Leucine Intake for Menstruation

Overseen By Arati Swaminadhan, BSc

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Hormonal contraceptives, Hormone therapy

Disqualifiers: Endocrine disorders, Pregnancy, Breastfeeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 15

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how much leucine, an essential amino acid vital for protein synthesis and overall health, women need during different phases of their menstrual cycle. Since the body cannot produce leucine naturally, understanding the right intake for women could enhance dietary guidelines. Researchers will randomly assign participants different leucine amounts to determine the most effective dosage. Women with regular menstrual cycles for the past year and without health conditions might be suitable for this study. As an unphased trial, this study provides a unique opportunity to contribute to important nutritional research that could benefit women's health.

Will I have to stop taking my current medications?

The trial requires that participants do not depend on medication that affects normal metabolism, as it could impact the study results. If your current medications alter your body's normal metabolism, you may need to stop taking them to participate.

What prior data suggests that this technique is safe for determining leucine requirements during the menstrual cycle?

Research has shown that leucine is generally safe for consumption. Although specific safety information about taking leucine during the menstrual cycle is lacking, it has been studied in various contexts. Leucine is an essential amino acid, meaning the body needs it to function properly but cannot produce it independently.

The study under consideration will test different leucine amounts, from low to high, to determine how much women need during different phases of their menstrual cycle. Similar research with pregnant and non-pregnant women has not raised major safety concerns.

Overall, leucine is an important nutrient, and while this study will examine the required amounts more closely, it is generally well-tolerated by most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for menstruation-related issues focus on hormone regulation or pain relief using medications like NSAIDs or hormonal contraceptives. However, leucine intake is unique because it explores the role of an essential amino acid in managing menstrual health. Researchers are excited about leucine because it is a natural dietary component that might offer a nutritional approach to managing menstrual symptoms. Unlike conventional treatments that often come with side effects, leucine could provide a safer and more holistic option by potentially optimizing the body's metabolic processes during the menstrual cycle.

What evidence suggests that leucine intake is effective for menstruation?

Research has shown that leucine, a key protein building block, is essential for protein synthesis and other vital body functions. Women's leucine needs might fluctuate during their menstrual cycle due to metabolic shifts affecting amino acid levels. For example, studies have found that women require more lysine during the luteal phase of their cycle. This trial will test various leucine intakes, from deficient to excess, to explore potential changes in leucine needs. Understanding these changes can help determine the appropriate leucine intake for women during different cycle phases. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for women who are experiencing their menstrual cycle. It's designed to understand if the current dietary recommendations for leucine, an essential amino acid important for health, are suitable during different phases of a woman's cycle.

Inclusion Criteria

Regular menstrual cycle (21-35 day cycle) for the past 12 months

Body mass index (BMI) of between 18 and 28 kg/m2

I have menstrual cycles.

Exclusion Criteria

People with non-traditional dietary practices

I am currently using hormonal birth control.

People who have given birth in the last 18 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Follicular Phase Testing

Participants are tested for leucine requirements during the follicular phase of the menstrual cycle using the indicator amino acid oxidation method.

Up to 7 days

Up to 7 visits (in-person)

Luteal Phase Testing

Participants are tested for leucine requirements during the luteal phase of the menstrual cycle using the indicator amino acid oxidation method.

Up to 7 days

Up to 7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the testing phases

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Leucine

Trial Overview The study is testing how much leucine women need at various stages of their menstrual cycle. Researchers will use diets with specific leucine levels, safe stable isotopes, and breath collection to measure requirements non-invasively.

How Is the Trial Designed?

Group I: Test Leucine Intake Experimental Treatment 1 Intervention

Randomly assigned one of 7 test leucine intakes that range from deficient to excess (10mg/kg/d to 85mg/kg/d). Participants may complete up to 7 study days in each menstrual phase, at different randomly assigned intakes.

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

In a study involving 23 women with premenstrual syndrome (PMS), isolated soy protein containing isoflavones significantly reduced total and physical PMS symptoms over two menstrual cycles, although the differences compared to placebo were not statistically significant.

Specific symptoms such as headaches, breast tenderness, cramps, and swelling were notably reduced after consuming the soy isoflavones, suggesting that they may help alleviate certain premenstrual symptoms through non-classical mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of consumption of soy isoflavones on behavioural, somatic and affective symptoms in women with premenstrual syndrome. Bryant, M., Cassidy, A., Hill, C., et al.[2023]

In a study of eight healthy women, protein metabolism was found to change during the menstrual cycle, with increased leucine flux and oxidation during the luteal phase compared to the follicular phase.

The study also noted that resting energy expenditure was higher in the luteal phase, which correlated with increased levels of the thyroid hormone triiodothyronine (T3), suggesting a potential link between hormonal fluctuations and protein metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased leucine flux and leucine oxidation during the luteal phase of the menstrual cycle in women. Lariviere, F., Moussalli, R., Garrel, DR.[2017]

The study found that healthy adult females have a higher lysine requirement during the luteal phase of their menstrual cycle (37.7 mg/kg/day) compared to the follicular phase (35.0 mg/kg/day), based on a detailed analysis involving five participants and multiple lysine intake levels.

Increased lysine needs during the luteal phase are likely due to higher amino acid catabolism, as indicated by elevated rates of phenylalanine oxidation and correlations with higher levels of estrogen and progesterone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase of menstrual cycle affects lysine requirement in healthy women. Kriengsinyos, W., Wykes, LJ., Goonewardene, LA., et al.[2022]

A study involving healthy young men showed that lower leucine intakes (7 or 14 mg/kg/d) led to negative nitrogen balance initially, indicating that the current recommended leucine requirement for adults may be too low.

The findings suggest that the actual leucine requirement is greater than 14 mg/kg/d, as participants on lower intakes had reduced protein synthesis and adaptation, while those on 30 mg/kg/d maintained better nitrogen balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leucine kinetics during three weeks at submaintenance-to-maintenance intakes of leucine in men: adaptation and accommodation. Young, VR., Gucalp, C., Rand, WM., et al.[2013]

This study is the first to show that HMB, a metabolite associated with muscle mass enhancement, appears in the plasma and urine of rats after they are given leucine, indicating that leucine can be converted into HMB in this model.

The research also identified two new metabolites of leucine in urine and found that a significant portion of the leucine dose is oxidized, suggesting that while leucine is important for muscle synthesis, a considerable amount is also broken down in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A (14)C-leucine absorption, distribution, metabolism and excretion (ADME) study in adult Sprague-Dawley rat reveals β-hydroxy-β-methylbutyrate as a metabolite. Lee, AJ., Beno, DW., Zhang, X., et al.[2018]

The study found that the new generation of combined oral contraceptives (OC) has only modest effects on plasma neutral amino acids and cholesterol levels, with a notable decrease in tyrosine levels, which is important for brain function.

In comparison to controls, users of the new OC showed a significant increase in threonine and decreases in glycine and citrulline, indicating that these contraceptives may have a different metabolic impact than older formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of oral contraceptives on plasma neutral amino acids and cholesterol during a menstrual cycle. Moller, SE., Moller, BM., Olesen, M., et al.[2019]

In a 10-week study involving 35 untrained perimenopausal and postmenopausal women, L-leucine supplementation during resistance training led to significant differences in adipokine levels, with higher leptin levels in the leucine group and higher visfatin levels in the placebo group.

Both groups experienced a decrease in adiponectin levels, which may be linked to increases in visceral adipose tissue, while the placebo group also saw a reduction in MCP-1 levels, suggesting that leucine may influence adipokine responses differently during resistance training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of L-Leucine Supplementation and Resistance Training on Adipokine Markers in Untrained Perimenopausal and Postmenopausal Women. Chapman-Lopez, TJ., Funderburk, LK., Heileson, JL., et al.[2023]

In a study involving 1234 women diagnosed with PMS and 2426 controls over 14 years, total protein intake was found to have no significant association with the development of PMS, indicating that higher protein consumption does not increase or decrease the risk of this condition.

The analysis also showed that specific sources of protein and amino acids, as well as substitutions of carbohydrates and fats for protein, did not affect the likelihood of developing PMS, suggesting that dietary protein is not a contributing factor to PMS risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein intake and the risk of premenstrual syndrome. Houghton, SC., Manson, JE., Whitcomb, BW., et al.[2023]

Leucine supplementation in ApcMin/+ mice led to decreased survival rates and muscle mass in male mice, indicating that it may worsen the effects of cancer cachexia in this group.

In female mice, leucine had no significant impact on body or muscle mass, and it did not effectively mitigate muscle or fat loss in either sex, suggesting that leucine is not a viable treatment for cachexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leucine Supplementation Exacerbates Morbidity in Male but Not Female Mice with Colorectal Cancer-Induced Cachexia. Schrems, ER., Haynie, WS., Perry, RA., et al.[2023]

The studies determined that the Tolerable Upper Intake Level (UL) for leucine is approximately 500 mg/kg/d for healthy elderly men, which is similar to the level found for young men, indicating a safe upper limit for supplementation.

Leucine oxidation rates plateaued at higher intakes, and blood ammonia levels increased above normal at intakes exceeding 550 mg/kg/d, suggesting that excessive leucine intake could lead to potential safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Leucine Supplementation in Elderly Men. Elango, R., Rasmussen, B., Madden, K.[2023]

Leucine supplementation may help prevent age-related muscle loss in elderly individuals, but safety assessments indicate that blood ammonia levels rise above normal at intakes greater than 550 mg/kg/day.

The study suggests that the upper limit for safe leucine intake in healthy elderly men is similar to that of young men, around 500 mg/kg/day, which translates to approximately 35 grams per day for a 70 kg individual.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the safety of leucine supplementation in healthy elderly men. Rasmussen, B., Gilbert, E., Turki, A., et al.[2018]

Leucine (Leu) is a crucial amino acid that boosts protein synthesis by activating the mTOR signaling pathway, which is important for muscle growth and energy metabolism.

Leu is primarily used for protein synthesis, with its metabolites, α-ketoisocaproate (α-KIC) and β-hydroxy-β-methylbutyrate (HMB), also playing significant roles in enhancing protein synthesis and regulating energy balance, suggesting potential benefits for growth and health in various animals, including humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of leucine and its metabolites in protein and energy metabolism. Duan, Y., Li, F., Li, Y., et al.[2022]

Leucine supplementation during resistance exercise significantly enhances mTORC1 signaling, which is crucial for muscle protein synthesis, compared to supplements without leucine, as shown by increased phosphorylation levels after exercise.

The presence of leucine also leads to lower levels of tyrosine and essential amino acids in muscle and plasma during recovery, indicating that leucine may help improve net protein balance by promoting protein synthesis and/or inhibiting protein breakdown.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of leucine in an essential amino acid supplement reduces activation of mTORC1 signalling following resistance exercise in young females. Moberg, M., Apró, W., Ohlsson, I., et al.[2021]

In a study of 36 untrained peri- and postmenopausal women, 10 weeks of resistance training significantly increased muscle strength in both groups, regardless of whether they received leucine or a placebo.

Leucine supplementation did not lead to any additional benefits in fat-free mass or serum hormone levels, indicating that resistance training alone was sufficient for strength gains in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of L-leucine Supplementation Coupled With Resistance Training in Untrained Midlife Women. Funderburk, LK., Beretich, KN., Chen, MD., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6167362/

Menstrual cycle rhythmicity: metabolic patterns in healthy ... The study found 208 metabolites changed significantly during the menstrual cycle, with 71 showing rhythmicity. Amino acids and lipids decreased ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06533501/leucine-requirements-during-the-menstrual-cycle

Leucine Requirements During the Menstrual Cycle This study aims to determine the leucine requirements during the phases of the menstrual cycle. Leucine is an essential amino acid (cannot be ...

3. withpower.com withpower.com/trial/leucine-intake-for-menstruation-f412c

Leucine Intake for Menstruation The study found that healthy adult females have a higher lysine requirement during the luteal phase of their menstrual cycle (37.7 mg/kg/day) compared to the ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S000291652301907X

Comparison of leucine and dispensable amino acid ... Leucine, glutamine, glycine, and cysteine fluxes were faster in women with a low BMI in both trimesters, but there was no difference in alanine flux between ...

5. journals.physiology.org journals.physiology.org/doi/full/10.1152/ajpendo.00262.2003

Phase of menstrual cycle affects lysine requirement in ... The aim of this study was to investigate whether the phases of the menstrual cycle affect lysine requirement in healthy adult females, as determined by the ...

6. mdpi.com mdpi.com/2072-6643/11/11/2650

The Impact of a Large Bolus Dose of l-leucine and ... The purpose of this study was to examine how Ile and Leu influence both GLP-1 and GIP, subsequent pancreatic hormones, and glycemia in healthy, inactive adults.