Betaine as a protective osmolyte
Supplemented betaine, which is not used as a methyl donor, can be used by (stressed) cells as an osmoprotectant. As a complete molecule, betaine has a neutral charge, but it has a region of both positive and negative charges (Figure 2). Having this specific characteristic, betaine is a zwitterion (dipolar ion) and this allows betaine to be both highly water soluble and able to hold water molecules. When betaine is taken up inside cells, it increases the water retention capacity of the cells. Thereby, betaine improves the cellular water balance in the gut, muscle and animal tissues. A better water balance by organic osmoprotectants, such as betaine, relieves the pressure on the ion pumps and stabilises the electrolyte concentration in and out of the cell. Thereby, betaine protects cells from the negative effects of dehydration, which results in reduced cellular activity, protein denaturation and loss of enzyme production. Higher plasma levels of betaine are advantageous, as it will increase the tolerance of cells to unfavourable conditions (e.g. in cases of renal failure).
Research with betaine in cats and dogs
The replacement of choline chloride with betaine in diet formulation is common practice in livestock nutrition. In pet food, there is less experience with the exchange of both functional nutrients. Until a few years ago, no scientific research was available about betaine in pet diets. Recently, several articles have been published and it is now clear that both dogs and cats can use betaine as a methyl donor, gain benefit from the osmoprotective function, and utilise other functionalities.
Choline used to compensate for low betaine levels
In a cross-over study with healthy dogs, comparing a traditional dry extruded diet with a plant-based diet, the circulating plasma levels of betaine and choline were both lower when the plant-based diet was fed2. The background level of betaine in the plant-based ingredients was significantly lower (Table 1), explaining the lower betaine levels in the plasma. However, the dietary choline levels were comparable between both diets due to the supplementation of choline chloride (on top of the choline present in food ingredients). The observed lower choline plasma levels could be explained by a lower absorption and/or de novo synthesis of choline in dogs receiving the plant-based diet. Alternatively, the lower plasma choline could be explained by the increased oxidation of choline to form betaine, for the delivery of sufficient methyl groups 2. This suggests that in dogs, more choline will be used as a methyl donor, to compensate for low betaine levels within pet food.
Betaine is a methyl donor in pets
Supplementation of betaine in pet food resulted in higher betaine plasma levels in both dogs 3,4 and cats 5,6. Moreover, additional dietary betaine increased different serum metabolites related to the transmethylation metabolism (Figure 1), including choline, dimethylglycine (DMG), sarcosine and methionine3,4,5,6. Levels of choline and several phosphatidylcholines were also elevated in healthy cats6, cats with chronic kidney disease6 and dogs with early renal disease4, when they received additional betaine in their diet. In all cases, the dietary choline levels were comparable between the control and test diets (Table 1). Indicating that choline is spared as a methyl donor by the addition of dietary betaine and thereby, choline can be used for other purposes like phosphatidylcholine synthesis. Besides, via the transmethylation metabolism (Figure 1), the methyl groups donated by betaine can also be used (via SAMe) for the synthesis of phosphatidylcholines. Collectively, phosphatidylcholine levels can be elevated by betaine supplementation via different routes 6. Results of the different studies demonstrate that betaine can replace (a proportion of) choline chloride in pet diets.