Appendix A: Why is Protein Restriction so Common?

from Dr. Bernstein’s book “Diabetes Solution”
© 2007 by Richard K. Bernstein, M.D.


About 30 percent of diabetics develop kidney disease (nephropathy). Diabetes is the greatest single cause of kidney failure in the United States. Early kidney changes can be found within two to three years of the onset of high blood sugars. As we discussed briefly in Chapter 9, the common restrictions on protein intake by diabetic patients derive from fear regarding this problem, and ignorance of the actual causes of diabetic kidney disease.

*If your physician finds all of this hard to believe, he or she might benefit from reading the seventy articles and abstracts on this subject contained in the Proceedings of the Fifteenth International Diabetes Foundation Satellite Symposium on “Diabetes and Macrovascular Complications,”Diabetes 45, Supplement 3, July 1996. Also worth reading is “Effects of Varying Carbohydrate Content of Diet in Patients with Non-Insulin Dependent Diabetes Mellitus,” by Garg et al., Jnl Amer Med Assoc 1994; 271:1421–1428.

By looking at how the kidney functions, one can better understand the relative roles of glucose and protein in the kidney failure of diabetes. The kidney filters wastes, glucose, drugs, and other potentially toxic materials from the blood and deposits them into the urine. It is the urine-making organ. A normal kidney contains about 6 million microscopic blood filters, called glomeruli. Figure A-1 illustrates how blood enters a glomerulus through a tiny artery called the incoming arteriole. The arteriole feeds a bundle or tuft of tiny vessels called capillaries. The capillaries contain tiny holes or pores that carry a negative electrical charge. The downstream ends of the capillaries merge into an outgoing arteriole, which is narrower than the incoming arteriole. This narrowing results in high fluid pressure when blood flows through the capillary tuft. The high pressure forces some of the water in the blood through the pores of the capillaries. This water dribbles into the capsule surrounding the capillary tuft. The capsule, acting like a funnel, empties the water into a pipelike structure called the tubule. The pores of the capillaries are of such a size that small molecules in the blood, such as glucose and urea, can pass through with the water to form urine. In a normal kidney, large molecules, such as proteins, cannot readily get through the pores. Since most blood proteins carry negative electrical charges, even the smaller proteins in the blood cannot easily get through the pores, because they are repelled by the negative charge on each pore.

The glomerular filtration rate (GFR) is a measure of how much filtering the kidneys perform in a given period of time. Many diabetics with frequent high blood sugars and normal kidneys will initially have an excessively high GFR. This is in part because blood glucose draws water into the bloodstream from the surrounding tissues, thus increasing blood volume, blood pressure, and blood flow through the kidneys. A GFR that is one-and-a-half to two times normal is not uncommon in diabetics with high blood sugars prior to the onset of permanent injury to their kidneys. These people may typically have as much glucose in a 24-hour urine collection as the weight of 5 to 50 packets of sugar. According to an Italian study, an increase in blood sugar from 80 mg/dl to 272 mg/dl resulted in an average GFR increase of 40 percent even in diabetics with kidneys that were not fully functional. Before we knew about glycosylation of proteins and the other toxic effects of glucose upon blood vessels, it was speculated that the cause of diabetic kidney disease (nephropathy) was this excessive filtration (hyperfiltration). The metabolism of dietary protein produces waste products such as urea and ammonium, which contain nitrogen.* It therefore had been speculated that in order to clear these wastes from the blood, people eating large amounts of protein would have elevated GFRs. As a result, diabetics have been urged to reduce their protein intake to low levels.

Studies by an Israeli group, however, of nondiabetic people on high protein (meat-eating) and very low protein (vegetarian) diets, disclosed no difference in GFRs. Furthermore, over many years on these diets, kidney function was unchanged between the two groups. A report from Denmark described a study in which type 1 diabetics without discernible kidney disease were put on protein-restricted diets, and experienced a very small reduction in GFR and no change in other measures of kidney function.

As long ago as 1984, a study appeared in the journal Diabetic Nephropathy demonstrating that elevated GFR is neither a necessary nor a sufficient condition for the development of diabetic kidney disease. This evidence would suggest that the currently prevailing admonition to all diabetics to reduce protein intake is unjustified.

*A 1995 article in the journal Nutritional Biochemistry, 6:411–437, demonstrated that a higher protein diet enables the kidneys to increase their capacity for net acid secretion as ammonium.

Studies on diabetic rats have shown the following: Rats with blood sugars maintained at 250 mg/dl rapidly develop diabetic nephropathy (kidney disease). If their dietary protein is increased, kidney destruction accelerates. At the same laboratory, diabetic rats with blood sugars maintained at 100 mg/dl live full lives and never develop nephropathy, no matter how much protein they consume. Diabetic rats with high blood sugars and significant nephropathy have shown total reversal of their kidney disease after blood sugars were normalized for several

Other studies have enabled researchers to piece together a scenario for the causes of diabetic nephropathy, where glycosylation of proteins, abnormal clotting factors, abnormal platelets, antibodies to glycosylated proteins, and so on, join together to injure glomerular capillaries. Early injury may only cause reduction of electrical charge on the pores. As a result, negatively charged proteins such as albumin leak through the pores and appear in the urine. Glycosylated proteins
leak through pores much earlier than normal proteins.

High blood pressure, and especially high serum insulin levels, can increase GFR and force even more protein to leak through the pores. If some of these proteins are glycosylated or glycated, they will stick to the mesangium, the tissue between the capillaries. Examination of diabetic glomeruli indeed discloses large deposits of glycated proteins and antibodies to glycated proteins in capillary walls and mesangium. As these deposits increase, the mesangium compresses the capillaries, causing pressure in the capillaries to increase (enlarging the pores) and larger proteins to leak from the pores. This leads to more thickening of the mesangium, more compression of the capillaries, and acceleration of destruction.

Eventually the mesangium and capillaries become a mass of scar tissue. Independently of this, both high blood sugars and glycated proteins cause mesangial cells to produce type IV collagen, a fibrous material that further increases their bulk. Increase in mesangial volume has been found to be commonplace in poorly controlled diabetes even before albumin or other proteins appear in the urine.

Many studies performed on humans show that when blood sugars improve, GFR improves and less protein leaks into the urine. When blood sugars remain high, however, there is further deterioration. There is a point of no return, where a glomerulus has been so injured that no amount of blood sugar improvement can revive it. Although this seems to be true for humans, blood sugar normalization has actually brought about the appearance of new glomeruli in rats.

Nowadays many diabetics who have lost all kidney function are treated by artificial kidneys (dialysis machines) that remove nitrogenous wastes from the blood. In order to reduce the weekly number of dialysis treatments, which are costly and unpleasant, patients are severely restricted in their consumption of both water and dietary protein. Instead of using large amounts of carbohydrate to replace the lost calories, many dialysis centers now recommend olive oil to their diabetics. Olive oil is high in monounsaturated fats, which are believed to lower the risk of heart disease.

Because the survival rate of diabetics on dialysis is so much lower than that of nondiabetics, some dialysis centers are now using low carbohydrate, high-protein diets for their diabetic patients.

In summary: Diabetic nephropathy does not appear if blood sugar is kept normal. Dietary protein does not cause diabetic nephropathy, but can possibly (still uncertain) slightly accelerate the process once there has been major, irreversible kidney damage. Dietary protein has no substantial effect upon the GFR of healthy kidneys, certainly not in comparison to the GFR increase caused by elevated blood sugar levels.*

The May 1996 Journal of the American Medical Association published a summary of fifty-six studies demonstrating that in nondiabetics increased protein consumption actually lowered blood pressure.