Side Effects of betaine: A Synthesis of Findings from 27 Studies

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Original Abstract of the Article

Major Research Findings

Betaine has been shown to have various health benefits, including lowering homocysteine levels, improving liver function, providing cardioprotective effects, and having anti-inflammatory effects. However, some studies have reported potential side effects of betaine. 13 suggests that betaine may affect the activity of heart cells. 25 reports that dimethylthetin, an analog of betaine, can cause damage to sheep lungs. Additionally, 14 suggests that betaine may be effective in treating liver disease associated with short bowel syndrome but also states that betaine may affect the digestive system.

Reasons for Side Effects

Betaine is involved in various metabolic processes in the body, and its mechanisms of action are complex. Therefore, the mechanisms by which betaine causes side effects are not yet fully understood. However, the following factors are thought to be involved in the side effects of betaine.

  • Effects due to lowering homocysteine levels
  • Interference with metabolic pathways
  • Impact on cell membranes
  • Effects on specific organs

Common Side Effects

Digestive System

Betaine may affect the digestive system. For example, 14 suggests that betaine may be effective in treating liver disease associated with short bowel syndrome but also states that betaine may affect the digestive system. 18 suggests that betaine may affect cell membranes and cause inflammation and ulcers in the digestive system.

Respiratory System

Dimethylthetin, an analog of betaine, has been reported to damage sheep lungs. In 25 , sheep that received dimethylthetin showed lung inflammation and necrosis, and death was also reported in some cases.

Heart

Betaine may affect the activity of heart cells. 13 suggests that betaine may affect the activity of heart cells. Specific side effects may include increased heart rate, atrial fibrillation, and heart failure.

Countermeasures for Side Effects

Digestive System

The following countermeasures can be considered to reduce digestive side effects from betaine.

  • Start with a small amount of betaine and gradually increase the amount
  • Take it with food
  • Drink with water
  • Take digestive medications if necessary

Respiratory System

The following countermeasures can be considered to reduce respiratory side effects from betaine.

  • Avoid using dimethylthetin, an analog of betaine, as it has been reported to damage sheep lungs
  • Consult a doctor before taking betaine

Heart

The following countermeasures can be considered to reduce heart-related side effects from betaine.

  • If you have underlying conditions such as heart disease or high blood pressure, consult a doctor before taking betaine
  • If you experience shortness of breath, chest pain, or palpitations while taking betaine, consult a doctor immediately

Comparison Across Studies

Commonalities

Multiple studies have shown that betaine may offer health benefits, but they also point out the possibility of side effects. These studies are important for gaining a deeper understanding of the efficacy and safety of betaine.

Differences

The frequency and severity of side effects of betaine vary across studies. The mechanisms underlying betaine side effects are not fully understood. Further research is needed.

Precautions for Real-life Applications

Betaine is widely available as a health food, but the possibility of side effects needs to be considered. It is important to consult a doctor or pharmacist before taking betaine.

Limitations of Current Research

There is still insufficient research on the side effects of betaine. In particular, further research is needed on the effects of long-term intake and side effects in specific populations.

Future Research Directions

The following research on the side effects of betaine is needed in the future.

  • Research on the effects of long-term betaine intake
  • Research on the side effects of betaine in specific populations
  • Research to elucidate the mechanisms of betaine side effects

Conclusion

Betaine is a nutrient that may offer health benefits, but it is important to be aware of the possibility of side effects. When taking betaine, it is essential to consult a doctor or pharmacist, understand the risks and benefits of side effects, and adhere to appropriate intake levels.

Literature analysis of 27 papers
Positive Content
20
Neutral Content
2
Negative Content
5
Article Type
4
0
0
0
26
1.

Nanozyme-based guanidinium peptides mediate surface reactive oxygen species for multidrug resistant bacterial infection management.

Author: ZhuXufeng, SunQiang, ChenJinjun, LiangChunmei, ChenLiang, QiYi, LuoHui, ChenLanmei, ChenJincan

Antibacterial agent
Wound healing
Toxicity

This study describes the development of a high-efficiency and low-toxicity antibacterial agent based on iridium oxide nanozymes (IrO<sub><i>x</i></sub> NPs) modified with guanidinium peptide-betaine (SNLP/BS-12). The resulting SBI NPs exhibited enhanced antibacterial activity and reduced cytotoxicity, suggesting their potential as a novel antibiotic candidate in the postantibiotic era.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Leishmanicidal effect of 1,3,4-thiadiazolium mesoionic salts on Leishmania amazonensis in vitro.

Author: Dos Santos RosaAlice, Frauches-SantosCristiane, SantanaRaissa Couto, GomesJanice S C, LimaKaroline, EchevarriaAurea, SaraivaElvira, Decote-RicardoDebora, AtellaGeorgia, Pinto-da-SilvaLucia H

Leishmaniasis treatment

This study analyzed the cytotoxic effects of mesoionic salts on Leishmania amazonensis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

Treatment experience in two adults with creatinfe transporter deficiency.

Author: SchjelderupJack, HopeSigrun, VatshelleChristian, van KarnebeekClara D M

Improved function
Well-tolerated

Betaine supplementation was well-tolerated and effective in adults with creatine transporter deficiency (CTD), while arginine and glycine were associated with adverse effects. Betaine may be a promising new treatment option for CTD.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

5.

The Use of Voltage Sensitive Dye di-4-ANEPPS and Video-Based Contractility Measurements to Assess Drug Effects on Excitation-Contraction Coupling in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Author: Hortigon-VinagreMaria Pura, ZamoraVictor, BurtonFrancis L, SmithGodfrey L

Cardiotoxicity assessment
Drug attrition
Drug failure

This study demonstrates the use of a novel technique combining contractility and voltage measurements on hiPSC-CMs for assessing drug cardiotoxicity, offering a mechanistic view of drug effects on cardiac cells.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Food, Acid Supplementation and Drug Absorption - a Complicated Gastric Mix: a Randomized Control Trial.

Author: SurofchyDalga D, FrassettoLynda A, BenetLeslie Z

Gastric side effects

Betaine hydrochloride (BHCl) was able to reacidify gastric pH after food-induced elevations in gastric pH, but a 4500 mg dose was required.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

8.

Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial.

Author: MazzaA, CiceroA F, RamazzinaE, LentiS, SchiavonL, CasigliaE, GussoniG

Reduces HCys levels
Safe and well tolerated

This study investigated the efficacy of nutraceuticals containing folate, vitamin B6, B12, B2, zinc, and betaine in lowering homocysteine (HCys) levels compared to conventional vitamin supplementation in hypertensive subjects with hyper-homocysteinemia. The study found that the nutraceutical group had significantly greater HCys reduction compared to the control group.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

9.

A randomized trial of Boswellia in association with betaine and myo-inositol in the management of breast fibroadenomas.

Author: PastaV, DinicolaS, GiulianiA, HarrathA H, AlwaselS H, TartagliaF, CucinaA, BizzarriM

Fibroadenoma regression
Anti-estrogenic side effects

This study proposes a synergistic approach using Boswellia, betaine, and myo-inositol to induce the regression of symptomatic fibroadenoma, targeting multiple pathways involved in inflammatory, metabolic, oxidative, and endocrine processes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Zwitterionic nanoparticles constructed from bioreducible RAFT-ROP double head agent for shell shedding triggered intracellular drug delivery.

Author: HuangPingsheng, LiuJinjian, WangWeiwei, ZhangYumin, ZhaoFuli, KongDeling, LiuJianfeng, DongAnjie

Anticancer therapy
Enhanced drug delivery
Low toxicity
Targeted delivery

Nanomedicines for cancer therapy often face challenges with drug delivery. This study developed novel bioreducible nanoparticles that overcome these barriers by releasing drugs rapidly and effectively within cells. The nanoparticles demonstrate superior antitumor activity and lower toxicity compared to free drugs in mice.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

A near-infrared fluorescent voltage-sensitive dye allows for moderate-throughput electrophysiological analyses of human induced pluripotent stem cell-derived cardiomyocytes.

Author: Lopez-IzquierdoAngelica, WarrenMark, RiedelMichael, ChoScott, LaiShuping, LuxRobert L, SpitzerKenneth W, BenjaminIvor J, Tristani-FirouziMartin, JouChuanchau J

Drug screening
Electrophysiological analysis

This study evaluates the use of the near-infrared fluorescent voltage-sensitive dye di-4-ANBDQBS for moderate-throughput electrophysiological analyses of human iPSC-CMs. The dye allowed for high-precision optical AP measurements, increasing throughput 10-fold compared to traditional patch-clamp techniques.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

14.

Betaine: a potential agent for the treatment of hepatopathy associated with short bowel syndrome.

Author: Teixeira AraújoGuilherme, DomeniciFernanda, EliasJorge, VannucchiHélio

Hepatopathy treatment

This study evaluated the efficacy of betaine in treating the hepatopathy associated with short bowel syndrome.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

16.

Vascular catheters with a nonleaching poly-sulfobetaine surface modification reduce thrombus formation and microbial attachment.

Author: SmithRoger S, ZhangZheng, BouchardMichael, LiJun, LappHeather S, BrotskeGregory R, LucchinoDavid L, WeaverDouglas, RothLaurence A, CouryArthur, BiggerstaffJohn, SukavaneshvarSivaprasad, LangerRobert, LooseChristopher

Catheter occlusion prevention
Infection prevention
Thrombotic embolism prevention
Venous thrombosis prevention

This study investigated the use of a nonleaching polymeric sulfobetaine (polySB) to modify the surface of venous catheters to reduce protein, cell, and microbial attachment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

19.

Measurement of action potential generation in isolated canine left ventricular midmyocardial myocytes.

Author: JohnsonDaniel M, HusseinLeyla, SpätjensRoel L H M G, ValentinJean-Pierre, VoldersPaul G A, Abi-GergesNajah

Proarrhythmic side effects

This study describes a protocol for assessing changes in action potential duration in canine ventricular myocytes utilizing optical imaging techniques. The protocol can be used at an early stage of drug discovery to assess proarrhythmic potential.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

20.

¹H NMR-based metabolic profiling of naproxen-induced toxicity in rats.

Author: JungJeeyoun, ParkMinhwa, ParkHye Jin, ShimSun Bo, ChoYang Ha, KimJinho, LeeHo-Sub, RyuDo Hyun, ChoiDonwoong, HwangGeum-Sook

Drug toxicity diagnosis

Naproxen-induced gastric damage in rats led to dose-dependent changes in urinary metabolite concentrations.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

22.

Metabolic profiling of kidney and urine in rats with lithium-induced nephrogenic diabetes insipidus by (1)H-NMR-based metabonomics.

Author: HwangGeum-Sook, YangJi-Young, RyuDo Hyun, KwonTae-Hwan

Li-induced renal effects

Lithium, a medication for bipolar disorder, can cause kidney side effects. This study used NMR-based metabonomics to identify changes in kidney and urine metabolites in rats with lithium-induced kidney problems.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

23.

Validation of a voltage-sensitive dye (di-4-ANEPPS)-based method for assessing drug-induced delayed repolarisation in beagle dog left ventricular midmyocardial myocytes.

Author: HardyMatthew E L, PollardChris E, SmallBen G, Bridgland-TaylorMatthew, WoodsAnn J, ValentinJean-Pierre, Abi-GergesNajah

Faster testing

Voltage-sensitive dye-based assays could potentially replace current electrophysiological methods for evaluating drug candidates in action potential duration (APD) assays.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

24.

Evaluations of the trans-sulfuration pathway in multiple liver toxicity studies.

Author: SchnackenbergLaura K, ChenMinjun, SunJinchun, HollandRicky D, DraganYvonne, TongWeida, WelshWilliam, BegerRichard D

Liver injury

This study investigated the effect of liver toxic compounds on the transulfuration pathway, which is involved in glutathione synthesis. Results showed that heptatotoxicants disturb this pathway by reducing SAMe levels and increasing creatine levels in urine.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

25.

Dimethylthetin treatment causes diffuse alveolar lung damage: a pilot study in a sheep model of Continuous Ambulatory Peritoneal Dialysis (CAPD).

Author: SlowSandy, VasudevamurthyMadhusudan, FraserRobin, McEntyreChristopher, LeverMichael, ChambersStephen, GeorgePeter

Hcy reduction
Alveolar damage
Lung toxicity

This study investigated the effects of dimethylthetin (DMT), a glycine betaine analogue, on plasma homocysteine (Hcy) concentrations in a sheep model of acute renal failure. However, DMT was found to be toxic to all four animals, leading to their death within 48 hours of treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

26.

Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole.

Author: PereiraRicardo de Souza

GERD symptom regression

A dietary supplement containing melatonin, l-tryptophan, vitamin B6, folic acid, vitamin B12, methionine, and betaine is effective in treating gastroesophageal reflux disease (GERD) and more effective than omeprazole.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

27.

Effect of aromatic ring-containing drugs on carnitine biosynthesis in rats with special regard to p-aminomethylbenzoic acid.

Author: DebreceniBalazs, FarkasViktoria, FischerGabor M, SandorAttila

This study investigated the effect of p-aminomethylbenzoic acid (PAMBA) on carnitine biosynthesis. PAMBA was found to inhibit the conversion of gamma-butyrobetaine to carnitine in the liver, potentially by reducing levels of alpha-ketoglutarate, a cofactor for the enzyme.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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