Vitamin D Supplementation for Hormonal Imbalance

Overseen By Giuliet L Kibler

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Southern California

Must not be taking: Exogenous hormones, Vitamin D

Disqualifiers: Pregnancy, Gynecological disease, Chronic diseases, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 3 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be taking Vitamin D supplements or exogenous hormones (hormones from outside the body) to participate.

What data supports the effectiveness of the drug Vitamin D for hormonal imbalance?

Research shows that both forms of Vitamin D, cholecalciferol (D3) and ergocalciferol (D2), can effectively increase vitamin D levels in the body, which is important for overall health. While these studies focus on vitamin D levels rather than hormonal imbalance directly, maintaining adequate vitamin D levels is crucial for various bodily functions, including hormone regulation. ^{1 2 3 4 5}

Is vitamin D supplementation safe for humans?

Vitamin D supplementation, particularly with cholecalciferol (vitamin D3), is generally considered safe for humans. Studies have shown that both cholecalciferol and calcifediol are effective and safe, with no increase in toxicity, even in long-term use. ^{1 6 7 8 9}

How does the drug Vitamin D differ from other treatments for hormonal imbalance?

Vitamin D, particularly in the form of cholecalciferol (D3), is unique because it is more effective than ergocalciferol (D2) in raising vitamin D levels in the body, which is important for hormone regulation. Unlike other treatments, Vitamin D3 is more potent and has a longer shelf life, making it a preferred choice for supplementation. ^{1 2 10 11 12}

What is the purpose of this trial?

Participation will take place over two visits to the Clinical Exercise Research Center (CERC) at the University of Southern California Health Sciences Campus. On the first visit, height, weight, and body composition by bioelectrical impedance are recorded. Questionnaires and withdrawal of a sample of blood (1 tablespoon) are also completed. The intervention begins the day following the first visit. The intervention protocol consists of three weeks of consuming either a placebo capsule or a 5000 IU Vitamin D capsule daily and completing a daily survey. The second visit to CERC immediately follows the 3-weeks intervention. In this visit, the same blood sampling protocol will be completed. The assignment of the intervention will be randomized (i.e., rolling a die), and participants are blinded to group assignment.

Research Team

Giuliet L Kibler

Principal Investigator

University of Southern California - Division of Biokinesiology and Physical Therapy

Eligibility Criteria

This trial is for females experiencing hormonal imbalance. Participants will need to visit the research center twice, complete questionnaires, and allow a small amount of blood to be drawn. They must take a daily capsule for three weeks and keep a survey diary.

Inclusion Criteria

I weigh at least 110 lbs.

I was assigned female at birth.

Completion and signature of the informed consent document

Exclusion Criteria

Pregnant

I have taken Vitamin D supplements in the last 3 months.

I weigh less than 110 lbs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Initial visit to record height, weight, body composition, complete questionnaires, and withdraw a blood sample

1 day

1 visit (in-person)

Treatment

Participants consume either a placebo capsule or a 5000 IU Vitamin D capsule daily for three weeks and complete a daily survey

3 weeks

Daily self-administration

Post-Treatment Assessment

Second visit to complete the same blood sampling protocol as the baseline assessment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• Vitamin D

Trial Overview The study tests if taking high-dose Vitamin D (5000 IU) affects testosterone levels compared to a placebo. It's randomized, meaning participants are put into the Vitamin D or placebo group by chance, and neither the researchers nor participants know who gets what until after the study.

Participant Groups

Group I: Vitamin D Group Experimental Treatment 1 Intervention

The treatment intervention will consist of three weeks of one 5000 IU cholecalciferol capsule (Pure Encapsulations, LLC) daily, with breakfast.

Group II: Placebo Group Placebo Group 1 Intervention

The control group will also take a daily, with breakfast, placebo capsule (Zeebo) for the three-week intervention.

Vitamin D is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vitamin D for:

• Rickets
• Osteomalacia
• Osteoporosis
• Hypocalcemia
• Hyperparathyroidism
• Malabsorption states
• Cirrhosis
• Obesity

Approved in European Union as Vitamin D for:

• Rickets
• Osteomalacia
• Osteoporosis
• Hypocalcemia
• Hyperparathyroidism
• Malabsorption states
• Cirrhosis
• Obesity

Approved in Canada as Vitamin D for:

• Rickets
• Osteomalacia
• Osteoporosis
• Hypocalcemia
• Hyperparathyroidism
• Malabsorption states
• Cirrhosis
• Obesity

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Findings from Research

In a study of 64 adults aged 65 and older, vitamin D3 (cholecalciferol) was found to be slightly more effective than vitamin D2 (ergocalciferol) in increasing serum 25-hydroxyvitamin D levels over one year, with 19% of participants still having low levels despite high compliance.

Neither vitamin D2 nor D3 caused toxicity or significant changes in serum calcium or other bone markers, but about 20% of individuals still had insufficient vitamin D levels after treatment, indicating variability in individual responses to supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. Binkley, N., Gemar, D., Engelke, J., et al.[2022]

In a study involving 40 healthy participants, both vitamin D2 and D3, when consumed at low doses (5 or 10 μg/d), significantly increased serum levels of their respective metabolites (25-OH-D2 and 25-OH-D3) over a 4-week period with minimal UV-B exposure.

The results indicated that vitamin D2 and D3 are equally effective in raising serum 25-hydroxy-vitamin D levels, suggesting that either form can be used to improve vitamin D status in individuals with low UV-B exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fortified malted milk drinks containing low-dose ergocalciferol and cholecalciferol do not differ in their capacity to raise serum 25-hydroxyvitamin D concentrations in healthy men and women not exposed to UV-B. Fisk, CM., Theobald, HE., Sanders, TA.[2018]

Cholecalciferol (vitamin D3) is the most effective and stable form of vitamin D for supplementation, while ergocalciferol (vitamin D2) is less potent and more prone to degradation during storage and cooking.

Current nutrition guidelines often overlook that calcidiol and calcitriol are not nutrients suitable for food fortification or dietary supplementation, emphasizing the need to focus on cholecalciferol for effective vitamin D intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D supplementation: cholecalciferol, calcifediol, and calcitriol. Vieth, R.[2021]

Calcifediol (25-OH-vitamin D3) is more effective than cholecalciferol (vitamin D3) in preventing and treating vitamin D deficiency, with a rapid onset of action and greater potency, as shown in studies lasting over 6 months.

Both calcifediol and cholecalciferol are safe for the general population, but calcifediol does not increase toxicity levels, making it a preferable option for vitamin D supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Vitamin D Deficiency with Calcifediol: Efficacy and Safety Profile and Predictability of Efficacy. Pérez-Castrillon, JL., Usategui-Martín, R., Pludowski, P.[2023]

Vitamin D3 (cholecalciferol) is more effective than Vitamin D2 (ergocalciferol) in raising serum levels of 25-hydroxyvitamin D, which is a key measure of vitamin D status in the body.

Due to its superior bioefficacy, Vitamin D2 should not be considered a suitable option for supplementation or fortification, as it has a shorter shelf life and less effective binding to vitamin D binding protein in plasma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The case against ergocalciferol (vitamin D2) as a vitamin supplement. Houghton, LA., Vieth, R.[2023]

In a study of 279 adults, both vitamin D2 and D3 supplements significantly increased 25-hydroxy D levels compared to placebo, with the highest increases observed in those taking D3 on a 2-weekly schedule.

The effectiveness of vitamin D2 and D3 in raising 25-hydroxy D levels was found to be influenced by dosing schedule and sex, with females showing a greater response to both forms of vitamin D.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential effects of vitamin D2 and D3 supplements on 25-hydroxyvitamin D level are dose, sex, and time dependent: a randomized controlled trial. Hammami, MM., Yusuf, A.[2018]

Vitamin D, including both D2 and D3, is crucial for regulating calcium and phosphate metabolism, which are essential for bone health and overall bodily functions.

The body produces vitamin D3 in the skin through sunlight exposure, and it is then converted into its active form, calcitriol, in the liver and kidneys, highlighting the importance of both sunlight and organ function in maintaining vitamin D levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vitamin D metabolism]. Kulda, V.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Fortified malted milk drinks containing low-dose ergocalciferol and cholecalciferol do not differ in their capacity to raise serum 25-hydroxyvitamin D concentrations in healthy men and women not exposed to UV-B. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Cholecalciferol v. ergocalciferol for 25-hydroxyvitamin D (25(OH)D) repletion in chronic kidney disease: a randomised clinical trial. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of plain cholecalciferol versus ergocalciferol in raising serum vitamin D level in Thai female healthcare workers. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Cholecalciferol (vitamin D3) therapy and vitamin D insufficiency in patients with chronic kidney disease: a randomized controlled pilot study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Vitamin D supplementation: cholecalciferol, calcifediol, and calcitriol. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the effectiveness of cholecalciferol in long-term care elderly patients with hypovitaminosis D. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment of Vitamin D Deficiency with Calcifediol: Efficacy and Safety Profile and Predictability of Efficacy. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Vitamin D3 seems more appropriate than D2 to sustain adequate levels of 25OHD: a pharmacokinetic approach. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

The case against ergocalciferol (vitamin D2) as a vitamin supplement. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Differential effects of vitamin D2 and D3 supplements on 25-hydroxyvitamin D level are dose, sex, and time dependent: a randomized controlled trial. [2018]

12. Czech Republic pubmed.ncbi.nlm.nih.gov

[Vitamin D metabolism]. [2013]