Betaine may be a beneficial nutrient to add to a specialty enteral formula for obesity

The most appropriate enteral formula for the severely obese population has yet to be determined. The obese patient in the intensive care unit (ICU) creates numerous difficulties for managing care, one being the ability to deliver appropriate and timely nutrition. Access for nutrition therapy, either enteral or parenteral, can also create a challenge. Currently, no specific guidelines are available on a national or international scale to address the issues of how and when to feed the obese patient in the ICU. A bias against feeding these patients exists, secondary to the perception that an enormous quantity of calories is stored in adipose tissue. Making a specialty enteral formula for obesity from existing commercial formulas and other modular nutrient components is not practical, secondary to difficulty with solubility issues, dilution of the formula, and safety concerns. Using today's concepts and current metabolic data, a formula could be produced that would address many of the specific metabolic derangements noted in obesity. This formula should have a high-protein, low-carbohydrate content with at least a portion of the lipid source coming from fish oil. Specific nutrients that may be beneficial in obesity include arginine, glutamine, leucine, L-carnitine, lipoic acid, S-adenosylmethionine, and betaine. Certain trace minerals such as magnesium, zinc, and selenium may also be of value in the obese population. The concept of a specific bariatric formulation for the ICU setting is theoretically sound, is scientifically based, and could be delivered to patients safely.

Martindale, R. G., M. DeLegge, et al. (2011). "Nutrition Delivery for Obese ICU Patients." Journal of Parenteral and Enteral Nutrition 35(5 suppl): 80S-87S.

Betaine has a hepatoprotective effect by increasing glutathione levels and glutathione-related enzyme activities in rats

The effects of betaine supplementation on D-galactosamine-induced liver injury were examined in terms of hepatic and serum enzyme activities and of the levels of glutathione and betaine-derived intermediates. The rats induced with liver injury showed marked increases in serum enzyme activity, but those receiving dietary supplementation of 1% betaine showed enzyme activity levels similar to a control group without liver injury. Administration of betaine also increased both hepatic and serum glutathione levels, even following D-galactosamine injection. The activity of glutathione-related enzymes was markedly decreased following injection of D-galactosamine, but remained comparable to that of the control group in rats receiving 1% betaine. The concentrations of hepatic S-adenosyl methionine and cysteine showed similar trends to that observed for hepatic glutathione levels. These results indicate that 1% betaine has a hepatoprotective effect by increasing hepatic and serum glutathione levels along with glutathione-related enzyme activities in rats.

Okada, T., et al., Amelioration of D-galactosamine-induced acute liver injury in rats by dietary supplementation with betaine derived from sugar beet molasses. Biosci Biotechnol Biochem, 2011. 75(7): p. 1335-41.

Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum

Oxidative stress is a hypothesis for the association of reactive oxygen species with cerebrovascular and neurodegenerative diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the cerebellum of rats. Thirty-two adult male Sprague–Dawley rats were divided into four equal groups (control, ethanol, betaine, and betaine plus ethanol) with different dietary regimens and were followed up for 1 month. Total homocysteine (tHcy) of plasma and cerebellum homogenate was determined by an Axis® homocysteine EIA kit, and antioxidant enzyme (glutathione peroxidase (GPx), SOD, and CAT) activities of cerebellum homogenate were measured chemically by a spectrophotometer. Lipid peroxidation of cerebellum was shown by the measurement of thiobarbituric reactive substances (TBARS) via a spectrophotometer. Ethanol-induced hyperhomocysteinemia was manifested by an increase in the concentrations of tHcy in the plasma and cerebellum homogenates of the ethanol group, while ethanol-induced oxidative stress was indicated via an increase in lipid peroxidation marker (TBARS) in cerebellum homogenates of ethanol-treated rats. In contrast, betaine prevented hyperhomocysteinemia and oxidative stress in the betaine plus ethanol group as well as the betaine group. The results of the present investigation indicated that the protective effect of betaine is probably related to its ability to strengthen the cerebellum membrane cells by enhancement of antioxidant enzyme activity principally GPx, while the methyl donor effect of betaine to reduce hyperhomocysteinemia has been explained previously and confirmed in the present study.

Alirezaei, M., et al., Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum. J Physiol Biochem, 2011. 67(4): p. 605-12.

Women who developed gestational diabetes had lower plasma betaine

This work describes an exploratory NMR metabonomic study of second trimester maternal urine and plasma, in an attempt to characterize the metabolic changes underlying prenatal disorders and identify possible early biomarkers. Fetal malformations have the strongest metabolic impact in both biofluids, suggesting effects due to hypoxia (leading to hypoxanthine increased excretion) and a need for enhanced gluconeogenesis, with higher ketone bodies (acetone and 3-hydroxybutyric acid) production and TCA cycle demand (suggested by glucogenic amino acids and cis-aconitate overproduction). Choline and nucleotide metabolisms also seem affected and a distinct plasma lipids profile is observed for mothers with fetuses affected by central nervous system malformations. Urine from women who subsequently develop gestational diabetes mellitus exhibits higher 3-hydroxyisovalerate and 2-hydroxyisobutyrate levels, probably due to altered biotin status and amino acid and/or gut metabolisms (the latter possibly related to higher BMI values). Other urinary changes suggest choline and nucleotide metabolic alterations, whereas lower plasma betaine and TMAO levels are found. Chromosomal disorders and pre-preterm delivery groups show urinary changes in choline and, in the latter case, in 2-hydroxyisobutyrate. These results show that NMR metabonomics of maternal biofluids enables the noninvasive detection of metabolic changes associated to prenatal disorders, thus unveiling potential disorder biomarkers.

Diaz, S.O., et al., Metabolic biomarkers of prenatal disorders: an exploratory NMR metabonomics study of second trimester maternal urine and blood plasma. J Proteome Res, 2011. 10(8): p. 3732-42.

High dietary betaine intake associated with less advanced AMD

Objective
We evaluated monozygotic twin pairs with discordant age-related macular degeneration (AMD) phenotypes to assess differences in behavioral and nutritional factors.

Design
Case series.

Participants
Caucasian male twin pairs from the United States Twin Study of Macular Degeneration.

Methods
Twin pairs were genotyped to confirm monozygosity. Ocular characteristics were evaluated based on fundus photographs using the Wisconsin Grading System and a 5-grade Clinical Age-Related Maculopathy Staging System. We selected twin pairs discordant in each of the following phenotypic categories: Stage of AMD (n = 28), drusen area (n = 60), drusen size (n = 40), and increased pigment area (n = 56). The Wilcoxon signed-rank test and linear regression were used to assess associations between behavioral and nutritional characteristics and each phenotype within discordant twin pairs.

Main Outcome Measures
Differences in smoking and dietary factors within twin pairs discordant for stage of AMD, drusen area, drusen size, and pigment area.

Results
Representative fundus photographs depict the discordant phenotypes. Pack-years of smoking were higher for the twin with the more advanced stage of AMD (P = 0.05). Higher dietary intake of vitamin D was present in the twins with less severe AMD (P = 0.01) and smaller drusen size (P = 0.05) compared with co-twins, adjusted for smoking and age. Dietary intakes of betaine and methionine were significantly higher in the twin with lower stage of AMD (P = 0.009) and smaller drusen area (P = 0.03), respectively.

Conclusions
The twin with the more advanced stage of AMD, larger drusen area, drusen size, and pigment area tended to be the heavier smoker. The twin with the earlier stage of AMD, smaller drusen size and area, and less pigment tended to have higher dietary vitamin D, betaine, or methionine intake. Results suggest that behavioral and nutritional factors associated with epigenetic mechanisms are involved in the etiology of AMD, in addition to genetic susceptibility.

Seddon, J.M., et al., Smoking, dietary betaine, methionine, and vitamin D in monozygotic twins with discordant macular degeneration: epigenetic implications. Ophthalmology, 2011. 118(7): p. 1386-94.

Serum betaine concentration is decreased in patients after bariatric surgery

Bariatric surgery significantly reduces the risk of cardiovascular diseases but has no effects on hyperhomocysteinemia, the risk factor for atherogenesis. We hypothesize that the decrease in serum betaine (involved in homocysteine metabolism) concentrations, after bariatric surgery, impairs conversion of homocysteine to methionine, leading to hyperhomocysteinemia. If this is true, it may be desirable to supply patients after bariatric surgery with betaine. Serum betaine and homocysteine concentrations were measured by liquid chromatography/mass spectrometry, in 16 obese patients, before and 6 months after bariatric surgery. Ten healthy individuals with normal body mass index served as controls. Serum betaine concentrations decreased to the values lower than in controls after bariatric surgery, whereas serum homocysteine concentrations remained elevated. In patients supplemented with B(12) and folate, no effect of bariatric surgery on serum concentrations of vitamins involved in homocysteine metabolism was observed. These results suggest that betaine deficit could be responsible for maintenance of hyperhomocysteinemia after bariatric surgery. We postulate that supplementation with betaine could be of therapeutic value for the treatment of hyperhomocysteinemia after bariatric surgery.

Sledzinski, T., et al., Decreased serum betaine concentrations in patients after bariatric surgery. Obes Surg, 2011. 21(10): p. 1634-9.

Betaine improves performance under heat stress in rabbit model

The objective of this study was to determine the effects of dietary betaine supplementation on growth performance, carcass characteristics, rectal temperature, respiration rate and immune response of growing rabbits under high ambient temperature.

A total of 120 weaned New Zealand White male rabbits, 6 weeks old, were randomly divided into five experimental treatments (24 each). Animals were fed ad libitum the basal diet supplemented with 0 (control), 250, 500, 750 and 1000 mg betaine/kg diet from 6 to 12 weeks of age. Animals were provided with water freely. The average daily temperature and relative humidity inside the rabbitry were 30.3 ± 0.9 °C and 76.2 ± 2.5%, respectively. Under heat stress conditions, diet significantly increased the body weight and hot carcass weight and significantly reduced the feed conversion. Dietary 1000 and 750 mg betaine/kg increased (P < 0.05) final body weights (2529.1 and 2418.5 g, respectively) compared with the control (2110.3 g). Betaine supplementation ameliorated some of the adverse effects of heat stress on immune responsiveness, rectal temperature and respiration rate. Dietary 250, 500, 750 and 1000 mg betaine/kg led to a decrease in rectal temperature (40.03, 39.85, 39.63 and 39.53 °C, respectively) compared with the control (40.20 °C). The inclusion of 1000 mg betaine/kg in the growing rabbits' diets nearly doubled the humoral and immune responses compared to the controls (P < 0.05) and significantly reduced rectal temperature and respiration rate. Serum T3, T4, total protein, globulin and total lipids were significantly increased while serum glucose concentration was significantly decreased due to dietary betaine.

In conclusion, supplemental dietary betaine enhanced growth performance and humoral and cell-mediated immunity as well as reduced rectal temperature and respiration rate in growing rabbits subjected to heat stress. From an economic point of view, high levels of betaine are not recommended because betaine is reasonably effective at lower, less expensive, doses.

Hassan et al (2011). "Effect of dietary betaine supplementation on growth, carcass and immunity of New Zealand White rabbits under high ambient temperature." Livestock Science 135(2-3): 103-109.