Betaine and Choline for Obesity

Overseen By Alison M. Duncan, RD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Guelph

Must not be taking: Hormone therapy

Disqualifiers: Pregnancy, Vegan diet, Smoking, Chronic illnesses, others

Compensation: Varies

Number of Visits: Unknown

Duration: 14 weeks

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether extra betaine and choline can improve metabolic health in overweight adults. Participants will join one of three groups: one group will consume three eggs daily with a supplement, another will take the supplement without eggs, and the last will receive a placebo (a substance with no active ingredients). Individuals with a BMI (a measure of body fat based on height and weight) between 25 and 35 who are willing to follow the study's egg-eating and fasting guidelines may be suitable candidates.

As an unphased trial, this study provides a unique opportunity to contribute to scientific understanding and potentially enhance metabolic health.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does exclude participants using hormone therapy, antibiotics, prebiotics, probiotics, or dietary fiber supplements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that betaine is generally safe for consumption. The FDA has approved its use in food and supplements. However, some studies suggest that taking 4 grams daily might raise certain cholesterol levels, such as LDL, often referred to as "bad" cholesterol. In contrast, European health authorities consider 400 milligrams per day to be safe.

Choline, an essential nutrient that supports many body functions, is naturally found in foods like eggs and meat. It is usually well-tolerated, but consuming very high amounts can lead to side effects such as sweating, a fishy body odor, or low blood pressure.

Overall, both betaine and choline have been well-studied and approved for use. Following the recommended doses is important to avoid potential issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments using betaine and choline for obesity because they offer a fresh approach by leveraging natural compounds. Unlike traditional treatments that often focus on appetite suppression or increasing metabolism through medication, these treatments aim to improve fat metabolism and liver function, potentially offering a more holistic and less invasive method. Betaine, also known as trimethylglycine, is thought to enhance the breakdown of fats, while choline supports lipid metabolism and liver health. By incorporating these compounds, the treatments could provide a safer alternative with fewer side effects compared to conventional obesity medications.

What evidence suggests that betaine and choline might be effective treatments for obesity?

Studies have shown that betaine can help reduce body fat and improve body shape. In humans, it significantly lowers total body fat. Animal studies demonstrated that betaine reduces body weight and fat buildup. Research also suggests that betaine may help balance gut bacteria, potentially preventing obesity. This trial will provide participants with different treatments involving betaine, such as daily supplements with or without eggs, to evaluate its potential benefits for improving metabolic health in individuals who are overweight. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 18-70 with a BMI of 25-35 kg/m2, non-smokers, willing to fast before lab visits and consume eggs as part of the study. Excluded are those using recreational drugs or certain supplements, with allergies to eggs, pregnant/breastfeeding women, vegans, smokers, or those with chronic illnesses.

Inclusion Criteria

Willing to fast before the baseline and dietary period lab visits

Willing to provide a 24-hr prior day food record at the dietary period lab visits

BMI between 25-35 kg/m2

Exclusion Criteria

Use of prebiotics, probiotics or dietary fiber (i.e., Metamucil) supplements in the last 2 months

I do not use recreational drugs.

BMI < 25 kg/m2 or BMI > 35 kg/m2

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo three 4-week dietary periods with different supplement and food combinations, each separated by a 1-week washout break

14 weeks

Visits at weeks 0, 4, 9, and 14 for sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Betaine
• Choline

Trial Overview

The trial is testing if adding betaine (found in beets) and choline (in eggs) can improve metabolic health in overweight adults. Participants will eat three eggs daily for four weeks and avoid them otherwise during the study.

How Is the Trial Designed?

Group I: Experimental: No eggs with daily supplement containing 3 g trimethylglycine Experimental Treatment 1 Intervention

Group II: Daily 3 whole eggs with daily supplement containing 3 g trimethylglycine Experimental Treatment 2 Interventions

Group III: Placebo Comparator: No eggs with daily supplement containing 3 g cellulose Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

University of Guelph

Lead Sponsor

Trials

87

Recruited

15,100+

Published Research Related to This Trial

In a study of 1938 adults aged 40-75, higher serum concentrations of choline were linked to less muscle mass loss in men and less fat gain in women with low baseline choline levels.

Similarly, higher serum betaine levels were associated with better maintenance of muscle mass and less fat gain in men with low baseline betaine concentrations, suggesting that both nutrients may positively influence body composition over a 3-year period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between serum choline and betaine concentrations and longitudinal changes of body composition in community-dwelling middle-aged and older Chinese adults. Zhong, RH., Long, JA., Wang, F., et al.[2021]

In a study involving female APOE*3-Leiden.CETP mice fed a Western-type diet for 16 weeks, dietary choline supplementation significantly reduced body fat gain and prevented inflammation in adipose tissue.

Choline improved liver health by enhancing fatty acid oxidation and reducing cholesterol levels, suggesting a mechanism where it promotes the uptake of fatty acids from triglyceride-rich particles, leading to better cholesterol management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary choline increases brown adipose tissue activation markers and improves cholesterol metabolism in female APOE*3-Leiden.CETP mice. Liu, C., Song, Z., Li, Z., et al.[2023]

Betaine supplementation in heterozygous mice for 8 weeks improved conditions like hypertriglyceridemia and hepatic steatosis, suggesting it may help reduce obesity-related issues by enhancing lipid breakdown and metabolism.

The study identified specific metabolic changes linked to betaine, such as increased α-ketoglutaric acid and unique biomarkers like histidine and alanine, indicating its distinct mechanism of action compared to choline supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Betaine and Choline Improve Lipid Homeostasis in Obesity by Participation in Mitochondrial Oxidative Demethylation. Sivanesan, S., Taylor, A., Zhang, J., et al.[2020]

In a study of 359 obese individuals aged 20 to 50, higher dietary intakes of choline and betaine were linked to lower blood pressure and lower levels of low-density lipoprotein (LDL) cholesterol, suggesting potential cardiovascular benefits.

While no significant differences in biochemical parameters were found across different levels of dietary choline intake, higher betaine intake was associated with reduced systolic and diastolic blood pressure, indicating its possible role in managing cardiovascular risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary choline and betaine intake, cardio-metabolic risk factors and prevalence of metabolic syndrome among overweight and obese adults. Abbasi, MSP., Tousi, AZ., Yazdani, Y., et al.[2023]

In a study of 3214 participants, higher dietary intakes of choline and betaine were significantly associated with lower body fat percentages and better overall body composition, suggesting these nutrients may play a role in weight management.

The research found that individuals with obesity had the lowest intakes of choline and betaine, while those with normal weight had the highest, indicating a potential link between these nutrients and healthy body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher Dietary Choline and Betaine Intakes Are Associated with Better Body Composition in the Adult Population of Newfoundland, Canada. Gao, X., Wang, Y., Randell, E., et al.[2019]

Maternal betaine supplementation in obese mice prevented fetal and placental overgrowth and downregulated key transporters and growth factors at an early stage of pregnancy (E12.5), but these effects diminished by later stages (E17.5).

At E17.5, betaine supplementation reduced fetal fat accumulation and liver triglyceride levels, while enhancing the expression of a gene that supports fat metabolism, indicating that betaine may have a unique role in managing fetal metabolic health compared to choline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal betaine supplementation affects fetal growth and lipid metabolism of high-fat fed mice in a temporal-specific manner. Joselit, Y., Nanobashvili, K., Jack-Roberts, C., et al.[2019]

In a study of 1081 participants, higher serum levels of choline and betaine were linked to lower body fat and better body composition in males, particularly in those not taking medications.

The research found that obese males had the lowest levels of choline and betaine, suggesting that these compounds may play a role in managing body weight and composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher serum choline and betaine levels are associated with better body composition in male but not female population. Gao, X., Randell, E., Zhou, H., et al.[2018]

In a study of 12 obese cats over 5 weeks, dietary choline supplementation did not change body weight or composition but significantly altered serum lipid profiles, indicating potential metabolic effects.

Choline may help reduce hepatic fat by enhancing fat mobilization and improving methionine recycling, which could be beneficial for managing obesity-related liver issues in cats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum Lipid, Amino Acid and Acylcarnitine Profiles of Obese Cats Supplemented with Dietary Choline and Fed to Maintenance Energy Requirements. Verbrugghe, A., Rankovic, A., Armstrong, S., et al.[2021]

Citations

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Association between dietary betaine intake and overweight ...

In animal models, betaine treatment effectively reduced body weight and fat accumulation8,9.

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Decoding Betaine: A Critical Analysis of Therapeutic ...

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Metabolic Effects of Betaine: A Randomized Clinical Trial of ...

Dietary betaine supplementation reduces weight gain, levels of insulin under fasted and fed conditions, and hepatic fat, and increases whole-body glucose ...