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. 2012 Oct 9;2012:105949. doi: 10.1155/2012/105949

Table 2.

Impact of experimental design on blood and tissue folate.

Animal model Experimental diet Abx Wire cages Length of feeding In vivo folate levels Citation
Rat studies quantifying impact of dietary intervention on blood and/or tissue folate status
Sprague-Dawley rats Amino acid defined (Dyets)
Control group:
8 mg/kg folate
Experimental group:
0 mg/kg folate		 No Yes 25 weeks Folate levels (nmol/g)
Control group:
Liver 27.11
Kidney 11.69
Spleen 3.74
Brain 0.65
Experimental group:
Liver 11.10
Kidney 4.79
Spleen 1.29
Brain 0.60
 [71]
Sprague-Dawley rats Amino acid defined (Dyets)
Control group:
2 mg/kg folate
Experimental groups:
0 mg/kg folate
8 mg/kg folate
20 mg/kg folate		 No Yes 8 weeks Control group:
Plasma folate (ng/mL)~50
Colonic folate (ng/mL)~650
Experimental groups:
Deficient
 Plasma folate (ng/mL)~25
 Colonic folate (ng/mL) ~480
Supplemented (8 mg/kg)
 Plasma folate (ng/mL) ~80
 Colonic folate (ng/mL) ~975
Supplemented (20 mg/kg)
 Plasma folate (ng/mL) ~140
 Colonic folate (ng/mL) ~975		 [83]
Sprague-Dawley rats AIN-76 semipurified diet
Control group:
8 mg/kg folate, no abx
Experimental groups:
0 mg/kg folate, no abx
0 mg/kg folate, with abx first 4 weeks of feeding
0 mg/kg folate, with abx last 4 weeks of feeding		 Yes and no Yes 12 weeks Whole blood folate
Control group:
657 ng/mL
Experimental group:
125 ng/mL (no abx)
114 ng/mL (abx first 4 weeks)
61 ng/mL (abx last 4 weeks) 		[72]
Sprague-Dawley rats AIN-76 semipurified diet
Control group:
8 mg/kg folate, no abx
Experimental groups:
0 mg/kg folate, no abx
0 mg/kg folate, with abx first 4 weeks of feeding
0 mg/kg folate, with abx 4 weeks after AOM		 Yes and no Yes 26 weeks Whole blood folate
Control group:
684 ng/mL
Experimental groups:
694 ng/mL (control + abx)
99 ng/mL (0 mg/kg, no abx)
100 ng/mL (0 mg/kg, abx first 4 weeks)
96 ng/mL (0 mg/kg, abx 4 weeks after AOM)
Colon folate
Control group:
9.6 ug/mg
Experimental groups:
8.0 ug/mg (control + abx)
2.7 ug/mg (0 mg/kg, no abx)
3.1 ug/mg (0 mg/kg, abx first 4 weeks)
4.3 ug/mg (0 mg/kg, abx 4 weeks after AOM)		 [73]
Sprague-Dawley rats AIN93 (G or M not Specified)
Control group:
2 mg/kg folate
Experimental group:
0 mg/kg folate		 No No 20 weeks Hepatic folate (nmol/g)
Control group:
17 nmol/g (weanling)
17 nmol/g (12 month old)
Experimental group:
2.7 nmol/g (weanling)
1.8 nmol/g (12 month old)		 [74]
Sprague Dawley rats AIN93 purified diet (G or M not specified)
Control group
2 mg/kg (folate-replete)
Experimental groups:
0 mg/kg
folate
8 mg/kg 		No Yes 20 weeks Plasma folate
    Young Old
Control group:
(umol/L) 34.1 30.6
[(ng/mL) 15.1 13.5]
Experimental group:
Deficient
  (umol/L) 1.5, 0.9
  [(ng/mL) 0.7 0.04]
Supplemented:
  (umol/L)  53.9 55.5
  [(ng/mL 23.8 24.6]
Colon (nmol/g)
Young Old
Control
 4.7 3.0
Deficient
 1.3 0.7
Supplemented
 5.6 4.4		 [75]
Fischer-344 rats AIN-93 diet
Control group:
2 mg/kg folate
Experimental group:
0 mg/kg folate
Note: selenium assessed in this paper, not evaluated here.		 No Yes 11 weeks Plasma folate
Control group:
277.4 nmol/L
[122.44 ng/mL]
Experimental group:
12.0 nmol/L
[5.30 ng/mL] 		[85]
Sprague-Dawley rats Amino acid defined (Dyets)
All animals fed same diet (2 mg/kg folate) for first 10 weeks; 5 weeks following completion of carcinogen exposure, experimental diets began.
Control group:
2 mg/kg folate
Experimental groups:
0 mg/kg folate
5 mg/kg folate
8 mg/kg folate		 Yes No 24 weeks Plasma folate
Control group:
32.2 ng/mL
Experimental groups:
Deficient
 6.0 ng/mL
Supplemented (5 mg/kg)
 72.8 ng/mL
Supplemented (8 mg/kg)
 78.2 ng/mL
Hepatic folate
Control group:
 7.7 ug/g
Experimental groups:
Deficient
 5.0 ug/g
Supplemented (5 mg/kg)
 8.5 ug/g
Supplemented (8 mg/kg)
 9.9 ug/g		 [76]
Male Hooded-Lister
rats 		AIN-93G purified diet with vitamin-free casein
Control group:
5 mg/kg folate
Experimental group:
0 mg/kg folate		 No Yes 6 weeks Folate value, ng/mg protein
Lymphocytes
 Control: 0.45
 Experimental: 0.27
Liver
 Control: 136.2
 Experimental: 93.9
Colon (descending)
 Control: 24.6
 Experimental: 9.9
Spleen
 Control: 16.5
 Experimental: 7.9
Kidney
 Control: 58.6
 Experimental: 26.6
Brain
 Control: 20.4
 Experimental: 15.3
Heart
 Control: 9.2
 Experimental: 3.4		 [82]
Mouse studies quantifying impact of dietary intervention on blood and/or tissue folate status
C57bl/6J mice, APCMin Amino acid defined (Dyets)
Control group:
2 mg/kg folate
Experimental group:
0 mg/kg folate
8 mg/kg folate*
20 mg/kg folate		 No No 3 months;
6 months		 Serum folate (ng/mL):
Control group:
39.0 (3 months)
35.4 (6 months)
Experimental group:
Depleted
 12.1 (3 months)
 10.8 (6 months)
Supplemented
 56.0 (3 months)
 46.0 (6 months)
Hypersupplemented
 49.9 (3 months)
 43.3 (6 months) 		[77]
C57bl/6 mice, β-pol+/− AIN-93G purified diet with vitamin-free casein
Control group:
2 mg/kg folate
Experimental group:
0 mg/kg folate		 Yes No 8 weeks Serum folate
Control group:
60 ng/mL
Experimental group:
<5 ng/mL		 [21]
C57bl/6 mice, Aag−/− AIN-93G purified diet with vitamin-free casein
Control group:
2 mg/kg folate
Experimental group:
0 mg/kg folate		 Yes Yes 4 weeks Liver folate
Control group
27.0 μg/g
Experimental group
1.2 μg/g		 [39]
          Apc +/+ crossed to SHMT genotype as indicated (+/+, +/−, −/−)
Control group: (5 weeks)
Plasma (ng/mL)
 58.56 (+/+)
 58.34 (+/−)
 40.82 (−/−)
Liver (fmol/ug pro)
 51.80 (+/+)
 56.65 (+/−)
 50.77 (−/−)
C57bl/6 mice,
Apc min/+ Shmt1 (+/− and −/−)		 AIN-93G purified diet
Control group:
2 mg/kg folate
2.5 g/kg choline
Experimental group:
0 mg/kg folate
0 g/kg choline		 No Yes 5 weeks (Apc+/+); 11 weeks (Apcmin/+) Colon (fmol/ugpro)
 35.14 (+/+)
 21.46 (+/−)
 17.09 (−/−)
Experimental group: (5 weeks)
Plasma (ng/mL)
 20.60 (+/+)
 38.95 (+/−)
 8.52 (−/−)
Liver (fmol/ug pro)
 47.26 (+/+)
 44.30 (+/−)
 48.88 (−/−)
Colon (fmol/ugpro)
 9.15 (+/+)
 18.04 (+/−)
 14.89 (−/−)
Apc min/+ crossed to Shmt genotype indicated (+/+, +/−, −/−)
Control group: (11 weeks)
Plasma (ng/mL)
 24.68 (+/+)
 20.91 (+/−)
 26.44 (−/−)
Liver (fmol/ug pro)
 45.72 (+/+)
 40.00 (+/−)
 41.50 (−/−)
Experimental group: (11 weeks)
Plasma (ng/mL)
 11.79 (+/+)
 8.37 (+/−)
 9.97 (−/−)
Liver (fmol/ug pro)
 28.49 (+/+)
 23.25 (+/−)
 29.44 (−/−)		 [68]
C57bl/6J mice, Shmt (+/− and −/−) AIN-93G purified diet
Control group:
2 mg/kg folate
2.5 g/kg choline
Experimental group:
0 mg/kg folate
0 g/kg choline		 No No 32 weeks Control group:
Plasma folate (ng/mL)
  (wt)  36.3
  (Tg)  46.8
Liver folate (fmol/ug pro)
  (wt)  43.1
  (Tg)  51.3
Experimental group:
Plasma folate (ng/mL)
  (wt)  7.4
  (Tg)  5.5
Liver folate (fmol/ug pro)
  (wt)  36.1
  (Tg)  34.0		 [68]
C57bl/6 mice, APC1638N Amino acid defined (Dyets)
Control group:
2 mg/kg folate
B-vitamin adequate
Experimental group:
0 mg/kg folate
B12, B6, and riboflavin deficient		 No No 16 weeks Control group:
Plasma folate (ng/mL) ~170
Colon folate (ng/g) ~500
Experimental group:
Plasma folate (ng/mL) ~110
Colon folate (ng/g) ~300		 [84]
C57bl/6 mice, APC1638N Maternal diet:
AIN93M (Dyets)
Control and experimental
Offspring diet:
AIN93G during first 16 weeks of life
AIN93M during last 16 weeks of life (Dyets)
Control and experimental
Control group:
2 mg/kg folate
6 mg/kg riboflavin
7 mg/kg B6
50 ug/kg B12
Experimental groups:
Deficient
 0.5 mg/kg folate
 2 mg/kg riboflavin
 2 mg/kg B6
 10 ug/kg B12
Supplemented
 8 mg/kg folate
 24 mg/kg riboflavin
 28 mg/kg B6
 200 ug/kg B12		 No No Maternal diet:
Fed 4 weeks preconception through weaning
Offspring diet:
32 weeks 		Maternal
Control group:
Plasma folate (ng/mL) 84.7
Hepatic folate (ug/g) 13.2
Experimental group:
Deficient
 Plasma folate (ng/mL) 81.4
 Hepatic folate (ug/g) 11.1
Supplemented
 Plasma folate (ng/mL) 104.4
 Hepatic folate (ug/g) 13.3
Offspring
Control group:
 Plasma folate (ng/mL) 52.5
 Hepatic folate (ug/g) 14.1
 Sm Int folate (ng/g) 1205.9
Experimental group:
Deficient
 Plasma folate (ng/mL) 59.3
 Hepatic folate (ug/g) 12.9
 Sm Int folate (ng/g) 1264.7
Supplemented
 Plasma folate (ng/mL) 50.2
 Hepatic folate (ug/g) 13.3
 Sm Int folate (ng/g) 1172.4		 [78]
Folate depletion studies presenting critical colorectal cancer endpoints, but without folate status information
Fisher 344 rats AIN93G
Control group:
2 mg/kg folate, −abx
Experimental groups:
0 mg/kg folate, −abx
0 mg/kg folate, +abx		 Yes and no No 5 weeks ND [15]
Fisher 344 rats NIH-31
Control group:
0.4% methionine
0.3% choline
2 mg/kg folate
Experimental group:
Low methionine
0% choline
0 mg/kg folate		 No No 36 weeks
54 weeks		 ND [79]
C57bl/6J mice Casein/soy based
Control group:
2 mg/kg folate
Experimental group:
0 mg/kg folate		 No No 10 weeks ND [80]
BALB/cAnNCrlBR mice Amino acid defined (Harlan Teklad)
Control group:
2 mg/kg folate
Experimental group:
0.3 mg/kg folate		 Yes No 12 to 14 months ND [81]
C57bl/6 mice Bpol+/− AIN93G (Dyets)
Control group:
2 mg/kg folate
Experimental group:
0 mg/kg folate		 Yes No 12 weeks total
(6 pre-DMH; 6 post-DMH)		 ND [59]
Albino rats AIN93M
Control group:
2 mg/kg folate
Experimental groups:
8 mg/kg folate
40 mg/kg folate		 No No 6 weeks total (4 weeks pre-AOM; 2 weeks post-AOM) ND [86]

Values in brackets [] have been calculated from published values for ease of comparison across studies; +/+, +/− and −/− refer to wildtype, heterozygous and null genotypes; ND: not determined.