Dietary Resistant Starch Prevents Urinary Excretion of Vitamin D Metabolites and Maintains Circulating 25-Hydroxycholecalciferol Concentrations in Zucker Diabetic Fatty Rats

Background: Type 2 diabetes (T2D) is the leading cause of nephropathy in the United States. Renal complications of T2D include proteinuria and suboptimal serum 25-hydroxycholecalciferol (25D) concentrations. 25D is the major circulating form of vitamin D and renal reabsorption of the 25D–vitamin D–binding protein (DBP) complex via megalin-mediated endocytosis is believed to determine whether 25D can be activated to 1,25-dihydroxycholecalciferol (1,25D) or returned to circulation. We previously demonstrated that excessive urinary excretion of 25D–DBP and albuminuria occurred in rats with type 1 diabetes (T1D) and T2D. Moreover, feeding rats with T1D high-amylose maize partially resistant to digestion [resistant starch (RS)] prevented excretion of 25D–DBP without significantly affecting hyperglycemia.

Objective: We used Zucker diabetic fatty (ZDF) rats, a model of obesity-related T2D, to determine whether feeding RS could similarly prevent loss of vitamin D and maintain serum 25D concentrations.

Methods: Lean control Zucker rats (n = 8) were fed a standard semi-purified diet (AIN-93G) and ZDF rats were fed either the AIN-93G diet (n = 8) or the AIN-93G diet in which cornstarch was replaced with RS (550 g/kg diet; 35% resistant to digestion) (n = 8) for 6 wk.

Results: RS attenuated hyperglycemia by 41% (P < 0.01) and prevented urinary DBP excretion and albuminuria, which were elevated 3.0- (P < 0.01) and 3.6-fold (P < 0.01), respectively, in control diet–fed ZDF rats. Additionally, urinary excretion of 25D (P = 0.01) and 1,25D (P = 0.03) was higher (89% and 97%, respectively), whereas serum 25D concentrations were 31% lower (P < 0.001) in ZDF rats fed the control diet compared with RS-fed ZDF rats. Histopathologic scoring of the kidney revealed that RS attenuated diabetes-mediated damage by 21% (P = 0.12) despite an 50% decrease in megalin protein abundance.

Conclusions: Taken together, these data provide evidence that suggests vitamin D balance can be maintained by dietary RS through nephroprotective actions in T2D, which are independent of vitamin D supplementation and renal expression of megalin.


Alex’s Notes: I’m a sucker for resistant starch (RS), ever since Adel Moussa wrote about the benefits of hydroxypropyl-distarch phosphate. And now it appears that RS helps maintain vitamin D levels, at least according to the title and abstract. So let’s take a closer look shall we.

Male ZDF (diabetic) and lean Zucker control rats were randomly assigned to a diet containing either cornstarch (550 g/kg diet, control diet) or high-amylose maize (550 g/kg diet) that was 35% resistant to digestion. Thus, rats were divided into three groups (n = 8 per group):

  1. Zucker lean control rats fed a standard control diet (LCs);
  2. ZDF rats fed a standard control diet containing 55% cornstarch (DCs); and
  3. ZDF rats fed an RS diet in which the cornstarch was replaced with an equivalent amount of high-amylose maize (DRSs).

All the rats were provided ad libitum access to food and water for six weeks. At the end of it all, the DCs growth was stunted by three weeks while the other groups continued to gain for all six weeks, and the DRSs gained 24% and 51% more weight than LCs and DCs, respectively. Fasting glucose concentrations were 3-fold higher in DCs relative to LCs, but only 1.4-fold higher in DRSs compared to LCs. Urinary creatinine concentrations were 91% and 86% higher in LCs and DRSs, respectively, compared with DCs, but there was no difference between LCs and DRSs; urinary total protein did not differ between LCs and DRSs, but was 4.2- and 1.6-fold higher in DCs compared with LCs and DRSs, respectively; and urinary albumin was 3.6-fold greater in DCs than in DRSs with no differences between LCs and DRSs

“The renal histopathologic score of DCs was highest among the treatments (48% higher than LCs) and renal pathologic scores of DRSs did not differ from LCs or DCs. Similarly, kidney weights in DCs were greater than in LCs and DRSs (16% and 26%, respectively), and we did not detect a difference in kidney weight between LCs and DRSs. The vitamin D status of DCs, as indicated by serum 25D concentrations, was 45% lower than in LCs and 31% lower than in DRSs. Serum 1,25D did not differ between groups regardless of serum 25D status.”

In other words, RS virtually prevented proteinuria and urinary excretion of vitamin D, thereby maintaining serum vitamin D concentrations. Moreover, RS promoted the most growth despite consuming 40% less food than DCs. This suggests that RS attenuated a glycemic insult to the kidney of diabetic rats fed the cornstarch-based control diet, and thus kidney function was protected, which in turn promoted vitamin D balance in hyperglycemic ZDF rats.

So why does this matter?

It is estimated that out of all documented cases of renal failure in the United States, 44% are caused by diabetes. Because the maintenance of circulating 25(OH)D and 1,25(OH)2D concentrations is dependent on kidney function, it is not surprising that compromised vitamin D status is a concern in diabetic patients. Of course given that the kidney plays a pivotal role in all nutrient reabsorption, the benefits of RS are likely seen with other vitamins and minerals as well.

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