Although uncontrolled hyperglycemia is the major factor, the link between diabetes and susceptibility to various secondary complications has not been unraveled. The polyol pathway of glucose metabolism is activated when intracellular glucose levels are high .The activation is immediately linked to hyperglycemia and occurs prominently in tissues that develop complications . In addition, polymorphisms associated with regions flanking the ALR2 gene have been implicated in human susceptibility to DR and other diabetic complications . There is also a strong evidence to show that diabetic complications including DR are associated with increased oxidative stress , and activation of polyol pathway is known to contribute to oxidative stress.
Vitamin C: An Efficient Way To Lower Sorbitol Levels
Author: Michael Murray, ND, and Michael Lyon, MD
Source: Beat Diabetes Naturally – The Best Foods, Herbs, Supplements, And Lifestyle Strategies To Optimize Your Diabetes Care
Attempts to prevent sorbitol accumulation with drugs have failed due to severe side effects. In contrast, vitamin C is able to accomplish what these drugs could not – safe and effective inhibition of sorbitol accumulation.
In one study in young adults with type I diabetes, baseline measurement of sorbitol in red blood cells were nearly double in these patients despite “adequate” dietary intakes of vitamin C. Vitamin C supplementation at a dosage of either 100 or 600 mg normalized sorbitol in red blood cells within 30 days. This correction of sorbitol accumulation was independent of changes in diabetic control as monitored by fasting glucose or hemoglobin A1C. In fact, overall diabetic control during the study was moderate to poor, indicating that the effect of vitamin C was not dependent on glucose concentration.
These results indicate that vitamin C may inhibit aldose reductase, the enzyme that converts glucose to sorbitol. A test-tube study was conducted to determine the necessary concentration of vitamin C required to inhibit aldose reductase in red blood cells. 2 At concentrations above 100 micromoles, vitamin C reduced sorbitol production by about 30 percent. Levels between 600 and 900 micromoles reduced sorbitol production by about 50 percent. Are these concentrations of vitamin C attainable with supplementation with vitamin C? Absolutely: in fact, the normal level of vitamin C in the plasma and red blood cells is 40 to 120 micromoles. One of the reasons that we recommend 500 to 1,500 mg of vitamin C daily is to boost blood levels into the higher range to inhibit sorbitol production. Remember that the transport of vitamin C into cells is facilitated by insulin, and as a result many diabetics do not have enough intracellular vitamin C. Therefore, a relative vitamin C deficiency exists in many diabetics despite adequate dietary consumption. Supplementation is required.