Web page written mostly during 2012-14, revised in late 2015 and early 2016.
A: Monte's Message (rephrased and extended)AmazonBooks2011, web
High vascular structure organs: heart, brain, lungs, liver, kidneys, insulin cells in pancreas, retina, skin. (See female thyroidMonte p.191)
*The 1.65 tsp MLD is for a 150 lb man or 165 lb women, a number derived from patient 17 killed by one tablespoon of 40%
methanol whiskey.m16 The conversion to 110 ppm is given in Sect C and the vulnerability of infants is discussed in Sect D.
**2500 ppm can be survived with no injury, symptoms or abnormal blood measures if high ethanol is administered quickly.m489
‡Patient 17: violent series of inhalations non-responsive to muscle relaxants, chest freezing at final massive inhalation.
†Centimeter size granulomatous panniculitis has been caused by ten days of diet soda @3-4cans/day, or aspartame
@4x50mg/day,m228, pp.102-103 (Granuloma = a granular mass, of phagocytes. Panniculitis = inflammation of fatty layer under the skin.)
†In the 1983 petition to which the FDA granted approval, 1.8 g/day of aspartame (probably in capsules but amount equivalent to
10 diet sodas/day) caused ≈1/7 of diabetic women to develop either fatal stroke or breast cancer in 8-11 weeks.m48, pp.181-182, ref6
High energy consumption at the button tips of axons and dendrites of nerve cells requires plentiful supply of mitochondria. These are made in the cell body near the nucleus and transported out axions along microtubules with a corresponding return flow of damaged proteins.ref Mitochondria wear out rapidly and are replaced every few weeks.
Formaldehyde can damage both the mitochondria and the microtubules.
If the damage rate of mitochondria is high compared to normal replacement rate, the button tips will loose energy supply and die - but after a time delay because of the many-hours to couple-day transit time of mitochondria out axons. The half life of methanol in the blood is 2⅓ hours or less, so it is mostly gone by the time lethal shortness of breath begins at 18-24 hours. Muscle twitching or cramps also occur, which might be due to disintegration of button tips with release of stored neurotransmitter into synaptic gaps.(EHT)
If the damage rate of mitochondria is low compared to normal replacement rate, the axon problem becomes, not axion death, but accumulation of formaldehyde physical damage to microtubule proteins, their stabilizing tau protein and/or myelin sheath removal. In Alzheimer's disease, formaldehyde binding and cross-links similar to paraformaldehyde polymerization are suggested here to be what cause the microtubules to knot up in the observed neurofibrillary tangles that eventually rupture the axon, after which phagocytosis of formaldehyde-tagged myelin increases. And similarly, it is suggested that formaldehyde polymerization outside neurons is what causes beta amyloid protein to accumulate into hard insoluble plaques instead of being broken down and eliminated normally. MS seems to be distinguished by myelin sheath damage from the start. In either case, damage is observed to start close to capillaries and slowly spreads outward, as predicted by MTFT.(EHT)
And since formaldehyde could effect enzymes and neurotransmitters, there may be reason to expect cases of psychological change, such as depression, well before effects from slow accrual of physical damage. Only very low levels of circulating methanol need be involved, because the brain has 400 miles of capillaries, which gives a lot of surface area for leakage of formaldehyde into brain tissue. A suggestion here is that this might simply impose extra need for cleaning up of waste products. PST is usually abundant for this purpose, but for individuals with modest or low PST, MTFT-induced cleanup load might lead to a bit higher production of MAO, and thereby reduction in dopamine including to the shell of the nucleus accumbens, resulting in depression. This can be tested. Is there a class of depression that lifts after one to three days of avoiding inadvertent methanol and phenolics? [Damage of MAO would not cause depression, because that would be like taking MAOI a known anti-depressant.](EHT)
water and carbon dioxide. Each step is fostered by a separate enzyme - ADH, ALDH or folate.
ALDH is resistant to the reactivity of formaldehyde, but other enzymes in the mitochondria are vulnerable.
In these names, A stands for Alcohol, AL for ALdehyde and DH for DeHydrogenaise.
Terminology used by Monte is: ADH -> "ADH I" or "bad ADH," and ALDH -> "ADH III" or "good ADH." Formate is the dissolved ionized form of formic acid, the small single-carbon vinegar compound in insect sting. Folate and folic acid are essentially the same thing, a large protein enzyme related to B vitamins.
Folate is recommended by the FDA and is a required grain supplement in many non-EU countries to reduce chance of neural tube defects during pregnancy. With in situ formaldehyde production the likely root cause, though, this is an indirect solution, so it's not surprising that these types of birth defects have been reduced by only 37%. Folate's second role in the human body is in the methylation of DNA, making it a mild carcinogen.m722
*In non-liver cells with less ALDH, the formaldehyde is less likely to be oxidized by
ALDH and more likely to react instead with some other molecule in or near the cell.
**There are two other pathways for metabolizing alcohols. They have the advantage of confining alde-
hydes to the interior of peroxisome and microsome substructures, but are not very effective in humans.
MTFT is claimed here to be a likely driver of today's chronic, non-germ diseases already cited. The word "epidemic" will be used to describe significant sustained rise in incidence rate over many years. In some cases the rise is still continuing and in some is being followed by high plateau. The main surge in new cases of diabetes, for instance, was from 1991 to 2009, but now with 9.3% of Americans afflicted.ref And a 30 years growth of cardiovascular disease has finally leveled off but still causes ¼ of deaths in the US and is spreading throughout the world.
Fruits and vegetables contain pectin, which has oxymethyl (also called methyl ester) side chains that potentially can dissolve off to form methanol. These side chains are normally so tightly bound that digestion can not dislodge them. But heating, enzymes used during juice processing and over ripening or shelf life can dissolve off these side chains and form methanol. USDA studies in the 1950s, for instance, found that methanol content increased by factors of 80-100 when orange and grapefruit juice are canned and stored.m280,m363GF,SectF Cooking would normally boil off the methanol, because its vaporization temperature is only 149°F, but modern rapid containerization after processing and heating, or post heating to kill the germs, traps the methanol in the food product. Here "container" means can, bottle, carton or pouch - as can of cranberry or spinach, bottle of tomato juice, jar of jam, carton of orange juice or vegetable broth or kids juice with straw. Smoked foods and tobacco smoke contain wood alcohol, and aspartame with intentional methanol in each molecule, has become society's super-dose since 1981.MonteDiet Pot-belly stoves and inadequately ventilated fireplaces may contribute as well.
Exposure to methanol by inhalation of smoke is a special case. The very rapid absorption from the lungs into the blood stream is probably faster than the time for absorption from the blood stream into other body fluids. This means that for a brief period dilution is into less fluid than usual making the blood alcohol concentration high. And a jump in methanol-to-ethanol ratio will then turn up the ADH enzyme's rate of production of formaldehyde. A cigarette delivers about 1/6 the amount of methanol as a diet soda, but the peak rate of formaldehyde production may be higher.
Skeletons and CT scans of mummified remains from many eras as far back as 1500 BC sometimes show signs of arthritis and arterial plaque, and one might guess that this was due to fireplace smoke and smoked foods.ref
The words used here to summarize Monte's work are quite different from his. He doesn't tabulate, refer to any model, assert three levels of methanol lethality or why there are two distinctly different low levels. But Table 1 with two paragraphs do summarize Monte's message in a compact form. The science is in understanding what is being debated and just what the acronym MTFT entails. Here's an introductory summary of the science.
All researchers agree that methanol itself is not harmful and that the harm comes from one of its metabolites. The disagreement is over which one, formaldehyde or formic acid. There is also disagreement about the (MLD) minimum lethal dose of methanol and whether test animals can be used to gauge human response to methanol.
This web site analyzes the difference in science as found by Tephly, Stegink & Filerm272&A4,R1&A4b,m121 and that of Monte. The science issues are covered mainly in Section H. The FDA FOIA and other related documents are reviewed in Section I. A short review of aspartame's political approval process is given in Appendix B paragraph 6.
Note that in Monte's MTFT model the immune system is presumed to act normally in the sense of removing all of what it perceives to be foreign. The usual concept of “auto-immune” diseases is the opposite, presuming that the immune system acts strangely and takes out only part of what it perceives to be foreign.
With the MTFT model late-onset partial type 1 diabetes makes sense as a new third form of diabetes and not just part of type 2 diabetes, which has somewhat surreptitiously been given a new definition to include the phenomenon.
And it seems a stretch to call the spatial non-uniformity of myelin sheath damage in MS and Alzheimers auto-immune. The damage is greatest near small veins and slowly spreads outward as MTFT suggests. The so-called “auto-immune” diseases could perhaps better be interpreted as innate immune.
A minor part of Monte's message concerns the likely cause of Type 1 diabetes - cow's milk during early infancy. This is something entirely different from MTFT, and he does not fully develop the theme. With just a little more information that is readily available, his evidence becomes quite compelling.Type1
At high enough level, alcohol supresses the central nervous system and causes breathing to stop. This is at 0.4% BAC for most people,L7 and the same for methanol and ethanol. Alcoholics, though, because of increased activity of an alternative microsomal metabolic pathway, can tolerate up to 0.6% BAC, a number that comes from Majchrowicz-Mendelson1971.m134&A2
The rest of this section is a little technical, reviewing three journal publications. Learned are: 1) Ethanol is an antidote for methanol poisoning. 2) The hangover effect from a binge of ethanol drinking is due to methanol. 3) A cure for hangover is to have a little tiny bit more ethanol. Blood BAC of ethanol needs to be only a fraction of that for methanol to force methanol to be excreted rather than metabolized. 4) Numbers for the half life of methanol and ethanol are tabulated for various conditions.
The 1971 experiment by Majchrowicz and Mendelson was highly informative - but also bold and apparently almost catastrophic. Nineteen long-term male alcoholics from a rehab program were asked to volunteer to return to another bout of their chronic binge drinking with the condition that they agree to have their blood ethanol and methanol measured throughout the incident. They were allowed to self-regulate the amount and duration of drinking except that they were limited to 32 oz/day of 50% whiskey. That's 2.8 times the maximum amount of ethanol that the human body can dissipate (a shot of 40%/hr), and methanol BAC's went up to half the lethal level of 110ppm, so the volunteers, known addicts with a problem, could kill themselves during the experiment if they didn't self-regulate. The binges lasted from 10 to 15 days, and at least one hit the limits of survivability with ethanol peaking at 0.63%.
What Majchrowicz & Mendelson demonstrated dramatically is that when there is significant ethanol in the blood, methanol can rise to high levels from sources internal to the body. And then after the drinking stops and ethanol is going down, this high level of methanol stays constant for many hours. It is not until ethanol BAC drops to 90 ppm and below that the methanol level begins also to drop. That's a delay of 15-18 hours, and significantly, it is when hangover symptoms begin. The peak in hangover symptoms corresponds with the maximum rate of methanol metabolism.
So Majchrowicz & Mendelson suggest that a way to avoid hangover is to not stop drinking precipitously, but instead to sip a small continuous amount of ethanol for several days after the partying. Fifteen years later, Jones1986m389 confirmed the same delayed methanol metabolism synchronous with hangover following a single evening of drinking. The consumption tested was a liter+ of 9.5% wine in two hours, with blood ethanol levels rising only briefly to almost 0.2%.
When no alcohol is being ingested, Jones1986 shows normal endogenous levels of blood alcohols to be about 1.8 for ethanol and 1.2 ppm for methanol. These are at the noise floor of the alcohol breath measurements, and there is no data comparing individuals.
Here are some additional experimental results, simplified for self-consistency but still rather difficult to read:
For high ingested ethanol the body's available ADH enzyme saturates at about 90 ppm = 0.009% BAC. Above this the ethanol dissipation rate is 0.036%/hr, which for an adult with an effective 50L of body fluid (a 150 lb male or 165 lb female) is the well-known shot per hour of 40% whiskey. (1 shot = 1.5 oz = 3Tbs = 45 mL) At saturation and below the dissipation rate is proportional to alcohol concentration and is BAC/τ½, with half-life value τ½ ethanol = 15 min. This is an awfully short half life for ethanol, but click the above figure. It is what Jones1986 measured, and there is no scatter in his data.
One has to be careful about interpreting the 142 min half live given in the Jones1986 plot for methanol, because the ADH enzyme has a much higher affinity for ethanol than for methanol. Monty states a sixteen times greater affinity but does not give a reference. This means that the endogenous methanol is not being metabolized and must be excreted, which is slow. The Jones measured half life for methanol is τ½ m excretion = 142 min ≈ 2⅓ hr.
Original recognition of the trend that ADH has a higher affinity for ethanol was in 1943 during assessment of accidental methanol poisonings, and three additional papers on the subject followed in the late 1940's. Then in 1952 Leaf&Zatmanm115&A1 did experiments with dramatically graphic results showing the inhibition of methanol metabolism by ethanol. They made a couple math mistakes - taking log10 rather than lne, and failing to fit their data to (.93v/V)[exp(t/τabs)-exp(t/τdis] - but one of their results used here is that τ½ m excretion is about ten times longer than τ½ m metabolize. The Leaf&Zatman results appear to have stimulated both the recognition in Røe1955 that ethanol can be used as an antidote for methanol poisoning and the Majchrowicz&Mendelson1971 experiments just described.
A striking example of the antidote effectiveness of ethanolm489 is an attempted suicide in 1982 by a woman who ingested 112 mL of methanol, some 20+ times the minimum lethal dose of ~6 mL for her size. Her methanol BAC responded proportionally, reaching some 23 times the lethal 110 pm of Table 1. But she suffered no injury, poisoning symptoms or abnormal blood measures, without administration of bicarbonate, because she was immediately given and maintained on a high level of ethanol.
And finally, the point that that even excretion of methanol becomes blocked by ethanol if ethanol BAC is high enough. This is implied by interpreting the Majchrowicz&Mendelson1971 plots using
the Leaf&Zatman1952 factor of ten for the ratio τ½ m excretion
/ τ½ m metaboliz. Clearer, is that in the above suicide case, the blood level methanol half life was 35 hours.
Summary: τ½ abs ≈ 30‑90 min, τ½ ethanol ADH = 15 min ≈* τ½ methanol ADH, τ½ m excretion ≈ 2⅓ hr, τ½ PEG = 5 hr with
implied endogenous ethanol production rate ≈ endogenous BAC / τ½ ethanol ADH ≈ 1.8ppm/15min ≈ 7ppm/hr
implied endogenous methanol production rate ≈ endogenous BAC / τ½ methanol excretion ≈ 1.2ppm/2⅓ hr ≈ .5ppm/hr
The Majchrowicz-Mendelson methanol free rate rise during the time its metabolism is blocked is >5ppm/24hr ≈ .3ppm/hr
*iff methanol BAC ≥? 16 times ethanol BAC
Dr. Monte argues that minimum in Minimum Lethal Dose means minimum - one number, not a large range of numbers as often suggested. There is a problem with the source data, though. It tends to be circumstantial from thousands of accidental methanol poisonings during prohibition when the poor and even the rich couldn't be sure of the ethanol versus methanol content of their beverage. And reports of surviving near poisoning from high levels of methanol are probably associated with imbibing both kinds of alcohol together, the ethanol providing protection against the methanol.
Dr. Monte uses the circumstances of patient 17 in a well-documented reportm16 from the Emory University School of Medicine to infer an accurate number for MLD. This was a 21 year old 117 lb female who tasted a tablespoon of 40% methanol whisky and then refused to take any more. She died three days later. Her MLD was .4x3 = 1.2 tsp of methanol. For a 150 lb women this scales to 1.5 tsp, the number Monte uses for MLD.
The number is scaled up a little further here to 1.65 tsp to adjust for sex and to fit what here will be used as a "standard" adult size, someone with body fluids totaling about 50 liters. That's an easy number to use for calculations and corresponds to a 150 lb man or 165 lb women. Then since 1.65 tsp = 8.1 mL, the lethal peak blood alcohol content BAC number should be about 8.1mL/50L = 160 ppm - but a little lower to account for metabolization during absorption. The modeling of "Absorption-Dissipation Curves" below suggests a 2/3 factor giving about 110 ppm peak.
What Monte brings to the table is new logic backed by 782+ references and much correlation with data. His mechanism for modern disease proliferation is referred to here as MTFT, Methanol Transported Formaldehyde Toxicity.
There are two parts, "MTF" and "T." The "MTF" is how formaldehyde gets into a variety of tissues. It's too reactive to last long enough to circulate in the blood. But methanol circulates, is passed freely without regulation into cells,ref and then is converted to local non-circulating formaldehyde. Most of the ADH that fosters this conversion is in the liver and stomach, but not all. ADH is also present in the cells of the inner two layers of blood vessel linings, of connective tissue, and of mammary tissue where there is little ALDH. The formaldehyde may diffuse within the cell, into mitochondria or out of the cell into interstitial spaces or neighboring cells.
The second "T" part refers to toxic damage caused by formaldehyde when persistently delivered into tissue in tiny amounts. Though there are basically just four or five damage modes. But depending on what tissue is being affected, these manifest as a wide range of disease.
1) Stimulation of innate-immune attack on cells or LDL whose protein markers become tagged with formaldehyde:m23 This may manifest as atherosclerosis or may appear to be auto-immune attack such as late-onset partial Type I diabetes, rheumatoid arthritis, its sister lupus, wasting of myelin in MS, or birth-defect autism. (And as pointed out, the so-called "auto-immune" diseases don't remove all the target tissue.)
2) Protein tagging and removal:
3) Protein binding, similar to the fundamental embalming chemistry of formaldehyde: This shows up in MS and especially Alzheimer's plaque as well as neurologic symptoms due to damage to the Tau protein of microtubules in axons. Brain tissue placed in formaldehyde will absorb almost its volume in several hours without itself increasing in volume. There is no anatomical change, only texture change from delicate to rubbery. With Alzheimer's, Monte sees the supply of formaldehyde as very slow leakage out from capillary linings, but the result eventually being similar. (He also points out that single-carbon attachments are invisible in microscopes and that the hunt for the bad actor has mostly been done looking at formaldehyde-preserved tissue.)
4) Mitochondrial enzyme damage: Formaldehyde is oxidized by ALDH in the mitochondria of the same cell where it is produced. Formaldehyde, perhaps surprisingly, may not cause much damage the ALDH enzyme, or at least, the damage it does to another enzyme internal to mitochondria is significantly worse. ADP is converted to ATP by a complicated process involving an enzyme called ATP synthase, but formaldehyde damages this enzyme and stops the basic supply of energy to all cellular processes. This causes most of the classic methanol poisoning symptoms from acidosis to vision, CNS and PNS dysfunction and death. In low persistent dose this should relate to lupus or macular degeneration.
4a) Infants: Though not mentioned by Monte, #3 probably also explains the super extreme vulnerability of infants to methanol swab. They have little myelin sheath and therefore neurons with particularly high energy consumption. Their nervous system can't tolerate any loss of energy supply.
4b) Delay: A second point not mentioned by Monte is that a reason for such long delay for onset of symptoms and death following methanol poisoning is probably the fact that mitochondria are generated only in nerve cell centers. Ability for energy supply at synaptic endings depends on transport of mitochondria along microtubules down long axons, a process that, depending on axon length, can take from some half day to a couple days - or may not be completed if the mitochondrion is damaged or if the transport microtubules are tangled by formaldehyde. The synaptic tip has a transit-time supply of mitochondria coming to it but will die when it stops getting energy, probably releasing its stores of neurotransmitters into the synaptic junction.
4c: Thresholding: The normal mitochondrial half life is weeks, so blindness and death by mitochondrial neuron damage might be a threshold phenomena.
5) Glucose transport enzyme damage in brain capillary epithelial cells. These cells are tightly packed forming the blood-brain barrier, so glucose has to be transported through them. Dr. Monte doesn't say so, but these should also be cells containing the ADH enzyme that generates formaldehyde from methanol, and a probable cascade of events is discussed in the proposed experiments section, "MTFT-Excitotoxin Synergism."
We use what here will be called the average adult, someone whose body contains V = 50 liters of fluid, which corresponds to about a 150 lb male or a 165 lb female or elderly male. Blood is 93% water, so if the amount of alcohol in body fluids is v', the blood alcohol concentration is BAC = .93v'/V.
The amount of alcohol in body fluids is less than the amount consumed for possibly two reasons. First is metabolization of about 10% of alcohol in the stomach. This does not apply to the effective methanol of aspartame, though, because dissolution of the oxy-methyl side chain to methanol does not occur until fluids reach the duodenum. And it doesn't apply to inhaled methanol in smoke.
The second and larger factor that reduces alcohol volume in body fluids is metabolization of the alcohol, mostly in the liver, during the time while it is being absorbed from the intestines into the blood. Depending on what else has been eaten and whether it is aspartame that has to be digested, the peak in BAC occurs somewhere between less than an hour to as much as two hours after the alcohol/aspartame is consumed. The peak is almost instantaneous for smoke-inhaled methanol.
We denote this delayed maximum BAC as BACm, and to simplify the calculations assume that the amount of alcohol/aspartame consumed is moderate or small so that enzyme saturation does not occur.
Here's an introductory calculation for a teaspoon of pure alcohol drunk by an adult. 1 teaspoon = 5mL = .005L, and if 2/3 of this is diluted into 50L, the over-all blood BAC would be .005/50 = 0.01% = 100 ppm times the 2/3 factor, which gives 67 ppm. And with dilution into only blood plasma, the peak BAC would be 17x67 = 1100 ppm = 0.11%.
Here's the calculation for a standard 12 oz can of diet soft drink. It contains 180-193mg of aspartame.NutraSweet,AspInfo Solution of the methyl esterfig results in 0.13x180mg/(792mg/mL) = .03mL = .00003L (=.61 of a drop) of methanol. Multiplying by 2/3 and dividing by 50L of total body fluids gives only .40 ppm for the over-all BAC. But for dilution into only blood plasma, the peak BAC is 17x0.4 = 6.8ppm, which is some 5-6 times endogenous. (For the larger 198mg number peak BAC would be 7.3ppm.)
If someone drinks diet soda repeatedly throughout the day, the mean methanol will build up. Appendix C7 indicates that if the drink spacing is 2.3 hr (equal to the metabolic half life of methanol), the mean BAC rises to about the single-drink overall BAC of 0.4 ppm, but that if the spacing is 1 hr, the mean trends to four times as much or 1.6 ppm. With the closer spacing of consumption, peak plasma BAC is raised to maybe 8 ppm.
There are some people like Charles FlemingAppF who was drinking 10 cans of diet soda during the 12-14 hour day, including two with bourbon in the evening, plus also using aspartame sweetener packs. He was probably also getting tobacco smoke at Phillip Morris where he worked and the typical inadvertent dose of methanol in containerized vegetable & fruit products.
This might have been enough to raise his daytime blood methanol BAC to three or more times the normal endogenous level and to have caused peaks maybe as high as 10 or more times endogenous.
The original test diabetic women were given 1.8 g/day of aspartame equivalent in quantity to 10 diet soft drinks per day, but probably in capsules.m48, pp.181-182, ref6 As pointed out with Table 1 there were severe consequences.
Final note using all 50L of body fluids: The production and excretion rates of endogenous methanol must be in steady state balance, so endogenous production = 50L(1.2ppm/2.3hr) = 50L(½ ppm/hr) = .025mL/hr = 0.5 drop/hr.
a) A Medical Science Inconsistency: The first and second metabolites of alcohols are aldehydes and carboxylic acids. For ethanol these are acetaldehyde and acetic acid. For methanol they are formaldehyde and formic acid. The FDA lists acetic and formic acid as GRAS, generally regarded as safe, food additives. Acetaldehyde is reactive stuff - lethal if it measurable in blood leaving the liver. But formaldehyde is even more reactive than acetaldehyde, so inclined to combine with proteins that it can not circulate in the blood.
Yet while acetaldehyde is considered to be the bad actor of ethanol, today's medical science switches and holds that the bad actor for methanol is formic acid, not formaldehyde.
b) A.G. Searle 1973 Double-Blind Study: The dose level was equivalent to 10 cans/day of diet soft drink or 3 mL/day of methanol. It was 1.8 g/day of aspartame. 77 diabetic patients were screened to have no other health issue and then about half were given the aspartame and half a placebo. 1/7 of the women given aspartame developed either fatal stroke or breast cancer in 8-11 weeks.
This report is contained in Searle's 1983 petition for use of aspartame in carbonated beverages.m48, pp.181-182, Ref6 Also, hyperplasia and breast adenocarcinoma had been found in laboratory rats fed methanol, but those animal results were withheld from the pathologist reviewing the study.Ref6 Click and read the A.G. Searle conclusion, "In summary, aspartame appears to be well tolerated by diabetic subjects as a safe sugar substitute."
c) Controlled, Repeatable Experiment with Lower-Dose Aspartame: 3-4 cans/day of diet soda has caused granuiomatous panniculitis lumps that after 10 days reached centimeters in size. Then after a period of secession, 200 mg/day of pure aspartame caused return of the condition in a similar period. That's 1/9 the dose level of the double-blind Searl experiment and equivalent to 1.1 cans/day or .033 mL/day of methanol. This was an open experiment done with a single patient, but with a demonstration of repeatability.m228, pp.102‑103
d) Epidemiology: 1) Fetal Alcohol Syndrome has responded inversely to reduction in smoking by pregnant women but proportionally to intake of methanol.
2) Ditto machines turn out to have been sadly unfortunate for teachers.
3) Dr. Monte gives 22 plots showing correlation over time between increase in a disease and society's increasing consumption of methanol. A suggestion here is that it is perhaps better to think of this epidemiologic data as a whole, as one graphic display with 22 curves rising together almost simultaneously. This mass rise is an issue all unto itself. And then Monte puts a plot of increasing aspartame/methanol consumption on the same page and points out correlation, giving reason why rise in some diseases should be delayed but others not. It's not proof, but it is suggestive.
These epidemiologic correlations are with low BAC methanol following the introduction of aspartame in 1981.
In the other direction of decreasing inadvertent methanol, society's transition from canned to frozen foods correlates with decrease in deaths from MS during the 1970's.
And most in the news lately,WP,NYT,NYT,WP but probably misinterpreted, is the decrease in incidence of diabetes since 1998-1999. The correlation is with diet soda consumption, not regular sodas. (Data versus total methanol consumption is needed.)
A counterexample to this interpretation is that while diet soda consumption has been going down the teen and college suicide rates have been going up.HS,Col.Caveat The answer proposed here involves still another area of medical controversy totally different from Monte and methanol, but it does logically have to be mentioned. A large part of the surge in bottled water and sports drinks like Gatorade has used RF&D colorings. Sorry for the complication, but data dictates.
Another data factor to track here is that in 2015 Kraft and in 2016 Mars are removing all RF&D's from their brands the way it's been done in the EU since 2010 for all products. EU teen and college suicide rates do not seem to be going up.
e) Phenomenology: Dr. Monte doles out a panoply of insights into disease phenomenology. He spreads these in comments throughout his book, though, so some of his main points are tabulated here to show their scope. Most fundamental perhaps is the distinction between innate-immune and auto-immune. The terminology will be explained later.
- The ethanol health benefit is both explained by and is proof of MTFT (also autopsies).
- The "auto-immune diseases" can't be auto-immune because the target tissue is not all removed.
- An Alzheimer's brain has the same rubbery feel as one stored in formaldehyde.
- There was no such disease as multiple scleroses until about 20 years after the invention of canning.
- The CDC accidentally discards neural tube birth defect data and then follows industry's ranking of the metabolites of methanol when it recommends somewhat dangerous dietary folate. Dr. Monte recommends reduction of methanol intake and not taking folate.
- He also presents evidence for (true) auto-immune nature of classic Type I diabetes, contrasting that it is not related to today's increasingly common late-onset Type I or MTFT. What he doesn't point out here but should is that Type I diabetes didn't exist until the invention of canned milk and has grown exponentially ever since.
f) Anatomical Fit: The fit between MTFT and what is observed in several of diseases is good, and to this reviewer sometimes striking, as for atherosclerosis, Alzheimer's and, surprisingly, autism.
Alzheimer's & MS: The myelin loss begins around the small capillaries exactly as MTFT suggests. An Alzheimer's brain has the same rubbery feel as a normal brain stored in formaldehyde.
Arteriosclerosis and specifically Atherosclerosis: "The atheroma is a swelling within the artery walls that is made up of an accumulation of macrophage cells (white blood cells) that have consumed too many LDLs, turned into foam cells and died. The swelling is found between the endothelium intima lining and the media of the artery. While the early stages have traditionally been called fatty streaks by pathologists, they are actually accumulations of macrophages that have taken up oxidized low-density lipoprotein (LDL)..."
Autism: Prenatal and lactation exposure to methanol in rat experiments may result in neural tube defects or, less dramatic but still severe, reduced brain size, hemorrhaging and much damage to neurons. The regions most reduced in size, with most hemorrhage and most severe nerve cell loss are the hippocampus, cerebellum and specifically the vermis of the cerebellum. This correlates with the fact that the main locations of ADH in the brain are blood vessel linings and the purkinje cells of the cerebellum.m637 And on page 206, Monte notes that, "it has now been discovered the cerebellum is known to be preferentially damaged in human autism,m622 and the vermism570 and hippocampus are the particular areas of the cerebellum most damaged and reduced in volume by the disease.m571 A recent study of suckling rats fed aspartame showed 'severe' major enzyme changes specifically in their hippocampus.m623 Another finding in the damaged area of our rat brain was an overabundance of macrophages." •Not mentioned by Monte, but perhaps most striking to this reviewer is correlation with the (dubious?) finding of reduced cerebellar volume and specifically the vermis in anatomical MRI measurements for ADHD.Castellanos2002,video,L (The data analysis involves adjustment of the mean by 14 standard deviations.)
Depression: There is no overtly observable anatomy for depression, but if the condition does involve MTFT it is reasonable that it should be immediate with no delay between cause and effect as in the above comparison plot. MTFT suggests mental function effects due to low ATP (mitochondrial enzyme damage but sub-lethal dose), and though not discussed by Monte, probably low supply of glucose (transport enzyme damage in capillary epithelial tissue). This would cause an opening of the blood-brain barrier (the tight packing of capillary epithelial cells), possibly allowing entry of problem compounds like excitotoxins. These should all be fast-acting effects.
Use of the acronym MTFT focuses exactly on the difference between Monte and much of the rest of the research community represented by the seminal works by Tephly, Stegink & Filerm272&A4, R1&A4b,m121 A central debate, as pointed out, is about which metabolite does the damage, formaldehyde or formic acid.
In test animals in which a lethal dose of formaldehyde is injected directly into the veins, the formaldehyde disappears within minutes,m122 and in people who have drunk formaldehyde to commit suicide it has been impossible to find formaldehyde in their blood by the time they get to a hospital.m236 Tephly says this is because the body's ALDH rapidly metabolizes formaldehyde to formic acid which then can be measured in the blood stream and causes acidity. And when folate is administered, the toxicity of methanol decreases. These three factors prove that the toxic metabolic byproduct of methanol must be formic acid, not formaldehyde. This has become the essence of mainstream thinking, both in industry and in medicine.
MedScape.comref and the Methanol InstituteL8 give nicely concise medical summaries of the Tephly point of view, stating that "After consumption, methanol is converted into formaldehyde and then into formic acid, which causes the blood to become acidic... Methanol poisoning can be treated if diagnosed within 10 to 30 hours of ingestion... Administration of sodium bicarbonate can neutralize formic acid and maintain proper pH balance."
Additional examples of formic acid proponents among medical professionals showed up in references for this web page, such as the toxicologist/pathologist with 20 years experience and 40 journal articles who reviewed the Diane Fleming murder conviction. He argues that the evidence for conviction is inadequate,Bayati because they did not "...measure formic acid in Chuck's blood and urine to confirm that Chuck's acidosis was caused by the accumulation of formic acid. ...Formic acid is the major metabolite of methanol that causes acidosis in humans and should be measured whenever methanol poisoning is suspected." And in the three-author 1994 study of birth defects in rats, the authors say,278Bolon1994 "Studies showing that adult rodents with a reduced capacity to detoxify formate (the putative methanol-derived neurotoxicant) develop functional and structural changes that are comparable to those observed in adult human patients with methanol toxicity (Makar and Tephly, '77; Eells, '91), while normal rodents are resistant because they metabolize formate efficiently (Roe,'82)."
Monte says the opposite, a) that formaldehyde is so reactive it rapidly combines with tissue and therefore can not enter the blood stream or be measured in circulation. People suffering from inhaling formaldehyde have primarily lung-related damage, not systemic illness. Then concerning methanol, he points out two additional features. b1) Methanol doesn't react with tissue and can circulate in the blood. b2) When it reaches tissues containing the ADH enzyme, it is converted to non-circulating reactive formaldehyde at those locations, usually diffusing not more than a distance of a few cell diameters. This is being dubbed here as MTF. Besides the liver, these locations of ADH include blood vessel linings, mammary tissue and connective tissues that produce collagen, including bone. The liver has enough ALDH to process formaldehyde with little harm, but not other ADH tissues, especially mammary tissue, so formaldehyde toxicity occurs. It is this mechanism for inflicting dispersed damage that here is called MTFT.
Monte devotes several paragraphs at the end of Chapter 4 to point out: that the FDA classifies formic acid as a harmless GRAS "Generally Recognized As Safe" food additive with a lethal dose level about the same as table salt,m365 that though commonly used in foods there is no recorded death due to its consumption in the last 100 years, that formic acid administered to monkeys causes no damage,m106 that he has used formic acid on salad when he ran out of vinegar, and that it can be found in the bloodstream only for those who have been poisoned with a very large lethal dose of methanol.
And it is perhaps worth noting that for much studied ethanol, mainstream finding switches the ranking of which metabolic byproduct is more dangerous, the aldehyde or the carboxylic acid. For ethanol, with the same enzymes acting as in Figure 2, it is the aldehyde (acetaldehyde) that is more reactive than the carboxylic acid (acetic acid = vinegar).L9 And the reason details are known about which tissues contain the ADH enzyme is because of concern about acetaldehyde.
There is also disagreement about why human blood turns acidic during methanol poisoning and whether monkeys are suitable animals for testing human sensitivity to methanol.
Tephly says it is formic acid that makes the blood acidic. But Monty says this acidity is from two causes, the more important being formaldehyde's powerful negative effect on cellular oxidation function. (Formaldehyde is 100 times more powerful than formate in inhibiting of cytochrome oxidase.m676) As mitochondrial enzymes become impaired, anaerobic respiration ensues, which results in lactic acid. And an observable fact in methanol poisoning is that lactic acid is measurable in the blood before formic acid can be detected and before acidosis develops. Also, note that for each methanol molecule converted to formaldehyde that causes damage to a mitochondrial enzyme, the lasting end effect will be per second, not just per molecule.
And an estimate the Ph change from formic acid alone. If this is done using Monte's number for MLD, 8 mL, the calculated number is too small. Normal blood Ph is 7.4 ± 0.5, and in severe acidosis methanol poisoning like that of Appendix F, blood Ph may go as low as 7.07.
If all of a minimal 8 mL lethal dose of methanol were converted without loss to its second metabolic oxidation byproduct, the peak concentration of this formic acid in the body would the same as in Table 1, (0.008/50)(2/3) = 0.011%. The Ph of pure formic acid is 2.3, so dilution to 0.011% should give a Ph change of no more than 2.3/log(.00016) ≈ -0.6. The first metabolic product, formaldehyde is pretty reactive stuff, and also as mentioned in humans has to be processed in the open cytosol rather than inside peroxisomes. So much of the metabolized methanol will not make it to the second stage formic acid. If half of it does, the Ph change due to formic acid would be -0.6log(2) = -0.2.
Tephly says monkeys are representative test animals. Monte says that, like other species, monkeys are also 100 times less sensitive to methanol than humans, because of a genetic anomaly of human catalase.
The issue of monkey susceptibility to methanol is one this reviewer doesn't yet fully understand. Tephly has several papers on the subject, and thrashing through that will be a study. But Monte's basic claims appears to stand: Catalase is the primary and ADH a secondary enzyme for oxidizing alcohol in all species from yeasts to primates - except for humans. In humans a genetic anomaly marginalizes the effectiveness catalase, leaving ADH the primary enzyme for oxidizing alcohol. And a particularly critical distinction here is location geometry, catalase being located inside peroxisomes that constrain reactive chemicals, but ADH being located throughout the cytosol of a cell. This means that in humans, but not other species, the formaldehyde produced in cells containing ADH is free to diffuse throughout the cell and to some extent out the cell wall. There is a reason for humans to be orders of magnitude more susceptible to methanol than all other species.
The gulf over DNA methylation is even more broadly based. Nature's process does not involve formaldehyde, but instead takes a methyl group from a methionine amino acid side chain of SAM and transfers it to replace a hydrogen at a precisely exact location on DNA, 99.98% of the time on a cytosine (C) nucleotide that is followed by a guanine (G), and simultaneously on both strands. In lab work with DNA in test tubes, addition of formaldehyde causes cross-linking between DNA and protein, not methylation. So there is reason to be skeptical when first hearing Monte's assertion that in vivo formaldehyde causes DNA methylation.
Particularly unfortunate in this reviewer's estimation is that in his book, p.47 last paragraph, Monte oversimplifies and does not distinguish between methyl ‑CH3 and oxymethyl ‑OCH3 side chains. In private communication he clarifies that, yes, it is the oxymethyl that formaldehyde forms on DNA or RNA as: -H + COH2 -> -OCH3, not -CH3. But there is then a separate process mediated by an enzyme readily available in the nucleus that does convert this to methyl.m225 It can not happen in vitro.
The key here to the potential disruptiveness of formaldehyde to DNA is that the first step of forming an oxymethyl -OCH3 is spontaneous and random, and not controlled by an enzyme.
|A final note about the fundamentals debate is that the Tephly, Stegink, Filer and the Medical School at the University of Iowa were funded for many years by A.G. Searle. Monte concludes that industry needs formate to be the bad actor of methanol, rather than formaldehyde, and needs monkeys to be accepted as human representative for testing, so that methanol will not seem as lethal as it really is. Aspartame would probably not have been approved, even by the political processes used, if the harmful metabolite of methanol had been thought to be formaldehyde. Balderdash sensationalism as the opposition says? Maybe, but probably not.|
And here are a couple speculations by this reviewer. The one-time metabolization of 1 ppm of methanol in an adult will produce some 1016 molecules of formaldehyde inside non-liver tissue. That's a lot of potential for harm, and it is not unreasonable that adding this a couple times a day for years or decades could be high risk.
Also, it may be relevant that arsenic is being discovered to cause life-threatening diseases when exposure is long term at about 10 ppm in well water. The disease locations for this arsenic poisoning are not the same as those for methanol, but are a subset.(Discover magazine, Oct.2013) And it is interesting that the many forms of arsenic all involve methyl attachments.
Another thing Monte brings to the table for the first time is the result of a Freedom-of-Information-Act request he knew to make because of difficulty reviewing documents at the FDA in 1983.L10, pp.iv&v Released in 2011, the document is an internal 1978 review by F.X. Collins of rabbit birth defect studies done by A.G. Searle and Hazelton Laboratories in 1974 and 1975.m677&A5 When pregnant rabbits were given aspartame on days 6 through 18 of their gestation, three things happened. They ate more and gained weight both during the time of administration of aspartame and after. Conception rate decreased slightly depending on dose. And their offspring had defects at rates of ½ or 2+ percent depending on dose level, but brain tissue was not analyzed microscopically for neurologic damage.
Dose level is a central issue in whether it was proper for Searle/Hazelton and then the FDA to withhold this data. Was too much aspartame administered to the rabbits or was it a dose level that scales to a range of normal for humans? The FDA's general recommendation is that consumption per day of a food ingredient should be less than 1/100 the dose known to cause any harm in animals. Also, in these experiments looking for effects, the dose administered is high compared to what humans are susceptible to, because rabbits are relatively immune to methanol.
Scaled for weight, the dose levels given to the rabbits were equivalent for a 150 lb (68 kg) human, to either 51 or 136 g/day of aspartame, and these two data points extrapolate to low birth defect rate at 23 g/day. The FDA's generally recommended limit would then be something like ¼ to ½ g/day of aspartame if the 1974 data were used. The current ADI for aspartame is set at 3.4 g/day.L11,L12 Less than 1 g/day is said to be the average amount of aspartame Americans consume, but there are some 3000 aspartame diet products, and 5.6 12 oz cans or one 2L bottle of diet soda contains 1 g of aspartame.
In contrast to these withheld 1974 results, Searle published favorable research for human subjects in 1985 in an international ObGyn journal.m100&A6 The report says, "Acute loading studies have been performed in human beings... No evidence of risk to the fetus was developed... Aspartame does not readily cross the placenta..."
Something is highly inconsistent here. The published results are totally favorable and in a journal optimal for encouraging aspartame consumption. The withheld results are the opposite, unfavorable, and would likely have prevented the approval of aspartame, or so Monte claims. His personal experience is of a fire in early 1990. His house was totaled and he regained consciousness in the hospital after too much smoke inhalation. This was two years after publication of birth defects in rats fed methanol, and the fire inspector reported many cigarette buts around a tree nearby the house, indicating stalking surveillance.
[Monte's methanol studies in rats were reported as Hoque1988,177 plus there is a post-publication update on pp.206&207 of Monte's book that gives improved analysis.
The methanol was delivered during pregnancy and gestation as continuous humidity @ 1.28 g/kg per day, which Hoque states as equivalent to 3 liters of aspartame soft drink per day for adult humans (but this reviewer calculates to be much higher).
Both the offspring and the mother rats were damaged. A notable correlation with the data is that besides capillary linings, the primary location of ADH in the brain is in the purkinje cells of the cerebellum. (See pp.206-207, Fig.12.5 for other anatomical analysis and correlation with autism.)]
[Bolon, Welsh and Morgan found similar results in 1994 but performed far more microscopic inspection and give much more analytic reporting of neurological damage.278Bolon1994 A significant shortcoming of this paper, though, is that the administered methanol is stated in units of 15,000 ppm humidity, with actual delivered dose level or information to calculate it never stated.]
And during 2008-2009 there was withholding of information from an especially convened FDA committee.(pp.196&197,Ch12) The Center for the Evaluation of Risks to Human Reproduction found methanol to be a potential developmental toxicant in humans and several times stated that humans are more susceptible to methanol than animals. But two committee members refused to sign the final CERHR report on methanol an accusation being:
|"As just one example, the missing pages from the 1986 NEDO (New Energy Development Organization) report, which I identified and provided to the CERHR contractor, were evidently never provided to members of the Panel. The pages in question included a table showing reductions in brain weight in a two-generation rat study that had been replicated in a special ancillary study..." m551 [Autistic children are often born with reduced brain size. Compare also pp.206&207.]|
(For what it's worth, here's a news article about industrial influence.)
Aspartame has always caused concern because of early animal studies and because of its component parts. One of the amino acid components of aspartame can act as a neurotransmitter, and the methanol component has long been regarded by some as suspicious. By now, though, aspartame is so widely used and so widely claimed to be safe that linking it to a long, disparate list of ailments is said by Wikipedia, ACSH and others to be Luddite conspiracy theory tied to the "Nancy Markle" email hoax.L13,L14,L15 Etc. by Garst.ref This doesn't match very well with in-depth histories.L16,L17
Aspartame's approval by corporate power can also be compared to that for leaded gasoline. Standard Oil powered through the science with the claim that there would be so little lead put in the atmosphere. G.D. Searle powered through the science by changing it. Monte balderdash sensationalism as some say? Maybe. But naysayers tend to dismiss before knowing what Monte is saying.
Government will invest $121M in a $230M program to foster a period of cooperation between normally competing pharmaceutical corporations. The four diseases to be addressed are: Alzheimer's, Type II diabetes, rheumatoid arthritis and lupus. The reason given for why a new approach is needed is that research has so far not been able to find cures for some of the world's most devastating diseases. The objective is, "to try to increase the odds of picking the right targets to go after for the next generation of drug development."
This can be taken as an admission of failure in research to date and that the new research goal is being scaled back. The announced goal is not to find what is causing the dramatic increase in disease or to turn back that increase, but rather try to be able to treat cases as they occur. (9.3% of Americans now have diabetes.)
And at the same time in mental as opposed to physical disease a similar admission is occurring. The way for research to address ADHD is being reexamined. This reviewer is quite sure that ADHD with comorbid conditions is due to an entirely separate cause, but is forced to admit that there might possibly be some relationship to methanol as mentioned above in reference to the cerebellar vermis. [There is also Indredavik2007m572 linking prenatal smoking (with its methanol) to ADHD.]
There appears to be repetition in the NIH AMP of a mistake already made at the onset of the human genome project. It was anticipated then that the heritability of common conditions like heart disease would be explained by correlation with a small set of common genetic variants. That didn't and couldn't happen, not for diseases showing epidemic expansion.
In the pure sciences when there have been decades of research thrashing, resolution has often been by fundamental paradigm change in how to think about the problem, a better known example being explanation of the baffling 1887 Michelson-Morley experiment by a combination of the 1905 special theory of relativity and the 1925 Schröedinger equation. Maybe today's decades of failure in research medicine is similarly lacking some concept fundamental. A common feature of the four diseases to be addressed in the AMP is that they all can be interpreted as relating to Monte's distinction between innate-immune and auto-immune.
Alzheimer's stands out in Figure 6 for its delay in getting to the top of the charts, and it does, too, in MTFT. According to Monte's model, Alzheimer's involves two toxicity mechanisms that should reasonably take time to effect - first innate-immune myelin removal starting at the predicted and observed location immediately around capillaries, and then at further distance, linking of protein giving the observed rubbery feel. Buildup at long diffusion distance should take a while to manifest, so it is reasonable that Alzheimer's should have taken longer to get to the top three in the charts. Contrast this to the fast action already discussed for depression. A new paradigm?
For diabetes, disease prevention might be facilitated with with far less than $250M simply by confirming and publicizing already available information.
a) The body's quick need for insulin after a high-pasta meal can be for more than the amount stored in the liver.[Fig.27.2, p,551, "Human Physiology," by G Pocock & CD RichardsOxford University Press, 1999] So even for people without diabetes, today's diets tend to raise blood sugar levels a little higher than normal, probably resulting in slight but accruing damage to body proteins and trend to onset of diabetes.
b) Type 1 diabetes is probably a (true) auto-immune response to cows milk before gut closing, as per Monte's references.Type1
c) In animal studies prenatal and infant exposure to excitotoxins can cause obesity in the adult.Blaylock1994,video
d) Do animal studies correlate diet soft drinks and sweeteners with weight? Though not confirmed in the rat experiments by Monte, the Searle/Hazelton studies discussed in Section H found that when rabbits were given aspartame for 24 days they ate more and gained weight both during the time of administration of aspartame and after.
My letter of March 18, 2014, was perhaps too polite and indirect, to be clear. What I really said is that: Dr. Murray's Feb 24 letter contains errors in every paragraph. So that of all the verbiage, what stands as valid statements are feelings, not technical critique. He assesses MTFT to be unscientific and too reductionist.
I was also too polite and indirect in my initial February 13 letter to the laureate director, too—with criticism of his newly announced AMP program indirect and left to attachments where apparently no one saw tham. I didn't get blunt about stating that these are director level issues until April 14.
The goal stated in the AMP announcement is to find medications for treating individuals. But nothing is said about the more basic issue of today's epidemic incidence rates as a whole. Shouldn't an exploratory development program at NIH seek to find why the disease are surging and how to drive the incidence rates back down to normal normal? The AMP doesn't. Its goal is to treat people after they are sick.
For $121M there is a lot missing. The NIH director does not respond.
AMP Announcement, February 4, 2014
Takken to Collins, February 13 MurrayToTakken, February 24 TakkenToMurray, March 18
Takken to Collins, March 18
Takken to Collins, April 14
Takken to House Reps, May 14
Takken to House Reps, August 15
Warner to Takken, June 11 & Oct 17
These letters were posted on September 10, 2014
President Obama, with NCI and NIH council, will be asking Congress in mid 2016 to fund a new $1B "moonshot" cancer initiative.4,5,SciAm
And NIH in 2014 invested $350M in a program called AMP with a goal of finding treatments for today's four worst modern ailments.1a,1b,2,3
These endeavors do not acknowledge the epidemic nature of the diseases being addressed or what the word "cure" should mean. The dramatic growth, for instance, of cardiovascular disease over 30 years has finally leveled off in the US due in part to highly effective modern interventions, but heart disease currently still causes about ¼ of all US deaths and is spreading worldwide.ref,bkup High tech treats sick people but has not solved the epidemic.
And that's even more true for ADHD (not related to methanol), for which treatment is still only palliative and for which the many heady years of high tech anatomical MRI studies have led to no improvement in outcomes.
In AMP and moonshot, the terms "cure" and even "cancer vaccine" don't mean what they connote. They mean "treatment," a medication or procedure for sustaining patients already afflicted. The aim is to reverse or mitigate harm, not prevent harm or reverse epidemic growth. (Money mangers should perhaps take special care with terminology so as not to inadvertently misrepresent to the paying public.)
MTFT is the opposite. It is about, "primum non nocere"—and about "cure" in a true sense of attempting to explain and therefore reverse the expansive growths of several non-germ diseases.
The billion dollar question: If not MTFT, what is or are the causal agents of these epidemics, and shouldn't at least half the money go to investigating this larger problem?
Dr. Monte's findings are counterintuitive. The usual reaction is that things like apple sauce, canned green beans, orange juice or a diet soft drink can’t have much methanol in them, are government approved, and besides, people have been eating and drinking these kinds of products for a long time without showing any signs of methanol poisoning.
This web page summarizes Monte's evidence that, yes, tiny amounts of methanol if repeated appear to cause harm. And this harm should come with symptoms totally different from that of Classical methanol poisoning. Here's an outline:
|Introduction:||How a tiny bit of methanol oft repeated could cause much harm|
|Figure 1:||Why low level symptoms totally different from classical methanol poisoning|
|Table 2 & Sect F:||Temporary peaks in low level methanol probably accrue the most damage|
|Table 1:||Monte’s message recast in context with other lethality modes|
|Section D:||Methanol-formaldehyde toxicity and disease mechanisms|
|Figure 2:||Primary metabolic pathway for methanol in humans (but not other species)|
|Section H:||Analysis of science from Tephly et al. versus science from Monte|
|Appendix F:||Example of methanol's strangeness in a real murder mystery|
Figure 2 serves as an introduction to Monte’s huge complaint. Researchers at the University of Iowa Medical School confirmed and published three (mis)concepts about methanol toxicity. These just happened to be beneficial for achieving approval of aspartame, and the works just happened to be funded by A.G. Searle Corp, the developer. Most important for approval were that the toxicity of methanol should not relate to formaldehyde and that the lethality not be too severe. This promulgation of faux scientific was in the early 1980’s and is still with us today, apparently vested even in referees for peer review journals.
We call it faux science both because it is incorrect and because it’s hold and tenure seems rather strange. You don’t need research to know that at least some of it is wrong. Formic acid, the promulgated and still identified bad guy with regards to methanol, is essentially just vinegar and classed by the FDA as a GRAS food additive. It can't be what makes methanol so lethal.
The approach here for presenting Monte's complaint is again rather the opposite of what he uses. His book does not cite the journal articles of Tephly et al. But in Section H here, the writings of the opponents are referenced, put side beside, and compared point by point. It's rather like watching a fencing match but with the judge being credibality of science. Guess who wins.
Several examples are given in Section H to point out how the Tephly et al. teachings are still believed, but perhaps the most interesting and saddest place to read about this is in the murder trial reviewed in Appendix F. Another reason to read Appendix F is to get oriented to the strangeness of how methanol works in the human body.
Monte’s MTFT model has not been and can not be tested directly. That’s because there is no animal model, and because it would be unethical to use humans in potentially debilitating experiments.
So proof has to come from epidemiology, inadvertent human experiments and a model with scientific self-consistency. The summary of Monte's evidence is given here in Sections G and H.
Three problems with Monte's book have been addressed. First, his thinking is too "out of the box" for the scientific community (Sect L, 2/25/14 & 3/18/14), but hopefully the present introduction will serve as a bridge for that problem. Second, writing style has been changed to more of a compressed reference document. And third, a few technical gaps in Monte's presentation have been filled in. Those usually started in attempts to prove him wrong but after study always ended up reinforcing his logic.
Monte’s charges of corporate, scientific, political, agency and scientific malfeasance with general scientific naivety are at first too broad to believe. But after much consideration, reading of his cited documents and note of funding sources, this reviewer has to conclude that his charges are both objective and correct, that:
|1) A.G. Seattle, the corporate developer of aspartame, was able to spend money to have basic science altered in such a way that it became more favorable for achieving FDA approval of aspartame. (Section H)|
|2) The FDA became a co-conspirator in this deception. (Section I)|
|3) Aspartame approval was achieved by political power chaperoned by a US President and his appointees. (Appendix B ¶6)|
|4) There is much collateral damage from the faux science because of misunderstanding of methanol in food products. (Intro, pectin)|
Further, Monte's charges probably don't go far enough. The machinations he exposes are, after all, pretty much just the flow from "normal" economic forces, and are, arguably, just an oft-seen repeat. Most familiar, perhaps, are some of the misrepresentations by big tobacco and energy, industries that compete in power with the US Government and even use government as in trade negotiations.
There is also a long record of pushing limits in the edibles industries: a) patent medicines using methanol for 40 years; b) the now usually forgotten string of incidents leading to creation and empowerments of the FDA; and less known, c) the food industry's success in the 1970s and still persisting that ADHD can't be caused by profitable additives. The US still does not admonish even FD&C colorings (or allow the FDA to regulate when tests are done on groups of compounds) even though the EU, China and even Kraft and Mars have taken action.
If there is any change with time it is increased sophistication in hiding manipulation. Though the US does not have assassinations as in Latin America, disregard for consumer well-being is an imbedded historical constant, the vested interest of corporations being profit, not health. Large industries - like those for energy, tobacco, pharmaceuticals, foods and banking - get return from spending lots of money on advertising, congressional influence, infiltration of regulation, research done their way, and general promulgation of their point of view which may mean subtle denigration of their opposition.
Edibles need to be appealing and convenient (achieved partly with coloring and preservatives), tasty (typically achieved with salt, sugar, fat and flavorings or flavor enhancers) and also be healthy (achieved with advertising). The health image staple, milk, for instance, tastes good because of its animal fat and sugar, but is nutrient depleted after being heated twice, and wonderfully appealing "all-natural" ice cream is an even bigger contrast in image and fact.
A huge, under-recognized new economic force for corporate profitability since WW II is ability to influence inclination to consume. More consumption, whether of food, ice cream, news, cars or borrowed money, is more profit. And aspartame is just one of many, many edibles successfully projected as desirable and healthy, in this case by reducing calories especially for diabetics.
And a final more personal conclusion: A young researcher inclined to be aloof of industry is probably not facing a bright academic career with funding and publications. There aren't many survivors like Monte, and he is having a hard time being heard or publishing in leading journals. I have come to ignore the sometimes stridency in his charges and to critique only the substance of what he writes.
He is a combination of revanchism and remarkable perception.