Deficiencies in vitamin B12 and glutathione (GSH) are associated with a number of diseases including type 2 diabetes mellitus. We tested newly diagnosed Indian diabetic patients for correlation between their vitamin B12 and GSH, and found it to be weak. Here we seek to examine the theoretical dependence of GSH on vitamin B12 with a mathematical model of 1-carbon metabolism due to Reed and co-workers. We study the methionine cycle of the Reed-Nijhout model by developing a simple “stylized model” that captures its essential topology and whose kinetics are analytically tractable. The analysis shows—somewhat counter-intuitively—that the flux responsible for the homeostasis of homocysteine is, in fact, peripheral to the methionine cycle. Elevation of homocysteine arises from reduced activity of methionine synthase, a vitamin B12-dependent enzyme, however, this does not increase GSH biosynthesis. The model suggests that the lack of vitamin B12–GSH correlation is explained by suppression of activity in the trans-sulfuration pathway that limits the synthesis of cysteine and GSH from homocysteine. We hypothesize this “cysteine-block” is an essential consequence of vitamin B12 deficiency. It can be clinically relevant to appreciate that these secondary effects of vitamin B12 deficiency could be central to its pathophysiology.

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U niversal health coverage (UHC) is an integral part of the United Nations sustainable development goals. The private sector plays a prominent role in achieving UHC, being the primary source of essential medicines for many people. However, many private healthcare facilities in low-and middle-income countries (LMICs) have insufficient stocks of essential medicines. Simultaneously, these same facilities carry excessive quantities of other drugs, leading to obsolescence. This suggests poor inventory control. To propose potential remedies it is vital to fully understand the underlying causes. In semistructured interviews with managers of private healthcare facilities in Nairobi, we asked them about their (1) inventory control systems, (2) inventory control skills, (3) time/human resource constraints, (4) budget constraints, (5) motivations for inventory control, and (6) suppliers. Our results suggest that the problems are driven by resource limitations (budget and time/human resources), managerial issues (relating to skills and systems), and market mechanisms that limit overage and underage costs. Unavailability at the supplier level and motivations for inventory control are relatively minor issues. We posit that the key causes are interlinked and stem from wider issues in the market and regulatory environment. Our results challenge prevalent beliefs about medicine supply chains in LMICs and lead to novel hypotheses. Testing these hypotheses could improve our understanding of inventory management in private healthcare facilities and aid progress in achieving UHC.

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