From the Guidelines
Creatine supplementation is not recommended for lowering homocysteine levels, as the current evidence does not support its effectiveness in reducing cardiovascular events in patients with peripheral artery disease (PAD) 1.
Key Points to Consider
- The 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease recommends against B-complex vitamin supplementation to lower homocysteine levels for prevention of cardiovascular events in patients with PAD, with a Class III: No Benefit designation and a Level of Evidence B-R 1.
- The HOPE-2 trial, which randomized 5,522 patients with atherosclerotic vascular disease or diabetes mellitus with additional risk factors to receive folic acid/vitamin B6/vitamin B12 or placebo, found no improvement in the primary endpoint of cardiovascular death, MI, or stroke despite lowering of homocysteine levels in the vitamin supplementation arm 1.
- While creatine supplementation may have a theoretical basis for reducing homocysteine levels, there is no strong evidence to support its use for this purpose, particularly in the context of PAD and cardiovascular disease prevention.
Clinical Implications
- Patients with PAD and elevated homocysteine levels should focus on established therapies for reducing cardiovascular risk, such as lifestyle modifications, statin therapy, and antiplatelet agents, rather than relying on creatine or B-complex vitamin supplementation.
- Healthcare providers should consult with patients about the potential benefits and limitations of various supplements and therapies, and prioritize evidence-based treatments for reducing cardiovascular risk.
From the Research
Creatine and Homocysteine
- There is no direct evidence that creatine supplementation lowers homocysteine levels 2, 3, 4.
- However, one study found a significant relationship between vitamin B12 and creatine levels, as well as between vitamin B6 and creatine levels 5.
- Vitamin B12, vitamin B6, and folate are known to be involved in homocysteine metabolism, and deficiencies in these vitamins can lead to elevated homocysteine levels 2, 5, 6.
- High-dose B-group vitamin supplementation has been shown to reduce homocysteine levels and increase vitamin B6 and vitamin B12 levels 5.
- Low maternal folate and high homocysteine values in mid-pregnancy have been associated with subsequent reduced fetal growth 6.
Mechanism of Action
- The mechanism by which creatine may affect homocysteine levels is unclear, but it may be related to the interaction between creatine and B vitamins, particularly vitamin B12 and vitamin B6 5.
- Further studies are needed to investigate the potential relationship between creatine supplementation and homocysteine levels 3, 4.