Practice Perfect 643
Albumin and Prealbumin are NOT for Nutrition... What?!!!!

placing drops into test tubes
I have a relatively long drive to work with an average drive time of 45 minutes, sometimes an hour, depending on the traffic. In fact, I drive so much that my 2014 car now has 106,000 miles. I see my car more than I see my children, I think!
Anyway, long drives in my car give me a lot of time to listen to new blogs and learn while on the go. For those of you interested in medical history while also learning about concepts pertinent to modern medicine I suggest Bedside Rounds. I’ve also recently been binge-listening to an excellent internal medicine podcast called The Curbsiders Internal Medicine Podcast, which is done by three Internists who interview experts on various medical topics. They provide high yield information in a light and often-funny format. They also have an excellent website that contains show notes with highlights and links to other resources discussed on the show.
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So…what a surprise it was about two weeks ago when I was driving to work, listening to one of the Curbsiders episodes when the topic of albumin and prealbumin came up, during which they communicated that albumin and prealbumin are NOT MARKERS OF NUTRITION!!
“What?! OMG! WHAT?”
“Wait…What?!!!”
“Albumin and prealbumin are not markers of nutrition?” I yelled, almost crashing my car in surprise and consternation.
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I may be revealing my ignorance, but I was always taught albumin reveals the nutritional status of a patient over the preceding three weeks, while prealbumin relates the past three days of nutrition.
Now, anyone who reads this blog knows I’m a highly skeptical person to begin with, and one of my favorite topics is demolishing sacred cows. I love learning new, updated information that proves prior knowledge wrong. But even I was taken aback at this new information!
Let’s look at this in a little more detail. First some background about albumin and prealbumin1
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Albumin is a major serum protein that is produced by the liver at a rate of 15g/day (200mg/kg). The half-life of albumin is approximately 20 days, and the normal serum level is 3.5 – 5.5 g/dL. Because albumin is a major marker of liver function, albumin levels below 3.0 g/dL indicate liver disease.
Prealbumin, also known as transthyretin, is NOT a precursor to albumin. Normal levels are 15-36 ng/dl. With a plasma half-life of two days, transthyretin is produced in the liver as a transport protein for the hormone thyroxine (T4) and retinol (Vitamin A). It is actually named transthyretin due to its TRANSport of THYroxine and RETINol. The reason it was originally named prealbumin was because it ran faster than albumin on electrophoresis testing.2 Due to its short half-life, transthyretin represents immediate dietary intake rather than long-term nutritional status.1
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The key to this discussion is that neither of these proteins are actually markers of nutritional status, yet to this day they are still used for this purpose by many. The confusion comes from an old 1972 study in The Lancet that found decreased prealbumin in malnourished children.3 However, these children also had inflammatory conditions, and that is the crux of the issue. Over time, prealbumin and albumin were accepted as nutritional markers. Except they actually represent something related but different. In reality…
Albumin and prealbumin are negative acute phase reactants and are decreased in inflammatory states.
Consider this for a moment. A diabetic patient with an infected foot ulcer is admitted to the hospital with a diagnosis of sepsis. Along with other labs, we find a CRP 32 mg/dL, ESR 60 mm/Hr, albumin 2.0 mg/dL, and prealbumin 10 mg/dL. CRP and ESR are increased from normal, while albumin and prealbumin are decreased. In this case, all four of these lab values are indicators of inflammation resulting from the infection and not malnutrition. While ESR and CRP are positive acute phase reactants, albumin and prealbumin demonstrate their negative acute phase reactant natures. It’s easy to see why someone might think a diabetic with an infection might also be malnourished.

The current evidence reveals that we should STOP using albumin and prealbumin as nutrition markers to determine nutritional status and BEGIN using the history and physical examination as our best means for this assessment

Supporting Evidence
More recent research supports this reality. Yeh and colleagues, in 2018, retrospectively analyzed a registry of 252 patients in a surgical intensive care unit receiving enteral nutrition and with labs including either CRP (9 patients), albumin (194 patients), prealbumin (13 patients), or a few other markers not of interest to our discussion here. These researchers found albumin and prealbumin to be inversely correlated with other markers of inflammation (as inflammation went up albumin and prealbumin went down). Also, significantly, for those with higher levels of nutrition on admission, the albumin and prealbumin were significantly elevated (p = 0.004). Even more convincing, when patients were administered nutrition in the ICU, their serum albumin and prealbumin levels did not change. The authors concluded albumin and prealbumin “should not be used to assess adequacy of nutrition delivery”.4
Not convinced? In 2015 Lee et al performed a systematic review to examine if albumin and prealbumin levels were elevated in otherwise healthy patients who were severely malnourished.5 Their review included a total of 63 studies. They found the serum albumin and prealbumin did not decline in these patients until they reached extremes of starvation (BMI < 12 or more than 6 weeks of starvation). This very strong evidence argues vehemently against the use of albumin and prealbumin as markers of nutrition.
The verdict: albumin and prealbumin are markers of inflammation and not nutritional status, and physicians should anticipate these values being low in patients with inflammatory disorders.
One might now ask the logical question, “If I can’t use albumin and prealbumin to predict my patient’s nutritional status, then what can I do?”
According to the American Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition’s 2012 consensus guidelines,6 nutritional status should be assessed using two or more of the following:
  1. Insufficient energy intake 
  2. Weight loss  
  3. Loss of muscle mass 
  4. Loss of subcutaneous fat 
  5. Localized or generalized fluid accumulation that may sometimes mask weight loss 
  6. Diminished functional status as measured by hand grip strength (determined using dynamometry) 
Note the lack of laboratory testing in the guidelines. As in all things, a detailed history and physical examination will reveal much by way of patient nutritional status. For those patients who are suspected to be mal- or undernourished, a referral to a nutritional expert is highly important.
Clearly, the use of laboratory values to evaluate and treat our patients requires us to rigorously remain up to date and adjust our methods accordingly. In this case, that means using the history and physical examination to determine nutritional status and avoiding the use of albumin and prealbumin as nutrition markers.
Best wishes.
Jarrod Shapiro Signature
Jarrod Shapiro, DPM
PRESENT Practice Perfect Editor
jarrod@podiatry.com
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References
  1. Shenkin A. Serum Prealbumin: Is It a Marker of Nutritional Status or of Risk of Malnutrition? Clin Chem. 2006 Dec;52(12):2177-2179.
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  2. Prealbumin. U.S. National Library of Medicine.meshb.nlm.nih.gov/record/ui?name=Prealbumin. Last accessed 2/15/19.
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  3. Ingenbleek Y, De Visscher M, De Nayer P. Measurement of Prealbumin as Index of Protein-Calorie Malnutrition. Lancet. 1972 Jul;15;2(7768):106-109.
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  4. Yeh DD, Johnson E, Harrison T, et al. Serum Levels of Albumin and Prealbumin Do Not Correlate With Nutrient Delivery in Surgical Intensive Care Unit Patients. Nutr Clin Pract. 2018 Jun;33(3):419-425.
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  5. Lee JL, Oh ES, Lee RW, Finucane TE. Serum Albumin and Prealbumin in Calorically Restricted, Nondiseased Individuals: A Systematic Review. Am J Med. 2015 Sept;128(9):1023.e1 – 1023.e22.
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  6. White JV, Guenter P, Jensen G, et al. Consensus Statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: Characteristics Recommended for the Identification and Documentation of Adult Malnutrition (Undernutrition). J Acad Nutr Diet. 2012 May;112(5):730-738.
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