Stiff Joints and Aching Knees?

Updated on 9 min read

Understanding the Hidden Biochemical Pathways Behind Joint Pain—and what you can do to support joint health naturally.

You love the outdoors but as time goes by, you’re finding it harder to hit the hills. As we age, joint stiffness and discomfort often become unwelcome companions. But did you know that the root cause of your knee pain may have many underlying reasons and can go beyond wear and tear? Emerging research reveals a significant link between joint health, methylation pathways (think B-vitamins), and a compound called homocysteine (HCY), one of several inflammatory markers.

Let’s unpack how this lesser-known biochemical process may be influencing your joint health—and what you can do to support it.

What if the key to easing joint pain lies in your genes, and the right nutrients could help you feel better?

Homocysteine, Nitric Oxide & the Methylation Pathway

Homocysteine is a naturally occurring amino acid (a building block of protein) produced during the body’s methylation cycle. When functioning optimally, your body recycles homocysteine using key food-derived nutrients like folate, B6, B2, B12, and choline. But when this system falters—often due to age, genetics, poor nutrition, alcohol, smoking, stress, or a combination of all—homocysteine levels can rise.

Elevated homocysteine is commonly associated with cardiovascular and neurodegenerative conditions but is also linked to osteoarthritis and high blood pressure. One reason? It interferes with nitric oxide (NO), a vasodilator critical for blood flow and blood pressure regulation. Research shows homocysteine can inhibit nitric oxide synthase, the enzyme required to produce NO.1) Checking your methylation pathways, may give you insights into your personal methylation capabilities and vulnerabilities in this regard. Supporting methylation may not only help joint health but also cardiovascular and brain health (see my programmes on heart and brain health Here).

Low nitric oxide contributes to stiff, inflamed, poorly oxygenated joints. As endothelial (cells lining the arteries) function declines with age, and oxidative stress rises, blood flow to cartilage diminishes. This can potentially worsen pain, swelling, and stiffness in the joints. Fortunately, some of this damage may be reversible to some extent, with adequate folate and antioxidant support.2)

What if you knew your homocysteine score? Could it help you to prevent damage to your cartilage?

Homocysteine and Osteoarthritis: A Hidden Link

It must be stressed that the different mechanisms of homocysteine toxicity are not mutually exclusive.3) Multiple health outcomes are related to elevated homocysteine.4)

One study offers a possible explanation for how homocysteine contributes directly to cartilage degradation: it impairs chondrocytes (cartilage cells) by increasing oxidative stress and disrupting cellular energy pathways.5) These disruptions may be particularly damaging to weight-bearing joints like the knees and hips—especially in women.

Mendelian randomization studies have shown that elevated homocysteine negatively impacts joint health, while higher folate and B12 levels are associated with protective effects.6) Though blood testing for homocysteine may not always be offered by your general practitioner, it’s a valuable biomarker for assessing both cardiovascular and joint health—and can guide targeted nutritional support. If you would like to be proactive about your health, then check out my Golden Wellness and Prime Nutrition group programme to find out about all the other important biomarkers currently associated with cardiovascular and brain health.

The Folate Factor: Supporting Knee Health Naturally

Dark green vegetables are packed with a B-vitamin called folate. A clinical trial examining folate intake in patients with knee osteoarthritis (KO) found something striking -higher daily folate intake over two years correlated with reduced knee pain, improved mobility, and stronger leg muscles.7) The benefit extended beyond just the knees. Participants also reported less pain in their lower back and feet and greater ease when climbing stairs—common trouble spots for aging adults.

Did you know that inflammation caused by homocysteine, directly or indirectly, could be one of the factors of joint inflammation?

B-Vitamins, Methylation & Joint Protection

In the same vein, research shows that ensuring adequate levels of folate and B12 may help slow the progression of osteoarthritis.8) These vitamins support the methylation pathway that recycles homocysteine and protect cells from oxidative damage (think “rust”).

In short, supporting methylation (B-vitamin status) nutritionally could be a vital step toward protecting your joints from inflammation and degeneration. Find out more about Methylation from Lifecodegx.

How does alcohol impact joint health?

Alcohol and Joint Pain: A Hidden Agitator

Alcohol can be deceptive. While a glass of wine now and then may seem harmless, regular or excessive consumption can dehydrate the body and increase friction between joints. It also depletes B-vitamins, folate, and magnesium—all critical for methylation and joint function.

A long-term study of nearly 3,000 participants found that excessive alcohol consumption significantly raised the risk of developing knee osteoarthritis—especially in women.(9,10) For women, even small increases in alcohol intake were linked to higher risk of rheumatoid arthritis.

If you’re dealing with joint pain, cutting back on alcohol isn’t just good for your liver—it’s a meaningful way to support your joints, muscles, and overall energy levels. Feel free to download my E-Book Beat the Booze to help you on your way.

Did you know that lack of protein could impact your joints?

Protein and Muscle: The Unsung Allies of Joint Health

We often forget that strong muscles are critical to supporting our joints. In several randomized controlled trials, combining exercise with protein supplementation improved muscle strength, reduced pain, and enhanced recovery from joint replacement surgeries. (11-13)

More recently, a clinical trial in older adults with mild knee osteoarthritis and sarcopenia (age-related muscle loss) found that 12 weeks of high plant protein supplementation improved mobility, muscle strength, and knee function.14)

For older women, whose muscle mass naturally declines with age, protein becomes more than a dietary add-on—it’s an essential joint protector.

You can take a few proactive steps to ensure your joint health for years to come.

Your Action Plan: Methylation, Muscles & Moderation

Here’s a personalised, forward-looking approach that may wish to consider:

  • Test your genetic methylation pathways by doing a Nutrigenomic test and find out how to best support yourself and your genes through diet and supplements.
  • Test Your Homocysteine: If you haven’t already, consider getting this simple blood test. It may offer valuable insights into your methylation status.
  • Make an appointment with your Nutritional Therapist to discuss what all this means for you in context of your overall health, diet, lifestyle and medications.
  • Remove the pressures that lead to diminished methylation capacity such as your alcohol intake. Even modest reductions in alcohol intake may lead to real benefits for your joints, blood pressure, and nutrient status.
  • Stay Active, Stay Strong: Resistance training, walking, and stretching support both mobility and vascular health.

Final Thoughts

Joint pain isn’t just about ageing—it’s about biochemistry. By supporting your methylation pathways, addressing homocysteine levels, supporting anti-oxidative pathways, and strengthening your muscles with quality protein, you be able to take meaningful steps to reduce joint pain and enhance vitality in your 60s, 70s, and beyond. Book a FREE 30-minute Mini Consultation HERE.

Anahita
Nutritional Therapist MSc | Functional Testing | Nutrigenomics

Disclaimer:

The dietary and lifestyle changes, supplements, and treatments discussed in this post may interact with medications or have contraindications for certain individuals. Therefore, this blog post is for general information and educational purposes only. It is not a substitute for medical advice, diagnosis, or treatment. Always consult your doctor or qualified health professional before making changes to your diet, lifestyle, supplements, or medications. Individual needs vary, and what works for one person may not be appropriate for another. The author is not liable for any outcomes from applying information in this post. If you are experiencing a medical issue or emergency, seek professional help immediately.

Want to Read More?

Here are a few recent studies on joint health and nutrition to explore:

  1. Stühlinger MC, Tsao PS, Her JH, Kimoto M, Balint RF, Cooke JP. Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine. Circulation. 2001 Nov 20;104(21):2569-75. doi: 10.1161/hc4601.098514. PMID: 11714652. Link
  2. Stanger O, Weger M. Interactions of homocysteine, nitric oxide, folate and radicals in the progressively damaged endothelium. Clin Chem Lab Med. 2003 Nov;41(11):1444-54. doi: 10.1515/CCLM.2003.222. PMID: 14656024 Link
  3. Alessandra F. Perna, Diego Ingrosso, Cinzia Lombardi, Filomena Acanfora, Ersilia Satta, Concetta Maria Cesare, Eleonora Violetti, Maria Maddalena Romano, Natale G. De Santo, Possible mechanisms of homocysteine toxicity, Kidney International, Volume 63, Supplement 84, 2003, Pages S137-S140, ISSN 0085-2538. Link
  4. Futao Zhou, Yue He, Xinhua Xie, Ning Guo, Wanjiao Chen, Yushi Zhao, Homocysteine and Multiple Health Outcomes: An Outcome-Wide Umbrella Review of Meta-analyses and Mendelian Randomization Studies, Advances in Nutrition, Volume 16, Issue 6, 2025, 100434, ISSN 2161-8313. Link
  5. Ching-Hou Ma, Yen Chun Chiu, Chin-Hsien Wu, I.-Ming Jou, Yuan-Kun Tu, Ching-Hsia Hung, Pei-Ling Hsieh, Kun-Ling Tsai, Homocysteine causes dysfunction of chondrocytes and oxidative stress through repression of SIRT1/AMPK pathway: A possible link between hyperhomocysteinemia and osteoarthritis, Redox Biology, Volume 15, 2018, Pages 504-512, ISSN 2213-2317. Link
  6. Hong H, Chen L, Zhong Y, Yang Z, Li W, Song C, Leng H. Associations of Homocysteine, Folate, and Vitamin B12 with Osteoarthritis: A Mendelian Randomization Study. Nutrients. 2023 Mar 28;15(7):1636. doi: 10.3390/nu15071636. PMID: 37049476; PMCID: PMC10096814. Link
  7. Liu, Z., Chen, Z., Wu, Z. et al. Associations between folate intake and knee pain, inflammation mediators and comorbid conditions in patients with symptomatic knee osteoarthritis. BMC Musculoskelet Disord 25, 973 (2024). Link
  8. Arthritis Australia. Link
  9. T. Liu, C. Xu, J.B. Driban, T. McAlindon, C.B. Eaton, B. Lu, Excessive alcohol consumption and the risk of knee osteoarthritis: a prospective study from the Osteoarthritis Initiative, Osteoarthritis and Cartilage, Volume 30, Issue 5, 2022, Pages 697-701, ISSN 1063-4584. Link
  10. VanEvery H, Yang W, Olsen N, Bao L, Lu B, Wu S, Cui L, Gao X. Alcohol Consumption and Risk of Rheumatoid Arthritis among Chinese Adults: A Prospective Study. Nutrients. 2021 Jun 29;13(7):2231. doi: 10.3390/nu13072231. PMID: 34209676; PMCID: PMC8308382. Link
  11. Liao CD, Wu YT, Tsauo JY, Chen PR, Tu YK, Chen HC, Liou TH. Effects of Protein Supplementation Combined with Exercise Training on Muscle Mass and Function in Older Adults with Lower-Extremity Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Trials. Nutrients. 2020 Aug 12;12(8):2422. doi: 10.3390/nu12082422. PMID: 32806718; PMCID: PMC7468926. Link
  12. Li M, Shi Q, Che X, Du X, Wang D, Song Y. Study of whey protein on muscle mass and functional rehabilitation in postoperative total knee arthroplasty patients. J Back Musculoskelet Rehabil. 2024;37(5):1381-1390. doi: 10.3233/BMR-240013. PMID: 38820012. Link
  13. Khani, Y., Salmani, A., Elahi, M. et al. Peri-operative protein or amino acid supplementation for total joint arthroplasty: a systematic review and meta-analysis. J Orthop Surg Res 20, 439 (2025). Link
  14. Qiming Wu, Zhuyan Xu, Wenhua Huang, Xiaoyan Qi, Jian Wu, Jun Du, Juntao Kan, Effect of high plant protein/peptide nutrition supplementation on knee osteoarthritis in older adults with sarcopenia: A randomized, double-blind, placebo-controlled trial, Clinical Nutrition, Volume 43, Issue 9, 2024, Pages 2177-2185, ISSN 0261-5614. Link

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