High dietary choline and betaine intake is associated with low insulin resistance

OBJECTIVE: Dietary betaine supplement could ameliorate insulin resistance (IR) in animals, but no data are available for choline. Reports on humans are rare. The aim of this study was to investigate the association between dietary choline and betaine intake and IR in humans.
METHODS: We assessed 2394 adults from the CODING (Complex Diseases in the Newfoundland population: Environment and Genetics) study. Intake of dietary choline and betaine was evaluated from the Willett Food Frequency Questionnaire. IR was estimated by homeostatic model assessment (HOMA-IR) and the quantitative insulin-sensitivity check index (QUICKI). Partial correlation analysis was used to determine the correlations of dietary choline and betaine intake with IR adjusted for major confounding factors.
RESULTS: Dietary choline and betaine intake was inversely correlated with levels of fasting glucose and insulin, HOMA-IR, HOMA-beta (r = -0.08 to -0.27 for choline and r = -0.06 to -0.16 for betaine; P < 0.05) and positively related to QUICKI (r = 0.16-0.25 for choline and r = 0.11-0.16 for betaine; P < 0.01) in both sexes after controlling for age, total calorie intake, and physical activity level. The significant associations disappeared in men after percent trunk fat was added as a confounding factor. Furthermore, individuals with the highest tertile of dietary choline and betaine intake had the lowest IR severity. Dietary choline and betaine intake, however, was the lowest in the high IR group, intermediate in the medium group, and the highest in the low IR group.
CONCLUSION: This study demonstrated that higher intake of dietary choline and betaine is associated with lower IR in the general population.

Gao, X., et al. (2017). "High dietary choline and betaine intake is associated with low insulin resistance in the Newfoundland population." Nutrition 33: 28-34.

Betaine raises brain serotonin levels and produces antidepressant-like effects in rats

The purpose of the present study was to examine the effect of Lycii Radicis Cortex (LRC) and betaine (BT) on immobility and neurochemical change in the forced swimming test (FST) in the rat. LRC, BT or fluoxentine was administered intraperitoneally to Sprague-Dawley rats three times (1, 5 and 23.5 h) before the FST. To investigate antidepressant-like effect, serotonin (5-HT) and norepinephrine (NE) were examined in the hippocampus and hypothalamus of rats. LRC (100 mg/kg) and BT (30, 100 mg/kg) significantly decreased the immobility time in the FST. LRC (100 mg/kg) significantly increased both 5-HT and NE levels in the hypothalamus of rats exposed to FST. BT (100 mg/kg) significantly increased 5-HT levels in the hypothalamus and hippocampus of rats. Taken together, these results demonstrated that improvement in the behavioral changes after LRC and BT administration may be mediated by elevation of 5-HT level in the hypothalamus and hippocampus, indicating a possible antidepressant-like activity. The present results suggest that the efficacy of LRC and BT in an animal model of depression may provide anti-depressant effects in human, which remains to be determined.

Kim, S.J., et al., Antidepressant-like effects of lycii radicis cortex and betaine in the forced swimming test in rats. Biomol Ther (Seoul), 2013. 21(1): p. 79-83

Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise

Our aim was to examine the effect of betaine supplementation on selected circulating hormonal measures and Akt muscle signaling proteins after an acute exercise session. Twelve trained men (age 19.7 +/- 1.23 years) underwent 2 weeks of supplementation with either betaine (B) (1.25 g BID) or placebo (P). Following a 2-week washout period, subjects underwent supplementation with the other treatment (B or P). Before and after each 2-week period, subjects performed an acute exercise session (AES). Circulating GH, IGF-1, cortisol, and insulin were measured. Vastus lateralis samples were analyzed for signaling proteins (Akt, p70 S6k, AMPK). B (vs. P) supplementation approached a significant increase in GH (mean +/- SD (Area under the curve, AUC), B: 40.72 +/- 6.14, P: 38.28 +/- 5.54, p = 0.060) and significantly increased IGF-1 (mean +/- SD (AUC), B: 106.19 +/- 13.45, P: 95.10 +/- 14.23, p = 0.010), but significantly decreased cortisol (mean +/- SD (AUC), B: 1,079.18 +/- 110.02, P: 1,228.53 +/- 130.32, p = 0.007). There was no difference in insulin (AUC). B increased resting Total muscle Akt (p = 0.003). B potentiated phosphorylation (relative to P) of Akt (Ser(473)) and p70 S6 k (Thr(389)) (p = 0.016 and p = 0.005, respectively). Phosphorylation of AMPK (Thr(172)) decreased during both treatments (both p = 0.001). Betaine (vs. placebo) supplementation enhanced both the anabolic endocrine profile and the corresponding anabolic signaling environment, suggesting increased protein synthesis.
Apicella, J.M., et al., Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise. Eur J Appl Physiol, 2013. 113(3): p. 793-802

Dietary factors associated with adiponectin

In this epidemiological study, dietary betaine and choline intake were not correlated with plasma HMW adiponectin levels.

Yannakoulia et al (2008). "Dietary factors associated with plasma high molecular weight and total adiponectin levels in apparently healthy women." Eur J Endocrinol 159(4): R5-10.

Betaine Reverses IR and NAFLD

Borgschulte et al (2008). "Betaine Treatment Reverses Insulin Resistance and Fatty Liver Disease Without Reducing Oxidative Stress or Endoplasmic Reticulum Stress in An Animal Model of NAFLD." Gastroenterology 134(4): A414.

Compared to a control diet, a high fat diet led to increased:

- body weight
- plasma insulin and homocysteine
- liver injury
- oxidative and endoplasmic reticulum stress

Addition of betaine (1.5%) to the high fat diet reduced:

- body weight
- plasma insulin and homocysteine
- liver injury

Papers 2004-7:

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