Betaine protected against thrombotic coagulation events in vivo and in vitro and decreased plasma lipid peroxidation

Betaine (N,N,N-trimethylglycine) is an important food component with established health benefits through its homocysteine-lowering effects, and is used to lower total homocysteine concentration in plasma of patients with homocystinuria. It is well established that hyperhomocysteinemia is an established risk factor for cardiovascular disease and stroke. However, the possible protective effect of betaine on coagulation events in vivo and in vitro has thus far not been studied. Betaine was given to mice at oral doses of either 10 mg/kg (n = 6) or 40 mg/kg (n = 6) for seven consecutive days, and control mice (n = 6) received water only. The thrombotic occlusion time in photochemically induced thrombosis in pial arterioles was significantly delayed in mice pretreated with betaine at doses of 10 mg/kg (P < 0.001) and 40 mg/kg (P < 0.01). Similar effects were observed in pial venules with 10 mg/kg (P < 0.05) and 40 mg/kg (P < 0.05) betaine. In vitro, in whole blood samples collected from untreated mice (n = 3-5), betaine (0.01-1 mg/mL) significantly reversed platelet aggregation induced by adenosine diphosphate (5 microM). The number of circulating platelets and plasma concentration of fibrinogen in vivo were not significantly affected by betaine pretreament compared with the control group. Lipid peroxidation (LPO) in mice pretreated with betaine was significantly reduced compared with the control group. Moreover, betaine (0.01-1 mg/mL) caused a dose-dependent and significant prolongation of PT (n = 5) and aPTT (n = 4-6). In conclusion, our data show that betaine protected against coagulation events in vivo and in vitro and decreased LPO in plasma.

Nemmar, A., et al., Betaine (N,N,N-trimethylglycine) averts photochemically-induced thrombosis in pial microvessels in vivo and platelet aggregation in vitro. Exp Biol Med (Maywood), 2015

Betaine showed beneficial brain antioxidant effects following administration of levodopa and benserazide (used in the treatment of Parkinson's disease)

The present study was designed to evaluate antioxidant effects of betaine in the brain following administration of levodopa and benserazide, which are routinely used in the treatment of Parkinson's disease. Sprague-Dawley male rats were divided into levodopa (LD), Betaine (Bet.), levodopa plus betaine (LD/Bet.), levodopa plus benserazide (LD/Ben.), levodopa plus betaine-benserazide (LD/Bet.-Ben.) and control groups. The experimental groups received LD 300 mg/kg, Bet. 1.5 % w/w of the total diet, Ben. 75 mg/kg and distilled water to controls for 10 consecutive days, orally. The concentration of plasma total homocysteine significantly increased in LD/Ben.-treated rats when compared to the other groups. Brain glutathione peroxidase (GPx) activity and glutathione content both elevated with betaine treatment in LD/Bet. and LD/Bet.-Ben groups. Superoxide dismutase activity was also higher in controls and betaine-treated rats in comparison with LD and LD/Ben. groups. Likewise, catalase activity significantly increased in control and betaine groups when compared to LD- and LD/Ben.-treated rats. In contrast, brain lipid peroxidation significantly increased in response to LD and LD/Ben. treatments. Regarding metabolism of LD in peripheral tissues, serumic dopamine concentration significantly increased in LD-treated rats in comparison with LD/Ben. group. The present results show beneficial antioxidant and methyl donor properties of betaine versus oxidative stress and hyperhomocysteinemia induced by levodopa and benserazide in an animal model.

Alirezaei, M., et al., Beneficial antioxidant properties of betaine against oxidative stress mediated by levodopa/benserazide in the brain of rats. J Physiol Sci, 2015

SAMe plus betaine is a safe and effective tool to counteract mild depression

BACKGROUND: S-adenosyl-L-methionine (SAMe), a safe, endogenous, pleiotropic methyl donor well known for its antidepressant role, has been assumed to have a possible role in increasing plasma levels of compounds known to be able to raise cardiovascular risk. Although the issue is still being debated, betaine (trimethylglycine), a specific methyl donor involved in the homocysteine circuit, may be able to reduce such a risk and/or, by determining a sparing effect on endogenous SAMe, may be able to improve the clinical efficiency of SAMe itself. Indeed, preliminary results have shown clinical improvement determined by an add-on therapy with betaine administered along with SAMe, versus SAMe alone, to patients affected by mild/moderate depression. AIM: To evaluate the safety and antidepressant role played by the association of SAMe plus betaine versus amitriptyline administered in untreated individuals with a recent diagnosis of mild depression. METHODS: This small, open-label, randomized, observational study enrolled 64 individuals with a diagnosis of mild depression according to the Zung Self-Rating Depression Scale. After randomization, they were treated with either Laroxyl((R)) (amitriptyline, 75 mg/day) or DDM Metile((R)) (enteric-coated SAMe, 500 mg/day, plus betaine, 250 mg/day) for 12 months. Assessment of clinical scores and tolerability was performed at T=0 and after 3, 6, and 12 months. RESULTS: After 3 months, both treatments showed a small and not statistically significant improvement. After 6 and 12 months, both treated groups demonstrated a more noticeable improved response, although the group treated with SAMe plus betaine showed better results in terms of score, number of individuals in remission, and side effects. Compliance was overlapping in both treatments. CONCLUSION: The association of SAMe plus betaine seems to be a safe and effective tool to counteract mild depression and also when used as monotherapy in subjects with a recent diagnosis.

Di Pierro, F. and R. Settembre, Preliminary results of a randomized controlled trial carried out with a fixed combination of S-adenosyl-L-methionine and betaine versus amitriptyline in patients with mild depression. Int J Gen Med, 2015. 8: p. 73-8