Wellness Foods Europe THE MAGAZINE FOR NUTRITION, FUNCTIONAL FOODS & BEVERAGES AND SUPPLEMENTS Zinc citrate – a highly bioavailable zinc source Reprint from Wellness Foods Europe issue 3/2014 Wellness Foods Europe Special salts Zinc citrate – a highly bioavailable zinc source Markus Gerhart, Jungbunzlauer Ladenburg GmbH Zinc, the versatile mineral, is about to be- Zinc is a component of about 300 enzymes and come the next star in the minerals catego- 2000 transcriptional factors, and 10 % of the ry. Profiting from its various health benefits human proteome contain zinc-binding motives. and its relatively low cost in use, zinc sales Impairment of intestinal zinc absorption results in supplements have shown a double digit in severe clinical manifestations like skin lesions, growth in 2012 and are starting to catch up developmental retardation, stunted growth and with calcium, magnesium and iron, the cate- immune deficiency. gory leaders. Its importance for human health was empha- sised by the European health claim regu lation, Zinc is an essential transition metal that is where zinc received more positive opinions (18 directly or indirectly involved in a wide varie- in total) than any other mineral. The range of ty of physiological processes. After discover- claims (Table 1) includes, amongst others, im- ing the necessity of zinc for Aspergillus niger, it portant health benefits like immunity, bone took another 100 years before its relevance for health, cognitive function and healthy vision. humans was recognised, when the zinc deficien- These health benefits can be clearly defined and cy syndrome was described for the first time by are easy for the consumer to understand. Even Prasad and his co-workers at the beginning of if the EU regu lations are not valid outside Eu- the 1960s. rope, they influence other regions in the world 18 | Wellness Foods Europe – November 2014 Special salts Wellness Foods Europe because they represent the first comprehensive proportion of animal products and particularly evaluation of health claims, while the respective meat in the diet. Nevertheless, people with spe- dossiers can be used by other authorities as well. cialised diets like vegetarians, as well as elderly people and individuals in which gastric dysfunc- Table 1: Authorised health claims in the EU ac- tions (e. g., gastric atrophy and achlorhydria), cording to latest wording (status 01.01.2014) of are at higher risk of suffering from zinc defi- Art. 13.1 health claims list of Regulation (EC) ciency. No 1924/20061. Characteristics of zinc compounds > A wide – Normal function of the immune system vari ety of zinc salts are available for use in func- – Normal DNA synthesis tional foods, dietary supplements and drug – Role in the process of cell division products. The most common forms are zinc – Protection of cells from oxidative stress oxide, zinc sulphate and zinc gluconate, the lat- – Maintenance of normal bones ter two (together with zinc acetate) being re- – Normal cognitive function commended by the WHO for use in syrups or – Normal fertility and reproduction dispersible tablets for diarrhoea treatment in in- – Normal macronutrient and carbohydrate fants. metabolism There are various properties that need to be – Normal acid-base metabolism considered when formulating with zinc salts. – Normal metabolism of vitamin A Taste and solubility, in particular, limit the use – Normal metabolism of fatty acids of some compounds in specific applications. – Maintenance of normal vision However, costs and bioavailability are further – Maintenance of normal skin factors that need to be considered (Table 2). – Maintenance of normal hair – Maintenance of normal nails Table 2: Commonly used zinc salts approved – Normal protein synthesis for fortification in the EU according to Regula- – Maintenance of normal testosterone levels in tion (EC) No. 1825/2006. blood Good dietary sources for zinc are primarily foods of animal origin, e. g., meat, liver, fish, as well as milk and cheese. Concerning plant origin, high levels are reported for wholemeal products and legumes. However, plant-derived zinc generally displays low bioavailability, as The recommended daily allowance (RDA) of intestinal zinc absorption is in many cases im- zinc is only 10 mg in the EU and the daily value paired by anti-nutritive factors like phytic acid. (DV) is 15 mg in the US, so only small amounts The global prevalence of zinc deficiency was are needed for typical formulations, thus estimated at 31 %, ranging from 4–73 % across making the usage of zinc very cost efficient. The sub-regions. Based on these estimates, zinc de- large variation of mineral content has a huge ficiency in children aged below five years was impact on dosage of the specific zinc form and estimated to cause 176,000 diarrhoea deaths, may thus provide some benefit on overall for- 406,000 pneumonia deaths and 207,000 ma- mulation cost. Additionally, for formulations laria deaths per year. Zinc deficiency is rather with limited space (e. g., multi-vitamin or multi- uncommon in populations with predominant- mineral formulations) compounds with high ly Western style nutrition because of the high zinc content may be preferred. November 2014 – Wellness Foods Europe | 19 Wellness Foods Europe Special salts Highly soluble salts like zinc sulphate, zinc relatively low solubility. However, trials in gluconate and zinc acetate have a strong me- the Jungbunzlauer Application Technology tallic, bitter and astringent taste that often Centre have shown that the addition of tripo- needs to be masked. Even at the typically low tassium citrate (or trisodium citrate) can in- dosage levels of zinc salts in fortified foods, crease its solubility and zinc citrate, or a these off-tastes can be noticeable. Particular- combination of zinc citrate and tripotassi- ly in the case of food supplements or drug um citrate, results in significantly less bitter products like syrups and dispersible or effer- composition, compared to other soluble zinc vescent tablets, off-tastes can limit the appli- sources like zinc sulphate or zinc gluconate cability of these compounds. However, bet- (Table 3). ter tasting zinc oxide is insoluble and existing data indicates that its bioavailability is at the Bioavailability of zinc salts > Intestinal absorp- lower end of available zinc compounds. In tion of zinc and its adequate utilisation by the contrast to the oxide form, zinc gluconate body – in other words, the bioavailability – de- stands out for its high bioavailability, but its pends on several factors, such as the chemi- low zinc content makes this compound much cal form of the zinc salts, dietary factors and more expensive. An alternative zinc salt with physio logical condition (Table 4). promising sensory properties is zinc citrate. It has been demonstrated in animal and This compound has a high zinc content of human trials that absorbability is strongly 31 %, is slightly soluble in water, is odour- related to the specific solubility of zinc com- less, and has relatively low costs. pounds in aqueous solution. Therefore, acidic Its usability in highly concentrated syrups inorganic zinc salts like zinc chloride or zinc as well as in compounds for the beverage in- sulphate, which are very soluble in aqueous so- dustry has often been questioned due to its lution, show suffi cient bioavailability, where- Table 3: Taste ranking test for bitterness for solutions containing 10 mg Zn2+ per 5 ml each; (Rank: 1= least pronounced bitterness). Values that do not share a common letter are significantly different (p < 0.05) Zinc sulfate and zinc gluconate have further been described as having a strong metallic and astringent taste (Source: Internal tasting panel (n=10) at Jungbunzlauer Ladenburg GmbH, Germany) Table 4: Factors affecting bioavailability of zinc 20 | Wellness Foods Europe – November 2014 Special salts Wellness Foods Europe as zinc absorption from the oxide or carbonate Figure 1: Detailed study procedure (the 3 dif- salt, which are practically insoluble in neutral ferent test supplements were administered in aqueous solution, is significantly lower. Zinc random order) salts with organic anions (zinc acetate, zinc lac- tate) and particularly with amino acid chelates like zinc histidine and other reversibly complex- ing anions (e. g., zinc gluconate or zinc citrate) are thought to have a generally higher bioavail- ability than zinc sulphate. However, human ab- sorption data to support the usage of zinc citrate has so far been very limited. BU: baseline urine; EU: enriched urine. (With kind permission of R. Wegmüller) From the published data on the absorption of zinc from supplements given to humans, it The study showed that there was a significantly would appear that zinc gluconate, zinc citrate, higher absorption of zinc from zinc citrate (me- and zinc sulphate are absorbed at a similar level, dian absorption 61.3 %; P = 0.006) and zinc glu- while zinc oxide is slightly less well absorbed. conate (median absorption 60.9 %; P = 0.009) In order to prove this assumption the ETH when compared with the one from zinc oxide Zurich, Switzerland recently compared the bio- (median absorption 49.9 %), see figure 2. The availability of two assumed high bioavailable absorption of zinc citrate did not significantly salts (zinc citrate and zinc gluconate) with the differ from that of zinc gluconate. supposed lower bioavailable zinc oxide2. The One further interesting finding was that two goal of this trial was to use the double-isotope (one male, one female) of the 15 participants tracer ratio (DITR) method to compare the ab- did not absorb zinc from zinc oxide and one sorption of these three compounds when they further participant absorbed the zinc oxide at were given as supplements without food. This a low level (14 %). This suggests that there is a procedure is recommended to maximise zinc portion of the population that is not able to ab- absorption and is usually advised for the treat- sorb zinc in its oxide form. It was hypothesised ment of diarrhoea.