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Dietary effects of sodium alginate in humans a

b

b

D. M. W. Anderson , W. G. Brydon , M. A. Eastwood & D. M. Sedgwick

b

a

Chemistry Department , The University , Edinburgh, EH9 3JJ, UK b

Gastrointestinal Unit , Western General Hospital , Edinburgh, EH4 2XU, UK Published online: 10 Jan 2009.

To cite this article: D. M. W. Anderson , W. G. Brydon , M. A. Eastwood & D. M. Sedgwick (1991) Dietary effects of sodium alginate in humans, Food Additives & Contaminants, 8:3, 237-248, DOI: 10.1080/02652039109373974 To link to this article: http://dx.doi.org/10.1080/02652039109373974

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FOOD ADDITIVES AND CONTAMINANTS, 1991, VOL. 8, NO. 3, 2 3 7 - 2 4 8

Dietary effects of sodium alginate in humans D. M. W. ANDERSON†, W. G. BRYDON‡, M. A. EASTWOOD‡ and D. M. SEDGWICK‡ †Chemistry Department, The University, Edinburgh EH9 3JJ, UK; ‡ Gastrointestinal Unit, Western General Hospital, Edinburgh EH4 2XU, UK

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(Received 30 August 1990; revised 22 November 1990; Accepted 21 December 1990) Following a 7-day control period, five male volunteers consumed a weight of sodium alginate corresponding to 175 mg/kg body weight for 7 days, followed by 200 mg sodium alginate per kg body weight for a further 16 days. Measurements before and at the end of the 23-day period of dietary supplementation showed that sodium alginate acted as a faecal bulking agent for all volunteers, giving a significant (p < 0.01) increase in daily wet weight, and also increases in the water content and daily dry weight, but no change in faecal pH. Although the dietary transit time remained constant for two volunteers, it decreased for two, and increased slightly for one, with little resulting change in the overall mean value. The ingestion of sodium alginate had no significant effect on (a) haematological indices, (b) plasma biochemistry parameters, (c) urinalysis parameters, (d) blood glucose and plasma insulin concentrations, (e) breath hydrogen concentrations. No allergic responses were reported by, nor observed in, any of the volunteers. The study therefore indicates that the ingestion of sodium alginate at a high level for 23 days caused no effects other than those normally associated with a polysaccharide bulking agent; in particular, the enzymatic and other sensitive indicators of adverse toxicological effects remained unchanged. Keywords: sodium alginate, dietary effects, bulking agent, transit time

Introduction

Sodium alginate has been approved for use as a food additive by all of the major international regulatory authorities since the inception of the present positive-list principle. In recent years there has been a tendency, welcomed and encouraged by the regulatory authorities and consumers, for direct evidence of the dietary effects of food hydrocolloids to be obtained in man to supplement the evidence derived from animal-based experiments. Such studies (Anderson et al. 1986, Eastwood et al. 1987) have had positive effects in terms of upward revisions of the Acceptable Daily Intake (ADI) originally assigned to the most widely used emulsifiers, stabilizers and thickeners. This study of sodium alginate in humans was therefore commissioned. The objectives were: (a) to demonstrate that daily consumption of sodium alginate at about 30 times the maximum actual average daily human exposure is tolerated without gastric upset or allergic response; (b) to determine the extent and nature, if any, of the dietary, biochemical, haematological and physiological changes resulting from the consumption of sodium alginate. The study was conducted in conformity with all regulatory requirements currently in force in Great Britain, and with the prior consideration and approval 0265-203X/91 $3.00 © 1991 Taylor & Francis Ltd.

D. M. W. Anderson et al.

238

of the appropriate authority i.e. the Ethics of Research Committee of the North Lothians District, Edinburgh, UK. Materials and methods

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The test article Sodium alginate, Lot EX 6015, was supplied by the Kelco Division of Merck & Co. Inc., San Diego, USA. The Test Article is retained in the Chemistry Laboratory, University of Edinburgh, UK, for reference purposes. Preliminary study in the rat As required by the Ethics of Research Committee, the Test Article was fed to 15 mature male rats at a dietary supplementation of 5% (w/w) for 30 days. The animals thrived and remained active and alert throughout. There was no incidence of diarrhoea nor loss of normal bowel habit. Urine was collected from each animal during the fourth week of dietary supplementation; there were no abnormal values for any of the standard urinalysis parameters. The Official Animal House Veterinary Officer (Mr David Shannon, BSc, MRCVS, DTVM) conducted full post-mortem examinations on all animals and certified that 'the rats were in good health and condition immediately prior to post-mortem examination: two rats showed mild distension of a portion of the ileum; ten rats showed distension of the caecum compared with the control animals; eight rats showed the colon distended to some degree with soft contents; formation of faecal pellets did not differ from that in the control animals'. Study in humans Five males (Volunteers F-K), all normal in health and free from gastrointestinal disease, participated; their ages ranged from 26-48 years with initial body weights ranging from 51 •3-92*1 kg and subsequent weights as shown in table 1. The study involved a 7-day initial control period, during which a volume of orange juice, equal to that to be used later to flavour/dilute the gel containing the Test Article, was consumed by all volunteers. Thereafter, each volunteer consumed, for the first 7 days of the test period, a weight of sodium alginate equal to 175 mg/kg body weight; this was increased to 200 mg/kg body weight for the remainder of the 23 days of dietary supplementation. In order to simulate the use of sodium alginate as a food additive as closely Table 1. Sodium alginate: age/weight of volunteers. Body weight (kg) Pre-dosing

Post-dosing

Age

Volunteer F G H i-i

K

Mean

(years)

Day 3

Day 8

Day 31

48 44 30 33 26 36

71-2 78-5 90-1 51-3 92-1 76-6

71-0 78-7 90-2 51-0 92-0 76-6

70-7 77-8 90-7 50-8 90-7 76-1

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Dietary effects of sodium alginate in humans

239

as possible, each volunteer consumed his pre-calculated allocation of sodium alginate in three measured portions at intervals each day. The individual portions were prepared in advance in 'polypots', fitted with lids, by adding the weighed aliquots of sodium alginate, with rapid stirring, to 220 ml cold distilled water. The hydrocolloid was then allowed to hydrate fully for 24 h to give a thick, but fluid, gel to which each volunteer then added the pre-determined amount of orange juice, immediately prior to consumption. During the initial control week (Day 3), each volunteer was interviewed to ascertain any past history of allergenicity. During the period of dietary supplementation, consumption of the Test Article was ensured by daily contact with one or other of the authors of this Report, and enquiries were made concerning any apparent allergic responses. Diet diaries were maintained by all volunteers during the control and dietary supplementation weeks. Following an overnight fast, blood was taken for glucose (Kadish et al. 1968) and insulin (Ashby and Speake 1975) measurements on the third day of the initial control period, immediately prior to consumption of 50 g glucose in 200 ml water. Thereafter, blood was taken at 30-min intervals for 4h. Fasting blood samples were also taken, prior to consumption of the glucose, for (a) serum lipid estimation of cholesterol and HDL cholesterol (Sigma 1982), (b) triglycérides (Egstein 1966), (c) haematological indices, (d) plasma chemistry analyses (urea, electrolytes, bicarbonate, alkaline phosphatase, calcium, phosphate, creatinine, uric acid, total protein, albumin, bilirubin, lactate dehydrogenase (LDH) and aspartate amino transferase (AST) using SMAC-2 (Technicon Instruments Co., Basingstoke, UK). During the glucose tolerance test, end alveolar air samples were taken at 30-min intervals for hydrogen determination (Tadesse et al. 1979). All of these tests were repeated on the last day of the dietary supplementation period (Day 31) and on the final day of the second control period (Day 38). A 24 h urine sample was taken by each volunteer for routine urinalysis during the initial control week and during the third week of dietary supplementation with sodium alginate. Complete 5-day faecal collections were made during Days 2-6 of the initial control period, and Days 16-20 of the dietary supplementation period, after consumption (1700 h) of a bolus of 40 radio-opaque markers to assess completeness ' of collection and gastrointestinal transit time, which was taken as the time for 80% of the markers to appear in the faeces (Hinton et al. 1969). The individual stools were weighed and homogenized in a known volume of water. Daily dry weight was determined from dried aliquots which were subsequently analysed for bile acids (Evrard and Janssen 1968), neutral sterols (Miettinen et al. 1965), fat (Varley 1962), and volatile fatty acids (Spiller et al. 1980); pH was determined on an aliquot of homogenized faeces. Faecal occult blood was determined on two separate aliquots of faeces (control and test periods) using Haemoccult test envelopes (Roehm Ltd, UK). Plasma glucose concentrations were estimated by an automated glucose oxidase method (Kadish etal. 1968); blood glucose concentration was estimated from this value using the haematocrit. Plasma insulin concentrations were estimated by a radio-immunoassay technique (Ashby and Speake 1975). A full blood analysis was made (automated Coulter S Counter and manual methods). Results Analysis of the diet diary records confirmed that all volunteers had maintained

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240

D. M. W. Anderson et al.

a uniform pattern of living, as stipulated in the Study Protocol. The volunteers' individual intakes of protein, fat, sugar, carbohydrate, fibre and alcohol in the final week of dietary supplementation did not differ significantly from those recorded for the control weeks. The faecal measurements before and after dietary supplementation with sodium alginate are shown in tables 2,3 and 12-14. The completeness of faecal collections was confirmed by the recovery of more than 90% of the markers in all collections. No occult blood was present in any sample. The effects on the haematological indices are shown for each volunteer in table 4 (Day 3, initial control week), table 5 (Day 31, final dietary supplementation week), table 6 (Day 38, final control week) and table 7 (comparison of the mean values (« = 5) for Days 3,31 and 38). The effects on the plasma chemistry parameters are shown in table 8 (Day 3, initial control week), table 9 (Day 31, final dietary supplementation week), table 10 (Day 38, final control week) and table 11 (comparison of the mean values (n = 5) for Days 3,31 and 38). Breath hydrogen concentrations for each volunteer remained unchanged at below 15 ppm and urinalysis parameters remained unchanged and within normal limits for each volunteer throughout the study; data are therefore not presented. None of the volunteers reported any allergic responses, gastrointestinal disturbances, feelings of distension or abdominal discomfort, or unusual looseness of bowel during the period of dietary supplementation with sodium alginate. Only Volunteer H reported any previous history of allergic responses (to tetanus injections). Unfortunately, towards the end of the third week of dietary supplementation, Volunteer H became a victim of a local epidemic of influenza. Although unwell, and under the care of his family doctor, Volunteer H was nevertheless persuaded not to discontinue his participation in this study as it was so close to completion and no drugs that may have influenced the results had been prescribed. The responses for blood glucose and serum insulin were essentially unchanged after the dietary supplementation period. Discussion On average, the faecal pH and gastrointestinal transit time showed little change after supplementation with sodium alginate (table 3), although the transit time remained essentially constant for only Volunteers H and J, with Volunteer G showing an increase and Volunteers F and K showing decreases. The 24-h faecal dry weight and water content both increased slightly for all volunteers; the 24-h wet weight increased considerably for all volunteers, resulting in a significant (p < 0-01) increase, from 145 ± 38 to 205 ± 58 g. In this respect, sodium alginate acts as a bulking agent, although not so effectively as either carboxymethylcellulose (Anderson et al. 1986) or xanthan gum (Eastwood etal. 1987). There were no significant changes in faecal total and individual neutral sterols (tables 3 and 12), nor in faecal total and individual bile acids (tables 3 and 13). Total faecal volatile fatty acids increased for four volunteers but decreased for one (tables 3 and 14). Tables 4-6 show that the individual volunteers' variations in haematological parameters differed to only a slight extent, with the exception of some of the

Table 2. The effect of ingestion of sodium alginates on faecal measurements After 23 days

Control period

Volunteer

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Volunteer F pH

Transit time (h) Wet weight (g/24h) Dry weight (g/24h) Water (%)

6-82 72 142 36 74

G

6-93 65 139 41 71

H 6- 46 48 164 40 75

J

6-91 48 88 24 73

K

6-80 48 192 42 78

X

6-78 56 145 37 74

SD

0-19 11 38 7 3

F

6-81 49 203 39 81

G

7-01 88 166 49 71

J

H 6v 70 48219 46 79

7- 83 43 143 28 81

K

6-20 22 293 50 83

X

6-91 50 205 42 79

SD

0-59 24 58 9 5

r

Table 3. The effect of ingestion of sodium alginate on faecal measurements. Control period

After 23 days

Volunteer H Fat (mmol/24h) Total volatile fatty acids (mmol/24h) Total bile acids (mmol/24h) Total neutral sterols (mmol/24h)

9-3

17-5

g

Volunteer SD

SD

H

18-2

15-6

13-0

14-7

3-6

11-3

21-0

14-3

13-2

15-3

15-0

3-7

11-12

8-04

19-06

10-46

16-49

13-03

4-57

21-19

14-12

17-26

18-84

21-10

18-50

2-95

0-84

0-40

0-57

0-49

0-91

0-64

0-22

1-22

1-12

1-09

0-42

0-89

0-95

0-32

1-74

1-27

1-58

0-83

1-11

1-31

0-36

1-48

1-48

1-52

0-84

g"

242

D. M. W. Anderson et al.

Table 4. Sodium alginate: haematology, Day 3 (control). Volunteer

Mean

G

H

J

K

(« = 5)

Accepted ranges

7-6

5-9

6-3

4-9

7-9

4-49 15-1 44-7 99-6 33-6 33-8 12-9

4-89 14-8 44-2 90-4 30-3 33-5 13-2

5-63 16-4 47-9 85-1 29-1 34-3 12-2

4-24 12-4 37-7 88-9 29-2 32-9 12-7

4-75 14-6 43-0 90-6 30-7 33-9 13-1

6-5 ±1-2 4-80 ±0-53 14-6± 1-4 43-5 ± 3-7 90-9 ±5-3 30-6±l-8 33-7 + 0-5 12-8 ±0-4 254 ± 52

4-8-10-8 4-2-5-4 12-16 37-47 81-99 27-31 33-37 11-5-14-5 130-400

60 ± 10 4 1 ± 1-1 32 ± 7

40-74 1-9-8 19-48 0-9-5-2 3-4-9 0-16-1

±S.D. F

WBC (x 109/£) RBC (x 1012/£) Hb (g/d£) Hct

MCV (f£) MCH (pg) MCHC (g/d£) RDW

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Platelets (x 109/e) Neutrophils (%) (x 109/e) Lymphocytes (%) (X 109/£) Monocytes (%) (x 109/£) Eosinophils (%) (x 109/C) Basophils (%) (x 109/O

279 74 5-6 22 1-7 2 0-5 1 01 0 0

292 53 3-6 32 1-7 6 0-4 2 0-1 2 0-1

164

261

66 4-3 32 2-0 3 0-2 1 01 0 0

52 2-5 39 1-9 8 0-4 1 0-1 0 0

274 54 4-3 37 2-9 2 0-2 6 0-5 1 0-1

2-0±0-5 4-2 ±2-4 0-3±0-l 2-2 ±2-4 0-5 ±0-02 0-6 ±0-09 0-04 ±0-01

0-7

0-0-8 0-1-5 0-0-2

Table 5. Sodium alginate: haematology, Day 31 (test). Volunteer F

WBC (x lO'/f) RBC(x 1012/£) Hb (g/d£) Hct

MCV («) MCH (pg) MCHC (g/de) RDW

Platelets (x 109/£) Neutrophils (%) (x 109/£) Lymphocytes (%) (x 109/£) Monocytes (%) (x 109/£) Eosinophils (%) (x 109/£) Basophils (%) (x 109/£) a

G

H

7-7

5-7

4-19 14-2 41-4 98-8 33-9 34-3 12-6

4-78 14-7 43-4 90-7 30-8 33-9 13-4

13-2a 5-54 16-1 47-6 86-0 29-1 33-8 12-7

257

256

57

47

K

6-7

6-8

4-35 13-0 38-6 88-8 29-9 33-7 13-2

4-70 14-4 42-6 90-6 30-6 33-8 13-3

247

239

63

39

Accepted ranges

6-7±0-8 b 4-71 ±0-52 14-5 ± 1-1 42-7 ±3-3 91-0±4-8 30-9+ 1-8 33-9±0-2 13-0±0-4 226 ± 54

4-8-10-8 4-2-5-4 12-16 37-47 81-99 27-31 33-37 11-5-14-5 130-400 40-74 1-9-8 19-48 0-9-5-2 3-4-9 0-16-1

3-00

2-11

1-72"

2-28

3-47

2 0-2 2 0-2 0 0

9 0-5 6 0-3 1

7 0-9 0 0 0 0

3 0-2 0 0 0 0

4 0-3 6 0-4 0

51 ± 10b 3-48 ±0-95 b 40 ± 7 * 2-71 ±0-63 b 5 ±2-9 0-4±0-3 2-8 ±2-3 0-2 ±0-2 0-2 ±0-04

0

0-01 ±0-03

4 ?9 39

Influenza infection.

130

J

Mean ±S.D. (n = 5)

2-68 37

0-06

80 a a

10-56 13"

4-22 34

2-65 51

0-7

0-0-8 0-1-5 0-0-09

Dietary effects of sodium alginate in humans

243

Table 6. Sodium alginate: haematology, Day 38 (final control week).

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Volunteer

Mean

F

G

H

J

K

Dietary effects of sodium alginate in humans.

Following a 7-day control period, five male volunteers consumed a weight of sodium alginate corresponding to 175 mg/kg body weight for 7 days, followe...
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