Synthesis of opposing views: a syncretic view of the many contradictions re vitamin C

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A model that makes sense of opposing views about vitamin C has the following “tenets” (by definition, tenets are tentatively held ideas, modifiable with every piece of data that does not fit the model):

  1. Pauling focused on the high rate of synthesis of vitamin C in animals that make it. He focused on the fact that if we ingest grams of vitamin C, we absorb grams of vitamin C. He noted that we absorb even more vitamin C when we are ill. Pauling focused on the proven utility of high dose vitamin C in the work of Dr. Frederick Klenner. He more or less ignored the high rate of urinary excretion of vitamin C.
  2. The US government focused on the high rate of urinary excretion and the fact that total body pools of vitamin C cannot be increased stably beyond about 1500-3000 mg. The government scientists ignored the fact that animals of our size make 200 times our RDA and that we absorb grams of vitamin C before we excrete all but about 100 mg of it per day and that we absorb more vitamin C when we are sick.
  3. As a rule, animals make about what they need of various nutrients. Exception: we make less choline than we need. As a consequence, animals do not make 200 times what they need.
  4. Both Pauling and the government scientists are making valid points. What is the explanation of these contradictory viewpoints?
  5. A possible explanation of the paradox is that vitamin C is accidentally absorbed (for example, oxidized vitamin C is absorbed by a glucose receptor) and deliberately excreted. This fails to explain why vitamin C is absorbed better when we are ill.
  6. Optimal tissue levels of vitamin C are at or near SL (saturating or near saturating levels). This explains why goats make 13 grams of vitamin C a day and why we absorb grams per day even though we need but 100 mg or so to replace losses of vitamin C (at 2-4% loss per day with a total body pool size of 1500-3000 mg).
  7. Supersaturating levels in serum and tissues occur for a short period of time following injection with high levels of sodium ascorbate.
  8. Chosen properly, an injection that achieves a therapeutic window of proper supersaturating levels of serum and tissue vitamin C, which I will call SSL1 (supersaturating level 1), avoids most of the toxicity and allows some antitumor, antiviral, antibacterial, and antifungal action, as well as some high level chelating of heavy metals. This explains the effectiveness of the use of injectable vitamin C as an adjunct cancer therapy and the many anecdotal results (more than 30 diseases treated) of Dr. Frederick Klenner re injection of high doses of vitamin C followed by high oral doses. Before even getting a diagnosis, Dr. Klenner treated everyone prophylactically with a high dose of injectable vitamin C, followed by multiple oral high dose vitamin C. When they came back for their diagnosis and treatment, they were in many cases on the road to recovery.
  9. Chosen improperly, there is a level of serum and tissue super-saturation, SSL2 (supersaturating level 2), at which there could be heavy damage to normal cells, especially if the kidneys are compromised. Possible mechanism: a catalytic cycle in which vitamin C binds regions in the genome in which copper is bound to cellular DNA, and creates single and double stand breaks. Vitamin C can be regenerated by various cellular antioxidants like glutathione (at 5-10 mM, glutathione is many times higher in concentration than cellular vitamin C), making this a highly destructive catalytic event.
  10. This toxic reaction or something like it or both explains why evolution has favored those animals whose kidneys excrete vitamin C so well and so rapidly, and this rapid excretion explains why vitamin C cannot ordinarily be driven to still higher concentrations in tissues (>=SSL2), given reasonably healthy kidney function.
  11. This explains the US government’s position – why take more than about 100 mg a day if it is all going to be excreted? Well yes, after tissue saturation has been achieved. I doubt that 100 mg a day can always maintain saturation in all tissues. When we are sick we absorb more vitamin C (as evidenced by higher bowel tolerance) and we consume more vitamin C when we are sick. When goats are sick they make twice as much vitamin C as when they are healthy.
  12. Nature’s program is to overdose the vitamin, thus achieving tissue saturation, and then excrete the excess as rapidly as possible to sidestep the toxic side reaction(s).
  13. Because of the toxic reaction(s) at SSL2, at inappropriately high supersaturating concentrations of vitamin C, no one with impaired kidney function should take Pauling type doses (18 grams a day).
  14. Re the government’s position: I would argue that vitamin C passing through the bowel may be doing us a world of good in keeping stools somewhat looser rather than too hard. I would also argue that vitamin C in urine is definitely doing us a world of good. First, in solubilizing substances like calcium (calcium oxalate and calcium phosphate stones are much less likely in someone taking high dose vitamin C). Second, and this is more speculative, in reducing the likelihood of UTI – the acidity of urine with lots of vitamin C likely makes it very uncomfortable for fimbriated bacteria trying to colonize the urinary tract.
  15. Also, re the government’s position: the total requirement for vitamin C cannot be deduced merely from mass balance studies. Two reasons – vitamin C is likely a member in a number of other nutrients’ ADME networks, and it will have an optimal dose for functioning there that is in addition to its own optimal dose (since a vitamin C molecule cannot be in two places at once). In addition, we need to write the total requirement of any nutrient as the sum of at least 4 independent parts: 1. the requirements of the entire gut. 2. the requirements of the blood stream and lymphatic systems. 3. the sum of the requirements of all tissues. 4. the requirements of the urinary system.

How general is this model? Might the same not be true of selenium and other nutrients in which the therapeutic window is rather narrow?

Nature plays with fire – it has to; life would never have come to be without doing so – and avoids getting burned most of the time thanks to many rounds of selective pressure that was at times so great that scientists estimate that ~90% of all species were extinguished. That is how nature comes up with such nearly flawless solutions to working with substances that can be as beneficial at one set of doses, between SL and SSL1, and so harmful at another set of doses, that is, >=SSL2.

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Possible problems with determining nutrient requirements by mass balance studies

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Determining the minimum daily requirement of a nutrient seems simple enough – just determine the mass balance, that is, how much of a nutrient is needed to replace obligatory daily losses, and do the experiment over a sufficiently long period of time to have confidence in the results.

However, this assumes that all nutrients in that particular nutrient’s ADME network are in place at optimal levels – highly unlikely in modern America.

Consider the absurdity of trying to define the minimum daily calcium requirement in a person with a clear deficiency of magnesium. Such a person inappropriately excretes calcium in his urine because magnesium is a nutrient in calcium’s ADME network.

The iron requirement in a person who is copper deficient cannot be defined, so important is copper in iron’s distribution (copper puts the D in iron’s ADME network; at least 3 copper-requiring proteins are involved in moving iron around the body).

In addition, it may be that some, many, or even all nutrients need to circulate throughout the body to grease the body’s gears so to speak – for these nutrients, the minimum daily amount needed is that amount necessary to maintain its balance, given optimal levels of all ADME nutrients, PLUS the amount needed to circulate through the body each and every day to keep everything running smoothly and everything else in balance.

Sodium, chloride, and vitamin C are almost certainly nutrients that need to pass throughout the body each and every day for optimal health. Is this true of all other nutrients?

Notice that my idea that the vitamin C requirement is the sum of the amount needed to maintain vitamin C balance PLUS the requirement that must circulate through the body comes close to Pauling’s idea that very high doses (multiple grams) of vitamin C are useful in preventing atherosclerosis – circulating high levels of C throughout the body hour by hour each day would keep the serum level consistently high and consistently protective against oxidative damage to key structures, provided that nothing untoward is making the vitamin C act like a pro-oxidant, in which case the vitamin C is likely attacking the culprit by bleaching it.

Why do I think that sodium chloride needs to cycle throughout our bodies?

Reason 1: Because our craving for salt is so much higher than what is needed to replace losses. This craving, present even in reasonably well nourished people, suggests the body has needs for salt that are greatly in excess of replacing insensible losses of sodium and chloride. So important is salt that it must even be added to sweets to make them taste better – first and foremost, if our taste for salt is not satisfied, we cannot thoroughly enjoy the sweetness of a sweet treat.

Reason 2: we absorb so much more sodium chloride than we need to maintain mass balance. Reasonable explanation: sodium chloride needs to circulate throughout the body. To maintain optimal health, we need more sodium chloride per day than what merely replaces daily losses.

Speculation: every essential nutrient is an essential nutrient in at least one other essential nutrient’s ADME network. If true, then sodium and chloride, each of which are essential nutrients, are essential nutrients in other essential nutrients’ ADME networks, and they may need to be temporarily at higher activities at particular locations for optimal bodily function. The same goes for vitamin C and who knows how many other essential and conditionally essential nutrients.

What evidence is there that vitamin C needs to circulate?

The evidence is a bit speculative:

Consider the goat, which is about our size. The goat makes about 13 grams of vitamin C a day. If its total body pools are like ours, about 1.5-3.0 grams, and its rate of turnover of vitamin C is about the same as ours, about 2%-4% per day, then as little as 4% of 1500-3000 mg (60-120 mg) is all that is needed to maintain homeostasis under the worst of conditions. Clearly the goat is making more than it “needs” Biological systems do not in general make 100 times more of something than they need to. So why make so much? Probably because something comparable to this amount of vitamin C, 13 grams, which is roughly 200 times the human RDA (60 mg/day, which is based on balance studies with a generous overage for safety), in all likelihood needs to circulate through the goat’s body each and every day. Is it not likely the same is true for us?

In addition, why does even a person with good vitamin C status still absorb grams of supplemental vitamin C only to excrete nearly all or all but what he/she needs to replace losses? Reasonable explanation: vitamin C needs to circulate throughout our bodies. Replacing losses is not enough. The assumptions behind mass balance studies are or may well be false.

Also, why does the body absorb so much more than it needs of supplemental B vitamins only to excrete what it does not need? Is there something not accounted for in current models of nutrition?

Could atherosclerosis be all but non-existent in us, as Pauling and Rath suggested, if we circulated many grams of vitamin C a day in proper and multiple doses throughout our bodies?

Has the US government misconstrued nutritional science, even when it is interpreting a “simple” balance study?

Does this apply even to cholesterol? Why does the body absorb up to a gram a day of additional cholesterol while remaining fully committed to making a gram a day?

Re poisons: In cases of accidental poisoning, why do we absorb so much more arsenic than we need (we need perhaps just 12 micrograms/day out of just 48 micrograms/day in our food supply)? I assume because mechanisms did not evolve to protect us from arsenic, which is not abundant in food, and so many other poisons. But mechanisms did evolve to protect us from iron poisoning, and food (10-20 mgs/day ingested) does contain enough iron to poison us, if we did not exclude all but 1-2 mg/day, although no known mechanism evolved to protect us from iron overload if the former mechanisms failed, as they do in hereditary hemochromatosis. Is the same true of salt, vitamin C, and the B vitamins? Mechanisms did not evolve to protect us from over-absorption of the minerals and the vitamins, and the over-absorption did not prove to be anywhere near as harmful as over-absorption of arsenic does, and iron would, if mechanisms did not exist to protect us from iron overload due to over-absorption?

The bull’s-eye diet: Not high fat, but sufficient fat

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By definition, high fat is too high and low fat is too low. What we want is just the right amount of each type of fat and thus the right amount of total fat.

The bull’s-eye diet is not high in fat, but it is higher in fat than most experts believe is healthy. It is way higher in fat than the low-fat vegan diet many believe is optimal, at least for heart health.

Because most people are under-nourished, they cannot find the optimal level of fat in their food using as guides either their taste buds or the meal’s ability to suppress their appetite for at least 6 hours. Any meal that can suppress appetite for at least 6 hours must have sufficient calories, sufficient protein and sufficient fat. Sufficient calories alone does not remove the sufficient protein and sufficient fat requirements. Low fat, low protein vegan dieting is running uphill when it comes to suppressing the appetite.

F, The amount of fat we need per meal, is that amount that will accomplish at least all of the following:

1. Form a good micellar emulsion with water and bile and other emulsifiers (like choline) and all of the useful and absorbable fat soluble substances and amphipathic substances (essential nutrients like linoleic acid and linolenic acid and vitamins D, E, A, and K), conditionally essential nutrients, and accessory nutrients like carotenoids and the amphipathic substance vitamin P [and biotin?]) in foods and supplements, resulting in sufficient absorption of these nutrients. Call this F1.

2. Satisfy our well-nourished appetite suppression system for many hours so that we are not gaining weight by giving in to hunger frequently. One meal a day is ideal, as in the Fast-5 approach. Two meals are better than three. So we are talking about satisfying the appetite for 6 hours (for three meals) or 12 hours (two meals) to 19 hours (1 meal per day). Call this F2.

3. Completely empty our gall bladders, so important because our gall bladders store 10-20 concentrated organic toxins and amphipathic toxins from the liver. Call this amount F3.

4. Provide sufficient antimicrobial activity in the lumen of the stomach in the presence of stomach acid – 6 log killing can be achieved with 1 mM free fatty acid at pH 3, while 10 mM free fatty acid can achieve almost the same at pH 4.5 (C.Q. Sun et al. / FEMS Immunology and Medical Microbiology 36 (2003) 9-17). Call this amount of fat F4. Salivary serous gland lipase (the principle products of this enzyme are free fatty acids and diacylglycerols) is able to penetrate fat globules and is thus active without the need for bile and in the presence of acid, down to at least pH 4.5 – so considerable digestion can occur right after eating a meal with sufficient fat before the stomach contents are acidified down to where pepsin is optimal.

5. Provide a well-nourished taste bud system with good taste – not too little fat, which does not taste good, and not too much, which tastes greasy. This satisfaction of the taste requirements also contributes in a virtuous circle to appetite suppression and mood stabilization later on. Call this amount F5.

6. Provide sufficient fat for mood stabilization (helps prevent depression, likely taste bud satisfaction contributes to a better overall mood). Call this F6.

7. Provide sufficient fat for lubrication in enteric and non-enteric tissues. Call this F7.

Is F=F1=F2=F3=F4=F5=F6=F7? Don’t know, but it would be fascinating if it worked out that way or even approximately the same. Would be fascinating if F is also the amount of fat that we can digest by salivary lipase and gastric lipases, and absorb without making either new enzymes (salivary, gastric, or pancreatic lipases) or more bile. This amount of fat may decrease as we age. We may need to supplement digestive enzymes as we age and stimulate our digestive process (with all natural digestive bitters, e.g.) in any way we can.

Note that our well-nourished bodies also tell us when we consume too much fat. Too much fat not only tastes greasy, but it makes stool float and at an even greater excess too much fat in the diet results in smelly diarrhea. Too much fat may also promote feelings ranging from mild anxiety to outright panic attack, and from mild nausea to vomiting.

How could any reasonably intelligent person fail to read these signals? The body is clearly saying that too much fat is not good for the body.

Stating the obvious once more: an undernourished person may have such reactions to too low a level of fat in his diet. Only a properly nourished body has properly functioning taste buds, appetite satiation, and appropriate responses to too little fat and protein, and too much fat and protein.

The antioxidant network is a relay system for removing free radicals from sites of major harmfulness

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In cell membranes, vitamin E is oxidized by free radicals. This is reduced by CoQ10, which itself is regenerated by the respiratory chain, to the degree that respiration is not “impaired.”

Or: diffusible vitamin C, or more optimally vitamin C held near the membrane by something (possibly including vitamin E), reduces vitamin E, glutathione reduces vitamin C, glutathione reductase reduces oxidized glutathione, and ultimately NADPH is regenerated by the oxidation of foodstuffs (pentose phosphate pathway oxidative cycle in which two glucose-6-phosphate are oxidized twice to produce four NADPH, two carbon dioxides, and two ribulose-5-P, which are non-oxidatively recycled back to one four carbon sugar plus one glucose-6-P, using transketolase, transaldolase, and phosphoglucose isomerase; in this way NADPH can be ramped up to appropriate levels for reduction of oxidized glutathione, keeping the antioxidant network [as noted above, involving minimally vitamin E, vitamin C, glutathione, glutathione reductase, and NADPH from the pentose phosphate pathway, but likely many more participants, including antioxidant enzymes and other small molecule antioxidants.] running smoothly, and reductive biosynthesis. When NADPH is sufficiently high, ribulose-5-phosphate can be used to make ribose-5-phosphate and its derivatives). NADPH is the ultimate or ground zero antioxidant in the body. NADH and FADH2, also regenerated from the oxidation of foodstuffs, serve as additional reservoirs of reducing power in the cell.

The above description is that of a relay shuttle, which carries away harmful molecules from the site where they would otherwise do the most damage.

The body uses the network principle, not the pharmaceutical principle, and thus achieves higher signal/noise ratios. The highest signal/noise ratio is never seen in any natural process near the maximum signal, as the pharmaceutical model presupposes. Rather the highest overall signal/noise ratio is achieved using concentrations of each component of a large network well off their maximal effective dose.

A shuttle network makes it obvious why it is not useful to overdose on any one component of the network. Optimal -not maximal- doses of ALL components (including the cofactors in the antioxidant enzymes) and precursors (in the case of making the enzymes and glutathione) make more sense in supplements.

Square Meal Poll #1

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A commercial square meal would be certified to contain 100% of all of our nutritional requirements, thus taking away all worries and concerns about nutrition and health-related nutrition issues (except of course those due to genetic problems). Square Meals are only about 670 calories, leaving the vast majority of our calories for our favorite foods.

50 grams of protein

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Below is a Table that helps one select sources to obtain the 50 grams of protein the average adult needs per day.

8 “servings” of protein is approximately 50 grams.

Foods

One Serving Equals

Meat, Fish, Cheese

One ounce

Eggs

One large egg

Milk or Yogurt

Six ounces

Cooked Legumes

One half cup

From the Table above, 50 grams of protein would be about 8 ounces of beef or chicken, 8 ounces of shrimp or salmon. 8 ounces of blue cheese used to top the salad. 8 large eggs. 2 large eggs, one quarter pound burger, and four ounces of cheese.

One caveat: When the sole protein source is legumes, be sure to supplement the amino acid methionine (at least one half a gram, 500 mg.) and vitamin B12.

How to create a Square Meal

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You need three things: (1) 50 grams of protein, (2) a pound of one or more dark green leafy vegetables, (3) a pound of other vegetables.

For example: Let’s make a shrimp spinach salad: (1) 8 ounces of cooked shrimp, (2) one pound of washed baby spinach leaves, (3) a pound of vegetables consisting of carrots, broccoli, tomatoes, celery, and cucumber. That is two and one half pounds of food, filling by design. That is the Square Meal. Easy. Square Meals average about 700 calories. If you are maintaining your weight on 2,000 calories, that leaves 1,300 calories in the “calorie bank” to enjoy any way you want.

Now to make the salad taste great, add your favorite dressing and toppings. These are borrowed from the “calorie bank.”

The Square Meal Diet Fundamentals

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1. Enjoy one square meal a day to satisfy all of your nutritional requirements for optimal health. Obtaining sufficient nutrition during dieting is extremely important, but it is overshadowed by all of the emphasis on the importance of weight loss. It is assumed that weight loss “outweighs” any damage done to the body by nutrient deprivation on “denial diets.” I assume the opposite. Weight loss without assuring proper nutrition is dangerous to health.

2. Enjoy your favorite foods.

3. To lose weight, gradually increase physical activity and gradually reduce the portion sizes of your favorite foods, but never give them up.

Welcome to the Square Meal Diet Blog

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I’m  Dr. Mark Collins, author of The Square Meal Diet: The Revolutionary Diet That Features Comfort Foods. This blog is to discuss technical issues relating to this diet.

A companion blog is devoted to recipes, The Square Meal Diet Recipe Blog. http://thesquaremealdietrecipe.wordpress.com/

Thanks for participating!      © 2011 Mark L. Collins

There are three or four nutritional requirements for each nutrient, essential and non-essential

The US government’s single nutrient requirement for each essential nutrient, with no more variation in the recommended amount other than by age, sex, and body size, and their mistaken idea that all non-essential nutrients have no nutritional requirements (amount required = 0 for all of them) for the maintenance of good health is too narrowly conceived, if not downright erroneous.

Example vitamin C. There are at least three separate nutritional requirements.

Requirement No 1 – the minimum requirement, the amount necessary to avoid scurvy. Roughly 10 mg per day.

Requirement No. 2 – the RDA, about 100 mg per day, the amount required to support basic immune and antioxidant functions, and enough to maintain bodily pools at these levels.

Requirement No. 3 – the optimal amount, approximately the amount the body is trying to absorb, which depends on conditions, more when we are sick (colds and flus), and much more when we are very sick (cancer cachexia). This is the amount needed to keep the body’s mucus flowing smoothly, by thinning the body’s entire lining of mucus, and is grams per day. It will not prevent a cold, but if you get a cold, you will find considerably more relief from about 3-6 grams a day, as per Requirement No. 3, than from the 100 mg of Requirement No. 2.

Similarly for all other nutrients, both non-essential and essential. If the body makes specific receptors for any nutrient, it is important to health, even if the body already makes a make-do amount. Some adverse consequence, perhaps psychiatric (who notices these, given that moderns are rather crazy to begin with?), perhaps only distantly related to the shortfall, will ensue, if one does not give the body what it is looking for, and that includes cholesterol and non-essential fats.

At least three levels, with the optimal level often close to what the body is trying to absorb. An obvious exception: the body is trying to absorb considerably more of certain nutrients like Na+, Cl-, and I-, and the explanation may be in the deep evolutionary past. We must give the body at least the first level of these nutrients, although the body will clearly take up to at least the third level of these nutrients.

Similarly for iodine/iodide. While the US RDA of 150 micrograms of iodide is generally enough to keep the thyroid gland functioning properly, it is not enough for breast health, and probably not enough to meet the requirements for brain health and oral health. The body is trying to absorb milligrams of Iodide, and that is nearer the optimum amount. Some experiments of Dr. Guy Abraham suggest that the body will readily absorb nearly 50 mg of an iodide/iodine mixture (since about 45 mg per day is excreted in a 24 hour urine), even when its thyroid is well-supplied with iodide.

As noted above: with NaCl, the body goes after iodide with abandon. No doubt the system evolved under stresses of rather severed deprivation, and this aggressiveness in the absorption of these nutrients is not really necessary when there is such abundance available to us that we have to be sensible in the amount of Na+, Cl-, and I- we give to our bodies.

When 150 micrograms of iodide a day is not enough for thyroid: when a person is overdosed with goitrogens, like F, Br, SCN, ClO4. For example, some people consume so much bromated white flour products that they have to be dosed with milligrams of iodide a day to compete with Br- for uptake at the sodium iodide symporter and to compete with Br- for oxidation by thyroid peroxidase in the thyroid follicle lumen, along with about 10 grams of NaCl per diem to drive the excess Br- into the urine, as in the protocol of Dr. Guy Abraham. He also uses 3 grams of vitamin C a day to help prevent oxidation of the halide binding site in the sodium iodide symporter (more of a problem when F- and ClO4- are also present at levels that interfere with normal thyroid function).

 

A brighter future requires brighter gatekeepers

Innovators are often small fry. Sometimes they do not even have college degrees, but they can see how to make things better, while layer upon layer of management does not.

As a rule, gatekeepers are neither innovative nor bright. They will not fund a novel idea unless their boss somehow likes it, and bosses of gatekeepers were once gatekeepers themselves, equally or perhaps more uninspiring., and some of them were promoted in part because of their tight-fisted control of the budget.

Gatekeepers tend to be clueless. That is why we have hundreds of such follies as the ubiquitous foxes guarding henhouses, superfund cleanup sites, speed bumps, audible car alarms, squeezable mayonnaise, brominated flour, 100% locally grown produce, choline-is-not-an-essential-nutrient-until-1998, and dietary-cholesterol-is-still-a-toxin. Gatekeepers cannot see the follies that we innovators immediately detect. We are bright sparks; they are not.

Until innovators hold the purse strings, the future of the world remains dim at best.

If you are a CEO and an intelligent risk taker, try giving a few purse strings to innovators or former innovators rather than to toady gatekeepers.

A crude estimate of liver insufficiency in America

Liver insufficiency is not liver disease. It is just some kind of liver metabolic insufficiency or impairment due mostly to poor stewardship of the body.

Roughly 20-25% of Americans have a noticeably higher serum cholesterol after a month of consuming 3-5 eggs a day.

Roughly 75-80% of Americans have approximately the same serum cholesterol after consuming 3-5 eggs a day.

Crude estimate of liver insufficiency in America: 20-25%, could be higher, as these data focus on proper bile production from dietary cholesterol, choline, and taurine, and successful bile secretion, i.e. no backup of dietary cholesterol (and/or bile acid salts) into the circulatory system, nearly all dietary cholesterol being confined to enterohepatic circulation in healthy individuals.

The prevalence of liver insufficiency should be considerably greater than the prevalence of cirrhosis, which is estimated to be less than 1% in the US.

The Epidemiology of Cirrhosis in the United States: A Population-based Study.

PMID: 25291348

CDC stats on the prevalence of all types of liver disease:

  • Number of adults with diagnosed liver disease: 3.9 million
  • Percent of adults with diagnosed liver disease: 1.6%

https://www.cdc.gov/nchs/fastats/liver-disease.htm.

Still a fraction of the number I am estimating, closer to 20%. Are their tests not sensitive enough to see real metabolic problems in liver?

Or is my estimate utter nonsense?

 

 

 

 

Nature plays with fire

Imagine a nutrient so vital that nature keeps its concentration near its saturation limit. Imagine further that when this nutrient massively precipitates in the kidneys (as during an episode of tumor lysis syndrome, when tumor cells are killed too rapidly and release massive amounts of uric acid from the breakdown of nucleic acids), it can actually kill a person. Doctors of course will treat this vital nutrient as a toxin.

As a rule, doctors think of the marvelous machine, the human body, as a right idiot. As a rule, doctors misunderstand everything they study.

When nature plays with fire, pay attention – the fire is so important as to be vital to health. We have to be proper stewards of our bodies. We have to give our bodies what they need and not a whole lot else.

The fire is not a toxin, and many factoids will tell you that this fire is not a toxin, if you do not filter them out of your interpretation, the ways doctors routinely do, whenever matters get a bit too intricate for them.

Synovial fluid is an ultrafiltrate of plasma. Its normal concentration of uric acid is roughly the same as plasma, nearly twice that in whole blood.

The normal concentration of uric acid in the synovial fluid of the average man is close to the saturation limit of uric acid in pure water at 25 degrees C. The solubility limits are not the same. Synovial fluid is not water, and biological tissues, even extremities like big toes, do not normally reach down to 25 degrees.

And even when saturation has been reached, crystallization does not necessarily and immediately occur. Often agitation is required to crystallize a supersaturated mixture. The stubbing of a big toe may be just the thing to trigger it.

When a toe is wounded, as part of the healing process, the marvelous machine acidifies the site of the wound, increasing the odds of precipitation of the uric acid as sodium urate.

Keeping external wounds properly acidified to aid healing and to keep infection risk as low as possible is something doctors pay too little attention to. Take a lesson from the marvelous machine, doctors! Ascorbic acid and citric acid are two acids I would try to apply repeatedly to every external wound during the healing process.

An infection in or near synovial fluid that produces acid could trigger precipitation, as could a non-acid producing infection that produces a sufficiently acidic response in the host. When the cells that line the synovial joint are injured or actually die, they release uric acid. This could be part of the trigger mechanism for precipitation of uric acid crystals in synovial fluid.

Whatever explains a particular case of gouty arthritis, one focuses on the site of occurrence. One does not treat circulating uric acid as a toxin, when kidney reabsorption alone says otherwise, and one does not refer solely to systemic events to explain local occurrences. Local occurrences occur because local conditions are in some way different from systemic conditions. Systemic conditions feed local occurrences, but the local situation is always at least subtly different. Small differences matter. Many small differences matter a lot.

Correlations are not causes

Consider the following possibilities:

  1. Higher organisms have better DNA repair and live longer than lower organisms. A correlation exists but it is neither causal nor contributory (neither a major nor a minor contributor).
  2. Higher organisms have better DNA repair than lower organisms, and in part because of this, live longer. Better DNA repair contributes to or drives (is the major contributor to) greater longevity.
  3. Higher organisms have better DNA repair than lower organisms, and solely because of this, live longer. Better DNA repair is the sole cause of their greater longevity. DNA damage is solely responsible for senescence and death.

Of the three possibilities listed, #2 is the most likely. The effect on longevity might be small, medium, or large. The best experiment is hard to do:

  1. Create a sufficiently large cohorts of different types of higher organisms whose DNA repair is no better than that of a mouse, and compare their longevity with mice and with other members of the higher species whose DNA repair is wild type. If possible, change nothing else. Of course, it is not possible to change nothing else. Intrinsic complexity rules! Interpretations are always suspect even when most people think they are crystal clear.

Rule: scientists lack imagination

Most scientists have sufficient intellectual discipline, but lack imagination and intellectual honesty. They conceive of phenomena too narrowly, often causally, when there are correlations that are better modeled without invoking causation, and lacking intellectual honesty, when their personal agendas are satisfied, scientists are satisfied with views that are flat-out contradicted by other data.

Philosophers, artists, and saints – Nietzsche’s triad of worthy human beings, scientists deliberately excluded – have too much imagination and not enough intellectual honesty and intellectual discipline.

Is there any person in the history of our world who has intellectual discipline, intellectual honesty, and sufficient imagination? Will there ever be?

To be in my list of worthy human beings, minimally, all three are required. I am still looking for an example.

Rule: Correlations are not causes

Hyperuricemia correlates most strongly with gout and less strongly with a number of other medical conditions, including elevated BP and elevated blood sugar.

Is hyperuricemia the cause of any of them?

No – but the underlying problems, kidney and liver insufficiency, are contributors to all of them.

Kidney and liver insufficiency are short of outright diseases and are more common than outright diseases.

A healthy liver balances the toxic loads on the body. It directs a portion of the toxins toward the circulatory system, the kidneys, the ureters, the bladder, and the urethra, and each of these things suffers the consequences, depending roughly on the product of the toxicity per unit concentration, the concentration of the toxins, and the time spent in contact with these organs/tissues. The liver directs the rest of the toxins to the gall bladder, which stores and concentrates the toxins, taking a real beating, to the small intestine, large intestine and the anus. Nothing gets the full load of toxicity that the liver was processing.

Any degree of liver insufficiency can increase total toxicity and exacerbate problems with the body’s management of total toxic loads and especially unbalanced toxic loads,

Kidney insufficiency increases the concentration of a large number of circulating toxins, and of some nutrients (the kidneys do not ordinarily reabsorb 90% of toxins; they do ordinarily reabsorb 90% of uric acid in the filtrate, consistent with uric acid being a nutrient, whose concentration in blood will rise when kidney filtration is subpar), like uric acid, and thus all sorts of medical conditions will correlate with kidney insufficiency. It is a real problem, a real menace to health.

High circulating uric acid, due mostly to kidney insufficiency, increases the odds of gout. But gout starts long before that with the development of an arthritic joint, itself a long and complicated tug of war process, followed by some kind of injury (like stubbing the toe), or insult (a recent surgery), or an infection in or near the joint, (could mild acidification of the joint be a common denominator in these triggers?) and given kidney insufficiency, too high a concentration of uric acid increases the odds of an acute gouty attack, most often in one synovial joint of one big toe.