Research
Vitamin D3
Adequate Vitamin D3 levels, especially when combined with calcium supplementation, have been shown in meta-analyses to reduce fracture risk in adults over 50 by up to about 19%, with specific studies showing reductions in the range of 14%-19% for total fractures and higher for hip fractures.aoj.amegroups+2
A meta-analysis summarized eight randomized controlled trials (RCTs) and found that daily supplementation of vitamin D (800–1,000 IU) plus calcium led to a 14-15% reduction in total fractures and up to a 30% reduction in hip fractures in adults over 50.aoj.amegroups
Another meta-analysis found that vitamin D doses between 482–770 IU/d reduced hip fractures by 18% and non-vertebral fractures by 20%.pmc.ncbi.nlm.nih
A systematic review reported high-quality evidence for a 16% reduction in hip fracture risk and 5% reduction in any fracture risk with 400–800 IU/day of vitamin D coadministered with calcium.pmc.ncbi.nlm.nih
The Annals of Joint expert summary recommends the daily allowance of 800–1,000 IU vitamin D and 1,200 mg calcium for adults over 50 at risk, in line with major guidelines.aoj.amegroups
Most studies agree that vitamin D alone at lower doses is likely ineffective, and benefits are strongest when paired with calcium supplementation. Results may be more pronounced in institutionalized older adults, but benefits are observed in community-dwelling older adults as well.pmc.ncbi.nlm.nih+1
Direct links to research studies and meta-analyses supporting these findings:
Expert consensus on vitamin D in osteoporosis — Annals of Jointaoj.amegroups
Vitamin D and Bone Health; Potential Mechanisms — NCBI/PMCpmc.ncbi.nlm.nih
Vitamin D Supplementation and Fractures in Adults: A Systematic Review — NCBI/PMCpmc.ncbi.nlm.nih
These peer-reviewed sources provide scientific evidence for the efficacy of vitamin D3 (with calcium) in reducing fracture risk by up to 19% in adults over 50.
- https://aoj.amegroups.org/article/view/9070/html
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3257679/
- https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2757873
- https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/vitamin-d-calcium-or-combined-supplementation-for-the-primary-prevention-of-fractures-in-adults-preventive-medication
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9081312/
- https://www.sciencedirect.com/science/article/pii/S1530891X25009656
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8852203/
- https://jamanetwork.com/journals/jama/fullarticle/2748796
- https://www.sciencedirect.com/science/article/abs/pii/S2213858723000633
- https://academic.oup.com/edrv/article/45/5/625/7659127
Vitamin K2, Bone Health, and MK-7
1. K2 Supplementation, Bone Mineral Density, and Fracture Risk
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Systematic Reviews and Meta-Analyses:
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Multiple meta-analyses and systematic reviews demonstrate that vitamin K2 (especially menaquinone forms) supplementation can help maintain or improve bone mineral density, and in some cases, reduce fracture risk—particularly in postmenopausal women or those with osteoporosis.pmc.ncbi.nlm.nih+3
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One meta-analysis with 6,425 subjects found a significant improvement in lumbar spine BMD and a reduction in fracture incidence after excluding one outlier study (RR = 0.43, P = 0.01).frontiersin
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A randomized controlled trial found that K2 supplementation (menatetrenone, or MK-4) effectively prevented the occurrence of new fractures in osteoporotic patients compared to controls during a 2-year period.academic.oup
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Additional reviews report that vitamin K status is associated with lower bone mineral density and higher fracture risk, supporting the recommendation for supplementation in at-risk populations.pmc.ncbi.nlm.nih+1
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Direct Research Links:
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PMC Article: Influence of Vitamin K on Bone Mineral Density and Osteoporosispmc.ncbi.nlm.nih
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PMC Article: Effect of Vitamin K on Bone Mineral Density and Fracture Risk in Adultspmc.ncbi.nlm.nih
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Frontiers: Systematic Review & Meta-Analysis of Randomized Controlled Trials on Vitamin K2frontiersin
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Journal of Bone and Mineral Research: Vitamin K2 (Menatetrenone) Prevents Fracturesacademic.oup
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2. MK-7 vs. Other Forms: Half-Life Comparisons
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MK-7 Half-Life:
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MK-7 (menaquinone-7) has a significantly longer half-life in the bloodstream compared to other K2 forms: ~3 days (72 hours).nbihealth+6
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One pharmacokinetic study showed a half-life of 68 hours for MK-7, and multiple sources also cite a range of 2.5–3.5 days.performancelab+4
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The extended half-life means that MK-7 remains in circulation longer and can sustain more consistent blood levels with less frequent dosing.
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MK-4 and K1 Half-Life:
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MK-4 typically has a half-life of only 1.5–2 hours, requiring multiple doses per day for steady serum levels.sciencedirect+3
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Vitamin K1’s half-life is similar, about 1–2 hours.wearefeel+1
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Direct Research Links:
Summary: Vitamin K2 supplementation, especially in the MK-7 form, is supported by research for its role in supporting bone health and reducing fracture risk, particularly among postmenopausal women and osteoporotic patients. The MK-7 form stands out for its long half-life (~3 days), offering superior bioavailability compared to MK-4 (1.5–2 hours) or K1, thus enabling easier dosing and more sustained blood levels.reddit+4
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7645307/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9138595/
- https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2022.979649/full
- https://academic.oup.com/jbmr/article-abstract/15/3/515/7515533
- https://academic.oup.com/ndt/article/38/10/2105/7190649
- https://www.nbihealth.com/mk4-or-mk7-which-is-better-for-bones/
- https://www.performancelab.com/blogs/multi/how-long-does-vitamin-k2-stay-in-the-body
- https://wearefeel.com/en-us/blogs/learn/forms-of-vitamin-k-k1-vs-k2-mk-7-menaquinone
- https://www.sciencedirect.com/science/article/abs/pii/S1098882325000231
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7238900/
- https://take2healthcare.com/menaquinone-7-vitamin-k2/
- https://www.reddit.com/r/Supplements/comments/1iu9lsg/how_long_does_it_take_k2_to_come_out_of_my_system/
- https://www.sciencedirect.com/science/article/abs/pii/S8756328211011379
- https://www.reddit.com/r/Supplements/comments/cto7sm/oral_bioavailability_of_vitamin_k2_mk4_vs_mk7/
- https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/410550
- https://www.mediq7.com/blog/which-one-is-the-best-form-for-vitamin-k2/
- https://article.imrpress.com/journal/IJVNR/87/5-6/Bioavailability%20and%20Chemical/Functional%20Aspects%20of%20Synthetic%20MK-7%20vs%20Fermentation-Derived%20MK-7%20in%20Randomised%20Controlled%20Trials/4e85b7841f9a34d31be232297698c880.pdf
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3502319/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9237441/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7230802/
Here are authoritative sources and studies supporting the role of Vitamin K2 (especially MK-7) in directing calcium to bones and teeth, rather than soft tissues:
A detailed review in the National Institutes of Health’s open research archive highlights that vitamin K2 (MK-7) activates osteocalcin, a protein produced by bone-building cells (osteoblasts), allowing calcium to bind to the bone matrix and enhancing bone mineralization. This same mechanism prevents unwanted calcium deposition in arteries, with clinical trials showing improved bone density and cardiovascular health in those supplemented with MK-7.pmc.ncbi.nlm.nih
Research published in Frontiers in Pharmacology explains how MK-7 facilitates the carboxylation of osteocalcin and matrix GLA protein (MGP), both critical for directing calcium to bones, teeth, and preventing its accumulation in blood vessels. Multiple clinical trials have demonstrated that MK-7 supplementation increases levels of active osteocalcin, resulting in stronger bones and reduced risk of vascular calcification.frontiersin
A resource from Metropolitan Dental Care describes that vitamin K2-dependent proteins—osteocalcin and matrix GLA protein—specifically direct calcium out of the bloodstream and into bones and teeth. When osteocalcin is activated by K2, fresh dentin is built in teeth, and bone mass is increased. These benefits are especially marked with the MK-7 form.metropolitandentalcarenyc
ClinicalTrials.gov records ongoing and completed controlled trials that investigate MK-7’s effects on bone mineral density and its potential to steer calcium to the correct locations, supporting its use in improving bone and vascular health.clinicaltrials+1
Summary of Mechanism:
Vitamin K2 (MK-7) activates bone and tooth proteins (mainly osteocalcin and matrix GLA protein).
This process enables the body to use dietary or supplemental calcium for strengthening bones and teeth.
It simultaneously inhibits the deposition of calcium in arteries and soft tissues, reducing risks associated with excess calcium intake.
These studies and reviews provide strong evidence that Vitamin K2 (MK-7) directs calcium to bones and teeth, supporting overall skeletal and dental health.
If you need direct links to the original studies or want help navigating the specific clinical trials or reviews, here are the referenced sources:
[NIH Review: Proper Calcium Use—Vitamin K2 as a Promoter of Bone and Cardiovascular Health]pmc.ncbi.nlm.nih
[Frontiers in Pharmacology: Molecular pathways and clinical trials MK-7]frontiersin
[Metropolitan Dental Care: How Vitamin K2 effects teeth and bones]metropolitandentalcarenyc
[ClinicalTrials.gov: Effect of Vitamin K2 (MK-7) on Cardiovascular and Bone Disease]clinicaltrials+1
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4566462/
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.896920/full
- https://www.metropolitandentalcarenyc.com/blog/vitamin-k2/
- https://clinicaltrials.gov/study/NCT02976246
- https://www.clinicaltrials.gov/study/NCT02976246?term=CHOLECALCIFEROL+AND+MENAQUINONE+7&viewType=Table&rank=8
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8483258/
- https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2022.979649/full
- https://www.youtube.com/watch?v=D_UJaEZe9gg
- https://menaq7.com/news/association-of-active-folate-and-vitamin-k2-a-new-approach-to-bone-health/
- https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2019.00006/full
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7926526/
- https://www.sciencedirect.com/science/article/pii/S0306987715000328
- https://www.sciencedirect.com/science/article/abs/pii/S037851222030284X
- https://www.healthline.com/nutrition/vitamin-k2
- https://resources.healthgrades.com/right-care/food-nutrition-and-diet/vitamin-k2
Calcium Synergy Research
Several scientific studies and reviews have evaluated whether combining vitamin D3 (cholecalciferol), vitamin K2, and calcium is more effective for building bone than calcium alone. Here are a few notable studies and reviews from peer-reviewed sources:
Key Scientific Studies
Iwamoto et al. (2000): Randomized Controlled Trial
This landmark study divided 92 postmenopausal women with osteoporosis into four groups: calcium alone, vitamin D3 alone, vitamin K2 alone, and a combination of vitamin D3 plus K2. Over two years, the group receiving both vitamin D3 and vitamin K2 showed a significantly greater increase in lumbar spine bone mineral density (BMD) than the calcium-alone group, and also greater than either D3 or K2 alone. The combination was thus found to be “useful in increasing the BMD of the lumbar spine in postmenopausal women with osteoporosis”.pubmed.ncbi.nlm.nih
Braam et al. (2003): Three-Year Intervention
In postmenopausal women (mean age 55–81), those supplemented with minerals, vitamin D, and vitamin K1 experienced reduced bone loss at the femoral neck compared to those with minerals and vitamin D only, or placebo. This points toward an additive or synergistic effect when all three nutrients are combined.pmc.ncbi.nlm.nih
Sato et al. (2005): Bone Density and Fracture Prevention
Postmenopausal women with Alzheimer’s were assigned to receive calcium, vitamin D, and vitamin K together. Significant increases in bone mineral density and a reduction in fracture risk were observed compared to the control group, notably outperforming calcium alone.pmc.ncbi.nlm.nih
Recent Systematic Reviews & Meta-analyses
Larger reviews summarize clinical trials and generally show that the combination of vitamin D3, K2, and calcium improves bone markers and BMD more effectively than calcium alone in most populations, particularly in postmenopausal women and older adults. Some studies also report a lower risk of fractures with the combined regimen.joinmidi+2
Mechanistic Rationale
Vitamin D3 helps increase calcium absorption from the gut.
Vitamin K2 activates proteins like osteocalcin, which direct calcium into bone tissue and prevent calcium buildup in arteries.
Calcium itself provides the raw material for building bone, but is not efficiently used without D3 and K2.viactiv+1
Important Notes
Not all studies found strong synergistic effects, especially in healthy populations over short study periods; however, the majority of longer-term research in osteoporotic or at-risk older adults supports the combination as superior to calcium alone for increasing bone density and reducing fracture risk.viactiv+1
Clinical guidelines still recommend consulting a healthcare provider regarding supplementation, particularly for those with underlying health conditions.joinmidi
In summary: Scientific studies demonstrate that the combination of vitamin D3, vitamin K2, and calcium is generally more effective at increasing bone mineral density and reducing fracture risk than calcium alone, particularly in at-risk populations such as postmenopausal women.pubmed.ncbi.nlm.nih+2
- https://pubmed.ncbi.nlm.nih.gov/11180916/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5613455/
- https://www.joinmidi.com/post/benefits-of-d3-and-k2
- https://viactiv.com/blogs/viactiv-blog/why-calcium-alone-isn-t-enough-the-power-of-vitamin-d-k2-in-bone-health
- https://www.sciencedirect.com/science/article/abs/pii/S037851222030284X
- https://www.sciencedirect.com/science/article/abs/pii/S0378512201002754
- https://www.nature.com/articles/s41598-025-99922-9
- https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2022.979649/full
- https://clinicaltrials.gov/study/NCT06867952?term=AREA%5BBasicSearch%5D%28Calcium%2C+Dietary+AND+VDR%29&rank=6
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8515712/
- https://www.health.harvard.edu/staying-healthy/too-much-vitamin-d-may-harm-bones-not-help
- https://www.casi.org/pilot-study-vitamins-d3-k2-bone-health
- https://www.bonehealthandosteoporosis.org/patients/treatment/calciumvitamin-d/
- https://www.webmd.com/osteoporosis/vitamin-d-for-osteoporosis
- https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-q-and-a-osteoporosis-and-supplements-for-bone-health/
BioPerine® (piperine extract) Enhancement
Clinical studies indicate that BioPerine® (piperine extract) enhances the absorption of some fat-soluble vitamins, but direct evidence for a 30% increase in absorption specifically for vitamin D3 and K2 is limited. Most clinical data shows significant bioavailability improvements for nutrients like β-carotene, coenzyme Q10, and other fat-soluble compounds, and mechanistic studies suggest similar effects for vitamins D and K.
Key findings from clinical research:
BioPerine® increased absorption of β-carotene (a fat-soluble vitamin) by nearly twofold (about 100%) in a human study when 5 mg BioPerine® was co-administered with 15 mg β-carotene.pmc.ncbi.nlm.nih+1
Coenzyme Q10, another fat-soluble compound, showed a 30% increase in area under the curve (AUC, a measure of bioavailability) when combined with BioPerine®.bioperine
Clinical studies and mechanistic reviews confirm BioPerine® enhances the absorption of fat-soluble vitamins (A, D, E, K) and other lipophilic nutrients, mainly by altering membrane fluidity and improving intestinal uptake.restorativemedicine+1
While BioPerine®’s benefit for D3 and K2 is widely claimed by supplement makers and supported by mechanistic rationale, the 30% figure is based mostly on clinical studies of similar fat-soluble nutrients (like CoQ10 and β-carotene), not directly on vitamin D3 or K2.
Summary Table: Evidence from Clinical Research
Nutrient | % Increase with BioPerine® | Source |
|---|---|---|
β-Carotene | ~100% (2-fold) | |
Coenzyme Q10 | ~30% | |
Curcumin | 2000% | |
Vitamin D3, K2 | (mechanism suggests enhancement) |
- https://bioperine.com/researchhighlight/
- https://restorativemedicine.org/library/monographs/piperine-black-pepper/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7353321/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11242131/
- https://en.vitamin360.com/p/usa-medical-k2-d3-with-bioperine-60-capsules
- https://clinicaltrials.gov/study/NCT03490955
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5613455/
- https://www.healthline.com/nutrition/bioperine-and-piperine-supplement-benefits
- https://meonutrition.com/products/6x-vitamin-k2-d3
- https://www.healthycell.com/blogs/articles/increase-vitamin-and-mineral-absorption
Multi-Source Collagen Superiority
1. Amino Acid Composition & Digestive Bioavailability
A 2019 study investigated plasma amino acid responses in healthy adults after ingestion of various protein sources, including collagen and bone broth. Key findings:
- Different collagens (hydrolyzed vs. non-hydrolyzed) led to varied plasma amino acid concentrations and absorption rates.
- Collagen proteins showed significantly higher glycine peaks, while other proteins excelled in leucine content.
- Bone broth—a naturally mixed collagen source containing primarily Type I and III—had the highest total amino acid area under the curve (AUC) over 180 minutes (ScienceDirect, Frontiers).
Relevance: Different types of collagen provide complementary amino acid release profiles, supporting the rationale for combining Type I, II, III, and V in one product.
2. Advantages of Combining Bovine, Marine, and Avian Collagens
Industry commentary (July 2025) notes potential benefits of blending sources:
- Broader amino acid profile: Type I & III (bovine/marine) for skin and connective tissue, Type II (avian cartilage) for joints, and Type V for fibrillar network stability.
- No known adverse interactions when combined.
(BUBS Naturals)
3. Processing Effects on Collagen Bioavailability
A 2019 review describes how collagen source and hydrolysis affect molecular weight, solubility, and absorption (PMC).
Relevance: Hydrolyzed Type I, II, III, and V collagens can be optimized for maximal uptake.
Focus Area | Findings |
|---|---|
Type synergy | Combining I, II, III, and V provides structural and functional diversity—skin, cartilage, vascular, and interstitial tissue support. |
Amino acid coverage | Broader range and sustained release from mixed sources compared to single-type collagen. |
Processing impact | Hydrolyzed peptides improve absorption; blending sources/type maximizes complementary profiles. |
Suggested Readings
- Frontiers in Nutrition – “Plasma Amino Acid Concentrations After the Ingestion of Collagen and Dairy Protein Sources”, RD Alcock et al. (2019). (Frontiers)
- BUBS Naturals – “Can You Mix Bovine and Marine Collagen for Optimal Health?” (2025). (BUBS Naturals)
- Molecules (MDPI) – “Hydrolyzed Collagen—Sources and Applications”, A. León‑López et al. (2019). (PMC)
This literature supports the concept that multi-type collagen blends, particularly I, II, III, and V, can offer a more complete amino acid spectrum and functional coverage than single-source supplements.
Skin Anti-Aging Benefits
1. ELASTEN® Randomized Controlled Trial (2019)
- Collagen Types: Primarily Type I & III (bovine skin).
- Results: +28% hydration, significant elasticity improvement, increased skin density, reduced roughness (p < 0.0001).
- Relevance: Types I & III form the dermal scaffold, supporting firmness and water retention.
- Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC6835901/
2. Systematic Review & Meta-Analysis (2023)
Collagen Types: Mostly Type I & III from bovine/marine; some included Type II (chicken sternal cartilage).
Results: Hydration SMD = 0.63 (p < 0.00001), Elasticity SMD = 0.72 (p < 0.00001).
Relevance: Confirms broad efficacy across multiple types; Type II’s proteoglycan support may indirectly affect dermal hydration and elasticity.
3. Reilly et al., Clinical Trial (2024)
Collagen Types: Hydrolyzed Type I & III with vitamin C co-factor.
Results: −44.6% collagen fragmentation, +13.8% hydration, +22.7% elasticity, −19.6% wrinkle depth (p < 0.01).
Relevance: Type I & III synergistically restore dermal matrix integrity and plumpness.
4. Low-Molecular-Weight Collagen Hydrolysate Trial (2024)
Collagen Types: Bovine Type I & III (≤1 kDa peptides).
Results: Reduced wrinkle depth, increased hydration, moderate elasticity gains in just 6 weeks.
Relevance: Smaller peptides may improve absorption, benefiting all targeted skin metrics.
5. Italian Collagen Supplement Study (2022)
Collagen Types: Hydrolyzed Type I & III.
Results: Significant hydration, elasticity, and wrinkle reduction by day 28, sustained at day 56.
Relevance: Direct human evidence for Types I & III improving visible skin parameters.
Link: https://jcadonline.com/efficacy-collagen-supplement-improve-skin/
6. Narrative Review (2023)
Collagen Types: Predominantly Type I & III, with mentions of Type V for fibrillar assembly support and Type II in joint + dermis interplay.
Results: Consistent skin hydration, elasticity, and wrinkle reduction across studies.
Relevance: Type V supports fibril organization of Types I & III, potentially enhancing skin structure and elasticity.
Link: https://www.sciencedirect.com/science/article/pii/S2405844023021680
Study / Year | Collagen Types | Duration | Key Outcomes | Link |
|---|---|---|---|---|
ELASTEN® RCT (2019) | I, III | 12 wks + 4 wk follow-up | ↑ Hydration +28%, ↑ Elasticity, ↑ Density, ↓ Roughness | |
Meta-Analysis (2023) | I, III, II | Various (4–24 wks) | ↑ Hydration (SMD 0.63), ↑ Elasticity (SMD 0.72) | |
Reilly et al. (2024) | I, III | 12 wks | ↓ Wrinkle depth 19.6%, ↑ Hydration 13.8%, ↑ Elasticity 22.7% | |
LMW Collagen Trial (2024) | I, III | 6 wks | ↓ Wrinkles, ↑ Hydration, moderate ↑ Elasticity | |
Italian RCT (2022) | I, III | 8 wks | ↑ Hydration, ↑ Elasticity, ↓ Wrinkles by day 28 | |
Narrative Review (2023) | I, III, II, V | Review | Consistent improvements in hydration, elasticity, wrinkle depth |
Joint Health & Mobility
Top 5 Clinical Studies: Collagen for Joint Health
1. Crowley et al., 2009 — UC-II® vs Glucosamine/Chondroitin in Knee OA (RCT)
Type: Undenatured Type II collagen (40 mg/day).
Population: Adults with knee osteoarthritis.
Duration: 90 days.
Results: Significant WOMAC pain reduction, improved knee function vs glucosamine/chondroitin group (p < 0.05).
2. Lugo et al., 2016 — UC-II® in Knee OA (Multicenter RCT)
Type: Undenatured Type II collagen (40 mg/day).
Population: Adults with knee osteoarthritis.
Duration: 180 days.
Results: Reduced pain and improved function vs placebo and vs glucosamine/chondroitin.
3. Bakilan et al., 2016 — Native Type II Collagen in Knee OA (RCT)
Type: Native Type II collagen.
Population: Adults with knee osteoarthritis.
Duration: 90 days.
Results: Significant improvements in pain (VAS), function (Lequesne, WOMAC), and inflammation biomarkers.
4. Benito-Ruiz et al., 2009 — Hydrolyzed Collagen in Knee OA (RCT)
Type: Hydrolyzed collagen (Types I & II) — 10 g/day.
Population: 250 adults with knee osteoarthritis.
Duration: 6 months.
Results: Significant pain reduction (VAS, WOMAC-pain) and improved joint comfort vs placebo.
5. Clark et al., 2008 — Collagen Hydrolysate in Athletes with Joint Pain (RCT)
Type: Hydrolyzed collagen (Types I & II) — 10 g/day.
Population: Athletes with activity-related joint pain.
Duration: 24 weeks.
Results: Reduced joint pain during activity vs placebo.
# | Study (Year) | Population | Collagen Type(s) & Dose | Duration | Key Outcomes |
1 | Adults with knee OA | Undenatured Type II (40 mg/day) | 90 d | ↓ WOMAC pain; ↑ function vs glucosamine/chondroitin | |
2 | Adults with knee OA | Undenatured Type II (40 mg/day) | 180 d | ↓ Pain; ↑ function vs placebo & G+C | |
3 | Adults with knee OA | Native Type II | 90 d | ↓ Pain (VAS); ↑ function (WOMAC, Lequesne); ↓ inflammation markers | |
4 | Knee OA adults (n=250) | Hydrolyzed Type I & II (10 g/day) | 6 mo | ↓ Pain (VAS, WOMAC); ↑ joint comfort | |
5 | Athletes with joint pain | Hydrolyzed Type I & II (10 g/day) | 24 wks | ↓ Activity-related joint pain vs placebo |
Muscle Mass & Recovery
Top Clinical Studies – Collagen + Exercise for Muscle Mass, Strength, and Recovery
Across multiple RCTs, collagen peptide supplementation (typically 15 g/day) combined with resistance or concurrent training consistently amplified improvements in muscle mass, strength, and recovery, compared to placebo. Meta-analytic data supports these effects—though with varying certainty—confirming the promise of collagen as an effective adjunct for musculoskeletal support.
1. Zdzieblik et al., 2015 – Elderly Men with Sarcopenia (RCT)
Population: Elderly men (~72 years) with sarcopenia (Class I or II)
Protocol: 12-week resistance training (3×/week) + 15 g/day hydrolyzed collagen peptides vs placebo
Results:
Fat-free mass (FFM): +4.2 kg (collagen) vs +2.9 kg (placebo) (P < 0.05)
Quadriceps strength: +16.5 Nm vs +7.3 Nm (P < 0.05)
Fat mass reduction: −5.4 kg vs −3.5 kg (P < 0.05)
Mechanism: Collagen provides glycine, proline, hydroxyproline and may support extracellular matrix remodeling post-exercise Frontiers+11ClinicalTrials.gov+11SpringerLink+11Wikipedia+10PMC+10MDPI+10MDPIFrontiers+1
2. Zdzieblik et al., 2021 – Middle-Aged, Untrained Men (RCT)
Population: Middle-aged, untrained men (~97 total participants)
Protocol: 12-week resistance training + 15 g/day collagen peptides vs placebo vs whey protein
Results:
FFM gain: 3.42 kg (collagen) vs 1.83 kg (placebo) (p = 0.010)
Fat mass loss: −5.28 kg vs −3.39 kg (p = 0.023)
Leg strength: 163 N increase vs 100 N (placebo)
No significant differences when compared to whey in exploratory analysis PMC+1Health+3PubMed+3Frontiers+3
Link: PubMed entry via reference in abstract
3. Bischof et al., 2023 – Collagen for Muscle Recovery (RCT)
Population: Sedentary males (~55 participants)
Protocol: 12-week concurrent training (resistance + endurance, 3×/week) + 15 g/day specific collagen peptides vs placebo; induced muscle damage via drop jumps
Results:
Faster recovery of maximal voluntary contraction (MVC), rate of force development (RFD), jump height
No change in body composition SpringerLink+1sciencedirect.com+10Frontiers+10Frontiers+10
Link: https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1266056/full
4. Bischof et al., 2024 – Markers of Muscle Damage (RCT)
Population: Sedentary to moderately active males
Protocol: 12-week concurrent training + 15 g/day collagen peptides vs placebo with induced muscle damage
Results:
Reduced post-exercise increases in myoglobin (MYO), creatine kinase (CK), and lactate dehydrogenase (LDH) (p < 0.05)
Indicates improved early recovery capacity SpringerLink+3Frontiers+3Frontiers+3
Link: https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1384112/full
5. Kirmse et al., 2024 – Meta-Analysis (Collagen Peptides + RT)
Scope: 13 RCTs, ~175 subjects for muscle size, 385 for strength
Findings:
Small but significant improvements: muscle size (SMD = 0.35, p = .002), maximal strength (SMD = 0.23, p < .01)
Certainty of evidence was low due to variability in study designs Frontiers+1businessinsider.com+10ciss-journal.org+10PMC+10
# | Study (Year) | Population | Collagen Type & Dose | Duration | Key Outcomes | Link |
|---|---|---|---|---|---|---|
1 | Zdzieblik et al. (2015) | Elderly sarcopenic men | Hydrolyzed collagen, 15 g/day | 12 weeks | ↑ FFM, ↑ strength, ↓ fat mass vs placebo | PMC:4594048 |
2 | Zdzieblik et al. (2021) | Middle-aged untrained men | Collagen peptides, 15 g/day | 12 weeks | Greater FFM gain, fat loss, strength vs placebo | PMC:8125453 |
3 | Bischof et al. (2023) | Sedentary males | Specific collagen peptides, 15 g/day | 12 weeks | Faster recovery of MVC, RFD, jump height | Frontiers Nutri 2023 |
4 | Bischof et al. (2024) | Sedentary/moderately active males | Collagen peptides, 15 g/day | 12 weeks | Lower CK, LDH, MYO post-exercise → improved recovery | Frontiers Nutri 2024 |
5 | Kirmse et al. (2024) | Healthy adults (meta-analysis) | Collagen peptides + RT | ≥8 weeks | Small yet significant ↑ muscle size & strength (low evidence) | German J Sports Med |
Bone Density Support
- Hydrolyzed collagen peptides (5 g/day) have demonstrated the ability to increase BMD in postmenopausal women over a 12-month period.
A 4-year follow-up confirmed continued gains in spine and femoral neck density, with no fractures reported.
Broader reviews reinforce this evidence but highlight a need for more high-quality bone-specific RCTs.
Preliminary observations and media coverage support clinical findings, though more direct data is desired.
1. König et al., 2018 — Collagen Peptides Increase BMD in Postmenopausal Women (RCT)
Population: 131 postmenopausal women with age-related reduced BMD.
Intervention: 5 g/day specific collagen peptides.
Duration: 12 months.
Outcomes:
Significant increases in T-scores at both lumbar spine and femoral neck vs placebo (spine +0.1 ± 0.26 vs –0.03 ± 0.18, p = 0.030; femoral neck +0.09 ± 0.24 vs –0.01 ± 0.19, p = 0.003).
Favorable shifts in bone formation marker (P1NP) and resorption marker (CTX‑1): increased P1NP, decreased CTX‑1.
Link: https://pubmed.ncbi.nlm.nih.gov/29337906/ PMC+4PubMed+4PMC+4
2. Zdzieblik et al., 2021 — 4-Year Follow-Up on Collagen Peptide Supplementation
Population: Subset of the original RCT participants continued supplementation.
Intervention: 5 g/day of the same bioactive collagen peptides (FORTIBONE®).
Duration: 4 years (open-label follow-up).
Outcomes:
Lumbar spine BMD increased by 5.8% to 8.2%; femoral neck BMD increased by 1.2% to 4.2%—all exceeding the 3% threshold for clinical relevance.
No fractures occurred during the follow-up.
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441532/ PMC
3. Medical News Today Summary — Collagen and Bone Density
Overview: Reports on small-scale studies showing that 1 year of daily collagen peptide supplementation led to measurable increases in BMD in the lower spine and upper leg of postmenopausal women, along with higher bone formation biomarkers.
Note: Media summary acknowledging limited but promising evidence.
Link: https://www.medicalnewstoday.com/articles/collagen-for-osteoporosis ClinicalTrials.gov+5UCLA Health+5PubMed+5Medical News Today
4. Systematic Review — Type I Collagen Hydrolysate Effects (Brueckheimer, 2025)
Scope: Systematic review of 36 RCTs (bones, muscles, joints), focusing on Type I hydrolyzed collagen.
Bone Health Findings: Few high-quality studies specifically on bone outcomes; some evidence (e.g., König et al.) suggests collagen supplementation might support BMD in postmenopausal women.
Link: https://orthopedicreviews.openmedicalpublishing.org/article/129086-the-effects-of-type-i-collagen-hydrolysate-supplementation-on-bones-muscles-and-joints-a-systematic-review?utm_source=chatgpt.com PMC+1
5. Human Kinetics Study — Jump Training + Collagen in Cyclists (2023)
Population: Elite road-race cyclists.
Intervention: Combined jump-training exercise and collagen supplementation.
Outcome: Assessed for impacts on bone mineral density.
Note: Study aimed to evaluate functional training + collagen but did not report BMD outcomes in detail.
Link: https://journals.humankinetics.com/view/journals/ijsnem/34/1/article-p38.xml ScienceDirect+9Human Kinetics Journals+9PMC+9
# | Study (Year) | Population | Collagen Type & Dose | Duration | Key Outcomes | Link |
|---|---|---|---|---|---|---|
1 | König et al. (2018) | Postmenopausal women (n=131) | Hydrolyzed collagen (5 g/day) | 12 months | ↑ BMD (spine & femoral neck); ↑ P1NP; ↓ CTX‑1 | |
2 | Zdzieblik follow-up (2021) | Subset of original RCT participants (n≈31) | Same peptide, 5 g/day | 4 years (open-label) | BMD ↑: 5.8–8.2% spine; 1.2–4.2% femoral neck; no fractures | |
3 | Medical News Today (2025) | Postmenopausal women (media summary) | Collagen peptides (unspecified dose) | 1 year | Reported BMD ↑ in spine & upper leg; ↑ bone formation biomarker | |
4 | Brueckheimer (2025) Review | Mixed (bones, joints, muscles) | Type I hydrolyzed collagen | Various RCTs | Limited bone outcomes; some support for BMD improvements (e.g. König study) | |
5 | Hilkens et al. (2023) | Elite cyclists | Collagen + jump exercise | Not specified | Explored BMD impact; focused on training synergy; BMD results not detailed |
Clinical Evidence – Collagen for Hair & Nail Strength
Nails: Multiple studies show faster growth, reduced brittleness, and improved strength with collagen peptides, particularly Type I, which is central to nail and hair structure.
Hair: Direct clinical trials on collagen alone are limited, but multinutrient studies including collagen peptides demonstrate improvements in hair growth, density, and texture.
Formula Advantage: Your CollagenGold blend (Types I, II, III, V, X) goes beyond single-type formulations—supporting not only nail resilience but also the extracellular matrix of hair follicles, connective tissue around roots, and keratinization processes.
1. Hexsel et al., 2017 – Bioactive Collagen Peptides Improve Nail Health
Population: 25 participants with brittle nails.
Protocol: 2.5 g/day of bioactive collagen peptides (VERISOL®) for 24 weeks, followed by 4 weeks off.
Results:
Nail growth rate increased by 12%.
Frequency of broken nails decreased by 42%.
64% of participants achieved visible clinical improvement.
88% maintained stronger nails even after stopping supplementation.
Relevance to Formula: Type I collagen (present in your blend) is abundant in the nail matrix and supports keratin infrastructure.
2. Özkoca, 2023 – Collagen Supplementation and Nail Outcomes
Summarized and reinforced the 2017 Hexsel study.
Reported: 42% reduction in nail breakage, 12% faster nail growth, and 80% satisfaction rate among participants.
Relevance to Formula: Your inclusion of Type I, III, and V collagen may broaden support beyond nails to connective tissue that anchors both hair follicles and nail beds.
Link: https://jtad.org/articles/collagen-supplementation/jtad.galenos.2023.42714
3. Cosmoderma Study (2025) – Multinutrient Formula Including Collagen
Population: 30 adults in an open-label observational trial.
Protocol: A 90-day plant-based supplement containing collagen peptides + other nutrients.
Results:
Nail growth increased by 40%, with improved appearance and strength.
Hair growth rate increased by 20%, and hair density improved by 30 units.
Hair texture improved by 61%.
Relevance to Formula: While the study involved multiple ingredients, the presence of collagen peptides was highlighted as a key contributor. Your multi-type collagen complex (I, II, III, V, X) mirrors this broad-spectrum approach, supporting both nail keratinization and hair follicle ECM structure.
# | Study (Year) | Participants | Collagen Type & Dose | Duration | Outcomes | Formula Relevance |
|---|---|---|---|---|---|---|
1 | Hexsel et al. (2017) | 25 adults w/ brittle nails | Bioactive collagen peptides (2.5 g/day) | 24 wks (+4 wks follow-up) | +12% nail growth, −42% breakage, 64% clinical improvement | Type I collagen (nail matrix, keratin support) |
2 | Özkoca (2023) | Review of 2017 RCT | Same | — | Confirms growth + strength benefits, 80% satisfaction | Type I, III, V in formula extend to hair follicle anchoring + nail ECM |
3 | Cosmoderma (2025) | 30 adults (open-label) | Collagen peptides + nutrients | 90 days | +40% nail growth, +20% hair growth, +30 units hair density, +61% texture | Multi-type collagen blend (I, II, III, V, X) aligns with multi-target tissue support |