Resveratrol for Osteopenia

Overseen By Sheau Ching Chai, PhD, RD

Age: Any Age

Sex: Female

Trial Phase: Academic

Sponsor: University of Delaware

Must not be taking: Blood thinners, Endocrine, Neuroactive

Disqualifiers: Osteoporosis, Cancer, Diabetes, Cardiovascular, others

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

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

68 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine whether daily supplementation of resveratrol would improve bone health in postmenopausal women.

Will I have to stop taking my current medications?

If you are taking blood thinners, endocrine, or neuroactive drugs, you will need to stop taking them to participate in this trial.

What evidence supports the effectiveness of the treatment resveratrol for osteopenia?

Research shows that resveratrol, a natural compound found in grapes and wine, may help improve bone mineral density in animal models, suggesting it could be beneficial for bone health and potentially help prevent osteoporosis. ^{1 2 3 4 5}

Is resveratrol generally safe for humans?

Resveratrol, found in red wine and available in supplements, has been studied for its health benefits, including anti-inflammatory and anti-cancer properties. While specific safety data for osteopenia is not available, resveratrol is generally considered safe in moderate amounts, but it's important to consult with a healthcare provider before starting any new supplement. ^{1 4 6 7 8}

How is the drug resveratrol unique in treating osteopenia?

Resveratrol is unique because it is a natural compound found in foods like grapes and wine, and it acts as a phytoestrogen (plant-based estrogen-like compound) that can improve bone mineral density without the side effects associated with hormone replacement therapy. It also helps balance inflammatory markers and bone metabolism, which may be beneficial for bone health. ^{1 2 3 5 9}

Research Team

Sheau Ching Chai, PhD, RD

Principal Investigator

University of Delaware

Eligibility Criteria

This trial is for postmenopausal women who are 1 to 5 years into menopause and have low bone mass but not full-blown osteoporosis. Participants should not be on hormone therapy or certain other medications, and must not have a range of conditions from kidney stones to cardiovascular disease. Smokers and those with extreme body weights or allergies to resveratrol-related substances cannot join.

Inclusion Criteria

I am a woman who became menopausal between 1 to 5 years ago and have low bone mass.

Exclusion Criteria

I have been diagnosed with a condition like diabetes, heart disease, or liver disease.

I experience severe menopausal symptoms, mood changes, or sleep issues.

Smokers (≥ 20 cigarettes per day)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 500 mg resveratrol or placebo daily for 24 weeks, along with 500 mg calcium and 400 IU vitamin D3

24 weeks

3 visits (in-person) at baseline, 12 weeks, and 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Resveratrol

Trial Overview The study is testing if taking resveratrol supplements every day can improve bone health in postmenopausal women with low bone mass. It's a comparison between the effects of resveratrol and placebo (a substance with no active drug).

Participant Groups

Group I: Resveratrol Experimental Treatment 1 Intervention

Dietary Supplement: Resveratrol (500 mg) + 500 mg calcium and 400 IU vitamin D3

Group II: Placebo Placebo Group 1 Intervention

Dietary Supplement: Placebo (500 mg) + 500 mg calcium and 400 IU vitamin D3

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

Approved in United States as Resveratrol for:

• Dietary supplement for cardiovascular health and antioxidant properties

Approved in European Union as Resveratrol for:

• Dietary supplement for cardiovascular health and antioxidant properties

Approved in Canada as Resveratrol for:

• Dietary supplement for cardiovascular health and antioxidant properties

Who Is Running the Clinical Trial?

University of Delaware

Lead Sponsor

Trials

167

Recruited

25,700+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

Resveratrol (RSVL) binds to the estrogen receptor-alpha (ER alpha) in a unique way compared to traditional agonists like diethylstilbestrol (DES), forming additional hydrogen bonds that may influence its distinct biological effects.

The study reveals that RSVL has a more favorable energy of interaction with the ER alpha binding pocket, suggesting it could have different health benefits while still being recognized by the receptor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recognition of resveratrol by the human estrogen receptor-alpha: a molecular modeling approach to understand its biological actions. el-Mowafy, AM., Abou-Zeid, LA., Edafiogho, I.[2018]

In a study involving 48 ovariectomized rats over 90 days, trans-resveratrol at a dose of 45 mg/kg body weight per day significantly improved bone mineral density compared to other treatment groups, suggesting its potential as a dietary alternative for preventing osteoporosis in postmenopausal women.

Trans-resveratrol also enhanced bone formation markers while reducing bone absorption markers, and importantly, it did not cause adverse effects like endometrial hyperplasia, indicating a safer profile compared to traditional hormone replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of resveratrol on bone mineral density in ovarectomized rats. Lin, Q., Huang, YM., Xiao, BX., et al.[2021]

Resveratrol significantly increased bone mineral density (BMD) in osteoporosis (OP) rat models, with effective doses ranging from less than 10 mg/kg to 60 mg/kg per day, indicating its potential as a treatment for OP.

The mechanism of action for resveratrol appears to involve improving bone microstructure and regulating calcium and phosphorus metabolism, although it did not significantly affect serum alkaline phosphatase or osteocalcin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of resveratrol in an animal model of osteoporosis: a meta-analysis of preclinical evidence. Zhao, J., Zhou, G., Yang, J., et al.[2023]

Trans-resveratrol (t-RESV), found in grape skins and red wine, shows significant anti-inflammatory and anticarcinogenic properties in various experimental models, highlighting its potential as a therapeutic agent.

The cis isomer of resveratrol (c-RESV) is less studied and not commercially available, leading to a gap in understanding its pharmacological effects compared to the well-researched t-RESV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative studies of the antioxidant effects of cis- and trans-resveratrol. Orallo, F.[2022]

Red wines contain significantly higher levels of beneficial compounds like resveratrol and piceid, averaging 4.37 mg/liter, compared to only 0.68 mg/liter in white wines, suggesting a stronger protective effect against cardiovascular disease from red wine consumption.

The study analyzed 42 wines from various regions in Japan, confirming that specific grape varieties, such as Pinot noir, Merlot, and Zweigeltrebe, have particularly high resveratrol content, which may contribute to their health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contents of resveratrol, piceid, and their isomers in commercially available wines made from grapes cultivated in Japan. Sato, M., Suzuki, Y., Okuda, T., et al.[2019]

Cis-resveratrol significantly reduces collagen-induced platelet aggregation in vitro, with a decrease of 43.5% at a concentration of 1 x 10(-5) M, indicating its potential as an anti-aggregating agent.

Trans-resveratrol also shows anti-aggregating effects but is slightly less effective than cis-resveratrol, suggesting that both isomers should be considered when evaluating resveratrol's overall activity in biological systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiplatelet activity of cis-resveratrol. Bertelli, AA., Giovannini, L., Bernini, W., et al.[2018]

Trans-resveratrol and its analogues, such as pterostilbene and piceatannol, show promising potential in preventing cancer and cardiovascular diseases due to their diverse bioactivities.

These polyphenols are primarily found in fruits and are now available in various pharmaceutical and dietary supplement forms, highlighting their growing importance in health and wellness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemopreventive and chemotherapeutic effect of trans-resveratrol and its analogues in cancer]. Mikstacka, R., Ignatowicz, E.[2018]

Synthetic cis-polymethoxystilbenes, derived from the biologically inactive cis-resveratrol, showed potent anti-cancer effects against metastatic B16 F10 melanoma cells, with an IC50 of less than 10 μM, indicating strong efficacy.

These compounds inhibited cell motility and proliferation more effectively than both cis- and trans-resveratrol, suggesting they could be promising candidates for chemotherapy in treating metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-tumor properties of cis-resveratrol methylated analogs in metastatic mouse melanoma cells. Morris, VL., Toseef, T., Nazumudeen, FB., et al.[2018]

In a study involving ovariectomized rats, resveratrol treatment for 4 weeks was shown to slightly increase bone mineral density (BMD) and restore the balance of RANKL/OPG, which is important for bone health.

Resveratrol also significantly reduced the expression of pro-inflammatory cytokines (IL-23, IL-17A, IL-1β, and TNF-α), suggesting it may help mitigate inflammation associated with postmenopausal osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resveratrol restores the level of key inflammatory cytokines and RANKL/OPG ratio in the femur of rat osteoporosis model. Khera, A., Kanta, P., Kalra, J., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Recognition of resveratrol by the human estrogen receptor-alpha: a molecular modeling approach to understand its biological actions. [2018]

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

Effects of resveratrol on bone mineral density in ovarectomized rats. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of resveratrol in an animal model of osteoporosis: a meta-analysis of preclinical evidence. [2023]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Comparative studies of the antioxidant effects of cis- and trans-resveratrol. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Contents of resveratrol, piceid, and their isomers in commercially available wines made from grapes cultivated in Japan. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Antiplatelet activity of cis-resveratrol. [2018]

7. Poland pubmed.ncbi.nlm.nih.gov

[Chemopreventive and chemotherapeutic effect of trans-resveratrol and its analogues in cancer]. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-tumor properties of cis-resveratrol methylated analogs in metastatic mouse melanoma cells. [2018]

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

Resveratrol restores the level of key inflammatory cytokines and RANKL/OPG ratio in the femur of rat osteoporosis model. [2020]