The effect of diet-induced weight loss on circulating homocysteine levels in people with obesity and type 2 diabetes

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Having type 2 diabetes (T2D) in combination with being overweight results in an additional increase in cardiovascular disease (CVD) risk. In addition, T2D and obesity are associated with increased levels of total homocysteine (tHcy), possibly contributing to the CVD risk. Weight loss dieting has positive effects on several CVD risk factors, but whether it affects tHcy remains unclear. Therefore, the aim of this study was to determine the effect of a calorie restricted diet on tHcy in overweight people with T2D. 


In this post-hoc analysis of the POWER study, adults with T2D and a BMI greater than 27 kg/m² were included from the outpatient diabetes clinic of the Erasmus Medical Center, Rotterdam. The patients were subjected to a very low-calorie diet with fortified meal replacements for 20 weeks. Before and after this intervention, blood samples were collected to measure tHcy and other CVD risk factors like glycaemic and lipid parameters. 


161 overweight participants with T2D were included, with a mean age of 54 years (range 26–74), mean weight of 104.6 ± 19.9 kg and mean HbA1c of 62.7 ± 14.3 mmol/mol. At baseline, men displayed higher tHcy than women, and tHcy level was positively correlated with body weight and triglyceride levels, while it was negatively correlated with renal function and HDL cholesterol. During the intervention, bodyweight was reduced by a mean of 9.7% (from 104.6 ± 19.9 to 94.5 ± 18.1 kg p < 0.001), and all measured glycaemic and lipid blood parameters improved significantly. However, tHcy remained unchanged (from 12.1 ± 4.1 to 12.1 ± 4.2 umol/L, p = 0.880). The change in tHcy during the intervention was negatively associated with the change in weight and BMI (p = 0.01 and p = 0.008, respectively). People who lost < 10 kg (n = 92) had a mean tHcy change of -0.47 umol/L, while people who lost more than ≥ 10 kg (n = 69) had a mean tHcy change of 0.60 umol/L (p = 0.021). 


In conclusion, our data show that a calorie restricted diet does not affect tHcy in people with T2D and obesity, despite the use of meal replacements fortified with folic acid and vitamin B12. Our data showed a negative correlation between change in tHcy levels and weight loss, suggesting that people who lost more weight (> 10 kg) showed an increase in tHcy. Future studies should explore the potential increase in tHcy induced by weight loss dieting and target the question if tHcy reduction strategies during weight loss could be clinically beneficial.

Original languageEnglish
Article number2
JournalNutrition Journal
Issue number1
Publication statusPublished - 3 Jan 2024

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