Vitamin E and Osteoarthritis: Does Vitamin E Influence Muscle Function and Integrity?

Ray Marks

Department of Health and Behavior Studies, Teachers College, Columbia University, USA

*Correspondence to: Dr. Ray Marks, Department of Health and Behavior Studies, Teachers College, Columbia University, USA.

Copyright © 2019 Dr. Ray Marks. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background
Osteoarthritis, a widespread chronic progressively disabling joint disease strongly associated with progressive lesions of the articular cartilage tissue lining synovial joints such as the hip and knee, is also commonly accompanied by pathological changes in the surrounding muscle, as well as bone. Often considered an inevitable component of aging with no currently truly effective means of preventing or treating this condition, discussions about the role played specifically by muscle in this disease has led to the idea that muscle is potentially an important treatment target, including primary, secondary, and tertiary levels of osteoarthritis prevention. Although vitamin E appears to be efficacious for treating osteoarthritis in its late stages [1], and a role for muscle in osteoarthritis pathology has been implicated in the disease cycle [2,3], alongside the potential of dietary factors in general for preventing and treating osteoarthritis [4,5], very few discussions have ensued as to whether vitamin E-a generic term referring to a total of 4 tocopherol and 4 tocotrienal derivatives [6] is of any import in specifically protecting against osteoarthritic muscle damage and atrophy [7], given its well established anti-inflammatory and neuroprotective functional influences [6].

In light of the enormity and extent of osteoarthritis disability incurred globally by aging adults, and some evidence that an inadequate vitamin E intake and/or subnormal plasma concentrations of this compound may be implicated as one possible understudied pathogenic factor, it was perceived that it may be useful to examine whether there is any evidence to support the possibility of a consistent directional association between vitamin E levels and aspects of muscle status such as muscle mass and muscle composition, frequently impaired in people with varying degrees of osteoarthritis. Given that human skeletal muscle is a vital organ involved in movement and force generation that suffers from deterioration in mass, strength, and regenerative capacity with aging [8], as well as in osteoarthritis [2], support for a linkage between these factors in the relevant literature was sought.

Aims
Accordingly, this present review aimed to examine the degree of consensus in favor of a clinically relevant role for vitamin E in predicting or influencing the extent or rate of muscle pathology found in osteoarthritis, either directly or indirectly. Since no specific approach can currently be shown to safely alter the natural course of osteoarthritis, or produce long-term, clinically relevant benefits in this condition, and exercise strongly advocated for this condition is often ineffective in the long-term, a further aim was to establish if vitamin E supplementation can possibly provide a novel and efficacious supplementary approach in this regard.

Methods
To obtain data relevant to the present topic of interest, a scoping review using the search terms Vitamin E and Muscle, Skeletal Muscle, Muscle Atrophy, Muscle Strength, or Muscle Cells, Vitamin E and Osteoarthritis, and Muscle and Osteoarthritis was applied. Acceptable information sources for this review included peer-reviewed literature reviews, case studies, cross-sectional studies and prospective studies, regardless of substrate studied.

The key data base used was PUBMED, although other data bases such as Google Scholar were searched. To identify key issues in this diverse literature, the available data published over the years 2000-2019 were specifically scanned, and relevant papers were then downloaded, and scrutinized. As well, a manual search of references in these papers was conducted, where indicated. The selected materials were then divided into those that discussed aspects of osteoarthritis related to vitamin E and muscle, plus studies representing laboratory research approaches that have examined vitamin E and muscle interactions of some sort, versus those that have been performed on human samples. A narrative perspective was chosen to depict the nature of the data, given the paucity of data and its obvious heterogeneity. For that reason, no distinction was made between studies examining vitamin E subgroups of tocopherols and tocotrienols or their isomers, and the terminology discussed in this paper follows that reported by the authors in the reviewed studies.

Results

General Observations
The overall finding of the literature search was that the number of articles matching the present key words was very limited, especially if compared to other related topics in this realm such as vitamin D and muscle, and osteoarthritis and exercise. Of the available vitamin E studies that examined its association with muscle, most were clearly preclinical in nature, with no consistent approach or substrate. Varied forms of vitamin E, as well as dosages, plus muscle features were evident and the diverse substrates or subjects studied in both the laboratory and clinic venues precluded any form of robust quantitative analysis. In addition, very few clinical studies focusing in some way on this present topic were well-designed, and the majority were observational or experimental rather than intervention studies. Many articles have recently focused on muscle problems in osteoarthritis, but none linked this feature of the disease specifically to osteoarthritis. To elaborate upon the prevailing literature in this regard, the key results identified in the literature are reported below in narrative and tabular formats.

Research Observations

Osteoarthritis and Muscle
Over and above the hallmark characteristic of osteoarthritis, namely its adverse effect on articular cartilage structure and function, the literature reveals a sizeable volume of contemporary research that indicates muscle strength losses, as well as muscle atrophy commonly accompany the osteoarthritic disease process [9-12]. As well muscle co-activation processes may be abnormal, as may fat content. Muscle inflammation, and deficits in muscle power, endurance, and function [13-17] also prevail. Other muscle related problems that adversely impact osteoarthritis progression include various degrees of:

• Muscle protein degradation
• Muscle atrophy of both fiber types
• Muscle proprioception changes
• Muscle fiber distribution abnormalities
• Muscle denervation
• Muscle contractile deficits
• Muscle fatigue
• Muscle inflammation
• Reduced muscle cross-sectional area
• Muscle inhibition
• Muscle weakness [18]

Important in the context of the present discussion is the observation that the underlying muscle problems and the general progression of osteoarthritis involve the presence of excess oxidative stress and inflammation [19,20] that can interact to foster a negative set of joint destructive processes. Although the origin of muscle dysfunction in osteoarthritis is not clear, a role for vitamin E through its impact on multiple pathways including muscle [1-22] cannot be ignored. Unfortunately, muscle problems in osteoarthritis, which may be both causative or reactive in nature [18], and which are key to improving life quality and joint status in this disease, are not readily resolved to any long-term degree through traditional therapeutic exercise approaches. While many reasons for this prevail, a role for vitamin E in this respect is not one that has been considered to any degree to date, despite some compelling evidence as outlined below that could potentially be exploited help to attenuate any ensuing potentially reversible strength and muscle endurance deficits.

Vitamin E and Muscle Evidence Base

In Vitro Studies

Although small in number, laboratory studies examining linkages between the antioxidant properties of vitamin E and muscle structure and function, generally support the view that while oxidative stress may contribute to muscle damage, the presence of adequate levels of vitamin E may protect against muscle damage and dysfunction [23,24]. In addition to helping to prevent muscle atrophy, vitamin E may help to offset potential muscle protein losses, as well as muscle cell damage, myoblast atrophy and myotube degeneration [23].

Its presence at adequate levels may also impact favorably on muscle lipid metabolism, as well as muscle inflammation, often associated with osteoarthritis, while a persistent state of vitamin E deficiency may foster the onset of a myopathy [25], as well as exercise induced fatigue [23], muscle atrophy [25], a heightened muscle proteolytic rate, and type I muscle fiber contractile dysfunction [23] as depicted in Table 1 below.

Clinical Studies
Among the few clinical studies that pertain to the present topic, as with laboratory outcomes, those below imply a positive role for vitamin E in the maintenance and functional status of muscle, despite their diversity and limited approaches and samples. See Table 2. While no study could be found that directly set out to explore vitamin E and its association with osteoarthritis muscle, a major reason provided for the observed benefits of vitamin E in some cases is its established impact on susceptibility to oxidative stresses [33], although its protective effect might impact several other functional pathways of osteoarthritic muscle tissue [32]. Unfortunately, even though quite a number of clinically oriented studies detailing vitamin E associations with osteoarthritis prevail, none assessed muscle related associations to any degree, other than providing estimates of function with and with or vitamin E presence [19], and not all were in agreement as to whether vitamin E is at all beneficial for preventing or treating osteoarthritis.

Discussion
The role of nutriceuticals as well as muscle in mediating or moderating osteoarthritic joint outcomes has received increasing support in the past decade or so due to the need to better understand the origins of the disease as well as to uncover novel non toxic solutions to this seemingly intractable progressive disease. At the same time, several laboratory and clinical studies confirm that vitamin E is essential for the maintenance of the structural and functional components of skeletal muscle [38,39], and that its deficiency produces muscle degeneration [40] as well as apoptosis and death of skeletal muscle cells [29,38,41]. A vitamin E deficiency is also found to produce dystrophy and alterations in the chemical composition and functional behavior of muscle [38] that closely resembles some features of osteoarthritic muscle pathology, which is susceptible to oxidative damage, and subsequent muscle mass as well as strength losses. Other data show that vitamin E deficiencies can influence those detrimental oxidative processes that impact muscle structure and function in older adults, regardless of health status, as well as the onset or rate of progression of any prevailing sarcopenia [24]. Angthong et al. report that as the concentration of vitamin E in synovial fluid decreases, the severity of knee osteoarthritis increases [42], a situation wherein the effects of low vitamin E levels as a risk factor for muscle weakness in osteoarthritis cannot be ruled out.

Moreover, acting directly on other features of muscle pathology found in osteoarthritis, such as muscle protein degradation, the presence of vitamin E may arguably either help to offset or reduce the extent of joint pathology attributable to muscle in this disease, that correlates with disease progression [38], or its absence may hasten muscle dysfunction and the ensuing rate of joint degeneration. Vitamin E also affects metabolic syndrome and cardiovascular disease features, as well as inflammation, pain, collagen degradation, and cellular damage [43] frequent correlates in osteoarthritis that could affect muscle function and its properties either positively or negatively, directly, as well as indirectly. Since muscle and muscle quality reportedly influence subchondral bone status, mobility status, joint shock absorption, cartilage nutrition, and joint stability and alignment, subject to further research, efforts to ensure vitamin E levels are not deficient, along with the use of vitamin E to reduce and prevent the degree of osteoarthritis muscle pathology that may ensue where indicated may yet provide a highly innovative as well as cost-effective efficacious approach to ameliorating the interactive cycle of osteoarthritic disability as a whole as portrayed in Figure 1.

Conclusion
Although data is limited and caution is advised in interpreting the available data, preliminary research strongly implies there is added value to ensuring desirable vitamin E serum levels prevail in the context of averting premature or excess muscle related deficits, especially among the older population, and sarcopenic older adult [43], very prone to injury and osteoarthritis and muscle pathology. In particular, and consistent with available data of a strong moderating or mediating association between vitamin E and muscle structure and function, as well as an increasing volume of evidence of a highly significant association between osteoarthritis and damage to the muscles surrounding the affected joint[s], it appears further consideration of this body of research, along with rigorous and thoughtful research in this area might not only prove highly revealing, but highly advantageous clinically in multiple ways.

Indeed, since there is little dispute in the current body of research describing vitamin E-linkages to muscle status, including a possible vitamin E muscle-strength connection in osteoarthritis [44], it appears a focus on examining the diverse forms of vitamin E and their potential influence on the various muscle mechanisms and derangements that prevail in osteoarthritis is likely to yield highly valuable clinical insights.

In this regard, and despite no proof -of-principle- trial in this regard, in favor of a viable role for vitamin E in fostering muscle maintenance and mass in osteoarthritis situations is its well-established anti-oxidative and anti-inflammatory properties [45] observed to protect muscle cells from damage caused by free radicals [27,46]. Other data show vitamin E can both positively as well as negatively influence skeletal muscle maintenance and fiber degeneration, among other muscle related deficits that raise the risk for pain, joint array of disabling functional features, pathology, and inflammation that is challenging to resplove. To the contrary, a parallel body of research data show Vitamin E is efficacious in fostering overall health benefits that may well impact osteoarthritis muscle dysfunction indirectly and favorably [47-49] as alluded to in Box 1.

Moreover, its possible role in reversing this disease cannot be ruled out in cases where muscle is the key pathogenic factor [49,50].

To this end, it is concluded that concerted efforts to continue to examine the proof of concepts presented in this overview will prove of immense value and may help reveal novel insights not only concerning the osteoarthritis disease process, but as to what is needed in specific cases to foster its prevention, amelioration, or optimal outcome.

Bibliography

1. Tantavisut, S., Tanavalee, A., Honsawek, S., Suantawee, T., Ngarmukos, S., et al. (2017). Effect of vitamin E on oxidative stress level in blood, synovial fluid, and synovial tissue in severe knee osteoarthritis: a randomized controlled study. BMC Musculoskelet Disord., 18(1), 281.
2. Jones, G. (2016). What's new in osteoarthritis pathogenesis? Intern Med J., 46(2), 229-236.
3. Felson, D. T. (2004) An update on the pathogenesis and epidemiology of osteoarthritis. Radiol Clin North Am., 42(1), 1-9.
4. Green, J. A., Hirst-Jones, K. L., Davidson, R. K., Jupp, O., Bao, Y., et al. (2014). The potential for dietary factors to prevent or treat osteoarthritis. Proc Nutr Soc., 73(2), 278-288.
5. Lei, M., Guo, C., Hua, L., Xue, S., Yu, D., et al. (2017). Crocin attenuates joint pain and muscle dysfunction in osteoarthritis rat. Inflammation., 40(6), 2086-2093.
6. Frati, A., Landi, D., Marinelli, C., Gianni, G., Fontana, L., et al. (2014). Nutraceutical properties of chestnut flours: Beneficial effects on skeletal muscle atrophy. Food Funct,. 5(11), 2870-2882.
7. Lee, S. Y., Ro, H. J., Chung, S. G., Kang, S. H., Seo, K. M., et al. (2016). Low skeletal muscle mass in the lower limbs is independently associated to knee osteoarthritis. PLoS One., 11(11), e0166385.
8. Lim, J. J., Wan Zurinah, W. N., Mouly, V. & Norwahidah, A. K. (2019). Tocotrienol-rich fraction (TRF) treatment promotes proliferation capacity of stress-induced premature senescence myoblasts and modulates the renewal of satellite cells: microarray analysis. Oxid Med Cell Longev., 9141343.
9. Chen, D., Shen, J., Zhao, W., Wang, T., Han, L., et al. (2017). Osteoarthritis: Toward a comprehensive understanding of pathological mechanism. Bone Res., 16044.
10. Herzog, W. & Longino, D. (2007). The role of muscles in joint degeneration and osteoarthritis. J Biomech., 40(Suppl 1), S54-63.
11. Jackson, B. D., Wluka, A. E., Teichtahl, A. J., Morris, M. E. & Cicuttini, F. M. (2004). Reviewing knee osteoarthritis--a biomechanical perspective. J Sci Med Sport., 7(3), 347-357.(2), 278-288.
12. Becker, R., Berth, A., Nehring, M. & Awiszus, F. (2004). Neuromuscular quadriceps dysfunction prior to osteoarthritis of the knee. J Orthop Res., 22(4), 768-773.
13. Astephen Wilson, J. L., Stanish, W. D. & Hubley-Kozey, C. L. (2016). Asymptomatic and symptomatic individuals with the same radiographic evidence of knee osteoarthritis walk with different knee moments and muscle activity. J Orthop Res.
14. Ferrari, M., Louati, K., Miquel, A., Behin, A., Benveniste, O., et al. (2015). Quickly progressive amyotrophy of the thigh: an unusual cause of rapid chondrolysis of the knee. Joint Bone Spine., 82(3), 203-205.
15. Tuna, S., Balcı, N., & Özçakar, L. (2016). The relationship between femoral cartilage thickness and muscle strength in knee osteoarthritis. Clin Rheumatol,. 35(8), 2073-2077.
16. Macías-Hernández, S. I., Miranda-Duarte, A., Ramírez-Mora, I., Cortés-González, S., Morones-Alba, J. D., et al. (2016). Knee muscle strength correlates with joint cartilage T2 relaxation time in young participants with risk factors for osteoarthritis. Clin Rheumatol., 35(8), 2087-2092.
17. Bamman, M. M,. Ferrando, A. A., Evans, R. P., Stec, M. J., Kelly, N. A., et al. (2015). Muscle inflammation susceptibility: a prognostic index of recovery potential after hip arthroplasty? Am J Physiol Endocrinol Metab., 308(8), E670-679.
18. Marks, R. (2015). Muscle and muscle mechanism as possible factors leading to osteoarthritis. SM J Orthop,, 1(2), 1008.
19. Chin, K. Y. & Ima-Nirwana, S. (2018). The role of vitamin E in preventing and treating osteoarthritis - a review of the current evidence. Frontiers Pharmacol., 9, 946.
20. Suantawee T., Tantavisut, S., Adisakwattana, S., Tanavalee, A., Yuktanandana, P., et al. (2013). Oxidative stress, vitamin E, and antioxidant capacity in knee osteoarthritis. J Clin Diagn Res., 7(9), 1855-1859.
21. Dehghan, M. (2015). Comparative effectiveness of B and E vitamins with diclofenac in reducing pain due to osteoarthritis of the knee. Med Arch., 69(2), 103-106.
22. Li XI., Dong, Z., Zhang, F., Dong, J. & Zhang, Y. (2016). Vitamin E slows down the progression of osteoarthritis. Exp Ther Med., 12(1), 18-22.
23. Chung, E., Mo, H., Wang, S., Zu, Y., Elfakhani, M., et al. (2018). Potential roles of vitamin E in age-related changes in skeletal muscle health. Nutr Res., 49, 23-36.
24. Khor, S. C., Abdul Karim, N., Ngah, W. Z., Yusof, Y. A., et al. (2014). Vitamin E in sarcopenia: current evidences on its role in prevention and treatment. Oxid Med Cell Longev., 914853.
25. Bedford, H. E., Valberg, S. J., Firshman, A. M., Lucio, M., Boyce, M. K., et al. (2013). Histopathologic findings in the sacrocaudalis dorsalis medialis muscle of horses with vitamin E-responsive muscle atrophy and weakness. J Am Vet Med Assoc., 242(8), 1127-1137.
26. Dahlin, K. J., Chan, A. C., Benson, E. S. & Hegarty, P. V. (1978). Rehabilitating effect of vitamin E therapy on the ultrastructural changes in skeletal muscles of vitamin E-deficient rabbits. Am J Clin Nutr., 31(1), 94-99.
27. Mâncio, R. D., Hermes, T. A., Macedo, A. B., Mizobuti, D. S., Valduga, A. H., et al. (2017). Vitamin E treatment decreases muscle injury in mdx mice. Nutrition., 43-44, 39-46.
28. Marzani, B., Balage, M., Vénien, A., Astruc, T., Papet, I., et al. (2008). Antioxidant supplementation restores defective leucine stimulation of protein synthesis in skeletal muscle from old rats. J Nutr., 138(11), 2205-2211.
29. Nunes, V. A., Gozzo, A. J., Cruz-Silva, I., Juliano, M. A., Viel, T. A., et al. (2005). Vitamin E prevents cell death induced by mild oxidative stress in chicken skeletal muscle cells. Comp Biochem Physiol C Toxicol Pharmacol., 141(3), 225-240.
30. Servais, S., Letexier, D., Favier, R., Duchamp, C. & Desplanches, D. (2007). Prevention of unloading-induced atrophy by vitamin E supplementation: links between oxidative stress and soleus muscle proteolysis? Free Radic Biol Med., 42(5), 627-635.
31. Terruzzi, I., Vacante, F., Senesi, P., Montesano, A., Codella, R., et al. (2018). Effect of hazelnut oil on muscle cell signalling and differentiation. J Oleo Sci., 67(10), 1315-1326.
32. von Grabowiecki, Y., Licona, C., Palamiuc, L., Abreu, P., Vidimar, V., et al. (2015). Regulation of a Notch3-Hes1 pathway and protective effect by a tocopherol-omega alkanol chain derivative in muscle atrophy. J Pharmacol Exp Ther., 352(1), 23-32.
33. Passerieux, E., Hayot, M., Jaussent, A., Carnac, G., Gouzi, F., et al. (2015). Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: a double-blind randomized controlled clinical trial. Free Radic Biol Med., 81, 158-169.
34. Chou, C. C., Sung, Y. C., Davison, G., Chen, C. Y. & Liao, Y. H. (2018). Short-term high-dose vitamin C and E supplementation attenuates muscle damage and inflammatory responses to repeated Taekwondo competitions: A randomized placebo-controlled trial. Int J Med Sci., 15(11), 1217-1226.
35. Meydani, M., Evans, W. J., Handelman, G., Biddle, L., Fielding, R. A., et al. (1993). Protective effect of vitamin E on exercise-induced oxidative damage in young and older adults. Am J Physiol., 264(5 Pt 2), R992-998.
36. Morrison, D., Hughes, J., Della Gatta, P.A., Mason, S., Lamon, S., et al. (2015). Vitamin C and E supplementation prevents some of the cellular adaptations to endurance-training in humans. Free Radic Biol Med., 89, 852-862.
37. Semba, R. D., Blaum, C., Guralnik, J. M., Moncrief, D. T., Ricks, M. O., et al. (2003). Carotenoid and vitamin E status are associated with indicators of sarcopenia among older women living in the community. Aging Clin Exp Res., 15/(6), 482-487.
38. Li, H., Zeng, C., Wei, J., Yang, T., Gao, S. G., et al. (2016). Associations between dietary antioxidants intake and radiographic knee osteoarthritis. Clin Rheumatol., 35(6), 1585-1592.
39. Chang, C. K., Huang, H. Y., Tseng, H. F., Hsuuw, Y. D. & Tso, T. K. (2007). Interaction of vitamin E and exercise training on oxidative stress and antioxidant enzyme activities in rat skeletal muscles. J Nutr Biochem., 18(1), 39-45.
40. Aggarwal, B. B., Sundaram, C., Prasad, S. & Kannappan, R. (2010). Tocotrienols, the vitamin E of the 21st century: Its potential against cancer and other chronic diseases. Biochem Pharmacol., 80(11), 1613-1631.

41. Nunes, V. A., Gozzo, A. J., Juliano, M. A., César, M. C., Sampaio, M. U., et al. (2003). Antioxidant dietary deficiency induces caspase activation in chick skeletal muscle cells. Braz J Med Biol Res., 36(8), 1047-1053.
42. Angthong, C., Morales, N. P., Sutipornpalangkul, W., Khadsongkram, A., Pinsornsak, P., et al. (2013). Can levels of antioxidants in synovial fluid predict the severity of primary knee osteoarthritis: A preliminary study. Springerplus., 2, 652.
43. Zheng, X. Y., Liang, J., Li, Y. S., & Tu, M. (2018). Role of fat-soluble vitamins in osteoarthritis management. J Clin Rheumatol., 24(3), 132-137.
44. Purcell, S., Thornberry, R., Elliott, S. A., Panton, L., Ormsbee, M. J., et al. (2016). Body composition, strength, and dietary intake of patients with hip or knee osteoarthritis. Can J Diet Pract Res., 77(2), 98-102.
45. Ter Borg, S., de Groot, L. C., Mijnarends, D. M., de Vries, J. H., Verlaan, S., et al. (2016). Differences in nutrient intake and biochemical nutrient status between sarcopenic and nonsarcopenic older adults-results from the Maastricht Sarcopenia Study. J Am Med Dir Assoc., 17(5), 393-401.
46. Baumgartner, H. K., Gerasimenko, J. V. Thorne, C., Ashurst, L. H., Barrow. S. L., et al. (2007). Caspase-8-mediated apoptosis induced by oxidative stress is independent of the intrinsic pathway and dependent on cathepsins. J Physiol Gastrointest Liver Physiol., 293, G296-G307.
47. Tonge, D. P., Bardsley, R. G., Parr, T., Maciewicz, R. A. & Jones, S. W. (2013). Evidence of changes to skeletal muscle contractile properties during the initiation of disease in the ageing guinea pig model of osteoarthritis. Longev Healthspan., 2(1), 15.
48. Bookbinder, L., Finno, C. J., Firshman, A. M., Katzman, S. A., Burns, E., et al. (2019). Impact of alpha-tocopherol deficiency and supplementation on sacrocaudalis and gluteal muscle fiber histopathology and morphology in horses. J Vet Intern Med.
49. Bhattacharya, I., Saxena, R. & Gupta, V. (2012). Efficacy of vitamin E in knee osteoarthritis management of North Indian geriatric population. Ther Adv Musculoskelet Dis., 4(1), 11-19.