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supplemental B12 and Folate (bulletproof-exec recs)

API (1993) Study of the relationship between folate studies and methanol toxicity.

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Evidence in support of the “folate trap” hypothesis

Alzheimer’s disease (AD) and dementia have enormous financial and social impacts on society. It is predicted that almost 36 million people will have dementia in 2010, a figure which is anticipated to double every 20 years as the world population ages. Prevention of AD or slowing of the progression of AD would provide significant benefits. There are multiple ways in which vitamin B12, vitamin B6, folate, and homocysteine (Hcy) play a role in the pathogenesis of AD. Vitamin B12, vitamin B6, and folate deficiencies are associated with various cognitive disorders, including dementia. Neuroinflammatory oxidative stress occurs early in AD pathology. Total blood Hcy levels are utilized as a marker to assist in diagnosing such deficiencies. Hcy contributes to pathological cascades involving amyloid plaques and neurofibrillary tangles (NFTs). This review provides a thorough description of several factors involved in the development of the pathological changes associated with AD, such as neuroinflammatory oxidative stress and methylation, apoptosis, NFTs, amyloid plaques, and cerebrospinal fluid biomarkers. The review also considers the rationale for a combined B-vitamin and antioxidant supplement (Cerefolin NAC) in treating and slowing AD-related cognitive decline.

Makar AB & Tephly TR (1976) Methanol poisoning in the folate deficient rat.
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La inhalación aguda de concentraciones de vapor de metanol por debajo de 260 mg/m3 o la ingestión de cantidades de hasta 20 mg/kg de metanol por parte de personas sanas o con una deficiencia moderada de folato no debe dar lugar a la acumulación de formiato por encima de las concentraciones endógenas.

implications for the “methyl folate trap hypothesis”.

Rietbrock N, Stieren B, & Malorny G (1966) [Influence of folic acid on methanol metabolism.].
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The role of retinal metabolism in methanol-induced retinal toxicity in folate-sufficient (FS) rats and folate-deficient (FR) rats, some of which were also pretreated with disulfiram (DSF), was examined by Garner et al.

The b-wave of the ERG is extremely sensitive to conditions that interfere with retinal energy metabolism and is reduced or abolished following brief ischaemia or the administration of metabolic poisons (Bresnick, 1989; Dowling, 1987).

The Role of Folate in Methionine Metabolism - Vitamins

Smith EN & Taylor RT (1982) Acute toxicity of methanol in the folate- deficient acatalasemic mouse.
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In a study of formate metabolism in young swine (Makar et al., 1990), it was found that the pig, compared to other species (mouse, rat, monkey and humans), has extremely low levels of hepatic folates.

Following uptake and distribution methanol is either excreted unchanged (direct excretion) in urine or exhaled breath, or it enters a metabolic pathway in the liver, whose ultimate product is carbon dioxide.

Root tissue was reported to be more sensitive; a decrease in metabolic rate was reported following brief exposures to > 10% methanol.
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This was confirmed in a subsequent short-duration inhalation study in which anaesthetized female cynomolgus monkeys were exposed for 2 h to methanol vapour (tagged with radiolabelled carbon) at concentrations of 13, 59, 262 and 1179 mg/m3 (10, 45, 200 and 900 ppm), and monkeys fed on a diet deficient in folic acid were exposed to 1179 mg/m3 (900 ppm) for the same duration (Medinsky et al., 1997).

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Oral methanol 72-h LD50 values ranged from 6.4 to 7.3 kg for mice with folic acid deficiency (FAD) diets, depending upon the concentration of methionine in the diet (0.2-1.8%).

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The pharmacokinetics of 14C-methanol and 14C-formate were studied in normal and folate-deficient (FD) female cynomolgus monkeys anaesthetized and exposed by lung-only inhalation to 13, 60, 260 and 1200 mg/m3 (10, 45, 200 and 900 ppm) 14C-methanol for 2 h to determine the concentration of methanol-derived formate to the total formate pool.

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Under acute inhalation conditions, folate-deficient Long-Evans male rats exposed to 4000 mg/m3 (3000 ppm) methanol for 20 h/day did not survive more than 4 days.

Effects of Different Cooking Methods on Nutritional …

The kinetic parameters that appeared to be most sensitive to the gestational stage were the rate constants associated with intercompartmental transfer (k12 and k21), although there was no obvious relationship between the estimate of these parameters and gestational stage.

How to cite this article: Chen L, Bode AM, Dong Z

Formic acid is believed to be the toxic metabolite responsible for the ocular toxicity in methanol-poisoned humans (Sharpe et al., 1982), and is also responsible for the ocular toxicity produced in non-human primates and folate-depleted rodents (Martin-Amat et al., 1977, 1978; Eells et al., 1983; Eells, 1991; Lee et al., 1994a,b).

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