Pick Your Chromium
In a recent clinical trial, reseearchers explored the effects of chromium picolinate (CrP) in patients with atypical depression (ATD).1 This common form of depression is marked by mood reactivity, increased appetite and weight gain, excessive sleeping, leaden paralysis and interpersonal rejection sensitivity. It may be more insidious and longer lasting than other forms of depression.
A pilot study followed 15 people with the ATD subtype of major depression and who had discontinued taking mood-altering medications. Ten received CrP at 400mcg/day for two weeks and 600mcg/day for another six weeks; the remaining five received placebo. After six weeks of intervention, the CrP group showed a strong response to the treatment (7 of the 10 on CrP; 0 of the 5 on placebo) but did not display a statistically significant change in the Hamilton Depression Scale score. Interestingly, the onset of improvement was rapid—within the first two weeks. Additionally, signs of appetite/binge eating reduction and reduced fatigue were noted in the CrP group. However, no changes in body weight were seen.
Recent animal and test-tube studies describing adverse effects associated with CrP appear to be species-specific, with contradictory evidence existing in humans.2,3 One study showed no increase in DNA damage among obese adult women receiving 400mcg/day CrP for eight weeks.4 It is of interest to note that the primary investigator who has undertaken chemical and animal studies is the inventor of a different, patented and synthetic form of chromium.5 Clearly more systematic human safety studies are needed, conducted by independent, unbiased researchers. The National Toxicology Program has a two-year animal study underway to assess the long-term safety of CrP.
Glutathione (GSH), also known as reduced glutathione, is the most abundant low molecular weight cellular thiol, which contains a free sulfhydryl (-SH) group. This tripeptide (L-g-glutamyl-L-cysteinyl-glycine) is abundant in several foods, especially brussels sprouts, asparagus tips, potatoes, orange juice and meats.6,7
In tumour-bearing states and during chemotherapy, GSH metabolism and compartmentalisation undergoes significant modifications. Several double-blind, placebo-controlled clinical studies have found intravenous GSH administered just prior to chemotherapy reduces the side effects, increases tolerability and may actually improve efficacy.8,9,10,11
Because GSH is a 'mini protein,' it is susceptible to enzymes that can degrade it into its constituent amino acids. However, in a few oral-dosing studies in humans, researchers suggest that a measurable portion eludes digestion and enters the circulation.12,13,14 One study in children with leukemia undergoing stem-cell transplantation received either vitamin E (400IU once daily, body weight <25 kg; 1000IU once daily if >25kg) alone or with oral GSH (100mg/day, body weight <25kg; 150mg/day if >25kg), in two or three divided doses.15 Veno-occlusive disease (VOD; obstruction of the veins), a frequent side effect of this type of transplantation, was seen in several of the children. They were then immediately placed on a high-dose oral GSH regimen (400600mg/day, in three doses) for at least 14 days.
The investigators found vitamin E with or without GSH to be effective at reducing the risk of developing VOD, while oral GSH alone was found to have therapeutic effects in those who developed VOD. This promising body of evidence warrants further investigation. Note: GSH therapy in individuals with cancer should be done under a physician's supervision.
Anthony Almada, BSc, MSc, is the president and chief scientific officer of IMAGINutrition Inc and has been a co-investigator on more than 60 randomised controlled trials. www.imaginutrition.com
1. Davidson JRT, et al. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry 2003;53:261-4.
2. Hepburn DD, et al. Nutritional supplement chromium picolinate causes sterility and lethal mutations in Drosophila melanogaster. Proc Natl Acad Sci USA 2003;100:3766-71.
3. Hepburn DD, et al. The nutritional supplement chromium picolinate generates oxidative DNA damage and peroxidized lipids in vivo. Polyhedron 2003;22:455-63.
4. Kato I, et al. Effect of supplementation with chromium picolinate on antibody titers to 5-hydroxymethyl uracil. Eur J Epidemiol 1998;14:621-6.
5. Vincent JB, Davis CM. Use of triaqua-mu3-oxohexakis-mu-propionatotrichromium (1+), [Cr3O(O2C CH2CH3)6 (H2O)3]+, as a nutritional supplement or in treatment of medical conditions. United States patent number 6197816, issued March 6, 2001.
6. Jones DP. Glutathione distribution in natural products: absorption and tissue distribution. Methods Enzymol 1995;252:3-13.
7. Mills BJ, et al. Glutathione and cyst(e)ine profiles of vegetables using high performance liquid chromatography with dual electrochemical detection. J Food Comp Anal 1997;10:90-101.
8. Smyth JF, et al. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: Results of a double-blind, randomised trial. Ann Oncol 1997;8:569-73.
9. Bohm S, et al. Dose intensification of platinum compounds with glutathione protection as induction chemotherapy for advanced ovarian carcinoma. Oncology 1999;57:115-20.
10. Cascinu S, et al. Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer. J Clin Oncol 1997;15:3313-19.
11. Cascinu S, et al. Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: A randomized, double-blind, placebo-controlled trial. J Clin Oncol 2002;20:3478-83.
12. Hunjan MK and Evered DF. Absorption of glutathione from the gastrointestinal tract. Biochim Biophys Acta 1985;815:184-8.
13. Jones DP, et al. Oral administration of glutathione (GSH) increases plasma GSH concentration in humans. FASEB J 1989;3:A1250.
14. Witschi A, et al. The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992;43:667-9.
15. Bin C, et al. Oral vitamin E and glutathione for the prevention and early treatment of veno-occlusive disease in children with acute leukemia undergoing hematopoietic stem cell transplantation. Blood 1999;94(10 Suppl. 1 Part 2):355b.