Capillary blood tests may overestimate ketosis: triangulation between three different measures of β-hydroxybutyrate

Abstract

The ketone body β-hydroxybutyrate (BHB), assessed by a point-of-care meter in venous whole blood (BHBv), was used as the main outcome in a study on nutritional ketosis in healthy older adults. Two other BHB measures were also used in the study for validation and exploratory purposes, and here we report findings on correlation and agreement between those three methods. Ketosis in the range of 0–1.5 mmol/L was induced in 15 healthy volunteers by intake of medium-chain fatty acids after a 12-h fast. BHBv was assessed at 12 time points for 4 h. The same point-of-care meter was also used to test capillary blood (BHBc) at three time points, and a laboratory test determined total ketones (TK) in plasma (BHBp + acetoacetate) at four time points. A total of 180 cases included simultaneous data on BHBv, BHBc, BHBp, and TK. TK correlated with BHBp (Pearson’s r = 0.99), BHBv ( r = 0.91), and BHBc ( r = 0.91), all P < 0.0001. BHBv and BHBp had good agreement in absolute values. However, the slope between BHBc and BHBv, measured with the same device, was in the range of 0.64–0.78 in different regression models, indicating substantially higher BHB concentrations in capillary versus venous blood. We conclude that all three methods are valid to detect relative changes in ketosis, but our results highlight the importance of method considerations and the possible need to adjust cutoffs, e.g., in the management of ketoacidosis and in the evaluation and comparison of dietary interventions.

Ketosis After Intake of Coconut Oil and Caprylic Acid—With and Without Glucose: A Cross-Over Study in Healthy Older Adults

“…BHB ≥0.5 mmol/L, measured by capillary finger pricks, has been used as a cut-off for ketosis clinically (23) and as a research outcome (5,24). As previously reported (21), exploratory analyses on our data revealed that a cut-off at 0.5 for capillary blood corresponded to 0.3 in venous blood (the outcome of the current article). Accordingly, at the mid-level some participants are above the threshold, and at the high level most of them would be defined to be in ketosis.…”

“…However, baseline ketones (with a small number of possible exceptions) indicated that they were not on a low-carbohydrate diet. Our main outcome, BHBv, only show concentrations with one decimal, but considering its high agreement with the laboratory test (21), this shortcoming should be outweighed by benefits of the large number of time-points to capture the transient dynamics of ketosis. Another strength of our study is the complete collection of rich data, assessed under well-controlled conditions.…”

“…Whole blood was drawn by a syringe through the venous catheter, and then applied to the test strip within ∼10 s. BHBv was validated against a laboratory assay on total ketones, calculated from plasma BHB (BHBp) + AcAc, at T0, 30, 60, & 120, which showed that the correlation was high (Pearson's r = 0.91, p < 0.0001; n = 360) for BHBv vs. BHBp, as well as for BHBv vs. total ketones). Also, the agreement between BHBv and BHBp was satisfactory (Lin's concordance coefficient of absolute agreement = 0.91) (21). A divergence in the ratio between BHB and AcAc has been reported after intake of C8 vs. coconut oil (11,12), which could potentially induce bias when only BHB is measured.…”

“…Details of the sampling and analyses of ketones has been described previously (21), and a summary of the procedure is given here. Our main outcome, BHB assessed in venous whole blood (BHBv), was measured with a point-of-care meter (Statstrip Xpress R ) at time points T0, 15, 30, 45, 60, 75, 90, 120, 150, 180, 210, and 240 (minutes).…”

Characterization of a high-resolution breath acetone meter for ketosis monitoring

“…First, the gold standard blood BHB measurement is a laboratory plasma, rather than a point-of-care (POC), test. In fact, a recent study has shown that ketone measurements from POC blood meters often differ from laboratory plasma BHB tests by 0.2mM (Norgren et al, 2020). This same study also demonstrated that results from the POC blood meter were dependent 8/12 Figure 7.…”