Urine dipsticks are not accurate for detecting mild ketosis during a severely energy restricted diet

Abstract

Background: Detection of the mild ketosis induced by severely energy-restricted diets may be a clinically useful way to monitor and promote dietary adherence. Mild ketosis is often assessed using urine dipsticks, but accuracy for this purpose has not been tested. Objective: To determine the accuracy of urine dipsticks to detect mild ketosis during adherence to a severely energy-restricted diet. Methods: Two hundred and sixty three (263) fasting urine and 263 fasting blood samples were taken from 50 women (mean [standard deviation, SD] age 58.0 [4.3] years and body mass index 34.3 [2.4] kg/m 2) before and at six time points during or for up to 10 weeks after 16 weeks of severe energy restriction, achieved with a total meal replacement diet. The amount of ketones (acetoacetate) in the urine was classified as '0 (Negative)', '+/− (Trace)', '+ (Weak)' or '++ (Medium)' by urine dipsticks (Ketostix, Bayer). The concentration of ketones (β-hydroxybutyrate) in the blood was measured with our reference method, a portable ketone monitor (FreeStyle Optium, Abbott). The diagnostic accuracy of the urine dipsticks was assessed from the percent of instances when a person was actually 'in ketosis' (as defined by a blood β-hydroxybutyrate concentration at or above three different thresholds) that were also identified by the urine dipsticks as being from a person in ketosis (the percent 'true positives' or sensitivity), as well as the percent of instances when a person was not in ketosis (as defined by the blood monitor result) was correctly identified as such with the urine dipstick (the percent 'true negatives' or specificity). Thresholds of ≥0.3mM, ≥0.5mM or ≥1.0mM were selected, because mean blood concentrations of β-hydroxybutyrate during ketogenic diets are approximately 0.5mM. Sensitivity and specificity were then used to generate receiver operating characteristic curves, with the area under these curves indicating the ability of the dipsticks to correctly identify people in ketosis (1 = perfect results, 0.5 = random results). Radhika V Seimon and Amanda Sainsbury contributed equally to this work.

Exogenous Ketone Supplements in Athletic Contexts: Past, Present, and Future

“…POC devices typically use a BDH enzyme-based amperometric strip to establish whole blood [R-βHB] [113][114][115]. R-βHB is preferred to AcAc for measuring circulating [KB] as an indicator of ketosis, and therefore the use of POC is preferable to urinary ketone measurement due to the inability of nitroprusside in the urinary sticks to detect βHB [114], especially during mild ketosis [120]. Other studies have used laboratory methods, including reagent and colorimetric kits for measurement of plasma or serum [R-βHB] from venous blood samples [35,36,44,47,49,54], whereas S-βHB has been determined alongside R-βHB using gas chromatography-mass spectrometry with a chiral column [34], hydrophilic interaction liquid chromatography (HILIC) coupled to electrospray tandem mass spectrometry [65], and the combination of ultraperformance liquid chromatography and electrospray ionisation mass spectrometry [21].…”

Feasibility of an MI-CBT ketogenic adherence program for older adults with mild cognitive impairment

“…It may be especially important to account for metabolic and age differences that may influence how quickly individuals shift into a state of ketosis [ 38 , 39 ]. Further, additional methods for testing ketone levels may be warranted, as recent studies suggest that urine ketone testing may not be sensitive to mild ketosis [ 40 ]. Finally, to enhance retention and engagement, future trials should examine differences between in-person and virtual meetings.…”

Effect of severe compared with moderate energy restriction on physical activity among postmenopausal female adults with obesity: a prespecified secondary analysis of the Type of Energy Manipulation for Promoting optimum metabolic health and body composition in Obesity (TEMPO) Diet randomized controlled Trial

“…In our Introduction section, we hypothesized—based on literature ( 15–17 )—that the elevated circulating ketone body concentrations observed during a severely energy-restricted diet may contribute to alterations in physical activity. However, this is unlikely because unpublished data from our team show that the differences between dietary intervention groups in circulating ketone body concentrations were only apparent between 0.25 and 4 mo inclusive (i.e., during the time when participants were on the total meal replacement diet; Seimon RV, McClintock S, Salis Z, Inan-Eroglu E, Gibson AA, Harper C, Das A, Roekenes J, King N, Markovic TP, Franklin J, Caterson ID, Byrne NM, Sainsbury A, unpublished results, 2022), whereas the differences between dietary intervention groups in physical activity were apparent at 4, 6, and 12 mo, inclusive.…”

“…For instance, compared with traditional food-based moderately energy-restricted diets, severely energy-restricted diets, a broad term used to describe very-low-energy diets (<3300 kJ/d or <800 kcal/d) and low-energy diets (<5000 kJ/d or <1200 kcal/d), which are typically administered using meal replacement products, may induce feelings of lethargy or light-headedness ( 14 ), which could potentially hinder physical activity. Alternatively, severely energy-restricted diets could potentially increase physical activity during adherence to the diet, via mildly elevated blood concentrations of endogenously produced ketone bodies ( 15 ), which are associated with a state of euphoria and which could potentially promote physical activity ( 16 ). Indeed, some clinical trials showed that supplementation with exogenously administered ketone bodies enhanced certain measures of physical performance, albeit a recent systematic review found equivocal and inconclusive findings ( 17 ).…”