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Title:
PRODUCTS AND METHOD
Document Type and Number:
WIPO Patent Application WO/2011/107421
Kind Code:
A1
Abstract:
A method for producing compositions for the supplementation of one or more of the essential mineral nutrients potassium and/or calcium and/or magnesium together with nisin, ε-polylysine or a mixture of nisin and ε-polylysine. When the nutrition supplements according to the invention are used, the concentration of cytokines in the body is decreased as compared with the present situation when the recited nutrients are supplemented according to the prior art. The invention can be applied to sodium-reduced salt alternatives enriched with potassium or potassium and magnesium, or potassium and calcium, or potassium, magnesium and calcium. The invention can be applied also to enrichment ingredients, aimed at enriching foods or juices with potassium and/or calcium and/or magnesium. It can also be applied to foods or juices enriched with potassium and/or calcium and/or magnesium; or to dietary supplements aimed at supplementation of potassium and/or calcium and/or magnesium.

Inventors:
KARPPANEN, Heikki (Riippakoivunkuja 5, Espoo, FIN-02130, FI)
KARPPANEN, Pasi (Keskiyöntie 18 B 1, Espoo, FIN-02210, FI)
MERVAALA, Eero (Kotitontuntie 17 C, Espoo, FIN-02200, FI)
Application Number:
EP2011/052895
Publication Date:
September 09, 2011
Filing Date:
February 28, 2011
Export Citation:
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Assignee:
EKAKOS OY (Riippakoivunkuja 5, Espoo, FIN-02130, FI)
KARPPANEN, Heikki (Riippakoivunkuja 5, Espoo, FIN-02130, FI)
KARPPANEN, Pasi (Keskiyöntie 18 B 1, Espoo, FIN-02210, FI)
MERVAALA, Eero (Kotitontuntie 17 C, Espoo, FIN-02200, FI)
International Classes:
A23L1/237; A23B4/00; A23L1/30; A23L1/302; A23L2/44; A23L2/52; A23L3/00; A61K31/00
Domestic Patent References:
1998-07-09
2009-11-12
Foreign References:
EP1723857A12006-11-22
US20060239940A12006-10-26
US4931305A1990-06-05
US20070003491A12007-01-04
US2744827A1956-05-08
GB713251A1954-08-11
US4597972A1986-07-01
US5759844A1998-06-02
US6294183B12001-09-25
US5294552A1994-03-15
US5434060A1995-07-18
US5900363A1999-05-04
US5453420A1995-09-26
US5009907A1991-04-23
US4584199A1986-04-22
FI601B
GB2015863A1979-09-19
GB2159413A1985-12-04
FI9700797W1997-12-17
Other References:
DATABASE FSTA [Online] INTERNATIONAL FOOD INFORMATION SERVICE (IFIS), FRANkFURT-MAIN, DE; TSUJITA T ET AL: "Antiobesity action of epsilon-polylysine, a potent inhibitor of pancreatic lipase.", XP002630134, Database accession no. FS-2007-03-Tb0362 & "Antiobesity action of epsilon-polylysine, a potent inhibitor of pancreatic lipase.", JOURNAL OF LIPID RESEARCH, vol. 47, no. 8, 2006, page 1852, JOURNAL OF LIPID RESEARCH 2006 BIOSCI., INTEGRATED CENT. FOR SCI., EHIME UNIV., SHITSUKAWA, TOON, EHIME 791-0295, JAPAN. E-MAIL TSUJITA@M.EHIME-U.AC.JP LNKD- DOI:10.1194/JLR.M600168-JLR200
YUDKIN JS; KUMARI M; HUMPHRIES SE; MOHAMED-ALI V: 'Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link' ATHEROSCLEROSIS vol. 148, no. 2, February 2000, pages 209 - 214
P. LIBBY: 'Inflammation and cardiovascular disease mechanisms' AM J CLIN NUTR vol. 83, 2006, pages 456S - 460S
B SOLIS-PEREYRA; N AATTOURI; D LEMONNIER: 'Role of food in the stimulation of cytokine production' AMERICAN JOURNAL OF CLINICAL NUTRITION vol. 66, 1997, pages 521S - 525S
P. LIBBY: 'Inflammation and cardiovascular disease mechanism' AM J CLIN NUTR vol. 83, 2006, pages 456S - 460S
USDA NATIONAL NUTRIENT DATABASE FOR STANDARD REFERENCE, RELEASE vol. 21, 2008,
'Journal of Nutrition', 1977 article 'COMMITTEE OF THE COUNCIL OF AMERICAN INSTITUTE OF NUTRITION', pages 1340 - 1348
USDA NATIONAL NUTRIENT DATABASE FOR STANDARD REFERENCE, RELEASE, [Online] vol. 21, 2008, Retrieved from the Internet:
USA DIETARY SUPPLEMENT HEALTH AND EDUCATION 1994,
Attorney, Agent or Firm:
OY JALO ANT-WUORINEN AB (Iso Roobertinkatu 4-6 A, Helsinki, FIN-00120, FI)
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Claims:
Claims

1. A product for providing supplementary oral amounts of at least one of the mineral nutrients selected from the group consisting of potassium (K), calcium (Ca) and magnesium (Mg), concomitantly with EPL, Nisin or a combination of EPL and Nisin,

said product being selected from the group consisting of salt alternatives, enrichment ingredients, food compositions, juice compositions or dietary sup- plement compositions, whereby the level (weight/weight) of EPL plus Nisin is

0.02 - 20 % in salt alternatives,

0.02 - 95 % in enrichment ingredients,

0.001 - 2 % in food compositions or juice compositions, and

2.5 - 95 % in dietary supplement compositions;

and the total level (weight/ weight) of the mineral nutrient(s), calculated as the free cations K+, Mg2+, Ca2+ is

5 - 50 % in salt alternatives or enrichment ingredients;

0.05 - 3 % in food compositions or juice compositions, and

5 to 45 % in dietary supplement compositions.

2. A salt alternative according to claim 1, wherein the combined level of EPL and Nisin is 0.02 - 10 %, the level of potassium chloride is 9 - 75 %, and the level of magnesium sulfate is 2.5 - 25 % of the total weight of the salt alternative.

3. A salt alternative according to claim 1, wherein the level of EPL is 0.02 - 10 %, the level of potassium chloride is 9 - 75 %, and the level of magnesium sul- fate is 2.5 - 25 % of the total weight of the salt alternative.

4. An enrichment ingredient according to claim 1, wherein the level of EPL is 0.02 - 95 % and the total level of the incorporated supplementary mineral nutrient^) K+, Mg2+, Ca2+ is 5 - 50 %. 5. An enrichment ingredient according to claim 1, wherein the level of Nisin is 0.02 - 95 % and the total level of the incorporated supplementary mineral nutrient^) K+, Mg2+, Ca2+ is 5 - 50 %.

6. An enrichment ingredient according to claim 1, wherein the combined level of EPL and Nisin is 0.02 - 95 % and the total level of the incorporated supplementary mineral nutrient(s) K+, Mg2+, Ca2+ is 5 - 50 %.

7. A food or juice composition according to claim 1, wherein the level of EPL is 0.001 - 2 % and the total level of the incorporated supplementary mineral nu- trient[s) K+, Mg2+, Ca2+ is 0.05 - 3 %.

8. A food or juice composition according to claim 1, wherein the combined level of EPL and Nisin is 0.001 - 2 % and the total level of the incorporated supplementary mineral nutrient(s) K+, Mg2+, Ca2+ is 0.05 - 3 %.

9. A food or juice composition according to claim 1, wherein the level of Nisin is 0.001 - 2 % and the total level of the incorporated supplementary mineral nutrients) K+, Mg2+, Ca2+ is 0.05 - 3 %. 10. A dietary supplement composition according to claim 1, wherein the level of EPL is 2.5 - 95 % and the total level of the incorporated mineral nutrient(s) K+, Mg2+, Ca2+ is 5 - 45 %.

11. A method of providing supplementary oral amounts of at least one of the mineral nutrients selected from the group consisting of potassium (K), calcium (Ca) and magnesium (Mg), concomitantly with EPL, Nisin or a combination of these, by producing salt alternatives, enrichment ingredients, food composi- tions, juice compositions or dietary supplement compositions, whereby the level (weight/weight) of EPL plus Nisin is

0.02 - 20 % in salt alternatives,

0.02 - 95 % in enrichment ingredients

0.001 - 2 % in food compositions or juice compositions,

and 2.5 - 95 % in dietary supplement compositions,

and the total level (weight/ weight) of the mineral nutrient(s), calculated as the free cations K+, Mg2+, Ca2+ is

5 - 50 % in salt alternative compositions or enrichment ingredients;

0.05 - 3 % in food compositions or juice compositions, and

5 to 45 % in dietary supplement compositions.

12. A method according to claim 11, comprising producing a salt alternative wherein the combined level of EPL and Nisin is 0.02 - 10 %, the level of potas- sium chloride is 9 - 75 %, and the level of magnesium sulfate is 2.5 - 25 % of the total weight of the salt alternative.

13. A method according to claim 11, comprising producing a salt alternative wherein the level of EPL is 0.02 - 10 %, the level of potassium chloride is 9 - 75 %, and the level of magnesium sulfate is 2.5 - 25 % of the total weight of the salt alternative.

14. A method according to claim 11, comprising producing an enrichment in- gredient wherein the level of EPL is 0.02 - 95 % and the total level of the incorporated supplementary mineral nutrientfs] K+, Mg2+, Ca2+ is 5 - 50 %.

15. A method according to claim 11, comprising producing an enrichment in- gredient wherein the level of Nisin is 0.02 - 95 % and the total level of the incorporated supplementary mineral nutrient(s) K+, Mg2+, Ca2+ is 5 - 50 %.

16. A method according to claim 11, comprising producing an enrichment ingredient wherein the combined level of EPL and Nisin is 0.02 - 95 % and the total level of the incorporated supplementary mineral nutrientfs) K+, Mg2+, Ca2+ is 5 - 50 %.

17. A method according to claim 11, comprising producing a food or juice composition wherein the level of EPL is 0.001 - 2 % and the total level of the incorporated supplementary mineral nutrientfs) K+, Mg2+, Ca2+ is 0.05 - 3 %. 18. A method according to claim 11, comprising producing a food or juice composition wherein the combined level of EPL and Nisin is 0.001 - 2 % and the total level of the incorporated supplementary mineral nutrient(s) K+, Mg2+, Ca2+ is 0.05 - 3 %. 19. A method according to claim 11, comprising producing a food or juice composition wherein the level of Nisin is 0.001 - 2 % and the total level of the incorporated supplementary mineral nutrientfs) K+, Mg2+, Ca2+ is 0.05 - 3 %.

20. A method according to claim 11, comprising producing a dietary supple- ment composition wherein the level of EPL is 2.5 - 95 % and the total level of the incorporated mineral nutrient(s) K+, Mg2+, Ca2+ is 5 - 45 %.

Description:
Products and method

Field of the invention The present invention relates to a novel principle of providing supplementary oral amounts of the essential mineral element nutrients potassium and/or calcium and/or magnesium so that the production and/or concentration of harmful cytokines can be decreased as compared with the cytokine concentrations, which are present in the body if the recited nutrients are supplemented ac- cording to the prior art. Suitable product types for the application of this invention are salt alternatives (salt substitutes], enrichment ingredients, and various foods and fruit juices.

The use of this invention is particularly useful in the prevention and basic treatment of hypertension (i.e., too high blood pressure), stroke and heart at- tacks as well as in the prevention and treatment of obesity.

It even markedly decreases the spoilage tendency, characteristic of many foods with low(ered) salt (sodium) concentration and containing enrichments of potassium and/or calcium and/or magnesium. Background of the invention

Ingestion of supplementary amounts of the mineral nutrients potassium, magnesium and calcium, achieved by the use of potassium- and magnesium enriched, sodium-reduced salt alternatives, foods enriched with the said nutri- ent(s), enrichment ingredients aimed at enriching foods and drinks, or dietary supplements or pharmaceutical preparations, has proved to exert beneficial health effects, especially on the heart and blood vessels and on metabolic functions.

Recently it has been found that interleukin-6 and other cytokines contribute to the development of hypertension, obesity, insulin resistance and coronary heart disease (Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V: Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2000 Feb;148(2): 209-214). It is well known that the development of the said pathological conditions is a slow process, which may take several months of even years until the pathological conditions become manifest [measurably detectable). However, increased concentrations of cytokines both promote the development of the said pathological conditions, and they are also good early indicators of the development of the said conditions. Prevention of the rise of cytokines or decrease of elevated cytokine levels are able to prevent the development of, and even has therapeutic effects in, the mentioned pathological conditions. Moreover, they are early indicators of such beneficial effects before the above-recited pathological conditions become measureable (mani- fest).

Several food factors have been known to increase the production of harmful cytokines and their levels in blood and/or other tissues (P. Libby: Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr 2006;

83(suppl]:456S- 460S; B Solis-Pereyra, N Aattouri and D Lemonnier: Role of food in the stimulation of cytokine production, American Journal of Clinical Nutrition 1997, Vol 66, 521S-525S). In the presence of elevated cytokine levels due to a high consumption of saturated fats a decrease in the intake of saturated fats is able to decrease harmful cytokines (P. Libby: Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr 2006; 83[suppl): 456S- 460S).

Unfortunately, like saturated fats, also supplementary dietary levels and oral amounts of each of the mineral nutrients potassium, magnesium and calcium can increase the level of cytokines in the body. Such an action decreases and may even prevent the benefits, which are otherwise produced by the favourable biological and pharmacological effects of potassium and/or calcium and/or magnesium supplementation. Therefore it would be highly desirable to have a practical method, capable of decreasing harmful cytokines and which could be easily applied in connection with the oral supplementation of one or more of the recited essential mineral nutrients. It has now been invented that the desired effects can be produced by taking advantage of the use of either nisin or ε-polylysine or the combination of the two compounds. Previously it has been described that both nisin (U.S. Pat. No. 2,744,827; British Pat. No. 713,251; U.S. Patent No. 4,597,972) and ε-polylysine are able to reduce food or beverage spoilage tendency (U.S. Patent No. 5,759,844; U.S. Patent No.

6,294,183; U.S. Patent No. 5,294,552]; U.S. Patent No. 5,434,060; U.S. Patent No. 5,759,844; U.S. Patent No. 5,900,363; U.S. Patent No. 5,453,420; U.S. Patent No. 5,009,907; U.S. Patent No. 4,584,199).

Nisin is produced by fermentation using the bacterium Lactococcus lactis. Nisin is a pentacyclic peptide composed of 34 amino acids. Nisin contains the unusual amino acids lanthionine and β-methyl lanthionine. There are two naturally occurring Nisin variants, Nisin A and Nisin Z. Nisin A differs from Nisin Z in a single amino acid residue at position 27, being histidine in Nisin A and asparagine in Nisin Z. Commercially, Nisin is obtained from the culturing of Lactococcus lactis on natural substrates, such as milk or dextrose.

It should be emphasized that orally ingested Nisin is broken down into amino acids by proteinases in the digestive system. Hence, extremely small if any amounts of Nisin are absorbed into the blood stream, and no Nisin can be found in organs and tissues after oral ingestion of Nisin. ε-Polylysine (epsilon-polylysine; hereinafter EPL) is a homo-polypeptide of ap- proximately 25 ~ 30 L-Lysine residues. Epsilon (ε) refers to the linkage of the lysine molecules. In contrast to normal peptide bond that is linked by the alpha-carbon group, the lysine amino acids are molecularly linked by the epsilon amino group and the alpha carboxyl group.

EPL belongs to the group of cationic surfactants. In water, EPL contains a posi- tively charged hydrophilic (amino) group and a hydrophobic (methylene) group.

Recently it has been reported (Tsujita, T. et al., 2006) that in vitro, EPL strongly inhibits the hydrolysis of trioleoylglycerol emulsified with phosphatidylcholine (PC) and taurocholate by either pancreatic lipase or carboxylester lipase. The EPL concentration required for 50% inhibition of pancreatic lipase, 0.12 mM, was very much lower than the concentration of orlistat, an established anti- obesity drug, required for the same effect. Gel-filtration experiments suggested that EPL did not bind strongly to pancreatic lipase, whereas orlistat did. EPL prevented the increase in body weight and weight of the liver and visceral adipose tissues (epididymal and retroperitoneal), which was induced by a high-fat diet. This anti-obesity effect of EPL was believed to result from the inhibition of lipase enzymes. The fecal weights of mice were increased by the high-fat diet containing EPL compared with the high-fat diet alone. Fecal lipid was also increased by the diet containing EPL. The authors concluded that the data clearly show that EPL has an anti-obesity function in mice fed a high-fat diet that acts by inhibiting intestinal absorption of dietary fat. EPL also decreased plasma triacylglycerol and plasma cholesterol concentrations and liver triacyl- glycerol content after they had been increased by the high-fat diet.

Definitions 1. Food

Food is usually defined as any substance, usually composed of carbohydrates, fats, proteins and water, that can be eaten or drunk by an animal, including humans, for nutrition or pleasure. In the context of this patent application the definition applies otherwise except salt, salt alternative, juice, beverage, enrichment ingredient, dietary supplement and pharmaceutical are entities, which are not considered food.

2. Diet

Diet is the sum of the food consumed by an animal, including humans.

3. Basal/basic level of the mineral nutrients potassium, calcium, and magnesium (K/Ca/Mg) in food, diet or juice composition

The reference "basal/basic" level of the mineral nutrients potassium, calcium, and magnesium (K/Ca/Mg) of each non-supplemented (or un-enriched / unfortified) food is defined as the level given in the USDA National Nutrient Database for Standard Reference, Release 21 (2008)

fhttp://www.nal,usda.gov/fnic/foodcomp/search/) . For the sake of clarity, "Basal/basic mineral nutrients potassium, calcium, and magnesium (K/Ca/Mg)", comprise all the amounts of mineral nutrients which are present in the composition without "supplementary oral amounts", i.e. they are inherently present in edible food items or natural drinking or mineral wa- ter in their natural, unprocessed state. "Basal/basic mineral nutrients potassium, calcium, and magnesium (K/Ca/Mg)", also comprise all the amounts of compounds, which are present in the conventional (basal), non-supplemented compositions of foods, diet or beverages, which have been produced by processing

a) for human consumption essentially according to the Good Manufacturing Practice (GMP) as advised by the guidelines of Codex Alimentarius, http://www.codexalimentarius.net/web/index en.jsp. Its texts are developed and maintained by the Codex Alimentarius Commission, a body that was established in 1963 by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO). The

Commission's main aims are stated as being to protect the health of consumers and ensure fair practices in the international food trade.

The mineral nutrients, which are present in the ingredients defined as basic ingredients in Codex Alimentarius and used for the production of the said items according to the Codex Alimentarius guidelines, also belong to the "Basal/basic mineral nutrients". b) for animals essentially according to the guidelines given by the American

Institute of Nutrition (AIN), as described in

COMMITTEE OF THE COUNCIL OF AMERICAN INSTITUTE OF NUTRI¬

TION, Report of the American Institute Nutrition Ad Hoc Committee on Standards for Nutritional Studies, Journal of Nutrition, 1977, pages 1340- 1348, USA. 4. "Supplementary = Enrichment oral amount" of mineral nutrient(s) calcium (Ca), potassium (K), or magnesium (Mg)

In the context of this patent application this condition is fulfilled if a food or juice is enriched or fortified with calcium, potassium and/or magnesium com- pound so that the concentration of at least one of the mineral nutrients [Ca, K, Mg) in food or juice is at least 25 % higher than the reference level given for each un-enriched and unfortified food in the USDA National Nutrient Database for Standard Reference, Release 21 [2008]

rhttp://www.nal.usda.gov/fnic/foodcomp/search/l.

In the context of this invention, a salt composition is considered to provide "supplementary or enrichment amounts" of

a) potassium if the potassium concentration is at least 5 %

b] magnesium if the magnesium concentration is at least 0.85 %

c) calcium if the calcium concentration is at least 0.25 %

5. Enrichment ingredient

"Enrichment ingredient" in the present patent application refers to any mixture or component part of mixture that contains at least one of the recited mineral nutrients, i.e. potassium and/or calcium and/or magnesium at the level given in the claims and/or examples, and also contains EPL and/or NIS compounds at the levels given in the claims and/or examples and goes to make a food, diet or juice so that it increases the levels of the recited compounds in the food, diet or juice beyond and over the conventional "basal/basic" levels as defined above, so that the so made food, diet or juice contains "supplementary oral amount(s)" of the recited mineral nutrient(s).

6. Salt alternative or salt substitute

In the context of this patent application this term refers to food ingredient or food additive that resemble common edible table salt, rock salt or sea salt regarding taste, appearance and uses but which, in comparison with common table salt, rock salt or sea salt, has at least 25 % less sodium than "Salt, table" in the USDA National Nutrient Database for Standard Reference, Release 21

[2008) [http://www.nal.usda.gov/fnic/foodcomp/search/. and the sodium chloride has been partly or completely replaced by other compounds than common salt. Such other compounds include but are not limited to at least one compound from the group of potassium chloride or other potassium compound^), and/or magnesium compound(s) and/or calcium compound(s).

7. Dietary supplement composition (or food supplement composition or nutritional supplement)

refers to compositions as defined in the USA Dietary Supplement Health and Education Act of 1994 (DSHEA]:

According to Section 3 of the Act, the term "dietary supplement":

"(1) means a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients:

(A) a vitamin;

(B) a mineral;

(C) an herb or other botanical;

(D) an amino acid;

(E) a dietary supplement used by man to supplement the diet by increasing the total dietary intake; or

(F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause (A), (B), (C), (D), or (E).

According to DSHEA, a dietary supplement is a product that is labelled as a dietary supplement and is not represented for use as a conventional food or as a sole item of a meal or the diet. The definition describes the variety of forms— capsule, powder, softgel, gelcap, tablet, liquid, or other form— in which these products can be ingested. This section of DSHEA specifically excludes dietary supplements from the definition of food additives in Section 409 of FDCA. ihttp://www.health.gov/dietsupp/chl.htm)"

8. Plant sterol/stanol

The term "plant sterol/stanol" refers to naturally occurring plant sterols and stanols, particularly beta-sitosterol and beta-sitostanol but also stigmasterol, campesterol, and dihydrobrassicasterol, and/or the hydrogenated forms, i.e the so-called stanols, of the aforementioned natural plant sterols. Both the sterols and stanols can be either unmodified parent compounds or their fatty acid esters. Also concentrates of tall oil, soy beans, rapeseeds, coconuts, corn, peanuts, or other natural sources containing at least 10 % of the said compound^) is referred to as "plant sterol/stanol".

Summary of the invention

An objective of the present invention was to create a method, which can be used to produce various compositions, which are practical for the supplemen- tation of one or more of the essential mineral nutrients potassium and/or calcium and/or magnesium so that concentration of cytokines in the body is decreased as compared with the present situation when the recited nutrients are supplemented according to the prior art. For example, in the invention in accordance with FI 60107 (which corresponds to GB 2015863) as well as in GB 2159413, mixtures of salts containing sodium chloride, potassium chloride and magnesium sulfate or chloride are described for supplementation of potassium and magnesium and for decreasing salt (sodium) intake. In PCT FI

1997/000797 supplementation of potassium and/or calcium and/or magnesium together with plant sterols is suggested. These prior arts fail to take the important role of cytokines into account.

It was discovered that incorporation of either NIS or EPL or a mixture of NIS and EPL in compositions, serving directly or indirectly oral supplementation with potassium and/or calcium and/or magnesium, decrease harmful cytokines in the body as compared with the cytokine concentrations, which are present in the body if the recited nutrients are supplemented according to the prior art. The invention can be applied to sodium-reduced salt alternatives enriched with potassium or potassium and magnesium, or potassium and calcium, or potassium, magnesium and calcium. The invention can be applied also to enrichment ingredients, aimed at enriching foods or fruit juices with potas- sium and/or calcium and/or magnesium. It can also be applied to foods or fruit juices enriched with potassium and/or calcium and/or magnesium. It can also be applied to dietary supplements aimed at supplementation of potassium and/or calcium and/or magnesium. Description of the invention According to the present invention salt alternatives, enrichment ingredients, food compositions, juice compositions and dietary supplement compositions are provided. In addition to physiologically acceptable potassium and/or calcium and/or magnesium compounds, the products and compositions according to the invention comprise Nisin or EPL or both Nisin and EPL.

In the following discussion, the expression "composition" refers to all types of products according to the invention.

It was discovered that compositions according to the present invention decrease cytokines in the body in the presence of oral ingestion of supplementary amounts of any one of the mineral nutrients potassium, calcium or magnesium, or two of them together, or all three of them together, when these essential mineral nutrients are derived from enrichments [or supplements] present in sodium-reduced, mineral nutrient-enriched salt alternatives, enrichment ingredients for foods or fruit juices, mineral nutrient-enriched foods or fruit juices, or dietary supplements for supplementation of potassium and/or cal- cium and/or magnesium.

In this invention appropriately high amounts of Nisin and, in particular, EPL are incorporated in the above recited product compositions, which have been enriched or supplemented with potassium and/or calcium and/or magnesium. Either Nisin or EPL may be incorporated in the recited compositions alone or both Nisin and EPL may be incorporated together.

After the production of the compositions containing one or more of the mineral element enrichments (potassium and/or calcium and/or magnesium) and Nisin or EPL or both Nisin and EPL, the recited products (i.e. sodium-reduced salt alternatives enriched with potassium or potassium and magnesium, or po- tassium and calcium, or potassium, magnesium and calcium; enrichment ingredients, aimed at enriching foods or fruit juices with potassium and/or calcium and/or magnesium; foods or fruit juices enriched with potassium and/or calcium and/or magnesium, or dietary supplements aimed at supplementation of potassium and/or calcium and/or magnesium) are used in the same manner as the corresponding products with compositions according to the prior art are used. In each case the use of the recited compositions leads ultimately to the ingestion of Nisin or EPL or the combination of Nisin and EPL concomitantly with one or more of the supplementary mineral nutrient(s) potassium and/or calcium and/or magnesium.

The invention functions well in each of the recited compositions. However, if beverages are enriched also with salt [sodium chloride), in addition to the recited beneficial mineral nutrients, the benefits of the incorporation of Nisin and/or EPL may be antagonized or even lost. Unfortunately, some sport drinks and energy drinks are supplemented (i.e. enriched) also with sodium chloride (salt) or other sodium compounds. Therefore, in spite of the fact that they may be enriched also with some of the beneficial nutrients potassium and/or calcium and/or magnesium, they are not eligible for the present invention.

The capability of Nisin and, in particular, that of EPL to decrease the cytokine levels in the blood and tissues in the presence of supplementation with potassium and/or calcium and/or magnesium is highly unexpected, since it is known that both Nisin and EPL are virtually not at all absorbed into the blood stream and, therefore, do not enter the blood stream and therefore do not reach the organs, in which the decrease of the cytokine levels can be found. Such a highly unexpected beneficial effect on cytokines augments markedly the salutary effects, which can be achieved by oral supplementary amounts of potassium, calcium or magnesium or any of their combinations alone, i.e. in the absence of concomitant EPL and/or Nisin supplementation.

Preferable magnesium compounds include, but are not limited to, in particular magnesium sulphate, magnesium chloride, magnesium hydroxide, magnesium oxide, and magnesium carbonate, but also many other compounds such as magnesium salts of amino acids, and other physiologically acceptable magnesium compounds are possible. Preferable calcium compounds include, but are not limited to, in particular calcium phosphates, calcium carbonate, calcium lactate, and calcium chloride, but also many other compounds such as calcium sulphate, calcium citrates, calcium tartrate, calcium acetate, calcium propionate, calcium alginate, calcium glutamate, calcium gluconate and other physiologically acceptable calcium compounds are possible.

Preferable potassium compounds include, but are not limited to, in particular potassium chloride, potassium (bi] carbonate, potassium lactate, and potassium sulphates, but also many other potassium compounds such as potassium phosphates, potassium tartrate, potassium acetate, potassium propionate, potassium alginate, potassium gluconate, and other physiologically acceptable potassium compounds are possible. Nisin A, in particular, but also other naturally occurring nisin variants, i.e. nisin Z, nisin Q, nisin F, nisin U or nisin U2, or a nisin derivative as described in WO/2009/135945, comprising at least one amino acid substitution in the peptide sequence encoding the hinge region of the protein, are appropriate also for this invention.

Normal commercially available EPL, i.e. a homo-polypeptide of approximately 25 ~ 30 L-Lysine residues, is useful for this invention.

Favourable compositions In an appropriate preparation for use as a salt alternative the combined level of EPL and Nisin is favourably 0.02 - 10 %, more favourably 0.1 - 5 %, and most favourably 0.3 - 3 %; and the total level of the incorporated supplementary mineral nutrient(s), calculated as the free cations K + , Mg 2+ , Ca 2+ is favourably 5 - 50 %, more favourably 9 - 40 % and most favourably 12 - 33 % of the total weight of the salt alternative.

In an appropriate preparation for use as an enrichment ingredient the combined level of EPL and Nisin is favourably 0.02 - 95 %, more favourably 1 - 80 %, and most favourably 5 - 70 %; and the total level of the incorporated supplementary mineral nutrient(s], calculated as the free cations K + , Mg 2+ , Ca 2+ is favourably 5 - 50 %, more favourably 9 - 40 % and most favourably 12 - 33 % of the total weight of the enrichment ingredient.

In an appropriate preparation for use as a food or juice the combined level of EPL and Nisin is favourably 0.001 - 2 %, more favourably 0.005 - 1.5 %, and most favourably 0.01 - 1 %; and the total level of the incorporated supplementary mineral nutrient(s], calculated as the free cations K + , Mg 2+ , Ca 2+ is favoura- bly 0.05 - 3 %, more favourably 0.1 - 2 % and most favourably 0.4 - 1.7 % of the total weight of the food or fruit juice.

In an appropriate preparation for use as a dietary supplement the combined level of EPL and Nisin is favourably 2.5 - 95 %, more favourably 5 - 80 %, and most favourably 7 - 70 %; and the total level of the incorporated supplementary mineral nutrientfs], calculated as the free cations K + , Mg 2+ , Ca 2+ is favourably 5 - 45 %, more favourably 7 - 35 % and most favourably 9 - 30 % of the total weight of the dietary supplement. Examples

Example 1

A salt alternative consisting essentially of approximately the following percentage amounts of

Potassium chloride [KG] 28

Magnesium sulphate (MgS0 4 -7H 2 0] 12

EPL 1.5

Sodium chloride (NaCl) 56

Lysine hydrochloride 2

The salt alternative is used instead of common salt in essentially the same way as common salt is used.

Example 2 A salt alternative consisting essentially of approximately the following percentage amounts of

Potassium chloride [KC1] 15

Magnesium sulphate (MgS0 4 -7H 2 0] 14

EPL 0.3

Sodium chloride (NaCl) 69

Lysine hydrochloride 1

The salt alternative is used instead of common salt in essentially the same way as common salt is used.

Example 3

A food composition, such that KC1, MgS04-7H 2 0 and EPL, with or without the presence of NaCl, are incorporated in food, each individually or in various combinations so that the proportions KC1: MgS0 4 7H 2 0: EPL in the ultimate edible food are approximately the same as in Examples 1 or in Example 2, and the total (i.e. sum] level of the different so incorporated components in the ultimate edible food item is 0.1 - 5 %.

Example 4

A salt alternative consisting essentially of approximately the following percentage amounts of

Potassium chloride [KG] 28

Magnesium sulphate (MgS0 4 -7H 2 0] 12

Nisin 3

Sodium chloride (NaCl) 55

Lysine hydrochloride 2

The salt alternative is used instead of common salt in essentially the same way as common salt is used in the corresponding food item.

Example 5

A food composition, such that KC1, MgS0 4 7H 2 0 and Nisin, with or without the presence of NaCl, are incorporated in food, each individually or in various combinations so that the proportions KC1: MgS0 4 -7H 2 0:Nisin in the ultimate edible food are approximately the same as in Examples 4, and the total (i.e. sum) level of the different so incorporated components in the ultimate edible food item is 0.1 - 5 %. Example 6

A salt alternative consisting essentially of approximately the following percentage amounts of

Potassium chloride [KCl] 28

Magnesium sulphate (MgS0 4 7H 2 0] 12

EPL 1

Nisin 0.7

Sodium chloride (NaCl) 56

Lysine hydrochloride 2

The salt alternative is used instead of common salt in essentially the same way as common salt is used.

Example 7

A food composition, such that KCl, MgS04-7H 2 0 , EPL and Nisin, with or without the presence of NaCl, are incorporated in food, each individually or in various combinations so that the proportions KCl: MgS04-7H 2 0:EPL:Nisin in the ultimate edible food are approximately the same as in Examples 6, and the total (i.e. sum) level of the different so incorporated components in the ultimate edible food item is 0.1 - 5 %. Example 8

A salt alternative consisting essentially of approximately the following percentage amounts of

Potassium chloride (KCl) 25

Magnesium sulphate (MgS04.7H20) 10

Sodium chloride (NaCl) 62 - 67

EPL and/or Nisin 0.3-3 The salt alternative is used instead of common salt in essentially the same way as common salt is used.

Example 9

A food composition, such that KC1, MgS04-7H 2 0 , EPL and Nisin, and NaCl, are incorporated in food, each individually or in various combinations so that the proportions KC1: MgS04-7H20:EPL and/or Nisin:NaCl in the ultimate edible food are approximately the same as in Examples 8, and the total (i.e. sum) level of the different so incorporated components in the ultimate edible food item is 0.1 - 5 %.

Example 10

An enrichment ingredient consisting essentially of the following compounds (as per cent of the total weight of the composition):

Potassium chloride (KC1) 10-20

Magnesium sulphate (MgS0 4 -7H 2 0) 4-8

EPL and/or Nisin 0.02-6

Sodium chloride (NaCl) 20-50

Lysine hydrochloride 0-4

Plant sterol/stanol 20-65

Example 11

A food composition consisting essentially of approximately the following amounts of

Boiled rice 1000 g

EPL 0.05 g

EPL is incorporated in the boiled rice after dissolving it in an appropriate, physiologically acceptable liquid.

Further, 5 -20 g (according to taste) of a mixture with approximately the following composition is also incorporated

Potassium chloride (KG) 52 g

Magnesium carbonate (MgC0 3 ) EPL

Sodium chloride (NaCl)

Gamma-poly-glutamic acid

Example 12

A salt alternative or enrichment ingredient consisting essentially of

Potassium chloride [KG] 52 g Magnesium carbonate (MgCOs) 1 g

Nisin and/or EPL 0.1 - 2

Sodium chloride (NaCl) 46 g

Gamma-poly-glutamic acid 0.1 g

Example 13

SAUSAGE

A pre-mix of approximately the following formulation is made:

Plant sterol/stanol 0.270 kg

Calcium chloride (CaCl 2 .6H 2 0) 0.057 kg

Magnesium sulphate (MgS0 4 -7H 2 0) 0.057 kg

Potassium chloride [KC1] 0.132 kg

Potassium lactate 0.090 kg

Sodium chloride (NaCl) 0.270 kg

Sodium lactate 0.090 kg

1-Lysine hydrochloride 0.010 kg

EPL 0.0045 kg

This pre-mix is thoroughly mixed with the following ingredients:

Meat, including natural fat 12.500 kg

Milk powder 0.840 kg

Potato starch 1.160 kg

Water 6.450 kg

Sodium nitrite (NaN0 2) 10 % solution) 0.030 kg

Spices 0.085 kg The sausage is processed according to generally known conventional industrial techniques.

Example 14

SALAD DRESSING

Vegetable oil 2.0000 kg

Calcium chloride (CaCh 6H 2 0) 0.0048 kg

Magnesium sulphate (MgS0 4 -7H 2 0] 0.0048 kg

Potassium chloride [KC1] 0.0112 kg

Sodium chloride (NaCl) 0.0228 kg

1-Lysine hydrochloride 0.0008 kg

EPL 0.0004 kg

Vinegar [10 weight %) 0.1200 kg

Plant sterol/stanol 0.2000 kg

Water 1.6360 kg

The salad dressing is prepared by homogenization by conventional industrial methods.

Example 15

A food selected from the group consisting of any processed milk product/dairy product such as milk, milk drink, fermented milk product, yoghurt, cheese, etc., cereal product, pasta and noodles, soup, broth, mayonnaise, gravy, sauce, food dressing, meat product, bakery product, vegetable product, seaweed product, cereal or starch based dessert, yellow-fat spread or other vege- table oil-based food, a soy-based beverage or soy-based food, fruit-based food, berry-based foods, a juice, alcoholic beverage, or fruit flavoured drink (beverage], but excluding salt-enriched sport drinks and salt enriched energy drinks or other salt-enriched drinks /beverages.

Into the said food EPL is incorporated at a level of 0.001 - 2 weight-% and the supplementary amount of calcium is 0.1 - 3 weight-%.

Example 16 A food selected from the group consisting of any processed milk product/dairy product such as milk, milk drink, fermented milk product, yoghurt, cheese, etc., cereal product, pasta and noodles, soup, broth, mayonnaise, gravy, sauce, food dressing, meat product, bakery product, vegetable product, seaweed product, cereal or starch based dessert, yellow-fat spread or other vegetable oil-based food, a soy-based beverage or soy-based food, fruit-based food, berry-based food, a juice , alcoholic beverage, or fruit flavoured drink (beverage), but excluding salt-enriched sport drinks and salt enriched energy drinks or other salt-enriched drinks /beverages. Into the said food EPL is incorporated at a level of 0.001 - 2 weight-%, and the supplementary amount of potassium is 0.2 - 3 weight-%.

Example 17

A food selected from the group consisting of any processed milk product/dairy product such as milk, milk drink, fermented milk product, yoghurt, cheese, etc., cereal product, pasta and noodles, soup, broth, mayonnaise, gravy, sauce, food dressing, meat product, bakery product, vegetable product, seaweed product, cereal or starch based dessert, yellow-fat spread or other vegetable oil-based food, a soy-based beverage or soy-based food, fruit-based food, berry-based food, a juice, alcoholic beverage, or fruit flavoured drink (beverage), but excluding salt-enriched sport drinks and salt enriched energy drinks or other salt-enriched drinks /beverages. Into the said food EPL is incorporated at a level of 0.001 - 2 weight-%, and the supplementary amount of magnesium is 0.1 - 3 weight-%.

Example 18

A food selected from the group consisting of any processed milk product/dairy product such as milk, milk drink, fermented milk product, yoghurt, cheese, etc., cereal product, pasta and noodles, soup, broth, mayonnaise, gravy, sauce, food dressing, meat product, bakery product, vegetable product, seaweed product, cereal or starch based dessert, yellow-fat spread or other vegetable oil-based food, fruit-based food, berry-based foods, a soy-based beverage or soy-based food, a drink (beverage), but excluding salt-enriched sport drinks and salt en- riched energy drinks or other salt-enriched drinks /beverages. Into the said food EPL is incorporated at a level of 0.001 - 2 weight-% and the supplementary amount (i.e. the amount over and beyond the level, which is normally present in the same food type such as juice without supplementation] of calcium plus potassium plus magnesium, or that of calcium plus potassium, or that of calcium plus magnesium, or that of potassium plus magnesium is 0.2 - 3 weight-%.

Example 19

Any of the examples 16 through 18 with the exception that Nisin alone or together with EPL is incorporated instead of EPL alone.

Example 20

A dietary supplement for magnesium supplementation with approximately the following composition:

Appropriate magnesium compound[s] such as, for example, oxide, hydroxide, lactate, sulphate, chloride etc. 0.25 g

(expressed as magnesium cation]

EPL 0.15 g

Excipients 0.15 g

One to four doses a day of the supplement (as tablet, capsule, powder or other form of dietary supplement] is ingested with a meal.

Example 21

A dietary supplement for potassium supplementation with approximately the following composition:

Appropriate potassium compound(s] such as, for example, citrate and/or chloride and/or phosphate and/or lactate 0.25 g

(expressed as the amount of potassium cation]

EPL 0.1 g

Excipients 0.15 g

One to four doses a day of the supplement (as tablet, capsule, powder or other form of dietary supplement] is ingested with a meal. Example 22

A dietary supplement for potassium and magnesium supplementation with approximately the following composition:

Appropriate potassium compound (s) 0.15 g

(expressed as the amount of potassium cation) and

Appropriate magnesium compound(s) 0.075 g

(expressed as magnesium cation)

EPL 0.05 g

Excipients 0.15 g

One to eight doses of the supplement (as tablet, capsule, powder or other form of dietary supplement) a day is ingested, preferentially with a meal.

Example 23

A dietary supplement for calcium supplementation with approximately the following composition:

Appropriate calcium compound(s) such as, for example, phosphate(s), lactate, chloride etc. 0.25 g

(expressed as calcium cation)

EPL 0.15 g

Excipients 0.15 g

One to eight doses of the supplement (as tablet, capsule, powder or other form of dietary supplement) a day is ingested, preferentially with a meal. Example 24

A food selected from the group consisting of processed milk products/dairy products like cheese, butter or butter-containing fat spread, cereal products, pasta and noodles, soup, broth, mayonnaise, gravy, sauce, food dressing, meat products, bakery products, vegetable products, seaweed products, cereals or starch based desserts, yellow-fat spreads or other vegetable oil-based foods, or soy-based foods or other foods into which EPL is incorporated at a level of 0.001 - 2 weight-%. Further, a mixture with approximately the following percentage composition is also incorporated at the level of 0.25 % - 4 % (according to taste and technological requirements)

Potassium chloride [KG] 28

Magnesium sulphate (MgS0 4 -7H 2 0] 12

EPL 1

Sodium chloride (NaCl) 56

Lysine hydrochloride 2

The order of incorporation may also be such that the said mixture is incorporated before the incorporation of EPL. The said mixture and EPL may also be incorporated simultaneously in the course of the manufacturing of the food.