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L-METHIONINE

L-Methionine, often used in its active form S-Adenosyl-L-Methionine (SAMe), is a naturally occurring substance in the human body that plays a crucial role in several biochemical processes. Clinical trials are investigating L-Methionine’s potential benefits across various health conditions, including depression, osteoarthritis, tobacco dependence, urinary tract infections, hot flashes, and hepatitis C. This molecule acts as a methyl donor in the central nervous system and may influence neurotransmitter production, inflammation, and other biological functions. As researchers continue to explore its therapeutic applications, L-Methionine offers promising possibilities as both a standalone treatment and a complementary therapy alongside conventional medications.

Table of Contents

What is L-Methionine?

L-Methionine is an essential amino acid that our body cannot produce on its own, so we must obtain it through diet or supplements. It plays a crucial role in many bodily functions, particularly in the central nervous system where it acts as a building block for important brain chemicals [1]. The body uses L-Methionine to make proteins and other important compounds that help with various processes, including mood regulation and joint health.

S-Adenosyl-L-Methionine (SAMe): The Active Form

When discussing the medicinal uses of L-Methionine, we’re often referring to its activated form called S-Adenosyl-L-Methionine, commonly abbreviated as SAMe. SAMe is the primary methyl donor for the central nervous system, which means it helps in the production of important brain chemicals like dopamine and norepinephrine [2]. These chemicals are responsible for regulating mood, energy levels, and overall brain function.

SAMe is available as an over-the-counter supplement in many countries and has been studied for various health conditions, showing promising results in several clinical trials.

Treatment for Depression

One of the most well-studied uses of SAMe is for treating depression. Clinical research suggests that SAMe may have antidepressant properties and could be effective in helping people with major depressive disorder.

In a double-blind, placebo-controlled study, researchers compared SAMe against both a conventional antidepressant (escitalopram, also known as Lexapro) and a placebo. Participants received either 1600 mg of SAMe per day (with the possibility of increasing to 3200 mg per day at 6 weeks), 10 mg of escitalopram (with the possibility of increasing to 20 mg per day), or a placebo [3]. The study measured depression symptoms using the Hamilton Rating Scale for Depression (HAM-D), a standard tool for assessing depression severity.

Another study looked at the potential benefits of L-methionine combined with betaine and folate for unipolar depression. These substances all play important roles in what’s called the “one-carbon cycle,” which is involved in producing SAMe naturally in the body [1].

Benefits for Osteoarthritis

SAMe has shown promise in helping people with osteoarthritis, particularly in the hands. Osteoarthritis is a condition that causes joint pain and stiffness due to cartilage breakdown.

A clinical trial investigated SAMe’s effects on hand discomfort and function in people with hand osteoarthritis. Participants took either 400 mg of SAMe twice daily (800 mg total per day) or a placebo for 8 weeks. After a one-week washout period, they switched treatments for another 8 weeks [4].

The study measured changes in hand discomfort using a visual analog scale (where 0 means no discomfort and 10 means maximum discomfort) and evaluated hand function using the Disability of Arm, Shoulder and Hand (DASH) survey. They also monitored side effects to assess SAMe’s tolerability compared to placebo.

Aid for Smoking Cessation

SAMe may help people quit smoking by addressing the uncomfortable withdrawal symptoms that often lead to relapse.

When someone stops smoking, their brain experiences a drop in dopamine and other neurotransmitters that were previously stimulated by nicotine. This drop contributes to withdrawal symptoms like irritability, anxiety, and cravings. Since SAMe helps with the production of these neurotransmitters, it may help reduce these withdrawal symptoms [2].

A randomized, blinded, placebo-controlled clinical trial evaluated SAMe for smoking abstinence. The study compared different doses of SAMe (800 mg per day and 1600 mg per day) against a placebo for 8 weeks. Researchers measured whether participants could maintain 7-day point prevalence smoking abstinence (not smoking for at least 7 days), confirmed by a breath test for carbon monoxide [2].

Prevention of Urinary Tract Infections

L-methionine has been studied for preventing urinary tract infections (UTIs), particularly in women undergoing pelvic surgery, who are at higher risk for developing post-operative UTIs.

A double-blind randomized controlled trial investigated whether a combination of L-methionine with Hibiscus Sabdariffa and Boswellia Leaf Extract could help prevent UTIs after pelvic reconstructive surgery or anti-incontinence procedures. Participants took either the combination treatment or a placebo twice daily for seven days before and after surgery (14 days total) [5].

The primary outcome was whether participants needed treatment for clinically suspected or culture-proven UTIs within three weeks after surgery. This approach may work because L-methionine can make urine more acidic, which creates a less favorable environment for bacteria that cause UTIs.

Managing Hot Flashes

Hot flashes—sudden feelings of warmth that spread over the body, often accompanied by sweating and redness—are a common symptom experienced by many women during menopause or after breast cancer treatment. Some women prefer not to take estrogen therapy for hot flashes due to concerns about breast cancer risk.

A phase II clinical trial evaluated SAMe for treating hot flashes in women with a history of breast cancer or those who did not wish to take estrogen. Participants received 400 mg of SAMe once daily for the first week of treatment and then increased to twice daily for the remainder of the study period (6 weeks total) [6].

The study measured hot flash frequency and severity using daily diaries, as well as quality of life measures and potential side effects. This treatment approach is based on SAMe’s ability to potentially modulate serotonin, a neurotransmitter that plays a role in temperature regulation.

Support for Hepatitis C Treatment

SAMe (also called AdoMet) has been studied as a supplementary treatment for chronic hepatitis C, particularly for patients who did not respond well to standard treatments.

A clinical trial investigated whether adding SAMe and betaine to the standard hepatitis C treatment (pegylated interferon alpha and ribavirin) could improve outcomes for patients who hadn’t responded to previous treatment attempts [7].

The rationale for this approach involves a cellular signaling pathway called STAT1, which hepatitis C virus can inhibit to reduce the effectiveness of interferon treatment. SAMe may help increase STAT1 methylation (a chemical modification), potentially improving interferon signaling and treatment effectiveness.

Dosage and Administration

The dosage of L-methionine or SAMe varies depending on the condition being treated:

  • For depression: Clinical trials have used 1600 mg of SAMe per day, sometimes increasing to 3200 mg per day if needed [3]
  • For osteoarthritis: A common dosage is 400 mg of SAMe twice daily (800 mg total per day) [4]
  • For smoking cessation: Studies have used 800 mg to 1600 mg of SAMe per day [2]
  • For hot flashes: A clinical trial used 400 mg of SAMe once daily for one week, then twice daily thereafter [6]

SAMe is typically taken orally in tablet or capsule form. In clinical studies, it’s often divided into two daily doses (morning and evening). It’s important to follow the dosage recommendations from your healthcare provider, as needs may vary based on individual factors.

Potential Side Effects

Based on clinical trials, SAMe appears to be generally well-tolerated by most people. One study specifically measured side effects using a questionnaire that assessed 15 different potential symptoms [6].

While specific side effects weren’t detailed in the clinical trial information, common side effects of SAMe reported in medical literature can include:

  • Digestive issues like nausea, diarrhea, or stomach discomfort
  • Anxiety or nervousness
  • Insomnia or sleep disturbances
  • Headache
  • Dry mouth

It’s important to note that SAMe may not be appropriate for people with certain conditions, particularly bipolar disorder, as it could potentially trigger manic episodes in susceptible individuals. Always consult with a healthcare provider before starting SAMe or any supplement, especially if you have existing health conditions or are taking other medications.

Condition Form/Dosage Study Design Key Outcomes Measured
Tobacco Dependence SAMe at 800 mg/day or 1600 mg/day Randomized, blinded, placebo-controlled, three-arm trial 7-day point prevalence smoking abstinence at week 8 (carbon monoxide <8ppm)
Osteoarthritis of Hands SAMe 400 mg twice daily Double-blind crossover study with 8-week periods and 1-week washout Hand discomfort (visual analog scale), function (DASH survey), tolerability
Major Depression SAMe 1600 mg/day (potential increase to 3200 mg) Double-blind comparison with escitalopram and placebo for 24 weeks Hamilton Rating Scale for Depression (HAM-D) scores
Urinary Tract Infection L-methionine with Hibiscus Sabdariffa and Boswellia Leaf Extract Double-blind randomized controlled trial, 7 days before and after surgery Treatment for UTI within 3 weeks of surgery
Unipolar Depression L-methionine with betaine and folate Open study, 6 weeks with 9 clinical visits Depressive symptoms
Hepatitis C S-adenosyl-L-methionine with betaine, pegylated interferon alpha2b, and ribavirin Combination therapy for non-responders to standard treatment Sustained response rate, early virologic response
Hot Flashes SAMe 400 mg once daily (days 8-14) then twice daily (days 15-49) Phase II trial for women with breast cancer history or avoiding estrogen Hot flash activity (score and frequency), quality of life measures

FAQ

  • What is L-Methionine and how does it work in the body? L-Methionine is an essential amino acid that the body converts to S-Adenosyl-L-Methionine (SAMe), which is the primary methyl donor for the central nervous system. SAMe works by donating methyl groups toward the production of neurotransmitters like dopamine and norepinephrine in the brain. This process can help regulate mood, reduce inflammation, and support various biochemical functions throughout the body. In clinical trials, L-Methionine and SAMe are being studied for their effects on conditions ranging from depression and osteoarthritis to tobacco dependence and urinary tract infections.
  • What health conditions are being studied with L-Methionine in clinical trials? Clinical trials are investigating L-Methionine (primarily as SAMe) for several health conditions, including: major depression, where it's compared with escitalopram and placebo; osteoarthritis of the hands, evaluating its effects on discomfort and function; tobacco dependence, where it may help with smoking abstinence by affecting dopamine levels; urinary tract infections, used in combination with Hibiscus Sabdariffa and Boswellia Leaf Extract for prevention after surgery; unipolar depression in combination with betaine and folate; chronic hepatitis C in combination with other treatments; and hot flashes in women, particularly those with a history of breast cancer or who cannot take estrogen.
  • What dosages of L-Methionine/SAMe are typically used in clinical trials? Dosages of L-Methionine/SAMe vary depending on the condition being treated. In the clinical trials reviewed, common dosages include: 400 mg twice daily (800 mg/day) for osteoarthritis of the hands; 800 mg/day to 1600 mg/day for tobacco dependence; 1600 mg/day with a possible increase to 3200 mg/day for depression; and 400 mg once daily for the first week and then twice daily for hot flashes. These dosages are specifically designed for research purposes, and the appropriate therapeutic dose may vary based on individual needs and the condition being treated.
  • How is SAMe being studied for depression compared to standard treatments? In a double-blind, placebo-controlled study, SAMe is being compared to escitalopram (an SSRI antidepressant) and placebo for treating major depressive disorder. Participants receive either SAMe (1600 mg per day, potentially increasing to 3200 mg), escitalopram (10 mg per day, potentially increasing to 20 mg), or placebo for 12 weeks. Those who respond continue their treatment for another 12 weeks, while non-responders receive a combination of SAMe and escitalopram. The primary outcome measure is the change in depression symptoms using the Hamilton Rating Scale for Depression (HAM-D). This study aims to determine whether SAMe, a natural substance, could be as effective as conventional antidepressants.
  • Are there any side effects or safety concerns with L-Methionine/SAMe reported in clinical trials? Clinical trials are actively monitoring the safety profile of L-Methionine/SAMe. While specific detailed side effect data isn't fully provided in the trial information, researchers are tracking adverse events and tolerability in all studies. For example, in the hot flashes study, researchers specifically measured side effects using a Side Effect Questionnaire (SEQ). In the depression trial, safety was monitored throughout the 24-week period. The osteoarthritis study included weekly surveys about side effects for 17 weeks. Generally, SAMe is described as 'well-tolerated' in the tobacco dependence study, but as with any medication or supplement, individual responses may vary, and safety monitoring is an important component of these clinical trials.

Ongoing Clinical Trials on L-METHIONINE

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Glossary

  • S-Adenosyl-L-Methionine (SAMe): The active form of L-Methionine that serves as the primary methyl donor for the central nervous system. It helps in the synthesis of neurotransmitters and other important compounds in the body.
  • Methyl donor: A substance that can transfer methyl groups (CH3) to other molecules, which is crucial for many biochemical reactions in the body including neurotransmitter synthesis and gene expression.
  • Monoamine neurotransmitters: Chemical messengers in the brain including dopamine, norepinephrine, and serotonin that regulate mood, emotions, and various physical functions.
  • Tobacco dependence: A chronic condition characterized by physical and psychological dependence on nicotine, making it difficult to stop using tobacco products.
  • Carbon monoxide (CO): A gas produced when smoking tobacco that is measured in expired breath to confirm smoking abstinence (levels below 8ppm indicate abstinence).
  • Osteoarthritis: A degenerative joint disease characterized by the breakdown of cartilage, causing pain, stiffness, and reduced function, especially in weight-bearing joints or, as studied in the trials, the hands.
  • Visual Analog Scale: A measurement tool used to quantify subjective experiences like pain or discomfort, typically represented as a continuous line with descriptors at each end (e.g., 0-10 scale where 0 is no discomfort and 10 is maximum discomfort).
  • DASH (Disability of Arm, Shoulder and Hand): A standardized questionnaire that measures physical function and symptoms in people with musculoskeletal disorders of the upper limb.
  • Major Depressive Disorder (MDD): A mental health condition characterized by persistent feelings of sadness, loss of interest in activities, and various other physical and emotional symptoms that significantly affect daily functioning.
  • Hamilton Rating Scale for Depression (HAM-D): A clinician-rated inventory used to assess the severity of depressive symptoms, with scores ranging from 0 to 68. Higher scores indicate more severe depression.
  • Escitalopram: A selective serotonin reuptake inhibitor (SSRI) antidepressant medication, marketed under the brand name Lexapro, used to treat depression and anxiety disorders.
  • Unipolar Depression: A form of depression characterized by episodes of low mood without the manic or hypomanic episodes seen in bipolar disorders.
  • Pelvic Organ Prolapse: A condition where one or more pelvic organs (bladder, uterus, rectum) drop from their normal position due to weakened supporting tissues.
  • Urinary Incontinence: The involuntary leakage of urine, which can be caused by various factors including weakened pelvic floor muscles or nerve damage.
  • Double-blind study: A research method where neither the participants nor the researchers know who is receiving which treatment, reducing the risk of bias in the results.
  • Placebo: An inactive substance designed to look like the drug being tested but containing no active ingredient, used to determine whether the active drug's effects are real or due to psychological factors.
  • Hepatitis C: A viral infection that causes liver inflammation and damage, which can lead to serious liver problems including cirrhosis if left untreated.
  • STAT1 methylation: A biochemical process involved in the body's immune response to viral infections, particularly relevant in hepatitis C treatment.
  • Hot flashes: Sudden feelings of warmth, often accompanied by sweating and redness of the face and neck, commonly experienced during menopause or as a side effect of certain cancer treatments.
  • Quality of life (QOL) measures: Standardized assessments used to evaluate how a person's well-being is affected by changes in their physical health, psychological state, and social relationships.
  • Profile of Mood States (POMS): A psychological assessment tool that measures different dimensions of mood including tension, depression, anger, vigor, fatigue, and confusion.

References

  1. https://clinicaltrials.gov/study/NCT00226356
  2. https://clinicaltrials.gov/study/NCT00722124
  3. https://clinicaltrials.gov/study/NCT00101452
  4. https://clinicaltrials.gov/study/NCT05363020
  5. https://clinicaltrials.gov/study/NCT02216253
  6. https://clinicaltrials.gov/study/NCT01140646
  7. https://clinicaltrials.gov/study/NCT00310336