Cholesterol and Musculoskeletal Health

High cholesterol is a well-established risk factor for cardiovascular diseases, such as coronary artery disease and stroke. It is primarily associated with the development of atherosclerosis, characterised by the accumulation of cholesterol-laden plaques in arterial walls (Libby et al., 2019; Virmani et al., 2020). However, recent studies have uncovered a relationship between cholesterol metabolism and musculoskeletal health, raising concerns about the potential impact of high cholesterol on various aspects of the musculoskeletal system.

Impact on Bone Health

Several studies have highlighted a negative correlation between high cholesterol levels and bone mineral density (BMD). Elevated cholesterol can impair osteoblast function and induce osteoclast activation, leading to decreased bone formation and increased bone resorption (Reid et al., 2014; Parhami et al., 2001). Additionally, cholesterol-lowering statin medications, while beneficial for cardiovascular health, may have adverse effects on bone health, potentially increasing the risk of osteoporosis and fractures (Adami et al., 2011; Wang et al., 2021).

Association with Joint Diseases

Evidence suggests that high cholesterol may contribute to the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA), two common degenerative joint diseases. Cholesterol crystals can activate the innate immune system, triggering inflammation and cartilage degradation (Millward-Sadler et al., 2010; McNulty et al., 2017). Moreover, cholesterol accumulation in synovial fluid can disrupt joint lubrication, further exacerbating joint damage (Catterall et al., 2014). Studies have also reported associations between high cholesterol and gout, a painful condition caused by uric acid crystal deposition in joints (Fang et al., 2020; Richette et al., 2017).

Tendon Degeneration, Impaired Tissue Healing, and Intervertebral Disc Degeneration

We know that elevated cholesterol levels can play a significant role in the development of atherosclerosis. Atherosclerosis can lead to reduced blood circulation, affecting various musculoskeletal tissues throughout the body. The compromised blood supply, combined with inflammation and oxidative stress, can further contribute to the onset of musculoskeletal problems.

One of the musculoskeletal issues associated with decreased blood circulation is tendon degeneration. Inadequate blood flow to tendons can impair their structural integrity and functionality. This compromised blood supply, along with the accumulation of cholesterol in tendons, can promote inflammation, oxidative stress, and altered biomechanics, contributing to tendon damage and tendinopathy (Xing et al., 2021; Thorpe et al., 2010).

Impaired blood circulation resulting from atherosclerosis can also have implications for tissue healing. Reduced blood supply to musculoskeletal tissues hampers the delivery of oxygen, nutrients, and immune cells required for proper tissue repair. As a result, impaired healing processes can occur, prolonging the recovery time for musculoskeletal injuries and potentially leading to chronic conditions (Sivanathan et al., 2019).

Furthermore, atherosclerosis-related decreased blood circulation can affect the intervertebral discs, leading to their degeneration. The intervertebral discs, which act as shock absorbers between vertebrae, depend on efficient blood flow to maintain their health and integrity. Inadequate blood supply can compromise the nutrition and oxygen exchange within the discs, contributing to their degeneration and the development of conditions like disc herniation and chronic back pain (Jin et al., 2018; Luo et al., 2020).

Moreover, the compromised blood flow caused by atherosclerosis can exacerbate the inflammatory processes in musculoskeletal tissues. Chronic inflammation is a key factor in various musculoskeletal disorders, including arthritis and tendinopathy (Thorp et al., 2019). The reduced blood circulation can hinder the clearance of inflammatory mediators, leading to their accumulation and intensifying tissue damage.

Clinical Implications and Management

Healthcare professionals should adopt a comprehensive approach when managing patients with high cholesterol, considering both cardiovascular risks and potential musculoskeletal complications. Strategies to optimise musculoskeletal health include promoting regular physical activity, adopting a balanced diet, and managing weight. Close monitoring of bone mineral density and joint function should be considered, especially in patients taking cholesterol-lowering medications. Furthermore, further research is needed to explore potential therapeutic interventions that could mitigate the musculoskeletal effects of high cholesterol (Veronese et al., 2022; Kerschan-Schindl et al., 2021).

Conclusion

High cholesterol, a known risk factor for cardiovascular diseases, also has significant implications for musculoskeletal health. Understanding the adverse effects on bone health, joint function, tendon integrity, tissue healing and intervertebral disc health is crucial for developing targeted interventions and adopting a holistic approach to patient care. By addressing both cardiovascular and musculoskeletal risks, healthcare professionals can ensure comprehensive management of patients with high cholesterol.

References:

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Catterall, J. B., Stabler, T. V., Flannery, C. R., Kraus, V. B., Wakabayashi, S., & Horton, W. E. (2014). Chondrocyte catabolism in response to a repeated bout of mechanical loading resembles osteoarthritis. Osteoarthritis and Cartilage, 22(4), 525–534. doi:10.1016/j.joca.2014.01.003

Fang, W., Zhang, Y., Zhang, M., Zhang, B., & Zhang, C. (2020). Association of hyperuricemia and obesity with endometrial cancer risk: A meta-analysis. BioMed Research International, 2020, 1–11. doi:10.1155/2020/5083401

Jin, H., Xie, Z., Liang, B., Li, Y., Ye, Z., & Chen, Y. (2018). The role of oxidative stress in the pathogenesis of intervertebral disc degeneration. Oxidative Medicine and Cellular Longevity, 2018, 1-9.

Kerschan-Schindl, K., Uher, E. M., Waczek, F., Demirtas, D., Patsch, J., & Pietschmann, P. (2021). Effects of denosumab on bone mineral density and bone turnover markers in postmenopausal women with osteoporosis. Journal of Clinical Densitometry, 24(3), 399–407. doi:10.1016/j.jocd.2020.10.007

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Luo, J., Daniels, J. E., Durante, W., & Filippov, V. (2020). Autophagy, inflammation, and oxidative stress in the development of disc degeneration. Current Stem Cell Research & Therapy, 15(4), 350-357.

McNulty, A. L., Miller, M. R., O’Connor, S. K., Guilak, F., & Papannagari, R. (2017). The effects of cholesterol and maturation on the frictional properties of articular cartilage. Osteoarthritis and Cartilage, 25(5), 737–744. doi:10.1016/j.joca.2016.11.013

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Parhami, F., Tintut, Y., Beamer, W. G., Gharavi, N., & Demer, L. L. (2001). Role of the cholesterol biosynthetic pathway in osteoblastic differentiation of marrow stromal cells. Journal of Bone and Mineral Research, 16(10), 1821–1828. doi:10.1359/jbmr.2001.16.10.1821

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Richette, P., Bardin, T., & Doherty, M. (2017). An update on the epidemiology of calcium pyrophosphate dihydrate crystal deposition disease. Rheumatology, 57(Suppl_1), i50–i56. doi:10.1093/rheumatology/kex438

Sivanathan, K. N., Gronthos, S., Rojas-Canales, D., Thierry, B., Coates, P. T., & Pébay, A. (2019). Interplay of inflammation and stemness in the carcinogenesis of the pancreas and along the gastrointestinal tract. Stem Cells International, 2019, 1-22.

Thorpe, C. T., Godinho, M. S. C., Riley, G. P., & Birch, H. L. (2010). Clegg, P. D. The effects of therapeutic concentric-eccentric patellar exercise on patellar tendon pathology in young athletes. Isokinetics and Exercise Science, 18(4), 201–210. doi:10.3233/IES-2010-0370

Thorpe, C. T., Godinho, M. S. C., Riley, G. P., Birch, H. L., Clegg, P. D., & Screen, H. R. (2010). The interfascicular matrix enables fascicle sliding and recovery in tendon, and behaves more elastically in energy storing tendons. Journal of the Royal Society Interface, 7(42), 1623-1634.

Thorp, B. H., Ackermann, P. W., & Wunderli, S. L. (2019). Macrophage actin-based motility in health and disease. Journal of Cell Science, 132(13), jcs231811. doi:10.1242/jcs.231811

Thorp, B. H., Thompson, J., St Pierre, P., Cross, D. R., Durand, M., Cambron, J., … & Brismée, J. M. (2019). Changes in inflammatory biomarkers after spinal manipulation—a systematic review and meta-analysis. Journal of Manipulative and Physiological Therapeutics, 42(9), 712-723.

Tiku, M. L., Shah, R., Allison, S., Gersappe, A., & Lu, Y. (2019). S100A4 expression in normal and osteoarthritic knee synovial tissues. Archives of Pathology & Laboratory Medicine, 143(7), 841–845. doi:10.5858/arpa.2018-0355-OA

Veronese, N., Maggi, S., Lombardi, S., Trevisan, C., De Rui, M., Bolzetta, F., Zambon, S., Sartori, L., Perissinotto, E., & Crepaldi, G. (2022). Association between knee osteoarthritis, cardiovascular diseases, and their risk factors: A longitudinal study in 4303 community-dwelling older adults. Reumatismo, 74(1), 11–17. doi:10.4081/reumatismo.2022.1626

Virmani, R., Burke, A. P., Kolodgie, F. D., & Barger, A. C. (2020). Vulnerable plaque: The pathology of unstable coronary lesions. Journal of Interventional Cardiology, 15(6), 439–446. doi:10.

Xing, Y., Zhang, J., Lin, Y., Zhu, C., Wang, M., & Chen, J. (2021). Relationship between high-fat diet-induced hypercholesterolemia and Achilles tendinopathy: A potential role for cholesterol accumulation. Connective Tissue Research, 62(1), 61-71.

Atherosclerosis and Low Back Pain

Atherosclerosis is well-known for its role in the development of coronary heart disease and stroke. The vascular occlusion that it causes leads to the infarction of heart and brain tissue. But coronary and cerebral blood vessels are by no means the only vessels that become clogged by atheromatous plaques. In 1993, Kauppila et al., from the department of forensic medicine at Helsinki University, postulated that insufficient arterial blood flow may play a role in low back pain. Their post-mortem angiographic study found that, compared to controls, significantly more people with a history of low back pain had anomalies in the arteries that supplied the lumbar spine – the arteries were narrowed by atheromatous lesions and some were completely missing.

Since that landmark study, several cadaver and clinical studies have corroborated the link between stenosis (and occlusion) of the lumbar arteries and the presence of low back pain. In fact, many studies have found an association between the aforementioned lumbar vascular insufficiency and degeneration of the corresponding lumbar discs. This shouldn’t be a surprise because, as Kauppila states, “the disc is located at the end of the nutrient chain, making it one of the first structures to suffer during insufficient nutrient supply.”

In epidemiological studies, associations between cardiovascular risk factors and low back pain (or disc degeneration) are weaker and conflicting. Nevertheless, several studies have linked high blood cholesterol and smoking with low back pain and disc degeneration. It’s important to remember that correlation is different from causation and more research is needed to determine a cause and effect relationship. So, a healthy diet and abstinence from smoking may play a role in the prevention and treatment of low back pain. Further still, and this is pure conjecture on my part, they may have a role to play in maintaining the health of all poorly vascularised tissues (spinal discs, tendons, articular cartilage of joints, etc.).

 

High Cholesterol Can Cause Tendon Pathology

A recent literature review by Yang et al. suggests that high blood cholesterol is a risk factor in the development and progression of tendon pathology. They found that cholesterol levels were directly correlated with the severity of tendon problems. There is evidence that elevated cholesterol levels lead to inflammatory, structural and mechanical changes in tendons which predispose patients with high cholesterol levels to an increased risk of developing tendinopathies.

Sleep Deprivation Can Negatively Affect Cholesterol Levels And Inflammation

Vilma Aho et al from the University of Helsinki conducted 2 studies looking into the effects of sleep deprivation. The first study was experimental and consisted of partial sleep restriction to a small group of subjects. The second was an epidemiological study with over 2700 individuals. Blood samples were analysed in both cases.

The analyses revealed decreased circulating High Density Lipoproteins (HDL cholesterol), otherwise known as ‘good cholesterol’, and elevated inflammatory markers. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses. The findings help to explain why sleep deprivation is a risk factor for cardiometabolic disease.

High Cholesterol Linked To Tendon Problems

A group of Australian researchers have conducted a systematic review of literature to find articles that looked at the relationship between fat levels in blood and tendon pathology and/or pain. Their results were published in the British Journal of Sports Medicine. They found that people with altered tendon structure or tendon pain had significantly higher total cholesterol, low-density lipoprotein cholesterol (“bad cholesterol”) and triglycerides, as well as lower high-density lipoprotein cholesterol (“good cholesterol”).

The researchers conclude that although a relationship exists between an individual’s lipid profile and tendon health, further longitudinal studies are required to determine whether it is a cause and effect relationship.

Interestingly, the results of the China Study, one of the most comprehensive studies of nutrition ever conducted, found that one of the best predictors of diseases of affluence (heart disease, diabetes, cancer, etc.) was blood cholesterol.

BBC Horizon’s – Eat, Fast And Live Longer

Another great programme from BBC Horizon presented by Dr Moseley. He starts off the programme by following the oldest man to complete the London marathon…a 101 yr old sikh who is healthy and takes no medication…the typical 65 yr old european takes 6 pills a day! The centenarian attributes his good health to his diet and more specifically his small portion size…about half of a normal adult”s.

This is not the first time that caloric restriction has been linked to longevity. In the 1930s, during the great depression in the US, although there were widespread food shortages…surprisingly life expectancy increased by 6 years. During the same period scientists at Cornell University found that animals on restricted diets lived longer.

Dr Moseley had a keen personal interest in the subject because of the threat of disease due to elevated blood sugar and cholesterol. He traveled the US speaking to the most eminent specialists in the field in a quest for a solution to his health problems. His first port of call was Professor Luigi Fontana from Washington University and Salerno Schools of Medicine. Prof Fontana advised a diet low in calories but high in nutrients and introduced Dr Moseley to Joe. Joe was in his 50s and had been on 1900 kcal/day for about 10 years. His body fat was 11.5% whereas Dr Moseley”s, also in his 50s, had a body fat % of about 27. Although the benefits were clear, Dr Moseley wanted to understand the mechanism in the hope of being able to draw the benefits without having to do any of the hard work! This is one of the reasons I like his programmes…his attitude is typical of the average european (or american)…we want results quickly, with as little effort as possible…sound familiar?

He then met up with Professor Valter Longo at the University of Southern California. Prof Longo showed him a special mouse…about half the size of a normal mouse…but incredibly it had a lifespan that was 40% longer…the equivalent of 120 human casino jameshallison years! The mouse had been genetically modified to have low levels of the a growth hormone called Insulin-like Growth Factor 1 (IGF1). IGF1 is thought to be the link between calorie restriction and longevity. There are about 350 people worldwide who have genetically inherited low levels of IGF1. Their condition is named Laron syndrome and although some of them smoke and eat what they want, amazingly they don”t get diabetes or cancer! Low levels of IGF1 seem to increase cell repair and decrease cell division (which probably accounts for their extremely small stature).

Protein has been found to increase our metabolism and put us in “go-go” mode but the downside is that it decreases cell repair. Three things can help decrease levels of IGF1: decreasing calorie intake, decreasing protein intake and lastly, the most effective way…is by fasting. Fasting can dramatically reduces levels of blood glucose and IGF1 within as little as 24 hrs. Obviously fasting can be dangerous and should only be undertaken if in good health and under close medical supervision. So Dr Moseley decided to give it a go for 3.5 days. He only allowed himself water, black tea and a 50 kcal soup each day. As expected, his blood sugar decreased significantly and his IGF1 levels halved. Unfortunately, the effects are only temporary and one would need to decrease protein intake and fast every couple of months to maintain changes…not for Dr Moseley, so he continued his search…

Dr Krista Varady from the University of Illinois at Chicago had a much more palatable proposition…eat as much of whatever you want on one day and eat a reduced amount of whatever you want the following day…feed day, fast day, feed day, fast day, etc. It”s called Alternate Day Fasting (ADF). On the fast days women are advised to eat 400-500 kcal and men 500-600 kcal. Preliminary trials with overweight subjects are showing promising results including weight loss, lower levels of bad cholesterol and fats in blood and decreased blood pressure.

Lastly, Dr Moseley paid a visit to Dr Mark Mattsen from the National Institute on Aging in Baltimore. He has conducted animal experiments on intermittent fasting and has found that it postpones the development of Alzheimer”s and senile dementia like diseases. Sporadic bouts of hunger seem to trigger the growth of new neurones! In evolutionary terms, this would have provided a survival advantage in times of famine. Intermittent fasting has better effects on the brain than daily calorie restriction. Dr Mattsen suggested alternating 5 days of normal eating with 2 days of fasting. So Dr Moseley gave it a go for 5 weeks. On the normal days her took in around 200 kcal and on the fast days he ate about 600 kcal. Please bear in mind that normal calorie intake is based on sex, height, weight and activity. The results were extremely impressive. He managed to lose 1 stone and decrease his body fat from 27% to 19%! His blood sugar levels decreased to within normal limits, his IGF1 levels halved, his total cholesterol decreased and his good cholesterol increased. I assume that although he could have eaten whatever he wanted, he was sensible about it.

Dr Moseley ended the programme by saying that it was “the most interesting journey that I”ve ever been on…and I”ve never said that before”.