Dr. Ron’s Research Review – March 13, 2019

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This week’s research review focuses on arsenic.

 

In a nationally representative sample of the US civilian population, fish (adults), rice (children), and rice cakes/crackers (adolescents) had the largest associations with urinary dimethylarsinic acid (DMA). For monomethylarsonic acid (MMA), rice beverage/milk (adults) and rice cakes/crackers (children, adolescents) had the largest associations. (deCastro et al., 2014)

Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. (Davis et al., 2017)

A total of 65 representative wines from the top four wine-producing states in the U.S. were analyzed for arsenic content. All samples contained arsenic levels that exceeded the U.S. Environmental Protection Agency (U.S. EPA) exposure limit for drinking water of 10 parts per billion (ppb) and all samples contained inorganic arsenic. The average arsenic detected among all samples studied was 23.3 ppb. (Wilson, 2015)

Ingestion of California wine does not pose a hazard due to inorganic arsenic content. (Monnot et al., 2016)

Arsenic in seafood is associated with increased thyroid-stimulating hormone (TSH) in healthy volunteers. These findings indicate that organic dietary As, apparently depending on chemical form, may influence thyroid hormones and function. (Molin et al., 2017)

Folic acid supplementation enhances arsenic methylation. Inorganic As (InAs) is methylated to monomethyl-arsenical species (MMAs) and dimethyl-arsenical species (DMAs), facilitating urinary excretion.  (Bozack et al., 2019)

Dr. Ron

 


Articles

 

Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh.
            (Bozack et al., 2019) Download
Background:  Arsenic exposure through drinking water persists in many regions. Inorganic As (InAs) is methylated to monomethyl-arsenical species (MMAs) and dimethyl-arsenical species (DMAs), facilitating urinary excretion. Arsenic methylation is dependent on one-carbon metabolism, which is influenced by nutritional factors such as folate and creatine. Objective:  This study investigated the effects of folic acid (FA) and/or creatine supplementation on the proportion of As metabolites in urine. Design:  In a 24-wk randomized, double-blinded, placebo-controlled trial, 622 participants were assigned to receive FA (400 or 800 μg per day), 3 g creatine per day, 400 μg FA + 3 g creatine per day, or placebo. The majority of participants were folate sufficient; all received As-removal water filters. From wk 12-24, half of the participants receiving FA received placebo. Results:  Among groups receiving FA, the mean decrease in ln(%InAs) and %MMAs and increase in %DMAs exceeded those of the placebo group at wk 6 and 12 (P < 0.05). In the creatine group, the mean decrease in %MMAs exceeded that of the placebo group at wk 6 and 12 (P < 0.05); creatine supplementation did not affect change in %InAs or %DMAs. The decrease in %MMAs at wk 6 and 12 was larger in the 800 µg FA than in the 400 µg FA group (P = 0.034). There were no differences in treatment effects between the 400 µg FA and creatine + FA groups. Data suggest a rebound in As metabolite proportions after FA cessation; at wk 24, log(%InAs) and %DMAs were not significantly different than baseline levels among participants who discontinued FA supplementation. Conclusions:  The results of this study confirm that FA supplementation rapidly and significantly increases methylation of InAs to DMAs. Further research is needed to understand the strong cross-sectional associations between urinary creatinine and As methylation in previous studies. This trial was registered at https://clinicaltrials.gov as NCT01050556.

Assessment of human dietary exposure to arsenic through rice.
            (Davis et al., 2017) Download
Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. This review summarizes epidemiologic studies that examined the association between rice consumption and biomarkers of arsenic exposure. After reviewing the literature we identified 20 studies, among them included 18 observational and 2 human experimental studies that reported on associations between rice consumption and an arsenic biomarker. Among individuals not exposed to contaminated water, rice is a source of i-As exposure - rice consumption has been consistently related to arsenic biomarkers, and the relationship has been clearly demonstrated in experimental studies. Early-life i-As exposure is of particular concern due to its association with lifelong adverse health outcomes. Maternal rice consumption during pregnancy also has been associated with infant toenail total arsenic concentrations indicating that dietary exposure during pregnancy results in fetal exposure. Thus, the collective evidence indicates that rice is an independent source of arsenic exposure in populations around the world and highlights the importance of investigating its affect on health.

Dietary sources of methylated arsenic species in urine of the United States population, NHANES 2003-2010.
            (deCastro et al., 2014) Download
BACKGROUND:  Arsenic is an ubiquitous element linked to carcinogenicity, neurotoxicity, as well as adverse respiratory, gastrointestinal, hepatic, and dermal health effects. OBJECTIVE:  Identify dietary sources of speciated arsenic: monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). METHODS:  Age-stratified, sample-weighted regression of NHANES (National Health and Nutrition Examination Survey) 2003-2010 data (∼8,300 participants ≥6 years old) characterized the association between urinary arsenic species and the additional mass consumed of USDA-standardized food groups (24-hour dietary recall data), controlling for potential confounders. RESULTS:  For all arsenic species, the rank-order of age strata for median urinary molar concentration was children 6-11 years > adults 20-84 years > adolescents 12-19 years, and for all age strata, the rank-order was DMA > MMA. Median urinary molar concentrations of methylated arsenic species ranged from 0.56 to 3.52 µmol/mol creatinine. Statistically significant increases in urinary arsenic species were associated with increased consumption of: fish (DMA); fruits (DMA, MMA); grain products (DMA, MMA); legumes, nuts, seeds (DMA); meat, poultry (DMA); rice (DMA, MMA); rice cakes/crackers (DMA, MMA); and sugars, sweets, beverages (MMA). And, for adults, rice beverage/milk (DMA, MMA). In addition, based on US (United States) median and 90th percentile consumption rates of each food group, exposure from the following food groups was highlighted: fish; fruits; grain products; legumes, nuts, seeds; meat, poultry; and sugars, sweets, beverages. CONCLUSIONS:  In a nationally representative sample of the US civilian, noninstitutionalized population, fish (adults), rice (children), and rice cakes/crackers (adolescents) had the largest associations with urinary DMA. For MMA, rice beverage/milk (adults) and rice cakes/crackers (children, adolescents) had the largest associations.


 

Arsenic in seafood is associated with increased thyroid-stimulating hormone (TSH) in healthy volunteers - A randomized controlled trial.
            (Molin et al., 2017) Download
BACKGROUND:  Exposure to exogenous elements like arsenic (As) may influence thyroid enzymes, thyroid-stimulating hormone (TSH), and the two principal thyroid hormones, free thyroxine (FT4) and free triiodothyronine (FT3), but little is known about how this is related to organic arsenicals, the main form in seafood. AIM:  To investigate whether a high intake of dietary arsenic from seafood can impact thyroid function and thyroid hormones by examining possible associations with changes in TSH, FT4, FT3 and the FT4:FT3-ratio in plasma. METHODS:  Thirty-eight healthy subjects were randomized into four groups. During a 14-day semi-controlled dietary study, the subjects ingested daily portions of either 150g cod, salmon, blue mussels or potato (control). Plasma concentrations of total As, FT3, FT4, TSH and selenium (Se), and urinary concentrations of iodine were monitored. RESULTS:  Plasma concentrations of TSH increased significantly in all seafood groups. The change in plasma As, with different coefficients for each seafood group, was the dominant factor in the optimal multiple regression model for change in TSH (R CONCLUSION:  Ingestion of seafood rich in various organic As species was strongly associated with an increase of the TSH concentrations in plasma. Change in TSH was positively associated with total plasma As, but varied with the type of seafood ingested. These findings indicate that organic dietary As, apparently depending on chemical form, may influence thyroid hormones and function.

Risks associated with arsenic exposure resulting from the consumption of California wines sold in the United States.
            (Monnot et al., 2016) Download
Concerns have recently been raised about the presence of arsenic (As) in wine. In this analysis, 101 different California wines were evaluated for organic and inorganic As concentration. The average concentrations of total inorganic As in red, blush and white wines were 6.12μg/L (range: 0.40-20.5μg/L), 21.6μg/L (range: 0.92-41.2μg/L) and 9.5μg/L (0.57-30.4μg/L). The average concentrations of total organic As in red, blush and white wines were 0.64μg/L (0.10-2.74μg/L), 0.99μg/L (0.50-2.28μg/L), and 0.51μg/L (0.10-1.78μg/L). A screening level risk assessment was conducted to assess the potential non-carcinogenic risk resulting from wine consumption. The hazard quotient (HQ) for the inorganic As RfD and the As content of red, blush and white wines was each less than one; indicating that the non-cancer health risk was insignificant. Results indicate that ingestion of California wine does not pose a hazard due to inorganic As content.


 

Arsenic Content in American Wine.
            (Wilson, 2015) Download
Recent studies that have investigated arsenic content in juice, rice, milk, broth (beef and chicken), and other foods have stimulated an interest in understanding how prevalent arsenic contamination is in the U.S. food and beverage supply. The study described here focused on quantifying arsenic levels in wine. A total of 65 representative wines from the top four wine-producing states in the U.S. were analyzed for arsenic content. All samples contained arsenic levels that exceeded the U.S. Environmental Protection Agency (U.S. EPA) exposure limit for drinking water of 10 parts per billion (ppb) and all samples contained inorganic arsenic. The average arsenic detected among all samples studied was 23.3 ppb. Lead, a common co-contaminant to arsenic, was detected in 58% of samples tested, but only 5% exceeded the U.S. EPA exposure limit for drinking water of 15 ppb. Arsenic levels in American wines exceeded those found in other studies involving water, bottled water, apple juice, apple juice blend, milk, rice syrup, and other beverages. When taken in the context of consumption patterns in the U.S., the pervasive presence of arsenic in wine can pose a potential health risk to regular adult wine drinkers.

 


References

Bozack, AK, et al. (2019), ‘Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh.’, Am J Clin Nutr, 109 (2), 380-91. PubMed: 30590411
Davis, MA, et al. (2017), ‘Assessment of human dietary exposure to arsenic through rice.’, Sci Total Environ, 586 1237-44. PubMed: 28233618
deCastro, BR, et al. (2014), ‘Dietary sources of methylated arsenic species in urine of the United States population, NHANES 2003-2010.’, PLoS One, 9 e108098. PubMed: 25251890
Molin, M, et al. (2017), ‘Arsenic in seafood is associated with increased thyroid-stimulating hormone (TSH) in healthy volunteers - A randomized controlled trial.’, J Trace Elem Med Biol, 44 1-7. PubMed: 28965562
Monnot, AD, et al. (2016), ‘Risks associated with arsenic exposure resulting from the consumption of California wines sold in the United States.’, Food Chem, 211 107-13. PubMed: 27283613
Wilson, D (2015), ‘Arsenic Content in American Wine.’, J Environ Health, 78 (3), 16-22. PubMed: 26591333