Is glycine an effective supplement for bone health in adults, and how should it be dosed alongside calcium and vitamin D?

Glycine Supplementation for Bone Health

Glycine supplementation shows promise for bone health based on emerging evidence, but it is not part of standard bone health guidelines and should be considered an adjunctive strategy rather than a replacement for established calcium and vitamin D recommendations.

Current Evidence for Glycine and Bone Health

The evidence for glycine specifically is limited but suggestive:

• Higher dietary glycine intake is associated with significantly higher spine bone mineral density (BMD) in twin studies, with a within-pair difference of 0.014 g/cm² (p = 0.026) when comparing twins with higher versus lower glycine intake 1
• Glycine is one of five nonessential amino acids (along with alanine, arginine, glutamic acid, and proline) that may support bone health through improved collagen synthesis and insulin-like growth factor 1 production 1
• The association appears independent of genetic background, as demonstrated in discordant monozygotic twin pairs 1

Practical Dosing Considerations

There is no established clinical dosing guideline for glycine supplementation specifically for bone health. The research evidence comes from dietary intake studies rather than supplementation trials 1. Therefore:

• Focus first on meeting established calcium and vitamin D requirements before considering glycine supplementation
• If pursuing glycine, consider it as part of overall protein intake rather than as an isolated supplement
• Prioritize protein from vegetable sources, which showed 13-19% lower prevalence of osteoporosis/osteopenia across multiple amino acids including glycine 1

Integration with Standard Bone Health Recommendations

Calcium Dosing Algorithm:

• Adults under 50 years: 1,000 mg total daily intake from all sources 2
• Adults over 50 years: 1,200 mg total daily intake from all sources 2, 3
• Divide doses: Take no more than 500-600 mg at once for optimal absorption 2, 4, 3
• Calcium carbonate: Take with food (requires gastric acid) 2, 3
• Calcium citrate: Can take between meals; preferred for patients on proton pump inhibitors 2, 3

Vitamin D Dosing Algorithm:

• Standard dose for adults ≥50 years: 800-1,000 IU daily 2, 3
• Target serum 25(OH)D level: ≥30 ng/mL (75 nmol/L) 2, 3
• Higher doses may be needed if baseline vitamin D is deficient, though evidence for doses >800 IU is mixed 5, 3
• Vitamin D3 (cholecalciferol) is preferred over D2 (ergocalciferol) for better efficacy 2, 3

Critical Caveats and Pitfalls

Do not use low-dose supplementation regimens (≤400 IU vitamin D3 and ≤1,000 mg calcium) in postmenopausal women, as the USPSTF recommends against this approach due to lack of fracture benefit and increased kidney stone risk (hazard ratio 1.17) 4, 5, 3

Prioritize dietary sources over supplements when possible, as calcium from food is associated with lower nephrolithiasis risk compared to supplements 2, 4

Glycine should not replace established interventions: The evidence for calcium and vitamin D is far more robust, with demonstrated fracture reduction in high-risk populations (particularly nursing home residents with vitamin D deficiency) 6, whereas glycine evidence is limited to observational BMD associations 1

Algorithmic Approach to Bone Health Supplementation

1. Assess baseline status: Check serum 25(OH)D levels and dietary calcium intake 2, 3
2. Correct severe vitamin D deficiency (<25 nmol/L) before starting potent anti-resorptive drugs to avoid hypocalcemia 6
3. Implement calcium: 1,200 mg daily for adults >50, divided into doses ≤500 mg 2, 4, 3
4. Implement vitamin D: 800-1,000 IU daily, targeting serum levels ≥30 ng/mL 2, 3
5. Optimize overall protein intake: Aim for adequate total protein (particularly from vegetable sources), which naturally provides glycine and other beneficial amino acids 1
6. Consider glycine supplementation only as an adjunct if standard measures are optimized and patient has documented low dietary intake 1

The evidence does not support routine glycine supplementation as a standalone bone health intervention, but ensuring adequate dietary protein intake (which contains glycine) is reasonable based on the observational data showing BMD benefits 1.