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In this 2004-02-20 article, MR provides evidence that Zinc deficiency may be especially common among CRONies. He believes he was suffering from such a deficit up until recently, and that several side effects he attributed to CR (e.g. slow wound healing) have improved substantially as a result of increasing his Zinc intake. CRONies should take a look at this post, and their Zinc intake.

Anyone who was at CR Society Conference II will recall my rant about the excess Zn
in typical multis, & all of the mayhem to which this would lead. Most of
the alarm on this relates to the fact that Cu tends to be marginal to
begin with in the standard North American diet: Zn & Cu are so structurally
similar that they compete for absrption & for enzymatic ligands, so that
an excess of one can create a secondary, functional deficiency in the secnd.

However, ths very pattern (OK Zn, low Cu [copper]) in SAD (std. American diet) is the result of a
combnation of eating a significant amount of meat (which is often
Zn-rich), & little (Cu-rich) vegetables. Since many CR folks eat less
meat than SAD, and nearly all eat much more vegetables, I have a sneaking
suspicion that for many of us the reverse is the case. Certainly, a
recent crunch of my diet:

[search CR Society Archives]

... shows that this is true for me.

As I noted at the time:

"As it happens, I had an appointment a few days ago with my more
'activist' & 'alternative' doc, who had me slosh a Zn sulfate solution
around in my mouth for 10 s, & based o the fact that I found it only
faintly unbleasant (as opposed to grossly bitter) diagnosed me with mild
Zn deficiency. I've not yet been able to find any reliable sources to
back up this test, however (tho' Lancet. 1996 Dec 7;348(9041):1592 may
be it), but in any case it's clear that my Zn:Cu needs boosted; for now,
I'm going to take the lazy way out & up my supplemental intake."

Now, the above paper was NOT it, and I did some digging & couldn't find
much of anything thru' obvious searches. I finally asked my doc, the
quality of whose notions re: health & nutrition is rather mixed, if he
had any evidence on the subject of the test & he immediately said,
"Absolutely: Bryce-Smith." It took him a while to dig up his material
(all secondary) -- but it WAS referenced. & what his material (& the
refs) was PRIMARILY about was not the test (which is just there as a
footnote, for convenient diagnosis), but about the fact that Zn
deficiency is rampant in anorexia nervosa & that its victims respond in
various clinically-important ways to supplementation. (I dug up a bunch
of these studies, & followed them thru' their bibliogrraphies to other
references; I won't cite much of this, but there's a significant body of
literature out there on the subject).

Now, this may seem obvious: anorexics, the standard line on the List
goes, eat shitty diets, which are Calorie reduced but also grossly
nutrient poor, so they're likely deficient in all KINDS of things --
incl. Zn. (NB, in what follows, that (1) below is evidence that this
obvious explanation is exactly right, & that there is nothing 'special'
about anorexia-asociated Zn deficient. Other studies -- & much
speculation -- beg to differ). But in fact, that explanation apparently
doesn't QUITE wash. (4), in fact, asserts that "Aside from symptioms
secondary to starvation, such as bradycardia, hypothermia, and
hypotension [all of which are negatively-connoted descriptions of common
effects of CR, NB], clinical symptoms of vitamin deficiencies have been
rarely reported. That does not surprise the clinician who is familiar
withthe eating habits of patients with anorexia nervosa. Often excessive
quantities of green vegetables, salads, and frit, sometimes supplemented
with daily vitamins, are consumed. Carbohydrate in sweets, bread, an
potatoes ... are strictly avoided."

Sound familiar?

Now, a diet low in Zn and high in Cu is bad enough, but there is SOME
evidence that might suggest that, perversely, the body LOSES more Zn
during weight loss -- a phenomenon that might reasonably be expected to
continue on long-term CR for reasons given below. A study (3) performed
" in five healthy non-obese young adults before, during and after a
four-day period of total starvation" found that "Plasma zinc
concentrations rapidly INCREASED in all subjects by a mean of 4 mumol/1
(25%) and returned to normal on refeeding. The excretion of
zinc in urine TREBLED and continued to rise on refeeding. ... From
knowledge of the intracellular concentrations of various minerals and
extent of breakdown of lean tissues (Nitrogen excretion), it is suggested that
... the amount of zinc in urine is only a small FRACTION of that which
is likely to be released from the breakdown of lean tissues ... [and]
that the continued excretion of zinc on refeeding is due to release of
zinc from tissues which 'buffered' it during the starvation period."

I am SPECULATING that this might continue after weight stabilization in
CR just because, while the amount of lean tissue we carry may be stable,
CR is well-known to increase protein turnover. This constant remodeling
of muscle & organ proteins MIGHT, if the above explanation is correct,
likeise be associated with ongoing, excessive Zn excretion.

On top of this, while there aren't many performance atheletes in our
numbers -- & while of course exercise is not per se part of CR --
certainly we, as a cohort, tend to be quite physically active as
compared to the hoi polloi. I stumbled across this (2) once I got on the
evidence trail:

"Endurance training effects on zinc status were assessed by comparing 13
highly trained (HT) and 10 untrained (UT) women. Blood and 24-h urine
samples before and after a 25-mg oral Zn load, and 3-d dietary records
were evaluated. Mean daily Zn intakes did not differ and were below the
Recommended Dietary Allowances for both groups. Fasting concentrations
of plasma Zn, serum albumin, alpha 2-macroglobulin, and erythrocyte Zn
content did not differ."

"However, HT women had significantly ... higher urinary Zn excretion
(HT: 6.7 +/- 0.8 and UT: 4.5 +/- 0.7 mumol/d) and reduced responses to
the oral Zn than did UT in terms of maximal responses (HT: 11.0 +/- 1.6
and UT: 16.2 +/- 1.2 mumol/L) and areas under the curve (HT: 34.8 +/-
2.7 and UT: 43.6 +/- 2.7
mumol.L-1.4h-1). The greater urinary Zn excretion by HT women may
reflect higher rates of skeletal muscle turnover. Whether their reduced
responses to the Zn load reflect differences in plasma volume, entry or
removal of plasma Zn, or absorption is unknown."

Put high dietary Cu together with marginal dietary + supplemental Zn and
extra Zn excretion due to CR and endurance training, & it would seem
that I -- & many CR folks -- are set up real nice-like for Zn deficiency.

Now, when my doc originally diagnosed me Zn deficient, I bumped my
supplement up to 15 mg. Something that I have noticed in the intervening
period, but hadn't connected with this until my SECOND, recent Dr visit
& subsequent digging in the literature, is that a coupel of irritants
I'd put down to the antiproliferative effects of CR seem to have been
significantly ameliorated -- & as I now know, they either are, ro
resemble, symptoms of Zn deficiency. Slower wound healing in CR is
well-known & documented in the rodents (search archives), & I'd
certainly noticed this in myself; but I recently took a v. nasty wipeout
during a jog. My hands were cut to ribbons (some bandaids are visible on
my recent Discovery Channel appearance if you look carefully), and I was
expecting to still have half-scabbed messes for AGES; instead, they've all
resolved themselves quickly.

Another sign of Zn deficiency is rough skin or skin lesions. For some
years now my fingertips have started to crack open in the winter. They
don't bleed, but it's not attractive, & sometimes they become irritated.
I've chalked this down to the v. dry winters 'round here, but I've only
been partly able to deal with the problem with petroleium jelly-based
antibiotic ointment, which ought to've both moisturized & facilitated
healing. Now, THIS winter, I still got a little, tiny bit of this -- but
MUCH less than for the last several years.

I've also on 2 occasions had soft, readily-tearing nails for a month or
so. This, again, is associated with Zn deficiency. I don't have these
now -- but, of course, I haven't for the greatmajority of my time on CR,
either, so this particular anecdote deserves particular contempt.

Another symptom is irritability. Who, me ? Seriously: lots of CR
folks have noticed irritability, which we usually put down to mild
hunger & elevated cortisol and excitattory neurotransmitters. Perhaps Zn
deficiency plays a role too.

Another symptom, which I DON'T AFAICS have, is loss of appetite. Still,
as one paper I skimmed noted, this fact might allow anorexics to
continue their nonconsumption of food -- or even exacerbate it. Lack of
hunger in CR folk might, alas, be at least partially, as well as the
result of clever strategies (bulk, MUFA, protein, low GI, etc) and
psychological adaptation.

Yet another is 'hypogeusia' (dulled taste sense) and/or 'dysgeusia' (weird
distortions thereof). AFAICS, I don't have this either -- BUT it's
interesting that (a) one of the most well-established of these effects
is the dulling of the tasate of bitter, which might facilitate
adaptation to eating a lot of Brassica vegetables, and (b) it was this
notion thath led the aforementioned Bryce-Smith to develop -- &
validate, at least to his satisfaction -- the Zn solution taste test.

So since they had Zn sulfate on hand, & knew it has a strong taste, they
figured they could use it both for diagnostic and treatment purposes.
They dissolved 1 g ZnSO4.7H20/L of distilled water, and had folks taste
5-10 mL. People who tasted little or nothing (like me) or who gradually
noticed a "dry," "mineral," "furry," or "sweet" taste they concluded
were deficient, & tended to respond clinically to supplements; others
(their unblinded control group was themselves & their staff) would
immediately notice a definite taste -- either neutral or v. unpleasant.(4)

Other overlapping symptoms include "weight loss, ... amenorrhea in
females, impotence in males [~loss of libido?]" (5).

After a whack of letters reporting clinical anecdotes, a small RCT was
finally performed some years ago (6). "In this randomized, double-blind,
placebo-controlled trial 100 mg of zinc gluconate [=14 mg Zn], or
placebo, was given daily to 35 female AN inpatients until they achieved
a 10% increase in body mass index (BMI). The rate of increase in BMI of
the zinc supplemented group (n = 16) was twice that of the placebo group
(n = 19), and this difference was statistically significant (p = .03).
The use of zinc supplementation should
be considered in the treatment of AN patients."

More concrete info & speculation is available in (5, 7-8 ), and by
following around in bibiographies.

People: CRUNCH YOUR DIETS [use software such as DWIDP or Nutribase]! If your Zn (DRI 11 mg; CR folks should prob
he higher by (say) 50%) &/or your Zn:Cu is low (should be ~10:1), bring
it up, by diet or supplements. And even so: check your symptoms, & see
if you can get a taste test.

See Dean's previous posts on CR-associated anemia:

[search CR Society Archives Ed.: This will be posted on the cron-web forum soon]

... for which, fortunately, a reliable, validated test (ferritin) is
readily available -- unlike Zn, AFAIK.

-MR


1: Lask B, Fosson A, Rolfe U, Thomas S.
Zinc deficiency and childhood-onset anorexia nervosa.
J Clin Psychiatry. 1993 Feb;54(2):63-6.
PMID: 8444822 [PubMed - indexed for MEDLINE]

2: Deuster PA, Day BA, Singh A, Douglass L, Moser-Veillon PB.
Zinc status of highly trained women runners and untrained women.
Am J Clin Nutr. 1989 Jun;49(6):1295-301.
PMID: 2729169 [PubMed - indexed for MEDLINE]

3: Elia M, Crozier C, Neale G.
Mineral metabolism during short-term starvation in man.
Clin Chim Acta. 1984 May 16;139(1):37-45.
PMID: 6723071 [PubMed - indexed for MEDLINE]


4. Bryce-Smith D, Simpson RI.
Anorexia, depression, and zinc deficiency.
Lancet. 1984 Nov 17;2(8412):1162-3. No abstract available.
PMID: 6150225 [PubMed - indexed for MEDLINE]

5. Bakan R.
The role of zinc in anorexia nervosa: etiology and treatment.
Med Hypotheses. 1979 Jul;5(7):731-6.
PMID: 514114 [PubMed - indexed for MEDLINE]

6: Birmingham CL, Goldner EM, Bakan R.
Controlled trial of zinc supplementation in anorexia nervosa.
Int J Eat Disord. 1994 Apr;15(3):251-5.
PMID: 8199605 [PubMed - indexed for MEDLINE]

7: Safai-Kutti S, Kutti J.
Zinc supplementation in anorexia nervosa.
Am J Clin Nutr. 1986 Oct;44(4):581-2. No abstract available.
PMID: 3766443 [PubMed - indexed for MEDLINE]

8: Casper RC, Kirschner B, Sandstead HH, Jacob RA, Davis JM.
An evaluation of trace metals, vitamins, and taste function in anorexia
nervosa.
Am J Clin Nutr. 1980 Aug;33(8):1801-8.
PMID: 7405882 [PubMed - indexed for MEDLINE]