Circulating ALT Levels in Healthy Volunteers Over Life-Span: Assessing Aging Paradox and Nutritional Implications

Abstract

Background: Two facts are generally recognized: (1) development of nonalcoholic fatty liver disease (NAFLD) is consistently linked to insulin resistance which has dietary implications and (2) circulating alanine aminotransferase (ALT) levels are reasonable markers predicting NAFLD status. In a recent cross-sectional study employing nondiabetic subjects, ALT values rose steadily within a normal range early in the life cycle but begin decreasing steadily around age 65 years. Objectives: Because of important nutritional implications, the association between ALT levels and aging in a significantly larger population of healthy volunteers was examined for corroborative purposes. A secondary goal was to gain further knowledge concerning mechanisms behind any age-related decline in ALT activity. Methods: Baseline data from over 10,000 physician-approved, nondiabetic subjects (age 21-84 years) of both genders who had volunteered for previous clinical investigations were assessed. Results: In this cross-sectional examination, the line of best fit (weighted) for average yearly circulating ALT levels displayed an upward surge from ages 21 to 64 years with a discernible steady downward decline around 65 years-mimicking earlier results. Examining linear lines of correlation in the younger and older age groups, the following calculations were determined: a significant positive slope for 21 to 64 years, r ¼ 0.42, n ¼ 44, p < 0.005, and a trending negative slope for 65 and beyond, r ¼ À0.43, n ¼ 20, p < 0.057. Using this same datum base, the correlations between age and fasting blood glucose (FBG) mimicked the ALT results by once more showing a similar upward rise in the younger and a steady decline the older group of volunteers. Conclusions: A paradoxical downward age-related (! 65 years) decline of circulating ALT coinciding with a comparable steady decrease in FBG levels was replicated in a larger population of volunteers. The close association of these two chemistries along with other findings suggest that altered glucose-insulin metabolism may participate via "survivor bias" in the ubiquitously found age-related decline of serum ALT-suggesting that nutritional measures could advance optimal health over the life-span.Abbreviations: ALT: alanine aminotransferase; AST: aspartate aminotransferase; FBG: fasting blood glucose; IR: insulin resistance; MS: metabolic syndrome; NAFLD: nonalcoholic fatty liver disease ARTICLE HISTORY

Serum alanine aminotransferase activity is age- and sex-depended but independently predicted by body mass index in both sexes. The Tromsø study

“…In women, an inversed U-form with signi cant and opposite directed age-ALT correlations on both sides of the 60-year cut-off is demonstrated. A similar pattern with ALT-maximum at 65-year of age was found equal for both sexes in a recent cross-sectional study in 10,000 non-diabetic subjects [11]. By showing a similar trend for age vs.…”

“…fasting glucose levels, glucose was suggested to entail a joint effect on the ALT levels across ages [11]. The same phenomenon is demonstrated in a study that included subjects living in aged home and participants recruited from three general practices (n = 335).…”

“…Higher prevalence of metabolic abnormalities in men may explain sex-differences in associations between ALT and metabolic syndrome [10]. Low levels have also been reported to be unfavourable and may be explained by higher age, sarcopenia and hepatic ageing [11]. Accordingly, a J-shaped ALT-mortality curve is demonstrated [12][13][14].…”

Interplay Between Insulin Resistance and Body Fat Mass in Evolution of Perturbations Linked to the Metabolic Syndrome in Non-Diabetics: Emphasis on Inflammatory Factors

“…Nevertheless, both have been described prominently in the makeup of the so-called "deadly triangle," where they have been linked to the aging process and its many chronic associated metabolic disordersparticularly many components of MS (Figure 1) (13)(14)(15). An important aspect of the triangle lies in the fact that interrupting or at least lessening the negative consequences of these two components early on, one or both, could possibly diminish their impact as well as many additional dependent disturbances contributing to the aging processand allow in many cases for an expanded healthier life-span (16).…”

“…In previous communications dealing with the relationship between IR and FM, we have often taken a logical explanatory route and stated that while IR can drive fat accumulation, the presence of excess body fat, especially that located viscerally, can in turn drive IR (13)(14)(15). Such appears to be the case for the relationship between MS and the commonly associated nonalcoholic fatty liver disease (NAFLD) (16)(17)(18)(19)(20)(21)(22)(23). In the words of Wainwright et al, "There is growing evidence that this relationship between NAFLD and metabolic syndrome is bidirectional, in that NAFLD can predispose to metabolic syndrome features, which can in turn exacerbate NAFLD or increase the risk of its development in those without a preexisting diagnosis" (24).…”