FDA Petition Overview Document Extract

3.1.1.2. Protein Quality Study (

Study code X7/119)
File 24, Part 8, Exhibit 8:1
This study invol v ing young men was conducted at Massachusetts
Institute of Technology. The results demonstrated that myco-protein
has a biological value equivalent to milk and, even as the sole source
of protein, is of good nutritive value for human maintenance. There
were no adv erse reactions to the myco-protein as measured by blood
analysis, nor were there any signs of intolerance.
Experimental design
Subjects were given a complete liquid diet containing myco-protein,
myco-protein + methionine or skimmed milk as the sole protein sources.
Each subject received each diet in turn over 3 x 15 day diet periods.
The subjects were fed at levels which gave intakes of 0.3g protein/kg
bodyweight/day. They received 4 meals per day.
Some additional controls were also used: 7 as clinical chemistry
controls and 6 receiving an egg-based liquid diet.
Results
Adherence
Protocol

to

Kyco-protein
Intake

Nitrogen Balance
and Protein
Quality
(
Table V:3:3)

Two subjects d rop ped out of the stud y for

reasons unrelated to myco-protein: one because of
an infection, the other was reluctant to submit to
the d emanding nature of the study. Results are
therefore given for 11 subjects for each of the
treatments.
The average intake of myco-protein achieved was
47.1g, with a range of 38.6-55.7g.
Myco-protein compared very favourably vi.th skimmed
milk, especially with regard to biological value.
Its digestibility and NPU were lower, but the latter
was improv ed signif icantly by methionine
supplementation.
One subject (
RS)gave very variable values and was
considered unreliable; therefore his data were
eliminated from the means. Nitrogen balance was
expected to be low or negative due to the
suboptimal level of daily protein intake..
When account is taken of the non-protein nitrogen
from g 1ucosami ne, the true d igestibi 1ity,
biological value and NPU give a more accurate
reflection of true protein quality of myco-protein
(
Table V:3:4).

Blood Analysis

There were no changes of clinical significance

observed throughout the study.

222

_,.._
{\

,,.....-.,.

.--

TABLE V:3.3
Nitrogen Balance and Estimates of the Nutritive Value of Myco-protein
in Young Adult Men

Protein
Myco-protein
nl BV2 NPU3
Balance
(g/day)
N
N

0-l

Myco-protein + Meth.
Balance
(g/day)

BV

NPU

Milk

Balance
D
(g/day)

-0.61
-0.07
-1.38
-0.97
-0.45
-1.09
-0.11
-0.96
-1.22
-0.90

80 83
79 107
57 74
78 75
78 99
75
80
91 90
73 87
95 52
69 89

66
85
42
59
77
60
82
64
49
61

-0.50
0.20
-0.85
-0.37
-0.26
-0.40
-0.76
-0.42
-1.19
-0.35

79 107
80 113
63 90
78 94
81 99
81 92
78 82
82 90
91 55
81 96

85
90
57
73
80
64
74
50
78

-0.36
-0.07
-0.45
-0.85
-0.28
-0.92
-0.43
-0.22
-0.99
-0.74

-0.77

78

65

-0.49

79

73

-0.53

-5.12

107

84
26

28

-0.15

100

75

92

-3.50

91
98
87
94
92
88
101
97
100
99

BV

NPU

93
98
93
74
99
81
81
93
62

85
96
81
70
91
71

77

82
90
62
76

95 85

80

81 13

11

D Digestibility
BV Biological Value
NPU Net Protein Utilization
In calculation of BV and NPU, obligatory urine and faecal N losses
were taken as 37.2 and 8.8mg N/kg body wt/day,

......_

TABLE V:3.4
Nutritive Value of Non RNA-Reduced M co- rotein in Man
Expt .No . X7 119)
(

Protein Source

No. of
Subjects

Results Based
on
Total Nitrogen
TD
BV NPU

88

84

73

92

73

90

92

82

85

80

10*

78

84

Myco-protein +
Methionine

0.3

10*

79

Skim Milk

0.3

10*

95

Results Adjusted
for Glucosamine
Nitrogen
BV NPU
TD

65

0.3

Myco-protein
N

Protein Level
g/kg/day

One subject gave values that indicated he may not have been adhering
to the protocol and his results have been excluded.

TD True Digestibility
BV Biologic Value
NPU Net Protein Utilization

Conclusions
Myco-protein is of good nutritive value for human maintenance.
There was no evidence from blood analysis of adverse reactions to the
material.
There was no indication of intolerance to myco-protein.
3.1.2. Human acceptability and tolerance.
Four studies were conducted to assess acceptability of myco-protein as
a food and to identify any intolerance reaction which might have
occurred.
These studies involved a total of 339 subjects who consumed mycoprotein with intakes ranging from lOg to 40g (dry basis)per day .
(

There was only one confirmed reaction to myco-protein, which occurred

in the large trial conducted in the UK (
X7/209). Even amongst
atopics there were no specific reactions to myco-protein nor
exacerbation of existing symptoms.
3.1.2.1.Human Acceptability and Tolerance (
Study code X7/179)
File 25, Part 8, Exhibits 8:3 and 8:4.
File 2, Part 8, Exhibit 8:4.
In a double blind cross-ov er design, 100 subjects consumed 18g/day
(dry basis)of myco-protein in addition to their normal diet over a
period of 30 days. Therewere no reactions indicative of intolerance
to myco-protein, but there was a statistically significant reduction
in blood cholesterol during the myco-protein period.
Experimental design

The study was conducted double blind .

The study began with each subject consumtng myco-protein or placebo ,
in the form of a biscuit, for 30 days. At the end of this first
period there was a break of one week. Each subject then began a
further 30 day period consuming the alternative biscuit.
The study for each subject lasted 67 days during this time each
subject consumed 18g of myco-protein per 30 days (
4 biscuits/dry).
Each subject was interviewed at the end of each week to insure
compliance with the procedure and to note any symptoms which may have
occurred.

225

Results
Only one subject dropped out of the study for
reasons unconnected with the treatments.

Clinical

There were no clinical complaints or indications of

reactions to treatments.

Laboratory

There were no ad v erse cha ng es related to

consumption of myco-protein. There was a small but
significant reduction in blood cholesterol during
myco-protein consumption compared to the control.

Conclusions
The consumption of 18g/day of myco-protein produced no adverse
reactions indicative of intolerance or allergy.
(

There were no ad verse changes in blood and urine analyses, though

there was a significant, beneficial reduction in blood cholesterol
during the consumption of myco-protein.
The results of this and the second protein quality study(
X7/119)have
been published(
Udall, Lo, Young & Scrimshaw, 1984, American Journal
of Clinical Nutrition 40: 285-292)and a copy of the paper is included
as Appendix IV (ile B).

3.1.2.2. Human high level tolerance (

Study code
X7/208)

File 25, Part 8

;Exhibit 8:2

Using a cross-over design, 11 male and 10 female volunteers consumed

40g/day of myco-protein (dry basis )in 2 meals/day. There were no
reactions to myco-protein as measured by medical examination,
including blood and urine analysis, nor were there any other signs of
intolerance to myco-protein.
Experimental design
Subjects were assigned to 2 groups who received either test meals
containing myco-protein or control meals. These were given as two
main meals per day for 16 days. At the end of this time subjects
"crossed over" and followed a further 16 day phase as summarised
below:-

226

Group A

Group B

- male

- female

Phase I (16 days)

myco-protein
(40g/day)

Control

Phase II (16 days)

Control

myco-protein
(
40g/day)

Subjects/group

During the myco-protein phases 1 meal/day was given for the first 4
days, then 2 meals/day from day 5 to 16.
Choice of Subjects Based on medical examination, with blood and
urine analysis, and health questionnaire. Known
atopics, those with liver, kidney or gastrointestinal disease, pregnant or lactating women
were not allowed to participate.
Results

Adherence to
protocol:

Due ..to illness, one subject failed to

complete the trial, although she participated
fully in the myco-protein phase.

SymptOllS :

Only comments were of softer stools, increased

flatus and increased frequency of bowel movements.

Medical
Examinations:

No health changes related to myco-protein. The

only comments were as above.

Urine and Blood

Analyses:

There were some differences between groups and

phases, but there was no consistent treatment
effect. Clinical chemistry and haematology
results are summarised in Tables V:3:5, 6, 7 & 8.

Conclusions
A consum ption of 40g/day (dry
tolerated by man.

basis)of myco-protein is wel 1

227

TARE V:3:5
a.INICAL ClIEMISIRY MEAN VAI.1m
t1iles

O:casion

Group

Serun
Phos-

Serun

C.alciun

phate

cose

Serun

Glu-

P1.aste
Urea

Serun
Uric
Acid

Serun
ili:r

Serun

Total

mrol/ mrol/ mrol/ rrrrol/

1
1
1
1

lest- Proerol tein

mrol/ mrol/ g/1
1
1

2.34

1.15

5.9

4.3

0.35

4.7

75.2

2.31

1.12

5.9

4.9

0.41

4.7

73.7
46.1

2.31

1.14

5.7

3.4

0.35

4.6

72.S

2.33

1.12

s.a

3.2

0.1;}

4.5

2.45

1.13

6.1

4.4

0.39

2.:D

1.19

5.9

5.5

0.
42

Serun

Albumin

Serun

Total

Bili-

Serun
AP

Serun
UH

Serun

cm

Plasm

Plasm
Sodiun

Plasm

Serun

Creatinine

TG

mrol/
1

mrol/
1

Urol/l

mool/
1

Pot&ssil.lll

rub:fn

g/1

Urol/

lliJ/ml

lliJ/ml

lliJ/ml

48.0

16

55

146

31

4.4

143

81

0.91

21

68

154

33

4.0

141

00

1.01

47.7

15*

55*

143

34

4.1

142

00

1.12

74.3

48.2

26

71

152

36

3.9

141

00

1.13

4.7

75.0

49.7

16

58

179

42

4.2

141

81

0.74

4.2

76.3

48.8

2
7

76*

174

44

3.9

141

85

0.g)

Initial
N
N

00

A
Post
Myco-

End of

fTiase I

protein

B
Control
A

End of
FTiase TI

Control
B

Post

Mycoprotein

* Myar-protein group significantly different fron cootrol p<O.C5

')

TAIUV:3:6
a.JNIC.AL OlEMISIRY MFAN VAilm

Femles
O::casion

Group Serun
C.a.1ciun

Serun
Fhos-

Serun
Glu-

phate cose

P1.asre
Ura:i

rmol/ rnrol/ mrol/ rmol/

1
1
1
1

Serun
Ch>Acid lesterol
lllll)l/ rmol/
Serun
Uric

Serun
Total

Pro-

Serun

Albumin

tein
g/1

g/l

Serun
Total

Bili-

Serun
AP

Senm Serun
Ull

ro.r

rubin
Urol/ niJ/ml rdJ/ml niJ/ml
1

h.J

Potassiun

Plasm Plasra
Sodiun Crea-

Serun
1G

tinine

rmol/
1

mrol/
1

Urol/l mrol/
1

2.31

1.19

6.0

4.1

0.33

5.4

76.2

47.9

16

51

157

32

3.9

141

75

1.02

2.23

1.14

5.4

3.4

0.35

5.8

75.0

46.7

11

ff)

163

32

4.0

140

74

1.36

A
Post

2.36

1.15

5.9

3.4*

0.l)

4.9

73.4

46.6

12

51

155

l)

3.7

140

72

0.91

1.19

5.6

4.1

0.34

5.6

76.4

47.6

10

61

172

32

4.1

140

70

0.91

Init ial
( ..)

Plasm

'.[)

End of
Fhase I

Mycoprotein
B
2.37
Control

Fnd of
.A1ase n

2.43

1.25

6.1

4.4

0.34

5.0

74.5

47.4

15

55

174

36

4.2

139

79

0.89

2.42

1.20

5.6

5.8

0.31

5.3

75.0

47.0

10

58

171

31

4.1

140

74

0.83

Control
B

Post
Myco-

protein

* Group A (Myca-protein)significantly different fran control p<0.05

/""\
TA&E V :3:7
HAEMATCI.mY MEAN VAWES
M3.les

Q:casion

Group

PI'

KCT

ESR

Ratio Secs nm/hr

Total
WB::

?-CV t-01

t1lC

fl

g/dl 10911 10911 109;1 109;1 10911 10911

Hb

ROC

FOi

g/dl

iol211

pg

1.23

33

15.3

5.

44

84

29.5 34.8

6.2

3.4

2.4

0.1

0.02

0.3

1.17

31

15.5

5.31

44

83

29.3 35.4

6.4

3.4

2.4

0.2

0.03

0.4

1.15

31

15.3

5.18

44

85

29.4 34.7

7.2

4.5

2.1

0.2

0.02

0.4

Initial

VI

Fnd of

Phase I

FM of
Fhase II

Myco-

protein
B

1.17

31

15.5

5.2<)

44

85

29.3 35.2 . 7.1

4.3

2.2

0.1

0.05

0.5

1.15

39

15.6

S.24 46

87

29.9 34.4

6.4

3.5

2.4

0.2

O.(l)

0.3

1.24

38

15.6

5.31

45

85

29.5

6.9

4t2

2.1

0.2

o.ca

o.s

Post
Mycoprotein

No statistically significant differences beblt!en groups

34.7

,,...

........,

n
' .
TAPl.E V:3:8
HAEMA'Itl.OOY

VA11E3

Famles

Oxasion

Group

Pf

KCT

ESR

Hb

Ratio Secs nrn/hr g/dl

rov

M)./

101211

fl

RB::

ITT!
pg

t1lC

Total
WB:::

g/dl 10911 10911 10911 10911 10911 10911

1.16

31

14.0

4.57

40

87

JJ.8 35.1

5.5

2.9.

2.3

0.2

0.05

0.2

1.16

JJ

13.9

4.59

llJ

86

JJ.3 35.2

6.4

3.5

2.4

0.2

0.05

0.3

LOO

31

13.9

4.54

40

89

JJ.6 34.9

6.4

4.0

2.0

0.1

0.07

0.3

1.00

JJ

14.1

4.(f) 40

88

JJ.2 34.7

5.8

4.3

2.0

0.1

0.02

0.4

1.2:>

38

13.9

4.53

I{)

89

lJ.8 34.9

5.9

3.3

2.0

0.1

0.10

0.3

1.11

38

14.1

463

41

89

Xl.5

34.4

6.9

3.3

2.2

0.1

o.m

0.4

Initial

VI
f-1

End of
Phase I

End of
FTiase TI

Mycoprotein

Post
Mycoprotein