Arsenic as the chronic poison (material cause) and deficiencies as the drivers of arsenic-related diseases

The metabolism of inorganic arsenic, As, involves two oxidative methylations and two reductions, and is as follows (the Roman numerals are the positive charges on the central Arsenic ion):

As(III) [toxic and poorly excreted]→ Me-As(V) → Me-As(III) [more toxic than arsenic and also poorly excreted] → Me-As(V)-Me → Me-As(III)-Me (least toxic to tissues because most easily excreted?), the latter being the primary product excreted in urine in the US, which rapidly oxidizes back to MeAs(V)Me, unless the urine is stabilized with antioxidants [does this not point to a deficiency of antioxidants in most peoples’ urine? Is healthy urine a reducing medium or is it not?]

Now the assumption: this is a detoxification pathway.

Bigger assumption: this is the optimal detoxification pathway. Not comfortable with this assumption because Americans are still malnourished in that those who over-consume animal products [meat, eggs, dairy, and fish] under-consume vegetables and those who over-consume vegetables under-consume animal products – both strike me as folly in the extreme, and many times Americans’ bodies are also stressed by the act of overfeeding (too many calories), and their minds are stressed about the weight gain overeating entails and many other things.

If this metabolic pathway is a detoxification pathway, then we can see why chronic low-level arsenic poisoning in general and one particular manifestation, blackfoot disease, is less common in the US than in places where nutrition is clearly inadequate and people are underfed, i.e. where there is a deficiency of animal protein, and its associated co-nutrients, and in my opinion, a deficiency in total calories. Basically, the people are emaciated vegetarians because their total muscle protein is dictated by the low level supportable on a low calorie vegetarian diet, a diet deficient in several essential amino acids, none more so than the central molecule of the methylation network, methionine, a network involved in arsenic metabolism.

Consider this evidence (Environ Health Perspect. 2005 Sep;113(9):1153-9. Dietary intake and arsenic methylation in a U.S. population. Steinmaus C1, Carrigan K, Kalman D, Atallah R, Yuan Y, Smith AH):

“In fact, several epidemiologic studies have reported associations between elevated urinary proportions of MMA and increased risks of arsenic-associated health effects. In four studies from arsenic-exposed regions in Taiwan, subjects who excreted high proportions of urinary arsenic as MMA (percent MMA) or had high urinary MMA:DMA ratios had skin and bladder cancer odds ratios (OR) that were two to five times higher than did subjects who excreted low proportions of urinary MMA or had low MMA:DMA ratios (Chen et al. 2003a, 2003b; Hsueh et al. 1997; Yu et al. 2000). Associations between high levels of urinary percent MMA and increased bladder cancer risks were also found in studies on arsenic-exposed populations in the United States and Argentina (Steinmaus et al. 2004).

Other studies have reported links between elevated urinary percent MMA or an elevated MMA:DMA ratio and increased risks of arsenic-caused skin lesions and increased rates of chromosomal aberrations (Del Razo et al. 1997; Maki-Paakkanen et al. 1998). The consistency of these associations, across different studies and different study populations, provides fairly strong evidence that individual differences in arsenic methylation patterns, and the environmental or genetic factors that cause these differences, play an important role in susceptibility to arsenic-caused disease.”

———

One possible conclusion: dietary deficiencies (such as almost complete absence of animal protein and its associated nutrients) drive poorer methylation of arsenic, which results in poorer detoxification of arsenic, and worse, an accumulation of a more toxic metabolite, monmethylarsenic (III). In areas where arsenic is prevalent in food and water, and animal protein and its associated nutrient intakes and total calories are low, this problem is particularly acute.

Alternative interpretation: what methylation/detoxification of arsenic takes place in these emaciated vegetarians takes its toll on their already underpowered methylation network, resulting in deficiencies in methylation in other areas critical to good health.

These same authors report that chronic low-level arsenic toxicity is less in the US, even where arsenic is prevalent in well water, and where nutrition would be described as “less inadequate” (my term) than in the third world, or equivalently in their words, “In our study, almost all subjects had intakes of protein, iron, vitamin A, thiamine, and other nutrients above U.S. recommended dietary allowance values.”

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