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EVM/01/04.REVISEDAug2002

_______________________________________________________________________________This paper has been prepared for consideration by the Expert Group on Vitamins and Minerals anddoes not necessarily represent the final views of the Group

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EXPERT GROUP ON VITAMINS AND MINERALS

REVISED REVIEW OF POTASSIUM

The attached review of potassium is a revised version of the paper presented tothe Expert Group on Vitamins and Minerals at the meeting on 9 February 2001.New information has been incorporated into the review to take account of someof the comments made by Members and to correct a number of minorinaccuracies.

The following annexes are also included:

Annex 1 Tables referred to in the review

Annex 2 Intakes of potassium from food and supplements in the UK

Annex 3 Summary table of selected nutrition related information andexisting guidance on intakes

Expert Group on Vitamins and Minerals SecretariatAugust 2002



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Potassium

Chemistry and Geochemistry

1. The alkaline, metallic element potassium (K) belongs to Group IA of the PeriodicTable and has an atomic weight of 39.1. It is a soft, silvery metal, which israpidly oxidised.

Natural Occurrence

2. The crustal abundance of potassium is 2.59%. Potassium is widely distributed innature in silicate rocks and also occurs in salt beds and seawater.

3. Potassium is not found as a pure metal in nature, being easily ionised to the cation(K+) through the loss of the outer electron. It is always combined with othersubstances, the most common form being the chloride salt (KCl) (Macrae et al.,1993). Important ore minerals are polyhalite, sylvite (KCl) and carnallite (KCl,MgCl2.6H2O).

Occurrence in food, food supplements and medicines

Food

4. Good food sources of potassium include milk, fruits (especially oranges, prunes,apples, pears, peaches, bananas and grapefruit), vegetables (especially broccoli,carrots, tomatoes and potatoes), fish, shellfish, beef, liver, chicken and turkey(NRC, 1989). Levels in food vary from up to 1740 mg/100 g of edible portion insoya beans, 1000 mg in parsley, 400 mg in banana and 350 mg/100 g of edibleportion in beef (Macrae et al., 1993).

5. Potassium chloride is the principal ingredient in salt substitutes used to satisfy theappetite for salt whilst restricting the intake of the sodium ion (Macrae et al.,1993). The potassium present in these salt substitutes is almost exclusively aspotassium chloride, either alone or mixed with other ions or salts such as sodium,calcium, magnesium, phosphate or choline (Saggar-Malik and Cappuccio, 1993).

6. Potassium bromate is a chemical oxidising agent used in flour milling, beermalting and in cheese making. It is not naturally occurring and is synthesised bypassing elemental bromine through a solution of potassium hydroxide.

7. Potassium nitrate and nitrite are used as food preservatives, mainly for curingmeats.

8. Food supplements in the UK can contain up to 80 mg potassium per tablet (OTC,2000). Potassium iodide is used as a food additive to supplement iodine intake iniodine deficient regions.



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Drinking water

9. A study of the mineral contents of mineral, spring, table and spa water inGermany (Willershausen et al., 2000) revealed the potassium content of watervaries widely. The potassium values of mineral water varied between 1.4 mg/land 611 mg/l. Natural spa waters had potassium levels varying from 1.88 mg/l to12830 mg/l.

Licensed medicinal products for oral use

10. Potassium chloride is generally the potassium source used to treat losses due tothe use of certain diuretics, diarrhoea, and other conditions.

11. Eleven medicinal products containing potassium chloride may be sold insupermarkets and other retail outlets, without the supervision of a pharmacist, forthe replacement of potassium lost in acute diarrhoea. Each dose provides 0.3 gpotassium chloride in addition to other constituents including sodium chloride anda carbohydrate source. The products are prepared by dissolving in water. Themaximum permitted strength of potassium chloride in the prepared solution is0.15%. The total daily dose of potassium chloride depends on the amount ofpotassium lost, but the maximum is generally 4.8 g per day.

12. Products for potassium loss caused by other conditions or drug treatment (such asthe use of certain diuretics) are available under the supervision of a pharmacist.

Other uses

13. Potassium chloride is used in fertiliser and plant nutrients.

Intake and exposure

Food

14. In the Dietary and Nutritional Survey of British Adults mean potassium intakeswere 3187 and 2434 mg/d in men and women respectively. The contributionmade by supplements was very small and average intakes including supplementswere similar to average intakes from food only (see Annex 2). In young peopleaged 15-18 years vegetables, potatoes and savoury snacks were the main source ofpotassium in this age group providing over one-third of their average intake.Potatoes and potato products alone provided almost a quarter of total intake (seeAnnex 2). Potassium intake from natural food content and food additives wasestimated to be about 3.3 g K/day (Snyder et al., 1975a).

15. One of the most widely used salt substitutes (Lo Salt) contains 9 mmol K/g.Swales (1991) estimated that an average discretionary salt intake of 2 to 2.5 g/daywould therefore increase a daily potassium intake of 2.5 g by about 0.78 g. Sopkoand Freeman (1977) analysed commercially available salt substitutes and found



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that all had very similar potassium content – that of 10-13 mEq1 of potassium pergram.

16. Most sports drinks contain potassium to replace losses in sweat induced byexercise. However, the losses are small and the amount present in rehydrationdrinks is between 3 - 6mmol/l (0.12 – 0.24g/l) which is similar to the potassiumconcentration of sweat (4 - 8 mmol/l and plasma (3.5 - 4.9mmol/l). There is littleevidence for its inclusion as the losses can normally be replaced by potassium infoods following exercise (Maughan 1998).

Drinking water

17. Under the terms of the Water Supply (Water Quality) Regulations 1989, themaximum level of potassium permitted in UK drinking water is 12 mg/l.

Recommended amounts

18. The Committee on Medical Aspects of Food and Nutrition Policy (COMA) (1991)has set a Reference Nutrient Intake (RNI) of 3500 mg/day (90 mmol/day) formales and females over 15 years old. COMA recommended an increase in theaverage intake of potassium by the adult population to about 3.5 g/day(90mmol/day) (DH, 1994) due to the fact that higher intakes of dietary potassiumare associated with lower blood pressures and fewer strokes, in part mitigating theeffect of sodium (see para 52).

19. In 1992 the European Scientific Committee on Food set a ‘Population ReferenceIntake’ of 3100 mg/day for both sexes from 11 years of age.

20. The NRC (1989) also recommended increasing the daily intake of potassium toabout 3500 mg/day (90 mmol) because of the considerable evidence for thebeneficial effects of potassium on hypertension. These figures would also coverintakes needed during pregnancy and lactation (Navarro and Vaquero, 1999).

21. Navarro and Vaquero (1999) summarised considerations needed forrecommendations on infants’ and children’s’ potassium intakes. They state thatdietary potassium intake must be higher than the amount required at the tissuelevel to allow for urinary, cutaneous and faecal losses, which may be higher inchildren. The authors said that generally nutrient requirements for infants frombirth to 15 weeks of age are estimated on a human milk potassium content basisand hence lower values are possibly obtained. Therefore, intake for infants of thisage should be increased appropriately, to about 78 mg K/100 kcal consumed, thisshould maintain the potassium balance in children of all ages.

22. In the elderly, potassium depletion is common, usually because of dietarydeficiencies and frequent drug therapy. Therefore, it has been suggested (Navarro

1 For potassium 1mEq = 1mM (39mg)



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and Vaquero, 1999) that the minimum satisfactory potassium intake is 2000 to3000 mg/day (51 to 77 mmol/day).

Analysis of tissue levels

23. Measurements of potassium tissue levels can be made by various techniquesincluding flame emission spectroscopy, which is usually used to determinepotassium in biological materials (Macrae et al., 1993). A modern technique formeasuring potassium in biological tissues is electron microprobe X ray analysis,but it is not practical for large samples of food or biological tissue.

24. Dilution of radioactive isotopes of potassium (40K) is a useful way of measuringthe overall content of potassium in a whole organism and also the distribution andconcentrations of potassium in various compartments of the organism/sample(Macrae et al., 1993).

25. Potassium is the third most abundant element in the body (after calcium andphosphorus) and constitutes about 5% of the mineral content of the body(Ensminger et al., 1995). Total body potassium is about 45-55 mmol/kg ofbodyweight (Macrae et al., 1993, Navarro and Vaquero, 1999). Therefore, a 70kg adult man contains about 135 g of potassium.

26. Of the 135 g body burden, approximately 84 g is in the muscle and 15 g is in theskeleton. Potassium is also stored in fat, blood, CNS, intestines, liver, lung andskin (Snyder et al., 1975a).

27. The distribution of potassium between cells is tightly controlled, with only 1.5 to2.5% of total body potassium being found in the extracellular fluid (Agarwal etal., 1994). The extracellular potassium concentration is a function of twovariables: 1). total body potassium content; and 2). the relative distribution ofpotassium between the extracellular and intracellular fluid compartments (Sternset al., 1981).

Interactions

28. There is an inter-relationship between potassium and sodium and variations in thesodium:potassium ratio can affect blood pressure. Excessive sodium intake candeplete the body’s supply of potassium (Ensminger et al., 1995).

29. Magnesium deficiency results in failure to retain potassium, and conversely,excessive levels of potassium may interfere with magnesium absorption(Ensminger et al., 1995).

30. Thallium interacts with potassium in many tissues in the body. Elsenhaus et al.(1991) lists these tissues: mammalian skeletal muscle, heart muscle, smoothmuscle of the uterus, nervous tissue, kidney and red blood cells, frog skin andpurified enzymes. For example, Gehring and Hammond (1967) investigated theinterrelationship between thallium and potassium in rats, dogs and sheep. They



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found that the rate of disappearance of thallium from animals increased as dietarypotassium increased. In dogs, the infusion of potassium increased the renalclearance of thallium and increased the mobilisation of thallium from tissues. TheNa- and K-activated adenosine triphosphatase mechanism can be activated by thesubstitution of thallium for potassium, therefore suggesting that the activetransport mechanism for potassium cannot differentiate between thallium andpotassium.

Absorption

Humans

31. Absorption of dietary potassium is very efficient, with more than 90% of ingestedpotassium being absorbed (NAS, 1980). Phillips and Giller (1973) measured thebalance of fluid and electrolytes in the small bowel by the slow marker perfusionmethod. When dietary intake of potassium was limited to 70 mEq a day, theterminal ileal potassium was 9.3 mEq/day indicating a net absorption by the smallbowel of about 85% of the dietary potassium intake.

32. Absorption rises in almost direct proportion to increasing intake, with faecalpotassium excretion changing only slightly as dietary potassium intakes vary overa wide range (Navarro and Vaquero, 1999).

33. The vast majority of intestinal potassium absorption occurs in the small intestine,with the contribution of the colon being trivial (Agarwal et al., 1994). Absorptionin the human small intestine is thought to take place mainly by passive diffusionin response to electrochemical gradients, reaching equilibrium between plasmaand lumen in the jejunum and ileum. Only the colon (and the distal nephron) canmodify K+ transport in response to variations in potassium status. The proximalcolon secretes K+ via a transcellular pathway, with active K+ uptake mediated by(Na+- K+)-ATPase and passive exit via a conductance pathway. The distal coloncan also both secrete and absorb K+ (Macrae et al., 1993).

34. The potassium form in salt substitutes, potassium chloride, is much more readilyabsorbed by the gastrointestinal tract (GIT) than potassium contained in food.This may have implications for the actual doses of potassium from these saltsubstitutes (Saggar-Malik and Cappuccio, 1993).

Distribution and metabolism/potassium balance

35. The bioavailability of potassium is high, with 90-95% of ingested potassium beingutilised in normal metabolic pathways. This is for two reasons: firstly, potassiumsalts are completely soluble because they are wholly ionic; and secondly, fewdietary components alter the digestive utilisation of potassium (Navarro andVaquero, 1999).

36. Potassium is transported mainly in ionic form in the extracellular liquid. Afteringestion of a meal (steak and water) by humans, the concentration of potassium



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was measured at multiple sites (Fordtran and Locklear, 1966). Polyethyleneglycol (PEG) was included in the water to act as a nonabsorbable volume marker.The PEG concentration increased ten-fold as the meal travelled distally throughthe small intestine because of the water absorption from the meal. As the waterwas being absorbed, the concentration of potassium decreased from about 20mEq/L in fluid aspirated from the duodenum to about 7 mEq/L in fluid aspiratedfrom, the mid-small bowel. Therefore, the duodenum and jejenum can absorbpotassium even more rapidly than water.

37. Since the amount of potassium found in extracellular fluid is so small, even smallshifts in the balance of potassium in and out of the cell can produce large changesin the potassium concentration (Sterns et al., 1981).

38. The metabolism of potassium bromate has been investigated (Fujii et al., 1984)and, when administered orally to rats the bromate was rapidly absorbed from thedigestive tract and partly excreted in the urine within two hours of administration.

Excretion

Animal

39. Experiments in dogs have aided elucidation of the basic mechanisms of renalexcretion of potassium. It has long been known that more potassium is found inthe urine than is filtered at the glomerulus (Mudge et al., 1948, Berliner andKennedy, 1948). This indicated that potassium must be secreted by the renaltubules. Secretion is accomplished by an ion exchange mechanism, in whichpotassium of the tubular cells is exchanged for the sodium of the glomerularfiltrate (Berliner et al., 1950).

Human

40. The mechanism of renal excretion previously elucidated in the dog was found tobe similar in man. Berliner et al. (1950) undertook clearance studies in ‘normal’(hospitalised patients with no evidence of cardiovascular or renal disease, of age20-50 years) humans. The results showed a secretion rate of up to 130 µEqK/minute after large oral doses (5 g) of potassium chloride.

41. The major excretory route is via the kidneys and urine. The amount of potassiumentering the glomerular filtrate each day is about 800 mEq, whereas daily intake isonly about 100 mEq. Therefore, to maintain normal body potassium balance only1/8 of the total daily tubular load of potassium can be excreted (Guyton, 1986).

42. The digestive juices contain relatively large amounts of potassium but most isreabsorbed and therefore loss in the faeces is small (normal faecal potassiumexcretion averaging about 9 mEq/day (Agarwal et al., 1994)). Sweat losses arealso small.



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Function

43. Potassium, together with its close relative sodium, is important in maintainingnormal osmotic pressure within cells. Approximately 98% of the total bodypotassium is located intracellularly, where the concentration can be 30 times thatof the extracellular concentration (Ensminger et al, 1995). The concentration inthe extracellular fluid is a critical determinant of neuromuscular excitability(Sterns et al, 1981).

44. The extracellular and intracellular balance of potassium is maintained by theenzyme K+-exchanging ATPase, found in the plasma membrane of virtually allanimal cells (Navarro and Vaquero, 1999).

45. Potassium is a cofactor for a number of enzymes including glyceroldehydrogenase, mitochondrial pyruvate carboxylase, pyruvate kinase, vitaminB12-dependent diol dehydratase, L-threonine dehydratase, adenosinetriphosphatase and aminoacyl transferase.

46. Potassium is required for the secretion of insulin by the pancreas (Ensminger et al,1995).

47. Potassium is also involved in phosphorylation of creatine, in carbohydratemetabolism and protein synthesis (Ensminger et al, 1995).

Deficiency

48. Potassium deficiency or hypokalaemia is defined as plasma potassiumconcentration below 137 mg/L-1 (3.5 mmol/L-1). Levels of 98 mg/L-1 (2.5mmol/L-1) or less may be associated with severe potassium depletion (total bodypotassium loss) (Macrae et al, 1993). Hypokalaemia may cause rapid andirregular heartbeats, muscle weakness, irritability and occasionally paralysis,nausea and vomiting, diarrhoea and swollen abdomen (Ensminger et al., 1995).

49. It can also induce growth retardation, with pronounced decrease in circulatingsomatomedin C and concomitant inhibition of protein synthesis (Macrae et al,1993).

50. Hypokalaemia can also predispose to hypertension. For example, Krishna et al.(1989) found that young normotensive men on a potassium intake of 390 mg/day(10 mmol/day) were less able to excrete an imposed sodium excess than whenthey had potassium intake of 90 mmol/day. At the same time, their bloodpressures increased.

51. Deficiencies of potassium rarely results from dietary lack, rather, they result fromcrash diets, diarrhoea, diabetic acidosis, vomiting, intense and prolongedsweating, body burns and heavy urine losses induced by diuretic drugs(Ensminger et al., 1995).



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Overview of reported beneficial effects

52. It is clear that potassium exerts a beneficial effect on hypertension, partly becauseof the effect of lowering blood pressure, and partly because of its protective effectagainst vascular damage and stroke (NRC, 1989). Numerous humansupplementation studies have been undertaken in hypertensive patients withpotassium chloride supplements of between 60 and 200 mmol. The majority ofthese have shown a beneficial effect on hypertension (that is a reduction in bloodpressure compared to placebo-treated controls) after potassium supplementation(Khaw and Thom, 1982, MacGregor et al., 1982, Overlack et al., 1983, Kaplan etal., 1985, Mathur et al., 1986, Matlou et al., 1986, Svetsky et al., 1986, Grobbeeet al., 1987, Obel, 1989, Patki et al., 1990, Siani et al., 1991, Fotherby and Potter,1992). However, some of these studies have found no beneficial effects ofpotassium supplementation on hypertension (Grimm et al., 1988, Grimm et al.,1990). None of these studies reported found adverse effects of potassiumsupplementation.

53. For example, Svetsky et al. (1986) used a randomised, double-blind studyassessing blood pressure response to 120 mEq/day oral potassium compared to aplacebo in 101 adults with mild hypertension. Results showed that the bloodpressure in the potassium-treated groups, after adjusting for differences in baselinevalues, had decreased by 3.4/1.8 mmHg more in potassium-recipients whencompared with placebo-recipients. The authors concluded that 120 mEq/day ofmicro-encapsulated potassium chloride was well tolerated and decreased bloodpressure in mild hypertensives.

54. In addition, epidemiological studies (MacGregor et al, 1982; Khaw and Barrett-Connor, 1984, Kaplan et al, 1985, Khaw and Barrett-Connor, 1987) and meta-analyses (Jiang et al, 1999, Cappuccio and MacGregor, 1991) have found that oralpotassium supplements lower blood pressure in humans (in both normotensive andhypertensive people). Epidemiological studies of dietary intake of potassium haveyielded equivocal results. Some have found dietary potassium intake has aninverse association with hypertension (Khaw and Barrett-Connor, 1988, Ascherioet al., 1992). However some epidemiological studies have found no associationbetween hypertension and dietary intake of potassium (Ascherio et al.,1996).

55. A study by the Intersalt Co-operative Research Group (1988) investigated therelationships between 24 hour urinary sodium and potassium excretion andurinary sodium:potassium ratio and the blood pressure of 10,079 men and womenaged 20-59 years from 52 international centres. Confounding variables taken intoconsideration were body mass and alcohol intake. The results showed thatpotassium excretion was negatively and independently associated with bloodpressure of individual subjects after adjustment for sodium excretion, body massindex and alcohol consumption. Also, the urinary sodium:potassium ratio wassignificantly related to the blood pressure in individual subjects.

56. The beneficial effects of potassium supplementation in the form of salt substituteshave also been investigated. For example, Perry (1986) undertook a randomised,cross over study of patients (13 women, 21-76 years old) with mild hypertensionwith a history of diuretic induced hypokalaemia. Three forms of potassium



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replacement were compared: salt substitute; potassium replacement; andpotassium-sparing diuretic. The results confirmed the efficacy of salt substitutesas therapy for Hypokalaemia. However, the authors acknowledge the limitationsof the study as a small number of patients and only women enrolled. In addition,the study was not conducted blind, either to the patients or the investigator.Weiner and Faraci (1979) reported two cases of patients (a 62 year old women anda 59 year old man, both admitted for heart surgery) whose potassium levels hadbeen maintained at therapeutic levels during admittance by the use of saltsubstitutes on hospital food (in addition to appropriate drugs).

57. Animal studies have also shown potassium to have a beneficial effect onhypertension. For example, Tobian et al. (1984) fed Dahl S rats with a dietsupplemented with either 4% NaCl, 4% NaCl and 3.8% potassium citrate, or 4%NaCl and 2.6% KCl for 24 weeks. The added potassium did not reduce bloodpressure but did reduce microscopic renal lesions. Focal tubular dilation wasscored blindly and the KCl treatment group showed a 50% improvement (p <0.001) for renal cortex, 30% improvement (p < 0.001) for outer medulla and a43% improvement (p < 0.001) for renal papilla. Both potassium citrate and KClalso eliminated the thickened walls and the narrowed lumens of the hypertensiverenal arterioles, without decreasing blood pressure.

58. Jansson (1996) listed potassium as an ‘anticarcinogenic’ agent in his review ofpotassium, sodium and cancer. A number of reasons are stated for this: cancer-causing drugs, such as dimethylhydrazine, increased sodium and decreasedpotassium concentration in cells, whereas anticarcinogens, such as indomethacin,have the opposite effect; during ageing, sodium enters the cells and potassiumleaves them and the rates of cancer increase; patients with hyperkalaemic diseases(e.g. Parkinson’s, Addisons) have reduced rates of cancer.

59. Animal studies have also shown abnormalities of kidney development in foetalmice when grown in organ culture with low concentrations of potassium (Crockerand Vernier, 1970). Kidneys from foetal mice grown in organ culture withpotassium concentrations of less than 9 mEq/l (10 to 14 day kidneys) and of lessthan 6 mEq/l (14 to 18 day kidneys) produced abnormal branching, failure ofnephron induction and occasional cystic dilatations of the ureteral bud comparedto those grown in high potassium concentrations (9 to 12 mEq/l). Wilson et al.(1968) found that treatment with teratogenic carbonic anhydrase inhibitors(acetazolamide and ethoxzolamide) gave a sharp decrease in maternal bloodpotassium. However, supplemental dosing with potassium did not prevent thecharacteristic malformations usually produced with these drugs, therefore theteratogenicity cannot be attributed to potassium deficiency.

Toxicity

Human toxicity – see Table 1

Acute Toxicity



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60. Acute human toxicity resulting from ingestion of potassium is not common.However, there are some examples of suicide attempts with potassium chloridetablets. For example, Peeters and Van Der Werf (1998) described epigastric painand vomiting in a 62-year old woman after a suicide attempt with 300 KCl slow-release tablets (representing a dose of 94 g potassium). On admission, the patienthad gastric distension caused by the huge number of pills and a gastroscopyrevealed a severely inflamed stomach. One month later, the necrotic mucosallining had sloughed off but there was tight antrial stenosis which necessitatedpartial gastric resection.

61. Illingworth and Proudfoot (1980) reported a case series of poisonings from slow-release potassium tablets. One 58-year old women took about 20 tablets ofbendrofluazide 2.5 mg with slow release KCl 630 mg and some phenylbutazone.She vomited after 30 minutes and became sweaty and breathless. Five hours afteringestion she was in left ventricular failure with cyanosis and widespread lungcrepitations. Gastric lavage recovered some tablet fragments and the patientsurvived, remaining nauseaous for three days. A 26-year old man took 10 tabletsof Distalgesic and about 40 slow-release KCl 600 mg. He rapidly vomited and onadmission was conscious with a regular pulse. However, during gastric lavage hesuffered cardiac arrest with asystole and resuscitation was unsuccessful.

62. Acute human toxicity from potassium can also result from accidentalingestion/overdose. For example, Wetli and Davis (1978) described two cases ofaccidental potassium supplement poisoning. First, a 32 year old women who hadbecome hypokalaemic was given slow-release KCl which she tookindiscriminately whenever weak or tired. Diarrhoea developed and despite beingadvised to stop taking the tablets, she was found dead the next day. Autopsyshowed she had ingested 47 KCl tablets. The occular fluid potassium level (18hours postmortem) was 10.8 mEq/L. Secondly, a 2-month old boy was given1500 mg KCl with breast milk twice a day for two days. A few hours after thefirst dose on the second day, the baby became listless and cyanotic and he stoppedbreathing. Serum K+ remained high until death 28 hours later. The authorsconcluded that the cases show people with compromised renal or cardiac functionmay die of accidental oral overdose of KCl.

63. In recent years, with the increasing use of salt substitutes containing potassiumchloride, there have been a number of deaths associated with the ingestion of largeamounts of salt substitute. For example, Restuccio (1992) describes the case of a53 year old white male who presented with chest tightness, nausea and vomitingand diarrhoea. The patient’s only medication was imipramine for depression buthe reported that he had been ‘drinking beer’ and using ‘Nu Salt’ earlier in theevening. He died of hyperkalaemia with resultant asystole. Autopsy revealed thepatient had ingested 21 g of Nu Salt, representing an oral bolus of 283 mmol ofpotassium. The authors concluded that the death was unusual because oralpotassium doses in this range have not been documented to cause arrythmia.However, it could be that whilst hypokalaemic patients must first replenish largebody stores before serum potassium returns to normal, in eukalaemic patients,body stores are normal and so it takes much less potassium to make themhyperkalaemic.



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64. An 8-month old infant was presented in hospital with stiffness, ‘rolling back’ ofthe eyes and difficulty in breathing (Kallen et al., 1976). The child had had a mildupper respiratory tract infection and this had caused emesis and diarrhoea. Thechild was found to have severe hyperkalaemia with blood potassium at 10.2mEq/L and it was later estimated the child had been fed up to 17.2 g of Morton’ssalt substitute by a sibling (equivalent to dose of about 26 mEq K/kg).

65. Keith et al. (1941) investigated the effect of large oral doses of potassium inhumans. Seven normal subjects ingested 12.5 to 17.5 g of KCl or bicarbonate andafter absorption, the clearances were estimated (urine samples, beforeadministration and then every half hour or hour). In five of the subjects,potassium clearance rose from normal fasting levels of 6-14 c.c. to 41-105 c.c.,but inulin levels remained within the normal range (inulin is a carbohydrate ofhigh molecular weight used to test kidney function). However, in two subjectsdisturbed renal excretion was seen (potassium clearance and concentration ofpotassium in the serum rose, but at the same time caused a decrease in inulin andurea clearance to less than normal levels). The decreased inulin clearanceindicates decreased glomerular filtration. From the results of the seven subjects, itappears a single dose of a potassium salt containing 80 to 100 mg K/kg bodyweight can be toxic. The authors concluded that there is considerable variation asto what constitutes a toxic dose of potassium salt. Due to discomfort in theepigastrium experienced by the subjects after ingestion of these large doses ofpotassium salts, the authors also investigated the effect of potassium on sensorynerve endings. Two healthy volunteers had intravenous injections of 1% solutionof potassium chloride, which caused severe burning pain. One of the previoussubjects (ingestion of 12.5 g KCl) had experienced parasthesia in his hands andfeet.

Sub-chronic Toxicity

66. Snyder et al. (1975b) describe the case of a 75 year old women admitted tohospital for progressive shortness of breath over four weeks. She had a history ofmyocardial infarction two years previously and was asymptomatic at homefollowing her usual ‘low salt diet’. However, 6 weeks before admission she begantaking LITE-SALT ad libitum. Since then, ankle oedema and shortness of breathdeveloped. She arrived in hospital with serious heart failure but responded well todiuretic therapy and was discharged asymptomatic.

67. A 31 year old body builder collapsed with a myocardial infarction (Appleby et al,1994). His serum potassium was 6.7 mmol/l and he had a run of ventriculartachycardia. He had been taking anabolic sterolds, amphetamines, frumil(frusemide and amiloride) and supplements of 5g/day potassium. The authorsconsidered that the hyperkalaemia was sue to the combination of potassiumsupplements and the potassium-sparing diuretic frusemide, this accounted for thetenting of T-waves seen on electrocardiogram (ECG) and may have contributed tothe tachycardia.

68. Busuttil (1990) reported 5 case of sudden cardiac death in young people followingimmediate exercise and suggested that hyperkalaemia may have contributed.



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Serum potassium rises during exercise and may reach 6.8 mmol/l compared to 5mmol/l, the upper limit of the normal range. Elevated potassium can cause animbalance of the transmembrane potassium gradient and a lowering of restingpotential across muscle cell membranes with a consequent impairment ofmembrane excitability. Increased extracellular potassium also causes shorteningon the cardiac action potential and an increased velocity of repolarization, with areduction of the Q-T interval and tenting of the T wave of ECG. Further loweringof the resting membrane potential causes a decreased upstroke velocity of theaction potential and reuslts from an even more elevated potassium ion level and aslowing on intraventricular conduction, and widening of the QRS complex on theECG. The atrial muscle is particularly sensitive to an alteration in extracellularpotassium and to its depolarisation effects but the SA and AV nodes are relativelyresistant at higher concentrations of potassium. The P-R interval widens and anirregular cardiac rhythm supervenes with eventual asystole.

Chronic Toxicity

69. Chronic toxicity has also been seen with slow-release potassium tablets. Bronsonand Gamelli (1987) describe the case of a 68-year old women who had hadhypertension for several years and was taking hydrochlorothiazide 50 mg/day plustwo 10 mEq wax-matrix KCl tablets chronically. The subject began experiencingnausea and abdominal cramp after meals, on admission she was found to have a 1cm long segment of stenosis of the small bowel in the midjejunum. It wasconcluded that the initial injury induced by the KCl was probably focal ulcerationwith subsequent oedema, which further contributed to injury by trappingsubsequent tablets at the site of injury.

Neurotoxicity

70. No data identified.

Carcinogenicity


Genotoxicity


Human supplementation studies

73. There have been numerous potassium supplementation studies because of theassociation of increased potassium intake with decreased risk of hypertension andheart disease. The majority of these studies have shown beneficial effects of



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potassium supplementation on hypertension (see paragraph 52). In these studies,where doses of up to 200 mM potassium are given for periods ranging from 4days to several years adverse effects are not generally reported as havingoccurred. However in many of the studies, it is not clear whether such effects werespecifically looked for. In a double blind study by Grimm et al (1988) groups ofmales aged 45-68y were given 96mM (3.7g) K/day or a placebo. Adverse effectsreported after 12 weeks included stomach pains, nausea and vomiting, diarrhoeaand bright red blood in the stools. The incidence was stated to be similar in thetwo treatment groups. The study was continued for 2 years (Grimm et al 1990)with similar side effects being reported at comparable rates between the twotreatment groups. It was stated that no adverse effects were apparent in 18 subjectsaged 66-79 given 60 mMol KCl/day (2.34g K) in an elixir or placebo for 4 weeks(Fotherby and Potter, 1992). In a double blind study conducted by Siani et al(1987) no adverse effects were reported in subjects aged 21-61 given 48 mM/day(1.9g K) potassium supplements.

74. As noted earlier, potassium salts have been associated with ulceration of the gut,the severity of this effect is dependent on factors such as the formulation of thetreatment and gut transit time. A number of human supplementation studies haveinvestigated this effect. McMahon et al. (1982) investigated the effect of KClsupplementation on the gastrointestinal tracts of 48 healthy young men. Theyfound that wax-matrix KCl preparations (32 mmol K+, 2.4 g KCl (1.25g K) threetimes a day for seven days – total daily dose 3.7g K) gave considerable mucosalpathology, with erosions, gastric ulcers, inflammatory lesions and bleeding atendoscopy. A microencapsulated form of KCl also caused mucosal lesions butsignificantly (P < 0.05) more were seen after treatment with wax-matrix KCl.These findings were confirmed by a further study, in which 225 healthy malesubjects received one of the following treatments: wax-matrix KCl tablets; KClliquid; microencapsulated KCl; a potassium-sparer; placebo for one or two weeks(McMahon et al., 1984). The doses used ranged from 24-96 mM K/day. Uppermucosal injury (erosions and ulcerations) was more frequent after wax-matrix KCltreatment. It was noted that gastro-intestinal symptoms were mild and did notcorrelate with endoscopic evidence of lesions. In hypertensive subjects treatedwith 40-80 mM (1.56-3.12 g K/day) slow-release wax-matrix KCL for an averageof 21 months 6/9 subjects had developed erosions compared with 1/9 matchedcontrols. Following 7 days of inpatient treatment, one of the 6 subjects witherosions developed an ulcer and a further 2 placebo subjects developed erosions.The authors concluded that cyto-adaptation to KCl treatment did not seem tooccur.

75. In addition, epidemiological studies have also indicated an association betweenpotassium chloride supplements and GIT disturbance (Lawson, 1974), small-bowel ulceration (Leijonmarck and Raf, 1985), erosions and ulcerations(McMahon et al., 1984), oesophagus, stomach and duodenum erosions(McLoughlin, 1985). Association of potassium chloride supplementation andoccurrence of hyperkalaemia has also been made, both through case reports (Perezet al., 1984, Leijonmarck and Raf, 1985) and through epidemiological studies(McMahon et al., 1982, doses varied from 32 mEq to 80 mEq, usually taken threetimes a day).



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Adverse drug reactions

76. Suspected adverse reactions to medicinal products are reported to the Committeeon Safety of Medicines/Medicines Control Agency. Many factors influence thenumber of reports received, and in most situations there is considerable "under-reporting" of reactions. Most of the adverse reactions reported relate to productsthat also contain other constituents, and may not therefore be attributable topotassium. Single constituent potassium chloride products are generally liquid oreffervescent preparations and only associate with a low number of adversereactions which show no trend or pattern to indicate a particular problem. Slow-release potassium chloride tablets are available when the liquid or effervescentpreparations are not tolerated, but they have been associated with a range ofgastrointestinal disorders including upper gastrointestinal ulceration andperforation, and related deaths.

Vulnerable groups

77. Infants are vulnerable to excessive potassium because their kidneys are immature.

78. In the elderly, depletion or excess of potassium is frequent. Saggar-Malik andCappucio (1993) state that although no adverse effects have been reported withthe use of high potassium diets in healthy people, increasing dietary potassium inthe elderly must be considered with caution.

79. Groups vulnerable to potassium toxicity are those with pre-existinghyperkalaemia, which can include people with renal disease, adrenalinsufficiency, acidosis, insulin deficiency, or digitalis intoxication. In addition,certain drugs predispose to hyperkalaemia, including potassium-sparing diuretics,β-adrenergic blockers, ACE inhibitors (Ray et al., 1999), NSAID’s, argininehydrochloride and succinylcholine.

Genetic groups

80. None identified.

Animal toxicity

Acute toxicity- see Table 2

81. The acute toxicity of potassium has been investigated in animals. Neathery et al.(1979) orally infused male Holstein calves (260 kg) with different dose levels(0.29, 0.58, 1.15, 1.73, 2.31 and 2.88 g K/kg bw) potassium in three litres ofwater. This was followed by a further three litres of water (controls received sixlitres of water). Animals which received potassium 1.15 g K/kg body weight andabove showed symptoms of breakdown of potassium homeostasis (changes inacid-base balance, respiratory and heart rates, hyperkalaemia and hypernatremia).



16

Three of five animals given 1.73 g K/kg, three of four given 2.31 g K/kg and theanimal given 2.88 g K/kg body weight died.

82. The effect of KCl has also been investigated in Wistar albino rats (Boyd andShanas, 1961). KCl was given by stomach tube in doses of 2.1, 2.4, 2.7, 3.3, 3.6and 3.9 g/kg body weight, with each dose dissolved in distilled water and given involume of 20 ml/kg body weight (on an empty stomach). The LD50 wascalculated to be 3.02 ± 0.14 g/kg body weight. Death was from respiratory failure(with or without convulsion) accompanied by gastroenteritis, dehydration of mostorgans and renal tubular necrosis.

83. The toxicity of potassium chloride and potassium chlorate was compared withboth the toxicity of other chloride and chlorate salts (sodium, calcium andmagnesium) and the toxicity of the salt alone by administering solutions of thesesalts ‘per os or injecting them intraperitoneally’ (Ulrich and Shternov, 1929).Albino rats, rabbits, guinea pigs and cats were used. The results showed thatpotassium chlorate is less toxic than potassium chloride.

84. Dietary administration of potassium may give more relevant results. Drescher etal. (1958) studied the effects of excessive potassium intake upon the bodypotassium stores in male Sprague Dawley rats (150-200 g). Control animalsreceived about 7 g of rat chow per 100 g body weight per day for three days,giving about 1.6 mEq K and 0.8 mEq Na/g body weight/day. ‘Potassium loaded’rats were allowed 6-7 g of the same feed in powdered form to which was added asolution containing 3.54 mEq of potassium, 2.66 mEq chloride and 0.88 mEqbicarbonate per ml for three days. Daily feed consumption and thus potassiumintake was estimated to the nearest gram. Toxic signs (as measured byelectrocardiographic changes or elevated plasma potassium concentrations) werenot seen in rats until the ingested intake of potassium was greater than 25.6mEq/100 g. Above this level, half the animals died with signs of potassiumintoxication within three days. The surviving half had a pathologic increase inplasma potassium concentration and characteristic electrocardiographic changesbut no significant change in total carcass potassium concentration.

85. The acute oral toxicity of KCl tablets has also been investigated (Diener et al.,1965). Rhesus monkeys (Macaca mulata) were medicated twice daily for fourand a half days by tablets (either placebo, KCl, thiazide, KCl-thiazide tablets orenteric-coated forms of the tablets) being placed at the back of the mouth and thenliquids administered by stomach tube. Treatment with KCl tablets resulted ingross intestinal lesions whereas the placebo and enteric-coated KCl tablets treatedmonkeys had no ulceration. The severity of the lesions produced by the KCltablets did not differ significantly from those produced by the tablets containingKCl and thiazide together. A direct relationship between the amount of Kingested and the severity of lesions produced was also obtained in the experiment.Additionally, ulceration usually occurred where the greatest amount of KCl wasreleased from the tablet.

86. The acute toxicity of potassium bromate has been investigated in male F344 rats(Kurata et al., 1992). Single intragastric doses of KBrO3 were given to male F344rats at dose levels of 0, 50, 300, 600 or 1200 mg/kg body weight. All rats treated



17

with 1200 mg KBrO3/kg and 4 of 5 rats treated with 600 mg KBrO3/kg diedwithin 24 hours of dosing. The remaining animals survived until sacrifice fourweeks later. Of the rats found dead, necrosis of the proximal tubules wasobserved in the kidneys. In the surviving rats given 300 mg KBrO3/kg basophilicregenerative tubules and focal accumulation of eosinophilic droplets in theproximal tubules were seen, but not in the untreated control group or the groupreceiving 50 mg KBrO3/kg.

87. The acute oral toxicity of potassium iodates has been investigated by Webster etal. (1966). Minimum lethal dose for potassium iodate (administered orally ingelatin capsules to eight fasted dogs) was estimated to be 200-250 mg/kg. Emesisoften occurred at these levels but when this was prevented by administration ofmorphine, symptoms of anorexia and prostration occurred and death often ensued.Pathological changes present at these high doses were fatty changes in the viscera,necrotic lesions in the liver, kidney, and mucosa of the GIT and urinary bladderand retinal degeneration.

Sub-chronic toxicity

88. Til et al. (1988, 1997) investigated the toxicity of potassium nitrite (KNO2) andconcluded that the sub-chronic toxicity (90 day) seen in Wistar rats (hypertrophyof the adrenal zona glomerulosa) treated with KNO2 in drinking water was not dueto the increased intake of potassium but was due to the nitrate.

89. The sub-chronic toxicity of potassium nitrite has been investigated by Til et al. Ina 1988 study, 6 week old Wistar rats were treated with potassium nitrite(concentrations not specified) in their drinking water for 90 days. There were nodeaths but hypertrophy of the adrenal zona glomerulosa was found in all treatedgroups (increased incidence and severity with increasing levels of nitrite in thewater). However, the authors concluded that the findings could not be attributedto the potassium in the drinking water solution since the potassium concentrationswere equal in all test groups and not found in a 2630 ppm potassium controlgroup.

90. A further study (Til et al., 1997) investigated the effects of nitrite, this timeincluding a sodium nitrite treatment group to rule out the possibility that effectsseen were due to the effect of potassium. Male and female Wistar rats (6 weeksold) were treated with either sodium nitrite or potassium nitrate for 90 days.Results showed slight hypertrophy of the adrenal zona glomerulosa with levels of100 mg KNO2/litre and higher. This could not be attributed to an increased intakeof K+ or Na, since the hypertrophy was not observed in the KCl control nor theNaCl control group.

91. Webster et al. (1959) studied the sub-chronic toxicity of potassium iodate byadministering doses of 0, 0.05, 0.10, 0.25, 0.50 and 0.75% KIO3 in the drinkingwater of female white Swiss mice for 15-16 weeks. Three mice in the 0.75%group died during the first week. In addition, experiments on guinea pigs (young,coloured guinea pigs of the Beltsville strain) were undertaken, giving 0, 0.05 and0.5% KIO3 in the drinking water for four weeks. Increased haemolysis was seen



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in the 0.25% KIO3 and higher concentration mouse groups. However, nosignificant pathologic changes were found except for some haemosiderindeposition in the renal tubules of a few mice in 0.25% and nearly all in 0.50% and0.75% KIO3 groups, attributable to haemolysis by iodate. The guinea pigsremained in good health for the four week period and showed no significantalterations in haematological parameters and no gross or microscopic changesattributable to potassium iodate.

92. Webster et al. (1966) undertook subsequent studies in four male and femalemongrel dogs. Repeated doses of potassium iodate at levels of 6-100 mg/kg weregiven in milk or by capsule for several months. Emesis followed by anorexia andlistlessness was seen in the four dogs but in the last 3-7 weeks of the experimentalperiod the weight and appetite stabilised at doses 60-90 mg/kg. Pathologicalchanges noted after treatment included haemosiderin in the spleen, liver andkidneys and mild to moderate inflammation of the mucosa of the gastrointestinaltract. The authors concluded that the maximum dose level for sub chronicexposure would be less than 60 mg/kg.

Chronic toxicity

93. Fisher et al. (1979) fed Wistar rats with five different bread-based diets (madefrom untreated flour, flour treated with 50 or 75 ppm potassium bromate, or withone of two mixtures of potassium bromate and other widely used food additives)for 104 weeks. Potassium bromate appeared to have no adverse effect on survivalrates in rats, actually giving a dose-related improvement in survival (P < 0.05)among female rats. There were no differences in any haematological parameters,organ-weight data or histopathological examination of tissues among control andtreated groups. The only possible adverse effect seen in treated rats wassignificantly lower blood-sugar values in both males and females in groups 50 and75 ppm potassium bromate compared to the controls, at month 24 only. However,the authors dismiss this result as insignificant because Ginnocchio et al. (1979)found the opposite results.

94. In this study (Ginnocchio et al., 1979) mice (of the Theiller’s Original strain) werefed one of five bread-based diets, where the bread was prepared from eitheruntreated flour (control), 50 or 75 ppm potassium bromate treated flour, or twomixtures of commonly used additives (bromate, ascorbic acid, benzoyl peroxideand chlorine dioxide) for 104 weeks. Anaemia was prevalent in males of allgroups including the controls and in females at 18 months. There were no dose-related differences in blood biochemistry in males, however females had a dose-related increase (P < 0.01) in blood-glucose levels observed at one and 12 monthsbut not at 18 months. Renal concentration and dilution tests and urine analyseswere all normal. When expressed relative to body weight, the pituitary, brain,kidney and thyroid weights of test groups were increased significantly and in adose-related manner when compared to the control groups. Lesions andabnormalities seen in histopathological examination were those commonly seen inaged mice and were similar in control and treated animals. Therefore, there wasno evidence that potassium bromate increased the incidence of neoplasms in mice(this study) or rats (Fisher et al., 1979).



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Neurotoxicity


Carcinogenicity

96. There are no data on the carcinogenicity of potassium itself. However, thecarcinogenicity of potassium bromate has been widely investigated in animalstudies, with equivocal results. Some studies have found that oral administrationof potassium bromate (in drinking water) is carcinogenic in rats, inducing renalcell tumours, thyroid follicular tumours and mesotheliomas on the tunica vaginalistestis in a dose-dependent manner (DeAngelo et al., 1998). Dose-dependentincreases in renal cell tumours have also been seen in additional studies withpotassium bromate (Kurokawa et al., 1983, 1986a, 1986b). Bromate rather thanpotassium is believed to be the active component.

97. However, some studies have given negative carcinogenicity results for potassiumbromate in animals. Subcutaneous injections of potassium bromate to newbornrats and mice (doses of 12.5 to 200 ml/g body weight to mice and of 12.5 to 100mg/kg body weight to mice either as a single injection 24 hours after birth or asfour weekly injections for four weeks) gave no significant increase in KBrO3-related incidences of tumours in any organ, except a slight increase in combinedincidences of lymphomas and leukaemias in male mice given 400-800 mgKBrO3/kg body weight (Matsushima et al., 1986).

98. Kurata et al. (1992) also found no evidence for the tumour-initiating ability ofKBrO3 in F344 rats when administered as a single intragastric dose (300 mg/kgbody weight) followed 2 weeks later by a diet containing 4000 ppm barbitalsodium or just basal diet, until the end of 104 weeks. Barbital sodium and basaldiet control groups were included in the experiment. The results showed thatdysplastic tubular foci neither significantly increased in incidence nor progressedto adenoma/carcinoma by continuous treatment with barbital sodium after a singleexposure to KBrO3.

99. The carcinogenicity of potassium iodide (KI) has been investigated in male andfemale F344/DuCrj rats (Takegawa et al., 2000). The rats were given potassiumiodide in their drinking water (concentrations 1, 10, 100 or 1000 ppm for 104weeks. In addition, a two-stage carcinogenicity study was undertaken, at 0 or1000 ppm for 83 weeks following a single injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN). The results in both males and femalesshowed follicular dilatation in the thyroid in the 10, 100 and 1000 ppm KIdrinking water group, but these changes were not neoplastic. The no effect levelwas determined as < 10 ppm. Neither focal hyperplasias, adenomas norcarcinomas derived from the follicular epithelium were increased despite thetreatment with KI for 2 years. However, squamous cell carcinomas were inducedin the salivary glands of the 1000 ppm KI drinking water group. In the two-stagecarcinogenicity study, thyroidal weights and the incidence of thyroid tumours



20

derived from the follicular epithelium were significantly increased in the DHPNwith KI group as compared with the DHPN alone group. The authors concludedthat these results suggested excess KI has a thyroid tumour-promoting effect butKI per se does not induce thyroid tumours in rats. As with bromate, iodide ratherthan potassium is thought to be the active component, via its effects on thyroidmetabolism.

100. Potassium has been studied for its promoting ability in carcinogenicity. Manyreports have linked increased urinary Na+ and/or K+ level and urinary alkalinity tothe development of urothelial hyperplasia and urinary bladder tumour promotion(Fukushima et al.,1986, Lina and Woutersen, 1989, Shibata et al., 1989). Toinvestigate this further, Lina et al. (1994) treated five week old male and femaleWistar rats with diets supplemented with 2% or 4% potassium hydrogen carbonateor with 3% KCl. Results showed that the feeding of potassium hydrogencarbonate gave alkalinuria and kaliuresis and resulted in simple epithelialhyperplasia and, after prolonged feeding, in papillary/nodular hyperplasia,papillomas and transitional-cell carcinomas of the urinary bladder. Feeding ofpotassium chloride gave only a slight increase in proliferative urothelial lesions.The authors concluded that potassium hydrogen carbonate is able to induceurinary bladder cancer without prior initiation by another chemical but KCl is onlya weak tumour promotor and could only induce a few (pre)neoplastic lesions.

Genotoxicity

In vitro

101. Parsons and Chipman (2000) investigated the effect of KBrO3 in isolated calfthymus DNA, human white blood cells and a rat kidney epithelial cell line (NRK-52E). The results showed that KBrO3 did not increase levels of 8-oxodeoxyguanosine (8-oxodG) in calf thymus DNA at concentrations up to 1.5mM. However, there was a dose-dependent increase in 8-oxodG in the presenceof both KBrO3 (0-1.5 mM) and GSH (0.5 mM). When GSH was substituted byN-acteylcysteine (0.5 mM) a similar dose-dependent profile was seen but the useof other reducing agents (including other thiols) in combination with KBrO3 didnot significantly increase the levels of 8-oxodG. KBrO3 induced DNA strandbreakage in both human white blood cells (treated with 5 mM KBrO3 for 15minutes) and rat kidney epithelial cells (treated with 1.5 mM KBrO3 for 15minutes). DNA oxidation was not evident when KClO3 (potassium chlorate) orKIO3 were tested instead of KBrO3. The results show that KBrO3-induced DNAdamage is largely dependent upon access to intracellular GSH.

102. KBrO3 was also found to be mutagenic in the Ames test (but not in achromosome aberration test using fibroblast cell line, CHL (Ishidate andYoshikawa, 1980).

In vivo

103. Kasai et al. (1987) used 5-week old F344 rats and gave them singleintragastric administrations of KBrO3, NaClO and NaClO2 at doses of 400, 900



21

and 250 mg/kg body weight, respectively. The liver and kidneys were thenextirpated 1, 3, 6, 12, 24 and 48 hours after treatment and 8-hydroxydeoxyguanosine (8-OH-dG) formation in DNA were quantified. In thekidney the 8-OH-dG in the DNA increased up to 6 residues/105 dG 24 hours afterKBrO3 administration. The results showed a positive correlation betweenformation of (8-OH-dG) in DNA and KBrO3 carcinogenesis and confirmed theinvolvement of oxygen radicals in the carcinogenic process. KBrO3 was alsofound to be mutagenic in a micronucleus test in 8-week old male ddy mice(Hayashi et al, 1988).

Reproductive toxicity


Mechanisms of toxicity

105. The mechanism of potassium bromate carcinogenicity has been widelyinvestigated. It has been found to cause lipid peroxidation in the kidney andsubsequently produces 8-hydroxydeoxyguanosine (8OHdG) in kidney DNA(Kurokawa et al., 1987, Sai et al., 1992).

Regulatory considerations

106. There is no Recommended Daily Allowance in the Food LabellingRegulations for potassium. The Infant Formula and Follow-on FormulaRegulations 1995 set a maximum level for potassium of 145mg/100kcal. TheProcessed Cereal-based Foods and Baby Foods for Infants and Young ChildrenRegulations recommend a maximum potassium content of 160mg/100kcal of thefood as sold. The Foods Intended for use in Energy Restricted Diets for WeightReduction Regulations (1997) recommend that whole diet products shouldprovide 3100 mg potassium and meal replacements 930 mg.

Existing recommendations on maximum intake levels

107. The Committee on Medical Aspects of Food and Nutrition Policy concludedthat intakes above 450 mmol (17.6g) may induce symptomatic hyperkalaemia insome individuals and would represent a threshold for acute toxicity but suchamounts would only be achieved by supplementation (DH, 1991). Usual dietaryintakes are unlikely to cause toxicity.

Existing recommendations on maximum supplementation levels.

108. None identified.



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Summary

109. Potassium is not found as a pure metal in nature but is always combined withother substances, the most common form being potassium chloride. Rich sourcesof potassium include milk, fruit and vegetables, fish, shellfish, chicken and turkey.Potassium compounds used in foods as preservatives include potassium bromate,potassium nitrite and potassium nitrate. Potassium chloride is used extensively in“salt substitutes” as an alternative to sodium chloride.

110. 90% of ingested potassium is absorbed, with the vast majority of absorptiontaking place in the small intestine. Bioavailability of potassium is also high, with90-95% of ingested potassium being utilised in metabolic pathways. The majorexcretory route of potassium is via the kidneys in urine.

111. Potassium functions in the body to maintain osmotic pressure within cells. Italso acts as a cofactor for a number of enzymes, aids secretion of insulin by thepancreas and is involved in carbohydrate metabolism and protein synthesis.

112. Substantial evidence exists to show potassium has a beneficial effect uponhypertension, lowering the blood pressure and having a protective effect againstvascular damage and stroke. This has been shown by numerous epidemiologicalstudies and human supplementation studies.

113. However, human supplementation studies have also shown some adverseeffects of potassium supplementation – namely the risk of hyperkalaemia invulnerable groups and gastrointestinal toxicity. The major risks of KCl treatmentare hyperkalaemia, cardiac arrest and oesophageal and small bowel ulceration(Saggar-Malik and Cappucio, 1993). There is no evidence for neurotoxicity,carcinogenicity or genotoxicity of potassium in humans.

114. The acute and sub-chronic toxicity of potassium has been investigated inanimals, mainly in the form of potassium chloride. The dietary administration oflarge doses of potassium results in death due to electrocardiograph abnormalitiesand cardiac arrest.

115. The carcinogenicity of potassium has not been investigated. However, thecarcinogenicity of potassium bromate has been investigated widely and hasyielded equivocal results. Some studies have shown potassium bromate can dose-dependently induce renal cell tumours, thyroid follicular tumours andmesotheliomas on the tunica vaginalis testis. However, other studies have shownnegative results for the carcinogenicity of potassium bromate. Potassium bromatehas also been found to be mutagenic in both in vitro and in vivo test systems(human and animal). Potassium chloride has been found to be a weak tumourpromotor, only inducing a few neoplastic changes in rats fed diets supplementedwith potassium chloride.



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Ishidate, M. and Yoshikawa, K. (1980). Chromosome Aberration Tests with ChineseHamster Cells In Vitro With and Without Metabolic Activation – A ComparativeStudy on Mutagens and Carcinogens. Archives of Toxicology Suppl. 4, 41-44.

Jansson, B. (1996). Potassium, Sodium, and Cancer: A Review. Journal ofEnvironmental Pathology, Toxicology and Oncology 15, 65-73.

Jiang, H. E. and Whelton, P. K. (1999). What is the Role of Dietary Sodium andPotassium in Hypertension and Target Organ Injury? The American Journal of theMedical Sciences 317, 152-159.



26

Kallen, R. J., Riegler, C. H. L., Cohen, H. S., Sutter, M. A. and Ong, R. T. (1976).Near-Fatal Hyperkalaemia Due to Ingestion of Salt Substitute by an Infant. Journal ofthe American Medical Association 235, 2125-2127.

Kaplan, N. M., Carnegie, A., Raskin, P., Heller, J. A. and Simmons, M. (1985).Potassium Supplementation in Hypertensive Patients with Diuretic-InducedHypokalaemia. The New England Journal of Medicine 312, 746-749.

Kasai, H., Nishimura, S., Kurokawa, Y. and Hayashi, Y. (1987). Oral Administrationof the Renal Carcinogen, Potassium Bromate, Specifically Produces 8-Hydroxydeoxyguanosine in Rat Target Organ DNA. Carcinogenesis 8, 1959-1961.

Keith, N. M., Osterberg, A. E. and Burchell, H. B. (1941). Some Effects ofPotassium Salts in Man. Annals of Internal Medicine 16, 879-892.

Khaw, K. T. and Thom, S. (1982). Randomised Double-Blind Cross-Over Trial ofPotassium on Blood-Pressure in Normal Subjects. The Lancet 2, 1127-1129.

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Khaw, K. T. and Barrett-Connor, E. (1987). Dietary Potassium and Stroke-Associated Mortality: A 12-Year Prospective Population Study. The New EnglandJournal of Medicine 316, 235-240.

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Kurokawa, Y., Hayashi, Y., Maekawa, A., Takahashi, M., Kokubo, T. and Odashima,S. (1983). Carcinogenicity of Potassium Bromate Administered Orally to F344 Rats.JNCI 71, 965-972.

Kurokawa, Y., Takayama, S., Konishi, Y., Hiasa, Y., Asahina, S., takahashi, M.,Maekawa, A. and Hayashi, Y. (1986a). Long-Term In Vivo Carcinogenecity Tests ofPotassium Bromate, Sodium Hypochlorite, and Sodium Chlorite Conducted in Japan.Environmental Health Perspectives 69, 221-235.

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27

Kurokawa, Y., Takamura, N., Matsuoka, C. Imazawa, T., Matsushima, Y., Onodera,H. and Hayashi, Y. (1987). Comparative Studies on Lipid Peroxidation in theKidney of Rats, Mice and Hamsters and on the Effect of Cysteine, Glutathione, andDiethylmaleate on Mortality and Nephrotoxicity After Administration of PotassiumBromate. Journal of the American College of Toxicology 6, 489-501.

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28

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Neathery, M. W., Miller, W. J., Whitlock, R. H., Genrty, R. P. and Allen, J. C.(1979). Potassium Toxicity and Acid-Base Balance from Large Oral Doses ofPotassium to Young Calves. Journal of Dairy Science 62, 1758-1765.

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Overlack, A., Muller, H. M., Kolloch, R., Ollig, A., Moch, B., Kleinmann, R., Kruck,F. and Stumpe, K. O. (1983). Long-Term Antihypertensive Effect of Oral Potassiumin Essential Hypertension. Journal of Hypertension 1 (suppl 2), 165-167.

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Perry, R. S. (1986). Salt Substitute as Potassium Replacement in HypertensivePatients. Clinical Pharmacy 5, 156-159.



29

Phillips, S. F. and Giller, J. (1973). The Contribution of the Colon to Electrolyte andWater Conservation in Man. Journal of Laboratory and Clinical Medicine 81, 733-746.

Ray, K. K., Dorman, S. and Watson, R. D. S. (1999). Severe Hyperkalaemia due tothe Concomitant Use of Salt Substitutes and ACE Inhibitors in Hypertension: APotentially Life Threatening Interaction. Journal of Human Hypertension 13, 717-720.

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Saggar-Malik, A. K. and Cappuccio, F. P. (1993). Potassium Supplements andPotassium-Sparing Diuretics: A Review and Guide to Appropriate Use. Drugs 46,986-1008.

Sai, K., Uchiyama, S., Ohno, Y., Hasegawa, R. and Kurokawa, Y. (1992).Generation of Active Oxygen Species In Vitro by the Interaction of PotassiumBromate with Rat Kidney Cells. Carcinogenesis 13, 333-339.

Shibata, M., Tamano, S., Kurata, Y., Hagiwara, A. and Fukushima, S. (1989).Participation of Urinary Na+, K+, pH and L-Ascorbic Acid in the ProliferativeResponse of the Bladder Epithelium After the Oral Administration of Various Saltsand/or Ascorbic Acid to Rats. Food and Chemical Toxicology 27, 403-413.

Siani, A., Strazzullo, P., Giacco, A., Pacioni, D., Celentano, E. and Mancini, M.(1991). Increasing the Dietary Potassium Intake Reduces the Need forAntihypertensive Medication. Annals of Internal Medicine 115, 753-759.

Snyder, W. S., Cook, M. J., Nasset, E. S., Harhausen, L. R., Howells, G. P. andTipton, I. H. (1975a). International Commission on Radiological Protection. Reportof the Task Group on Reference Man. New York. ICRP Publication 23.

Snyder, E. L., Dixon, T. and Bresnitz, E. (1975b). Abuse of Salt ‘Substitute’. TheNew England Journal of Medicine 292, 320.

Sopko, J. A. and Freeman, R. M. (1977). Salt Substitutes as a Source of Potassium.Journal of the American Medical Association 238, 608-610.

Sterns, R. H., Cox, M., Feig, P. U. and Singer, I. (1981). Internal Potassium Balanceand the Control of the Plasma Potassium Concentration 60, 339-354.

Svetsky, L. P., Yarger, W. E., Feussner, J. R., DeLong, E. and Klotman, P. E. (1986).Placebo-Controlled Trial of Oral Potassium in the Treatment of Mild Hypertension.Clinical Research 34, 487A.

Swales, J. D. (1991). Salt Substitutes and Potassium Intake. The British MedicalJournal 303, 10834-1085.



30

Takegawa, K., Mitsumori, K., Onodera, H., Shimo, T., Kitaura, K., Yasuhara, K.,Hirose, M. and Takahashi, M. (2000). Studies on the Carcinogenicity of PotassiumIodide in F344 Rats. Food and Chemical Toxicology 38, 773-781.

Til, H. P., Falke, H. E., Kuper, C. F. and Willems, M. I. (1988). Evaluation of theOral Toxicity of Potassium Nitrite in a 13-Week Drinking Water Study in Rats. Foodand Chemical Toxicology 26, 851-859.

Til, H. P., Kuper, C. F. and Falke, H. E. (1997). Nitrite-Induced Adrenal Effects inRats and the Consequences for the No-Observed-Effect Level. Food and ChemicalToxicology 35, 349-355.

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Webster, S. H., Rice, M. E., Highman, B. and Stohlman, E. F. (1959). TheToxicology of Potassium and Sodium Iodates II. Subacute Toxicity of PotassiumIodate in Mice and Guinea Pigs. Toxicology 1, 87-96.

Webster, S. H., Stohlman, E. F. and Highman, B. (1966). The Toxicology ofPotassium and Sodium Iodates III. Acute and Subacute Oral Toxicity of PotassiumIodate in Dogs. Toxicology and Applied Pharmacology 8, 185-192.

Weiner, B. and Faraci, P. A. (1979). Salt Substitute as a Potassium Supplement.American Journal of Hospital Pharmacy 36, 444-446.

Wetli, C. V. and Davis, J. H. (1978). Fatal Hyperkalaemia From AccidentalOverdose of Potassium Chloride. Journal of American Medical Association 240,1339.

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31

ANNEX 1 TO EVM/01/04

Tables referred to in the review


_______________________________________________________________________________This paper has been prepared for consideration by the Expert Group on Vitamins and Minerals and does not necessarily represent the final views of the Group

32

Table 1. Human Toxicity

Subject Symptoms Dose Comment ReferenceAcute ToxicityWoman 62y Gastric distention, inflamed stomach,

necrotic mucosal lining sloughed off,antrial stenosis remaining

94g Peeters and van derWeef (1998)

Woman, 52y Vomiting, sweaty, breathless, leftventricular failure, cyanosis, lungcrepitations

0.63g KCl x 20 (approx 6.6g K)

Bendrofluazide andphenylbutazone also taken

Illingworth andProudfoot, 1980

Man, 26 y Vomiting, fatal cardiac arrest 0.6g KCl x 40 (approx 12.5gK)

Distalgesic also taken Illingworth andProudfoot, 1980

Woman, 32 y Presented with diarrhoea, subsequentlyfound dead

47 KCl tablets Wetli and Davis, 1978

Boy, 2 mo Listlessness cyanosis, ceased breathing,fatal 28h later

3g KCl/day for 2 days(approx 1.56g)

Wetli and Davis, 1978

Man, 53 Chest tightness, nausea, vomiting. Diedof hyperkalaemia with asystole

283 mM (approx 11g K) Restuccio, 1992

Infant, 8 mo Stiffness, eye rolling back, breathingdifficulties

26 mEq K (approx 1g K) Kallen et al, 1976

7 Adult volunteers 2/7 subjects showed disturbed renalexcretion

12.5-17.5g KCl orbicarbonate. 80-100 mgK/kg bw considered toxic(5.6 – 7 g in a 70 kg adult)

Keith et al, 1941

Sub-chronic ToxicityWoman, 75 y Shortness of breath, oedema, heart failure Lite-salt substitute ad lib for

6 weeksSnyder et al, 1975

Man, 31 y Collapse due to myocardial infarction 5g/day potassiumsupplements. Durationunknown

Subjects also taking anabolicsteroids, amphetamines andpotassium sparing diuretics

Appleby et al, 1994.

Chronic ToxicityWoman, 68 y Nausea and abdominal cramps, stenosis

of the small bowel, probably caused byfocal alteration.

2x 10mEq KCL tablets/dayfor several years (approx0.78g/day)

Bronson and Gamelli,1987



33



34

Table 2. Acute animal toxicity

Species Endpoint Dose Duration NOAEL/LOAEL Comment ReferenceWistar rats Gastroenteritis, dehydration

death from respiratory failure2.1-3.9 g/kg bwKCl by stomachtube

Single dose LD50 = 3.02 +/- 0.14g/kg body weight

Boyd and Shanas,1961

SpragueDawley rats

Elevated plasma potassium,electrocardiographic changes.Total intakes in excess of 25.6mEq (approx 1g) lethal to halftreated animals

Solution of 3.54mM K (138mg/kg bw/day)added to chow

3 days Toxic signs observedat doses >258 mEq/kgbw (approx1g)

Drescher et al, 1958

F344 rats Lethal to 4/5 and 5/5 rats treatedwith 0.6 or 1.2 g/kg, necrosis ofproximal tubules apparent.Basophilic regenerative tubulesand focal eosinophillic dropletsat 0.3 g/kg bw

Up to 1.2g/kg bwKbrO3 intra-gastric

Single dose + 1 monthobservation

NOAEL 50 mg/kg bw Kurata et al, 1992

Albino rats,rabbits, guineapigs and cats

KCl, KClO3 Single dose Lethal dose in rats=0.82g KCL and 1.5gKClO3

Ulrich and Shternov,1929

Dogs Emesis, anorexia, prostration,fatty changes in organs, necrosisin liver, kidney, bladder and gutmucosae

KIO3 Single dose Minimum lethal dose200-250 mg/kg

Webster et al, 1966

Macaques Gastro-intestinal lesions Up to 2000mgKCl/animal indifferentformulations

Twice daily for 4.5days

NOAEL =100mg/animal(enteric coatedtablets)

Diener al, 1965

Holstein Calves Breakdown of potassiumhomseostasis (changes in acid-base balance, respiratory andheart rates). Dose fatal to 3/5, ¾and 1/1 animal given 1.73, 2.31and 2.88 g/kg respectively

0.29-2.88g K/kgbw/day as Kclinwater

Single dose Neathery et al (1979)



35

Table 3 Sub-Chronic Animal Toxicity

Species Endpoint Dose Duration NOAEL/LOAEL Comment ReferenceWistar rats Hypertrophy of adrenal

zona glomerulosaKNO2 not specified.2630 ppm K in allgroups

90 days Effects not due topotassium

Til et al, 1988

Swiss mice Some deaths in 0.75%group, increasedhaemolysis at 0.25% andabove

Up to 0.75% KIO3in drinking water

15-16 weeks Webster et al, 1959.

Guinea pigs No effects observed Up to 0.5% KIO3 indrinking water

4 weeks 0.5% Webster et al, 1959.

Dogs Emesis, anorexia andlistlessnes

6-100 mg/kg bwKIO3 in milk orcapsule

2 months Webster et al, 1966.



36

Table 4 Chronic Toxicity and Carcinogenicity in animals

Species Endpoint Dose Duration NOAEL/LOAEL Comment ReferenceWistar rats Decreased blood

sugar50 or 75 ppm KbrO3 104 weeks 75 ppm Blood sugar effect not

considered significant.No increase inneoplasms found.

Fisher et al, 1979

Male F344 rats Tumours in kidney,thyroid andmesothelium

0.02 to 0.4 mg/LKBrO3 (equivalent to1.5 to 30 mg/kgbw/day)

100 weeks DeAngelo et al, 1998

F344 rats Renal cell tumoursand mesotheliomas ofthe peritoneum (malesonly)

250 and 500 ppmKBrO3

110 weeks Kurokawa et al, 1983

F344 rats None Single intra-gastricdose of 300 mg/kg bwKBrO3 followed bydiet containingbarbital sodium

104 weeks Kurata et al, 1992

F344 rats Squamous cellcarcinomas in salivaryglands. Increasedthyroid weights andthyroid follicular celltumours when givenafter DHPN injection

Up to 1000 ppm KI indrinking water. Somegroups given DHPNinjection first

83 weeks Takegawa et al, 2000

Newborn F344 rats None Single or 4 weekly scinjection of 12.5 to800 mg/kg bw KBrO3

80 weeks Matsushima et al,1986

Theiller’s originalmice

Increased blood sugarat 1 and 12 months(not at 18 months)

50 or 75 ppm KbrO3 104 weeks 75 ppm Blood sugar effect notconsideredsignificant.No increasein neoplasms found

Ginocchio et al, 1979



37

B6C3F1 mice Renal tumours inmale mice.

0.08 to 0.8 mg/LKBrO3 (equivalent to9.1 to 77.8 mg/kgbw/day)

100 weeks DeAngelo et al, 1998

Newborn ICR mice Marginal increase inlymphomas in malesin 400-800 mg/kggroup

Single or 4 weekly scinjection of 12.5 to800 mg/kg bw KBrO3

80 weeks Matsushima et al,1986



38

ANNEX 2 TO EVM/01/02/01

INTAKES OF POTASSIUM FROM FOOD AND SUPPLEMENTS

The data presented on potassium intakes are obtained from dietary surveys of specificpopulation age groups in Britain carried out over the last 15 years23456. In each surveyfood consumption data were collected by means of a dietary record (usually weighed)kept for 4 or 7 consecutive days. Nutrient intakes were calculated using a set ofnutrient composition data contemporaneous with the time of the survey. Thereforesome apparent differences in intakes between population age groups may be due tochanges in the nutrient composition data and reflect changes in the nutrientcomposition of manufactured foods over time.

Total intakes of Potassium

Table 1 provides information on the absolute intakes of potassium by the Britishpopulation, classified by age and sex. Mean and median intake and the upper andlower end of the intake distribution (defined as upper and lower 2.5 percentilesrespectively) are given.

Average intake of potassium from food was lowest for infants aged 6-12 months andhighest for males aged 35-49 years. The trend was for intake from food to increasewith age until adulthood and decrease with age for older people aged 65 years andover. The contribution of supplements was very small and average intakes includingsupplements were similar to average intakes from food only.

Intakes from food only and all sources at the 97.5%ile were between 1.3-1.7 times themedian for all population groups. The mean intake of potassium from food sourcesand all sources for infants, pre-school children and children aged 4-10 years exceededthe RNI for these groups. Mean intakes for young people aged 11-18 years, adults andpeople aged 65 years and over were below the RNI. The mean intake of potassium forfemales aged 85 years and over free living in the community was 1951mg/day fromfood and 1962mg/day from all sources below the LRNI (2000mg/day) for thispopulation group.

Table 2 provides information on potassium intakes adjusted for body weight classifiedby age and sex. Potassium intakes adjusted for body weight displayed a trend todecrease with age for males and females.

Sources of Potassium in the diet

Table 3 indicates the contribution made by different types of food to average intakesof potassium by young people aged 15-18 years. This data set was collected in 1997

2 Food and nutrient intakes of British infants. 19863 National Diet and Nutrition Survey of children aged 1½-4½ years. 1992/34 National Diet and Nutrition Survey of young people aged 4-18 years. 1997/85 Dietary and nutritional survey of British adults. 1986/76 National Diet and Nutrition Survey of people aged 65 years and over. 1994/5



39

and so most closely reflects current eating habits. Vegetables, potatoes and savourysnacks were the main source of potassium in this age group providing over one-thirdof their average daily intake. Potatoes and potato products alone provided almost aquarter of total intake. This was followed by meat and meat products, cereal andcereal products and milk and milk products which each provided about 14% of totalintake. .

The main sources of potassium were similar for people aged 16-64 and 65 years andover. Beverages contributed slightly more in these age groups. The contribution ofmilk and cereals was higher for older people living in institutions. The main source ofpotassium for children aged 11/2-41/2 years was milk and milk products (31%)followed by vegetables, potatoes and savoury snacks (23%). Family foods (all foodsother than commercial infant foods, infant formula and milk) and cows milk were themain sources for infants.

Potassium intakes from supplements

The number of consumers of dietary supplements containing potassium was verysmall and they provided zero or negligible contribution to mean intakes. The inclusionof prescribed supplements containing potassium had the effect of a very smallincrease on the average intake from all sources for males and females aged 65-84years free living in the community.

If we consider consumers of supplements containing potassium separately we canexpect the proportion of intake from supplements to be much higher. Table 4 showsthe number of consumers of dietary supplements containing potassium in each agegroup. The table also provides information on the mean, median and range of intakesof potassium from supplements for those who consumed them. The use ofsupplements containing potassium was low in all population groups. In particular usewas especially low in the pre-school children and young people. The highestprevalence of potassium supplement use was in older people living in institutions.Within the group 2.5% and 2.4% of males and females respectively were takingsupplements containing potassium.

The range of intakes varied substantially between the different population groups andthe overall range was from 0.2 – 1089 mg/day. The highest intake was for olderfemales free living in the community.

Diet and Nutrition Surveys BranchNutrition Division

Food Standards AgencyJanuary 2001



40

Table 1: Total intakes of Potassium

Absolute Potassium intake (mg/day)7

Age/sex Food Only Food and Supplements2.5% ile Mean Median 97.5

% ile2.5% ile Mean Median 97.5% ile

Infants (1986)6-12mthsM&F

681 1352 1340 2190 * * * *

Pre-school children(1992/3)1½-2½yrs/M&F

716 1476 1431 2466 716 1476 1431 2466

2½-3½yrs/M&F

760 1513 1486 2538 760 1513 1486 2538

3½-4½ yrs/M 784 1573 1531 2555 784 1573 1531 25553½-4½ yrs/F 807 1501 1459 2268 807 1501 1459 2268Young people(1997/8)4-6 yrs/M 1045 1944 1889 3019 1045 1944 1889 30194-6 yrs/F 1016 1774 1661 2721 1016 1774 1661 27217-10 yrs/M 1280 2136 2086 3110 1280 2136 2086 31107-10 yrs/F 1098 2019 2029 2827 1098 2019 2029 282711-14 yrs/M 1201 2392 2344 3653 1201 2392 2344 365311-14 yrs/F 1176 2100 2025 3159 1176 2100 2025 315915-18 yrs/M 1636 2833 2775 4416 1636 2833 2775 441615-18 yrs/F 1063 2162 2148 3334 1063 2162 2148 3334Adults (1986/7)16-24 yrs/M 1511 3018 3006 4618 1511 3018 3006 461816-24 yrs/F 1107 2259 2228 3582 1107 2259 2228 358225-34 yrs/M 1758 3237 3223 4802 1758 3237 3223 480225-34 yrs/F 1137 2324 2297 3831 1137 2324 2297 383135-49 yrs/M 1846 3279 3197 5099 1846 3279 3197 509935-49 yrs/F 1390 2562 2510 4280 1390 2562 2510 428050-64 yrs/M 1774 3155 3089 4699 1774 3155 3089 469950-64 yrs/F 1175 2476 2418 4009 1175 2476 2418 4009Older people free-living inthe community (1994/5)65-74yrs/M 1379 2831 2789 4211 1346(1379) 2833(2831) 2805(2789) 4191(4211)65-74yrs/F 1277 2326 2270 3806 1292(1277) 2329(2326) 2278(2270) 3799(3806)75-84 yrs/M 1444 2526 2445 3955 1457(1444) 2529(2527) 2444(2445) 3954(3955)75-84 yrs/F 1067 2090 2015 3129 1074(1074) 2092(2091) 2015(2015) 3130(3129)85 & over/M 1208 2306 2261 3345 1211(1208) 2306(2306) 2266(2261) 3344(3345)85 & over/F 871 1951 1910 3055 869(871) 1962(1962) 1932(1930) 3233(3231)Older people living ininstitutions (1994/5)65-84 yrs/M 1386 2433 2343 3895 1453(1410) 2434(2434) 2341(2343) 3835(3895)65-84 yrs/F 1318 2261 2258 3021 1360(1360) 2265(2265) 2278(2258) 3024(3021)85 & over/M 1334 2415 2355 3568 1335(1334) 2421(2421) 2347(2355) 3559(3568)85 & over/F 1194 2042 1997 3242 1185(1194) 2051(2051) 2011(2023) 3173(3242)

*Data unavailable

7 Data in brackets = intakes from food and supplements, excluding prescribed supplements.



41

Table 2: Bodyweight adjusted Potassium intake

Bodyweight adjusted Potassium intake (mg/kgbwt /day)8

Age/sex intakes from food and supplements9

Mean Median 97.5% ileInfants (1986)10

6-12mths/M&F 141 139 230Pre-school children (1992/3)1½-2½ yrs/M&F 121 116 2082½-3½ yrs/M&F 104 101 1733½-4½ yrs/M 95 93 1473½-4½ yrs/F 92 91 139Young people (1997/8)4-6 yrs/M 92 88 1384-6 yrs/F 88 84 1377-10 yrs/M 72 71 1097-10 yrs/F 66 63 9811-14 yrs/M 53 53 8511-14 yrs/F 45 42 7915-18 yrs/M 43 41 7215-18 yrs/F 37 36 61Adults (1986/7)16-24 yrs/M 44 44 7516-24 yrs/F 38 37 6125-34 yrs/M 43 43 6825-34 yrs/F 38 38 6535-49 yrs/M 43 42 6935-49 yrs/F 40 39 7250-64 yrs/M 41 40 6550-64 yrs/F 39 38 66Older people free-living in the community (1994/5)65-74 yrs/M 37 36 5865-74 yrs/F 36 34 6475-84 yrs/M 35 34 5675-84 yrs/F 33 32 5585 and over/M 34 33 5485 and over/F 34 33 58Older people living in institutions (1994/5)65-84 yrs/M 37 35 6165-84 yrs/F 38 38 5685 and over/M 36 36 5985 and over/F 36 34 60

8 Body weights measured for each subject for all age groups except infants aged 6-12 months wherereported body weights were used.9 Data includes intakes from prescribed supplements.10 Intakes for infants aged 6-12 months are from food only.



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Table 3: Sources of Potassium in the diet11

Contribution of food types to average dailyintake of Potassium

Food Type Mg/day % of total

Cereal and cereal products 356 14- of which all breakfast cereals 240 10

Milk and milk products 337 13- of which semi-skimmed milk 165 7

Egg and egg dishes 16 1Fat spreads 5 <1Meat and meat products 371 15

- of which chicken and turkey dishes 125 5Fish and fish dishes 49 2Vegetables, potatoes and savoury snacks 918 37

- of which potatoes & potato products 590 23Fruits and nuts 99 4Sugar, confectionery and preserves 69 3Beverages 225 9Miscellaneous 63 2

Total intake from food 2508 100Intake from dietary supplements 0 0Total intake from food and supplements 2508 100

11 NDNS: young people aged 4-18 years. 1997/8. 15-18 year group.



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Table 4: Potassium intake from supplements12

Consumers ofPotassium

supplements

Potassium intake from supplements(consumers only) (mg/day)

Age/sex Number % Mean Median RangeInfants (1986)6-12 mths/M&F * * * * *Pre-school children (1992/3)1½-4½ yrs/M&F 1 0.1 6.0 6.0 6.0Young people (1997/8)4-6 yrs/M&F 1 0.3 0.8 0.8 0.87-10 yrs/M&F 2 0.4 1.0 0.4 0.4 – 1.611-14 yrs/M 0 0 - - -11-14 yrs/F 0 0 - - -15-18 yrs/M 1 0.6 36.0 36.0 36.015-18 yrs/F 1 0.5 8.0 8.0 8.0Adults (1986/7)16-64 yrs/M 10 0.9 59.8 26.9 0.2 – 240.016-64 yrs/F 13 1.2 11.5 4.9 0.3 – 68.6Older people free-living in thecommunity (1994/5)65 and over/M 9 1.4 146.0 25.5 2.3 – 624.065 and over/F 12 1.9 218.5 109.3 1.3 – 1088.5Older people livingin institutions (1994/5)65 and over/M 5 2.5 164.1 106.5 46.9 – 297.565 and over/F 5 2.4 223.0 119.9 93.8 – 541.5* Data unavailable- Zero intake

12 Data includes intakes from prescribed Potassium supplements.



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ANNEX 3 TO EVM/01/04

Potassium : Summary table of selected nutrition related information and existingguidance on regulations

Unit of usage Mg/day mg/100 kcalMale Female

UK DRV’s 13

AdultsLRNIRNIInfantsLRNIRNI

1600-20003100-3500

400-450800-850

1600-20003100-3500

400-450800-850

Mean adult UK dietary intakefrom all sources (food only)Adults (16-64)14

65 years and over15

free living institutionalised

3187

2715 (2715)2429 (2426)

2434

2208 (2207)2148 (2141)

RegulationsInfant formula16

Infant foods17

Weight reduction18

whole daily diet replacement meal replacement

3100 per dayat least 500 per meal

Minimum: 60mg/100kcalMaximum: 145mg/100kcal

Maximum 160mg/100kcal(of the food as sold)

Maximum total safe daily intake13 17.6g/d

13 Committee on Medical Aspects of Food and Nutrition Policy (1991). Dietary Reference Values forFood Energy and Nutrients for the United Kingdom. Report on Health and Social Subjects 41.London: HMSO.14 Dietary and nutritional survey of British adults. 1986/715 National Diet and Nutrition Survey of people aged 65 years and over. 1994/516 The Infant Formula and Follow-on Formula Regulations 199517 The Processed Cereal-based Foods and Baby Foods for Infants and Young Children Regulations1999 (amended)18 The Foods Intended for Use in Energy Restricted Diets for Weight Reduction Regulations 1997.



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expert group on vitamins and minerals revised review … · 2013-10-31 · this paper has been...

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