The intake of total dietary energy at baseline did not differ between groups, nor did absolute amounts of protein, carbohydrate, and fat (Table ). Relative to total energy intake, the intakes of protein, carbohydrate, and fat energy at baseline for LC and LF, expressed as percent of total energy, were 15.9%, 50.2%, and 32.6; and 16.6%, 47.7%, and 34.9%; respectively.
Dietary data at baseline and during LF and LC interventions.
Dietary intervention decreased mean total energy intake to 1470 kcal in LF and to 1705 kcal/day in LC (p < 0.01), representing mean changes from baseline of -32.5% and -26.5%, respectively. During intervention, carbohydrate intake averaged 212 g/day (57% of total energy) in LF compared to 53 g/day (12% of total energy intake) in LC. Protein intake averaged 94 g/day (19% of total energy) in LF and 115 g/day (28% of total energy) in LC. Fat intake averaged 37 g/day (23% of total energy) in LF and 112 g/day (59% of total energy) in LC. All between-group differences in macronutrient gram intake were significant (p < 1e-10, Table ).
Body mass and composition
There were no differences in body size or composition between groups at baseline. With diet intervention, the change in total body, fat, and lean masses were significantly greater in LC (Table ).
Baseline and change in total body mass and composition for LC and LF.
Figure depicts the baseline and changes in % body fat profiles in the LF and LC study populations. The distributions are approximately normal and the baseline percent body fat levels for LF (35.4 ± 7.8%) and LC (34.5% ± 7.3%) were not different between groups. Overall LC induced an absolute decrease in % body fat of 2.98 ± 2.62%, reflecting losses of 4.8 kg of fat mass and 1.42 kg of lean mass, compared to a % fat decrease of 1.92 ± 1.63% in LF (p < 0.01), reflecting losses of 3.18 kg for fat mass and 0.70 kg for lean mass. Men outnumbered women in both study groups and had lower baseline % body fat in both groups (33.7 vs. 37.6 LF, and 32.9 vs. 38.0 LC) (Table ). The change in % body fat (Δ%BF) due to diet was greater for men versus women (Table ). For physiogenomics analyses, we employed gender as a covariate to account for the difference.
Figure 1 Distribution of baseline and change in percent body fat for LF (top) and LC (bottom) groups. The vertical axes (Frequency) indicates the number of patients observed within a given 10% interval up to 60% (baseline, left panels) or within a given 2% or (more ...)
Table lists the results of the association tests, comparing LF and LC groups. A single SNP rs322695 in the RARB gene was significantly associated with Δ%BF for both the LF and LC interventions (p < 0.0001 and p < 0.0121, respectively). SNPs in the HNMT (rs3100722, p < 0.002) and PFKL genes (rs2838549, p < 0.002) were significant only for the LF group. Conversely, the rs5950584 SNP in the AGTR2 gene was significant only for the LC group (p < 0.0001). The FDR-corrected p values yield an estimate of the false positive rate. The following SNPs, RARB rs322695, HNMT rs1269140, and PFKL rs2838549 and associations in LF, and the AGTR2 SNP rs5950584 association in LC are clearly significant after the FDR correction (p < 0.005, p < 0.041, p < 0.041, and p < 0.041, respectively). All remaining genes showed no significant association in either treatment group, and no gene showed significance for both diet treatments after adjusting for multiple tests.
Significance levels of gene SNPs associated with % body fat change profiles for carbohydrate-restricted (LC) and fat-restricted (LF) diet treatments.
Figure shows the top three markers (according to p value) related to LF response. The first panel shows the LOESS curve for SNP rs322695 of the RARB gene. The frequency of the minor allele increases as the Δ%BF response to the LF diet becomes less pronounced (i.e., no loss of relative fat mass). The minor allele is completely absent among subjects with the largest decreases in %BF, and the frequency is <10% among subjects whose decrease in %BF exceeded 1%. This finding indicates a strong association between the RARB marker and response to LF. Similar patterns are seen for HNMT rs3100722 and PFKL SNP rs2838549. The SNPs, RARB SNP rs322695, HNMT SNP rs3100722, and PFKL SNP rs2838549, are considered "torpid" markers for responsiveness to the LF diet.
Figure 2 Physiogenomic representation of the most significant genetic associations found in the low fat diet group. Individual patient genotypes (circles) of each SNP are overlaid on the distribution of Δ%BF (thin line). Each circle represents a patient, (more ...)
Figure shows the top three markers associated with Δ%BF through LC. The first panel in Figure shows the LOESS curve for SNP rs5950584 of the AGTR2 gene. The frequency of the minor allele is 30% in the Δ%BF range that is less than -5%, and the minor allele is completely absent among subjects with subtle change in Δ%BF (i.e., no loss of relative fat). A similar pattern is seen with the GYS2 SNP rs1478290. These two SNPs are considered reactive markers. The third panel shows the RARB SNP rs322695 response. The minor allele shows a higher frequency in the subject with little response in Δ%BF, indicating that the RARB SNP rs322695 is a torpid marker of responsiveness to LC diet also.
Figure 3 Physiogenomic representation of the most significant genetic associations found in the low carbohydrate group. See Figure 2 legend for details regarding individual patient genotypes (circles), the distribution of Δ%BF (thin line), and the LOESS (more ...)