Higher Dietary Choline and Betaine Intakes Are Associated with Better Body Composition

BACKGROUND: Choline is an essential nutrient and betaine is an osmolyte and methyl donor. Both are important to maintain health including adequate lipid metabolism. Supplementation of dietary choline and betaine increase muscle mass and reduce body fat in animals. However, little data is available regarding the role of dietary choline and betaine on body composition in humans.
OBJECTIVE: To investigate the association between dietary choline and betaine intakes with body composition in a large population based cross-sectional study. DESIGN: A total of 3214 subjects from the CODING (Complex Disease in Newfoundland population: Environment and Genetics) study were assessed. Dietary choline and betaine intakes were computed from the Willett Food Frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry following a 12-hour fast. Major confounding factors including age, sex, total calorie intake and physical activity level were controlled in all analyses.
RESULT: Significantly inverse correlations were found between dietary choline and betaine intakes, with all obesity measurements: total percent body fat (%BF), percent trunk fat (%TF), percent android fat (%AF), percent gynoid fat (%GF) and anthropometrics: weight, body mass index, waist circumference, waist-to-hip ratio in both women and men (r range from -0.13 to -0.47 for choline and -0.09 to -0.26 for betaine. Dietary choline intake had stronger association than betaine. Moreover, obese subjects had the lowest dietary choline and betaine intakes, with overweight subjects in the middle, and normal weight subjects consumed the highest dietary choline and betaine. Vice versa, when subjects were ranked according to dietary choline and betaine intakes, subjects with the highest intake of both had the lowest %TF, %AF, %GF, %BF and highest %LM among the groups in both sexes.
CONCLUSION: Our findings indicate that high dietary choline and betaine intakes are significantly associated with favorable body composition in humans.

Gao, X., et al. (2016). "Higher Dietary Choline and Betaine Intakes Are Associated with Better Body Composition in the Adult Population of Newfoundland, Canada." PLoS ONE 11(5): e0155403.

Maternal betaine supplementation during gestation enhances gene expression in skeletal muscle of newborn piglets

Betaine has been widely used in animal and human nutrition to promote muscle growth and performance, yet it remains unknown whether maternal betaine supplementation during gestation affects the metabolic characteristics of neonatal skeletal muscles. In the present study, feeding sows with betaine-supplemented diets throughout gestation significantly up-regulated the expression of mtDNA-encoded OXPHOS genes including COX1, COX2 and ND5, in the muscle of newborn piglets, which was associated with enhanced mitochondrial COX enzyme activity. Concurrently, maternal betaine supplementation increased plasma betaine concentration and muscle expression of methyl transfer enzymes, BHMT and GNMT in offspring piglets. Nevertheless, Dnmt3a was down-regulated at the level of both mRNA and protein, which was associated with hypomethylated mtDNA D-loop region. These results suggest that maternal betaine supplementation during gestation enhances expression of mtDNA-encoded genes through D-loop DNA hypomethylation in skeletal muscle of newborn piglets.

Jia, Y., et al., Maternal betaine supplementation during gestation enhances expression of mtDNA-encoded genes through D-loop DNA hypomethylation in skeletal muscle of newborn piglets. J Agric Food Chem, 2015.

The beneficial effects of betaine on dysfunctional adipose tissue and N6-methyladenosine mRNA methylation requires the AMP-activated protein kinase alpha1 subunit

The current study was conducted to determine whether betaine could improve fatty acid oxidation, mitochondrial function and N6-methyladenosine (m6A) mRNA methylation in adipose tissue in high-fat-induced mice and how AMP-activated protein kinase alpha1 subunit (AMPKalpha1) was involved. AMPKalpha1 knockout mice and wild-type mice were fed either a low-fat diet, high-fat diet or high-fat diet supplemented with betaine in the drinking water for 8weeks. Our results showed that mitochondrial genes (PGC1alpha) and beta-oxidation-related genes (CPT1a) at protein level were increased in wild-type mice supplemented with betaine when compared with those in mice with high-fat diet. Betaine also decreased FTO expression and improved m6A methylation in adipose tissue of wild-type mice with high-fat diet. However, betaine failed to exert the abovementioned effects in AMPKalpha1 knockout mice. In adipocytes isolated from mice with high-fat diet, betaine treatment increased lipolysis and lipid oxidation. Moreover, betaine decreased FTO expression and increased m6A methylation. However, while AMPKalpha1 was knockdown, no remarkable changes in adipocytes were observed under betaine treatment. Our results indicated that betaine supplementation rectified mRNA hypomethylation and high FTO expression induced by high-fat diet, which may contribute to its beneficial effects on impaired adipose tissue function. Our results suggested that the AMPKalpha1 subunit is required for the beneficial effects of betaine on dysfunctional adipose tissue and m6A methylation. These results may provide the foundation for a mechanism that links m6A methylation status in RNA, AMPKalpha1 phosphorylation and dysfunctional adipose tissue induced by high-fat diet.

Zhou, X., et al., The beneficial effects of betaine on dysfunctional adipose tissue and N6-methyladenosine mRNA methylation requires the AMP-activated protein kinase alpha1 subunit. J Nutr Biochem, 2015

Effects of dietary betaine on growth performance, fat deposition and serum lipids in broilers subjected to chronic heat stress

We evaluated the effects of supplementing betaine on growth performance, fat deposition and lipid metabolism status in broilers kept under chronic heat stress. Five hundred and forty chicks were randomly divided into six groups and the two normal temperature groups were held at normal ambient temperature and fed the basal diet (CONT) and basal diet plus 0.1% betaine, respectively. Heat stressed (HS) broilers were held at 32 +/- 1 degrees C from days 22 to 42 and fed the basal diet containing variable levels of betaine. Broilers were examined at days 28, 35 and 42 for body weight, feed consumption, fat deposition and serum lipids. The CONT and betaine-supplemented groups showed higher (P < 0.01 or P < 0.05) feed consumption, body weight gain, and lower feed : gain ratio compared with the HS-CONT group. Meanwhile, heat stress increased abdominal, intermuscular and subcutaneous fat deposition, whereas the supplemental betaine significantly decreased those compared with the HS-CONT group. Additionally, betaine supplementation significantly decreased triglyceride, free fatty acids, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol compared with HS-CONT. Chronic HS reduces broiler production performance. However, betaine can reverse these negative effects partially and thus improve carcass composition by changing lipid metabolism.

He, S., et al., Effects of dietary betaine on growth performance, fat deposition and serum lipids in broilers subjected to chronic heat stress. Anim Sci J, 2015.

Higher serum concentrations of betaine is associated with better profiles of body fat and fat distribution in Chinese adults

Objective: Animal studies have suggested that betaine but not choline may improve body composition, but little evidence is available in humans. We examined the associations of serum concentrations of choline and betaine with body composition and fat distribution in adults.
Methods: This community-based study recruited 1996 adults (W/M: 1380/616) aged 40-75 in urban Guangzhou, China. General information and anthropometric measurements were taken, and serum choline and betaine levels were assessed by HPLC-MS between July 2008 and June 2010. After 3.2 years, 1623 of the 1996 participants were measured for fat mass (FM and %FM) over the total body (TB), trunk, limbs, android (A) and gynoid (G) regions. The %FM ratios of the A/G and the trunk and limbs were determined by dual-energy X-ray absorptiometry (DXA).
Results: Univariate analyses showed that higher serum betaine levels were significantly associated with lower values of adiposity indices, except in the case of the %FM at the gynoid area. After adjusting for potential covariates, similar associations were observed. The mean percentage differences between quartiles 4 and 1 of the serum betaine levels were -4.9% (weight), -4.7% (BMI), -2.5% (WC), -7.9% (TB FM) and -3.4% (TB %FM). The mean differences in the FM and %FM were much more pronounced at the trunk (-10.0% and -4.5%) or android areas (-10.7% and -4.7%) than those at the limbs (-0.8% and -2.3%) or gynoid areas (-0.6% and -1.4%). Such favorable associations were stronger in men than in women. No significant associations between serum choline and the adiposity indices were observed, except in the cases of body weight and BMI.
Conclusions: Greater circulating betaine, but not choline, was dose-dependently associated with better body composition and fat distribution due to a lower fat mass in the trunk regions in this population.

Chen, Y.-m., et al., Higher serum concentrations of betaine rather than choline is associated with better profiles of DXA-derived body fat and fat distribution in Chinese adults. Int J Obes, 2014.

The effect of dietary alpha-lipoic acid, betaine, l-carnitine, and swimming on the obesity of mice induced by a high-fat diet

We evaluate the effect of supplementation, at 300 mg kg-1 body weight (BW), with the antioxidants alpha-lipoic acid (AL), betaine (BT), l-carnitine (LC), and the combination of these and exercise on obesity induced by a 9 week high-fat diet (HFD) in mice. Healthy 5 week-old male C57BL/6J mice were divided into 9 groups: (1) CON, control group fed with a commercial mice chow containing 10% crude fat; (2) HFD, high fat diet group fed with a commercial mice chow containing 60% crude fat; (3) HFD-AL, HFD group fed with AL; (4) HFD-BT, HFD group fed with BT; (5) HFD-LC, HFD group fed with LC; (6) HFD-SW, HFD with swimming as an exercise; (7) HFD-SWAL, HFD-AL with swimming; (8) HFD-SWBT, HFD-BT with swimming, and (9) HFD-SWLC, HFD-LC with swimming. The BW of mice with LC and swimming reduced the increase of BW after 9 weeks. Relative adipose tissue weights were reduced by the combinations of antioxidant supplementation and swimming. Levels of serum glucose and leptin were reduced in the HFD-SWLC group when compared with the HFD group. Serum triglyceride and total cholesterol and the size of adipose were also decreased in the HFD-LC and HFD-SWLC groups. These results show that LC at a dose of 300 mg kg-1 BW was the most effective for reducing fat accumulation in mice with HFD for 9 weeks. In addition, exercise should be given in combination to enhance the BW reduction and serum lipid level.

Jang, A., et al., The effect of dietary alpha-lipoic acid, betaine, l-carnitine, and swimming on the obesity of mice induced by a high-fat diet. Food Funct, 2014

Betaine supplementation improved body composition, arm size, bench press work capacity, attenuated the rise in urinary HCTL, and tended to improve power but not strength

BACKGROUND: This study investigated the effects of long term betaine supplementation on body composition, performance, and homocysteine thiolactone (HCTL) in experienced strength trained men. METHODS: Twenty-three subjects were matched for training experience (4.8 +/- 2.3 years) and body fat percentage (BF%: 16.9 +/- 8.0%), randomly assigned to either a placebo (PL; n = 12) or betaine group (BET; n = 11; 2.5 g/day), and completed a 6 week periodized training program consisting of 3 two-week micro-cycles. Bench press and back squat training volumes were recorded and changes in training volume were assessed at each micro-cycle. Fasting urine was collected at baseline (BL), weeks 2, 4 and 6, and assayed for HCTL. Subjects were tested prior to and following 6 weeks of treatment. Arm and thigh cross sectional area (CSA) was estimated via girth and skin fold measurements. Body density was estimated via skin fold calipers and used to estimate BF%, fat mass (FM), and lean body mass (LBM). Performance was assessed via vertical jump (VJ), bench press 1 RM (BP), and back squat 1 RM (BS).
RESULTS: Arm CSA increased significantly (p < .05) in BET but not PL. No differences existed between group and time for changes in thigh CSA. Back squat training volume increased significantly (p < .05) for both groups throughout training. Bench press training volume was significantly (p < .05) improved for BET compared to PL at microcycles one and three. Body composition (BF%, FM, LBM) improved significantly (p < .05) in BET but not PL. No differences were found in performance variables (BP, BS, VJ) between groups, except there was a trend (p = .07) for increased VJ power in BET versus PL. A significant interaction (p < .05) existed for HCTL, with increases from BL to week 2 in PL, but not BET. Additionally, HCTL remained elevated at week 4 in PL, but not BET.
CONCLUSION: Six-weeks of betaine supplementation improved body composition, arm size, bench press work capacity, attenuated the rise in urinary HCTL, and tended to improve power (p = .07) but not strength.

Cholewa, J.M., et al., Effects of betaine on body composition, performance, and homocysteine thiolactone. J Int Soc Sports Nutr, 2013. 10(1): p. 39

Effects of Betaine on Energy Utilization in Growing Pigs - A Review

One of the well known biological functions of betaine is that of a methyl donor. Therefore, betaine may partly replace choline and methionine in the diet. Another widely documented role of betaine is to restore and maintain the osmotic balance. As an organic osmotic compound, betaine regulates the water balance, thus exerting a stabilizing influence on tissue metabolism, particularly within the digestive tract. As a donor of methyl groups necessary for various reactions in the body, betaine is indirectly involved in lipid metabolism. Due to its metabolic functions, betaine is also believed to play a significant role in energy metabolism in pigs. Of particular note are the results of experiments in which a positive effect of betaine supplementation was observed as the energy content of the diet was decreased.

Lipinski, K., et al., Effects of Betaine on Energy Utilization in Growing Pigs - A Review. Annals of Animal Science, 2012. 12(3): p. 291-300

Plasma choline metabolites associate with metabolic stress among young overweight men in a genotype-specific manner

We aimed to test the hypotheses that (i) plasma choline metabolites differ between normal (body mass index (BMI)<25 and="and" kg="kg" m="m" overweight="overweight">/=25 kg m(-2)) men, and (ii) an elevated BMI alters associations between plasma choline metabolites and indicators of metabolic stress.
DESIGN: This was a cross-sectional study. A one-time fasting blood sample was obtained for measurements of the choline metabolites and metabolic stress indicators (that is, serum alanine aminotransferase (ALT), glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and homocysteine), and for genotype determination.
SUBJECTS: The analysis was conducted with 237 Mexican American men with a median age of 22 years.
RESULTS: Compared with men with a normal BMI (n=98), those with an elevated BMI (n=139) had 6% lower (P=0.049) plasma betaine and an 11% lower (P=0.002) plasma betaine to choline ratio. Among men with an elevated BMI, plasma betaine and the plasma betaine to choline ratio positively associated (P</=0.044) with a favorable serum cholesterol profile, and inversely associated (P=0.001) with serum ALT, a marker of liver dysfunction. The phosphatidylethanolamine N-methyltransferase (PEMT) 5465Gshort right arrowA (rs7946) genotype interacted (P</=0.007) with the plasma betaine to choline ratio to modulate indicators of metabolic stress with stronger inverse associations observed among overweight men with the PEMT 5465GG genotype.
CONCLUSIONS: Plasma choline metabolites predict metabolic stress among overweight men often in a genotype-specific manner. The diminished betaine among overweight men coupled with the inverse association between betaine and metabolic stress suggest that betaine supplementation may be effective in mitigating some of the metabolic insults arising from lipid overload.

Yan, J., et al., Plasma choline metabolites associate with metabolic stress among young overweight men in a genotype-specific manner. Nutr Diabetes, 2012. 2: p. e49

Effects of dietary supplementation with betaine on a nonalcoholic steatohepatitis (NASH) mouse model.

The effects of betaine supplementation on non-alcoholic steatohepatitis (NASH) model mice were examined by measuring the accumulation of fat in the livers of NASH model mice compared to a control. Betaine from sugar beets was provided to the model mice as a dietary supplement. After 3 wk of dietary supplementation. there were no significant differences in body weight or liver weight between the groups. However, the liver to body weight ratio in the high-fat diet with betaine (HM) group was significantly higher than that in the high-fat diet (HF) group. There were no differences in scrum triglyceride (TG) concentrations. AST and ALT activities, or hepatic glutathione concentrations between the groups. Hepatic TG level in the Ha group was significantly lower than that in the HF group. Hepatic cells obtained from the HF group showed increased occurrence of explosive puff and necrosis as compared with those in the HFB group. Betaine supplementation had an inhibitory effect on fat accumulation in the liver: the Oil red-positive area in the Ha group (0.82 +/- 0.85%) was significantly smaller than that in the HF group (9.06 +/- 2.24%). These results indicate the potential of betaine to serve as an agent for amelioration of hepatic steatosis in NASH model mice.

Kawakami, S., et al., Effects of dietary supplementation with betaine on a nonalcoholic steatohepatitis (NASH) mouse model. Journal of Nutritional Science and Vitaminology, 2012. 58(5): p. 371-5

Antioxidant effect of betaine on adipose tissue when added to a high fat diet

Although well-established, the underlying mechanisms involved in obesity-related plasma adiponectin decline remain elusive. Oxidative stress is associated with obesity and insulin resistance and considered to contribute to the progression toward obesity-related metabolic disorders. In this study, we investigated the effects of 4-hydroxynonenal (4-HNE), the most abundant lipid peroxidation end product, on adiponectin production and its potential implication in obesity-related adiponectin decrease. Long-term high-fat diet feeding led to obesity in mouse, accompanied by decreased plasma adiponectin and increased adipose tissue 4-HNE content. Exposure of adipocytes to exogenous 4-HNE resulted in decreased adiponectin secretion in a dose-dependent manner, which was consistent with significantly decreased intracellular adiponectin protein abundance. In contrast, adiponectin gene expression was significantly elevated by 4-HNE treatment, which was concomitant with increased peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression and transactivity. The effect was abolished by T0070907, a PPAR-γ antagonist, suggesting that PPAR-γ activation plays a critical role in this process. To gain insight into mechanisms involved in adiponectin protein decrease, we examined the effects of 4-HNE on adiponectin protein degradation. Cycloheximide (CHX)-chase assay revealed that 4-HNE exposure accelerated adiponectin protein degradation, which was prevented by MG132, a potent proteasome inhibitor. Immunoprecipitation assay showed that 4-HNE exposure increased ubiquitinated adiponectin protein levels. These data altogether indicated that 4-HNE enhanced adiponectin protein degradation via ubiquitin–proteasome system. Finally, we demonstrated that supplementation of HF diet with betaine, an antioxidant and methyl donor, alleviated high-fat-induced adipose tissue 4-HNE increase and attenuated plasma adiponectin decline. Taken together, our findings suggest that the lipid peroxidation product 4-HNE can differentially regulates adiponectin gene expression and protein abundance and may play a mechanistic role in obesity-related plasma adiponectin decline.

Wang, Z., et al., 4-Hydroxynonenal differentially regulates adiponectin gene expression and secretion via activating PPARgamma and accelerating ubiquitin-proteasome degradation. Mol Cell Endocrinol, 2011. 349(2): p. 222-31.

Plasma Lipids and Betaine Are Related in an Acute Coronary Syndrome Cohort

Background

Low plasma betaine has been associated with unfavorable plasma lipid profiles and cardiovascular risk. In some studies raised plasma betaine after supplementation is associated with elevations in plasma lipids. We aimed to measure the relationships between plasma and urine betaine and plasma lipids, and the effects of lipid-lowering drugs on these.

Methodology

Fasting plasma samples were collected from 531 subjects (and urine samples from 415) 4 months after hospitalization for an acute coronary syndrome episode. In this cross-sectional study, plasma betaine and dimethylglycine concentrations and urine excretions were compared with plasma lipid concentrations. Subgroup comparisons were made for gender, with and without diabetes mellitus, and for drug treatment.

Principal Findings

Plasma betaine negatively correlated with triglyceride (Spearman's rs = −0.22, p<0.0001) and non-high-density lipoprotein cholesterol (rs = −0.27, p<0.0001). Plasma betaine was a predictor of BMI (p<0.05) and plasma non-high-density lipoprotein cholesterol and triglyceride (p<0.001) independently of gender, age and the presence of diabetes. Using data grouped by plasma betaine decile, increasing plasma betaine was linearly related to decreases in BMI (p = 0.008) and plasma non-HDL cholesterol (p = 0.002). In a non-linear relationship betaine was negatively associated with elevated plasma triglycerides (p = 0.004) only for plasma betaine >45 µmol/L. Subjects taking statins had higher plasma betaine concentrations (p<0.001). Subjects treated with a fibrate had lower plasma betaine (p = 0.003) possibly caused by elevated urine betaine loss (p<0.001). The ratio of coenzyme Q to non-high-density lipoprotein cholesterol was higher in subjects with higher plasma betaine, and in subjects taking a statin.

Conclusion

Low plasma betaine concentrations correlated with an unfavourable lipid profile. Betaine deficiency may be common in the study population. Controlled clinical trials of betaine supplementation should be conducted in appropriate populations to determine whether correction affects cardiovascular risk.

Lever, M., et al., Plasma lipids and betaine are related in an acute coronary syndrome cohort. PLoS One, 2011. 6(7): p. e21666.

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.

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.

Cytosol betaine decreases with a high fat diet

Liver and serum metabolites of obese and lean mice fed on high fat or normal diets were analyzed using ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry, gas chromatography-mass spectrometry, and partial least-squares-discriminant analysis (PLS-DA).

Obese and lean groups were clearly discriminated from each other on PLS-DA score plot and major metabolites contributing to the discrimination were assigned as lipid metabolites (fatty acids, phosphatidylcholines (PCs), and lysophosphatidylcholines (lysoPCs)), lipid metabolism intermediates (betaine, carnitine, and acylcarnitines), amino acids, acidic compounds, monosaccharides, and serotonin. A high-fat diet increased lipid metabolites but decreased lipid metabolism intermediates and the NAD/NADH ratio, indicating that abnormal lipid and energy metabolism induced by a high-fat diet resulted in fat accumulation via decreased beta-oxidation. In addition, this study revealed that the levels of many metabolites, including serotonin, betaine, pipecolic acid, and uric acid, were positively or negatively related to obesity-associated diseases.

On the basis of these metabolites, we proposed a metabolic pathway related to high-fat diet-induced obesity. These metabolites can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, the level changes of these metabolites can be used to assess the risk of obesity and the therapeutic effect of obesity management.

Kim et al (2010). "Metabolomic analysis of livers and serum from high-fat diet induced obese mice." J Proteome Res 10(2): 722-31.

Betaine supplementation improves abdominal fat traits and decreases transcription of lipogenenis genes

Experiments were conducted to investigate the effect of betaine supplementation on mRNA expression levels of lipogenesis genes and CpG methylation of lipoprotein lipase gene (LPL) in broilers.

From 22 days of age, 78 broilers were feed basal diet without betaine and basal diet supplemented with 0.1% betaine, respectively, and at 56 and 66 days of age, the traits of 15 chickens (7 males and 8 females) of each group were recorded and abdominal fat pads were collected. The mRNA expression levels of several lipogenesis gene were analyzed by semi-quantitative RT-PCR and real-time quantitative RT-PCR (qPCR), respectively. The CpG methylation profile at the promoter region of LPL gene in 66-day-old broilers was determined by bisulfite sequencing. The average daily gain and percent abdominal fat traits were slightly improved in 56-day-old and 66-day-old broilers after dietary supplementation of betaine to diet. After adding 0.1% betaine to diet, the mRNA levels of fatty acid synthase (FAS) and adipocyte-type fatty acid-binding protein genes in abdominal adipose were significantly decreased in 56-day-old broilers, and those of LPL and FAS genes in abdominal adipose were significantly decreased in 66-day-old broilers comparing with the control group (P < 0.05 and P < 0.001). Moreover, in 66-day-old broilers fed 0.1% betaine diet, a different CpG methylation pattern was observed: the CpG dinucleotides of 1st, 6th, 7th, 8th and from 10th to 50th were less methylated; however, those of 2nd, 5th and 9th were more heavily methylated.

The results suggest that transcription of some lipogenesis genes was decreased by betaine supplementation and betaine may decrease LPL mRNA expression by altering CpG methylation pattern on LPL promoter region.


Xing et al (2010). "Effect of dietary betaine supplementation on lipogenesis gene expression and CpG methylation of lipoprotein lipase gene in broilers." Mol Biol Rep 38(3): 1975-81.

Developing fatty liver

The authors evaluated the effects of betaine supplementation on goose liver weight, liver/body weight, serum parameters and morphological changes.

Compared with the control and overfed groups, the geese that were fed the betaine diet showed increased liver weight and decreased abdominal adipose tissue weight compared with the overfeeding groups. Betaine treatment also significantly increased ChE, HDL, LDH and ALT levels. Decreased macrovesicular steatosis and increased microvesicular steatosis were observed in the betaine-treated group, and the lipid was well-distributed in the betaine supplement group. The expression of S14α mRNA in the livers of the betaine-treated geese was higher than that in the control or the overfed geese. The DNA methylation pattern in the S14α gene transcription start site may not be related to the expression of S14α transcript in response to betaine supplementation.

Su et al (2009). "The effects of dietary betaine supplementation on fatty liver performance, serum parameters, histological changes, methylation status and the mRNA expression level of Spot14[alpha] in Landes goose fatty liver." Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology. Epub May

Improved growth performance

120 female pigs were fed either a control commercial diet or the control diet supplemented with 2, 4 and 6% betaine for 31 days. Pigs fed betaine had:

- lower average daily feed intake (ADFI) (for 2% diet)
- higher average daily gain (ADG)
- lower feed conversion ratio (FCR)
- increased loin CIE a* (redness)
- higher loin shear force value
- decreased total blood cholesterol concentrations
- increased saturated fatty acid and decreased unsaturated fatty acid levels in muscle
- increased betaine concentrations in the loin muscle

It was concluded that dietary betaine supplementation of finishing pigs can improve growth performance, reduce blood cholesterol concentrations, and produce detectable betaine concentrations in the lion muscle.

Yang et al (2009). "Effects of dietary glycine betaine on growth and pork quality of finishing pigs." Asian-Australasion J Animal Sci 22(5): 706.

Greater daily gain and lean deposition in pigs

This study investigated the interactions between dietary ractopamine and betaine on growth and carcass characteristics in restrictively fed pigs. Pigs fed betaine had:

- greater daily gain (+8%)
- greater lean deposition (+5%)
- no effect on fat deposition

Dunshea et al (2009). "Dietary betaine and ractopamine combine to increase lean tissue deposition in finisher pigs, particularly gilts." Animal Production Science 49(1): 65-70.

Improved Body Weight and Biochemistry

Lu et al (2008). "Effects of betaine on body weight and biochemical index of obese rats fed high-fat diet." Acta Nutr Sinica 30(3): 311-5.

This study, published in Chinese, compared rats fed for 8 weeks on these diets:

- control
- high fat (HF)
- HF plus low betaine (15 mg/kg bwt) (HF/LB)
- HF plus medium betaine (30 mg/kg bwt) (HF/MB)
- HF plus high betaine (60 mg/kg bwt) (HF/HB)

Results for weight compared to control showed:

- HF diet led to greatest weight gain (i.e. 14% greater body weight at 8 weeks)
- HF/HB diet led to slowest weight gain (i.e. 7% greater body weight at 8 weeks)

Results for blood markers showed:

HF diet compared to control led to:

- higher fasting glucose and insulin
- higher malonaldehyde (MDA - marker of oxidative stress) and lower total antioxidant capacity (TAOC)
- lower HDL and higher LDL cholesterol
- higher free fatty acids (FFA)
- unchanged total cholesterol and triglyerides (TG)

Compared to HF diet:

- HF/HB diet led to improved blood glucose, MDA, TG and FFA
- HF/LB diet led to improved blood insulin, MDA and TAOC