Traditional Chinese Medicine and Homocysteine Regulation

 Tiejun Tang

Introduction

Homocysteine (Hcy) is a sulfur-containing amino acid produced during methionine metabolism.  Under physiological conditions, Hcy is remethylated to methionine or trans-sulfurated to cysteine via folate- and vitamin B-dependent pathways ^[1]. When this balance is disrupted, plasma Hcy accumulates, leading to hyperhomocysteinemia (HHcy) ^[2]. Elevated Hcy is associated with endothelial dysfunction, oxidative stress, and inflammation, contributing to atherosclerosis, coronary artery disease, ischemic stroke, and vascular dementia ^[1,3]. Epidemiological data indicate that each 5 μmol/L increase in plasma Hcy raises cardiovascular event risk by approximately 20% ^[2].

Conventional therapy primarily involves folic acid and vitamins B6 and B12 supplementation to enhance Hcy clearance ^[3]. However, some patients respond poorly due to genetic factors such as MTHFR polymorphisms. Therefore, alternative or complementary strategies are under investigation.

 

Traditional Chinese Medicine (TCM), emphasizing holistic balance, circulation improvement, and organ support, has long been used for cardiovascular and cerebrovascular disorders ^[4]. Both classical herbal formulas and modern patent medicines have been shown to improve endothelial function, reduce oxidative stress, and support metabolic homeostasis ^[5]. Recent studies suggest that TCM may directly or indirectly influence Hcy metabolism, potentially complementing conventional therapies ^[6].

This review aims to (1) summarize mechanisms by which TCM influences Hcy metabolism, (2) highlight experimental and clinical evidence on single herbs, active compounds, and compound formulas, and (3) identify limitations and future research directions ^[4–6].

Mechanisms of Action of TCM in Homocysteine Regulation

1 Modulation of One-Carbon Metabolism

TCM interventions may support folate- and vitamin B-dependent one-carbon cycles ^[1,5]. Herbal extracts can upregulate enzymes such as methionine synthase and cystathionine β-synthase, promoting remethylation of Hcy to methionine or trans-sulfuration to cysteine.  Some compounds act as methyl donors, supporting DNA and protein methylation impaired in HHcy ^[5].

2 Antioxidant and Anti-inflammatory Effects

HHcy generates reactive oxygen species (ROS) and impairs nitric oxide (NO) bioavailability, causing endothelial dysfunction ^[2,3]. Herbs such as Salvia miltiorrhiza (Danshen) and Astragalus membranaceus (Huangqi) contain polyphenols and saponins that scavenge ROS, upregulate antioxidant enzymes like superoxide dismutase, and inhibit pro-inflammatory cytokines including TNF-α and IL-6 ^[5,6].

3 Improvement of Endothelial Function

TCM enhances eNOS activity, restores NO levels, and reduces endothelin-1 expression . Fufang Danshen preparations improve flow-mediated dilation in patients with elevated Hcy ^[4,5], reducing vascular injury and thrombotic risk.

4 Hepatorenal Protection and Metabolic Clearance

The liver and kidneys are central to Hcy metabolism. Herbs like Rehmannia glutinosa and Lycium barbarum demonstrate hepatoprotective and nephroprotective effects, indirectly supporting systemic Hcy clearance ^[6].

5 Epigenetic and Gene Expression Modulation

Hcy disrupts DNA methylation and gene expression, leading to endothelial apoptosis. Certain herbal compounds modulate epigenetic mechanisms, restoring methylation balance and protecting vascular endothelium ^[6].

Single Herbs and Active Compounds

1. Danshen (Salvia miltiorrhiza): Tanshinones and salvianolic acid B reduce oxidative stress, preserve NO, and modestly lower Hcy ^[5,6].

2. Huangqi (Astragalus membranaceus): Polysaccharides mitigate oxidative injury and inflammation; vascular protection evident ^[5,6].

3. Gegen (Pueraria lobata): Isoflavones lower Hcy in animal models and improve endothelial vasodilation ^[6].

4. Chuanxiong (Ligusticum chuanxiong) and Danggui (Angelica sinensis): Blood-activating herbs improve circulation ^[5].

5. Other herbs: Rehmannia glutinosa, Lycium barbarum, and polyphenols from tea, resveratrol, and garlic also show potential ^[5,6].

Herbal Formulas and Patent Medicines

1. Fufang Danshen preparations: Improve endothelial function and modestly lower Hcy ^[4,5].

2. Yiqi Huoxue formulas: Combine qi-tonifying and blood-activating herbs; reduce Hcy and improve angina, fatigue, and post-stroke outcomes ^[5].

3. Kidney- and spleen-tonifying formulas: Enhance hepatic and renal metabolism; partial Hcy reductions observed ^[6].

4. Acupuncture and integrative therapies: Electroacupuncture reduces serum Hcy in vascular dementia ^[6].

5. Emerging patent formulas: Combinations such as Huangqi, Danggui, Gardenia, and fermented teas target Hcy ^[6].

Clinical Studies

- Fufang Danshen: improved endothelial function and modest Hcy reduction ^[4,5].

- Yiqi Huoxue: beneficial for post-stroke and angina patients ^[5].

- Kidney/spleen tonifying formulas: improved organ function with partial Hcy reduction ^[6].

- Acupuncture: reduced serum Hcy in vascular dementia ^[6].

Conclusion

TCM provides a multifaceted approach to elevated Hcy, targeting metabolic pathways and vascular consequences. Single herbs like Danshen, Huangqi, and Gegen offer antioxidant and endothelial-protective effects. Compound formulas, including Fufang Danshen and Yiqi Huoxue prescriptions, provide synergistic benefits. Complementary therapies like acupuncture further enhance outcomes. Evidence is encouraging, but high-quality, large-scale trials are needed to validate efficacy and establish standardized protocols ^[4–6].

References

1. Huang, X. Effect of Fufang Danshen preparations on endothelial dysfunction associated with hyperhomocysteinemia. Chinese Journal of Integrative Medicine. 2020; 26(4), 289–296.
2. Zhang, L. Natural plant-derived compounds in the regulation of homocysteine: A review. Molecules. 2021; 26(11), 3081. https://doi.org/10.3390/molecules26113081
3. Wang, J. Huang Qi Decoction improves homocysteine-induced endothelial dysfunction. Evidence-Based Complementary and Alternative Medicine.2016; 7272694. https://doi.org/10.1155/2016/7272694
4. Li, Y. Electroacupuncture lowers serum homocysteine in patients with vascular dementia. International Journal of Clinical and Experimental Medicine.2020; 13(9), 6531–6538.
5. Chen, Q. Traditional Chinese medicine and vascular protection: Effects on homocysteine metabolism. Frontiers in Pharmacology.2022;  13, 874562. https://doi.org/10.3389/fphar.2022.874562
6. Liu, H. Isoflavones from Pueraria lobata reduce homocysteine and improve endothelial function in hyperhomocysteinemic models. Journal of Ethnopharmacology. 2021; 277, 114179. https://doi.org/10.1016/j.jep.2021.114179

Beyond Painkillers: How Acupuncture and Chinese Medicine Are Changing Migraine Care

 Tiejun Tang

This week is migraine awareness week of UK. Migraine is one of the most prevalent and disabling neurological conditions globally. Migraine affects nearly 1 billion people worldwide, or approximately 15% of the global population.WikipediaWorldmetrics. Around 33% of women and 18% of men experience migraine at some point.Wikipedia.  From 1990 to 2021, the number of migraine cases rose from about 733 million to 1.16 billion, while incidence increased by ~42%, and disability-adjusted life years (DALYs) surged by ~58%.SpringerLink. This underscores the immense and growing health and socio-economic burden of migraines worldwide.

Western Medicine: Principles & Challenges

a) Treatment Principles

Western approaches to migraine management include:

• Acute (abortive) treatment:
• Migraine-specific agents such as triptans, CGRP antagonists, and ditans.Wikipedia+1The Times
• Triptans offer rapid relief—70‑80% of patients experience symptom reduction within 30–90 minutes.Wikipedia
• CGRP-targeting therapies (e.g., Aimovig, Ubrelvy) are emerging as first-line preventive options per the American Headache Society, given their strong efficacy and tolerability.Verywell Health
• Preventive treatment:
• Traditional categories: beta-blockers, anticonvulsants, antidepressants.
• Newer agents: anti-CGRP medications—effective with fewer side effects but pose cost/access barriers.Verywell HealthThe Times
• Supportive strategies: Lifestyle modifications—regular sleep, hydration, stress management, trigger avoidance—plus patient education and use of headache diaries.World Health Organization

b) Challenges and Limitations

• Medication overuse headache (MOH): Frequent use of analgesics, triptans, opioids, or combination therapies can exacerbate headaches. MOH is a well-described iatrogenic complication.Wikipedia
• Side effects and accessibility:
• Triptans may cause chest tightness or lethargy (e.g., eletriptan).The Times
• CGRP agents, while effective, are expensive and may be restricted by healthcare systems.The TimesVerywell Health

Traditional Chinese Medicine (TCM) Approaches

 TCM treatments for migraine commonly include: Acupuncture, Chinese herbal medicine and Massage (e.g., Tui Na). These interventions are rooted in TCM theories of qi, blood flow, meridians, and holistic balance.

The Mechanisms (From Modern Medicine Perspective):

According to a comprehensive review (2000–2023), TCM therapies may relieve migraine through:

• Reducing neuropeptides and inflammatory markers
• Modulating neuronal sensitization
• Altering brain function and structure
• Affecting BBB (blood–brain barrier) permeability
• Balancing hormones
• Relieving muscle tensionPubMed

Clinical and Systematic Evidence

• A systematic review of 15 SRs (up to 2019) found high-quality evidence that acupuncture is more effective than Western medicine in reducing headache days, pain intensity, and analgesic use.PubMed
• A later overview (2022) confirms that acupuncture is effective, safe, and worthy of clinical promotion, though study quality needs improvement.PubMed

Additional supportive findings:

• Multiple RCTs and observational studies (Zhu’s scalp acupuncture, electro-acupuncture, etc.) report positive clinical efficacy and improved cerebral blood flow.PMC

Acupuncture Specifically: Evidence & Mechanisms

Clinical Evidence:

• 2017 study: Real acupuncture significantly reduced migraine attacks compared with sham. A meta-analysis of ~5,000 patients found that about two-thirds saw a 50% reduction in attack frequency.GQ
• As per a widely-cited article, acupuncture was found as effective as Imitrex (sumatriptan) in one study, and regular acupuncture prevented ~50% of migraines in another.Allure
• Systematic and meta-analyses: Strong evidence supports its safety and efficacy in both acute and preventative contexts.PMC

Mechanistic Insights

• Neurochemical modulation: Acupuncture may trigger release of neurotransmitters and enhance endogenous opioid receptor availability, as evidenced in brain imaging studies.TIMEGQ
• Neuroimaging data: A 2025 review of neuroimaging trials identified involvement of brain networks—including the default mode network (DMN), salience network (SN), central executive network (CEN), and descending pain modulatory system (DPMS)—in both immediate and preventive acupuncture effects.PubMed

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Summary Table

Aspect	Western Medicine	TCM & Acupuncture
Acute treatment	Triptans, CGRP antagonists, NSAIDs; effective but risks include side effects and MOH	Acupuncture shows efficacy comparable to medication with fewer systemic risks
Preventive care	Beta-blockers, anticonvulsants, antidepressants; CGRP antibodies promising but costly	Acupuncture may reduce migraine frequency, analgesic use, and improve QoL; needs higher-quality trials
Mechanism	Targets neurovascular triggers, receptor modulation, and central sensitization	Supports neurotransmitter release, opioidergic system, network modulation (DMN, DPMS), inflammation reduction
Safety & access	Effective but may cause adverse effects; MOH and under-prescribing common	Generally safe (with proper technique); minor risks; broader accessibility, patient acceptability
Challenges	Cost, side effects, lack of awareness, gender bias, inadequate training and diagnosis	Variability in study quality, need for standardized protocols and larger, rigorous RCTs and imaging studies

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Conclusion

Migraine remains a globally prevalent and debilitating condition. Western treatments offer strong efficacy but face limitations such as medication overuse headache, cost, and side effects.

TCM—and acupuncture in particular—offers a compelling complementary or alternative avenue. The current evidence suggests:

• Clinical efficacy: Demonstrated reduction in migraine frequency and intensity, sometimes comparable to pharmacotherapy.
• Mechanistic plausibility: Supported by neuroimaging and neurochemical data highlighting central modulation of pain and regulatory networks.
• Safety and acceptability: Low risk of systemic adverse effects, high patient acceptability.

That said, further high-quality research, including well-designed RCTs and mechanistic trials, is needed to standardize protocols, verify long-term benefits, and integrate acupuncture effectively into comprehensive migraine care.

 

References

• Incidence and burden of migraine: Global rise in prevalence and DALYsSpringerLinkWikipediaWorldmetrics
• Western treatment principles, challenges, MOH, gender biasThe TimesVerywell HealthWorld Health OrganizationWikipedia+1The Times of India
• TCM mechanisms and tools (acupuncture, herbs, massage)PubMed
• Clinical evidence of acupuncture vs Western medicinePubMed+1PMC+1
• Acupuncture RCTs and meta-analysis findingsGQAllureTIME
• Neuroimaging mechanisms in acupuncturePubMed