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Specialist Advice — 20 minutes

Fasting and laboratory tests

Raymond Lepage, PhD, Doctor in Biochemistry
Raymond Lepage, PhD, Doctor in Biochemistry
Science popularizer

The requirement to fast before a having a blood sample taken for laboratory analysis probably dates back to the creation of the very first medical laboratories. It is well known that recent food intake temporarily alters the results of numerous biochemical tests, either upwards (glucose, insulin, triglycerides, folic acid, serum iron, etc.) or downwards (phosphorus). In addition to altering the levels of certain substances, blood samples taken from non-fasting patients have long interfered with the results of numerous other laboratory techniques. For all these reasons, laboratories have defined universal conditions for fasting, applicable to everyone, regardless of the test(s) prescribed, because universal conditions are easier to define and apply.

Fasting and laboratory tests

The introduction of new tests, such as glycated hemoglobin (HbA1c) for diagnosing and monitoring diabetes, as well as the continuous improvement of testing techniques, are changing the game. Situations where fasting is unavoidable are now rare! Nowadays, the conditions to be met are indicated for each laboratory test and specify which tests require fasting and how long the fast should last.

Imposing unnecessary fasting may even harm some patients. Because of fasting, testing centres are congested in the early morning, and patients of all ages are often turned away because they are a few minutes short of a 12-hour fast that was probably not even necessary. People may lie about the time of their last meal (sometimes with the knowledge of their attending physician) to avoid having to return. Some diabetic patients have their meal, medication or insulin schedules disrupted by these fasting restrictions.

Evolution of tests with a fasting requirement

Traditionally, these tests were almost always accompanied by a fasting requirement. Some of these instructions are no longer justified today.

Lipid test: Fasting no longer needed

The compulsory 12-hour fast, with abstention from alcohol for 24 hours or more, has long been an essential requirement for the lipid test. However, this is no longer the case, according to the latest recommendations of learned societies, both in Europe and North America. [1]

There are many reasons to abandon the fasting requirement for the majority of people. Essentially, it is because eating does not significantly affect measures of total cholesterol, HDL cholesterol (good cholesterol) and non-HDL cholesterol (a new measure of bad cholesterol). It is well known that the other measure of bad cholesterol (LDL cholesterol), which has been used for years as a target for statin treatment, may be slightly affected when triglyceride levels are too high (> 4.0 mmol/L). We now know that the portion of cholesterol called “non-HDL” is a much better indicator of bad cholesterol than LDL-cholesterol, because it includes all rather than just some of the molecules that cause atherosclerosis. Another major advantage of measuring the proportion of non-HDL cholesterol is that it is not influenced by recent food or alcohol intake.

Triglycerides: fasting is rarely required

Food and alcohol consumption continues to affect triglyceride levels. This is an inescapable biological reality, not a dosage interference. However, this information (a high triglyceride level after a meal) is useful, even irreplaceable in certain situations. In many people, triglyceride levels are actually normal on an empty stomach, but above normal for several hours after a meal. However, a number of very high-quality studies show that, regardless of normal cholesterol levels, people with high triglyceride levels after a meal are at significantly higher risk of developing cardiovascular disease than those whose triglyceride levels remain normal after eating. The increase in risk is easy to calculate – it is roughly equivalent to the measured triglyceride level. A fasting triglyceride level of 2.5 mmol/L roughly corresponds to a 2.5-fold increase in the risk of cardiovascular disease, while a level of 4.5 mmol/L corresponds to a four- to five-fold increase in the risk of developing cardiovascular disease. [2] We lack this information in patients who are subjected to an often annual dose of triglycerides after fasting exceptionally for 12 hours. The same is true for patients who drink alcohol every day, or nearly every day of the year and who very exceptionally abstain from alcohol for 24 or 48 hours, once a year, before having a lipid test. However, the fasting guideline remains in place for monitoring people with fasting triglyceride levels higher than 4.5 mmol/L.

Glucose: fasting not always necessary

Screening for diabetes based on blood glucose levels (glycemia) is of course the other essential part of mandatory fasting before a blood test. Given the significant rise in the number of patients with type 2 diabetes around the world, as well as the serious long-term consequences of this treatable chronic disease, early screening for diabetes in people at risk is recommended. However, the diagnostic criteria have evolved over the years. Recently, the criteria for fasting glucose or two-hour post-load glucose has been supplemented by glycated hemoglobin (HbA1c). HbA1c reflects the average glucose levels during the four to six weeks before the sample is taken and is therefore a very good indicator of diabetes. For a long time, the measurement of HbA1c levels has been limited to monitoring diabetic patients for the purpose of adjusting their treatment. Today, the recommendations of most learned societies interested in diabetes propose to rely not on all three indicators at the same time, but on either HbA1c levels, fasting glucose levels or two-hour post-load glucose levels. While the learned societies equate fasting glucose, two-hour post-load glucose and HbA1c as the tests of choice for screening, particularly for type 2 diabetes, they do not take into account the fact that, unlike the other two, HbA1c does not require fasting. There is no problem in opting for HbA1c in a non-fasting patient. On the contrary, if we make it easier to comply with the test, more patients can participate in screening efforts. And if we combine this test with a non-fasting lipid test done at the same time, we are effectively doubling the chances of detecting two of the most prevalent diseases in the Western world.

Choosing HbA1c seems to offer an interesting benefit for diagnosing prediabetes, i.e. the grey area of blood glucose levels between a clearly normal result and a clearly diabetic result. Since HbA1c levels are linked to average glucose levels over several weeks, 24 hours a day (including meals, stressful episodes, etc.), the information provided by HbA1c is much more useful, and the scientific literature indicates a closer link between HbA1c levels and the long-term effects of diabetes than between HbA1c levels and fasting glucose levels. [3] Once again, the number of patients for whom fasting glucose testing (after an eight-hour fast rather than a 12-hour fast) is recommended is relatively small. The requirement to fast for everyone could be replaced by special instructions from the attending physician who is knowledgeable of the literature.

Other tests

Other tests, such as measuring serum folic acid levels, are also affected by food or vitamin supplements. However, folic acid testing is now considered unnecessary and has already been removed from the list of tests available in many hospital laboratories. When a rare folic acid deficiency is clinically suspected, it is the folic acid level in red blood cells that should be checked, as this measurement is not affected by eating.

As for other tests, such as calcium, phosphorus, creatinine, sodium, etc., you only have to look at the wide variation in fasting times required by various laboratories to realize that these restrictions are not based on evidence. It is difficult to justify imposing a 12-hour fast at Hospital A when Hospital B requires none!

Toward fewer and fewer fasting restrictions

In conclusion, major clinical studies (meta-analyses) confirm that fasting restrictions do not need to be universal given improved dosing techniques, the emergence of new clinical indicators and the disappearance of others. Fasting, like any other special condition for blood collection, should be limited to the small number of patients for whom this indication remains essential. Only the health care professional knows their patient’s medical condition, and it is their responsibility to identify the small number of cases where more stringent testing conditions should apply.

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Sources3
  1. Anderson, T.J., Grégoire, J., Pearson, G.J. et al. “2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult.” Canadian Journal of Cardiology (2016): #32, 1263-82.
  2. Langsted, A. and Nordestgaard, B.G. “Nonfasting Lipid Profiles: The Way of the Future.” Clinical Chemistry (2015): #61(9), 1123-5.
  3. Selvin, E., Steffes, M.W., Zhu, H., Matsushita, K. et al. “Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults.” The New England Journal of Medicine (2010): #362(9), 800-11.
Raymond Lepage, PhD, Doctor in Biochemistry
Raymond Lepage, PhD, Doctor in Biochemistry
Science popularizer
For about 50 years, Raymond Lepage worked as a clinical biochemist in charge of public and private laboratories. An associate clinical professor at the Faculty of Medicine of the Université de Montréal and an associate professor at the Université de Sherbrooke, he has also been a consultant, researcher, legal expert and conference speaker. He has authored or co-authored more than 100 publications for scientific conferences and journals, and now devotes part of his semi-retirement to popularizing science.