Chromium in AOR Ortho-Core causes DNA damage

Just when you thought one company might have all the answers, a bomb like this gets dropped..

Cytotoxicity and oxidative mechanisms of different forms of chromium.
Bagchi D, Stohs SJ, Downs BW, Bagchi M, Preuss HG. Toxicology 180(1):5-22 2002.

Chromium exists mostly in two valence states in nature: hexavalent chromium [chromium(VI)] and trivalent chromium [chromium(III)]. Chromium(VI) is commonly used in industrial chrome plating, welding, painting, metal finishes, steel manufacturing, alloy, cast iron and wood treatment, and is a proven toxin, mutagen and carcinogen. The mechanistic cytotoxicity of chromium(VI) is not completely understood, however, a large number of studies demonstrated that chromium(VI) induces oxidative stress, DNA damage, apoptotic cell death and altered gene expression. Conversely, chromium(III) is essential for proper insulin function and is required for normal protein, fat and carbohydrate metabolism, and is acknowledged as a dietary supplement. In this paper, comparative concentration- and time-dependent effects of chromium(VI) and chromium(III) were demonstrated on increased production of reactive oxygen species (ROS) and lipid peroxidation, enhanced excretion of urinary lipid metabolites, DNA fragmentation and apoptotic cell death in both in vitro and in vivo models. Chromium(VI) demonstrated significantly higher toxicity as compared with chromium(III). To evaluate the role of p53 gene, the dose-dependent effects of chromium(VI) were assessed in female C57BL/6Ntac and p53-deficient C57BL/6TSG p53 mice on enhanced production of ROS, lipid peroxidation and DNA fragmentation in hepatic and brain tissues. Chromium(VI) induced more pronounced oxidative damage in multiple target organs in p53 deficient mice. Comparative studies of chromium(III) picolinate and niacin-bound chromium(III), two popular dietary supplements, reveal that chromium(III) picolinate produces significantly more oxidative stress and DNA damage. Studies have implicated the toxicity of chromium picolinate in renal impairment, skin blisters and pustules, anemia, hemolysis, tissue edema, liver dysfunction; neuronal cell injury, impaired cognitive, perceptual and motor activity; enhanced production of hydroxyl radicals, chromosomal aberration, depletion of antioxidant enzymes, and DNA damage. Recently, chromium picolinate has been shown to be mutagenic and picolinic acid moiety appears to be responsible as studies show that picolinic acid alone is clastogenic. Niacin-bound chromium(III) has been demonstrated to be more bioavailable and efficacious and no toxicity has been reported. In summary, these studies demonstrate that a cascade of cellular events including oxidative stress, genomic DNA damage and modulation of apoptotic regulatory gene p53 are involved in chromium(VI)-induced toxicity and carcinogenesis. The safety of chromium(III) is largely dependent on the ligand, and adequate clinical studies are warranted to demonstrate the safety and efficacy of chromium(III) for human consumption.

I sent an e-mail to AOR looking for a response on the issue.

LEF 1 - AOR 1

at what doses?

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Hopefully someone will dig a little deeper to answer that, I'm curious too.

Nevertheless, both forms are dirt cheap, and we see that LEF has wisely gone with chromium polynicotinate. There is no excuse for using picolinate if it is more toxic at any dose. The niacin bound form is more bioavailable anyway.

Do a pubmed search of "picolinic acid toxicity". The recent spate of citations (I don't have time to read now) suggest that toxicity isn't being found consistently, wrt Cr-picolinate. Still, I share this concern after reading this paper years back, as well, and since a typical dose of Chromium bound to niacin gives about 30mg of niacin, I've chosen to get niacin as a supplement in this fashion. I'm more concerned about diet supplements that provide 800mcg per serving of Cr-Picolinate, and might easily be abused, exposing the user to even higher amounts of Cr and picolinic acid.

well something thats toxic at 20g/kg but not at the 100-200mcg dose you would be taking normally is not dangerous....that study doesnt mean much without dosages.

my multi actually contains 3 forms of chromium:

150mcg @ 1:3:1 picolinate:nicotinate:glutathionate

LEF has wisely gone with chromium polynicotinate.

Hmmmph.

Too bad LEF can't seem to pass a simple quality test and keep a toxin out of their Chromium product (source: consumerlabs.com).

I don't think it's legal to post the results...but they failed with a contaminated product (chromium VI (3.85%))

Funny -- Jarrow recalled a product that failed just for a potency discrepancy. I don't know if LEF recalled theirs for a much more serious offense.

As for this issue, AOR is extremely picky about what they put into that formula and why...I'd be shocked if they didn't have a very good answer.

Too bad LEF can't seem to pass a simple quality test and keep a toxin out of their Chromium product (source: consumerlabs.com).

Do we (ImmInst) have a group subscription rate for Consumer Labs?

Funny -- Jarrow recalled a product that failed just for a potency discrepancy. I don't know if LEF recalled theirs for a much more serious offense.

As for this issue, AOR is extremely picky about what they put into that formula and why...I'd be shocked if they didn't have a very good answer.

what jarrow product failed? jarrow buys alot of their stuff from AOR.

Just checked my recent buy of LEF Mix Tabs and they are using ChromeMate a "biologically active oxygen-coordinated niacin-bound chromium complex" which appears to match the above cited "Niacin-bound chromium(III) has been demonstrated to be more bioavailable and efficacious and no toxicity has been reported". I would like to see the Consumer Labs report, but I understand that it should not be posted. Were they talking about the current LEF Mix?

I alternate daily with Ortho Core and LEF Mix, so I am also interested in the response from AOR.

edit: response received from AOR Support

Edited by focus, 12 February 2006 - 01:00 AM.

I think this can be seen by the general public?

http://www.consumerl...?recallid=10103

Were they talking about the current LEF Mix?

It was the Chromium product they sell, not the LEF mix.

However, only LEF knows if they use the same source for both.

Somebody should question them on their forum...if it hasn't been raised there already. I don't have the time to look right now.

Unfortunately, I am on the road and neither have access to all the reams of studies I have on the subject at AOR HQ, nor time to address this in detail now. I can assure all that we saw this review at the time and looked into it in detail. The studies suggesting toxicity are almost entirely in vitro or in totally unphysiological or irrelevant model systems; there is also a sole, highly confounded medical anecdote report.

Here is the draft report on Cr Pic from the Nat'l Academy of Sciences' Institute of Medicine -- the folks who set the RDA, who are not exactly pushers of supplements or of envelopes:

Institute of Medicine
Introduction and Prototype Monograph for Chromium Picolinate
http://www.iom.edu/File.aspx?ID=19558

"B.  Conclusions and Recommendations About the Safety of the Ingredient Based on the  Strength of the Scientific Evidence
    Considering the totality of the data reviewed, there is neither consistent evidence of  reasonable expectation of harm from chromium picolinate nor sufficient evidence to raise  concern regarding the safety or toxicity of chromium picolinate when used in the intended manner for a length of time consistent with the published clinical data, i.e., up to 1.6 mg Cr  picolinate/day [200 μg Cr(III)/day] for 3-6 months.    This conclusion is consistent with the findings of the Agency for Toxic Substances and  Disease Registry in a recent toxicological profile for chromium (ATSDR, 2000). 

------------

Several additional human clinical trials at 200, 400, 600, or nearly 1000 mcg Cr (as picolinate)/d have appeared in print since then:

http://www.ncbi.nlm....l=pubmed_DocSum
http://www.ncbi.nlm....l=pubmed_DocSum
http://www.ncbi.nlm....l=pubmed_DocSum
http://www.ncbi.nlm....l=pubmed_DocSum

There have been additioinal studies presented scientific meetings since then at 600 mcg/da which have not yet been published; note that none of these studies have reported safety problems. As well, the National Toxicology Program has also published a safety study of chronic, high-dose Cr picolinate in the time since the above review was written:

http://www.ncbi.nlm....l=pubmed_docsum

Groups of 10 male and 10 female F344/N rats and B6C3F(1) mice were exposed to 0, 80, 240, 2000, 10,000, or 50,000 ppm CPM in feed for 13 weeks. CPM administration produced no effect on body weight gain or survival of rats or mice. Organ weights and organ/body weight ratios in exposed animals were generally unaffected by CPM. No compound-related changes in hematology and clinical chemistry parameters were observed. There were no histopathological lesions attributed to CPM in rats or mice.

This follows up on an earlier in vivo rodent study of similar conclusions:

http://www.ncbi.nlm....l=pubmed_docsum

Lack of toxicity of chromium chloride and chromium picolinate in rats.
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. .... 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: [b]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.[b] Animals consuming the picolinate supplemented diets had several-fold higher Cr concentrations in both the liver and kidney than those fed Cr chloride.

The available evidence overwhelmingly supports the safety of this form of the nutrient. Moreover, contrary to the cited review, there is nearly no evidence in humans for the efficacy of the specific, available niacin-bound chromium forms (though its bioavailability does seem to be high). Indeed, if you look through the literature, the efficacy of most forms of chromium is highly dubious; we chose chromium picolinate precisely because it is the best-documented from both a safety and an efficacy viewpoint.

AOR

Thank you for taking the time to put this information together and reply, I feel better about taking Ortho-Core with this much research behind its formulation (don't be offended if I supplement with some extra ChromeMate though ).

I remember Tom Matthews, the former highly knowledgeable
moderator of LEF's forums, mentioned some years ago that
the evidence on chromium picolinate's toxicity is not very
strong.

In any case, doses below 600 mcg are relatively safe.

Here is a recent newswire press release regarding Chromium:

http://www.latimes.c...s-pe-california

Looks like its back to being good again. You can do a Google News ( not web ) search on chromium picolonate and see all the articles.

Whoops, wrong link..sorry..thats why we need a preview feature here ..lets try again:

http://www.newkerala...ullnews&id=5094

I hope this one works..sorry.

It works..I vote we get a posting preview feature so I don't embarrass myself again.
Good thing it was not one of my porn links!

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I'm pretty sure you can delete your own posts.