Allometric scaling of dietary linoleic acid on changes in tissue arachidonic acid using human equivalent diets in mice

The ability to extrapolate nutritional intervention data from experimental rodent models to humans requires standardization of dietary design. The inability to translate the level of nutrients from animal models to humans has contributed to contradictory findings between species. It is hypothesized that dietary linoleic acid (LA) promotes chronic and acute diseases by enriching tissues with arachidonic acid (AA), its downstream metabolite. However, levels of LA in rodent diets are notoriously erratic making interspecies comparisons unreliable. Therefore, the ability to extrapolate the biological effects of dietary LA from experimental rodents to humans necessitates an allometric scaling model that is rooted within a human equivalent context. To determine the physiological effect of dietary LA on tissue AA, a mathematical model for extrapolating nutrients based on energy was designed to mimic human equivalent doses. C57BL/6J mice were divided into 9 groups fed a background diet equivalent to that of the US diet (including LA, ALA, AA, EPA, DHA) with supplemental doses of LA (up to 2.3x) or AA (up to 5x). Changes in the phospholipid fatty acid compositions were monitored in plasma and erythrocytes and compared to data from humans supplemented with equivalent doses of LA or AA. Increasing dietary LA had little effect on tissue AA, while supplementing diets with AA significantly increased tissue AA levels, recapitulating results from human trials. Thus, interspecies comparisons for dietary LA between rodents and humans can be achieved when rodents are provided human equivalent doses based on differences in metabolic activity as defined by energy consumption

Allometric scaling of dietary linoleic acid on changes in tissue arachidonic acid using human equivalent diets in mice

<p>Abstract</p> <p>Background</p> <p>It is hypothesized that dietary linoleic acid (LA) promotes chronic and acute diseases in humans by enriching tissues with arachidonic acid (AA), its downstream metabolite, and dietary studies with rodents have been useful for validation. However, levels of LA in research diets of rodents, as published in the literature, are notoriously erratic making interspecies comparisons unreliable. Therefore, the ability to extrapolate the biological effects of dietary LA from experimental rodents to humans necessitates an allometric scaling model that is rooted within a human equivalent context.</p> <p>Methods</p> <p>To determine the physiological response of dietary LA on tissue AA, a mathematical model for extrapolating nutrients based on energy was used, as opposed to differences in body weight. C57BL/6J mice were divided into 9 groups fed a background diet equivalent to that of the US diet (% energy) with supplemental doses of LA or AA. Changes in the phospholipid fatty acid compositions were monitored in plasma and erythrocytes and compared to data from humans supplemented with equivalent doses of LA or AA.</p> <p>Results</p> <p>Increasing dietary LA had little effect on tissue AA, while supplementing diets with AA significantly increased tissue AA levels, importantly recapitulating results from human trials.</p> <p>Conclusions</p> <p>Thus, interspecies comparisons for dietary LA between rodents and humans can be achieved when rodents are provided human equivalent doses based on differences in metabolic activity as defined by energy consumption.</p

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination