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A low carbohydrate, high protein diet suppresses intratumoral androgen synthesis and slows castration-resistant prostate tumor growth in mice.

The Journal of steroid biochemistry and molecular biology
June 1, 2015
H Bobby Fokidis et al. (11 authors)
Journal ArticleResearch Support, Non-U.S. Gov'tAnimal Study
Study Details

Study Goal

The researchers aimed to determine the impact of a low carbohydrate diet compared to a Western diet on prostate cancer tumor growth and steroid regulation in mice.

Results Summary

The study found that a low carbohydrate diet significantly reduced tumor growth rate in castrated mice but not in intact mice. It also altered steroid profiles and cholesterol levels, with lower DHT concentrations in the low carb group.

Population

Mice bearing LNCaP xenograft tumors (intact and castrated).

Effective Dosage

Not specified

Duration

Not specified

Interactions

None mentioned

Extracted Claims (16)
InterventionDirectionEndpointPopulationDosageImpactClaim #
low carbohydrate diet
decrease
tumor growth rate
castrated mice
-
saw a statistically significant reduction
#1
low carbohydrate diet
no change
LNCaP tumor progression (total tumor volume)
intact mice
-
No differences
#2
low carbohydrate diet
no change
serum PSA
-
-
No correlation
#3
low carbohydrate diet
neutral
Steroid profiles, alongside serum cholesterol and cholesteryl ester levels
-
-
significantly altered
#4
low carbohydrate diet
decrease
DHT concentration
CRPC-bearing mice
58%
was 58% that of
#5
low carbohydrate diet
increase
AKR1C3 protein levels
tumors isolated from intact mice
-
had higher
#6
low carbohydrate diet
decrease
HSD17B2 protein levels
intact mice
-
had lower
#7
low carbohydrate diet
increase
HSD17B2
CRPC tumors from mice
-
had higher concentrations
#8
low carbohydrate diet
increase
SRD5A1 enzymes
CRPC tumors from mice
-
had higher concentrations
#9
low carbohydrate diet
no change
serum insulin
castrated mice
-
no correlation
#10
low carbohydrate diet
no change
GH serum levels
castrated mice
-
no correlation
#11
low carbohydrate diet
no change
insulin receptor (IR) in tumor tissue
castrated mice
-
no correlation
#12
low carbohydrate diet
no change
IGF-1R in tumor tissue
castrated mice
-
no correlation
#13
Western diet
increase
serum insulin
Intact mice
-
had higher
#14
Western diet
increase
blood glucose
Intact mice
-
associated with significantly higher
#15
Western diet
increase
tumor tissue IR
Intact mice
-
associated with significantly higher
#16
Abstract

Dietary factors continue to preside as dominant influences in prostate cancer prevalence and progression-free survival following primary treatment. We investigated the influence of a low carbohydrate diet, compared to a typical Western diet, on prostate cancer (PCa) tumor growth in vivo. LNCaP xenograft tumor growth was studied in both intact and castrated mice, representing a more advanced castration resistant PCa (CRPC). No differences in LNCaP tumor progression (total tumor volume) with diet was observed for intact mice (P = 0.471) however, castrated mice on the Low Carb diet saw a statistically significant reduction in tumor growth rate compared with Western diet fed mice (P = 0.017). No correlation with serum PSA was observed. Steroid profiles, alongside serum cholesterol and cholesteryl ester levels, were significantly altered by both diet and castration. Specifically, DHT concentration with the Low Carb diet was 58% that of the CRPC-bearing mice on the Western diet. Enzymes in the steroidogenesis pathway were directly impacted and tumors isolated from intact mice on the Low Carb diet had higher AKR1C3 protein levels and lower HSD17B2 protein levels than intact mice on the Western diet (ARK1C3: P = 0.074; HSD17B2: P = 0.091, with α = 0.1). In contrast, CRPC tumors from mice on Low Carb diets had higher concentrations of both HSD17B2 (P = 0.016) and SRD5A1 (P = 0.058 with α = 0.1) enzymes. There was no correlation between tumor growth in castrated mice for Low Carb diet versus Western diet and (a) serum insulin (b) GH serum levels (c) insulin receptor (IR) or (d) IGF-1R in tumor tissue. Intact mice fed Western diet had higher serum insulin which was associated with significantly higher blood glucose and tumor tissue IR. We conclude that both diet and castration have a significant impact on the endocrinology of mice bearing LNCaP xenograft tumors. The observed effects of diet on cholesterol and steroid regulation impact tumor tissue DHT specifically and are likely to be mechanistic drivers behind the observed tumor growth suppression.

Medical Subject Headings (MeSH)
3-Hydroxysteroid Dehydrogenases3-Oxo-5-alpha-Steroid 4-DehydrogenaseAdenocarcinomaAldo-Keto Reductase Family 1 Member C3AndrogensAnimalsBlood GlucoseCastrationCholesterolCholesterol EstersDiet, Carbohydrate-RestrictedDiet, WesternDietary ProteinsEstradiol DehydrogenasesGene Expression RegulationGrowth HormoneHumansHydroxyprostaglandin DehydrogenasesInsulinMaleMembrane ProteinsMiceNeoplasm TransplantationProstateProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantReceptor, IGF Type 1Receptor, InsulinTransplantation, HeterologousTumor Burden
Study Links
Quality Scores
SafetyNot Assessed
Efficacy75/10
Quality85/10
Citation Metrics
Total Citations23
Citations/Year2.3
Relative Citation Ratio0.87
NIH Percentile45%
Research Impact Scores
APT Score0.25
Weight Score0.91
Normalized Score0.67
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