The results of this study indicate that consumption of 15–30 g/d of HAM-RS2 improved SI
in overweight and obese men. The improvement in SI
relative to control is consistent with data from other studies of HAM-RS2 conducted in men and women in short-term and longer-term feeding trials (14
). However, the present study is the first to our knowledge to show such improvements in SI
at a level of intake as low as 15 g/d HAM-RS2. A previous study did not show an effect following intakes of 12 g/d HAM-RS2 for 6 wk; however, HOMA%S was used as an indicator of SI
, which is less sensitive compared to the method used in the present study (33
). The magnitude of the increase in SI
in men is similar to that observed with weight loss of ~10% of body weight in obese individuals (34
It is unclear why SI
increased in men but not women in the present trial. One of the potential mechanisms for the insulin-sensitizing effects of fermentable fiber is that absorption of SCFA generated in the colon due to fermentation may trigger a reduction in release of FFA and glycerol from adipose depots, presumably through direct or indirect inhibition of hormone sensitive lipase (18
). Numerous studies have demonstrated that maintenance of a lower FFA level for several hours enhances SI
and elevation for several hours has the opposite effect (37
). Hoeg et al. (41
) recently showed that increasing FFA concentrations via intralipid infusion resulted in a decrease in whole-body SI
by 38% in men but only 26% in matched women (P
< 0.05). These results suggest that women are less sensitive to changes in circulating concentrations of FFA. Thus, if HAM-RS2 affects SI
via alterations in FFA levels, the effect might be more readily detectable in men than in women. In the present study, there were no differences in pretest FFA levels in men or women across treatment conditions. However, fasting FFA concentrations were obtained in the morning and may not reflect those that prevail overnight, because sympathetic activation in the morning hours may raise levels more in participants with lower values than in those with higher values (42
). It has been suggested that FFA concentrations in the late evening and overnight periods may be important determinants of SI
and secretion (22
Acetate, the predominant SCFA in plasma, was greater in women after HAM-RS2 consumption compared to control. Differences in the timing and fraction of HAM-RS2 reaching the colon and capacity for colonic fermentation may influence the timing and quantity of SCFA absorption differently in men and women. Although there is considerable individual variability, men generally have accelerated transit times compared with women, which may influence substrate availability for fermentation in the large bowel (44
). Studies in which transit time is accelerated by a pharmacological agent (cisapride) have shown that this produced an increase in fermentation, as measured by breath hydrogen and concentrations of fecal SCFA (45
). Weickert et al. (46
) showed a modest but significant 8% improvement in SI
assessed by euglycemic-hyperinsulinemic clamp in overweight and obese women consuming a fermentable cereal fiber for 72 h, and the effect appeared somewhat larger (13%) in the subset of women with evidence of colonic fermentation as demonstrated by increased breath hydrogen. There is also some evidence of changes in starch fermentation over the course of the menstrual cycle (47
). However, results from other studies have not supported the thesis that there are differences in fermentation between men and women (48
). Because breath hydrogen was not assessed in the present study, it is not possible to determine to what extent differences in HAM-RS2 fermentation in the colon, if any, may have influenced the results.
There is evidence that SI
varies across phases of the menstrual cycle, with observed values higher in the follicular phase and lower in the luteal phase (49
). In the present study, there was some qualitative evidence that menstrual cycle may have confounded the results in premenopausal women, because there was a greater tendency to show improvement among women for whom tests were conducted during the same phase of the menstrual cycle than for women whose tests were not phase concordant. The sample of premenopausal women was too small to provide a meaningful statistical analysis of this effect. However, postmenopausal women also had a lower response than men, suggesting that confounding due to menstrual cycle phase cannot entirely explain the difference in SI
responses between men and women. Exclusion of women using contraceptive or postmenopausal sex hormones from the analysis did not alter the results.
Another possible explanation may relate to differences between men and women in baseline SI. During the control condition, SI was ~26% higher for women than for men. It is possible that RS-induced improvements in SI are more likely in individuals with lower baseline levels. However, a post hoc analysis of responses in participants higher and lower than the median SI value within each sex did not provide clear evidence to support this possibility. Future research to better understand sex differences in SI and relationships to fermentation capacity, SCFA, FFA, and circulating hormones is warranted.
The present study has several limitations. Dietary intake, including dietary fiber, was not assessed; therefore, we cannot rule out that changes in dietary composition influenced the study results or a treatment × fiber intake interaction. However, each participant acted as his or her own control and maintained his or her usual dietary habits except for consumption of the study product, reducing the likelihood of such effects. Neither breath hydrogen nor fecal SCFA were measured, and levels of FFA, SCFA, adiponectin, hsCRP, and other blood analytes were measured only once at the end of each treatment condition and in the fasting state. Nevertheless, the improvement in SI observed in men at an intake as low as 15 g/d extends the results reported in previous studies after feeding 30–60 g/d of HAM-RS2.
In conclusion, the present results showed that consumption of 15 and 30 g/d of HAM-RS2 improved SI in overweight and obese men. No significant change in SI was observed in women for reasons that remain to be determined. Additional investigation will be required to further delineate the mechanisms responsible for improved SI during HAM-RS2 consumption.