Plasma Lithium Levels in a General Population: A Cross-Sectional Analysis of Metabolic and Dietary Correlates

Abstract

Initial evidence suggests that lithium might affect life expectancy and the risk for different disease conditions, but most studies were conducted in patients on lithium medication. Little is known about the association of blood lithium levels within the physiological range with cardiometabolic risk factors and diet. We measured plasma lithium in a community-based sample from Northern Germany (samples taken between 2010 and 2012). All participants (aged 25-82 years) underwent standardized examinations and completed a semi-quantitative food frequency questionnaire. Of several variables tested, the estimated glomerular filtration rate (eGFR) was statistically significantly (inversely) associated with lithium levels, mainly in individuals with slightly impaired renal function (eGFR < 75 mL/min/1.73 m²). Besides, lithium levels were positively associated with age and alcohol intake. Using reduced rank regression, we identified a dietary pattern explaining 8.63% variation in plasma lithium levels. Higher lithium levels were associated with higher intakes of potatoes, leafy vegetables, root vegetables, fruits, tea, beer, wine and dietetic products and lower intakes of pasta, rice, pork, chocolate, sweets, soft drinks, other alcoholic beverages, sauces and snacks. Our observations suggest that plasma lithium levels are associated inversely with kidney function, particularly in individuals with slightly impaired renal function, and positively with age and alcohol intake. Lithium at physiological levels was moderately related to an exploratory dietary pattern.

Keywords: dietary correlates; general population; metabolic risk factors; plasma lithium levels; renal function.

Figure 1

Association of log-transformed lithium plasma levels with eGFR, age and alcohol intake (each variable modeled individually) using RCS. Legend to the Figure: Restricted cubic splines (RCS) regression for the association of plasma lithium concentrations in 928 participants with: (a) estimated glomerular filtration rate (eGFR); (b) age; and (c) alcohol intake. The solid line indicates estimated differences in log lithium and dashed lines indicate 95% CI derived from RCS regression, with four knots placed at the 5th, 35th, 65th and 95th percentiles of the distribution, using the 50th percentile as a reference, of: (a) eGFR values; (b) age; and (c) alcohol intake. Estimated differences were adjusted for age, sex, diastolic blood pressure, eGFR, alcohol intake and smoking status. Wald p values are: (a) eGFR, p for nonlinearity 0.0006 and p for overall association <0.0001; (b) age, p for nonlinearity 0.29 and p for overall association 0.002; and (c) alcohol intake, p for nonlinearity 0.46 and p for overall association 0.002.