*Dr. Francisco Gomes is executive manager, aqua, for Novus International.
Use of DL-2-hydroxy-4-methylthiobutanoic acid (HMTBa), a methionine-hydroxy analog, as a functional and economical source of methionine supplementation in aquaculture feeds has been expanding.
Traditionally, DL-methionine, a racemic mixture of D- and L-isomers of methionine, was used in this role. Both HMTBa and DL-methionine are sources of methionine activity, with the D- and L-isomers of HMTBa and D-isomer of DL-methionine being converted to L-methionine, the form used in protein synthesis. Both offer cost savings and performance as a replacement for fish meal.
Use of HMTBa as a supplement in fish and shrimp feeds has become widely accepted for at least four reasons: (1) it offers notable flexibility when formulating based on nutrient requirements, (2) it allows lower crude protein levels to be fed, (3) it reduces ration costs and (4) it allows for rapid dietary adjustments.
The research and knowledge on supplementation with HMTBa continue to evolve.
In a 2011 National Research Council (NRC) review of protein and amino acid requirements of fish and shrimp, it was suggested that DL-HMTBa is not as available or efficacious as other methionine sources such as DL-methionine or L-methionine. The published literature in aquaculture and poultry, summarized in the NRC review, addressed the relative bioavailability of DL-HMTBa to DL-methionine and recommended a range of 75-80%.
Yet, when generating unbiased estimates of bioavailability that effectively represent the information published in the literature, it is critical to consider all available literature. The NRC 2011 report, unfortunately, omitted several publications in which the relative bioavailability of DL-HMTBa to DL-methionine in poultry and aquaculture species were higher than the range reported.
Specifically, the report fails to incorporate several meta-analyses from large numbers of trials that concluded ranges of relative bioefficacy up to 100%.
The 2011 NRC review cites differences in absorption dynamics between HMTBa and DL-methionine as a cause for differences in biological efficiency and uses the poultry literature as an example.
However, contrary to this view, articles in several peer-reviewed publications demonstrated the efficient absorption, availability, metabolism and biological efficiency of HMTBa in numerous livestock species.
A recent study with the turbot, Psetta maxima, indicated that HMTBa appears in the circulation system following feeding at a similar rate as L-methionine, thus indicating that, in fish, HMTBa is absorbed as well as L-methionine.
For aquatic species, the body of literature comparing the relative bioavailability of DL-HMTBa to DL-methionine is not as extensive as in terrestrial livestock species. The NRC report identified six publications in which comparisons of DL-HMTBa to DL-methionine were conducted.
Two of the six publications reported bioavailability values for DL-HMTBa higher than 80%. Goff and Gatlin (2004) reported equal bioavailability for DL-HMTBa in two experimental trials that directly compared L-methionine, DL-methionine and DL-HMTBa. Other trials in the literature did not report equal relative bioavailability.
It is, therefore, reasonable to believe that the upper value of the range of relative bioavailability should be higher than 80% and include 100%.
Differing dose response
The wide range of bioavailability estimates reported in the literature for DL-HMTBa has been a source of debate in the scientific community for five decades.
Although DL-methionine and DL-HMTBa are sources of methionine activity, their chemical structure, manner and site of absorption, transport in the body and conversion to L-methionine by the tissues are quite different.
Because of these differences, the two compounds do not follow the same dose response curve due primarily to differences in feed intake at the extremes of the dose response curves.
Multiple individual studies have demonstrated performance differences under specific conditions that have favored each compound, which has contributed to the controversy. The wide range of bioavailability estimates reported by the different meta-analyses of large numbers of poultry studies is driven by the different — and frequently incorrect — statistical dose response models used to determine the relative bioavailability.
Since DL-methionine and HMTBa are different compounds (one is an amino acid, and the other is an organic acid) and are metabolized very differently in the body once absorbed, the assumption that they should have identical dose response curves cannot be made without testing it out.
Furthermore, it has been scientifically proved that HMTBa and DL-methionine do not ever follow the same form of dose response, and therefore, one would obtain differing bioavailability estimates depending on where along the dose response curve the estimates are made.
It becomes critical, therefore, when reviewing the HMTBa literature, that all published statistical approaches are considered when reporting an unbiased range of relative bioavailability. In so doing, a value of 100% relative bioavailability for DL-HMTBa would certainly be included in that range.
Supplementing feeds for fish and shrimp with HMTBa represents an opportunity to reduce formulation costs. HMTBa is quickly becoming a cost-effective replacement for fish meal.
Goff, J.B., and D.M. Gatlin. 2004. Evaluation of different sulfur amino acid compounds in the diet of red drum, Sciaenops ocellatus, and sparing value of cystine for methionine. Aquaculture 241:465-477.
National Research Council. 2011. Nutrient Requirements of Fish & Shrimp. Animal Nutrition Series. The National Academies Press, Washington, D.C.