerisics TABLE 3. Mulivariae Regression Coefficiens of Sysolic Blood Pressure (mm Hg) on Specific Variables Variable Milk consumpion (4 oz unis/day) * Proein (g) Fas (g) Carbohydraes (g) Coffee (g) Alcohol (g) Educaion (levels) Blood glucose (mg/dl) Relaive weigh Hear rae (bpm) O.387 Cigarees smoked (no./day) Age () (R 2 ) (0.157) (0.136) *p < p < * * * I O.35O (0.129) (0.115)

4 MILK CONSUMPTION AND BLOOD PRESSUREJGarcia-Palmieri e al. 325 TABLE 4. Comparison of Sandardized Muliple Regression Coefficiens of Milk in Models Conaining Sysolic and Diasolic Blood Pressure Measuremens Ace group () Regression model* SBP DBP SBP DBP Sd coeff of milk Sd coeff of milk SBP model: sysolic blood pressure (dependen variable); milk, proein, fas, carbohydraes, coffee, alcohol, educaion, blood glucose, relaive weigh, hear raes, cigarees smoked, age (independen variables). DBP model: diasolic blood pressure (dependen variable); same independen variables as above. ^Coefficien of milk sandardized by dividing by sandard deviaion of SBP or DBP. o adequaely describe he variaion in blood pressure. The percenage of variaion of blood pressure described by his model (R-squared) was beween 11.5% and 15.7% depending on age and geographic area. The variable, milk consumpion, alhough saisically significan, conribued only slighly o he explanaion since removal of he milk variable reduced he R- squared by a difference of 0.5% a mos. In muliple regression, here is a possibiliy ha highly correlaed variables may confuse he inerpreaion of individual coefficiens. In his analysis, he variables of proein, fas, and carbohydraes were highly correlaed wih each oher, bu when hey were dropped from he model, here was lile change in he coefficien for milk. The variables of proein, fas, and carbohydraes had a low correlaion wih blood pressure. The resuls of he regression analysis were nearly he same when diasolic blood pressure was used in he model. The resuls are compared in Table 4 where he regression coefficien for milk has been sandardized so ha is magniude is roughly comparable in he models wih sysolic and diasolic blood pressure. The magniude of he effec of milk on diasolic blood pressure was slighly less han on sysolic blood pressure, and in he older age group i did no reach saisical significance. The possible effec of coffee use as a confounder was more carefully invesigaed. The relaionship beween coffee and milk consumpion, as measured by a correlaion coefficien of abou 0.2, could have been an imporan confounding facor since coffee has an inverse relaionship wih blood pressure (Table 3). There was, however, a considerable range of milk use a each level of coffee consumpion. The prevalence raes of hyperension by increasing milk use were sraified by coffee consumpion (Table 5). When we conrolled for coffee consumpion by sraifying according o ounces of coffee consumed, we found a decreasing prevalence of hyperension wih increasing milk use. Thus, he resuls are consisen wih hose from he mulivariae analysis. A similar analysis sraifying by alcohol consumpion showed an inverse associaion beween sysolic blood pressure and milk in boh drinkers and eeoalers (Table 5). To invesigae a possible confounding or ineracive effec of weigh, prevalence raes of hyperension by milk levels were calculaed in he leaner group (relaive weigh less han 110) and in he heavier group (greaer han 110). A relaive weigh index of 100 means a weigh equivalen o he ideal weigh san- TABLE 5. Age-Adjused Prevalence of Hyperension by Milk Consumpion and Alcohol Use, Coffee Use, and Relaive Weigh Milk consumpion 28 or more oz No Alcohol use Yes oz Coffee use oz Relaive weigh < SI Toal No. wih known values Urban i nen 28 or more oz Toal No. wih known values

5 326 HYPERTENSION VOL 6, No 3, MAY-JUNE 1984 dards published by he Meropolian Life Insurance Company 10 in An inverse rend was seen in he urban area for boh relaive weigh groups, which was also suggesed in he leaner rural group (Table 5). While milk conribues several unique facors o he die, such as lacose, rypophan, and riboflavin, i is also he main conribuor of calcium. Milk provides slighly more han 60% of all calcium inake, wih peas and beans conribuing he nex larges percenage (around 10%). However, when he amoun of calcium of he specified food groups was correlaed wih sysolic blood pressure, calcium from milk showed he larges correlaion. An alernaive mehod of displaying he resuls is o presen mean values of calcium inake by classes of hyperensive, borderline, and normal. Figure 1 shows ha he mean inakes of calcium from nondairy sources were nearly idenical for all of he blood pressure groups for each age and area. There was also lile difference in he mean values of calcium from dairy sources oher han milk, such as cheese and ice cream. The mean value of calcium from milk was less in he hyperensive individuals. A furher possible confounder in his analysis is ha he urban populaion was approximaely 15% black. The ehnic classificaion of black or whie in his sudy was based on skin color deerminaion, and hus he groups were subsequenly described as dark- or lighskinned. In Puero Rico, he dark-skinned populaion has slighly higher blood pressure and generally a greaer degree of lacose inolerance. When our analysis of he urban area was sraified by skin color, he correlaion beween blood pressure and milk consumpion was sronger in dark-skinned han ligh-skinned individuals (Table 6). Also, he muliple regression TABLE 6. Prevalence of Hyperension by Milk Consumpion; Correlaion and Regression of Milk Consumpion and Blood Pressure in Those wih Ligh and Dark Skin, Urban Area Only Milk consumpion 28 or 32 oz >32oz Toal No. Correlaion of milk wih SBP DBP Sandardized coefficien of milk in* SBP model b DBP model b Ligh skinned Hyperension Correlaion coefficiens Muliple regression Dark skinned prevalence Sandardized by dividing by he sandard deviaion of SBP or DBP. 1, CALCIUM FROM: I NON DAIRY I DAIRY-NOT MILK c I H DAIRY-MILK 200 AGE IN YEARS FIGURE 1. Mean value of calcium inake and wo sandard errors by hyperension saus (hyperension, borderline and normal). Daa from he Puero Rico Hear Healh Program populaion free of coronary hear disease and no on anihyperensive medicaion.

6 MILK CONSUMPTION AND BLOOD PRESSVRE/Garcia-Palmieri e al. 327 coefficiens for milk were larger in dark-skinned han ligh-skinned Puero Ricans. An inconsisen finding in Table 6 is ha he muliple regression coefficien in urban ligh-skinned men aged 55 o 64 years was no saisically significan, alhough for hose aged 45 o 54 years i was srongly significan. Discussion The average daily inake of milk of 16 oz per day repored in our sudy is comparable o ha repored by Fernandez and coworkers" from an island wide nuriion survey carried ou in 1966 on a represenaive sample of he enire Puero Rico populaion. In ha survey rural aduls repored consuming an average of 1.8 cups of milk per day and urban inakes averaged 2.2 cups per day, usually wih coffee. Alhough Puero Rico has a coronary hear disease rae approximaely half ha of he U.S. mainland, hyperension is prevalen and is he mos imporan predicor of subsequen cardiovascular disease. 16 Thus, he idenificaion of poenial addiional blood pressure correlaes has public healh implicaions for his populaion. The Puero Rico Hear Healh Program has colleced an exensive daa se on a large group of middle-aged Puero Rican men. Because of he availabiliy of hese 24-hour die recall daa colleced in a sandardized manner, i was possible o explore, by oher mehodology, he conclusion in a caseconrol sudy repor 1 of an inverse relaionship beween dieary calcium and hyperension. The iniial analysis of he daa, using correlaion coefficiens, suggesed a modes inverse associaion of milk consumpion and blood pressure. From his invesigaion we canno be cerain if his weak associaion indicaes a rue relaionship or merely a poorly measured one. The laer siuaion is possible since i is unlikely ha a single 24-hour die recall is adequae o characerize an individual's usual inake of dairy producs or calcium. Unforunaely, muliple 24-hour recall daa on he same individual, which would give a beer esimae of usual inake, are no available in his populaion. Furher analyses indicaed ha hose drinking no milk had wice he prevalence of hyperension as hose who drank a quar or more per day. An inensive search for confounding variables among nuriional and nonnuriional facors was aemped, bu wih mulivariae analysis he relaionship persised in hree of four age/area subgroups. Possible confounding wih coffee and alcohol was explored. The same inverse relaionship persised in separae groups of beverage drinkers and nondrinkers. Since he average cheese consumpion in his sudy was small, a saisfacory comparison wih one of he previously repored sudies was no possible. 1 However, here was no a major rend oward a lower frequency of hyperension wih increasing calcium from nonmilk dairy sources (Figure 1). Mos of he difference appeared o be from calcium in milk. I was no surprising ha when he various sources of calcium were combined and paricipans were classified by hyperensive saus, a similar inverse rend was found in hree of he four groups. Generally, he borderline hyperensive subjecs had an inermediary calcium inake. No saisfacory explanaion exiss for he inconsisen findings in he young rural group. An imporan issue ha could be addressed somewha in his paricular populaion was he possibiliy ha a subgroup wih significanly higher blood pressure and a poenial lacase deficiency by virue of darker skin color migh, because of he unpleasan side effecs of milk ingesion, avoid dairy producs. Skin color had previously been assessed in urban men in his populaion. 17 Alhough he milk/blood pressure relaionship was slighly less consisen in he ligh- han in he dark-skinned individuals, his explanaion does no accoun for he blood pressure/milk relaionship. I is no possible in Puero Rico o idenify subgroups exacly comparable o he designaion on he mainland of black or whie. 17 Since he mechanism for an associaion beween milk consumpion per se or dieary calcium from milk and blood pressure is uncerain, he relaionship mus be invesigaed furher in diverse populaions as well as in laboraory siuaions. I will be necessary o deermine wheher a covariable of milk ha affecs blood pressure could be operaing. There could be culural or social facors associaed wih milk drinking ha have an unmeasured impac on blood pressure. Oher foods consumed wih milk producs could be affecing absorpion of calcium. 18 I is also possible ha a high milk-conaining die migh decrease absorpion of race meals, such as cadmium and lead, which have been implicaed in he pahogenesis of hyperension. 19 Some oher subsances in milk, such as rypophan, 20 lacose, riboflavin, or forificaion wih Viamin D, could also be imporan facors. Alhough he chain of causaion has been posulaed o involve decreased dieary calcium inake leading o lower ionized serum calcium which in urn resuls in higher blood pressure, 2 he inconsisen findings from Keseloo and Geboers 7 ha increased oal serum calcium and urinary calcium are relaed posiively o blood pressure needs resoluion. The known hypoensive effecs of calcium-channel blocking drugs mus be considered as well. Even if a causal relaionship is acceped, he public healh implicaions of he findings mus be carefully considered. Since his is a very large populaion, saisical significance does no direcly ranslae ino a pracical program for individuals. For example, from he mulivariae regression coefficiens in Table 3, which relae milk inake o sysolic blood pressure, one would predic ha drinking wo glasses of milk (16 oz) per day would be associaed wih a decrease in sysolic blood pressure of only abou 2 mm Hg, as compared o a nondrinker. Of course, even his modes relaionship is only heoreical and would require a clinical invesigaion o confirm. In he Puero Rico populaion, he esimaed mean inake of calcium is already approxi-

7 328 HYPERTENSION VOL 6, No 3, MAY-JUNE 1984 maely 900 mg per day. This is a value well wihin he range of he recommended daily dieary allowances for calcium for adul men esablished by he Food and Nuriion Board of he Naional Academy of Sciences Naional Research Council. 21 In addiion, while milk consumpion is associaed wih blood pressure in a beneficial way, milk also conribues a large amoun of sauraed fay acids o he die. In his sudy, he correlaion beween milk consumpion and oal sauraed fay acids in he die was abou Dieary sudies generally show low bu posiive correlaions beween sauraed fay acid inake and serum choleserol. In he Puero Rico sudy, his ranslaes ino a small bu consisenly posiive correlaion beween milk consumpion and serum choleserol ha is beween and 0.05 depending upon age group and geographic area. The possible implicaions for he developmen of coronary hear disease mus be considered. Of course, skim milk or calcium supplemenaion migh be an alernaive for increasing calcium inake while mainaining a low sauraed fa inake. Before major dieary changes can be recommended, furher sudies are necessary o clarify he eiological naure of he relaionship as well as o define he risks and benefis of any recommended changes. Acknowledgmen The auhors appreciae he encouragemen of Dr. William Zukel in pursuing he presen analysis. References 1. McCarron DA, Morris CD, Cole C. Dieary calcium in human hyperension. Science 1982;217: McCarron DA. Low serum concenraions of ionized calcium in paiens wih hyperension. N Engl J Med 1982;307: Bclizan JM, Vallar J. The relaionship beween calcium inake and edema-, proeinuria-, and hyperension-gesosis: an hypohesis. Am J Clin Nur 198O;33:22O2-221O 4. Reed D, McGee D, Yano K. Biological and social correlaes of blood pressure among Japanese men in Hawaii. Hyperension 1982;4: Sanon JL, Braiman LE, Riley AM, Khoo CS, Smih JL. Demographic, dieary, life syle, and anhropomenc correlaes of blood pressure. Hyperension 1982;4(SupplII):II Harlan WR, Hull AL, Schmonder RP, Thompson FE, Larkin FA, Landis JR. Dieary inake and cardiovascular risk facors. Par I: Blood pressure correlaes. NCHS Series DHDS, U.S. Public Healh Service. Publ No PHS. Washingon DC: U.S. Governmen Prining Office, February, Keseloo H, Geboers J. Calcium and blood pressure. Lance 1982; 1: Blum M, Kirsen M, Worhy MH Jr. Reversible hyperension caused by he hypercalcemia of hyperparahyroidism, viamin D oxiciy, and calcium infusion. JAMA 1977;237: Garcia-Palmieri MR, Cosas R Jr, Cruz-Vidal M, e al. Risk facors and prevalence of coronary hear disease in Puero Rico. Circulaion 1970;42: Meropolian Life Insurance Company. New weigh sandards for men and women. Sa Bull Meropolian Life Insurance Company 1959;40:l 11. Rodriguez M, Cosas R Jr, Cordero E, Tilloson J, Garcia- Palmieri MR. Dieary inerviews in an epidemiological sudy of coronary arery disease in Puero Rico. Bol Asoc Med P Rico 1969; Garcia-Palmieri MR, Tilloson J, Cordero E e al. Nurien inake and serum lipids in urban and rural Puero Rican men. Am J Clin Nur 1977;30: Wan BK, Merrill AL. Composiion of foods. Agriculure Handbook No 8. U.S. Deparmen of Agriculure Caalog Number Al. 76:8/963. Washingon DC: U.S. Governmen Prining Office, Leung WW, Flores M. Food composiion able for use in Lain America. Behesda Maryland: The Inerdeparmenal Commiee on Nuriion for Naional Defense, Fernandez NA, Burgos JC, Asenjo C, Rosa I. Nuriional saus of Puero Rican populaion maser sample survey. Am J Clin Nur I971;24: Cosas R Jr, Garcia-Palmieri MR, Cruz-Vidal M, Sorlie P. Expeced risk of coronary hear disease in Puero Rican men. Bol Asoc Med P Rico: 1980;72:98-l Cosas R Jr, Garcia-Palmieri MR, Sorlie P, Herzmark MA. Coronary hear disease risk facors in men wih ligh and dark skin in Puero Rico. AJPH 1981;71: Leich I. Calcium and phosphorus. In: Beaon GH, McHenry EW, eds. Nuriion a comprehensive reaise. Volume 1. Macronunens and nurien elemens. New York: Academic Press, 1964: Friberg L, Piscaor M, Nordberg GF, Kjellsrom T. Cadmium in he environmen. 2nd ed. Cleveland: CRC Press. 1974: Barney CC, Threae RM, Kika DC, Fregly MJ. Effecs of seroonin and L-5-hydroxyrypophan on plasma renin aciviy in ras. Pharm Biochem Behavior 1981;414: Food and Nuriion Board. Recommended dieary allowances. 9h revised ed. Washingon, D.C.: Naional Academy of Sciences, Naional Research Council, 1980