Soma R. Mitra

Nutritional Factors and Susceptibility to Arsenic-Caused Skin Lesions in West Bengal, India

There has been widespread speculation about whether nutritional deficiencies increase the susceptibility to arsenic health effects. This is the first study to investigate whether dietary micronutrient and macronutrient intake modulates the well-established human risk of arsenic-induced skin lesions, including alterations in skin pigmentation and keratoses. The study was conducted in West Bengal, India, which along with Bangladesh constitutes the largest population in the world exposed to arsenic from drinking water. In this case–control study design, cases were patients with arsenic-induced skin lesions and had < 500 μg/L arsenic in their drinking water. For each case, an age- and sex-matched control was selected from participants of a 1995–1996 cross-sectional survey, whose drinking water at that time also contained < 500 μg/L arsenic. Nutritional assessment was based on a 24-hr recall for major dietary constituents and a 1-week recall for less common constituents. Modest increases in risk were related to being in the lowest quintiles of intake of animal protein [odds ratio (OR) = 1.94; 95% confidence interval (CI), 1.05–3.59], calcium (OR = 1.89; 95% CI, 1.04–3.43), fiber (OR = 2.20; 95% CI, 1.15–4.21), and folate (OR = 1.67; 95% CI, 0.87–3.2). Conditional logistic regression suggested that the strongest associations were with low calcium, low animal protein, low folate, and low fiber intake. Nutrient intake was not related to arsenic exposure. We conclude that low intake of calcium, animal protein, folate, and fiber may increase susceptibility to arsenic-caused skin lesions. However, in light of the small magnitude of increased risks related to these dietary deficiencies, prevention should focus on reducing exposure to arsenic.

Arsenic in Drinking Water and Skin Lesions: Dose-Response Data from West Bengal, India

Background. Over 6 million people live in areas of West Bengal, India, where groundwater sources are contaminated with naturally occurring arsenic. The key objective of this nested case-control study was to characterize the dose-response relation between low arsenic concentrations in drinking water and arsenic-induced skin keratoses and hyperpigmentation. Methods. We selected cases (persons with arsenic-induced skin lesions) and age- and sex-matched controls from participants in a 1995–1996 cross-sectional survey in West Bengal. We used a detailed assessment of arsenic exposure that covered at least 20 years. Participants were reexamined between 1998 and 2000. Consensus agreement by four physicians reviewing the skin lesion photographs confirmed the diagnosis in 87% of cases clinically diagnosed in the field. Results. The average peak arsenic concentration in drinking water was 325 &mgr;g/liter for cases and 180 &mgr;g/liter for controls. The average latency for skin lesions was 23 years from first exposure. We found strong dose-response gradients with both peak and average arsenic water concentrations. Conclusions. The lowest peak arsenic ingested by a confirmed case was 115 &mgr;g/liter. Confirmation of case diagnosis and intensive longitudinal exposure assessment provide the basis for a detailed dose-response evaluation of arsenic-caused skin lesions.

Creatinine, Diet, Micronutrients, and Arsenic Methylation in West Bengal, India

Background: Ingested inorganic arsenic (InAs) is methylated to monomethylated (MMA) and dimethylated metabolites (DMA). Methylation may have an important role in arsenic toxicity, because the monomethylated trivalent metabolite [MMA(III)] is highly toxic. Objectives: We assessed the relationship of creatinine and nutrition—using dietary intake and blood concentrations of micronutrients—with arsenic metabolism, as reflected in the proportions of InAS, MMA, and DMA in urine, in the first study that incorporated both dietary and micronutrient data. Methods: We studied methylation patterns and nutritional factors in 405 persons who were selected from a cross-sectional survey of 7,638 people in an arsenic-exposed population in West Bengal, India. We assessed associations of urine creatinine and nutritional factors (19 dietary intake variables and 16 blood micronutrients) with arsenic metabolites in urine. Results: Urinary creatinine had the strongest relationship with overall arsenic methylation to DMA. Those with the highest urinary creatinine concentrations had 7.2% more arsenic as DMA compared with those with low creatinine (p < 0.001). Animal fat intake had the strongest relationship with MMA% (highest tertile animal fat intake had 2.3% more arsenic as MMA, p < 0.001). Low serum selenium and low folate were also associated with increased MMA%. Conclusions: Urine creatinine concentration was the strongest biological marker of arsenic methylation efficiency, and therefore should not be used to adjust for urine concentration in arsenic studies. The new finding that animal fat intake has a positive relationship with MMA% warrants further assessment in other studies. Increased MMA% was also associated, to a lesser extent, with low serum selenium and folate.

Vitamin D status and markers of bone turnover in Caucasian and South Asian postmenopausal women living in the UK

Suboptimal vitamin D status among the South Asian UK population is widely reported; however, its impact on bone health is unclear. The aim of the present study was to conduct a comparative investigation of vitamin D status in postmenopausal South Asian (SA) and Caucasian (C) women and its relationship to parathyroid hormone (PTH) concentration, biochemical markers of bone turnover and bone quality. A cross-sectional study of community-dwelling women aged 50-66 years was carried out. A total of sixty-six SA women of Pakistani origin and forty-two C women living in the same community were recruited. Fasting blood was taken for the measurement of vitamin D, PTH and biochemical markers of bone turnover, including type-1 collagen beta C-telopeptide (betaCTX), procollagen type-1 amino-terminal propeptide (P1NP), and bone-specific alkaline phosphatase (BAP) activity. Bone quality was assessed using broadband ultrasound attenuation (BUA). Total serum 25-hydroxyvitamin D (25(OH)D) was significantly lower in the SA women than the C women (medians: SA 10.5 v. C 47.1 nmol/l; P < 0.001) This was associated with a significantly elevated serum PTH concentration in the SA group (medians: SA 7.3 v. C 4.5 pmol/l; P < 0.01). BAP activity was also significantly higher in the SA group, indicating elevated osteoblast activity and bone turnover (medians: SA 23.0 v. C 20.0 U/l; P < 0.05). No significant differences were observed between the two groups for P1NP, betaCTX or BUA. Although the SA women had significantly higher serum PTH and lower 25(OH)D concentrations than C women, this was not associated with significantly higher markers of bone resorption, or reduced bone quality in the SA women.

Daily Consumption of a Fruit and Vegetable Smoothie Alters Facial Skin Color.

Consumption of dietary carotenoids or carotenoid supplements can alter the color (yellowness) of human skin through increased carotenoid deposition in the skin. As fruit and vegetables are the main dietary sources of carotenoids, skin yellowness may be a function of regular fruit and vegetable consumption. However, most previous studies have used tablets or capsules to supplement carotenoid intake, and less is known of the impact of increased fruit and vegetable consumption on skin color. Here, we examined skin color changes in an Asian population (Malaysian Chinese ethnicity) over a six week dietary intervention with a carotenoid-rich fruit smoothie. Eighty one university students (34 males, 47 females; mean age 20.48) were assigned randomly to consuming either a fruit smoothie (intervention group) or mineral water (control group) daily for six weeks. Participants’ skin yellowness (CIELab b*), redness (a*) and luminance (L*) were measured at baseline, twice during the intervention period and at a two-week follow-up, using a handheld reflectance spectrophotometer. Results showed a large increment in skin yellowness (p<0.001) and slight increment in skin redness (p<0.001) after 4 weeks of intervention for participants in the intervention group. Skin yellowness and skin redness remained elevated at the two week follow up measurement. In conclusion, intervention with a carotenoid-rich fruit smoothie is associated with increased skin redness and yellowness in an Asian population. Changes in the reflectance spectrum of the skin suggest that this color change was caused by carotenoid deposition in the skin.

Trace mineral status in Caucasian and South Asian postmenopausal women living in the UK

Zinc, Selenium and Copper are essential trace minerals that are important for human health and data suggests there is a high prevalence of inadequate intake in the UK with the prevalence of inadequate intake being higher in females than in males. Previous data from this laboratory has also indicated that South Asian (SA) females may be more at risk of micronutrient deficiency than Caucasian (C) females. The aim of this study was to investigate this further and conduct a comparative investigation of Zn, Se and Cu status in postmenopausal SA and C females. Apparently healthy postmenopausal C and SA females of 50–65 years of age and at least one year post menopause were identified for this study. Dietary information was collected using an interviewer administered food frequency questionnaire (FFQ) which was developed to study nutrient intakes of an adult Pakistani, European and African-Caribbean community in inner city Britain. Fasting blood samples were collected and plasma was stored at 70 C until analysis. The Se, Cu, and Zn content of plasma samples was measured by inductively coupled plasma-mass spectroscopy (ICP-MS).

Relationship of Creatinine and Nutrition with Arsenic Metabolism: Smith et al. Respond.

We thank Hall and Gamble for their interest in our findings. In our article (Basu et al. 2011), we cited their earlier results concerning urinary dimethylarsinic acid (DMA) and creatinine concentrations, noting that in 2005 they reported a strong correlation between urinary creatinine and the percentage of DMA (DMA%) (Gamble et al. 2005). We also noted rather similar findings from another group working in Bangladesh (Nermell et al. 2008), so together with our findings in India, there are three separate studies that have reported this association (Basu et al. 2011; Gamble et al 2005; Nermell et al 2008). Our results highlight the strength of the relationship between urinary creatinine and urinary DMA%, which was stronger than the relationship between DMA% and any of the 19 dietary factors and 16 blood micronutrients that we investigated. Gamble and Hall state that they had previously reported (Gamble and Liu 2005) that one implication of the observed association between urinary creatinine and arsenic methylation was that urinary As should not be expressed as per gram creatinine to correct for urine concentrations. This is not quite what they said, although they did point out risks in expressing urinary arsenic per gram of creatinine. However, in that letter (Gamble and Liu 2005) and again in this one, they state that urinary creatinine should be included as a covariate in regression models. We do not agree with this recommendation. Steinmaus et al. (2009) reported a spurious relationship between low-level arsenic concentrations and diabetes in the United States after including urinary creatinine in a regression model. They noted that urinary creatinine concentrations may change as a consequence of diabetes, which is known to affect renal function, and that it is not appropriate to adjust for a factor that is a consequence of the disease being studied. We also do not agree with Gamble and Hall’s criticism of our blood sample handling, which they appear to have raised because our folate findings were different from theirs (e.g., Gamble et al. 2005). For our study (Basu et al. 2011), blood samples were collected in remote villages, and on occasion they had to be stored on ice for up to 24 hr. Gamble and Hall state that “this 24-hr delay can be problematic for some nutrients, especially folate, which is extremely sensitive to oxidative degradation.” In support of this statement they cite Drammeh et al. (2008), who found reductions in serum folate concentrations (about 30%) from whole blood stored for 1 day at 32°C. However, storing blood samples on ice at about 0°C is not the same as storing at 32°C, so this result is not relevant. In addition, Drammeh et al. cited a study that reported stable plasma folate levels during storage of up to 7 days at 4°C (Kubasik et al. 1979). We therefore do not think our findings should be criticized based on sample storage. However, this does not mean we suggest that folate is not related to DMA%. Findings may vary from study to study, and we accept that Gamble et al. have reported several studies suggesting that folate is associated with small increases in arsenic methylation, including a randomized trial with folate supplements (Gamble et al. 2006). In a study of pregnant women in Bangladesh, a small association between folate and arsenic methylation was reported (Gardner et al. 2011; Li et al. 2008); the authors concluded that nutritional status has a marginal influence on the metabolism of arsenic in pregnant women. Although the overall evidence suggests that folate may increase arsenic methylation, the magnitude of the effect is small and in our opinion of little consequence. In their letter Gamble et al. report they are now conducting a randomized trial with creatine. Well-run randomized trials of nutritional supplements with sufficient statistical power typically require a large amount of public health funds and resources. We suggest that randomized trials should be conducted only on people whose exposure to arsenic has ceased. However, it is clear that exposures did not cease in the randomized trial of folate they conducted, but that exposures remained markedly elevated based on urine arsenic concentrations (Gamble et al. 2006). The purpose of a randomized trial of folate or creatine is to determine whether these agents might affect arsenic methylation to help reduce arsenic toxicity and increase excretion. However, the relevance of this goal is questionable because we already know the best and most appropriate way to reduce arsenic toxicity—by reducing exposure. The first priority should be to stop exposure to arsenic. If exposure to arsenic ceased, there would be very little arsenic to methylate and enhancement of methylation with supplements would not be necessary.