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Antioxidant and anti-inflammatory treatment worsen cognitive and psychological scores after sepsis

10th March 2023

Antioxidant and anti-inflammatory therapy given to patients following sepsis led to worse cognitive and psychological scores after 6 months

Antioxidant and anti-inflammatory treatment for those who survived sepsis resulted in lower cognitive and psychological scores compared to placebo after 6 months according to a randomised trial by the VICTAS investigators.

Evidence suggests that patients with sepsis exhibit long-term neurological sequelae, particularly substantial declines in cognitive function. In fact, according to the Sepsis Alliance, the presence of Post-traumatic stress disorder, depression and anxiety are not unusual among sepsis survivors. It is thought that the presence of oxidative damage is an important factor in post-sepsis cognitive impairment. Additionally, in animal models, deficiency of the vitamin thiamine, also enhances oxidative stress and inflammatory response changes and some preliminary data indicates a synergistic effect of vitamin C and hydrocortisone on endothelial barrier protection in patients with sepsis. Given these findings, could a triple combination of vitamin C, hydrocortisone and thiamine, have a positive impact on cognitive, psychological and functional outcomes in those who survive sepsis?

The VICTAS trial attempted to answer this question and randomised 1:1, sepsis survivors to either triple combination therapy, consisting of intravenous vitamin C, thiamine and hydrocortisone or placebo. The combination was administered within 4 hours of randomisation and every 6 hours thereafter for up to 96 hours. The outcomes of interest were cognitive performance, risk of posttraumatic stress disorder and functional status, all of which were assessed 6 months after randomisation.

Antioxidant, anti-inflammatory treatment outcomes

A total of 213 participants with a median age of 57 years (52.6% male) were included and randomised to the triple therapy (108) or placebo.

At 6 months, the triple therapy group had significantly lower immediate memory (i.e., cognitive) scores than placebo participants (adjusted odds ratio, aOR = 0.49, 95% CI 0.26 – 0.89, p = 0.02) and a higher odds of posttraumatic stress disorder (aOR = 3.51, 95% CI 1.18 – 10.40, p = 0.02). In contrast, there was a lower odds among triple group participants, of receiving formal psychiatric, psychological, or mental health care during the 6 months after discharge. However, there were no significant differences in measures of functional support.

The authors concluded that in sepsis survivors, treatment with vitamin C, thiamine, and hydrocortisone made worse, cognitive and psychological outcomes and made no difference to functional outcomes at 6 months compared to placebo.

Roberson SW et al. Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial. JAMA Netw Open 2023

Taking vitamin C with iron has no effect on haemoglobin levels

20th November 2020

Vitamin C is a dietary constituent which has been shown to promote iron absorption in the duodenum and upper jejunum.

Oral iron is always oxidised to the Fe3+ state, irrespective of how it is taken and requires an acidic environment for adequate absorption. Vitamin C creates a more acidic environment and can prevent the oxidation of iron to the ferric form. However, whether the common practice of advising that vitamin C is taken alongside iron supplements to enhance iron absorption is beneficial has never been tested.

As a result, for this study a team from the Department of Haematology, Huashan Hospital, Shanghai, China, undertook a randomised, open-label trial in adult patients with newly diagnosed iron-deficiency anaemia (IDA). Participants were given 100mg oral iron tablets plus 200mg of vitamin C or 100 mg of iron alone every 8 hours for a total of 3 months and the authors assessed treatment compliance by determining the number of iron and vitamin tablets returned at the end of the study. Included patients had a haemoglobin level less than 13g/dl for men or less than 12g/dl for women. Although treatment continued for 3 months, the primary outcome measure, the change from baseline in haemoglobin levels, was assessed after two weeks. Secondary outcomes included the increase in serum ferritin after 8 weeks and the haemoglobin level after 4 and 8 weeks.

A total of 440 patients with a mean age of 38.3 years (96.8% women) were randomised and treatment compliance was 98.2%. The mean baseline haemoglobin level was 8.76g/dl in both groups and serum ferritin, 5.89 in the vitamin C group and 6.34 in the iron only group. After two weeks, the change from baseline in haemoglobin levels was 2.00g/dl in the vitamin C group and 1.84g/dl in the iron only group which was not significant. Similarly, the mean change in serum ferritin levels were 35.75ng/ml vs 34.48ng/ml (vitamin C vs iron only). Furthermore, there were no differences in haemoglobin levels after 2, 4, 6 or 8 weeks. The authors concluded that it is unnecessary to add in vitamin C to the iron regime for patients with IDA.

Li N et al. The efficacy and safety of vitamin D for iron supplementation in adult patients with iron deficiency anaemia: A randomised clinical trial. JAMA Network Open 2020;3(11):e2023644. doi:10.1001/jamanetworkopen.2020.23644 (R