Biomed Res Trace Elements 16(3) : 203-207, 2005 203

Review Articles

Recent progress in exploring the essentiality of the ultratrace element rubidium to the nutrition of animals and man

Manfred Anke, Ljubomir Angelow, Ralf Mtiller*), Sabine Anke

Institute of Nutrition and Environment, Faculty of Biology and Pharmacy, Friedrich Schiller University Jena, D-07743 Jena, Germany ; *) Society of Ecology and Environmental Chemistry Ltd., Zittauer Str. 27, 99091 Erfurt, Germany

Abstract Rubidium-poor nutrition with 280 pg Rb/kg diet DM reduced feed intake, pre- and postnatal growth rate and conception rate of goats significantly. The most important finding was the extremely high abortion rate (> 80%) of rubidium-deficient goats. Goats with abortion had a progesterone level of only 7% of the normal amount. The plasma estradiol level in aborting goats ranged from 37 to 280 nmol/1. The normative requirement of goats, and animals in general, might reach < 400 pglkg feed dry matter (DM). Rubidium (Rb) deficiency is not to be expected in humans. None of the 70 female and 70 male subjects investigated ingested less than 400 pg Rb/day. Thus, the rubidium requirement of humans - if it should exist - might be rated as < 400 pg/day.

Ke ywords rubidium, essentiality for animals, geological influences, intake by man, foodstuffs

Introduction goats was 14% Iower than that of controls. On the 9lst Glendening et al. Ll] were the first to examine the day of life, the weight of kids from both groups essentiality of rubidium in rats fed purified diets with differed significantly by 22%. After weaning (10lst - variable supplements of rubidium, , and potas- 268th day of life), only the intrauterinely rubidium- sium, but obtained no evidence that rubidium is an depleted kids grew at a significantly slower rate. essential element L2]. Afterwards, the essentiality of Bought-in kids given rubidium-poor feed developed rubidium in animals was tested in experiments normally ; with their mothers' milk, they had received repeated six times with intrauterinely rubidium- and stored sufficient rubidium for normal growth. depleted goats and their kids. The semisynthetic feed However, after depletion of the storage during first of control goats contained 10 mg Rb/kg DM as pregnancy, these kids showed symptoms of rubidium compared to < 280 pg Rb/kg DM in the rubidium- def iciency. deficient feed [3, 4] (Table 1). Further information to The rubidium-poor nutrition influenced the number materials and methods are given by Anke et al. [5]. of goats without heat and the number of unsuccessful first inseminations only insignificantly, though notice- Essentiality of rubidium for animals ably (Table 1). The conception rate of rubidium- The rubidium-poor nutrition of the she-goats de- deficient goats was significantly lower that that of creased the feed intake significantly, i.e. by 16% controls, but the most important point noted was the yearly. extremely high abortion and miscarriage rates in the The birth weight of kids from rubidium-deficient rubidium-deficient animals. Here, the fetuses were regularly aborted during the 3rd to 5th months. Kids Address correspondence to : born after day 125 of pregnancy were occasionally Manfred Anke, Am Steiger 12, viable if bottle-fed with mother's milk. One-third of D-07743 Jena, Germany the viable kids died within the first 91 days of life, E-mail : [email protected] with a highly significant difference from the number TEL : + +49 3641 448536 of control kids that died (Table 1). FAX : + +3641 448536 Analyses of 35 blood and blood plasma components 204 Biomed Res Trace Elements 16(3) : 203-207, 2005

Table 1 Influence of rubidium-poor nutrition on feed intake, growth, reproduction performance, milk production, mortality and serum content of progesterone and estradiol

%1) Control goats = 100 % rubidrum deficrent goats x % p2) Srgnifrcance level Student test

Table 2 Progesterone and estradiol contents in the blood plasma of control and rubidium-deficient goats (nmol/L)

xl) = Arithmetic mean; s2) = Standard deviation; n3) = Number Fp4) Slgnifrcance level m

one- or multifactorial variance analysis showed significant changes only in creatinine, phos- reduced rubidium content in all tissues when compar- phorus, and progesterone . Goats that ed with rats receiving 8120 pg Rblkg DM L7] . Hence, underwent abortion or miscarriage had a significantly rubidium was designated as an essential element L8]. lower plasma progesterone status. Rubidium is likely The amount of rubidium in the food chain is much to play a role in the preservation of pregnancy, and higher than that of other well-known essential trace both control and rubidium-deficient goats that were elements, except for , manganese, and . pregnant in the 3rd and 4th months had normal Rubidium deficiency experiments in six generations of plasma progesterone and estradiol levels (Table 2). animals showed that a rubidium offer of less than 280 Rubidium-deficient goats that had either aborted or pg/kg semisynthetic diet resulted in decreased feed miscarried had a plasma progesterone level that was intake, Iower weight gain and an increased rate of only 7% of the normal value. The plasma estradiol abortion, while premature births were increased by up level in goats that aborted ranged from 37 to 280 nmol to 80%･ A rubidium offer which meets requirements L. The pregnancy-preserving properties of progester- appears important for the normal development of one are dependent upon a normal rubidium status, and fetuses. A rubidium offer below 280 pglkg food DM in this respect rubidium is available within the food was apparently insufficient to normalize the body chain in sufficient amounts to prevent deficiency [4, deposits. In practice, the rubidium offer to animals 6] . and humans is much higher, and consequently Rats recervmg 540 pg Rb/kg DM diet showed a rubidium-deficiency symptoms are of no major con- Recent progress in exploring the essentiality of the ultratrace element rubidium to the nutrition of animals and man 205

cern. Experiments with 1000 pg Rb/kg feed DM lce Age, and the sediments of the Triassic (Bunter, resulted in normal growth and reproductive perfor- Muschelkalk, Keuper), whose rubidium contents mance. Hence, it follows that the rubidium require- disappeared with the water as well. The absolutely ment of goats might reach < 400 pglkg feed DM L9, 10, 10west relative index (21), and thus the lowest ll, 12]. rubidium content of the flora, was found on Keuper weathering soils. In plants, the rubidium content Influence of the geological origin of the soil on the varies more remarkably with the geological origin of rubidium content of the vegetation the soil than do other element contents [10, 11, 13]. Despite its abundant occurrence in the Earth's crust (310 mg/kg), rubidium is an ultratrace element that Rubidium intake by humans in Germany has almost been forgotten by science and industry. In Germany, the rubidium intake by adults with The four indicator plants (rye, wheat, field red clover, mixed diets was investigated in 10 populations using meadow red clover) accumulated the highest amount the duplicate portion technique (Table 4). It was of rubidium on gneiss weathering soils, which there- shown that after the reunification of Germany, both fore was given the relative index 100 (Table 3). Gneiss sexes took in 25% more rubidium than before, and weathering soils produce the rubidium-richest flora in that this finding was in very good agreement with the Central Europe. The plant populations on granite significantly higher rubidium content in foodstuffs. weathering soils also proved to be rubidium-rich. Furthermore, it was registered that women consumed Compared to gneiss weathering soils, the alluvial a 15% more rubidium-rich (as DM) diet than men [11J , riverside soils of brooks, rivers and streams still most likely because women apparently prefer produce a relatively rubidium-rich flora with a rela- rubidium-richer foodstuffs (cocoa products, fruits, tive index of 58. The clay minerals of these formations vegetables, coffee). bind the rubidium of the water during flooding. Slate Despite the availability of apparently similar food- weathering soils (relative index 48) still deliver more stuffs at all supermarkets, the location affected bioavailable rubidium than the formations of the rubidium intake because of the different rubidium Quaternary (10ess, boulder clay, diluvial sands), from contents of drinking water. Notably, people who which rubidium was washed out by water during the drank rubidium-rich drinking water from rubidium-

Table 3 Influence of the geological origin of the site on the rubidium content of the flora in Central Europe (n=873)

Geological origin of the site Relative index Gneiss weathering soils l OO Granite weathering soils 78 Rotliegende weathering soils 65 Phyllite weathering soils 60 Alluvial riverside soils 58 Slate weathering soils (Devonian, Silurian, Culm) 48 Bog, peat soils 37 Loess 33 Boulder clay 32 Bunter weathering soils 30 Muschelkalk weathering soils 27 Diluvial sands 26 Keuper weathering soils 21

Table 4 Rubidium intake by adult Germans with mixed and ovolacto-vegetarian diets depending on time and gender (pg/day), average of a week (n=980) 206 Bromed Res Trace Elements 16(3) : 203-207, 2005

rich gneiss regions took in significantly more chain (59 mglkg DM). Vegetables (5 mg/kg DM in rubidium than those in other areas. In Belgium, people potatoes to 68 mglkg in asparagus) and fruits (5 mgl with mixed diets took in 2.2 ~ 0.3 mg Rb/day [16], kg DM in apples to 29 mglkg in oranges and kiwis) which is similar to the Rb intake by German omnivor- contain much more rubidium than do cereal products es [15]. (Table 5). On average, the rubidium intake by both sexes This is particularly true for lettuce, carrots, kohl- decreased by about 15% from age 20 to age 60 years, rabi, kiwi and asparagus, which accumulate rubidium but body weight had no effect on rubidium intake. It contents up to 68 mglkg DM. Apart from black tea, was also surprising that both sexes took in significant- asparagus belongs to the foodstuffs which are richest ly more rubidium in winter than in summer, but this in rubidium, but this high rubidium content is also due may have been due to a higher consumption of choco- to the short life of asparagus. late and coffee in winter than in summer [11, 14, 15J. The rubidium delivered to the food chain by animal foodstuffs is relatively little compared to vegetables Rubidium contents of foodstuffs and beverages and fruits, but relatively much compared to cereal All cereal products and sugar proved to be products. The rubidium content in meat, offal, sau- rubidium-poor (Table 5). Bread contains small sage, and eggs varies between 1.5 and 23 mg/kg DM. amounts of rubidium from additives, and this is also Due to their relatively high fat content, certain types true for pasta and cakes which, on the other hand, of sausage contain less rubidium (1.5-4.0 mglkg DM) obtain much of their rubidium from eggs and milk. than beef, mutton, pork and poultry meat, which Coarse-grained whole-rye bread and crisp bread, as deliver between 7 to 23 mg Rb/kg DM into the food well as rolled oats, are richer in rubidium than pulses. chain. The reason for this phenomenon is that rye and oats prefer acid soils. The effect of additives becomes Discussion particularly evident when the rubidium proportions in Rubidium deficiency is not to be expected in ani- vanilla and chocolate pudding are compared. Cocoa mals and humans. The normative requirement of delivers considerable rubidium amounts into the food rubidium for animals might reach < 400 pglkg diet

Table 5 The rubidium contents of foods (mglkg dry matter) and beverages (/lg/1) (n 1666)

13 ,~ 20 l

~.~ 16 - 18 -1 12 11 18 - ~~' 20 - 13 l 14 16 o ::1 12 ~ 14 = {: 8~ 12 i ~10 1 E6 J:o :52 .El EI 8 a: ot 1- _H__E _ ____ll 2 6d ~ __ I =j _ 1 1: :a5 ¥q~,59~<59~)/~q5~~ ~g) q~ g;~ gg)/~(~~(~~s¥c~~F59~ gg) (59~~~~n;~;~~ 4 a: ¥ ¥¥ ¥ ¥q/q;q;q/c~F5~; O t - ~~ _ T_ Rubidium(~¥r5~5 intake p9lday (on the avera9e ot a.7 week) ~ (~~ 9Sb g~~) .~(~g) ~5~¥c5~¥S~~¥<599) ¥f~(5~¥c~~9q!¥q;~cl;F5~~q;~59;~)q/~~q;~(Vq;~: ~~.1~~~;F59; Figure I Frequency distribution of the daily J¥(5<5 c~¥'5 rubidium intake by women Rubidlum intake pglday (on the average of a week) Figure 2 Frequency distribution of the daily rubidium intake by men Recent progress in exploring the essentiality of the ultratrace element rubidium to the nutrition of animals and man 207

DM. In humans, none of the 70 female and 70 male 8 ) Yokoi K : A study on possible essentiality nature subjects investigated ingested (on average) Iess than of and rubidium. J. Jpn. Soc. Nutr. Food Sci. 400 pg Rb a day (Figures I and 2). Thus, the rubidium 50 : 15-20, 1997. requirement of humans - should it exist - might be 9 ) Angelow L, Anke M : Rubidium in der Nahrungs- rated as < 400 pg per day. kette. Mengen- und Spurenelemente ; 14 : 285-300, 1994. References 10) Anke M, Angelow L : Rubidium. In : lvlerian, E., 1 ) Glendening BL, Schrenk WG, Parrish DB : Effects Anke, M., Ihnat, M., Stoeppler, M. editors. Wiley of rubidium in purified diets fed rats. J. Nutr. 60 : - VHC Verlag GmbH and Co KGaA, Weinheim, 563-569, 1956. Germany, 2004 : pp. 547-563. 2 ) Nielsen FH : Rubidium. In : Mertz W (editor) : 11) Anke M, Angelow L, Glei M, Anke S, Lbsch E, Trace Elements in Human and Animal Nutrition, Gunstheimer G : The biological essentiality of Academy Press, Inc : Orlando, 1986 : pp. 431-434. rubidium. In : Ermidou-Pollet, S. (editor) : Interna- 3 ) Angelow L : Rubidium in der Nahrungskette. tional Symposium on Trace Elements in Human : Qualification for lectureship. Faculty of Biology New Perspectives, G. Morogianni : Acharnai, and Pharmacy, Friedrich Schiller University Athens, Greece, 1997 : pp. 245-263. Jena, Germany, 1994. 12) Anke M, Angelow L : The biological importance 4 ) Anke M, GUrtler H, Angelow L, Gottschalk J, of rubidium. In : Pais, I. editor. International Drobner C, Anke S. 11ling-GUnther H, MUller M, Trace Element Symposium, Budapest, Hungary, Arnhold W, Sch~fer U : Rubidium - an essential 1994 : pp. 241-262. element for animals and humans. In : Fischer 13) K0~1a T, Skibniewska E, Debski B, Urbanska- PWF, L'Abb~ MR, Cockell KA and Gibson RS, Slanka G : Rubidium in the trophic chain soil- editors. Trace Elements in Man and Animals plants-animals. In : Ermidou-Pollet, S., Pollet, S. TEMA-9, NRC Research Press : Ottawa, Canada, editors. 3*d International Symposium on Trace 1997 : pp. 189-191. Elements in Humans : New Perspectives. G. 5 ) Anke M, Arnhold W, Schafer U : Recent progress Morogiannis, Acharnai, Greece, 2001 : pp. 190-203. in exploring the essentiality of the ultratrace 14) Anke M, Angelow L, Glei M:, Muller M, Gunsth- element in the nutrition of animal and eimer U, Rbhrig B, Rother C, Schmidt P : man. Biomed. Res. Trace Elements ; in press. Rubidium in the food chain of humans : Origins 6 ) Anke M, Angelow L, Schmidt A, GUrtler H : and intakes. In : Fischer PWF, L'Abbe, MR., Rubidium an essential element for animals and Cockell, KA, Gibson, RS, editors. Trace Elements man ? In : Anke, M., Meissner, D. and Mills CF. in Man and Animals - 9. NRC Research Press. editors. Trace Element in Man and Animals Ottawa, Canada, 1997 : pp. 186-188. TEMA-8, Verlag Media Touristik, Gersdorf, 15) Anke M, Angelow L : Rubidium in the food chain. Germany, 1993 : pp. 719-723. Fresenius. J. Anal. Chem ; 352 : 236-239, 1995. 7 ) Yokoi K, Kimura M, Itokawa Y : Effect of low - 16) Hendrix P, Van Cauwenbergh R, Robberecht H, rubidium diet on macro - levels in rat Deelska H : Daily dietary rubidium intake in tissues. J. Jpn. Soc. Nutr. Food Sci. 50 : 295-299, Belgium using duplicate portion sampling. Z. 1994. Lebensm. Unters. Forsch. A. 204 : 165-167, 1997.