Elemental chromium (Cr) is an essential micronutrient. It is required for optimal
insulin activity and normal carbohydrate and lipid metabolism. Tri-valent chromium
(Cr3+) is recommended for the treatment of diabetes and obesity. There is evidence that
Cr3+ may have antidepressant properties, possibly by enhancement of monoamine function
through its ability to increase amino acid transport to the brain. The aim of the
present study was to investigate further the possible effects of Cr3+ treatment on peripheral amino acid availability and brain monoamine function in the
rat. We undertook three studies in rats. The first was a time-course study in which
animals were administered single doses of 50 mg/kg of Cr3+ picolinate and the second a dose-response study in which animals were given either
20 or 50 mg/kg Cr3+ picolinate versus vehicle alone via the intra-peritoneal route. In the third, animals
were fed a diet containing Cr3+ picolinate (100 mg/kg) or a similar control diet for two weeks and were then sacrificed.
Blood was sampled and brains were removed for later analysis. Results from the Cr3+ time-course study defined an optimal time for sampling of two hours after dosing.
Results from the second study showed dose-related responses to Cr3+ treatment for a number of measured biochemical parameters including serum corticosterone.
In the sub-chronic treatment study Cr3+ significantly increased serum free tryptophan (TRP), non-esterified free fatty acids
(NEFFAs), corticosterone, together with brain TRP, serotonin (5-hydroxytryptamine,
5-HT), noradrenaline (NA) and pineal melatonin. From other studies in our laboratory
we have shown that Cr3+ treatment can modify brain 5-HT function, perhaps by altering the sensitivity of
central 5-HT2A receptors. The peripheral effect of Cr3+ picolinate treatments and their consequential central effect on increased serotonergic
and noradrenergic function may suggest that Cr3+ could have some antidepressant-like actions. Future studies to confirm this are to
be done.
Key words
Cr3+ picolinate - TRP - 5-HT - NA - Melatonin - NEFFAs - corticosterone
References
- 1
Anderson R A.
Chromium, glucose tolerance, diabetes and lipid metabolism.
J Advancement Med.
1995;
8
37-39
- 2
Anderson R A, Bryden N A, Polansky M M.
Lack of toxicity of chromium chloride and chromium picolinate in rats.
J Amm Coll Nutrition.
1997;
16(3)
273-279
- 3
Attenburrow M -J, Odontiadis J, Murray B J, Cowen P J, Franklin M.
Chromium treatment decreases the sensitivity of 5-HT2A receptors.
Psychopharmacol..
2001;
159
132-136
- 4
Biggio G, Fadda F, Fanny P, Tagliamonte A, Gessa G L.
Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic
acid by tryptophan-free diet.
Life Sciences.
1974;
14
1321-1329
- 5 Burns T G, Brown G M. The effeects of acute and chronic desmethylimmipramine treatment
on pineal and serum melatonin and N-acetylserotonin. In: Brown GM, Wainwright SD (eds)
The pineal gland: endocrine aspects. Pergamon Press Oxford; 1985: 25-30
- 6
Chi J D, Odontiadis J, Franklin M.
Simultaneous determination of catecholamines in rat brain tissue by high-performance
liquid chromatography.
J Chrom B.
1999;
731
361-367
- 7
Cowen P J, Fraser S, Grahame-Smith D G, Green A R, Stanford C.
The effect of chronic antidepressant administration on β-adrenoceptor function in
the rat pineal.
Br J Pharmac.
1983;
78
89-96
- 8
Curzon G, Freidal J, Knott P J.
The effects of fatty acids on the binding of tryptophan to plasma protein.
Nature.
1973;
242
198-200
- 9
Evans G W.
The effect chromium picolinate on insulin controlled parameters in humans.
Intl J Biosoc Med Res.
1989;
1
163-180
- 10
Fernstrom J D.
The effect of nutritional factors on brain amino acid levels and monoamine synthesis.
Fed Proc.
1976;
35
1151-1156
- 11 Franklin M. Sub-chronic treatment effects of an extract of hypericum perforatum
(ST John’s wort, LI 160) on neuroendocrine responses to the 5-HT2 agonist, DOI in
the rat. Pharmacopsychiat (in press)
- 12
Franklin M.
Researching the antidepressant actions of Hypericum perforatum (St John’s wort) in
animals and man.
Pharmacopsychiat.
2001;
34(Suppl 1)
S29-37
- 13
Gartside S E, Ellis P M, Sharp T, Cowen P J.
Selective 5-HT1A and 5-HT2 receptor-mediated adrenocorticotropin release in the rat: effect of repeated antidepressant
treatments.
Eur J Pharmacol.
1992;
221
27-33
- 14
Franklin M, Clement E M, Campling G, Cowen P J.
Effect of venlafaxine on pinea; melatonin and noradrenaline in the male rat.
J Psychopharmacol.
1998;
12(4)
371
- 15 Goodman H M. The Physiologist 1970 13: 75
- 16
Jacobson A M.
Depression and diabetes.
Diabetes Care.
1993;
16
1621-1623
- 17
Jovanic-Peterson L, Gutierrez M, Peterson C M.
Chromium supplementation for gestational diabetic women improves glucose tolerance
and decreases hyperinsulinemia (Abstract).
J Am Coll Nutr.
1995;
14
530
- 18
Kaats G R, Wise J A, Blum K.
The short-term therapeutic efficacy of treating obesity with a plan of improved nutrition
and moderate calorie control restriction.
Current Ther Res.
1992;
51
261-274
- 19
Klein D C, Berg G R, Weller J.
Melatonin synthesis adenosine 3′,5′- monophosphate and norepinephrine stimulate N-acetyl-transferase.
Science.
1970;
168
979-980
- 20
McCarty M F.
Enhancing central and peripheral insulin activity as a strategy for the treatment
of endogenous depression - an adjuvant role for chromium picolinate?.
Med Hypotheses.
1994;
43
247-252
- 21
Maj J, Bijak M, Dziedzicka-Waslewska M, Rogoz R, Rogoz Z, Skuza G, Tokarski T.
The effects of paroxetine given repeatedly on the 5-HT receptor subpopulations in
the rat brain.
Psychopharmacol.
1996;
127
237-240
- 22
Meltzer H Y.
Serotonergic function in the affective disorders: the effect of antidepressants and
lithium on the 5-hydroxytryptophan-induced increase in serum cortisol.
Ann NY Acad Sci.
1984;
430
115-137
- 23
McLeod M N, Gaynes B N, Golden R N.
Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in
5 patients.
J Clin Psych.
1999;
60(4)
237-240
- 24
Moyer J A, Greenberg L H, Frazer A, Brunswick D J, Mendels J, Weiss B.
Opposite effects of acute and repeated administration of desmethylimmipramine on adrenergic
responsivness in rat pineal gland.
Life Science.
1979;
24
2237-2244
- 25
Nathan R S, Sachar E J, Asnis G M.
Relative insulin insensitivity and cortisol secretion in depressed patients.
Psych Res.
1981;
4
291-300
- 26
Perez-Cruet J, Chase TN and Murphy D L.
Dietary regulation of brain tryptophan metabolism by plasma ratio of free tryptophan
and neutral amino acids in humans.
Nature.
1974;
248
693-695
- 27
Schwartz M W, Figlwicz D P, Baskin D G.
A hormonal regulator of energy balance.
Endocr Rev.
1992;
13
387-413
- 28
Tagliamonte A, Tagliamonte P, Perez-Cruet J, Stern S, Gessa G L.
Effect of psychotropic drugs on tryptophan concentration in the rat brain.
J Pharmacol Exp Ther.
1971;
177
475-480
- 29
Van de Kar L.
Neuroendocrine pharmacology of serotonergic (5-HT) neurons.
Annu Rev Pharmacol Toxicol.
1991;
31
289-320
- 30
Wilkinson G, Borsey D Q, Leslie P.
Psychiatric disorder in patients with insulin-dependent diabetes mellitus attending
a general hospital clinic i) two-stage screening and ii) detection by physicians.
Psych Med.
1987;
17
515-517
- 31
Wright J H, Jacisin J J, Radin N S.
Glucose metabolism in unipolar depression.
Brit J Psych.
1978;
132
386-393
Dr. Mike Franklin
University of Oxford Department of Psychiatry
Warneford Hospital
Headington, Oxford OX3 7JX.
Phone: 44 1865 226470
Fax: 44 1865 223615
Email: michael.franklin@psychiatry.ox.ac.uk