Linda J. Harvey

Methods of assessment of iodine status in humans: a systematic review

BACKGROUND Zinc is an essential micronutrient for human health and has numerous structural and biochemical roles. The search for a reliable, sensitive, and specific index of zinc status has been the subject of considerable research, which has resulted in the identification of a number of potentially useful biomarkers. OBJECTIVE The objective was to assess the usefulness of biomarkers of zinc status in humans. DESIGN The methods included a structured search strategy using Ovid MEDLINE, EMBASE (Ovid), and the Cochrane Library CENTRAL databases; formal inclusion and exclusion criteria; data extraction into an Access database; quality and validity assessment; and meta-analysis. RESULTS Data on 32 potential biomarkers from 46 publications were analyzed. Plasma zinc concentration responded in a dose-dependent manner to dietary manipulation in adults, women, men, pregnant and lactating women, the elderly, and those at low and moderate baseline zinc status. Urinary zinc excretion responded to zinc status overall and in all subgroups for which there were sufficient data. Hair zinc concentration also responded, but there were insufficient studies for subgroup analysis. Platelet, polymorphonuclear cell, mononuclear cell, and erythrocyte zinc concentration and alkaline phosphatase activity did not appear to be effective biomarkers of zinc status. CONCLUSIONS This systematic review confirms that in healthy individuals, plasma, urinary, and hair zinc are reliable biomarkers of zinc status. Further high-quality studies using these biomarkers are required, particularly in infants, adolescents, and immigrant population groups for whom there are limited data. Studies are also required to fully assess a range of additional potential zinc biomarkers.

Impact of menstrual blood loss and diet on iron deficiency among women in the UK

Women of childbearing age are at risk of Fe deficiency if insufficient dietary Fe is available to replace menstrual and other Fe losses. Haem Fe represents 10-15 % of dietary Fe intake in meat-rich diets but may contribute 40 % of the total absorbed Fe. The aim of the present study was to determine the relative effects of type of diet and menstrual Fe loss on Fe status in women. Ninety healthy premenopausal women were recruited according to their habitual diet: red meat, poultry/fish or lacto-ovo-vegetarian. Intake of Fe was determined by analysing 7 d duplicate diets, and menstrual Fe loss was measured using the alkaline haematin method. A substantial proportion of women (60 % red meat, 40 % lacto-ovo-vegetarian, 20 % poultry/fish) had low Fe stores (serum ferritin <10 microg/l), but the median serum ferritin concentration was significantly lower in the red meat group (6.8 microg/l (interquartile range 3.3, 16.25)) than in the poultry/fish group (17.5 microg/l (interquartile range 11.3, 22.4) (P<0.01). The mean and standard deviation of dietary Fe intake were significantly different between the groups (P=0.025); the red meat group had a significantly lower intake (10.9 (sd 4.3) mg/d) than the lacto-ovo-vegetarians (14.5 (sd 5.5) mg/d), whereas that of the poultry/fish group (12.8 (sd 5.1) mg/d) was not significantly different from the other groups. There was no relationship between total Fe intake and Fe status, but menstrual Fe loss (P=0.001) and dietary group (P=0.040) were significant predictors of Fe status: poultry/fish diets were associated with higher Fe stores than lacto-ovo-vegetarian diets. Identifying individuals with high menstrual losses should be a key component of strategies to prevent Fe deficiency.

Selenium and prostate cancer: systematic review and meta-analysis

BACKGROUND Prostate cancer is a growing public health problem. Several human studies have shown a potentially protective effect of selenium, but the conclusions from published reports are inconsistent. OBJECTIVE The objective was to examine the evidence for relations between selenium intake, selenium status, and prostate cancer risk. DESIGN This was a systematic review and meta-analysis of randomized controlled trials, case-control studies, and prospective cohort studies. The World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project database was searched up to September 2010. The studies included reported measurements of selenium intake or status (plasma, serum, or toenail selenium), assessments of prostate cancer cases (number of events), and the RR in the adult population. Meta-analyses were performed, and study quality, heterogeneity, and small study effects were assessed. Dose-response meta-analyses were used, with restricted cubic splines and fractional polynomials for nonlinear trends, to investigate the association between selenium status and prostate cancer risk. RESULTS Twelve studies with a total of 13,254 participants and 5007 cases of prostate cancer were included. The relation between plasma/serum selenium and prostate cancer in a nonlinear dose-response meta-analysis showed that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL. Three high-quality studies included in the meta-analysis of toenail selenium and cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29; 95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94 μg/g. CONCLUSION The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.

Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women.

Hepcidin plays a major role in iron homeostasis, but understanding its role has been hampered by the absence of analytical methods for quantification in blood. A commercial ELISA has been developed for serum prohepcidin, a hepcidin precursor, and there is interest in its potential use in the clinical and research arena. We investigated the association between serum prohepcidin concentration and iron absorption in healthy men, and its relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients, and pregnant women. Iron absorption was determined in thirty healthy men (fifteen wild-type, fifteen C282Y heterozygote) using the stable isotope red cell incorporation technique. Iron status was measured in 138 healthy men (ninety-one wild-type, forty-seven C282Y heterozygote), six hereditary haemochromatosis patients, and thirteen pregnant women. Mean serum prohepcidin concentrations were 214 (SD 118) ng/ml [208 (SD 122) ng/ml in wild-type and 225 (SD 109) ng/ml in C282Y heterozygotes] in healthy men, 177 (SD 36) ng/ml in haemochromatosis patients, and 159 (SD 59) ng/ml in pregnant women. There was no relationship between serum prohepcidin concentration and serum ferritin in any subject groups, nor was it associated with efficiency of iron absorption. Serum prohepcidin is not a useful biomarker for clinical or research purposes.

The absorption of iron from whole diets: a systematic review

BACKGROUND Absorption factors are required to convert physiologic requirements for iron into Dietary Reference Values, but the absorption from single meals cannot be used to estimate dietary iron absorption. OBJECTIVE The objective was to conduct a systematic review of iron absorption from whole diets. DESIGN A structured search was completed by using the Medline, EMBASE, and Cochrane CENTRAL databases from inception to November 2011. Formal inclusion and exclusion criteria were applied, and data extraction, validity assessment, and meta-analyses were undertaken. RESULTS Nineteen studies from the United States, Europe, and Mexico were included. Absorption from diets was higher with an enhancer (standard mean difference: 0.53; 95% CI: 0.21, 0.85; P = 0.001) and was also higher when compared with low-bioavailability diets (standard mean difference: 0.96; 95% CI: 0.51, 1.41; P < 0.0001); however, single inhibitors did not reduce absorption (possibly because of the limited number of studies and participants and their heterogeneity). A regression equation to calculate iron absorption was derived by pooling data for iron status (serum and plasma ferritin) and dietary enhancers and inhibitors from 58 individuals (all from US studies): log[nonheme-iron absorption, %] = -0.73 log[ferritin, μg/L] + 0.11 [modifier] + 1.82. In individuals with serum ferritin concentrations from 6 to 80 μg/L, predicted absorption ranged from 2.1% to 23.0%. CONCLUSIONS Large variations were observed in mean nonheme-iron absorption (0.7-22.9%) between studies, which depended on iron status (diet had a greater effect at low serum and plasma ferritin concentrations) and dietary enhancers and inhibitors. Iron absorption was predicted from serum ferritin concentrations and dietary modifiers by using a regression equation. Extrapolation of these findings to developing countries and to men and women of different ages will require additional high-quality controlled trials.

EURRECA—Estimating Zinc Requirements for Deriving Dietary Reference Values

Zinc was selected as a priority micronutrient for EURRECA, because there is significant heterogeneity in the Dietary Reference Values (DRVs) across Europe. In addition, the prevalence of inadequate zinc intakes was thought to be high among all population groups worldwide, and the public health concern is considerable. In accordance with the EURRECA consortium principles and protocols, a series of literature reviews were undertaken in order to develop best practice guidelines for assessing dietary zinc intake and zinc status. These were incorporated into subsequent literature search strategies and protocols for studies investigating the relationships between zinc intake, status and health, as well as studies relating to the factorial approach (including bioavailability) for setting dietary recommendations. EMBASE (Ovid), Cochrane Library CENTRAL, and MEDLINE (Ovid) databases were searched for studies published up to February 2010 and collated into a series of Endnote databases that are available for the use of future DRV panels. Meta-analyses of data extracted from these publications were performed where possible in order to address specific questions relating to factors affecting dietary recommendations. This review has highlighted the need for more high quality studies to address gaps in current knowledge, in particular the continued search for a reliable biomarker of zinc status and the influence of genetic polymorphisms on individual dietary requirements. In addition, there is a need to further develop models of the effect of dietary inhibitors of zinc absorption and their impact on population dietary zinc requirements.

Effects of Dietary Fish Oil Supplementation on the Phospholipid Composition and Fluidity of Cell Membranes from Human Volunteers

Background: Membrane fluidity is an important aspect of cellular physiology which may be manipulated by diet. Methods: We studied the effect of dietary fish oil on the membrane composition of erythrocytes and cheek cells, and on membrane fluidity of erythrocytes as assessed by fluorescence recovery after photobleaching (FRAP). Healthy volunteers received a daily supplement of fish oil (930 mg EPA, 630 mg DHA) for 42 days. Results: The intervention reduced the ratio of n-6 to total fatty acid in the phospholipid fraction of erythroctye membranes but the n-3 fraction remained stable and the ratio of cholesterol to phospholipid increased. The level of EPA and DHA in cheek cells increased significantly during the intervention period. The mean diffusion coefficient of the fluorescent probe in erythrocyte membranes increased from 7.2 ± 0.7 × 10–9 cm2/s at the start to 9.8 ± 0.5 × 10–9 cm2/s after 21 days. Membrane fluidity remained higher than the initial value 42 days after withdrawal of the supplement. Fish oil also reduced platelet aggregation in response to ADP but there was no effect on plasma lipid profiles. Conclusion: We conclude that n-3 fatty acids influence erythrocyte membrane composition at relatively low levels of supplementation by a mechanism which does not necessarily involve an increase in the level of EPA or DHA present in the membrane.

Assessing potential biomarkers of micronutrient status by using a systematic review methodology: methods

BACKGROUND To explore the relation between micronutrient status and health, it is important to understand which markers of micronutrient status can be relied on and under what circumstances. OBJECTIVE The objective of this article was to develop a common systematic review methodology for use in the assessment of micronutrient status for selenium, iodine, copper, zinc, riboflavin, vitamin B-12, vitamin D, and omega-3 (n-3) long-chain polyunsaturated fatty acids. DESIGN We developed a methodology on the basis of defining studies that clearly altered micronutrient status and then pooled data on the effects of this intervention on each specific biomarker to assess objectively the response of various status markers to changes in intake. RESULTS The generic methodology included defining, and systematically searching for, studies that resulted in a change in micronutrient status. Study inclusion, data extraction, and assessment of validity were conducted with a minimum of 10% independent duplication. For each study and each potential biomarker, the highest dose and longest duration intervention data were selected to assess the statistical significance of any change in intake on the status biomarker. The consistency of biomarker response was explored by subgrouping the studies according to baseline micronutrient status, sex, population group, supplementation type, dose, duration, and analytic method. CONCLUSION This methodology allows systematic assessment of the usefulness of a number of biomarkers for a selection of micronutrients.

Fish consumption and markers of colorectal cancer risk: a multicenter randomized controlled trial

BACKGROUND Diet is a major factor in the etiology of colorectal cancer, with high fish consumption possibly decreasing colorectal cancer risk, as was shown in several observational studies. To date, no intervention trials have examined the possible beneficial effects of fish intake on colorectal cancer risk. OBJECTIVE The objective was to investigate the effects of a 6-mo intervention with oil-rich or lean fish on apoptosis and mitosis within the colonic crypt. DESIGN In a multicenter, randomized, controlled intervention trial, patients with colorectal polyps, inactive ulcerative colitis, or no macroscopic signs of disease were recruited (n = 242) and randomly allocated to receive dietary advice plus either 300 g oil-rich fish (salmon) per week (n = 82), 300 g lean fish (cod) per week (n = 78), or only dietary advice (DA) (n = 82). Apoptosis and mitosis were measured in colonic biopsy samples collected before and after intervention (n = 213). RESULTS The total number of apoptotic cells per crypt did not increase in the salmon or cod group: -0.10 (95% CI: -0.36, 0.16) and -0.06 (95% CI: -0.32, 0.20), respectively, compared with the DA group. The total number of mitotic cells per crypt decreased nonsignificantly in the salmon group (-0.87; 95% CI: -2.41, 0.68) and in the cod group (-1.04; 95% CI: -2.62, 0.53) compared with the DA group. Furthermore, the distribution of mitosis within the crypt did not significantly change in either group. CONCLUSION An increase in the consumption of either oil-rich or lean fish to 2 portions weekly over 6 mo does not markedly change apoptotic and mitotic rates in the colonic mucosa. This trial was registered at www.clinicaltrials.gov as NCT00145015.

Increased Consumption of Fatty and Lean Fish Reduces Serum C-Reactive Protein Concentrations but Not Inflammation Markers in Feces and in Colonic Biopsies

Fish consumption is associated with a reduced colorectal cancer risk. A possible mechanism by which fish consumption could decrease colorectal cancer risk is by reducing inflammation. However, thus far, intervention studies investigating both systemic and local gut inflammation markers are lacking. Our objective in this study was to investigate the effects of fatty and lean fish consumption on inflammation markers in serum, feces, and gut. In an intervention study, participants were randomly allocated to receive dietary advice (DA) plus either 300 g of fatty fish (salmon) or 300 g of lean fish (cod) per week for 6 mo, or only DA. Serum C-reactive protein (CRP) concentrations were measured pre- and postintervention (n = 161). In a subgroup (n = 52), we explored the effects of the fish intervention on fecal calprotectin and a wide range of cytokines and chemokines in fecal water and in colonic biopsies. Serum CRP concentrations were lower in the salmon (-0.5 mg/L; 95% CI -0.9, -0.2) and cod (-0.4 mg/L; 95% CI -0.7, 0.0) groups compared with the DA group. None of the inflammation markers in fecal water and colonic biopsies differed between the DA group and the groups that consumed extra fish. In conclusion, increasing salmon or cod consumption for 6 mo resulted in lower concentrations of the systemic inflammation marker CRP. However, exploratory analysis of local markers of inflammation in the colon or feces did not reveal an effect of fish consumption.