Homocysteine and related problems

Homocystine and Musculoskeletal problems

Elevated levels of the amino acid serum Homocysteine is related to several musculoskeletal problems in addition to risk for atherosclerosis, stroke, myocardial infarction, and possibly Alzheimer’s disease. Complex changes occur in muscles cells and blood vessel lining (endothelium). Hyperhomocysteinemia (increased blood levels of Homocysteine) induces oxidative stress and chronic inflammation. This can interfere with body composition and physical function in middle-aged and older adults. The normal level of blood homocysteine is

This is actually a very interesting emerging concept in tendon biology. The relationship between elevated homocysteine and rotator cuff pathology is being explored more recently.

What is Homocysteine?

Homocysteine is an amino acid produced during the metabolism of methionine, which comes from dietary protein. Normally the body converts it into other useful molecules using vitamins B6, B12, and folic acid.

If this conversion does not happen efficiently, homocysteine levels rise in the blood.

Why do we measure it?

Elevated homocysteine (hyperhomocysteinemia) is associated with:

• Cardiovascular disease
• Stroke risk
• Peripheral vascular disease
• Deep vein thrombosis
• Sometimes recurrent pregnancy loss

It is considered a marker of endothelial dysfunction and vascular inflammation.

Common causes of high homocysteine

The most frequent reason I see clinically is vitamin deficiency, especially:

• Vitamin B12 deficiency
• Folate deficiency
• Vitamin B6 deficiency

Other causes include:

• Chronic kidney disease
• Hypothyroidism
• Smoking
• Excess alcohol
• Certain genetic polymorphisms (like MTHFR mutation)

In many Indian patients, especially vegetarians, B12 deficiency is extremely common, so a mildly elevated homocysteine often reflects that rather than a primary vascular disease.

Homocysteine and Rotator Cuff Tears

Rotator cuff tears are one of the common causes of shoulder pain. While overuse, aging, and injury are well-known reasons, recent research suggests that certain metabolic factors in the body may also influence tendon health.

One such factor is homocysteine, a naturally occurring amino acid in the blood. Normally, the body keeps homocysteine levels under control with the help of vitamins B12, B6, and folic acid.

When homocysteine levels become high, it can affect the quality and strength of collagen, which is the main structural protein that makes up tendons. This may weaken the rotator cuff tendons and make them more prone to degeneration or tears over time.

High homocysteine can also affect small blood vessels, reducing the blood supply to tendons. Since rotator cuff tendons already have limited blood flow, this may further affect healing and recovery.

The good news is that elevated homocysteine is often related to vitamin deficiencies, especially vitamin B12 and folic acid, and can usually be corrected with proper treatment and diet.

Maintaining good nutrition, controlling metabolic health, and addressing vitamin deficiencies can help support healthy tendons and better healing of shoulder injuries.

How do we treat high homocysteine?

Treatment is usually straightforward:

• Vitamin B12 supplementation
• Folic acid
• Vitamin B6
• Dietary improvement (green vegetables, legumes, eggs, fish)

Levels usually normalize within a few weeks to months.

References :

1. Kositsawat J, Vogrin S, French C, Gebauer M, Candow DG, Duque G, Kirk B. Relationship Between Plasma Homocysteine and Bone Density, Lean Mass, Muscle Strength and Physical Function in 1480 Middle-Aged and Older Adults: Data from NHANES. Calcif Tissue Int. 2023 Jan;112(1):45-54. doi: 10.1007/s00223-022-01037-0. Epub 2022 Nov 7. PMID: 36344761; PMCID: PMC9813058.
2. Fu L, Wang Y, Hu YQ. Causal effects of B vitamins and homocysteine on obesity and musculoskeletal diseases: A Mendelian randomization study. Front Nutr. 2022 Nov 24;9:1048122. doi: 10.3389/fnut.2022.1048122. PMID: 36505230; PMCID: PMC9731309.
3. Mu ZJ, Fu JL, Sun LN, Chan P, Xiu SL. Associations between homocysteine, inflammatory cytokines and sarcopenia in Chinese older adults with type 2 diabetes. BMC Geriatr. 2021;21:692. doi: 10.1186/s12877-021-02622-y.
4. Ates Bulut E, Soysal P, Aydin AE, Dokuzlar O, Kocyigit SE, Isik AT. Vitamin B12 deficiency might be related to sarcopenia in older adults. Exp Gerontol. 2017;95:136–140. doi: 10.1016/j.exger.2017.05.017.
5. Faraci FM. Hyperhomocysteinemia: a million ways to lose control. Arterioscler Thromb Vasc Biol. 2003 Mar 1;23(3):371-3. doi: 10.1161/01.ATV.0000063607.56590.7F. PMID: 12639825.