The Journal of Nutrition Vol. 127 No. 12 December 1997, pp. 2378
Copyright ©1997 by the American Society for Nutritional Sciences

A Response to Dr. Olson

James L. Hargrove

Associate Professor, The University of Georgia, Athens, GA 30602-3622

LITERATURE CITED

Dear Dr. Visek:

Thank you for forwarding Dr. Olson's comments concerning the likelihood that a vitamin K deficiency may have been responsible for the prolonged prothrombin times caused by the low protein diets used in the study reported by Chang et al. (1997), "Low dietary protein impairs blood coagulation in BHE/cdb rats." Dr. Olson's argument that vitamin K may have been limiting is persuasive, and the reasons that we chose that experimental design are no longer important. The study must be repeated to eliminate vitamin K as a confounding variable and to evaluate other aspects of liver function.

It may be worthwhile to restate evidence that loss of liver function produces a coagulation defect that is not completely restored by administration of vitamin K (Munoz and Maddrey 1988). Evidence concerning the coagulation deficit that occurs in humans with kwashiorkor suggests that the abnormal prothrombin times are not only the result of vitamin K deficiency, but of insufficient dietary protein, and that these problems are exacerbated by prior gastroenteritis. Hassanein and Tankovsky (1973) observed disturbances in factors II, VII and X in patients with kwashiorkor, but not in patients with marasmus (except in 2 patients who had severe diarrhea). They then treated the patients for three days with 20 mg of vitamin K-1 alone, or with a combination of protein and vitamin K. The results indicated that treatment with vitamin K restored factor VII to a normal range, but did not restore factors II and X. However, normal values for all coagulation factors were found after treatment with the combination of protein and vitamin K.

The counterpoint to this view is that patients with marasmus do not develop abnormal coagulation, despite subsisting on diets that are often extremely low in protein. Therefore, it is not merely low protein intake that leads to abnormal bleeding. In regard to a rodent model of protein malnutrition, the question could be rephrased to ask whether diets with low protein content but adequate vitamin K can promote abnormal coagulation in the absence of other signs of poor liver function. This question can not be answered based on the data in our study (Chang et al. 1997). It is ironic that the original AIN-76 diet not only contained inadequate vitamin K, but also promoted fatty infiltration of the liver (Bacon et al. 1984). In any event, it is essential that a more comprehensive set of liver function tests be conducted.

With chagrin, I thank Dr. Olson for explaining why a low casein diet makes the problem of vitamin K deficiency more severe, and apologize to any colleagues who may have been misled by this report. I hope that this discussion at least serves to clarify the issues involved, and I accept the responsibility to answer the question of whether a low protein diet can alter coagulation in the absence of other signs of liver dysfunction.

FOOTNOTES

Manuscript received 30 July 1997. Initial reviews completed 22 August 1997. Revision accepted 22 August 1997.

LITERATURE CITED

• Bacon B. R., Park C. H., Fowell E. M., MacLaren C. E. Hepatic steatosis in rats fed diets with varying concentrations of sucrose. Fund. Appl. Toxicol. 1984; 4:819-826 [Medline]
• Chang, Y.-L., Sohn, H.-S., Chan, K.-C., Berdanier, C. D. & Hargrove, J. L. (1997) Low dietary protein impairs blood coagulation in BHE/cdb rats. J. Nutr. 127, 1279-1283.
• Hassanein E. A., Tankovsky I. Disturbances of coagulation mechanism in protein-calorie malnutrition. Trop. Geograph. Med. 1973; 25:158-162
• Munoz S. J., Maddrey W. C. Major complications of acute and chronic liver disease. Gastroenterol. Clin. North Amer. 1988; 17:265-287

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