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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether daily resveratrol intake can improve bone health in postmenopausal women. Resveratrol, a compound in red wine and grapes, might benefit bones. Participants will receive either resveratrol with calcium and vitamin D3 or a placebo (a look-alike pill with no active ingredients) with the same nutrients. Suitable candidates are women who have been postmenopausal for 1 to 10 years, have low bone mass, and do not have osteoporosis or certain other medical conditions. As an unphased trial, this study offers a unique opportunity to contribute to scientific knowledge and potentially benefit from an innovative approach to bone health.

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.

Is there any evidence suggesting that resveratrol is likely to be safe for humans?

Research has shown that resveratrol is generally safe for people. Studies have found that doses up to 5 grams per day are usually well-tolerated, with no serious side effects reported. Therefore, the lower dose used in this trial (500 mg) is likely safe for most individuals. However, as with any supplement, reactions can vary. It is important to consult a healthcare provider before starting a new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for osteopenia, which typically include bisphosphonates or hormone therapy, resveratrol is a natural compound found in red wine and grapes. Researchers are excited about resveratrol because it offers a new mechanism of action by potentially enhancing bone density through its antioxidant properties, which may help reduce bone loss. Additionally, resveratrol is combined with calcium and vitamin D3, known to support bone health, providing a holistic approach to managing osteopenia. This combination could offer a more natural and possibly safer alternative to traditional medications, sparking significant interest in its potential benefits.

What evidence suggests that resveratrol might be an effective treatment for osteopenia?

This trial will compare the effects of Resveratrol with a placebo on bone health in individuals with osteopenia. Research has shown mixed results regarding resveratrol's ability to improve bone health. One study found that resveratrol increased bone strength in postmenopausal women. However, other studies did not observe significant changes in bone strength or health markers. In animal studies, resveratrol improved bone structure and calcium balance. These mixed results suggest resveratrol might benefit some individuals, but more research is needed to confirm its effects on bone health. ^{3 6 7 8 9}

Who Is on the Research Team?

Sheau Ching Chai, PhD, RD

Principal Investigator

University of Delaware

Are You a Good Fit for This Trial?

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

Smokers (≥ 20 cigarettes per day)

Intolerance or allergic reaction to resveratrol, microcrystalline cellulose, grapes, red wine, or blueberries

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8380387/

Effects of resveratrol supplementation on bone quality The results of the study showed a significant increase in serum alkaline phosphatase (ALP) and bone alkaline phosphatase (BAP) values after ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10414791/

Effects of resveratrol in an animal model of osteoporosis Resveratrol can increase BMD in OP rat models, and its mechanism of action may be related to improving bone microstructure and regulating calcium and ...

3. bmccomplementmedtherapies.biomedcentral.com bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-021-03381-4

Effects of resveratrol supplementation on bone quality Resveratrol supplementation did not show any significant effect on BMD or serum bone markers with the current evidence.

4. researchgate.net researchgate.net/publication/354059473_Effects_of_resveratrol_supplementation_on_bone_quality_a_systematic_review_and_meta-analysis_of_randomized_controlled_trials

(PDF) Effects of resveratrol supplementation on bone quality Supplementation of resveratrol had no statistically significant effects on areal bone mineral density (aBMD) at lumbar spine (MD: -0.02, 95% CI: − 0.05, 0.01, p ...

5. veriteresveratrol.com veriteresveratrol.com/2020/07/study-shows-improvements-in-bone-mineral-density-of-postmenopausal-women/

Long-Term Resveratrol Study Shows Improvements in ... News Release: Long-Term Resveratrol Study Shows Improvements in Bone Mineral Density of Postmenopausal Women. July 7th, 2020.

6. en.wikipedia.org en.wikipedia.org/wiki/Resveratrol

Resveratrol Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol or polyphenol and a phytoalexin produced by several plants

7. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Resveratrol

Resveratrol | C14H12O3 | CID 445154 - PubChem - NIH Resveratrol is a plant polyphenol found in high concentrations in red grapes that has been proposed as a treatment for hyperlipidemia and to prevent fatty liver

8. s3-us-west-2.amazonaws.com s3-us-west-2.amazonaws.com/drugbank/cite_this/attachments/files/000/001/706/original/resveratrol_508.pdf?1538174757

trans-Resveratrol [501-36-0] Review of Toxicological ... Human Studies: Adverse effects of resveratrol have not been reported; a recommended dosage of 5-10 mg (22-44 µmol) per day was stated to be " ...

9. consensus.app consensus.app/home/blog/what-is-resveratrol-other-names-cis-resveratrol-phytoalexin-wine-extract/

Cis-Resveratrol, Phytoalexin, Wine Extract Resveratrol (3,5,4′-trihydroxy-trans-stilbene) belongs to the ... Resveratrol is generally safe at doses up to 5 g/day, but its rapid ...