Nutrient deficiencies drive alternative metabolisms

Keeping in mind that thiamine is just one of many nutrients we may be deficient in, consider the effect of a simple thiamine deficiency, common in alcoholics (drinking too much inflames the digestive tract and reduces the efficiency of absorption of many nutrients including thiamine; detoxification of alcohol consumes other nutrients) and diabetics (who over-excrete thiamine due to poor reabsorption coupled with extreme diuresis), and which is more common than doctors think because deficiencies develop locally well before they are seen systemically (the only place doctors look), because drinking too much is quite common and probably underreported (and drinking too much leads to numerous other deficiencies, including magnesium, which is a required cofactor of thiamine in its active form, TPP), because we under-consume raw foods, because common foods contain a number of different natural antagonists of thiamine, because we both over-cook and over-reheat foods (thiamine is heat labile, while thiamine antagonists present naturally in foods are heat stable – heating enriches the antagonists at the expense of thiamine), because we have poor eating habits, because the majority of people do not take supplements, and those who do are somewhat irregular in their supplementation, because foods high in thiamine are either cooked (whole grains) or seriously under-consumed (raw green leafy vegetables), and because “foodstuffs” like white flour that are supplemented with thiamine mononitrate are destined to have the thiamine destroyed (and possibly turned into toxic compounds that may also antagonize the remaining thiamine – the sole saving grace here is the low dose of thiamine in the food) by cooking, and because of the naturally low body pools of thiamine (about 30 mg) coupled to a short ~15d average half-life of the vitamin (obviously diabetics would have a shorter half-life due to their poor kidney reabsorption of the vitamin). Finally, consider another limitation of thiamine that has barely been explored: thiamine is reactive with oxygen and oxygen radicals. Yes, thiamine is also an antioxidant and can be consumed by the body in that capacity, more so in individuals who are under oxidative stress

Just “low thiamine reserves + short half-life of thiamine + heat lability of thiamine” is enough to suggest that thiamine deficiency is widespread. Adding diabetics and alcohol abusers to the list of thiamine-deficient people means that the problem in this country and the world at large is huge.

In view of this evidence, how can anyone possibly think we Americans as a whole are sufficient in thiamine?

More speculatively, if thiamine is consumed by oxidative stress (acts as an antioxidant), then the problem of thiamine deficiency and its extent are even more common than this evidence would lead one to believe.

When any nutrient is deficient, the body borrows from stores and then makes somewhat workable substitutions until it no longer can. In the case of thiamine, the stores are naturally low and there is as far as I know no substitute for thiamine.

What does the body do? It has to regenerate ATP from ADP at a sufficient rate to meet its needs. The following facts make a simple prediction:

  1. No thiamine is required to run glycolysis
  2. No thiamine is required to convert pyruvate to lactate
  3. Thiamine is required to convert pyruvate to acetyl CoA
  4. Thiamine is required to run the TCA cycle (conversion of alphaketoglutarate to succinyl CoA)
  5. No thiamine is required to run OXPHOS
  6. Thiamine is required to run the pentose phosphate shunt, which generates NADPH as the ground zero antioxidant in the body.

Thus, in the case of thiamine deficiency, not serious enough to manifest as beriberi, Wernicke’s encephalopathy, or Korsakoff’s syndrome, we predict:

  1. The body will produce more and more ATP by conversion of glucose to lactate.
  2. The liver will use 6 ATP to convert this lactate to glucose to keep the body going.
  3. Appetite will increase. As a result, the person will begin to eat more, which supplies more than enough calories to meet the extra calories wasted by the Cori cycle (takes 6 ATP for the liver to make glucose from lactate, while only 2 ATP are generated by converting glucose to lactate in muscles), and gain weight, and suffer from the sequelae of weight gain.
  4. TCA and OXPHOS will become less and less important in ATP production. Mitochondria will begin to power down.
  5. A selection process will begin by which cells that run glycolysis faster will overgrow those that run it less slowly. Over time, sugar-fermenting cells that can run glycolysis at 50 or more times the normal rate may be found. These cells will be able to produce energy at a sufficient rate with glycolysis-fermentation to support fast tumor growth.
  6. The person will be under increasing oxidative stress because NADPH production will be reduced. A1c will rise, acute phase proteins will rise, AGE-products will increase, mitochondria may become impaired, and the free radicals produced in mitochondria may damage nuclear DNA, eventually leading to an increased risk for development of cancer.
  7. As thiamine deficiency increases, less essential thiamine-requiring reactions will be inhibited, their enzymes turned over, and the thiamine recycled to the enzymes with greater affinity for thiamine, which in the ideal case would be those most crucial for short-term survival (the body’s focus is always on the short term survival).
  8. As thiamine deficiency increases, peripheral neuropathy and peripheral edema may begin, and in more extreme cases, Korsakoff’s syndrome, Wernicke’s encephalopathy, and in the most extreme case, wet beriberi, cardiomegaly and congestive heart failure.

Note that the symptoms of diabetes and those of thiamine deficiency overlap a lot. How much of this is due to sugar excess -doctors think this EXCESS is the more important- and how much is thiamine deficiency and other nutrient deficiencies?

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