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PubMed1982

The influence of intraruminal and intraduodenal infusion of picolinic acid on metabolism of 65Zn in sheep.

Two experiments with sheep were carried out to study the influence of picolinic acid on zinc metabolism. In the first experiment, sheep were infused with water into the duodenum and with picolinic acid into the rumen or duodenum. All the sheep were then intraduodenally dosed with 65Zn. In the second experiment, sheep were intraduodenally infused with water or picolinic acid and then intravenously dosed with 65Zn. Necessary sampling of urine, faeces, blood or digesta were carried out in both experiments. The infusion with picolinic acid did not affect the faecal excretion or endogenous secretion of 65Zn but increased the urinary excretion of the radioisotope and ruminal solubility of zinc. However, te duodenal and ileal solubilities of zinc were not affected by the treatment. It was concluded that an exogenous supplement of picolinic acid is not effective in promoting higher absorption of zinc in ruminant animals.

Animals↗

PubMed1997

Comparative induction of oxidative stress in cultured J774A.1 macrophage cells by chromium picolinate and chromium nicotinate.

The concentration-dependent effects of chromium picolinate and chromium nicotinate were assessed on the enhanced production of reactive oxygen species including superoxide anion and hydroxyl radicals, and lipid peroxidation and DNA fragmentation in cultured macrophage J774A.1 cells. The macrophage cells were incubated with 0-50 micrograms/ml [corrected] concentrations of these chromium (III) salts for 0 and 24 hrs at 37 degrees C. Concentration-dependent effects were observed. Lipid peroxidation increased by 1.3-1.5-fold following treatment of these cells with chromium picolinate while at these same concentrations of chromium nicotinate approximately 1.2-1.8-fold increases in lipid peroxidation were observed. Increases of 1.0-1.5-fold occurred in the production of superoxide anion as determined by cytochrome c reduction following treatment with chromium picolinate while with these same concentrations and conditions only 1.1-1.2-fold increases in cytochrome c reduction were observed following treatment with chromium nicotinate. Approximately 1.2-1.5-fold increases in hydroxyl radical production were observed following treatment of these macrophage cells with increasing concentrations of chromium picolinate and chromium nicotinate. Incubation of the cells with 30-50 micrograms/ml concentrations of chromium picolinate produced 1.2-1.6 fold increases in DNA fragmentation, while under these same conditions with chromium nicotinate 1.2-1.3-fold increases in DNA fragmentation occurred. No significant loss in cell viability was observed with either chromium salt. These results demonstrate that incubation of macrophage J774A.1 cells with these chromium salts induces low levels of oxidative stress as demonstrated by the biochemical assay techniques employed in this study.

Cells, Cultured↗

PubMed2006

Relaxation dynamics of highly vibrationally excited picoline isomers (E(vib) = 38 300 cm(-1)) with CO2: the role of state density in impulsive collisions.

Strong collisions of highly vibrationally excited picoline isomers and CO2 (00(0)0) were investigated using high resolution transient IR absorption probing to investigate the role of donor state density. Vibrationally excited 3-picoline and 4-picoline (3-methylpyridine and 4 methylpyridine) with E(vib) = 38300 cm(-1) were prepared by 266 nm excitation followed by rapid internal conversion. Transient IR probe measurements of the nascent rotational and translational energy gain in CO2 (00(0)0) show that large DeltaE collisions for 3- and 4-picoline are similar to those for excited 2-picoline. The probability distributions for the large DeltaE energy transfer of the three isomers have similar dependence on DeltaE. The results are compared with other earlier results demonstrating that the shape of the large DeltaE probability distribution correlates with the DeltaE dependence of the donor vibrational state density. The results are discussed in terms of the GRETCHEN model for collisional relaxation.

Journal Article↗

PubMed1994

Picolinic acid as a matrix for laser mass spectrometry of nucleic acids and proteins.

We found that picolinic acid is a very good matrix for matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry of oligonucleotides, proteins and tRNA. Among the oligonucleotides, picolinic acid was shown to be effective for homo-oligonucleotides, d(G)40 and d(C)60, and for mixed-base oligonucleotides up to 190 bases. In the case of the single-stranded oligonucleotides, and of double-stranded ones as well, only parent ions corresponding to single-stranded DNA were observed. The efficiency for MALDI of oligonucleotides using the picolinic acid matrix was superior to that using 3-hydroxypicolinic acid. MALDI of transfer RNA phenylalanine-specific (tRNA(Phe)), a 76-base ribonucleic acid, was detected with a signal-to-noise ratio of > 10. By comparison with 3-hydroxypicolinic acid the results with picolinic acid are notably superior for all oligonucleotides.

Base Sequence↗

PubMed1987

Comparative absorption of zinc picolinate, zinc citrate and zinc gluconate in humans.

The comparative absorption of zinc after oral administration of three different complexed forms was studied in 15 healthy human volunteers in a double-blind four-period crossover trial. The individuals were randomly divided into four groups. Each group rotated for four week periods through a random sequence of oral supplementation including: zinc picolinate, zinc citrate, and zinc gluconate (equivalent to 50 mg elemental zinc per day) and placebo. Zinc was measured in hair, urine, erythrocyte and serum before and after each period. At the end of four weeks hair, urine and erythrocyte zinc levels rose significantly (p less than 0.005, p less than 0.001, and p less than 0.001) during zinc picolinate administration. There was no significant change in any of these parameters from zinc gluconate, zinc citrate or placebo administration. There was a small, insignificant rise in serum zinc during zinc picolinate, zinc citrate and placebo supplementation. The results of this study suggest that zinc absorption in humans can be improved by complexing zinc with picolinic acid.

Administration, Oral↗

PubMed1983

[Effect of different concentrations of various zinc complexes (picolinate, citrate, 8-hydroxyquinolate) in comparison with sulfate on zinc supply status in rats].

12 groups of 8 young male Sprague-Dawley rats received a semisynthetic casein-diet, whose zinc concentration (1.3 ppm) was adjusted to 5, 10 and 15 ppm by supplementation of various Zn complexes or salts like Zn citrate, Zn picolinate, Zn 8-hydroxyquinolate and Zn sulfate. After 24 days all animals were killed and examined on parameters of zinc supply status. The weight gain of the animals with 5 ppm dietary zinc was strongly reduced compared to groups with the higher dietary zinc content. The type of the supplemented Zn compound showed in no way an influence on the live-weight of the animals. The zinc concentration of the tissues, too, was only dependent on the level of the dietary zinc concentration and not on the type of supplemented zinc compound. The activity of the alkaline phosphatase in serum, a zinc metalloenzyme, was altogether reduced in the zinc-deficient animals with 5 ppm dietary zinc content, but showed a significant higher activity in the citrate and 8-hydroxyquinolate group than in the sulfate and picolinate group. Also the percent zinc-binding capacity of serum, a good indicator for estimating the zinc supply status of rats, showed a better zinc supply of the citrate group with 5 as well as 10 ppm dietary zinc, compared with the other groups on the same dietary zinc content. The serum zinc concentration of rats with 5 ppm as Zn citrate was more than twice higher than in animals given zinc as picolinate, 8-hydroxyquinolate or sulfate. The results indicate a better utilization of zinc chelated by citric acid than by picolinic acid, 8-hydroxyquinoline or as salt like sulfate. But the higher bioavailability of zinc in human milk should not only be attributed to the presence of citrate.

Alkaline Phosphatase↗

PubMed2005

Vibrational and microbiological study on alkaline metal picolinates and o-iodobenzoates.

FT-IR and Raman experimental data were assigned to appropriate bond vibrations and used to compare the different electronic charge distributions in the aromatic rings and carboxylic anions of various lithium, sodium, potassium, rubidium and caesium o-iodobenzoates and picolinates. Then principal component analysis (PCA) was applied in order to attempt to distinguish the biological activities of these compounds according to selected band wavenumbers. The growth of the bacteria Escherichia coli and Bacillus subtilis and the yeasts Saccharomyces cerevisiae and Hansenula anomala under optimal growth conditions were measured after 24 hours of incubation by the classical plate method. The influence of the picolinates and o-iodobenzoates on the growth of these microorganisms, again after 24 hours of incubation, was also measured and compared to the effect of sodium benzoate, which was used as a reference material. In general, the o-iodobenzoates exhibited more activity against the microorganisms than the picolinates. A statistically significant linear correlation between the spectral data and the degree of influence of a given compound on microorganism growth was established. The correlation coefficients for the o-iodobenzoates were 0.696, -0.628, 0.693 and 0.755 for E. coli, B. subtilis, H. anomala and S. cerevisiae, respectively, and for the picolinates they were 0.818, 0.826, 0.821 and 0.877 for E. coli, B. subtilis, H. anomala and S. cerevisiae, respectively. Therefore, IR spectroscopy is shown to be a rapid and reliable analytical tool for preliminary estimation of the antimicrobial properties of newly synthesized compounds, that can be applied before microbial performance tests.

Bacillus subtilis↗

PubMed2004

Augmented inhibition of Candida albicans growth by murine neutrophils in the presence of a tryptophan metabolite, picolinic acid.

The effects of picolinic acid (PLA), a product of tryptophan catabolism, on anti- Candida activity of neutrophils were studied. Casein-induced peritoneal neutrophils of C3H/He mice partially inhibited mycelial growth of Candida albicans when cultured with C. albicans for 16 h in vitro. The growth inhibition of Candida was augmented by a combination of neutrophils and more than 4 mM picolinic acid. Especially in the presence of 200 U/ml murine interferon-gamma (IFN-gamma), 2 mM picolinic acid augmented the anti- Candida activity of neutrophils. The physiological significance of the augmenting effects of picolinic acid is discussed.

Animals↗

PubMed1990

Is picolinic acid a glycine agonist at strychnine-sensitive receptors?

By means of unit recording and electrophoretic application, the effect of picolinic acid on feline spinal interneurons in situ was studied in comparison with glycine. Picolinic acid inhibited neuronal firing in 60% of neurons and in some cases the inhibitory actions were antagonized by strychnine. Inhibition of firing by glycine, which was also strychnine-sensitive, was reduced in case of concomitant administration of picolinic acid. These results suggest that picolinic acid might act as a glycine agonist at strychnine-sensitive receptors.

Animals↗

PubMed1993

Homologous physiological effects of phenformin and chromium picolinate.

The insulin-sensitizing drug phenformin, in addition to its clinical utility in type II diabetes, has been reported to lower blood lipids, reduce body fat, enhance cellular immunity, and--in rodents--to increase mean lifespan and retard the development of growth of cancer. Initial studies with the insulin-sensitizing nutrient chromium picolinate indicate that it aids glucose tolerance in type II diabetes, lowers elevated LDL cholesterol, reduces body fat while increasing lean mass, and--in rats--increases median lifespan. These effects are thus analogous to those reported for phenformin; chromium picolinate should be tested to determine whether it likewise has a favorable impact on cellular immunity and cancer risk. The ability of both phenformin and chromium picolinate to increase lifespan suggests that age-related insulin resistance may play a profound role in the aging process. It may not be coincidental that caloric restriction--the best documented technique for increasing lifespan--markedly increases insulin sensitivity. Safe, appropriate measures for promoting lifelong insulin sensitivity include a low-fat diet, exercise training, and supplemental chromium picolinate.

Adipose Tissue↗

PubMed1995

Histological and ultrastructural changes in the rat brain following systemic administration of picolinic acid.

Picolinic acid was administered intraperitoneally in a dose of 30, 60, or 100 mmol, once every 24 h for 8 days. Histologically, under normal conditions as well as when picolinic acid was administered in a dose of 30 mmol the brain formations exhibited characteristic features. When picolinic acid was administered in a dose of 60 mmol or 100 mmol, the alterations were profound and developed selectively in hippocampus, being much less intense in the substantia nigra and striatum. In such cases, injuries of neuronal cell bodies were accompanied by symptoms of spongiosis. Within the hippocampus, the neuronal cell body injury was selectively restricted to the hilar and CA3 regions of stratum pyramidale. Tissue spongiosis was more intense at the granular layer, particularly within the hilus and in the mossy fiber area at CA3. Histochemically, a variable intensity of the reaction of succinic and alpha-glycerophosphate dehydrogenases was demonstrated. A decrease in their activities was observed in areas where the neuronal cell body injuries and spongiosis took place. No changes in the Ca-ATP-ase activity in brain formation after picolinic acid treatment were observed. Ultrastructurally, the changes within substantia nigra were manifested by neuronal cell bodies of the dark type and dendritic degenerations. Also less damaged neuronal cell bodies were seen. They were swollen, depleted of polyribosomes with dilated elements of RER and altered mitochondria. Some of the dendritic profiles were swollen with lucent cytoplasm. Most of the boutons in synaptic contact zones were unchanged. Most presynaptic terminals which were in junction with dark dendrites were swollen with or without crystal-like aggregates of synaptic vesicles.

Animals↗

PubMed1998

Effect of supplementation with chromium picolinate on antibody titers to 5-hydroxymethyl uracil.

Recent in vitro studies have shown that chromium (III) compounds such as chromium picolinate, a popular dietary supplement among people trying to lose weight, produce chromosome damage. We monitored levels of DNA damage in a chromium picolinate supplement trial by measuring antibodies titers to an oxidized DNA base, 5-hydroxymethyl-2'-deoxyuridine (HMdU), by enzyme-linked immunosorbent assays. Ten obese volunteer women completed a 8-week course of 400 micrograms chromium picolinate per day. In either absolute titers or percent of the baseline value, there were no changes in antibody titers at 4 or 8 weeks. The titers were very stable within individuals and those of one individual rarely crossed over others, which was reflected in an intraclass correlation coefficient of 0.99 (95% confidence interval: 0.96-1.00). There were no effects on glucose and lipid metabolism in this period. The results of this trial suggest that chromium (III) picolinate in a dose typically used for nutrient supplementation dose not increase oxidative DNA damage, as measured by anti-HMdU antibody levels.

Analysis of Variance↗

PubMed2003

Chromium picolinate for reducing body weight: meta-analysis of randomized trials.

The aim of this meta-analysis was to assess the evidence of chromium picolinate for reducing body weight. Literature searches were conducted on Medline, Embase, The Cochrane Library, Amed and Ciscom. Nine experts and four manufacturers of commercial preparations containing chromium picolinate were asked to contribute published and unpublished studies. There were no restrictions regarding the language of publication. The screening of studies, selection, data extraction, validation and the assessment of methodological quality were performed independently by two reviewers. To be included, studies were required to state that they were randomized, double-blind and placebo-controlled, and report on body weight. Ten trials met all inclusion criteria and provided data, which were suitable for statistical pooling. For body weight a significant differential effect was found in favour of chromium picolinate (weighted mean difference: -1.1 kg; 95% confidence interval (CI): -1.8 to -0.4 kg, n=489). Sensitivity analysis suggests that this effect is largely dependent on the results of a single trial (weighted mean difference: -0.9 kg; 95% CI: -2.0 to 0.2 kg, n=335). Three of the reviewed trials reported on adverse events, indicating their absence in the treatment groups. In conclusion, our meta-analysis suggests a relatively small effect of chromium picolinate compared with placebo for reducing body weight. The clinical relevance of the effect is debatable and the lack of robustness means that the result has to be interpreted with caution.

Dietary Supplements↗

PubMed2003

Effects of treatment with chromium picolinate on peripheral amino acid availability and brain monoamine function in the rat.

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.

Animals↗

PubMed1997

Lack of toxicity of chromium chloride and chromium picolinate in rats.

OBJECTIVE: To evaluate the safety of chromium (Cr) as a nutrient supplement. Several recent studies have reported beneficial effects of supplemental Cr at levels higher than the upper limit of the suggested intake for Cr. Trivalent Cr is considered relatively nontoxic but some recent unconfirmed studies have questioned its toxicity. We evaluated the toxicity of Cr chloride and a more bioavailable form of trivalent Cr, Cr tripicolinate. METHODS: Harlan Sprague Dawley rats (4 weeks of age) were fed a stock diet to which was added 0, 5, 25, 50 or 100 mg of Cr per kg of diet as chloride or picolinate. Fasting blood samples were taken at 11 and 17 weeks and animals sacrificed at 24 weeks of age. Lack of toxicity was demonstrated by blood and histological measurements. Chromium incorporation into tissues was determined by graphite furnace atomic absorption. RESULTS: There were no statistically significant differences in body weight, organ weights or blood variables among all the groups tested at 11, 17 and 24 weeks. Blood variables measured were glucose, cholesterol, triglycerides, blood urea nitrogen, lactic acid dehydrogenase, transaminases, total protein and creatinine. Histological evaluation of the liver and kidney of control and animals fed 100 mg/kg Cr as Cr chloride or picolinate also did not show any detectable differences. Liver and kidney Cr concentrations increased linearly for both the Cr chloride and picolinate fed animals. CONCLUSIONS: These data demonstrate a lack of toxicity of trivalent Cr, at levels that are on a per kg basis, several thousand times the upper limit of the estimated safe and adequate daily dietary intake for humans. Animals consuming the picolinate supplemented diets had several-fold higher Cr concentrations in both the liver and kidney than those fed Cr chloride.

Animals↗

PubMed1985

The iron-chelating agent picolinic acid enhances transferrin receptors expression in human erythroleukaemic cell lines.

Picolinic acid, a metal chelating molecule, was administered to human erythroleukaemic cell lines (K 562 and HEL) that were grown in serum-containing media. Picolinic acid inhibited both iron uptake and cell growth. Furthermore, picolinic acid was shown to markedly decrease the level of ferritin in the cells. In spite of the inhibition of cell growth, picolinic acid induced a marked increase in the transferrin-binding capacity of the cells. This phenomenon was due to a two-five-fold enhancement of the rate of transferrin receptor biosynthesis. Other iron-chelating compounds, capable of reducing the level of intracellular iron, also elicited a marked enhancement of the transferrin-binding capacity of the cells. However, the addition of iron, as ferric ammonium citrate, in the culture medium elicited a marked increase in the level of ferritin and a strong decrease in the transferrin-binding capacity of the cells. On the basis of these data we propose that a feed-back mechanism is involved in the regulation of transferrin receptors: when the cells accumulate iron they decrease the number of transferrin receptors in order to prevent further accumulation of iron; when no or low iron is available to the cells, the number of transferrin receptors markedly increases as a compensatory mechanism.

Cell Line↗

PubMed1995

[Therapeutic efficacy of zinc picolinate in patients with taste disorders].

We studied the therapeutic efficacy of zinc picolinate in patients with zinc-deficient and idiopathic taste disorders. Efficacy was assessed in a double-blind study. The following findings were obtained: 1. There was a significant difference between the zinc picolinate and placebo groups in the grade of improvement shown by the filter-paper disk method. 2. There was a significant difference between the zinc picolinate and placebo groups in the serum zinc concentration. 3. There was no significant difference between the two groups in the degree of total subjective recovery or the grade of improvement, as shown by in the whole mouth method. 4. We conclude that the administration of zinc picolinate is effective for patients with zinc-deficient and idiopathic taste disorders.

Double-Blind Method↗

PubMedDate not supplied

Urinary excretion of chromium by humans following ingestion of chromium picolinate. Implications for biomonitoring.

This study investigated the variability in urinary chromium (Cr) excretion following the ingestion of Cr picolinate by human volunteers. A pharmacokinetic model was used to estimate the bioavailability of Cr from ingested Cr picolinate using known distribution patterns and elimination rates of Cr by humans. The possible advantages of using sequential, individual spot, or 24-hr urine sample collection for biomonitoring of Cr exposure were examined. Background concentrations of urinary Cr determined from the spot samples in this study compared well with values reported by others. The variability in urinary excretion of Cr in untreated volunteers indicated that it is virtually impossible to distinguish exposures to most occupational and virtually all environmental exposures to Cr. Sequential urine sampling was found superior to both 24-hr and spot urine collection for indicating exposure to Cr picolinate. The extent of absorption of Cr from the picolinate matrix in the gastrointestinal tract was 2.80 +/- 1.14% (SD). It was estimated that 10 mg of soil containing between 7,400 and 52,000 mg Cr(III)/kg would have to be ingested by an adult to result in urinary excretion of Cr clearly above the upper bound of Cr in urine from background populations (1.8 microgram Cr/liter), depending on certain assumptions regarding bioavailability. This study supports the results of other recent work that demonstrated urinary excretion of Cr resulting from low-level environmental exposure is unlikely to be distinguished from that resulting from dietary uptake.

Administration, Oral↗