Category Archives: physiology

Vitamin A and E, killer supplements; B, C, and D are meh.

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It’s often assumed that vitamins and minerals are good for you, so good for you that people buy all sorts of supplements providing more than the normal does in hopes of curing disease. Extra doses are a mistake unless you really have a mis-balanced diet. I know of no material that is good in small does that is not toxic in large doses. This has been shown to be so for water, exercise, weight loss, and it’s true for vitamins, too. That’s why there is an RDA (a Recommended Daily Allowance). 

Lets begin with Vitamin A. That’s beta carotene and its relatives, a vitamin found in green and orange fruits and vegetables. In small doses it’s good. It prevents night blindness, and is an anti-oxidant. It was hoped that Vitamin A would turn out to cure cancer too. It didn’t. In fact, it seems to make cancer worse. A study was preformed with 1029 men and women chosen random from a pool that was considered high risk for cancer: smokers, former smokers, and people exposed to asbestos. They were given either15 mg of beta carotene and 25,000 IU of vitamin A (5 times the RDA) or a placebo. Those taking the placebo did better than those taking the vitamin A. The results were presented in the New England Journal of Medicine, read it here, with some key findings summarized in the graph below.

Comparison of cumulative mortality and cardiovascular disease between those receiving Vitamin A (5 times RDA) and those receiving a placebo. From Omenn et. al, Clearly, this much vitamin A does more harm than good.

The main causes of death were, as typical, cardiovascular disease and cancer. As the graph shows, the rates of death were higher among people getting the Vitamin A than among those getting nothing, the placebo. Why that is so is not totally clear, but I have a theory that I presented in a paper at Michigan state. The theory is that your body uses oxidation to fight cancer. The theory might be right, or wrong, but what is always noticed is that too much of a good thing is never a good thing. The excess deaths from vitamin A were so significant that the study had to be cancelled after 5 1/2 years. There was no responsible way to continue. 

Vitamin E is another popular vitamin, an anti-oxidant, proposed to cure cancer. As with the vitamin A study, a large number of people who were at high risk  were selected and given either a large dose  of vitamin or a placebo. In this case, 35,000 men over 50 years old were given either vitamin E (400 to 660 IU, about 20 times the RDA) and/or selenium or a placebo. Selenium was added to the test because, while it isn’t an antioxidant, it is associated with elevated levels of an anti-oxidant enzyme. The hope was that these supplements would prevent cancer and perhaps ward off Alzheimer’s too. The full results are presented here, and the key data is summarized in the figure below. As with vitamin A, it turns out that high doses of vitamin E did more harm than good. It dramatically increased the rate of cancer and promoted some other problems too, including diabetes.  This study had to be cut short, to only 7 years, because  of the health damage observed. The long term effects were tracked for another two years; the negative effects are seen to level out, but there is still significant excess mortality among the vitamin takers. 

Cumulative incidence of prostate cancer with supplements of selenium and/or vitamin E compared to placebo.

Cumulative incidence of prostate cancer with supplements of selenium and/or vitamin E compared to placebo.

Selenium did not show any harmful or particularly beneficial effects in these tests, by the way, and it may have reduced the deadliness of the Vitamin A.. 

My theory, that the body fights cancer and other disease by oxidation, by rusting it away, would explain why too much antioxidant will kill you. It laves you defenseless against disease As for why selenium didn’t cause excess deaths, perhaps there are other mechanisms in play when the body sees excess selenium when already pumped with other anti oxidant. We studied antioxidant health foods (on rats) at Michigan State and found the same negative effects. The above studies are among the few done with humans. Meanwhile, as I’ve noted, small doses of radiation seem to do some good, as do small doses of chocolate, alcohol, and caffeine. The key words here are “small doses.” Alcoholics do die young. Exercise helps too, but only in moderation, and since bicycle helmets discourage bicycling, the net result of bicycle helmet laws may be to decrease life-span. 

What about vitamins B, C, and D? In normal doses, they’re OK, but as with vitamin A and E you start to see medical problems as soon as you start taking more– about  12 times the RDA. Large does of vitamin B are sometimes recommended by ‘health experts’ for headaches and sleeplessness. Instead they are known to produce skin problems, headaches and memory problems; fatigue, numbness, bowel problems, sensitivity to light, and in yet-larger doses, twitching nerves. That’s not as bad as cancer, but it’s enough that you might want to take something else for headaches and sleeplessness. Large does of Vitamin C and D are not known to provide any health benefits, but result in depression, stomach problems, bowel problems, frequent urination, and kidney stones. Vitamin C degrades to uric acid and oxalic acid, key components of kidney stones. Vitamin D produces kidney stones too, in this case by increasing calcium uptake and excretion. A recent report on vitamin D from the Mayo clinic is titled: Vitamin D, not as toxic as first thought. (see it here). The danger level is 12 times of the RDA, but many pills contain that much, or more. And some put the mega does in a form, like gummy vitamins” that is just asking to be abused by a child. The pills positively scream, “Take too many of me and be super healthy.”

It strikes me that the stomach, bowel, and skin problems that result from excess vitamins are just the problems that supplement sellers claim to cure: headaches, tiredness, problems of the nerves, stomach, and skin.  I’d suggest not taking vitamins in excess of the RDA — especially if you have skin, stomach or nerve problems. For stomach problems; try some peniiiain cheese. If you have a headache, try an aspirin or an advil. 

In case you should want to know what I do for myself, every other day or so, I take 1/2 of a multivitamin, a “One-A-Day Men’s Health Formula.” This 1/2 pill provides 35% of the RDA of Vitamin A, 37% of the RDA of Vitamin E, and 78% of the RDA of selenium, etc. I figure these are good amounts and that I’ll get the rest of my vitamins and minerals from food. I don’t take any other herbs, oils, or spices, either, but do take a baby aspirin daily for my heart. 

Robert Buxbaum, May 23, 2019. I was responsible for the statistics on several health studies while at MichiganState University (the test subjects were rats), and I did work on nerves, and on hydrogen in metals, and nuclear stuff.  I’ve written about statistics too, like here, talking about abnormal distributions. They’re common in health studies. If you don’t do this analysis, it will mess up the validity of your ANOVA tests. That said,  here’s how you do an anova test. 

West’s Batman vs Zen Batmen

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“Holy kleenex Batman, it was right under our noses and we blew it.” I came of age with Adam West’s Batman on TV and a relatively sane Batman in the comic books. Batman was a sort of urban cowboy: a loner, but a law-abiding, honest loner. A proud American who was polite to the police and to the ordinary citizen. He was both good, and “nice.” Back then, as today, no one died by the hand of Batman, but that was largely because he worked with the police who made the final arrests

bat-buddah

More recent Batmen have been not nice, and arguably not good either. They do not work with the police but act above the law. Their ethos is not from US civics class, but from dark training in eastern monasteries by masters of kung fu. It’s a morality no one quite understands, not least himself. Quite literally, ‘He is a dark and stormy knight.’

A few days ago, I found this plastic Batman-Buddah for sale on e-Bay and I started wondering about how far our current movie Batmen have moved from those of the 60s. And on the deep, Zen thoughts that Batman now expounds on life and crime. These zen thoughts are pretty messed up, as psychologists have noted.

Example. In a recent Batman movie, Batman beats up an invasive wannabe wearing hockey pads. He gets asked: “What gives you the right? What’s the difference between you and me?” The response, “I’m not wearing hockey pads.” This is to say, the current Batman believe his physical prowess makes him above the law. Some more comments:
“Sometimes it’s only madness that makes us what we are.”
“That mask — it’s not to hide who I am, but to create what I am.”
“I won’t kill you, but I don’t have to save you.”

When he speaks to the Joker, it’s not clear which one is crazier. E.g.. Batman tells the Joker that he doesn’t kill because, “If you kill a killer, the number of killers remains the same.” To which Joker replies: “Unless you kill more than one….” That sounds sane to me.

By contrast. consider Adam West as Batman in the 1960s: “Underneath this garb, we’re perfectly ordinary Americans.” Another quote: “A reporter’s lot is not easy, making exciting stories out of plain, average, ordinary people like Robin and me.” Though this comment is “off” it’s nice to see that this Batman feels for peoples’ problems, respects their professions, and does not profess to be better than they are. He’s weird, but not a psychopath, and he leaves Gotham city pretty much the way you find it at the beginning of a comic or episode.

Not a classic Batmobile, but I like the concept.

Not a classic Batmobile, but I like it. Adam West’s Batman always strove to be socially responsible. 

By contrast, the current, dark, depressive Batmen always leave Gotham City in shambles, with piles of dead and destroyed buildings and infrastructure. Given the damage Batman does, you wonder why anyone calls for Batman; current Batmen never works with the police, quite.

And where’s Robin. To the extent that Robin appears at all, his relationship with Batman is more frenemy than ally. Batgirl too is mostly absent, and has changed. The original Batgirl was connected to the police. She was Barbara Gordon, Police Commissioner Gordon’s daughter, a positive female with a good relationship with her supportive, non-sexist father (an early version of Kim Possible’s dad) and with society as a whole. The current Batgirl appears is the butler’s daughter, and except for one brief appearance, you never see her, not at Wayne Manor, not anywhere. Somehow she’s Batgirl though it’s presented that didn’t know what her dad was up to.

Here are some real interactions between Adam West as Batman with Robin. He shows an interest in Robin’s education and well-being, something currently lacking:

AW Batman: “Haven’t you noticed how we always escape the vicious ensnarements of our enemies?” Robin: “Yeah, because we’re smarter than they are!”  Batman: “I like to think it’s because our hearts are pure.”

AW Batman: “Better put 5 cents in the meter.” Robin: “No policeman’s going to give the Batmobile a ticket.” Batman: “This money goes to building better roads. We all must do our part.”

Robin: “You can’t get away from Batman that easy!” AW Batman: “Easily.” Robin: “Easily.”
“Good grammar is essential, Robin.” Robin: “Thank you.” Batman: “You’re welcome.”

Robin/Dick: “What’s so important about Chopin?” Batman: “All music is important, Dick. It’s the universal language. One of our best hopes for the eventual realization of the brotherhood of man.” Dick: “Gosh Bruce, yes, you’re right. I’ll practice harder from now on.”

AW Batman: “That’s one trouble with dual identities, Robin. Dual responsibilities.”

“Even crime fighters must eat. And especially you. You’re a growing boy and you need your nutrition.”

“What took you so long, Batgirl?” Batgirl: “Rush hour traffic, plus all the lights were against me. And you wouldn’t want me to speed, would you?” Robin: “Your good driving habits almost cost us our lives!” Batman: “Rules are rules, Robin. But you do have a point.”

And finally, AW Batman: “I think you should acquire a taste for opera, Robin, as one does for poetry and olives.”

Clearly this Batman takes an interest in Robin’s health and education, and in Batgirl’s. Robin is his ward, after all, a foster child. And Batgirl is a protege, as well as the daughter of a friend.

The modern Batman claims, “It’s not who I am underneath, but what I do that defines me.” It’s, more or less, a quote from Karl Jung that shows pride in one’s art, but it also shows an attachment to job over self. This approach appeared in the olden days, in the form of Catwoman, a woman with her own moral code, and proud of it. Batman found her odious, abhorrent, and “insegrievious”. The only difference between her and the Joker, he says, is the amount of damage done. I’m sorry to find that recent, Zen Batmen and Supermen might as well be Cat-women, or Jokers. To quote Robin: “Holy strawberries, Batman, we’re in a jam.”

Robert Buxbaum, June 26, 2017. Insegeivious is a made-up word, and I love it. I also love the humor of Robin’s “holy xxx” comments.

you are what you eat?

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The simplest understanding of this phrase is that you should eat good, healthy foods to be healthy, and that this will make you healthy in body and mind.

The author of the study published this book against GM foods simultaneously with release of his paper.

The author of this book against unhealthy foods faked his analysis to support the book.

Clearly there is some truth to this. Crazy people look crazy and often eat crazy. Even ‘normal’ people, if they eat too much are likely to become fat, lazy, and sick. There is a socio- economic effect (fat people earn less), and a physiological evidence that gut bacteria affects anxiety and depression (at least in rats). My sense here is at the diet extremes though. There is little, or no evidence to suggest you can make yourself more intelligent (or kind or good) by eating more of the right stuff, or just the right foods in just the right amounts. A better diet can make you look better, but there is a core lie at work when you extend this to imply that the real you is your body, or so tied to your body that a healthy mind can not be found in a sickly body. But most evidence is that the mind is the real you, and (following Socrates) that beautiful minds are found in sickly bodies. I’ve seen few (basically, no) healthy poets, writers, or great artists. Neither are there scientists of note (that I can recall) who lived without smoking, drinking, and any bad habits. Many creative people did drugs. George Orwell smoked cigarette, and died of TB, but wrote well to the end. There is no evidence that bad writing or thinking can be improved by health foods. Stupid is as stupid does, and many healthy people are clearly dolts.

Not that it’s always clear what constitutes good health, or what constitutes good food for health, or what constitutes a good mind. Skinny people may be admired and may earn more, but it is not clear they are healthy. Yule Gibbons, the natural food guru died young of stomach cancer. Adele Davis, another the author of “eat right to be healthy,” died of brain cancer. And Jim Fix, “the running doctor” died young of a heat attack while running. Their health foods may have killed them, and that unhealthy foods, like chocolate and coffee can be good for you. It’s likely a question of balance. While a person will feel better who dresses well, the extreme is probably no good. Very often, a person is drawn after his self-image to be the person he pretends. Show me a man who eats only vegetarian, and I’ll show you someone who sees himself as spiritual, or wants to be seen as spiritual. And that man is likely to be drawn to acting spiritual. Among the vegetarians you find Einstein, George B. Shaw, and Gandhi, people who may have been spiritual from the start, but may have been kept to spirituality from their diets. You also find Hitler: spirituality can take all sorts of forms.

Ward Sullivan in the New Yorker

Ward Sullivan in the New Yorker. People eat, drink, and dress like who they are. And people become like those they eat drink and dress like.

Choice of diet also helps select the people you run into. If you eat vegetarian, you’re likely to associate with other vegetarians, and you will likely behave like them. If you eat Chinese, Greek, or Mexican food, you’re likely to associate with these communities and behave like them. Similarly, an orthodox Jew or Moslem is tied to his community with every dinner and every purchase from the kosher or halal store.

And now we come to the bizarre science of bio-systems. Each person is a complex bio-system, with more non-human DNA than human, and more non-human cells than human. A person has a vast army of bugs on him, and a similarly vast pool of bugs within him. Recent research suggests that what we eat affects this bio-system, and through it our mental state. For whatever the mechanism, show me someone who drinks only 30 year Scotch or 40-year-old French wine, and I’ll show you a food snob. By contrast, show me someone who eats good, cheap food, and drinks good, cheap wine or Scotch (Lauder’s or Dewar’s), and I’ll show you a decent person very much like myself, a clever man who either is a man of the people or who wants to be known as one.”Dis-moi ce que tu manges, je te dirai ce que tu es.” [Tell me what you eat and I will tell you what you are].

Robert E. Buxbaum, February, 2015. My 16-year-old daughter asked me to write on this topic. Perhaps she didn’t know what it meant, or how true I thought it was, or perhaps she liked my challenges of being 16.

Nerves are tensegrity structures and grow when pulled

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No one quite knows how nerve cells learn stuff. It is incorrectly thought that you can not get new nerves in the brain, nor that you can get brain cells to grow out further, but people have made new nerve cells, and when I was a professor at Michigan State, a Physiology colleague and I got brain and sensory nerves to grow out axons by pulling on them without the use of drugs.

I had just moved to Michigan State as a fresh PhD (Princeton) as an assistant professor of chemical engineering. Steve Heidemann was a few years ahead of me, a Physiology professor PhD from Princeton. We were both new Yorkers. He had been studying nerve structure, and wondered about how the growth cone makes nerves grow out axons (the axon is the long, stringy part of the nerve). A thought was that nerves were structured as Snelson-Fuller tensegrity structures, but it was not obvious how that would relate to growth or anything else. A Snelson-Fuller structure is shown below the structure stands erect not by compression, as in a pyramid or igloo, but rather because tension in the wires helps lift the metal pipes, and puts them in compression. The nerve cell, shown further below is similar with actin-protein as the outer, tensed skin, and a microtubule-protein core as the compress pipes. 

A Snelson-Fuller tensegrity sculpture in the graduate college courtyard at Princeton, where Steve and I got our PhDs

A Snelson-Fuller tensegrity sculpture in the graduate college courtyard at Princeton, an inspiration for our work.

Biothermodynamics was pretty basic 30 years ago (It still is today), and it was incorrectly thought that objects were more stable when put in compression. It didn’t take too much thermodynamics on my part to show otherwise, and so I started a part-time career in cell physiology. Consider first how mechanical force should affect the Gibbs free energy, G, of assembled microtubules. For any process at constant temperature and pressure, ∆G = work. If force is applied we expect some elastic work will be put into the assembled Mts in an amount  ∫f dz, where f is the force at every compression, and ∫dz is the integral of the distance traveled. Assuming a small force, or a constant spring, f = kz with k as the spring constant. Integrating the above, ∆G = ∫kz dz = kz2; ∆G is always positive whether z is positive or negative, that is the microtubule is most stable with no force, and is made less stable by any force, tension or compression. 

A cell showing what appears to be tensegrity. The microtubules in green surrounded by actin in red. If the actin is under tension the microtubules are in compression. From here.

A cell showing what appears to be tensegrity. The microtubules (green) surrounded by actin (red). In nerves Heidemann and I showed actin is in tension the microtubules in compression.

Assuming that microtubules in the nerve- axon are generally in compression as in the Snelson-Fuller structure, then pulling on the axon could potentially reduce the compression. Normally, this is done by a growth cone, we posited, but we could also do it by pulling. In either case, a decrease in the compression of the assembled microtubules should favor microtubule assembly.

To calculate the rates, I used absolute rate theory, something I’d learned from Dr. Mortimer Kostin, a most-excellent thermodynamics professor. I assumed that the free energy of the monomer was unaffected by force, and that the microtubules were in pseudo- equilibrium with the monomer. Growth rates were predicted to be proportional to the decrease in G, and the prediction matched experimental data. 

Our few efforts to cure nerve disease by pulling did not produce immediate results; it turns out to by hard to pull on nerves in the body. Still, we gained some publicity, and a variety of people seem to have found scientific and/or philosophical inspiration in this sort of tensegrity model for nerve growth. I particularly like this review article by Don Ingber in Scientific American. A little more out there is this view of consciousness life and the fate of the universe (where I got the cell picture). In general, tensegrity structures are more tough and flexible than normal construction. A tensegrity structure will bend easily, but rarely break. It seems likely that your body is held together this way, and because of this you can carry heavy things, and still move with flexibility. It also seems likely that bones are structured this way; as with nerves; they are reasonably flexible, and can be made to grow by pulling.

Now that I think about it, we should have done more theoretical or experimental work in this direction. I imagine that  pulling on the nerve also affects the stability of the actin network by affecting the chain configuration entropy. This might slow actin assembly, or perhaps not. It might have been worthwhile to look at new ways to pull, or at bone growth. In our in-vivo work we used an external magnetic field to pull. We might have looked at NASA funding too, since it’s been observed that astronauts grow in outer space by a solid inch or two, and their bodies deteriorate. Presumably, the lack of gravity causes the calcite in the bones to grow, making a person less of a tensegrity structure. The muscle must grow too, just to keep up, but I don’t have a theory for muscle.

Robert Buxbaum, February 2, 2014. Vaguely related to this, I’ve written about architecture, art, and mechanical design.

Slowing Cancer with Fish and Unhealth Food

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Some 25 years ago, while still a chemical engineering professor at Michigan State University, I did some statistical work for a group in the Physiology department on the relationship between diet and cancer. The research involved giving cancer to groups of rats and feeding them different diets of the same calorie intake to see which promoted or slowed the disease. It had been determined that low-calorie diets slowed cancer growth, and were good for longevity in general, while overweight rats died young (true in humans too, by the way, though there’s a limit and starvation will kill you).

The group found that fish oil was generally good for you, but they found that there were several unhealthy foods that slowed cancer growth in rats. The statistics were clouded by the fact that cancer growth rates are not normally distributed, and I was brought in to help untangle the observations.

With help from probability paper (a favorite trick of mine), I confirmed that healthy rats fared better on healthily diets, but cancerous rats did better with some unhealth food. Sick or well, all rats did best with fish oil, and all rats did pretty well with olive oil, but the cancerous rats did better with lard or palm oil (normally an unhealthy diet) and very poorly with corn oil or canola, oils that are normally healthful. The results are published in several articles in the journals “Cancer” and “Cancer Research.”

Among vitamins, they found something similar (it was before I joined the group). Several anti-oxidizing vitamins, A, D and E made things worse for carcinogenic rats while being good for healthy rats (and for people in moderation). Moderation is key; too much of a good thing isn’t good, and a diet with too much fish oil promotes cancer.

What seems to be happening is that the cancer cells grow at the same rate with all of the equi-caloric diets, but that there was a difference the rate of natural cancer cell death. More cancer cells died when the rat was fed junk food oils than those fed a diet of corn oil and canola. Similarly, the reason anti-oxidizing vitamins hurt cancerous rats was that fewer cancer cells died when the rats were fed these vitamins. A working hypothesis is that the junk oils (and the fish oil) produced free radicals that did more damage to the cancer than to the rats. In healthy rats (and people), these free radicals are bad, promoting cell mutation, cell degradation, and sometimes cancer. But perhaps our body use these same free radicals to fight disease.

Larger amounts of vitamins A, D, and E hurt cancerous-rats by removing the free radicals they normally use fight the disease, or so our model went. Bad oils and fish-oil in moderation, with calorie intake held constant, helped slow the cancer, by a presumed mechanism of adding a few more free radicals. Fish oil, it can be assumed, killed some healthy cells in the healthy rats too, but not enough to cause problems when taken in moderation. Even healthy people are often benefitted by poisons like sunlight, coffee, alcohol and radiation.

At this point, a warning is in-order: Don’t rely on fish oil and lard as home remedies if you’ve got cancer. Rats are not people, and your calorie intake is not held artificially constant with no other treatments given. Get treated by a real doctor — he or she will use radiation and/ or real drugs, and those will form the right amount of free radicals, targeted to the right places. Our rats were given massive amounts of cancer and had no other treatment besides diet. Excess vitamin A has been shown to be bad for humans under treatment for lung cancer, and that’s perhaps because of the mechanism we imagine, or perhaps everything works by some other mechanism. However it works, a little fish in your diet is probably a good idea whether you are sick or well.

A simpler health trick is that it couldn’t hurt most Americans is a lower calorie diet, especially if combined with exercise. Dr. Mites, a colleague of mine in the department (now deceased at 90+) liked to say that, if exercise could be put into a pill, it would be the most prescribed drug in America. There are few things that would benefit most Americans more than (moderate) exercise. There was a sign in the physiology office, perhaps his doing, “If it’s physical, it’s therapy.”

Anyway these are some useful things I learned as an associate professor in the physiology department at Michigan State. I ended up writing 30-35 physiology papers, e.g. on how cells crawl and cell regulation through architecture; and I met a lot of cool people. Perhaps I’ll blog more about health, biology, the body, or about non-normal statistics and probability paper. Please tell me what you’re interested in, or give me some keen insights of your own.

Dr. Robert Buxbaum is a Chemical Engineer who mostly works in hydrogen I’ve published some 75 technical papers, including two each in Science and Nature: fancy magazines that you’d normally have to pay for, but this blog is free. August 14, 2013