From: sbharris@ix.netcom.com(Steven B. Harris) Subject: Re: Your opinion on the best multivitamin available? Date: 20 Jul 1997 Newsgroups: sci.med.nutrition,sci.life-extension,misc.health.alternative Tom Matthews: >>1) VRP's EXTEND does have more biotin than LIFE EXTENSION MIX. I don't know why The Life Extension Foundation does not add more low cost biotin to their formula. Perhaps this comparison effort will cause them to do so.<< I think the main problem is that biotin is NOT low cost. It's pretty expensive as far as vitamins go. I suspect it's the MOST expensive per RDA. Biotin has a downside, of course, and that is that it's a necessary nutrient for many bacteria. I've sometimes wondered if one of the functions of avidin in eggwhite is not to sequester biotin so bacteria have a harder time growing inside the egg (which isn't always sterile). This is akin to what the human body does with iron in infections and inflammation, and for the same reason. Biotin, like iron, is not a nutrient you want to give to anyone fighting an infection. >> 2) The leading cause of death and disability amongst people over age 50 is arterial blood clotting. EXTEND has vitamin K that promotes blood clotting.<< As discussed in another post, I know of no reason to think that excess vitamin K promotes blood clotting. Vitamin K is involved in bone formation, however, and might be something people at risk for osteoporosis might want to be sure they get enough of. >: 3) EXTEND has boron, which is beneficial for most people. Boron can >: boost testosterone levels, which means a man with benign prostate >: enlargement of prostate cancer would not want to take EXTEND since >: the boron could worsen his condition. There was ONE study suggesting boron raises testosterone in post menopausal women. Has it been repeated? I can't find anything at all about boron in men, dispite a huge amount of hype in the male body-builder crowd. I think that boron is a fad which is vastly overrated. Steve Harris, M.D. From: sbharris@ix.netcom.com(Steven B. Harris) Newsgroups: sci.med.nutrition,misc.health.alternative Subject: Re: Natural versus synthetic vitamin supplements Date: 30 Dec 1997 10:45:48 GMT In <689tmk$g8e@bgtnsc03.worldnet.att.net> tonnyb@worldnet.att.net (Anthony Brea D.C.) writes: > >On 29 Dec 1997 18:39:58 GMT, fritz@sde.hp.com (Gary Fritz) wrote: > >>Bryan Shelton (bryan@shell.c-com.net) wrote: >>: However, I don't claim that my body has some kind of psychic ability >>: to tell a "natural" molecule of some vitamin from a chemically >>: IDENTICAL molecule from a synthetic source. >> ...and... >>: "Natural" and synthetic vitamin molecules are IDENTICAL. >> >>Yes, as far as it goes. The molecules found in the synthetic vitamin >>are (assuming they are properly synthesized) chemically identical to >>the equivalent molecule in the natural vitamin. If you **isolated** >>the molecule from the natural vitamin, I would assume it would work >>identically to the synthetic vitamin. >> >>Gary > >Not necessarily. > >Although synthetic vitamins may be identical to the natural in composition >and have identical chemical properties, the 3 dimensional configuration are >variable. The different arrangements are called isomers. Synthetic >preparations contain all possible configurations mixed together in equal >amounts. > >Isomers can be likened to a pair of gloves. Both gloves are identical in >compostion, size and shape but their 3 dimensional configuration differ. >Only one glove fits comfortably on each hand and they are not >interchangeable. > >Non-identical synthetic isomers often differ in their biological function. >In many cases the synthetic isomers are poorly functional, non-functional, >or antagonistic to the naturally occuring isomer. > >Anthony B The only cases I know of where this really happens is with vitamin E. If you buy the dl-tocopheral, made by DuPont or you get the 8 isomer stew, only one of which is the natural one. But if you buy the d-alpha, made by ADm (Archer-Daniel-Midlands, Supermarket to the world, yada), you get a semi-sythetic stuff with only one isomer in it-- the natural one. Every other vitamin I know if is synthesized as the correct sterio-isomer. Biotin and pantothenate are the correct d forms. Ascorbate is the correct L. B12 isn't even synthesized, but made by bacteria and used from that source by everyone. And many vitamins, like folate and niacin and B6 and beta carotene, don't even have stereoisomers. From: sbharris@ix.netcom.com(Steven B. Harris) Newsgroups: sci.med.nutrition Subject: Re: Artificial vitamins and minerals vs. natural Date: 15 Apr 1998 06:48:33 GMT In <35345148.CCA@tir.com> "J.A. Brown" <josquin@tir.com> writes: >But there's a real question how well most people can assimilate vitamins >that are chemically synthesized into mere analogs of the vitamins in real >food and how well they can assimilate minerals that are mined from the >ground. (The classic example is artificial calcium supplements, which are >mostly the same stuff as limestone, blackboard chalk, or plaster of >paris.) If you have to take 10 times as much of an artificial supplement >to get the same benefit as a natural supplement -- and also risk an upset >stomach in the process -- the cost advantage of the artificial stuff >fades pretty quickly. Yeah, but you'll have to give some examples. In most cases, the straight mineral from the ground works perfectly well (exception-- GTF). In fact, there are a lot of animals that GET their minerals from licking them off the face of a mountain. What-- I'm supposed to get fancy chelates while that goat or cow up there is licking up ore veins or salt deposits like a miner? Same with vitamins. Synthesized folate is more active than the forms found in foods, which have to be whittled down to size first before the body can use them. So why should you have to? You spend a lot of money for pyridoxal 5 phosphate, the primo vitamin B6. In your gut, you cleave off the phosphate anyway-- you might as well have taken pyridoxal. Then you have to put the phosphate back on again. Shoulda saved your money. Can you utilize NAD or NADH directly from your food, without breaking it down to niacinamide first? Evidence is not good that you can, dispite considerable hucksterism. And it's tens of thousands of times more expensive than the dirt cheap niacinamide, which is about a dollar a POUND industrially. So which should you take? Knowing that your body is fully capable of taking the industrial chemical and making NAD very efficiently? Knowing that you turn tryptophane into niacinamide in your body anyway, so this is not something it's unfamiliar with? When you take these super expensive-form vitamins, are you treating your cells, or your anxieties? Steve Harris, M.D. From: sbharris@ix.netcom.com(Steven B. Harris) Newsgroups: sci.med.nutrition,sci.med,misc.health.alternative,sci.med.pharmacy, sci.life-extension Subject: Re: Folate and B12 tox (was: Vitamin C , 500mg, harmful !!!!) Date: 19 Apr 1998 17:47:10 GMT In <35399E12.634F@itis.com> Brian Daly <bdaly@itis.com> writes: >Hello Steve, > >I've never heard of the active or passive dose ranges of vitamins. Is >it something that is true of many or all vitamins? It's true of most vitamins. The active range reflects the saturation of the body's active transport system. The passive range is how much more you can get in over that, by megadosing. B12 is a clearest example of how different the two can be. > Also, how in general >are studies done to determine recomended vitamin amounts, and what >effects vitamins have in the body? thanks, BD Too complicated a question to answer in general. See a good nutrition text, or a technical work like Machlin's Handbook of Vitamins. Your medical library will also have things like Nutrition Reviews, which are helpful. The RDAs (these days, RDI's) are set by the Food and Nutrition Board of the National Research Council of the National Academy of Sciences (U.S.), and differ a bit from FAO/WHO and European recommendations. The recommendations are based on all kinds of different approaches from all kinds of different evidence, and the arguing about recommendations can be intense, even in (especially in) the scientific bodies making the recommendations. No short and simple summary is possible. Steve Harris, M.D. From: sbharris@ix.netcom.com(Steven B. Harris) Newsgroups: sci.life-extension,sci.med.nutrition Subject: Re: vitamins during fast ???? Date: 12 Jul 1998 05:15:18 GMT In <35A6AD14.6B6B@netcom.ca> Tom Matthews <tmatth@netcom.ca> writes: >> Should I continue taking these during my fast ? Is it better not to >> take any vitamin supplements during a fast ?. > >However, if you are bound and determined to do it, it probably will not >hurt you. IMO, you should discontinue most of your vitamins during your >fast, perhaps continuing only with a bit of vitamin C. Maybe some of the >other water soluble/unstored ones also (B's). To really decide this >question one would need to look into the metabolic biochemical conditions >of the body during fasting. It may well be that certain vitamins are even >*more* necessary. I just don't know and I am not much interested except >from a curiosity/theoretical viewpoint. You body's need for vitamins continues during fasting, since of course all metabolic processes continue. You don't need quite as much of some vitamins (B2 and B3 comes to mind) because your energy use drops. Vitamin supplements taken will increase "duration time" to death in a water fast, in large animals such as humans, who can run out of vitamins before running out of energy on long fasts (more than a month). They don't help smaller animals with faster metabolisms when starving--- these critters (if they don't estivate or hybernate or go into torpor or something) invariably run out of energy first, and die from that. From: sbharris@ix.netcom.com(Steven B. Harris) Newsgroups: sci.med Subject: Re: sensitive to cold Date: 23 Feb 1999 00:28:47 GMT In <19990222114646.06128.00000664@ngol05.aol.com> shapere@aol.comicrelief (Shapere) writes: >BTW I have some B-complex around...it has: > >thiamin 50mg >riboflavin 50mg >niacin 50mg >pyridoxine 50mg >folate 400mcg >B12 50mcg >biotin 50mcg >pantothenic acid 50mg > >(Look okay?) I took one this morning; should it help immediately, or is >it one of those chronic dosing things? > >-elizabeth Dunno. Most of my patients who are trying to diet complain of the effect of vitamins pretty fast (by the next office visit). But I keep them on them on vitamins anyway (essential if you're not eating enough calories and are actually losing weight), and tell them to excercise more to make up for it. BTW, I get some complaints that B vitamins have a mild stimulatory action also, which is probably why most people instinctively insist on taking them in the AM, dispite sometimes not eating then (and therefore getting stomach irritation or poorer absorption.) So watch for that effect, and take them with the first food of the day. Doctor Sadisticus From: sbharris@ix.netcom.com(Steven B. Harris) Newsgroups: sci.med.nutrition Subject: Re: lots of questions Date: 29 Mar 1999 10:58:35 GMT In <01bc3b9d$c4a23400$c003ea18@pavilion.lvcablemodem.com> "vegas4" <petika@nospam.pclv.com> writes: >Hello there, > >I am fairly new to this newsgroup and have been studying nutrition >personally for a couple of years, but I am confused about a lot of things >and wonder if anyone out there might have some information for me. Let's >get started: > >1. How many vitamins are actually in our foods. I heard once that since >our soil is so depleted that our foods can't possibly have the nutrients >we think they have, then we prepare them and they lose even more. Are >there any facts out there regarding this? Lots of facts. Soil depletion has nothing to do with vitamin content, since vitamins are made in plants from air and water, basically. Plants don't make any vitamins that contain minerals, unless you count phosphate (a pretty common mineral). Plants don't make vitamins for animals (with the possibly exception of citrus fruits plants that make vitamin C to lure primates)-- they make them for themselves. If the plant is growing well, it has enough vitamins. Minerals are a different story, but even here most of it is the same. Only a couple of minerals (selenium being the main one) are definitely important to animals but not very important overall to the plant. Out of all the rest, the plant either needs the stuff as much as the eater does, or else the value of the mineral to animals is not well established, and/or natural deficiency syndromes from eating mineral poor plants have never even been described. >2. When we take vitamins, how much is actually being absorbed and used by >our bodies. Are the vitamins we take really what we think they are? Usually. Most vitamins now meet USP standards for dissolution. Your urine turns bright orange, which means that pill disolved, the B2 got into your blood and thence your kidneys, and so has been available to every cell. Most vitamins are well absorbed in pure form, if taken with a meal. If you doubt the dissolution part, put your favorite vitamin pill in a glass of plain water for a couple of hours. Or buy vitamins in gelatin capsules, which are guaranteed to disolve, and which contain very little but pure vitamin powders (my personal favorite being the Twinlab company's "Daily One" and "Daily Two" products (not to be confused with One-A-Day-- look for the Twinlab part), available at most health food stores and not a few large grocery chains. >3. I know certain vitamins work together and others don't i.e vitamin c >helps your body absorb iron while calcium doesn't. What about multiple >vitamins do you actully absorb everything with all the vitamins working >against each other? Yes. Nutrients "work against" each other in foods, too, remember! There is some antagonistic effect, but it's usually small. If you take RDAs of minerals (where the major antagonisms occur) it's not a problem, with the possible exception of calcium (where the RDA overwhelms the minor minerals). If you're taking calcium pills, I would probably not take any in the meal where you take the multivitamins. They themselves don't have room for enough calcium to cause problems (One-A-Day type multivits put calcium on the label only to make themelves look more complete to people who are novices on the subject). There are a few vitamins which attempt to separate all the nutrients with interactions (copper and zinc, for example) into two pills, to be taken AM and PM. Solovits and some other brands you can find in upscale retail stores are examples, and you can take these if the issue really bothers you mentally. But generally, it's not a major issue so long as you mind the caveats noted above. From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: alt.health,sci.med,sci.med.nutrition,sci.med.cardiology Subject: Free Radicals Bad! Antioxidants Good! Not. (was Re: Body Saturation with Vitamins (was Re: Green Tea) Date: Sun, 17 Feb 2002 16:50:02 -0700 Message-ID: <a4pfqs$au2$1@nntp9.atl.mindspring.net> "DB" <wired123@pacbell.net> wrote in message news:T4Qb8.574$aM2.572087481@newssvr21.news.prodigy.com... > Steve Harris wrote: > > COMMENT > > Well, pick one out. Your reason for taking any of these more than once a > > day is? > > I assume you are only speaking of vitamins and minerals. Not plant based > extracts, medications, or other nutrients that are found in the body. > Otherwise you would be quite mistaken, doc. > > One very obvious reason to take some multiple times is to increase the > amount absorbed in order to save money. COMMENT: These are therapeutic uses, however-- you're using them basically like drugs. Or else you're fiddling around with something really inefficient (a lycopene capsule nerd who could instead be having a marinara dish with olive oil). > Animals don't abuse their health, oh wise one. They live in a static, > stable environment with a healthy diet. COMMENT: So they do. And it's a great hypothesis that taking vitamins will protect you from all those nasty things you do to your body. Alas, the evidence is lacking. Atherosclerosis and Alzheimer's may be the two most interesting topics in nutritional prevention, and the animal models for both are lousy (for either expense or mechanistic reasons). > >> Simple! To keep your blood levels of vitamin c within a certain > >> quantitative range of possible values. > > > > COMMENT: > > Which you want to do, why? You're treating a number, you fool. There > > are no prospective trials of vitamin C in humans for any chronic > > disease, so how could you possibly know what any given number means? > > Was one of your parents a troll? You know damn well how damaging free > radicals are and it is basic common sense that loading up with a lot of > antioxidants will protect the body from some of this harm. COMMENT: This is no troll. I'm quite serious. Ever since Pearson and Shaw popularized the idea that free radicals were The Cause of All Disease and Aging in the early 80's, we've been on some kind of crazy bandwagon that free radicals are entirely bad, and the less of them you have, the better off you are. Well, it isn't true. For example a free-radical molecule called nitric oxide is used by the body as a major signal molecule for all kinds of things, including regulating blood flow. And that's not all-- this and other radicals are utilized by the body to kill bacteria, and to activate the inflammatory response. Which itself is a double-edged sword. Inflammation isn't all bad; nature gave it to you for a reason. Besides being necessary to fight bugs, inflammation activates healing and tissue growth as well. The more you abuse your body, the MORE you need it, in some ways. Finding the right balance is one of the key balancing acts that faces doctors every day in the ICU with patients who have septic shock (SIRS), ARDS, resuscitation encephalopathy, and so and so on. And in outpatient medicine as well. The COX-2 inhibitor which might be preventing your Alzheimer's disease is also preventing healing of ulcers in your stomach. And so on. Time for an illustration. You might suppose that since antioxidants are good for arteriosclerosis (everybody knows that, right), that adding a mix of them to heart disease patients who have lipid problems would be good for them, and keep them from having as many heart attacks. Well, if the lipid problems are low HDLs, the answer is that antioxidants don't do that much good. Statin-plus-niacin works far better. And if you should hedge by adding antioxidants TO the statin-plus-niacin, you cut the beneficial effect in half. Yep. Same study, beautifully controlled. Why is this?? We don't know. My own guess is that HDL is partly made in response to inflammation in the liver CAUSED by the near overdose levels of nicotinic acid necessary to induce it, and if you damp down that inflammatory response too much, you damp out niacin's ability to raise HDL. Wups. But whatever the reason turns out to be, the point still stands. I post the abstract below to illustrate the idea that you can NOT just cookbook your way out by dumping antioxidant vitamins on every medical problem. N Engl J Med 2001 Nov 29;345(22):1583-92 (Comment in:N Engl J Med. 2001 Nov 29;345(22):1636-7.) Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P, Frohlich J, Albers JJ. Department of Medicine, University of Washington School of Medicine, Seattle 98195, USA. BACKGROUND: Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. We studied simvastatin-niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of HDL. METHODS: In a three-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels and normal LDL cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, vitamins, simvastatin-niacin plus antioxidants; or placebos. The end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization). RESULTS: The mean levels of LDL and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by -42 percent and +26 percent, respectively) in the simvastatin-niacin group. The protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants. The average stenosis progressed by 3.9 percent with placebos, 1.8 percent with antioxidants (P=0.16 for the comparison with the placebo group), and 0.7 percent with simvastatin-niacin plus antioxidants (P=0.004) and regressed by 0.4 percent with simvastatin-niacin alone (P<0.001). The frequency of the clinical end point was 24 percent with placebos; 3 percent with simvastatin-niacin alone; 21 percent in the antioxidant-therapy group; and 14 percent in the simvastatin-niacin-plus-antioxidants group. CONCLUSIONS: Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels. The use of antioxidant vitamins in this setting must be questioned. Publication Types: Clinical Trial Randomized Controlled Trial > > No research published in JAMA says you should take vitamin C pills more > > than once a day. It'll be a red letter day when anybody writing in JAMA > > suggests taking vitamin C pills at all. > > Cuz they're all ultra-conservative wimps like you? We need more > theoretical nutrition researchers. Like in physics. Not ones who > continually spout crap like "There is no published evidence backing up > that claim." COMMENT: Theoretical nutrition researchers never would have done the trial above, because they would already have decided the results were in the bag. Oops, they weren't. The THEORY is very complicated. If you look at the cellular level at what vitamin C does, it isn't all nice, and the studies don't all show that the more of it you have the better off you are. I'll quote just one for illustration. Brain Res 2001 Mar 23;895(1-2):66-72 Related Articles, Books, LinkOut Oxidative stress induced by ascorbate causes neuronal damage in an in vitro system. Song JH, Shin SH, Ross GM. Department of Physiology, Botterell Hall, Queen's University, Kingston, Ontario, Canada, K7L 3N6. Of particular physiological interest, ascorbate, the ionized form of ascorbic acid, possesses strong reducing properties. However, it has been shown to induce oxidative stress and lead to apoptosis under certain experimental conditions. Ascorbate in the brain is released during hypoxia, including stroke, and is subsequently oxidized in plasma. The oxidized product (dehydroascorbate) is transported into neurons via a glucose transporter (GLUT) during a reperfusion period. The dehydroascorbate taken up by cells is reduced to ascorbate by both enzymatic and non-enzymatic processes, and the ascorbate is stored in cells. This reduction process causes an oxidative stress, due to coupling of redox reactions, which can induce cellular damage and trigger apoptosis. Ascorbate treatment decreased cellular glutathione (GSH) content, and increased the rates of lipid peroxide production in rat cortical slices. Wortmannin, a specific inhibitor of phosphatidylinositol (PI)-3-kinase (a key enzyme in GLUT translocation), prevented the ascorbate induced-decrease of GSH content, and suppressed ascorbate-induced lipid peroxide production. However, wortmannin was ineffective in reducing hydrogen peroxide (H(2)O(2))-induced oxidative stress. The oxidative stress caused ceramide accumulation, which was proportionally changed with lipid peroxides when the cortical slices were treated with ascorbate. These differential effects support the hypothesis that GLUT efficiently transports the dehydroascorbate into neurons, causing oxidative stress. PMID: 11259761 [PubMed - indexed for MEDLINE] Now, this is just cells in a jar, but you were talking about THEORY, weren't you? How theoretical do you really want to be? SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: alt.health,sci.med,sci.med.nutrition,sci.med.cardiology Subject: Re: Free Radicals Bad! Antioxidants Good! Not. (was Re: Body Saturation with Vitamins (was Re: Green Tea) Date: Mon, 18 Feb 2002 12:00:00 -0700 Message-ID: <a4rj7e$gv$1@slb7.atl.mindspring.net> "Jay Tanzman" <jtanzman@sph.llu.edu> wrote in message news:3C7140B9.D8404AC5@sph.llu.edu... > > > Steve Harris wrote: > > > N Engl J Med 2001 Nov 29;345(22):1583-92 (Comment in:N Engl J Med. > > 2001 Nov 29;345(22):1636-7.) Simvastatin and niacin, antioxidant > > vitamins, or the combination for the prevention of coronary disease. > > > > Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, > > Marino EK, Bolson EL, Alaupovic P, Frohlich J, Albers JJ. > > > > BACKGROUND: Both lipid-modifying therapy and antioxidant vitamins are > > thought to have benefit in patients with coronary disease. We studied > > simvastatin-niacin and antioxidant-vitamin therapy, alone and > > together, for cardiovascular protection in patients with coronary > > disease and low plasma levels of HDL. METHODS: In a three-year, > > double-blind trial, 160 patients with coronary disease, low HDL > > cholesterol levels and normal LDL cholesterol levels were randomly > > assigned to receive one of four regimens: simvastatin plus niacin, > > vitamins, simvastatin-niacin plus antioxidants; or placebos. ... > > I wouldn't call a single trial with 40 persons per treatment arm > conclusive, but this is certainly interesting. > > -Jay These are groups of 40, which means that any given comparison (trial) of one treatment vs another contains 80 patients. Sure, the absolute number goes into the pot, but it's balanced by the size of the effect. That's what we have p values for, don't you know. An N of 80 is certainly large enough to have a decent p value. And a randomized blinded controlled prospective study of 80 is worth any number of retrospective uncontrolled epidemiologic regressions, no matter how large. Yes, the finding of the study will need to be confirmed independently before we take it as gospel. There's always the possiblility of sampling bias, or error, or fraud. SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: alt.health,sci.med,sci.med.nutrition,sci.med.cardiology Subject: Re: Free Radicals Bad! Antioxidants Good! Not. (was Re: Body Saturation with Vitamins (was Re: Green Tea) Date: Mon, 18 Feb 2002 13:53:02 -0700 Message-ID: <a4rpra$287$1@slb2.atl.mindspring.net> "Jay Tanzman" <jtanzman@sph.llu.edu> wrote in message news:3C7155BF.5C2887DF@sph.llu.edu... > In a small trial (eg, 40 x 40), the p-value can be small due to >confounding. Comment: yes, but the odds are against it. That is precisely what the p value tells you: the odds of your accidentally "confounding" (I'm not sure I'd use this word here) your study by sampling error with respect to causal agents, when you randomize groups. It doesn't protect against some hidden bias if you didn't sample blindly, and it doesn't guarantee that your result is inductively valid across all groups (much less the one you "think" you sampled). But it does protect you against randomization sampling errors. That's the point. >In a trial of this size, simple randomization cannot be relied on to >control for confounding. Why not? You can rely on it to the limit of your p value. It's never 100%, but it's more than 95% and often more than 99%. > (For this reason, incidentally, a small RCT may be more confounded than > a large _prospective_ observational study which has been controlled in > the analysis.) Why is that? You can never know if you're controlled post-hoc for all the confounders. On the other hand, you can pretty much guarantee (to the limit of p) that you've randomized all the ones you don't know about, IF you randomize. Sample variances should be caused by variables you don't know about and can't control. That's the whole IDEA of randomizing. I presume that people publishing in NEJM will have pre-stratified for anything already strongly known to influence outcome in such a study. And/or will do post-hoc control tests for things they didn't, but knew about and were suspicious of. SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.med.nutrition,sci.med,misc.health.alternative, sci.life-extension,sci.med.cardiology Subject: The Many Faces of Vitamin C (was Re: Half-life of vitamins in the body - was Re: Green Tea) Date: Mon, 18 Feb 2002 15:09:55 -0700 Message-ID: <a4rubk$3v2$1@nntp9.atl.mindspring.net> "Brandon J. Van Every" <vanevery@3DProgrammer.com> wrote in message news:od2c8.18694$P21.1760944@newsread1.prod.itd.earthlink.net... > Another thought from the peanut gallery. I have no nutritional > knowledge, I am a computer programmer. But why are you guys fixating on > the input levels of vitamin C vs. the output levels in the urine? What > if maintaining vitamin C at some threshold in the body for some period > of time has a *side effect* ? Sets off some process that ordinarily > doesn't occur or something. Maybe a healthy process. The vitamin gets > flushed out pronto, it may not be relevant, but the process it sets in > motion may be. COMMENT: There's no way to tell, but with a prospective randomized study. Retrospective epidemiology is good for ruling out causal relations, but it's very poor evidence for ruling them in, due to the possiblity of confounders. And that's even when it's used properly-- when in many cases it isn't. For instance vitamin C tissue levels don't correlate at all with cardiovascular disease in the NHANES II except in people who drink quite a lot of alcohol. If you control for alcohol you get no significant effect, and that's quite _strong_ evidence that if vitamin C has any big pro-vascular-health effect in non-drinkers, it can't be _large_, or else it would have to show up here. That should make people think about no drinking so much (and not drinking anything but red wine when they DO drink) before it makes them think of popping vitamin C pills. As for vitamin C plasma levels, if you ignore drinking, they weakly correlate with cardiovascular disease risk across very broad ranges from lowest to highest, but that doesn't mean there's any epidemiologic difference between cardiovascular disease at (say) the levels you equilibrate at, when you take a pill once a day, and your average higher levels when you take MORE than one pill a day. We do have a confused person here who thinks that a curve drawn through many points can be taken as gospel across levels at the high end of the curve-- but he is (well) a confused person. Ignore this stuff. Now let me note some hair-raisers, while we're at it. Vitamin C may epidemiologically decrease vascular risk in male drinkers a little, but the exact same evidence from the exact same study suggests that vitamin C intake increases risk of CANCER in women a LOT. You don't get to pick which one you're going to believe, if you insist on believing every positive correlation you get from post-hoc retrospective epidemiology. Taking this stuff at face value, you might conclude that vitamin C pills might (say)) protect a male Nobel Prize Winner from vascular disease and let him die in old age, but (at the same time) might kill his wife with some nasty tumor <here I look at sky innocently and whistle>. But read the following and see what you think. And don't listen to everyone who says they're a health expert. There's no substitute for reading the studies yourself, and knowning a bit about statistics. And for being wise about that fact that there are few panaceas in life. SBH ========================= J Am Coll Nutr 2001 Jun;20(3):255-63 Related Articles, Books, LinkOut Relation of serum ascorbic acid to mortality among US adults. Simon JA, Hudes ES, Tice JA. General Internal Medicine Section, Veterans Affairs Medical Center, San Francisco, California 94121, USA. jasimon@itsa.ucsf.edu PURPOSE: To examine the relation between serum ascorbic acid (SAA), a marker of dietary intake (including supplements), and cause-specific mortality. SUBJECTS AND METHODS: We analyzed data from a probability sample of 8,453 Americans age > or = 30 years at baseline enrolled in the Second National Health and Nutrition Examination Survey (NHANES II), who were followed for mortality endpoints. We calculated relative hazard ratios as measures of disease association comparing the mortality rates in three biologically relevant SAA categories. RESULTS: Participants with normal to high SAA levels had a marginally significant 21% to 25% decreased risk of fatal cardiovascular disease (CVD) (p for trend = 0.09) and a 25% to 29% decreased risk of all-cause mortality (p for trend <0.001) compared to participants with low levels. Because we determined that gender modified the association between SAA levels and cancer death, we analyzed these associations stratified by gender. Among men, normal to high SAA levels were associated with an approximately 30% decreased risk of cancer deaths, whereas such SAA levels were associated with an approximately two-fold increased risk of cancer deaths among women. This association among women persisted even after adjustment for baseline prevalent cancer and exclusion for early cancer death or exclusion for prevalent cancer. CONCLUSIONS: Low SAA levels were marginally associated with an increased risk of fatal CVD and significantly associated with an increased risk for all-cause mortality. Low SAA levels were also a risk factor for cancer death in men, but unexpectedly were associated with a decreased risk of cancer death in women. If the association between low SAA levels and all-cause mortality is causal, increasing the consumption of ascorbic acid, and thereby SAA levels, could decrease the risk of death among Americans with low ascorbic acid intakes. PMID: 11444422 [PubMed - indexed for MEDLINE] From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.life-extension,sci.med,sci.med.nutrition Subject: Re: Money Talks in Science :-( Date: Sun, 3 Mar 2002 12:06:52 -0800 Message-ID: <a5tvn6$85m$1@slb2.atl.mindspring.net> Mark wrote in message <36db9135.0203030302.15a71430@posting.google.com>... >"Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> wrote in message news:<a4skur$jv3$1@nntp9.atl.mindspring.net>... > > >> Taking them isn't quite the issue (though it is a separate issue). The >> question before us is why act as though you need to take a vitamin pill >> every few hours or you're going to turn white and your teeth fall out by >> morning. That's using vitamins like religious talismans, not as gifts of >> science. The best that can be said of it is that it's using vitamins as >> pharmaceuticals-- when there's no particularly good evidence that they do >> anything for your general health when used that way. >> >> <whack> <plonk> > > > >I believe for the same reason most people wouldn't eat a single 3000 >kcal meal as their daily food intake. Just a thought. :O) COMMENT: Of course you can get by eating just once a day, though it's not terribly comfortable for a lot of people. Still, you should acknowledge that comfort is really the only issue here, too-- not health. Or are you suggesting that if you eat 1000 kcal three times a day rather than 3000 kcal once a day, that you'll somehow be healthier? I deny it, and defy you to find me prospective calorie-intake-controlled evidence for it. I hope you're not going to claim that continuous eating is likely to make you age more slowly? Sorry, but the best evidence in aniamls is actually that it makes no difference either way; it's the balance of weekly calories vs. metabolic demand that has the aging effect, and eating frequency is not a variable. You get the same anti-aging benefits of a restricted diet if you feed three times a day in mice, as if you feed three times a week, so long as the diets are isocaloric. Those studies were done by Nilsen at al more than a decade ago. This whole thing reminds me of the Diet for a Small Planet flap of 30 years ago, wherein the gurus thought you had to have some kind of amino-acid complete protein for every meal, and spent all their time spinning out complicated rice+beans or legume+corn recipes for their followers. It was all a complete obsessive-compulsive waste of time! Your body is cleverer than that, when it comes to amino acid storage. And when it comes to micronutrient storage, it's cleverer still. Though if you'd like to do this, or wash your hands 20 times a day, or some other complicated ritual, in order to keep you from thinking about your own old age and death or something, be my guest. But recognize that it's a quirk or fetish or religion at best, a mental illness at worst. You have little enough time as it is. I suggest you spend it on things where the payoff is better. For the time, effort, and money it takes you to take supplements more than once a day, you can make considerable traction in likely the more important questions of what nutrient supplements to take. SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.med.nutrition Subject: Re: Five Questions for Steve Harris Date: Fri, 8 Mar 2002 17:49:05 -0800 Message-ID: <a6bpl3$c4n$1@slb6.atl.mindspring.net> Michael Stevens wrote in message ... >This brings me to the subject of this post- Five questions for Steve >Harris > >1) Do you personally take the lef extension mix or any other >multi-vitamin? I currently take Twinlab's "Daily One without iron" 3x a week (Mon-Wed-Fri). I'd be tempted to take it more, but I suspect the body needs a vacation from supplements, and I know my own certainly needs a vacation from 200 mcg a day of selenium (which is what this gives you if you take it EVERY day). I get garlicy sweat and aftertaste at those levels-- probably a personal biochemical quirk. So this is a good compromise. I've also recently been taking an extra 800 mcg of folate/day in an attempt to see how low I can push my homocysteine levels. Answer is that this gets me down to 5.7 umole/L from the previous 9, which is pretty good. So I may continue it indefinitely. Folate is cheap. My current supplement is Target stores generic 400 mcg pills (500 for about $5 if I remember correctly). >2) Any opinion on DHEA supplementation? Seems a risky thing to do for the few proven benefits (a mood elevator for middle aged women?). Long term studies are conspicuously lacking. >3.) Do food-based vitamins have any advantages over synthetic vitamins? None to my knowledge. There are some synthetic molecules which have no vitamin activity (xxS-tocopherols, for example-- none of the isomers with the kink between the croman ring and side-chain are active). The question here is whether it's worth the money to pay NOT to eat the inactive stuff. I don't know, but it's not that much more to buy a multi with only the RRR, so I do. It's still likely semi-synthetic, of course. The general rule is that almost all vitamins in supplements (with a few exceptions like biotin and B12) are synthetic. >4.) Do you believe the obesity epidemic has anything to do with the >increase in SSRI usage among the general population ( is there a >serotonergic link)? Not directly, as all the SSRIs have been pretty neutral with regard to (long term) weight loss or gain. It may well be that the same stresses that cause people to take SSRIs also cause them to overeat (the comfort in comfort foods is serotonin production). And the lower self esteem of the obese certainly makes them targets for SSRIs. But the underlying problems are high-fat easily-available junk foods and lack of exercise. No news there. I'm 15 lbs overweight myself, and in the process of removing it. I wish there were some magic answers! You simply have to deliberately exercise and stop the junk food completely. Alas! >5.) Do you think any of the stuff currently promoted as the next big >thing nutritionally (DHEA, CLA, Grape Seed Extract, etc.) will >actually turn out to be of any real benefit? I'd be surprised if any of the pills will turn out to be useful for the average person. Which is not to say that the same will turn out to be true of foods or food classes. On the strength of consistently good epidemiology I eat extra nuts, fruit, fish, vegetables (which I hate, but partly cheat by drinking V8 like it was a vitamin), and red wine for the nightcap. >Steve, take six months off posting and write a book on nutrition. >Seriously... Seriously, the world does not need (or rather, would not appreciate) another nutrition book. Particularly not a sober one. However, I'm thinking about doing one on resuscitation, which is the area where my current research lies. Again, thanks for the kind word. SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.med.nutrition Subject: Re: Five Questions for Steve Harris Date: Sat, 9 Mar 2002 15:33:37 -0800 Message-ID: <a6e638$4ms$1@slb2.atl.mindspring.net> Bruce Bowen wrote in message ... >"Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> wrote in message news:<a6bpl3$c4n$1@slb6.atl.mindspring.net>... >> >> I've also recently been taking an extra 800 mcg of folate/day in an >> attempt to see how low I can push my homocysteine levels. Answer is >> that this gets me down to 5.7 umole/L from the previous 9, which is >> pretty good. So I may continue it indefinitely. Folate is cheap. >> >> SBH > > Any "self" data for TMG? > > The local "Whole Foods Market" sells a supplement called >"Homocysteine Modulators" by "Solgar" that consists of (per pill): > >B6 25 mg 1250% >B12 250 ug 4166% >Folic Acid 200 ug 50% >TMG 500 mg (from beets) >Pyridoxal-5-Phosphate 3 mg >Dibencozide 3 mg That last being another form of B12: the adenosyl-coenzyme version. Making you wonder why they didn't used the methyl-B12 version if this is a homocysteine lowering formula ;-(. The "B-12" in the formula is undoubtedly cyanocobalamin. The P5P is in homeopathic doses, and it's kind of a silly supplement anyway. Your body cleaves off the phosphate on absorption, and then what's the evidence that pyridoxal does anything for you that pyridoxine doesn't? Are there really people who have difficulty making enough pyridoxal from megadoses of pyridoxine? I doubt that very much. If I had to lower my homocysteines any more, methyl-B12, then TMG are what I'd try next. But I've never had to. I've put a few patients on TMG (betaine) formulas whose homocysteines were resistant to further lowering with vitamins, and so far as I can tell, it did nothing. I should do another medline search to see if any additional evidence for this maneuver has turned up. SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.med.nutrition Subject: Re: Five Questions for Steve Harris Date: Sun, 10 Mar 2002 19:55:36 -0700 Message-ID: <a6h6ga$ov4$1@slb3.atl.mindspring.net> "Michael" <mikalra@lycos.com> wrote in message news:69779556.0203101027.71055418@posting.google.com... > Yes. Note the dosage, however: 6g. Every clinical trial I have ever > seen which has shown TMG to work uses doses within a couple of grams > of this (eg 1-4). By contrast, nearly all supplements (as eg the one > referenced in a previous post) are yielding a daily dose in the 1-2 g > range. > > Siunce, per the above trial, TMG doesnt' have all THAT big an impact > on Hcy in normals, even at 'proper' doses, it's unlikely that 1500 mg > is gonna do diddley in those not suffering with very specific genetic > or nutritional problems. That's probably it-- 1500 mg/d was what I was using. On my next tough case I'll push it to 6 g/d. But yikes, that's going to be expensive. Somebody needs to make a cheap TMG/betaine only supplment without all the extra junk in it, so you can do this easily. Note for would-be sophisticates: the pronunciation of betaine is BEET-uh-een. It was originally derived from beets, and since it's trimethylglycine, the "ine" is pronounced as in "glycine." SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.life-extension,sci.med.nutrition Subject: Re: EU vitamin ban -can cutting vitamin intake be dangerous? Date: Mon, 18 Mar 2002 14:08:32 -0700 Message-ID: <a75l78$d56$1@nntp9.atl.mindspring.net> "suzee" <qiuser@nidlink.com> wrote in message news:3C958641.45C3@nidlink.com... > CharlesSWaters wrote: > > > > RDA is minimum, not optimum. > > > > -- > > As I understand it, the RDA is what will keep you alive - not > necessarily in the best of health. It used to be called the *minimum* > daily allowance. The name was changed to *required* which makes one > think that's all that's needed. > > sue No. The only kind of "RDA" that still exists, the Recommended *DAILY* Allowance, is set at the top of the DRI (Dietary Reference Intake) range for most (ie, nonpregnant o lactating) people. That RDailyA is still around so that authorities can have a single number they can put on the side of a box, with a % of that, per serving. This number is the one for the age group which needs the most of that stuff (except for pregnant or lactating women) and will be high for most all other groups (except as noted). Effectively, the RDailyAs are usually set by the needs of men, except for calcium, which is set a little higher, due to the needs of women. It was the old RDA, the Recommended DIETARY Allowance, was less than our modern version of the RDA, but still not a minimum. The DRI takes into account age and reproductive status, and is a range, all less than the RDailyA (except as noted). None of these numbers is a minimum, but rather the number likely to result in good body loading for a given nutrient, for nearly everyone described in the reference population. The idea of RDAs (of either sort) as a minimum was always a big nutritional myth, however. Nutritionists have always known better, but the public still hasn't gotten the message. SBH From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com> Newsgroups: sci.med.nutrition Subject: Re: why biotin dosage is low ? Date: Tue, 11 Jun 2002 16:21:20 -0700 Message-ID: <ae60t6$8bh$1@slb5.atl.mindspring.net> campaign wrote in message ... >...even in multi-vitamin products that have 100% of most vitamins (like >Centrum), the level of biotin is always low. Why? Does biotin interfere >with other vitamins? No, it's merely expensive. Try a nice high quality vitamin like Twinlab Daily One, and you'll see more biotin. -- I welcome email from any being clever enough to fix my address. It's open book. A prize to the first spambot that passes my Turing test. From: Steve Harris <sbharris@ix.netcom.com> Newsgroups: alt.health,misc.health.alternative,sci.med.nutrition Subject: Re: Alternative treatments for progressive heart failure? Date: 10 Aug 2005 19:12:32 -0700 Message-ID: <1123726352.899880.92280@o13g2000cwo.googlegroups.com> George Lagergren wrote: > "Nor" <Nor@mindless-dot-com.no-spam.invalid> wrote: > > My father only has 30% of his heart working and he was recently > > diagnosed with progressive heart failure. The doctors told him there > > was nothing else they could do. Is anyone aware of any treatments for > > PHF? > > Perhaps taking a "food-form" type nutritional supplements from > Standard Process may help. > SP makes "food-form" vitamins like natural Vitamin B complex (which > includes Vitamin B-4) and natural Vitamin E complex (which includes > Vitamins E-2 & E-3). COMMENT: Snake oil. From a company that does "reflex testing", sells Willard water, and does "body scans" (no CT or MRI involved). The Standard Process products contain "whole foods." And they would dearly like you to believe the vitamins are extracted or entirely derived from whole foods. If you don't read the fine print. No vitamin company gets their vitamins from foods. No vitamin company could afford to. Vitamin "B4" was a scientific mistake, and no such thing exists (anymore than B7. B8, B9, B10, or B-11. Or B13 or 15). There is no vitamin E-2 or E-3, just various vitamers of vitamin E, don't have numbers. And finally, since vitamin E as d-alpha tocopherol increased heart failure in the HOPE trial, and did no good for the otherwise, it's the LAST thing you'd want to take if you had heart failure. Diabetes Care. 2002 Nov;25(11):1919-27. Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. Lonn E, Yusuf S, Hoogwerf B, Pogue J, Yi Q, Zinman B, Bosch J, Dagenais G, Mann JF, Gerstein HC; HOPE Study; MICRO-HOPE Study. Department of Medicine and Population Health Institute, McMaster University, Hamilton, Ontario, Canada. lonnem@mcmaster.ca OBJECTIVES: Experimental and observational studies suggest that vitamin E may reduce the risk of cardiovascular (CV) events and of microvascular complications in people with diabetes. However, data from randomized clinical trials are limited. Therefore, we evaluated the effects of vitamin E supplementation on major CV outcomes and on the development of nephropathy in people with diabetes. RESEARCH DESIGN AND METHODS: The Heart Outcomes Prevention Evaluation (HOPE) trial is a randomized clinical trial with a 2 x 2 factorial design, which evaluated the effects of vitamin E and of ramipril in patients at high risk for CV events. Patients were eligible for the study if they were 55 years or older and if they had CV disease or diabetes with at least one additional coronary risk factor. The study was designed to recruit a large number of people with diabetes, and the analyses of the effects of vitamin E in this group were replanned. Patients were randomly allocated to daily treatment with 400 IU vitamin E and with 10 mg ramipril or their respective placebos and were followed for an average of 4.5 years. The primary study outcome was the composite of myocardial infarction, stroke, or CV death. Secondary outcomes included total mortality, hospitalizations for heart failure, hospitalizations for unstable angina, revascularizations, and overt nephropathy. RESULTS: There were 3,654 people with diabetes. Vitamin E had a neutral effect on the primary study outcome (relative risk = 1.03, 95% CI 0.88-1.21; P = 0.70), on each component of the composite primary outcome, and on all predefined secondary outcomes. CONCLUSIONS: The daily administration of 400 IU vitamin E for an average of 4.5 years to middle-aged and elderly people with diabetes and CV disease and/or additional coronary risk factor(s) has no effect on CV outcomes or nephropathy. Publication Types: Clinical Trial Multicenter Study Randomized Controlled Trial PMID: 12401733 [PubMed - indexed for MEDLINE] From: Steve Harris <sbharris@ix.netcom.com> Newsgroups: sci.med.nutrition Subject: Re: Vitamin pill assimilation Date: 12 Sep 2005 13:49:02 -0700 Message-ID: <1126558142.346971.143970@o13g2000cwo.googlegroups.com> OmManiPadmeOmelet wrote: > > COMMENT: > > As noted, you're seeing a metabolite of B2, which is yellow. Yes, this > > is a good index of how fast all the you take vitamins hit your blood > > stream, and how fast the excess of those that are water-soluble get > > dumped overboard by the kidneys, when they hit the blood in large > > amounts. > > > > That's how fast ALL nutrients in a meal are assimilated, sorted, > > metabolized, stored and otherwise dealt with, also. Pretty fast. 6-8 > > hours, and it's over with. > > > > SBH > > And this is WHY B vitamins need to be taken daily...... > -- > Om. Well, they don't. And neither does vitamin C. Just because your body dumps excess over stored amounts fast, doesn't mean it dumps the amount IN your stores just as fast. That's a common mistake that's been around a very long time. Never make the mistake of thinking something your body needs to survive, has ONE excretion half-life. In general, that's NEVER going to be right. For vitamin C, if you exceed your renal threshhold, the half-life of the extra is measured in hours. But once you get down to the top of your storage level the excretion and use half-life goes up to days, and then (as you eat into your stores) at least 3 weeks. B vitamins act similarly. The times are different but the principles are the same. If you got no B vitamins at all beyond one megadose tablet every couple of weeks, you'd do just fine. Amounts absorbed at one time (10 to 20 mg) compared with amounts used in a day (a 1 mg or so), compared with body stores of B vitamins (many 10's of mg for most of them), gives you the general time scale idea. SBH |
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