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.
I never thought about this. Please don't make me start worrying about scurvy! I don't think I can take it. Something must have triggered this post from you, Peter; has your own neph expressed some concern? What recommendation has your own healthcare team given to you?
Posted by: MooseMom | Tuesday, March 29, 2011 at 10:09 PM
Dear MooseMom, the article in question just came out a few days ago. I don't believe that they meant their article to be alarmist, nor the one from December. Instead, this is welcome information on a subject that I have researched in the past with little to guide my own medical decisions on these issues.
The article on Vitamin D is a very helpful article to me personally since I have been well aware of the risks of vascular calcification with Vitamin D supplementation. Likewise, low levels have risks as well, perhaps more so than we completely understand at present. The take home message of that article for dialysis patients is to keep the phosphorus levels low and in normal ranges to avoid calcification of the arteries and veins. Actually, this is information that we have long known as well, but it is a good confirmation and helps to categorize some patients who may benefit and some who may be at risk of Vitamin D therapy. I would be very hesitant to take vitamin D if my phosphorus levels were elevated.
The issue of scurvy as reported in this article is on a subclinical basis and that is why I used the term bordering on scurvy. Vitamin deficiency is a well described complication of dialysis noted back in the 1960's when many of their patients developed nerve damage that was reversed with vitamin supplementation. In all that time that has transpired since, we have had few definitive articles showing the optimal dosage. Thankfully, it appears to be a hot topic of late which is good. We should finally have some clear guidance soon.
Posted by: Peter Laird, MD | Tuesday, March 29, 2011 at 11:56 PM
There is a great need for understanding (re: studies) of the micronutrient deficiencies of those on hemodialysis --both standard and extended. How much supplementation beyond the standard renal multivitamin is necessary to help people on dialysis thrive?
Coenzyme Q10 and L-carnitine are just two micronutrients which serum levels tend to be low in hemodialysis patients. I think it's safe to say that currently, supplementation of these micronutrients (and their eventual endpoints) are controversial at best. Yes, more studies I suppose.
But for those of us who toil in the vineyards of hemodialysis, shall we wait for the RCT?
Posted by: Zach | Wednesday, March 30, 2011 at 07:06 AM
How is one tested for levels of these micronutrients? Standard blood tests?
Posted by: MooseMom | Wednesday, March 30, 2011 at 09:25 AM
Dear MooseMom, vitamin levels are routine blood tests that your physicians can order. However, since deficiencies are so prevalent in the dialysis population, your physician may not feel it is necessary to document what is the overwhelming situation for those of us on dialysis and the tests can be on the expensive side. It may make for an interesting discussion of why you wish to have the levels tested.
Posted by: Peter Laird, MD | Wednesday, March 30, 2011 at 12:25 PM
Peter, I read a lot of posts from dialysis patients who are not "thriving" and are not sure why. Their labs are OK, and nothing is obviously wrong, but they are just not "well". I guess one could just put that down to being on dialysis, but there IS a reason although that reason may be difficult to discern. Do you think that in a lot of these patients who are not "thriving", one or more vitamin/micronutrient deficiencies may be the cause?
Posted by: MooseMom | Wednesday, March 30, 2011 at 01:51 PM
Dear MooseMom, as the articles above clarify, vitamin deficiencies do likely play a part in the over all wellness of dialysis patients, but as in all areas of study in dialysis patients, there is a multitude of factors that affect fatigue and general well being. My approach is to maximize dietary factors as best I understand them, exercise and get as much dialysis as I can. Above and beyond that becomes difficult to define, but the first three are easily achievable with diligence and I believe do make a significant difference as evidenced in many medical papers on these issues.
Posted by: Peter Laird, MD | Wednesday, March 30, 2011 at 04:01 PM