Vitamin Supplements: The Dialysis Paradox

By Peter Laird, MD

Vitamin supplements are a favorite of health advocates who help generate the demand in this billion dollar industry, yet recent studies point to the paradox of adverse outcomes from these same supplements in high dosages. The difficulty of defining the proper role that vitamin supplements play is especially unsettled in dialysis patients who suffer the opposite extreme of documented vitamin deficits as a result of washing out water soluble vitamins during dialysis. Unfortunately, in some instances, the data on supplementing these deficiencies comes at a risk as well.

Vitamin C levels are especially low in dialysis patients according to a recent study looking at dialysis patients undergoing usual in-center schedules compared to extended hours dialysis protocols. Despite the low vitamin C level which borders on the development of scurvy, supplementation of vitamin C also increases oxalate levels even at low dosages of vitamin C which can build up in dialysis patients causing severe effects:

Water-soluble vitamin levels in extended hours hemodialysis

The major finding of this study was the high prevalence of vitamin C deficiency in extended hours hemodialysis patients compared with conventional dialysis patients. This is not unexpected as ascorbic acid is the smallest molecule (MW 176 g/mol) of the vitamins we assayed, and is readily removed by dialysis.24 As the prevalence of more frequent and longer hours (quotidian) dialysis is increasing, the importance of the assessment and supplementation of vitamin C in this patient group is demonstrated.

Traditionally, vitamin C has been used sparingly in patients with end-stage renal failure, as its metabolism generates oxalate. Increased levels of oxalate can cause deposition of calcium oxalate crystals in tissues (oxalosis), with cardiac, renal, and bone manifestations reported historically.27 The appropriate dose of vitamin C for patients with renal failure, as well as the impact of vitamin C dose on oxalate levels has been the subject of much debate. The European Best Practice Guidelines recommends 75 to 90 mg/day;18 however, this dose may not be sufficient to correct vitamin C deficiency in either extended or CHD patients. For example, a study of 18 conventional patients on 100 mg vitamin C daily found 5 patients had ascorbate levels in the range of deficiency (<0.30 mg/dL).15 The dose was increased to 500 mg/day for 2 weeks, which corrected the deficiency, and increased the mean plasma ascorbate from 0.69 to 1.82 mg/dL (39–103.5 μmol/L). However, because of a median increase in oxalate levels of 17%, the authors advised against high-dose vitamin C.

The balance between vitamin C levels too high or too low in extended hours dialysis remains a subject of debate with few studies available to guide the individual patient on what is the optimal strategy, truly leading to a vitamin supplement paradox between deficiency or harm from producing excessive oxalate levels with enough supplement to correct the deficiency. This is one area of study that demands a quick resolution since both extremes can cause harm to the patient. As of yet, there is no consensus on how to proceed.

Vitamin D likewise defies definition of optimal dosage at both ends of the spectrum as well. Low levels of vitamin D can precipitate rickets and is suspected to increase the risk of cancer as well as increasing the risk of death from cardiovascular disease, it brings on cognitive impairment, and may be an important factor in the prevention of diabetes and other health related conditions. Paradoxically, several studies in the female population at risk of osteoporosis showed a tendency to induce vascular calcification with vitamin D supplementation which is likewise demonstrated in dialysis patients as well.

Dialysis patients are especially at risk of vascular calcifications and mineral bone disorders due to the loss of enzymes that activate vitamin D synthesized in the skin by exposure to sunlight. A recent study suggested that vitamin D supplementation increases vascular calcifications in dialysis patients when phosphorus levels run high:

The dualistic role of vitamin D in vascular calcifications

The current treatment approach of providing vitamin D analogs to patients with CKD often poses a dilemma, as studies linked vitamin D treatment to subsequent vascular calcification. Recent genetic studies, however, have shown that vascular calcification can be prevented by reducing serum phosphate levels, even in the presence of extremely high serum 1,25-dihydroxyvitamin D and calcium levels. This article will briefly summarize the dual effects of vitamin D in vascular calcification and will provide evidence of vitamin D-dependent and -independent vascular calcification.

Certainly dietary guidelines for dialysis patients include eating several servings of fruits and vegetables every day which contain many of these vitamins as well as taking a daily vitamin specifically designed for dialysis patients. Data on the efficacy of this recommendation remains scant. Vitamin D is an important element in improving anemia as is Vitamin C, but at what cost. The balance between deficiency and too many vitamin supplements remains for future studies. In the mean time, for those taking vitamin D or its analogs, one key noted in the study above is keeping phosphorus levels in check. Likewise, there is hope that extended dialysis schedules may be able to remove the excess oxalate from increased vitamin C supplements but this remains unproven to date.

Until we have the studies available, discuss the risks and benefits with your medical team of vitamin supplementation which in the case of dialysis patients is mandatory to avoid the known consequences of severe deficiencies, control your phosphorus, eat a diet complemented with fruits and vegetables, exercise regularly which is perhaps the best “vitamin” we have, and do all things in moderation including vitamin supplements. Sometimes too much of a good thing is actually harmful.

Thanks, Peter, this is great information! I knew about vit. C and oxalate, but didn’t realize how deficient most folks were in vitamin C. I have to wonder whether (carefully and within potassium limits) eating FOODS with vitamin C wouldn’t, perhaps, be more effective than supplements. Has anyone looked at that?

Dori, as with many issues with this “orphan” disease we call ESRD, there are few studies to guide us on these issues. Unfortunately, I am not aware of any well done studies on vitamin C and natural supplements in the diet with fruits and vegetables. I am glad that there appears to be quite a bit of movement in the last few months to define the correct vitamin status in the different dialysis situations, conventional and extended or more frequent.