Efficacy Evaluation of 16 Weeks' Dietary Supplementation With Iron Bis-glycinate Plus Vitamin C on Cognitive Function, Subjective Mood, Fatigue, Health and Well-being
Condition: Cognitive Function and Mood; Non-anaemic Iron Deficiency
MeSH terms: Iron Deficiencies; Fatigue
Study type: Interventional

Summary: 
      Iron deficiency is the most prevalent nutritional deficiency worldwide with one in four
      estimated to be affected by iron deficiency anaemia. Women of reproductive age are at
      greatest risk for iron deficiency and anaemia due to iron losses during menstruation and
      childbirth as well as the increased need for iron throughout pregnancy. However, iron
      deficiency without anaemia is at least twice as common as iron deficiency anaemia with
      females aged 11-49 at the biggest risk of all. Despite this, it is commonly left undiagnosed.
      Those who are iron deficient non-anaemic can still suffer from the same common consequences
      of iron deficiency anaemia; these include unexplained fatigue, mood changes and decreased
      cognitive performance. However, randomised controlled trials (RCTs) assessing the effect of
      iron supplementation upon cognitive performance, mood, fatigue and well-being in non-anaemic
      iron deficient women of reproductive age are limited. There is also a lack of well-defined
      diagnostic criteria for non-anaemic iron deficiency, which makes comparisons across RCTs
      difficult. However, there is evidence to suggest that a haemoglobin cut off of ≥120 g/L and
      serum ferritin ≤ 20 µg/L provides an accurate indication of non-anaemic iron deficiency in
      women of reproductive age; this is inclusive of the ability to recognise iron-associated
      deficits in psychological and physiological functioning. Additionally, previous RCTs could be
      improved by utilising a lower dose of iron in a bis-glycinate chelate form, which is
      evidenced to have superior bioavailability, tolerability and subsequent efficacy compared to
      ferrous formulations. Iron bis-glycinate absorption is also negatively associated to serum
      ferritin levels, which is suggestive of a non-anaemic iron deficient population benefitting
      most from it's administration. The current study aims to build upon previous iron RCTs in
      populations of non-anaemic iron deficient and iron sufficient women of reproductive age by
      investigating the effects of 16-weeks supplementation with either iron bis-glycinate chelate
      alone, iron bis-glycinate plus vitamin C (as ascorbic acid) or matched placebo upon cognitive
      performance, subjective mood, fatigue, health and well-being.
    

Detailed description: 
      Each participant will be required to attend the laboratory on four occasions. The first is
      comprised of a screening/training visit, which will take place in the afternoon for
      approximately 2.5 hours. This will also be between days 21-28/ the week before onset of their
      menstrual cycle. If they do not have menstrual bleeds then this appointment can be any
      afternoon. This will comprise: briefing of requirements of the study; obtaining of informed
      consent; confirmation of eligibility to take part, including collection of demographic data
      and health screening, and training on the cognitive and mood measures. The training session
      will follow standard operating procedures to decrease the chance of learning effects during
      main trials. Extra training will be given where necessary.

      Participants will be required to complete questionnaires based upon food frequency, caffeine
      consumption and to estimate the number of hours of exercise completed on a weekly basis. A
      menstrual cycle questionnaire will also be completed to estimate menstrual blood loss and so
      that participants attend their testing visit during days 7-14 of their cycle. If participants
      do not have a menstrual cycle due to contraceptive methods, then appointments will be
      approximately two weeks apart. A finger-prick and venous blood sample will be collected from
      participants, which will be analysed for iron status. Those whose haemoglobin levels are
      <120g/L will be advised to seek advice from their GP. Participants who fell into the iron
      status category of iron sufficient (haemoglobin ≥120 g/L and serum ferritin > 20 µg/L) or
      non-anaemic iron deficient (haemoglobin ≥120 g/L and serum ferritin ≤ 20 µg/L) will be
      informed of their eligibility for the intervention study by email or phone between the
      initial visit and their next.

      For the testing visit, participants will be asked to fast for 12 hours prior to the visit,
      avoiding intake of all food and drink with the exception of water. They will also be asked to
      avoid alcohol and refrain from intake of 'over the counter' medication for 24 hours.
      Participants will arrive at the laboratory at a designated time in the morning. The following
      procedures will take place prior to cognitive and mood testing:

        -  Review of continued conformity to eligibility criteria

        -  Adverse event and concomitant medication assessment

        -  Ensure that participant is in good health Participants will then complete the baseline
           cognitive and mood assessments. Following this, participants are informed of their iron
           status and will be briefed regarding the requirements of the intervention study.
           Following this, informed consent will be obtained prior to randomising participants to
           one of three treatments and providing them with a treatment diary to log treatment
           consumption and any adverse events experienced.

      Participants will return to the laboratory after 8 weeks to exchange treatment bottles and
      diaries in order to check compliance.

      Participants will finally return to the laboratory after a further 8 weeks (16 weeks total).
      The same procedures will take place prior to cognitive and mood testing as completed at the
      baseline testing visit, with the addition of finger prick and venous blood sample and weight
      measurement. Participants will then complete the same cognitive and mood assessments as
      completed during the baseline testing visit.
    

Intervention name(s): Iron Bis-Glycinate Chelate and Vitamin C; Iron Bis-Glycinate Chelate; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 28 mg iron 240 mg vitamin C; 28 mg iron; Matched placebo
Intervention MeSH terms: Iron; Chelating Agents
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will receive either iron and vitamin C, iron alone or placebo for a period of 16 weeks to consume daily
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Cognition; Mood; Fatigue; Well-being; Women's health; Iron supplementation; Vitamin C