The importance of ADME networks in nutrient sufficiency

The RDA has been defined as EAR + 2 STD, where EAR is the estimated average requirement and STD = the standard deviation of the requirement, usually taken as only 10%, when 20-30% would make more sense of biological data.

For vitamin B6, this works out to about 1.3 mg per day for a typical adult.

If true, then 97.5% of all individuals will meet their B6 requirement with this 1.3 mg per day intake.

Now in the latest NHANES that investigated this, in 2003-4, only 95% of a substantial segment of the population, namely American males taking supplements, which is just less than half of all American males, was found to be adequate with a simple measure of B6 adequacy, namely serum levels of vitamin B6 greater than 20 nM.

Supplements, whether multivitamins or vitamin B boosters, typically have 10x RDA of vitamin B6 – so clearly, even 13 mg of B6 was not enough to get 97.5% of all American males to B6 adequacy. The numbers were much worse for another large population, women on oral contraceptives who do not supplement. Something is clearly wrong.

The NHANES study authors correctly conclude (https://www.ncbi.nlm.nih.gov/pubmed/18469270):

“In conclusion, our findings were inconsistent with the idea that the current RDAs for vitamin B-6 guarantee adequate vitamin B-6 status for nearly everyone. Furthermore, intakes between 3 and 4.9 mg/d would likely leave some smokers, blacks, seniors, and current and former OC [oral contraceptive] users with inadequate status.”

The errors of the government’s treatment of nutrition are difficult to catalogue because they are loosey-goosey in their definitions and they are not rigorous in their analysis. But here are some of their most egregious errors:

  1. The 10% CV in RDA does not come close to representing biological variation. Consider just the effect that taking different prescription drugs has on the % CVs of the RDAs of a large population. I take no prescription drugs; most people take a few; and some people take a huge number, but they are different sets of drugs, and different drugs create different conditionally essential requirements in the population.
  2. Government scientists have a loosey-goosey definition of causation (contra my causation = S.I.N.) in which they firmly believe, and this error leads to numerous misinterpretations.
  3. When no other measures of nutritional adequacy are available, they use the estimated intakes of Americans, who are “apparently healthy,” a contradiction in terms, based on notoriously inaccurate dietary surveys.
  4. They over-rely on nutrient balance studies as being definitive of requirements. Not even close to true.
  5. They treat the human body as one compartment, when it must be treated as at least 3 separate requirements for the purposes of nutritional adequacy (the gut, the circulatory/urinary system, and the rest of the body), and they treat nutrients excreted as waste as “simply waste” and not nutrients. Even when some nutrient is waste and is going to be excreted, experience shows that the body can still use it to do something productive before passing it and sometimes even while it is being excreted (think of acidic urine’s effect on a UTI with an acidophobic organism). Thus, waste is never simply waste. Think of uric acid in the bloodstream; think of bilirubin in the bloodstream; think of citrate, vitamin C, and magnesium in a urine sample with enough oxalate and calcium to otherwise promote calcium oxalate stone formation. Are the citrate, vitamin C, and magnesium in this urine sample simply waste? No way!
  6. They treat every nutrient’s requirement as independent of every other nutrient, when in fact, every nutrient has an ADME network that in part determines its requirement and makes the CV of the population requirement quite large. Together, all nutrients and their ADME networks comprise a giant web of interrelated requirements and a huge %CV. This is major – this is one of the reasons why one can take 10x the RDA of vitamin B6 and still not be B6-sufficient. Consider another example: suppose someone is seriously deficient in both iron and copper. How much iron would he have to take in order to cure anemia? Given that copper is critical to the proper function of at least 3 iron transport proteins in the D part in iron’s ADME network, can that iron requirement even be defined?
  7. They naively believe in the single nutrient deficiency and thus in the validity of studies that presuppose this giant error, and this goes hand in hand with their underestimation of the importance of conditionally essential nutrients and their misunderstanding of the web of interrelatedness of nutrients, essential, conditionally essential, and non-essential.
  8. Their recommended diet has always been unbalanced – too much grain, too little green leafy vegetables, and now too little animal products, which have some of the conditionally essential nutrients whose importance they routinely underestimate. Their undue restrictions on animal products are due in part to their overestimation of the ill effects of excesses (of pseudo-toxins like cholesterol and saturated fat) and their underestimation of the seriousness of the ill effects of deficiencies, including conditionally essential deficiencies. In the 1980s and 1990s, for example, the government was telling us to seriously limit egg consumption (due to its high levels of the pseudo-toxins cholesterol and saturated fat), for example, when they had not recognized that choline is an essential nutrient and that eggs are the only food commonly consumed with high levels of that essential nutrient. Yet even when choline was not recognized as essential (until 1998), there was an abundance of evidence to suggest that it was at least conditionally essential, and this they ignored as unimportant.
  9. They determine deficiencies using concentrations in plasma rather than biological activities in tissues with the highest requirements.
  10. They look for deficiencies in all of the wrong places – particularly plasma or serum for magnesium, calcium, potassium, sodium, and liver (an organ that stores vitamin K) for vitamin K deficiency (using clotting factors made in the liver rather than using some protein not made in liver), when a sensible person would look in saliva or skin cells or some other low priority compartment for evidence of deficiencies, and would follow the metabolic signatures (when something is deficient, its product is diminished and its precursor and its alternative metabolites increase in concentration) in tissues and even in urine, rather than measure concentrations in plasma or urine of the nutrient itself.
  11. They uncritically rely on clinical studies, when clearly the clinical studies are using people who are too sick, people often past the point of disease reversibility, and they look at single nutrients as potential cures for the most part, when the population is deficient in multiple nutrients and thus cannot respond appropriately to single nutrient supplements.
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