Multivitamin Scares. (was Re: How about supplemental calcium??)
Steve Harris
"David Rind" <dr...@caregroup.harvard.edu> wrote in message
news:b9448e$kv6$1...@reader1.panix.com...
> Walter E. wrote:
> > I read the recent story (and the thread in this NG)
regarding the dangers
> > associated with excess vitamin intake.
> >
> > I am a 74 yo male. I told my wife "I told you so" and I
stopped taking
> > my worthless One-a-day vitamins. Needless to say that we
eat a well balanced
> > diet with lots of fruit and vegies. We are reasonably
healthy.
> >
> > Now, what do I do with the calcium supplement pills that
have been foisted
> > on me for years? Is there any valid reason for routinely
chewing calcium
> > tablets? Am I going to collapse in a boneless heap if I
stop taking extra
> > calcium to the tune of 1500 mg a day?
> >
>
> I didn't read the recent thread in this ng, but while
there are
> reasons to be cautious about certain vitamins
(particularly vitamin
> A, both as beta carotene and retinol for somewhat
different reasons),
> I don't think going to the other extreme of "all vitamin
supplements
> are worthless or harmful" is justified by the evidence.
Comment:
Hear, hear. We recently got a spate of amazingly stupid
anti-multivitamin articles, based on just two very small
pieces of evidence:
1) Pre-formed vitamin A is more toxic than we thought, with
problems occurring in supplementation very near the RDI
dose.
2) Vitamin E supposedly increases stroke risk.
The first is interesting but old news, in a sense. We all
knew pre-formed retinyl palmitate type vitamin A supplements
were not that great an idea, and that is why the best
supplements (Twinlab Daily One, for example, which I take)
have the A as beta-carotene. There are large safety studies
on beta carotene, and it's not dangerous except possibly in
smokers. The body makes only as much retinol out of beta
carotene as it needs, and retinol bone toxicity does NOT
occur with beta carotene. There is some evidence that
beta-carotene may influence the risk of smokers getting lung
cancer, possibly through it's conversion to retinoic acid, a
growth factor for epithelial cells and perhaps a cancer
promoter. Vitamin-wise I think smokers would be smarter to
supplement with B-complex and C only.
The stuff about vitamin E and stroke qualifies are nearly an
outright lie. ONE study from Finland has found a risk in
smokers ONLY of combination of antioxidants related to
stroke-- any they had slightly more of ONE TYPE of stroke,
the hemorrhagic type stroke, but made up for it by having
fewer of the thrombotic type. Overall, antioxidants seemed
to be positively affect risk of total stroke in those at
risk for stroke (not only smokers). Thus, smokers with high
blood pressure at risk for the hemorrhagic type stroke might
think about avoiding E supplements (this is megadose E here,
not the amount in the usual one a day vitamin). But we can't
even say that for sure. Vitamin E reminds one of aspirin,
here.
The very best quality evidence we have for the effect of
megadose (400 IU) vitamin E on stoke and other
cardiovascular endpoints, is the large randomized
prospective placebo control HOPE trial. In that trial,
vitamin E flunked out, with no effect on any cardiovascular
endpoint, either positive OR negative (including in the
smokers). This was rather surprising in view of the
epidemiology (high blood levels of E are epidemiologically
associated with low stroke and cardiovascular risk), but at
least HOPE shows once and for all that vitamin E even in
megadoses can't be very dangerous.
So there you are. Take your multivitamin, so long as it has
only beta carotene for the A and no retinyl palmitate. If
you're a smoker, don't take vitamin A supplements of any
kind, including those in multivitamins. If you smoke, you
might consider the all-B-with-C type vitamin, with a
multimineral. Whether or not an extra vitamin E pill will
hurt or help you is up for grabs.
Steve Harris, MD
Nelson J. Navarro
"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
news:b96qvf$mjq$1...@slb3.atl.mindspring.net...
>
>
> The very best quality evidence we have for the effect of
> megadose (400 IU) vitamin E on stoke and other
> cardiovascular endpoints, is the large randomized
> prospective placebo control HOPE trial. In that trial,
> vitamin E flunked out, with no effect on any cardiovascular
> endpoint, either positive OR negative (including in the
> smokers). This was rather surprising in view of the
> epidemiology (high blood levels of E are epidemiologically
> associated with low stroke and cardiovascular risk), but at
> least HOPE shows once and for all that vitamin E even in
> megadoses can't be very dangerous.
>
As always, the question is, what flavor of vitamin E was used in this study?
Probably straight dl-alpha tocopherol.
The evidence continues to accumulate regarding the importance of gamma
tocopherol, especially with regard to inflammatory processes, and yet people
continue to waste their time studying straight alpha tocopherol.
Have you seen the following?
Am J Clin Nutr 2003 Mar;77(3):700-6 Related Articles, Links
Comment in:
Am J Clin Nutr. 2003 Mar;77(3):530-1.
Mixed tocopherols inhibit platelet aggregation in humans: potential
mechanisms.
Liu M, Wallmon A, Olsson-Mortlock C, Wallin R, Saldeen T.
Department of Surgical Sciences, Section of Forensic Medicine, University of
Uppsala, Sweden.
BACKGROUND: Epidemiologic studies have shown an inverse correlation between
acute coronary events and high intake of dietary vitamin E. Recent clinical
studies, however, failed to show any beneficial effects of alpha-tocopherol
on cardiovascular events. Absence of tocopherols other than alpha-tocopherol
in the clinical studies may account for the conflicting results. OBJECTIVE:
This study compared the effect of a mixed tocopherol preparation rich in
gamma-tocopherol with that of alpha-tocopherol on platelet aggregation in
humans and addressed the potential mechanisms of the effect. DESIGN:
Forty-six subjects were randomly divided into 3 groups: alpha-tocopherol,
mixed tocopherols, and control. ADP and phorbol 12-myristate
13-acetate-induced platelet aggregation, nitric oxide (NO) release,
activation of endothelial constitutive nitric-oxide synthase (ecNOS; EC
1.14.13.39) and of protein kinase C (PKC), and ecNOS, superoxide dismutase
(SOD; EC 1.15.1.1), and PKC protein content in platelets were measured
before and after 8 wk of administration of tocopherols. RESULTS: ADP-induced
platelet aggregation decreased significantly in the mixed tocopherol group
but not in the alpha-tocopherol and control groups. NO release, ecNOS
activation, and SOD protein content in platelets increased in the
tocopherol-treated groups. PKC activation in platelets was markedly
decreased in the tocopherol-treated groups. Mixed tocopherols were more
potent than alpha-tocopherol alone in modulating NO release and ecNOS
activation but not SOD protein content or PKC activation. CONCLUSIONS: Mixed
tocopherols were more potent in preventing platelet aggregation than was
alpha-tocopherol alone. Effects of mixed tocopherols were associated with
increased NO release, ecNOS activation, and SOD protein content in
platelets, which may contribute to the effect on platelet aggregation.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12600864 [PubMed - indexed for MEDLINE]
FASEB J 2003 May;17(8):816-22 Related Articles, Links
Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory
eicosanoids and inflammation damage in rats.
Jiang Q, Ames BN.
Division of Biochemistry and Molecular Biology, University of California,
Berkeley; and Children's Hospital Oakland Research Institute, Oakland,
California 94609-1673, USA.
Gamma-tocopherol (gammaT), the major form of vitamin E in U.S. diets, and
its physiological metabolite 2, 7,
8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), in contrast
to alpha-tocopherol (alphaT), the primary vitamin E in supplements, inhibit
cyclooxygenase-catalyzed synthesis of prostaglandin E2 (PGE2) in activated
macrophages and epithelial cells. Here we report that in carrageenan-induced
inflammation in male Wistar rats, administration of gammaT (33 or 100 mg/kg)
and gamma-CEHC (2 mg/pouch), but not alphaT (33 mg/kg), significantly
reduced PGE2 synthesis at the site of inflammation. gammaT, but not alphaT,
significantly inhibited the formation of leukotriene B4, a potent
chemotactic agent synthesized by the 5-lipoxygenase of neutrophils. Although
gammaT had no effect on neutrophil infiltration, it significantly attenuated
the partial loss of food consumption caused by inflammation-associated
discomfort. Administration of gammaT led consistently to a significant
reduction of inflammation-mediated increase in 8-isoprostane, a biomarker of
lipid peroxidation. gammaT at 100 mg/kg reduced TNF-alpha (65%;P=0.069),
total nitrate/nitrite (40%;P=0.1), and lactate dehydrogenase activity
(30%;P=0.067). Collectively, gammaT inhibits proinflammatory PGE2 and LTB4,
decreases TNF-alpha, and attenuates inflammation-mediated damage. These
findings provide strong evidence that gammaT shows anti-inflammatory
activities in vivo that may be important for human disease prevention and
therapy.
PMID: 12724340 [PubMed - in process]
Regards,
Nelson
Tim Tyler
: "Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
:> The very best quality evidence we have for the effect of
:> megadose (400 IU) vitamin E on stoke and other
:> cardiovascular endpoints, is the large randomized
:> prospective placebo control HOPE trial. In that trial,
:> vitamin E flunked out, with no effect on any cardiovascular
:> endpoint, either positive OR negative (including in the
:> smokers). This was rather surprising in view of the
:> epidemiology (high blood levels of E are epidemiologically
:> associated with low stroke and cardiovascular risk), but at
:> least HOPE shows once and for all that vitamin E even in
:> megadoses can't be very dangerous.
: As always, the question is, what flavor of vitamin E was used in this study?
: Probably straight dl-alpha tocopherol.
HOPE study abstract [PMID: 10639540] just says: "natural sources".
--
__________
|im |yler http://timtyler.org/ t...@tt1.org
Sherdan
> 1) Pre-formed vitamin A is more toxic than we thought, with
> problems occurring in supplementation very near the RDI
> dose.
> 2) Vitamin E supposedly increases stroke risk.
>
> The first is interesting but old news, in a sense. We all
> knew pre-formed retinyl palmitate type vitamin A supplements
> were not that great an idea, and that is why the best
> supplements (Twinlab Daily One, for example, which I take)
> have the A as beta-carotene. There are large safety studies
> on beta carotene, and it's not dangerous except possibly in
> smokers.
>
Dr. Harris,
Got to ask this 'cause I've been curious. I am an ex-smoker - going
on 15 years since I quit. In the above senario would I still be
considered a smoker since the threat of cancer never really ever goes
away in someone who smoked and then quit?????
Thanks much!
Sherdan
Steve Harris
"Sherdan" <D9...@AOL.com> wrote in message
news:bd9e1543.03050...@posting.google.com...
Short answer: nobody knows.
If I had to guess, I'd guess that the risk from beta
carotene goes down at about the same rate as the excess lung
cancer risk after you quit-- half of it 7 years after
quitting, and much of the rest in the next 7. By the time
you're out at 15 you're probably okay, and missed the
bullet.
On the other hand, why risk it, though? If you have a
computer, you're not likely vitamin A deficient in your
diet. Beta carotene is not that hot a preventive for
anything in comparatively rich healthy Westerners.
SBH
Thomas Carter
Hi Sherdan,
No, the original study that spotted the link found it only in
current smokers. Theories as to the mechanics of the link also support
this nonassociation for ex smokers.
Thomas
Steve Harris
"Sherdan" <D9...@AOL.com> wrote in message
news:bd9e1543.03050...@posting.google.com...
> Got to ask this 'cause I've been curious. I am an
ex-smoker - going
> on 15 years since I quit. In the above senario would I
still be
> considered a smoker since the threat of cancer never
really ever goes
> away in someone who smoked and then quit?????
As noted, the excess risk of cancer DOES go away after you
quit, with a "half-life" of about 7 years. By now, after 15
years of quitting *at least* 3/4ths of your excess risk of
cancer due to smoking is gone.
So it really is good to quit.
BTW, most of your excess risk for heart problems goes away
in the first two years after quitting. Much faster.
SBH
michaelprice
> As noted, the excess risk of cancer DOES go away after you
> quit, with a "half-life" of about 7 years. By now, after 15
> years of quitting *at least* 3/4ths of your excess risk of
> cancer due to smoking is gone.
Well, not really. The bad news is that the excess risk from cancer
for ex-smokers does not "go away", it just stops growing. The risk
only goes away *relative* to a continuing smoker.
The damage done to your DNA remains and hence your
increased susceptibility to cancer stays. Smoking and then quitting
leaves you with a life-long, constant excess risk. Sorry.
> So it really is good to quit.
But better to have never started.
> BTW, most of your excess risk for heart problems goes away
> in the first two years after quitting. Much faster.
True. CVD rates drop in absolute terms after smoking cessation,
unlike cancer rates which do not.
Cheers,
Michael C Price
----------------------------------------
http://mcp.longevity-report.com
http://www.hedweb.com/manworld.htm
David Rind
> The first is interesting but old news, in a sense. We all
> knew pre-formed retinyl palmitate type vitamin A supplements
> were not that great an idea, and that is why the best
> supplements (Twinlab Daily One, for example, which I take)
> have the A as beta-carotene. There are large safety studies
> on beta carotene, and it's not dangerous except possibly in
> smokers. The body makes only as much retinol out of beta
> carotene as it needs, and retinol bone toxicity does NOT
> occur with beta carotene. There is some evidence that
> beta-carotene may influence the risk of smokers getting lung
> cancer, possibly through it's conversion to retinoic acid, a
> growth factor for epithelial cells and perhaps a cancer
> promoter. Vitamin-wise I think smokers would be smarter to
> supplement with B-complex and C only.
The risk in smokers may not be only for cancer. At least one
of the large trials of supplementation found an increased
risk of cardiac events when beta carotene was given for
secondary prevention of CHD, and one primary prevention
trial also found an increase in cardiac events (though
other primary prevention supplementation trials did not).
--
David Rind
dr...@caregroup.harvard.edu
Thomas Carter
>The very best quality evidence we have for the effect of
>megadose (400 IU) vitamin E on stoke and other
>cardiovascular endpoints, is the large randomized
>prospective placebo controled HOPE trial. In that trial,
>vitamin E flunked out, with no effect on any cardiovascular
>endpoint, either positive OR negative (including in the
>smokers).
It gave about a ten to one chance that E caused an increase
(midpoint, 17%) in hemorrhagic stroke in this setting of
cardiovascular patients, 77% of whom also took the powerful blood
thinner aspirin. Most also took other powerful cardiovascular drugs.
And all were under doctor's care. The stroke result is an indication
that the patients blood was at the optimum coagubility level without
vitamin E. Since the short term (one to five yr) protective mechanism
of E is mainly due to its blood thinning effect, it's not too
surprising in retrospect that E had no more effect than a second
aspirin tablet might have had.
>This was rather surprising in view of the
>epidemiology (high blood levels of E are epidemiologically
>associated with low stroke and cardiovascular risk), but at
>least HOPE shows once and for all that vitamin E even in
>megadoses can't be very dangerous.
Yes, the epidemiology is almost unanimous in favor of E, while
the clinical studies are at first glance contradictory. This
contradiction can be resolved, however, by assuming that E gives no
additional benefits in the short term to those who are taking aspirin
and/or other well prescribed cardiovascular drugs, or whom have had
test showing their blood coagubility level is already satisfactory.
I know of only three randomized intervention trials of E in which
the cohort was not, or presumably not taking much aspirin. They all
show a benefit for E. The large Chinese study of the general
population gave a 10% over all mortality benefit. The CHAOS study of
cardiovascular patients gave a 50% combined end point benefit. It was
published in '96, and I guess it ran in about '94. They weren't
prescribing much aspirin back then in England, especially since a
large English study had recently been published showing no benefit in
British doctors who took it, and they were misprescribing other
cardiovascular drugs. (calcium channel blockers, e g). I happened to
read some of the many criticism of the CHAOS study and it appeared to
me that the only reason it was so widely criticized was that it
supported vitamin use. In fact the medical profession seemed to me to
be very reminiscent of the supplement crowd who contorted themselves
into logical knots in an effort to explain away the original beta
carotene in smokers study. Doctors, like all of us lose much of their
analytical ability when faced with unpleasant facts. The third study
also gave a 50% benefit for E. It was in dialysis patients who are not
given aspirin much because dialysis eliminates it rapidly. They are
also under prescribed other drugs because of difficulties in getting
and keeping the right plasma levels.
If I were under a doctor's care for CVD and taking aspirin, I
would see no reason to take alpha tocopherol alone for short term
protection, but for those of use in the general population, with a
long term outlook, and full spectrum Vit E available, the HOPE study
is far from the best, and may not be far from the worst study to
study.
This is an archetypical example of the power that the much
maligned epidemiological studies can have over the "gold standard"
clinical trials. I will address this issue in another thread.
Thomas
Tom Kobzina
> only beta carotene for the A and no retinyl palmitate.
Not so fast:
1) Variability in conversion of beta-carotene to vitamin A in men as
measured by using a double-tracer study design.
Hickenbottom SJ, Follett JR, Lin Y, Dueker SR, Burri BJ, Neidlinger
TR, Clifford AJ.
Department of Nutrition, University of California, Davis, CA 95616,
USA.
BACKGROUND: The vitamin A activity of beta-carotene is variable and
surprisingly low in women. The reasons for this are not well
understood. The vitamin A activity of beta-carotene in men is still
uncertain. Contributions of dietary factors compared with individual
traits are largely unknown. OBJECTIVE: Our objective was to measure
the intrinsic variability in the vitamin A activity of beta-carotene
among healthy, well-fed men living in a controlled environment.
DESIGN: We used a double-tracer test-retest design. We dosed 11
healthy men orally with 30 micromol hexadeuterated (D6) retinyl
acetate (all-trans-19,19,19,20,20,20-[2H6]retinyl acetate) and then
with 37 micromol D6 beta-carotene
(19,19,19,19',19',19'-[2H6]beta-carotene) 1 wk later. Doses were taken
with breakfasts containing 16 g fat. We measured D6 retinol, D6
beta-carotene, and trideuterated (D3) retinol (derived from D6
beta-carotene) concentrations in plasma. Areas under the plasma
concentration x time since dosing curves (AUCs) were determined for D6
retinol, D6 beta-carotene, and D3 retinol. RESULTS: All men had
detectable D6 retinol concentrations in plasma. The mean (+/-SE)
absorption of D6 beta-carotene in all subjects was 2.235 +/- 0.925%,
and the mean conversion ratio was 0.0296 +/- 0.0108 mol retinol to 1
mol beta-carotene. Only 6 of 11 men had sufficient plasma
concentrations of D6 beta-carotene and D3 retinol that we could
measure. The mean absorption of D6 beta-carotene in these 6 subjects
was 4.097 +/- 1.208%, and the mean conversion ratio was 0.0540 +/-
0.0128 mol retinol to 1 mol beta-carotene. CONCLUSION: The vitamin A
activity of beta-carotene, even when measured under controlled
conditions, can be surprisingly low and variable.
PMID: 11976165
2) Variability of the conversion of beta-carotene to vitamin A in
women measured by using a double-tracer study design.
Lin Y, Dueker SR, Burri BJ, Neidlinger TR, Clifford AJ.
Department of Nutrition, University of California, Davis, CA 95616,
USA.
BACKGROUND: Blood beta-carotene and vitamin A responses to oral
beta-carotene are variable in humans. Some individuals are
characterized as responders and others as low- or nonresponders. A
better understanding of the conditions that produce the variability is
important to help design public health programs that ensure vitamin A
sufficiency. OBJECTIVE: Our objective was to assess variability in
absorption and conversion of beta-carotene to vitamin A in vivo in
humans by using a novel double-tracer inverted question
markhexadeuterated (D(6)) beta-carotene and D(6) retinyl acetate
approach. DESIGN: Eleven healthy women were housed at the US
Department of Agriculture Western Human Nutrition Research Center
metabolic unit for 44 d, where they consumed diets adequate in
vitamins and minerals except for carotenoids. After an adaptation
period, the women were given 30 micromol D(6) retinyl acetate orally,
followed 1 wk later with 37 micromol D(6) beta-carotene (approximately
equimolar doses). Time-dependent plasma concentration curves were
determined for D(6) retinol, D(6) beta-carotene, and trideuterated
(D(3)) retinol (derived from D(6) beta-carotene). RESULTS: Mean
(+/-SE) absorption of D(6) beta-carotene was 3.3 +/- 1.3% for all
subjects. The mean conversion ratio was 0.81 +/- 0.34 mol D(3) retinol
to 1 mol D(6) beta-carotene for all subjects. However, only 6 of the
11 subjects had plasma D(6) beta-carotene and D(3) retinol
concentrations that we could measure. The mean absorption of D(6)
beta-carotene in these 6 subjects was 6.1 +/- 0.02% and their
conversion ratio was 1.47 +/- 0.49 mol D(3) retinol to 1 mol D(6)
beta-carotene. The remaining 5 subjects were low responders with
</=0.01% absorption and a mean conversion ratio of 0.014 +/- 0.004 mol
D(3) retinol to 1 mol D(6) beta-carotene. CONCLUSION: Variable
absorption and conversion of beta-carotene to vitamin A both
contribute to the variable response to consumption of beta-carotene.
Our double-tracer approach is adaptable for identifying efficient
converters of carotenoid to retinoid.
PMID: 10837297
3) Absorption and conversion of 11,12-(3)H-beta-carotene to vitamin A
in Sprague-Dawley rats of different vitamin A status.
Goswami BC, Ivanoff KD, Barua AB.
Department of Biochemistry, Biophysics & Molecular Biology, Iowa State
University, Ames 50011, USA.
The aim of this study was to determine the bioavailability and
bioconversion to vitamin A of a single oral dose in oil or an aqueous
dispersion of labeled beta-carotene in rats of different vitamin A
status. Weanling Sprague-Dawley rats were fed a vitamin A-deficient
diet and supplemented for 4 wk with 0, 7, 21 and 63 micro g/(rat. d)
of retinyl acetate. The rats, of different vitamin A status, were then
given a single oral dose of 11,12-(3)H-beta-carotene (0.15 micro mol)
dissolved in corn oil or dispersed in aqueous Tween 80. The rats were
killed 4 or 24 h after the dose, and serum, liver, the entire
digestive tract, other tissues, urine and feces were analyzed for
carotenoids, retinoids and associated radioactivity. At 4 h after the
dose, 85 +/- 9% of the administered radioactivity was recovered.
Almost 50% of the dose was present as intact beta-carotene in the
large intestine where further absorption and conversion was ruled out.
The absorption of beta-carotene was very low, and < 5% of the
radioactive dose was converted to retinoids. The absorption and
conversion to vitamin A did not differ among rats of different vitamin
A status. The results suggest that a single oral dose of beta-carotene
might not be an effective way of raising vitamin A stores in the body.
PMID: 12514282