Vitamins: no benefit in the critically ill

I’ve written previously about several well-run studies that failed to show any benefit of vitamins in long-term use to promote good health (see here). Are vitamins useful in helping the critically ill? An excellent article in today’s New England Journal of Medicine suggests that, in this setting too, vitamins have no benefit.

Researchers looked at 1,223 patients who were critically ill and in the intensive care units at hospitals participating in the study. Investigators looked at two interventions:

  • glutamine – Glutamine is an amino acid, a molecule the body uses in building muscle and various proteins. It is thought it might play a role in wound healing and in keeping the gastrointestinal tract healthy in ill patients. Of note, glutamine is also marketed as a supplement for body builders.
  • anitoxidants/vitamins — Vitamin supplementation consisted of a mix of 800 μg of selenium, 20 mg of zinc, 10 mg of beta carotene, 500 mg of vitamin E, and 1500 mg of vitamin C (selenium was given both IV and oral/via the gut, all other vitamins were oral/via the gut)

Scientists thought it would be valuable to study glutamine because critically ill patients experience muscle deterioration with corresponding drops in glutamine levels. It was postulated that glutamine supplementation might preserve muscle mass and health.

The research published today was done in critically sick patients. These patients were in the ICU and had high risks of mortality (death). In fact, the endpoint of the study was mortality measured at one and six months. The results are as follows:

Mortality rates:  Do either vitamins or glutamine lower death rate?

  Death at 1 month Death at 6 months
Standard care/ Placebo group 27.2% 37.2%
Glutamine supplementation 32.4% 43.7%
Standard care/ Placebo group 28.8% 40.6%
Vitamin supplements 30.8% 40.4%
   (each intervention had its own placebo comparison group)

Vitamins provided no benefit to these critically ill patients. The fact that patients who received vitamins did slightly worse statistically is noise, not a real finding.

Glutamine supplementation, on the other hand, appeared to do harm. The primary endpoint of the study was mortality at 28 days. The statistical analysis was inconclusive about whether the harm from glutamine was due to chance or was a real finding. (For those interested in the statistics, P = 0.05; less than 0.044 was the threshold for statistical significance due to an interim look.)

While I personally view the result of no benefit for vitamins to be the more interesting finding, there is an important takeaway message in the glutamine part of the trial. The message is: intervention is not always good. In critically ill patients, glutamine levels are low. This study shows that raising glutaime levels is not helpful. Indeed, perhaps the body actually induces low glutamine levels as a protective mechanism (this is purely conjecture of something possible – there is no scientific rationale for thinking this is the case). The point is, we humans are an arrogant lot. We like to intervene. Sometimes interventions are good. As examples, it is appropriate to lower LDL (bad) cholesterol, and it is appropriate to replace low levels of thyroid hormone. These interventions yield clinical benefits.

However, just because  certain blood levels (of anything, not just glutamine as in this case) are abnormal does not automatically mean we should intervene/force them back to normal. For example, a recent trial showed that using niacin (vitamin b3) to increase HDL (good) cholesterol had no benefit (see here). As another example, studies have shown that high homocysteine levels (a protein that can be measured in the blood) are associated with higher risk of heart attacks, but lowering homocysteine (which can be done using folate, aka vitamin b9) has no benefit. There is a fad now to check levels of vitamin D and advise supplementation of vitamin D if levels are low. There is no medical evidence for doing so. I’m not saying vitamin D supplementation is bad . . . I’m just saying that we don’t know (there are several large studies underway and we’ll have the answer to this question in a few years). Trying to correct glutamine levels in sick patients might cause harm. It is important to be careful and to collect evidence before acting to try to correct a lab value.

source: A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients (NEJM)

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