Cadmium Body Burden Clinical Trial
Official title:
Crabmeat and Health Study: Do Brown Crabmeat Consumers Have a Higher Body Burden of Cadmium Compared to Non-crabmeat Consumers?
The brown meat from crab may contain high levels of the heavy metal cadmium. Cadmium is found
in the environment and long-term exposure can cause accumulation in the body. High cadmium
levels can be toxic to the kidney and have been statistically associated with an increased
risk of cancer in the lungs, endometrium, bladder, and breast. This study aims to investigate
if regular consumers of brown crabmeat have a higher body burden of cadmium than
nonconsumers. This is important as no other studies that have addressed this subject. The
results of this research may provide guidance on the consumption of brown meat from crab.
The hypothesis of the proposal is that regular habitual consumption of brown crabmeat
increases the body burden of cadmium.
This study will recruit 25 healthy participants who consume brown crab meat and 25 healthy
participants who do not consume brown crab meat. Volunteers will be eligible if they are ages
40 years and older, non-smokers, and have not had significant occupational exposure to
cadmium. Eligibility will be determined using a questionnaire that consenting volunteers will
be asked to complete.
Eligible participants will be asked to attend a study visit at the Rowett Institute or at a
GP practice in Stromness (depending on participant location). Participants will be weighed
and asked to provide a urine sample as well as a 40 ml (2-3 tbsp.) non-fasted blood sample.
The blood and urine samples will be processed at the Rowett Institute or at the Balfour
Hospital in Kirkwall (depending on where the study visit took place). Analysis will be
completed at the Rowett Institute where whole blood will be analysed for cadmium, selenium,
and zinc and the serum for creatinine and ferritin. Urine samples will be measured for
cadmium, B2-microglobulin and creatinine.
Recruitment is expected to take place over 4 months. Study participants will have the option
of receiving feedback on their cadmium, zinc, selenium and ferritin levels.
Crab meat is low in fat and is a good source of sustainable protein that also provides high
levels of minerals (Se, Zn, I), vitamins (B12) and long chain omega-3 fatty acids. However,
crab meat can also contain high levels of the heavy metal cadmium (Cd), both in the white
meat but especially so in the brown meat (the hepatopancreas and liver). While European
legislation sets a limit of 0.5mg Cd/kg wet weight for the white meat from crab, there
currently is no limit set for the brown meat from crab due to the large range in
concentrations found across member states.
Cd occurs in an inorganic form as an environmental contaminant, both through natural
occurrence and from agricultural and industrial sources. The general population is exposed to
Cd from various sources, including smoking, but in the non-smoking general population, food
is the principal source. Cd is predominantly toxic to the kidney, but it also causes bone
demineralisation and is statistically associated with increased risk of cancer in the lung,
endometrium, bladder and breast. Moreover, blood Cd levels as low as 0.5 - 0.8 µg/l have been
associated with chronic disease. A study of 8,989 US adults from the National Health and
Nutrition Examination Survey (NHANES) found such levels to be associated with all-cause
mortality, cardiovascular disease, and heart disease after around 5 years follow up and
adjustments for a number of potential confounding factors (Tellez-Plaza et al. 2012).
Cd is thought to be absorbed within the body through the use of the same transport pathways
as essential metals including zinc, calcium and iron in the intestine. After absorption, Cd
is transported in the blood to the liver where it forms a complex with metallothionein, a low
molecular weight family of proteins. In the kidney, the Cd-metallothionein complex is
filtered in the glomeruli and then reabsorbed in the renal tubules. Although absorption of Cd
from the diet in humans is comparatively low (3-5%), it is efficiently retained in the kidney
and liver, with a long biological half-life (10 to 30 years). Cd excreted in the urine is a
well-characterized exposure biomarker and can be used as a quantitative indicator of
cumulative internal dose.
Accumulation of Cd increases with age (Olsson et al, 2002), with 50yrs being the age where
urinary cadmium is maximal (WHO/FAO, 2004). Cd is primarily toxic to the kidney, especially
to the proximal tubular cells where accumulation over time may cause a decrease in the
glomerular filtration rate and eventually, renal failure. Cd causes bone demineralisation,
either through direct bone damage or indirectly as a result of renal dysfunction. It is
through long term accumulation of Cd that its toxic effects are mainly manifested. As Cd has
a high affinity for the main intestinal iron transporter (Kim et al, 2007), the absorption of
Cd is influenced by body iron status and there is a close inverse association between serum
ferritin (a marker of iron stores) and blood Cd (Berglund et al, 1994). In this regard,
studies on human populations have shown increasing blood Cd levels with decreasing serum
ferritin in women at fertile age and during pregnancy due to their generally decreased iron
status (Berglund et al., 1994).
There is concern that Cd from crab meat consumption can contribute greatly to the body's Cd
burden however, no studies have investigated whether the Cd present in crabmeat increases the
levels of Cd in the body and similarly, it is not known whether higher Cd intakes in regular
crab meat eaters is associated with increased incidence of kidney damage. This study will
examine some of these issues. There is evidence from some studies suggesting that selenium
and perhaps zinc, which are both present at high levels in crab meat, may counteract the
toxicity of Cd (Lindh et al, 1996; Skröder et al, 2015). Moreover, some evidence may suggest
that the bioavailability of Cd from crab meat may be less compared to Cd in other foods (Lind
et al, 1995). The study will investigate whether volunteers who regularly consume brown
crabmeat have higher levels of Cd compared to volunteers who do not consume crabmeat. A
frequency questionnaire will be designed to estimate participants' total brown crabmeat
intake and to evaluate Cd exposure from crab consumption and this will be compared to the Cd
body burden (assessed as urinary Cd and blood Cd levels) to determine whether an association
between these variables exists and whether regular crab meat consumers have a higher body
burden of Cd compared to non-crabmeat consumers.
HYPOTHESIS
The central hypothesis is that regular habitual consumption of brown crabmeat increases the
body burden of cadmium
OBJECTIVES The objective of the study is to determine if regular brown crabmeat consumers
have an increased body burden of cadmium compared to non-crabmeat consumers.
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