Plant stanol esters might optimise the immune response and improve the SARS-CoV-2/COVID-19 vaccine efficacy in overweight and obese subjects

With great interest, we have read the letter by Rayman and Calder recently published in the British Journal of Nutrition(1). In that letter, the importance of an optimal nutritional adequacy to optimise the efficacy of the COVID-19 vaccine was emphasised. In that respect, older subjects were mentioned as a target group, as they are characterised by a weakened immune response, as shown by poor responses to several vaccines, amongst others the Oxford COVID-19 vaccine(2). Since it has been suggested that poor vaccination responses in older people are related to deficiencies in minerals and vitamins, Rayman and Calder suggested that nutritional supplements containing different vitamins and minerals should be provided to all subjects aged 70 years and older for a period of week before and after they get vaccinated. Besides older people, there is also another group at risk with a poor vaccination response: people with overweight or obesity(3–5). In fact, a recent trial showed that the response to the COVID-19 vaccination of BioNTech/Pfizerwas also impaired for people with a higher BMI(6). More specifically, the antibody response was more efficient in under-weight and normal-weight groups v. the pre-obesity and obesity groups (P< 0·0001). This association was confirmed after adjusting for age (P= 0·003). There was even a significant relation between four BMI classes and antibody titters (p= 0·02). It is possible that improving nutritional status would strengthen the immune response of subjects with overweight and obesity, since they often do not have an optimal nutritional status because of low dietary quality. However, based on our earlier studies, we suggest to consider also an alternative intervention. In an earlier double-blind placebo-controlled human intervention study in asthma patients, we found that 4-week consumption of plant stanol ester enriched foods prior to vaccination as well as 4 weeks after vaccination, significantly increased IgG antibody titters against hepatitis A (antiHAV titters) in response to a hepatitis A vaccination, while IgE levels decreased(7). Antibody titters in overweight or obese subjects (BMI> 25 kg/m2) from the control group were at least half of those in normal-weight subjects (BMI< 25 kg/ m2), showing that a high BMI indeed compromised the immune response. Moreover, upon plant stanol ester consumption, antibody titters increased by 18 % in normal-weight asthma patients and by 73 % in asthma patients with overweight and obesity. However, antibody titters in the high-BMI group after plant stanol ester consumption were still lower as compared with subjects with normal weight in the control arm (Fig. 1)(8). The suggested underlying mechanism for this effect may relate to effects on T cell behaviour. In more detail, we postulated that effects of plant stanol ester consumption increased the activity of the regulatory T cells, which in asthma patients dampened the Th2 response and improved the Th1 response. Based on these findings, we now hypothesise that people with a higher BMI might particularly benefit from plant stanol