3.3 Identification
of Variables (Markers)
Qualitative and/or qualitative variables are the characteristics that
are measured in the study and must be clearly identified and
defined. Only those that are necessary for the study should be
identified. At least one outcome variable must be considered, and
also, those variables which could lead to confusion or modify the
effect. Here, the time interval between the intervention and the
response of the marker must be defined.
Markers of intake, status, or functional effects to assess the
effect of a dietary/pharmacological intervention with nutrients or
with bioactive compounds, can be biochemical, functional, or clinical measurements. In intervention studies, these are used to assess
the endpoints (i.e., surrogate disease endpoints or those related to
optimal health or adequate nutritional status), that will eventually
be used to support decisions in relation with food, nutrition and
health [23–25]. Recent carotenoid exposure may be assessed using
analytical markers with relatively “fast turnover” (i.e., postprandial
TRL fraction, serum, breast milk) or storage tissue (i.e., adipose
tissue, macular pigment) for functional test biomarkers. As for
overexposure to carotenoids, markers include clinical signs (i.e.,
carotenodermia, corneal rings and retinopathy) and biochemical
measurements (hypercarotenemia, xanthophyll esters) [25]. It is
generally recommended to use more than one biomarker to assess
how diet relates to each disease.
Blood tests (serum/plasma) are the most simple and frequently
used way to assess carotenoid status and response to an intervention
but do not adequately reflect the organism’s response to pharmacological doses. Moreover, the carotenoid clearance may differ
between subjects and type of carotenoid. More recently, stool
samples have been used but with the limitation, inter alia, of possible carotenoid oxidation in the large intestine and retention by
microorganisms. In postprandial studies, carotenoid concentrations are assessed in HDL cholesterol or LDL cholesterol and in
chylomicrons (useful for the assessment of physiological doses but
encountering difficulty in metabolic aspects due to the rapid turnover or transfer among lipoproteins) [25].
An important aspect to be considered in carotenoid intake is
the concentration supplied (in both physiological and pharmacological doses) as metabolism (absorption and transport) appears to
be different depending on the amount supplied. In addition, when
pharmacological doses are administered, safety aspects (related to
direct or indirect actions) such as the capacity of provitamin A
carotenoids to be converted into retinol should be checked as
well [8]. In general, when assessing the effect of food components
on the risk of chronic diseases, the biomarkers used should provide
information on the stage of the disease in which dietary intervention would be effective for an early diagnosis or a better prognosis
of the disease being studied. Therefore, the proper biomarkers
must be selected when dealing with each disease (intermediate
368
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of Variables (Markers)
Qualitative and/or qualitative variables are the characteristics that
are measured in the study and must be clearly identified and
defined. Only those that are necessary for the study should be
identified. At least one outcome variable must be considered, and
also, those variables which could lead to confusion or modify the
effect. Here, the time interval between the intervention and the
response of the marker must be defined.
Markers of intake, status, or functional effects to assess the
effect of a dietary/pharmacological intervention with nutrients or
with bioactive compounds, can be biochemical, functional, or clinical measurements. In intervention studies, these are used to assess
the endpoints (i.e., surrogate disease endpoints or those related to
optimal health or adequate nutritional status), that will eventually
be used to support decisions in relation with food, nutrition and
health [23–25]. Recent carotenoid exposure may be assessed using
analytical markers with relatively “fast turnover” (i.e., postprandial
TRL fraction, serum, breast milk) or storage tissue (i.e., adipose
tissue, macular pigment) for functional test biomarkers. As for
overexposure to carotenoids, markers include clinical signs (i.e.,
carotenodermia, corneal rings and retinopathy) and biochemical
measurements (hypercarotenemia, xanthophyll esters) [25]. It is
generally recommended to use more than one biomarker to assess
how diet relates to each disease.
Blood tests (serum/plasma) are the most simple and frequently
used way to assess carotenoid status and response to an intervention
but do not adequately reflect the organism’s response to pharmacological doses. Moreover, the carotenoid clearance may differ
between subjects and type of carotenoid. More recently, stool
samples have been used but with the limitation, inter alia, of possible carotenoid oxidation in the large intestine and retention by
microorganisms. In postprandial studies, carotenoid concentrations are assessed in HDL cholesterol or LDL cholesterol and in
chylomicrons (useful for the assessment of physiological doses but
encountering difficulty in metabolic aspects due to the rapid turnover or transfer among lipoproteins) [25].
An important aspect to be considered in carotenoid intake is
the concentration supplied (in both physiological and pharmacological doses) as metabolism (absorption and transport) appears to
be different depending on the amount supplied. In addition, when
pharmacological doses are administered, safety aspects (related to
direct or indirect actions) such as the capacity of provitamin A
carotenoids to be converted into retinol should be checked as
well [8]. In general, when assessing the effect of food components
on the risk of chronic diseases, the biomarkers used should provide
information on the stage of the disease in which dietary intervention would be effective for an early diagnosis or a better prognosis
of the disease being studied. Therefore, the proper biomarkers
must be selected when dealing with each disease (intermediate
368
Begon ˜ a Olmedilla-Alonso