"Responsible companies look to the Council for Responsible Nutrition's (CRN) safe upper levels for product formulations," explained co-author Andrew Shao, PhD.
John Hathcock, PhD., said that the risk assessments could also be seen as a public confidence issue, allowing consumers to rely on the safety of doses in supplements.
CRN's Hathcock and Shao told NutraIngredients-USA.com that the assessments were warranted because no safe dosage levels for the nutrients have been established, in addition to increasing public awareness and usage of the nutrients, and their increasing use in dietary supplements.
The authors applied a safety evaluation method as described in the CRN's Vitamin and Mineral Safety, 2nd Edition which contains the basic features of the US Food and Nutrition Board's risk assessment method, as well as the observed safe limit (OSL) modification adopted as a highest observed intake (HOI) in the FAO/WHO 2006 report.
The absence of any critical effects prevented the expression of the limits as no observed adverse effect levels (NOAEL). Values were presented as OSLs.
And since the OSL based on human trials did not require correction from dietary intakes or endogenous synthesis, said the authors, and the OSL was therefore identified as safe upper level for supplements (USL).
For CoQ10, an USL of 1200 mg per day was concluded. If the figure had been extrapolated from animal studies the USL would have been 600 mg/d. However, data from seven human clinical trials using relatively high doses were available.
The final value of 1200 mg/d was based on two clinical trials with good monitoring, said Hathcock. Other trials reported no adverse effects for doses in excess of 2400 mg/d but the authors noted that limitations and uncertainties in the studies at these higher doses precluded use of these values as an USL.
More than 30 peer-reviewed, published human randomized clinical trials (RCT) were assessed for lutein with doses ranging from eight to 40 mg/d. Shao told NutraIngredients-USA that neither animal or human studies showed any adverse effects at any dose, but based on the data from the RCTs an USL of 20 mg/d was proposed.
For all-trans lutein, based on extrapolation from animal studies, an USL of 38 mg/d was proposed.
Sixteen RCTs were assessed to establish safe doses for lycopene. The data was sufficient to enable Shao and Hathcock to conclude an USL of 75 mg/d. (Extrapolation from animal studies yielded an USL of 270 mg/d).
The amino acid creatine is available as a dietary supplement in liquid, tablet and powder forms, chiefly in the form of creatine monohydrate. Evidence from well-designed, randomized clinical trials in humans indicated that an USL is 5 grams per day, said Hathcock and Shao.
Shao stressed that risk assessments were an on-going process and that there was a constant need to evaluate the science behind the OSLs.
And Hathcock and Shao have also been busy performing risk assessments for carnitine and glucosamine and chrondroitin, due to be published soon in the same journal.
The risk assessments are available on-line from the peer-reviewed journal, Regulatory Toxicology and Pharmacology CoQ10, doi: 10.1016/j.yrtph.2006.05.006 Lycopene and lutein: doi: 10.1016/j.yrtph.2006.05.007 Creatine monohydrate: doi: 10.1016/j.yrtph.2006.05.005