16 Weeks' Dietary Supplementation With Iron and Iron + Vitamin C on Cerebral Blood Flow and Energy Expenditure in Women of Reproductive Age
Condition: Iron; Cerebral Blood Flow; Energy Metabolism; Cognitive Function
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. It is postulated that for any cognitive and behavioural change to
      occur, a complementary change in neural functioning is required. A recent cross-sectional
      study has identified increases in cognitive demand to produce decrements in measures of
      cognitive performance and increases in brain activity and metabolic measures; the magnitude
      of such are evidenced to be directly related to iron status. However, such measures do not
      provide an estimate of overall oxygen consumption that is specific to the brain in order to
      be able to associate changes in cognitive performance and energy expenditure specifically to
      the brain itself. The current study aims to investigate the parallel effects of iron
      supplementation on cerebral haemodynamics and energy metabolism to determine the ability of
      iron to modulate whole body energy metabolism and utilisation of metabolic substrates at rest
      and during cognitive demand in a sample of non-anaemic iron deficient and iron sufficient
      women of reproductive age.
    

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. This will include the option to enrol in an additional
      assessment of neuroimaging and energy metabolism.

      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 and additional assessment. Following this, informed consent will be
      obtained prior to starting the additional assessment. Participants will have a frequency
      domain near-infrared spectroscopy headband attached to the forehead to measure cerebral blood
      flow at rest for five minutes. Following this, participants will instead have a continuous
      wave near-infrared spectroscopy headband attached to the forehead to measure cerebral blood
      flow, and a face mask fitted to measure expired air. Participants will have another five
      minute rest before completing an additional battery of cognitive tasks for approximately
      35-40 minutes. Once complete, participants will be randomised to one of three treatments and
      be provided 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, mood and neuroimaging and
      energy metabolism 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 only; 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: Iron supplementation; Cerebral blood flow; Near infrared spectroscopy; Indirect calorimetry; Energy metabolism